PT J
AU Gu, JK
   Wu, M
   Guo, RY
   Yan, KG
   Lei, JL
   Gao, N
   Yang, MJ
AF Gu, Jinke
   Wu, Meng
   Guo, Runyu
   Yan, Kaige
   Lei, Jianlin
   Gao, Ning
   Yang, Maojun
TI The architecture of the mammalian respirasome
SO NATURE
LA English
DT Article
ID respiratory complex-i; mitochondrial electron-transport; bovine heart-mitochondria; em structure determination; cytochrome bc(1) complex; oxidative-phosphorylation; chain supercomplexes; cryo-em; paracoccus-denitrificans; cryoelectron tomography
AB The respiratory chain complexes I, III and IV (CI, CIII and CIV) are present in the bacterial membrane or the inner mitochondrial membrane and have a role of transferring electrons and establishing the proton gradient for ATP synthesis by complex V. The respiratory chain complexes can assemble into supercomplexes (SCs), but their precise arrangement is unknown. Here we report a 5.4 angstrom cryo-electron microscopy structure of the major 1.7 megadalton SCI1III2IV1 respirasome purified from porcine heart. The CIII dimer and CIV bind at the same side of the L-shaped CI, with their transmembrane domains essentially aligned to form a transmembrane disk. Compared to free CI, the CI in the respirasome is more compact because of interactions with CIII and CIV. The NDUFA11 and NDUFB9 supernumerary subunits of CI contribute to the oligomerization of CI and CIII. The structure of the respirasome provides information on the precise arrangements of the respiratory chain complexes in mitochondria.
C1 [Gu, Jinke; Wu, Meng; Guo, Runyu; Yan, Kaige; Lei, Jianlin; Gao, Ning; Yang, Maojun] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Minist Educ,Key Lab Prot Sci,Sch Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University
RP Gao, N; Yang, MJ (corresponding author), Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Minist Educ,Key Lab Prot Sci,Sch Life Sci, Beijing 100084, Peoples R China.
EM ninggao@tsinghua.edu.cn; maojunyang@tsinghua.edu.cn
FU Ministry of Science and Technology [2016YFA0501101, 2012CB911101, 2013CB910404, 2016YFA0500700]; National Outstanding Young Scholar Science Foundation; National Natural Science Foundation of China [31030020, 31170679, 31422016]
NR 67
TC 290
Z9 320
U1 3
U2 209
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 639
EP +
DI 10.1038/nature19359
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700041
PM 27654917
DA 2026-03-09
ER

PT J
AU Kotschy, A
   Szlavik, Z
   Murray, J
   Davidson, J
   Maragno, AL
   Le Toumelin-Braizat, G
   Chanrion, M
   Kelly, GL
   Gong, JN
   Moujalled, DM
   Bruno, A
   Sekei, MC
   Paczal, A
   Szabo, ZB
   Sipos, S
   Radics, G
   Proszenyak, A
   Balint, B
   Ondi, L
   Blasko, G
   Robertson, A
   Surgenor, A
   Dokurno, P
   Chen, I
   Matassova, N
   Smith, J
   Pedder, C
   Graham, C
   Studeny, A
   Lysiak-Auvity, G
   Girard, AM
   Gravé, F
   Segal, D
   Riffkin, CD
   Pomilio, G
   Galbraith, LCA
   Aubrey, BJ
   Brennan, MS
   Herold, MJ
   Chang, C
   Guasconi, G
   Auquil, NC
   Melchiore, F
   Guigal-Stephan, N
   Lockhart, B
   Colland, F
   Hickman, JA
   Roberts, AW
   Huang, DCS
   Wei, AH
   Strasser, A
   Lessene, G
   Geneste, O
AF Kotschy, Andras
   Szlavik, Zoltan
   Murray, James
   Davidson, James
   Maragno, Ana Leticia
   Le Toumelin-Braizat, Gaetane
   Chanrion, Maia
   Kelly, Gemma L.
   Gong, Jia-Nan
   Moujalled, Donia M.
   Bruno, Alain
   Sekei, Marton C.
   Paczal, Attila
   Szabo, Zoltan B.
   Sipos, Szabolcs
   Radics, Gabor
   Proszenyak, Agnes
   Balint, Balazs
   Ondi, Levente
   Blasko, Gabor
   Robertson, Alan
   Surgenor, Allan
   Dokurno, Pawel
   Chen, Ijen
   Matassova, Natalia
   Smith, Julia
   Pedder, Christopher
   Graham, Christopher
   Studeny, Aurelie
   Lysiak-Auvity, Gaelle
   Girard, Anne-Marie
   Grave, Fabienne
   Segal, David
   Riffkin, Chris D.
   Pomilio, Giovanna
   Galbraith, Laura C. A.
   Aubrey, Brandon J.
   Brennan, Margs S.
   Herold, Marco J.
   Chang, Catherine
   Guasconi, Ghislaine
   Auquil, Nicolas C.
   Melchiore, Fabien
   Guigal-Stephan, Nolwen
   Lockhart, Brian
   Colland, Frederic
   Hickman, John A.
   Roberts, Andrew W.
   Huang, David C. S.
   Wei, Andrew H.
   Strasser, Andreas
   Lessene, Guillaume
   Geneste, Olivier
TI The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models
SO NATURE
LA English
DT Article
ID anti-apoptotic mcl-1; bcl-xl; multiple-myeloma; high-affinity; tumor-cells; survival; protein; combination; dependency; navitoclax
AB Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours.
C1 [Kotschy, Andras; Szlavik, Zoltan; Sekei, Marton C.; Paczal, Attila; Szabo, Zoltan B.; Sipos, Szabolcs; Radics, Gabor; Proszenyak, Agnes; Balint, Balazs; Ondi, Levente; Blasko, Gabor] Servier Res Inst Med Chem, H-1031 Budapest, Hungary.
   [Murray, James; Davidson, James; Robertson, Alan; Surgenor, Allan; Dokurno, Pawel; Chen, Ijen; Matassova, Natalia; Smith, Julia; Pedder, Christopher; Graham, Christopher] Vernalis R&D Ltd, Cambridge CB21 6GB, England.
   [Maragno, Ana Leticia; Le Toumelin-Braizat, Gaetane; Chanrion, Maia; Bruno, Alain; Studeny, Aurelie; Lysiak-Auvity, Gaelle; Girard, Anne-Marie; Grave, Fabienne; Guasconi, Ghislaine; Auquil, Nicolas C.; Colland, Frederic; Hickman, John A.; Geneste, Olivier] Inst Rech Servier Oncol, R&D Unit, F-78290 Croissy Sur Seine, France.
   [Kelly, Gemma L.; Gong, Jia-Nan; Segal, David; Riffkin, Chris D.; Galbraith, Laura C. A.; Aubrey, Brandon J.; Brennan, Margs S.; Herold, Marco J.; Chang, Catherine; Roberts, Andrew W.; Huang, David C. S.; Strasser, Andreas; Lessene, Guillaume] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia.
   [Kelly, Gemma L.; Gong, Jia-Nan; Segal, David; Riffkin, Chris D.; Galbraith, Laura C. A.; Aubrey, Brandon J.; Brennan, Margs S.; Herold, Marco J.; Chang, Catherine; Roberts, Andrew W.; Huang, David C. S.; Strasser, Andreas; Lessene, Guillaume] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia.
   [Moujalled, Donia M.; Pomilio, Giovanna; Wei, Andrew H.] Monash Univ, Australian Ctr Blood Dis, Melbourne, Vic 3004, Australia.
   [Aubrey, Brandon J.] Royal Melbourne Hosp, Victorian Comprehens Canc Ctr, Dept Clin Haematol & Bone Marrow Transplantat, Melbourne, Vic 3050, Australia.
   [Melchiore, Fabien; Guigal-Stephan, Nolwen; Lockhart, Brian] Inst Rech Servier, Biomarker Res Div, F-78290 Croissy Sur Seine, France.
   [Roberts, Andrew W.] Univ Melbourne, Fac Med, Melbourne, Vic 3010, Australia.
   [Wei, Andrew H.] Alfred Hosp, Dept Clin Haematol, Melbourne, Vic 3004, Australia.
   [Lessene, Guillaume] Univ Melbourne, Dept Pharmacol & Pharmaceut, Melbourne, Vic 3010, Australia.
C3 Servier; Vernalis; Servier; Institut de Recherches Internationales Servier; Walter & Eliza Hall Institute; University of Melbourne; Monash University; University of Melbourne; Melbourne Health; Royal Melbourne Hospital; Servier; Institut de Recherches Internationales Servier; University of Melbourne; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; University of Melbourne
RP Geneste, O (corresponding author), Inst Rech Servier Oncol, R&D Unit, F-78290 Croissy Sur Seine, France.
EM olivier.geneste@servier.com
FU National Health and Medical Research Council Australia (NHMRC) [GNT1016647, GNT1016701, GNT1020363, GNT1086291, GNT1049720, GNT1057742, GNT1079560]; Leukemia and Lymphoma Society (SCOR grant) [7001-03]; Cancer Council [1086157 GLK]; Kay Kendall Leukemia Fund Intermediate Fellowship [KKL331]; Victoria Cancer Agency; Australian Cancer Research Foundation; Victorian State Government Operational Infrastructure Support (OIS) grant; estate of Anthony (Toni) Redstone OAM
NR 51
TC 853
Z9 1004
U1 3
U2 177
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 477
EP +
DI 10.1038/nature19830
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400050
PM 27760111
DA 2026-03-09
ER

PT J
AU Hosseini, H
   Obradovic, MMS
   Hoffmann, M
   Harper, KL
   Sosa, MS
   Werner-Klein, M
   Nanduri, LK
   Werno, C
   Ehrl, C
   Maneck, M
   Patwary, N
   Haunschild, G
   Guzvic, M
   Reimelt, C
   Grauvogl, M
   Eichner, N
   Weber, F
   Hartkopf, AD
   Taran, FA
   Rucker, SYB
   Fehm, T
   Rack, B
   Buchholz, S
   Spang, R
   Eister, GM
   Aguirre-Ghiso, JA
   Klein, CA
AF Hosseini, Hedayatollah
   Obradovic, Milan M. S.
   Hoffmann, Martin
   Harper, Kathryn L.
   Sosa, Maria Soledad
   Werner-Klein, Melanie
   Nanduri, Lahiri Kanth
   Werno, Christian
   Ehrl, Carolin
   Maneck, Matthias
   Patwary, Nina
   Haunschild, Gundula
   Guzvic, Miodrag
   Reimelt, Christian
   Grauvogl, Michael
   Eichner, Norbert
   Weber, Florian
   Hartkopf, Andreas D.
   Taran, Florin-Andrei
   Rucker, Sara Y. B.
   Fehm, Tanja
   Rack, Brigitte
   Buchholz, Stefan
   Spang, Rainer
   Eister, Gunter M.
   Aguirre-Ghiso, Julio A.
   Klein, Christoph A.
TI Early dissemination seeds metastasis in breast cancer
SO NATURE
LA English
DT Article
ID disseminated tumor-cells; bone-marrow; mouse model; mammary; single; tumorigenesis; normalization; expression; mutations; gene
AB Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination.
C1 [Hosseini, Hedayatollah; Obradovic, Milan M. S.; Nanduri, Lahiri Kanth; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Guzvic, Miodrag; Reimelt, Christian; Klein, Christoph A.] Univ Regensburg, Expt Med & Therapy Res, D-93053 Regensburg, Germany.
   [Hoffmann, Martin; Werno, Christian; Klein, Christoph A.] Fraunhofer Inst Toxicol & Expt Med, Project Grp Personalized Tumour Therapy, D-93053 Regensburg, Germany.
   [Harper, Kathryn L.; Sosa, Maria Soledad; Aguirre-Ghiso, Julio A.] Icahn Sch Med Mt Sinai, Div Hematol & Oncol, Dept Med, Dept Otolaryngol,Dept Oncol Sci,Tisch Canc Inst,B, New York, NY 10029 USA.
   [Werner-Klein, Melanie] Univ Regensburg, Inst Immunol, D-93053 Regensburg, Germany.
   [Grauvogl, Michael; Spang, Rainer] Univ Regensburg, Inst Funct Genom, Dept Stat Bioinformat, D-93053 Regensburg, Germany.
   [Eichner, Norbert; Eister, Gunter M.] Univ Regensburg, Biochem Ctr Regensburg BZR, Lab RNA Biol, D-93053 Regensburg, Germany.
   [Weber, Florian] Univ Regensburg, Inst Pathol, D-93053 Regensburg, Germany.
   [Hartkopf, Andreas D.; Taran, Florin-Andrei; Rucker, Sara Y. B.] Univ Tubingen, Dept Gynecol & Obstet, D-72076 Tubingen, Germany.
   [Fehm, Tanja] Univ Dusseldorf, Dept Gynecol & Obstet, D-40225 Dusseldorf, Germany.
   [Rack, Brigitte] Univ Munich, Dept Gynecol & Obstet, D-80337 Munich, Germany.
   [Buchholz, Stefan] Univ Med Ctr Regensburg, Dept Gynecol & Obstet, D-93053 Regensburg, Germany.
   [Obradovic, Milan M. S.] Univ Basel, Univ Basel Hosp, Dept Biomed, Tumor Heterogene Metastasis & Resistance, CH-4031 Basel, Switzerland.
   [Sosa, Maria Soledad] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Pharmacol Sci, One Gustave L Levy Pl, New York, NY 10029 USA.
   [Nanduri, Lahiri Kanth] Tech Univ Dresden, Dept Gastrointestinal Thorac & Vasc Surg, Med Fak Carl Gustav Carus, D-01307 Dresden, Germany.
C3 University of Regensburg; Fraunhofer Gesellschaft; Fraunhofer Germany; Fraunhofer Toxicology & Experimental Medicine; Icahn School of Medicine at Mount Sinai; University of Regensburg; University of Regensburg; University of Regensburg; University of Regensburg; Eberhard Karls University of Tubingen; Heinrich Heine University Dusseldorf; University of Munich; University of Regensburg; University of Basel; Icahn School of Medicine at Mount Sinai; Technische Universitat Dresden; Carl Gustav Carus University Hospital
RP Klein, CA (corresponding author), Univ Regensburg, Expt Med & Therapy Res, D-93053 Regensburg, Germany.; Klein, CA (corresponding author), Fraunhofer Inst Toxicol & Expt Med, Project Grp Personalized Tumour Therapy, D-93053 Regensburg, Germany.
EM christoph.klein@ukr.de
FU DFG [Kl 1233/2-1, KL 1233/3-1, KL 1233/10-1, Me2064/4-1, SP 938/2-1, INST 89/341-1 FUGG]; Dr Josef Steiner Foundation; ERC [322602]; SWCRF [CA109182, CA196521, CA163131, BC132674, F31 CA183185, BC112380]; NIH [1S10RR024745]; European Research Council (ERC) [322602] Funding Source: European Research Council (ERC); National Cancer Institute [R01CA109182, P30CA196521] Funding Source: NIH RePORTER
NR 55
TC 524
Z9 595
U1 2
U2 189
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 552
EP +
DI 10.1038/nature20785
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500045
PM 27974799
DA 2026-03-09
ER

PT J
AU Jacobsson, D
   Panciera, F
   Tersoff, J
   Reuter, MC
   Lehmann, S
   Hofmann, S
   Dick, KA
   Ross, FM
AF Jacobsson, Daniel
   Panciera, Federico
   Tersoff, Jerry
   Reuter, Mark C.
   Lehmann, Sebastian
   Hofmann, Stephan
   Dick, Kimberly A.
   Ross, Frances M.
TI Interface dynamics and crystal phase switching in GaAs nanowires
SO NATURE
LA English
DT Article
ID self-catalyzed gaas; iii-v nanowires; phosphide nanowires; silicon nanowires; growth-kinetics; solid growth; zinc blende; inas; mechanisms; zincblende
AB Controlled formation of non-equilibrium crystal structures is one of the most important challenges in crystal growth. Catalytically grown nanowires are ideal systems for studying the fundamental physics of phase selection, and could lead to new electronic applications based on the engineering of crystal phases. Here we image gallium arsenide (GaAs) nanowires during growth as they switch between phases as a result of varying growth conditions. We find clear differences between the growth dynamics of the phases, including differences in interface morphology, step flow and catalyst geometry. We explain these differences, and the phase selection, using a model that relates the catalyst volume, the contact angle at the trijunction (the point at which solid, liquid and vapour meet) and the nucleation site of each new layer of GaAs. This model allows us to predict the conditions under which each phase should be observed, and use these predictions to design GaAs heterostructures. These results could apply to phase selection in other nanowire systems.
C1 [Jacobsson, Daniel; Lehmann, Sebastian; Dick, Kimberly A.] Lund Univ, Solid State Phys & NanoLund, Box 118, S-22100 Lund, Sweden.
   [Jacobsson, Daniel; Dick, Kimberly A.] Lund Univ, Ctr Anal & Synth, Box 124, S-22100 Lund, Sweden.
   [Panciera, Federico; Hofmann, Stephan] Univ Cambridge, Dept Engn, 9 JJ Thomson Ave, Cambridge CB3 0FA, England.
   [Panciera, Federico; Tersoff, Jerry; Reuter, Mark C.; Ross, Frances M.] IBM TJ Watson Res Ctr, 1101 Kitchawan Rd, Yorktown Hts, NY 10598 USA.
C3 Lund University; Lund University; University of Cambridge; International Business Machines (IBM); IBM USA
RP Jacobsson, D (corresponding author), Lund Univ, Solid State Phys & NanoLund, Box 118, S-22100 Lund, Sweden.; Jacobsson, D (corresponding author), Lund Univ, Ctr Anal & Synth, Box 124, S-22100 Lund, Sweden.; Ross, FM (corresponding author), IBM TJ Watson Res Ctr, 1101 Kitchawan Rd, Yorktown Hts, NY 10598 USA.
EM Daniel.jacobsson@ftf.lth.se; fmross@us.ibm.com
FU Knut and Alice Wallenberg Foundation (KAW); Swedish Research Council (VR); Nanometer Structure Consortium at Lund University (nmC@LU); ERC [279342]; European Research Council (ERC) [279342] Funding Source: European Research Council (ERC)
NR 46
TC 312
Z9 345
U1 1
U2 424
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 317
EP +
DI 10.1038/nature17148
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300042
PM 26983538
DA 2026-03-09
ER

PT J
AU Li, ZF
   Alyamani, M
   Li, JN
   Rogacki, K
   Abazeed, M
   Upadhyay, SK
   Balk, SP
   Taplin, ME
   Auchus, RJ
   Sharifi, N
AF Li, Zhenfei
   Alyamani, Mohammad
   Li, Jianneng
   Rogacki, Kevin
   Abazeed, Mohamed
   Upadhyay, Sunil K.
   Balk, Steven P.
   Taplin, Mary-Ellen
   Auchus, Richard J.
   Sharifi, Nima
TI Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy
SO NATURE
LA English
DT Article
ID androgen-receptor; steroid 5-alpha-reductase; cyp17a1 inhibition; dihydrotestosterone; dehydrogenase; activation; resistance; biology; rat; men
AB Abiraterone blocks androgen synthesis and prolongs survival in patients with castration-resistant prostate cancer, which is otherwise driven by intratumoral androgen synthesis(1,2). Abiraterone is metabolized in patients to Delta(4)-abiraterone (D4A), which has even greater anti-tumour activity and is structurally similar to endogenous steroidal 5 alpha-reductase substrates, such as testosterone(3). Here, we show that D4A is converted to at least three 5 alpha-reduced and three 5 beta-reduced metabolites in human serum. The initial 5 alpha-reduced metabolite, 3-keto-5 alpha-abiraterone, is present at higher concentrations than D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor agonist, which promotes prostate cancer progression. In a clinical trial of abiraterone alone, followed by abiraterone plus dutasteride (a 5 alpha-reductase inhibitor), 3-keto-5 alpha-abiraterone and downstream metabolites were depleted by the addition of dutasteride, while D4A concentrations rose, showing that dutasteride effectively blocks production of a tumour-promoting metabolite and permits D4A accumulation. Furthermore, dutasteride did not deplete the three 5 beta-reduced metabolites, which were also clinically detectable, demonstrating the specific biochemical effects of pharmacological 5 alpha-reductase inhibition on abiraterone metabolism. Our findings suggest a previously unappreciated and biochemically specific method of clinically fine-tuning abiraterone metabolism to optimize therapy.
C1 [Li, Zhenfei; Alyamani, Mohammad; Li, Jianneng; Sharifi, Nima] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA.
   [Rogacki, Kevin; Abazeed, Mohamed] Cleveland Clin, Taussig Canc Inst, Dept Radiat Oncol, Cleveland, OH 44195 USA.
   [Upadhyay, Sunil K.; Auchus, Richard J.] Univ Michigan, Sch Med, Dept Pharmacol, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA.
   [Upadhyay, Sunil K.; Auchus, Richard J.] Univ Michigan, Sch Med, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA.
   [Balk, Steven P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
   [Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
   [Sharifi, Nima] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH 44195 USA.
   [Sharifi, Nima] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Cleveland Clinic Foundation; Cleveland Clinic Foundation
RP Sharifi, N (corresponding author), Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA.; Sharifi, N (corresponding author), Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH 44195 USA.; Sharifi, N (corresponding author), Cleveland Clin, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH 44195 USA.
EM sharifn@ccf.org
FU Howard Hughes Medical Institute; Prostate Cancer Foundation; American Cancer Society [12-038-01-CCE]; National Cancer Institute [R01CA168899, R01CA172382, R01CA190289, P01 CA163227, P50 CA090381]; US Army Medical Research and Materiel Command [PC121382]; National Cancer Institute [P01CA163227, R01CA172382] Funding Source: NIH RePORTER
NR 31
TC 143
Z9 161
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 547
EP +
DI 10.1038/nature17954
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100044
PM 27225130
DA 2026-03-09
ER

PT J
AU Tirosh, I
   Venteicher, AS
   Hebert, C
   Escalante, LE
   Patel, AP
   Yizhak, K
   Fisher, JM
   Rodman, C
   Mount, C
   Filbin, MG
   Neftel, C
   Desai, N
   Nyman, J
   Izar, B
   Luo, CC
   Francis, JM
   Patel, AA
   Onozato, ML
   Riggi, N
   Livak, KJ
   Gennert, D
   Satija, R
   Nahed, BV
   Curry, WT
   Martuza, RL
   Mylvaganam, R
   Iafrate, AJ
   Frosch, MP
   Golub, TR
   Rivera, MN
   Getz, G
   Rozenblatt-Rosen, O
   Cahill, DP
   Monje, M
   Bernstein, BE
   Louis, DN
   Regev, A
   Suvà, ML
AF Tirosh, Itay
   Venteicher, Andrew S.
   Hebert, Christine
   Escalante, Leah E. .
   Patel, Anoop P.
   Yizhak, Keren
   Fisher, Jonathan M. .
   Rodman, Christopher
   Mount, Christopher
   Filbin, Mariella G.
   Neftel, Cyril
   Desai, Niyati
   Nyman, Jackson
   Izar, Benjamin
   Luo, Christina C.
   Francis, Joshua M. .
   Patel, Aanand A.
   Onozato, Maristela L.
   Riggi, Nicolo
   Livak, Kenneth J.
   Gennert, Dave
   Satija, Rahul
   Nahed, Brian V. .
   Curry, William T.
   Martuza, Robert L.
   Mylvaganam, Ravindra
   Iafrate, A. John
   Frosch, Matthew P.
   Golub, Todd R.
   Rivera, Miguel N. .
   Getz, Gad
   Rozenblatt-Rosen, Orit
   Cahill, Daniel P.
   Monje, Michelle
   Bernstein, Bradley E. .
   Louis, David N.
   Regev, Aviv
   Suva, Mario L.
TI Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
SO NATURE
LA English
DT Article
ID expression; mutations; cycle; differentiation; quantification; tumorigenicity; transcriptome; astrocytes; neurons; markers
AB Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny(1). Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
C1 [Tirosh, Itay; Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah E. .; Yizhak, Keren; Fisher, Jonathan M. .; Rodman, Christopher; Filbin, Mariella G.; Neftel, Cyril; Nyman, Jackson; Izar, Benjamin; Francis, Joshua M. .; Livak, Kenneth J.; Gennert, Dave; Satija, Rahul; Golub, Todd R.; Rivera, Miguel N. .; Getz, Gad; Rozenblatt-Rosen, Orit; Bernstein, Bradley E. .; Regev, Aviv; Suva, Mario L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah E. .; Yizhak, Keren; Filbin, Mariella G.; Neftel, Cyril; Desai, Niyati; Luo, Christina C.; Patel, Aanand A.; Onozato, Maristela L.; Riggi, Nicolo; Mylvaganam, Ravindra; Iafrate, A. John; Frosch, Matthew P.; Rivera, Miguel N. .; Getz, Gad; Bernstein, Bradley E. .; Louis, David N.; Suva, Mario L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah E. .; Yizhak, Keren; Filbin, Mariella G.; Neftel, Cyril; Desai, Niyati; Luo, Christina C.; Patel, Aanand A.; Onozato, Maristela L.; Riggi, Nicolo; Mylvaganam, Ravindra; Iafrate, A. John; Frosch, Matthew P.; Rivera, Miguel N. .; Getz, Gad; Bernstein, Bradley E. .; Louis, David N.; Suva, Mario L.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
   [Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah E. .; Patel, Anoop P.; Yizhak, Keren; Filbin, Mariella G.; Neftel, Cyril; Desai, Niyati; Luo, Christina C.; Patel, Aanand A.; Onozato, Maristela L.; Riggi, Nicolo; Nahed, Brian V. .; Curry, William T.; Martuza, Robert L.; Mylvaganam, Ravindra; Iafrate, A. John; Frosch, Matthew P.; Rivera, Miguel N. .; Getz, Gad; Cahill, Daniel P.; Bernstein, Bradley E. .; Louis, David N.; Suva, Mario L.] Harvard Med Sch, Boston, MA 02114 USA.
   [Venteicher, Andrew S.; Patel, Anoop P.; Nahed, Brian V. .; Curry, William T.; Martuza, Robert L.; Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
   [Mount, Christopher; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Mount, Christopher; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
   [Mount, Christopher; Monje, Michelle] Stanford Univ, Sch Med, Dept Pediat & Pathol, Stanford, CA 94305 USA.
   [Filbin, Mariella G.; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
   [Filbin, Mariella G.; Golub, Todd R.] Childrens Hosp, Ctr Canc, Boston, MA 02215 USA.
   [Francis, Joshua M. .] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Golub, Todd R.; Regev, Aviv] MIT, Koch Inst, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Stanford University; Stanford University; Stanford University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Regev, A; Suvà, ML (corresponding author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.; Suvà, ML (corresponding author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Suvà, ML (corresponding author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.; Suvà, ML (corresponding author), Harvard Med Sch, Boston, MA 02114 USA.; Regev, A (corresponding author), MIT, Koch Inst, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
EM aregev@broadinstitute.org; suva.mario@mgh.harvard.edu
FU National Brain Tumor Society; Smith Family Foundation; NIH-NCI SPORE on brain cancer Career Enhancement Project and Developmental Research Project; Broad Institute Broadnext10 program; American Cancer Society; MGH department of Pathology; NIH [NS065743]; American Brain Tumor Association and Neurosurgery Research and Education Foundation; Human Frontier Science Program fellowship; Rothschild fellowship; Howard Hughes Medicine Institute; Klarman Cell Observatory, STARR cancer consortium, NCI [1U24CA180922]; Koch Institute Support from the National Cancer Institute [P30-CA14051]; Ludwig Center and the Broad Institute; California Institute of Regenerative Medicine (CIRM) [RB4-06093, RN3-06510]; Virginia and D.K. Ludwig Fund for Cancer Research;  [1S10RR023440-01A1]; National Cancer Institute [U24CA180922, P30CA014051] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R25NS065743] Funding Source: NIH RePORTER
NR 39
TC 846
Z9 1009
U1 1
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 309
EP +
DI 10.1038/nature20123
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500049
PM 27806376
DA 2026-03-09
ER

PT J
AU Shen, JR
   Bartlett, SD
   Zayed, A
   Allwood, AC
   Mazzolai, B
   Mattoli, V
   Minderer, M
   Harvey, CD
   Donato, F
   Moser, EI
   Miller, MC
   Williams, SL
AF Shen, Jian-Ren
   Bartlett, Stephen D.
   Zayed, Amro
   Allwood, Abigail C.
   Mazzolai, Barbara
   Mattoli, Virgilio
   Minderer, Matthias
   Harvey, Christopher D.
   Donato, Flavio
   Moser, Edvard I.
   Miller, M. Coleman
   Williams, Susan L.
TI RESOLUTION BEYOND THE DIFFRACTION LIMIT
SO NATURE
LA English
DT Article
NR 0
TC 0
Z9 0
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 536
EP 537
DI 10.1038/540536a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA VI4ZS
UT WOS:000491118000001
DA 2026-03-09
ER

PT J
AU Stanley, SA
   Kelly, L
   Latcha, KN
   Schmidt, SF
   Yu, XF
   Nectow, AR
   Sauer, J
   Dyke, JP
   Dordick, JS
   Friedman, JM
AF Stanley, Sarah A.
   Kelly, Leah
   Latcha, Kaamashri N.
   Schmidt, Sarah F.
   Yu, Xiaofei
   Nectow, Alexander R.
   Sauer, Jeremy
   Dyke, Jonathan P.
   Dordick, Jonathan S.
   Friedman, Jeffrey M.
TI Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism
SO NATURE
LA English
DT Article
ID glucose-homeostasis; brain; receptor; glucagon; key
AB Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1)(1). Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons(2). Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types.
C1 [Stanley, Sarah A.; Kelly, Leah; Latcha, Kaamashri N.; Schmidt, Sarah F.; Yu, Xiaofei; Nectow, Alexander R.; Friedman, Jeffrey M.] Rockefeller Univ, Lab Mol Genet, New York, NY 10065 USA.
   [Sauer, Jeremy; Dordick, Jonathan S.] Rensselaer Polytech Inst, Dept Chem & Biol Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
   [Dyke, Jonathan P.] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA.
   [Friedman, Jeffrey M.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Rockefeller University; Rensselaer Polytechnic Institute; Cornell University; Weill Cornell Medicine; Howard Hughes Medical Institute
RP Friedman, JM (corresponding author), Rockefeller Univ, Lab Mol Genet, New York, NY 10065 USA.; Friedman, JM (corresponding author), Howard Hughes Med Inst, New York, NY 10065 USA.
EM friedj@mail.rockefeller.edu
FU Howard Hughes Medical Institute; JPB Foundation; National Institutes of Health [GM095654, MH105941]; Rensselaer Fellowship under an NIH predoctoral training grant [GM067545]; Robertson Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK026687] Funding Source: NIH RePORTER
NR 29
TC 206
Z9 243
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 647
EP +
DI 10.1038/nature17183
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400040
PM 27007848
DA 2026-03-09
ER

PT J
AU Pillay, S
   Meyer, NL
   Puschnik, AS
   Davulcu, O
   Diep, J
   Ishikawa, Y
   Jae, LT
   Wosen, JE
   Nagamine, CM
   Chapman, MS
   Carette, JE
AF Pillay, S.
   Meyer, N. L.
   Puschnik, A. S.
   Davulcu, O.
   Diep, J.
   Ishikawa, Y.
   Jae, L. T.
   Wosen, J. E.
   Nagamine, C. M.
   Chapman, M. S.
   Carette, J. E.
TI An essential receptor for adeno-associated virus infection
SO NATURE
LA English
DT Article
ID growth-factor receptor; entry requires; gene-therapy; transduction; endocytosis; coreceptor; expression; transport; retromer; vectors
AB Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity(1). They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe(3). Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration(1,4), yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.
C1 [Pillay, S.; Puschnik, A. S.; Diep, J.; Wosen, J. E.; Carette, J. E.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, 299 Campus Dr, Stanford, CA 94305 USA.
   [Meyer, N. L.; Davulcu, O.; Ishikawa, Y.; Chapman, M. S.] Oregon Hlth & Sci Univ, Sch Med, Dept Biochem & Mol Biol, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA.
   [Ishikawa, Y.] Shriners Hosp Children, 3101 Sam Jackson Pk Rd, Portland, OR 97239 USA.
   [Jae, L. T.] Netherlands Canc Inst, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Nagamine, C. M.] Stanford Univ, Dept Comparat Med, Sch Med, 287 Campus Dr, Stanford, CA 94305 USA.
C3 Stanford University; Oregon Health & Science University; Netherlands Cancer Institute; Stanford University
RP Carette, JE (corresponding author), Stanford Univ, Dept Microbiol & Immunol, Sch Med, 299 Campus Dr, Stanford, CA 94305 USA.; Chapman, MS (corresponding author), Oregon Hlth & Sci Univ, Sch Med, Dept Biochem & Mol Biol, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM chapmami@ohsu.edu; carette@stanford.edu
FU NIH [R01 GM066875, DP2 AI104557, U19 AI109662]
CR Balazs AB, 2012, NATURE, V481, P81, DOI 10.1038/nature10660
   Beglova N, 2005, TRENDS BIOCHEM SCI, V30, P309, DOI 10.1016/j.tibs.2005.03.007
   BENJAMINI Y, 1995, J ROY STAT SOC B, V57, P289, DOI 10.1111/j.2517-6161.1995.tb02031.x
   Bhella D, 2015, PHILOS T R SOC B, V370, P0, DOI 10.1098/rstb.2014.0035
   Bonifacino JS, 2011, TRENDS CELL BIOL, V21, P159, DOI 10.1016/j.tcb.2010.11.003
   Campeau E, 2009, PLOS ONE, V4, P0, DOI 10.1371/journal.pone.0006529
   Carette JE, 2011, NATURE, V477, P340, DOI 10.1038/nature10348
   Ellis BL, 2013, VIROL J, V10, P0, DOI 10.1186/1743-422X-10-74
   Gaudet D, 2012, CURR OPIN LIPIDOL, V23, P310, DOI 10.1097/MOL.0b013e3283555a7e
   Ghosh P, 2003, NAT REV MOL CELL BIO, V4, P202, DOI 10.1038/nrm1050
   Hansen J, 2000, J VIROL, V74, P992, DOI 10.1128/JVI.74.2.992-996.2000
   Holster S, 2013, J BIOCH MOL BIOL POS, V2, P45
   Ibraghimov-Beskrovnaya O, 2000, HUM MOL GENET, V9, P1641, DOI 10.1093/hmg/9.11.1641
   Jae LT, 2014, SCIENCE, V344, P1506, DOI 10.1126/science.1252480
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   Kelly BT, 2011, CURR OPIN CELL BIOL, V23, P404, DOI 10.1016/j.ceb.2011.03.004
   Kotterman MA, 2014, NAT REV GENET, V15, P445, DOI 10.1038/nrg3742
   Lisowski L, 2014, NATURE, V506, P382, DOI 10.1038/nature12875
   Maxfield FR, 2004, NAT REV MOL CELL BIO, V5, P121, DOI 10.1038/nrm1315
   McGough IJ, 2011, TRAFFIC, V12, P963, DOI 10.1111/j.1600-0854.2011.01201.x
   Nathwani AC, 2011, NEW ENGL J MED, V365, P2357, DOI 10.1056/NEJMoa1108046
   Nonnenmacher M, 2012, GENE THER, V19, P649, DOI 10.1038/gt.2012.6
   Nonnenmacher M, 2011, CELL HOST MICROBE, V10, P563, DOI 10.1016/j.chom.2011.10.014
   Ohka S, 2004, J VIROL, V78, P7186, DOI 10.1128/JVI.78.13.7186-7198.2004
   Poelmans G, 2011, MOL PSYCHIATR, V16, P365, DOI 10.1038/mp.2010.105
   Qing K, 1999, NAT MED, V5, P71, DOI 10.1038/4758
   Ran FA, 2015, NATURE, V520, P186, DOI 10.1038/nature14299
   Ran FA, 2013, NAT PROTOC, V8, P2281, DOI 10.1038/nprot.2013.143
   Sanjana NE, 2012, NAT PROTOC, V7, P171, DOI 10.1038/nprot.2011.431
   Seaman MNJ, 2004, J CELL BIOL, V165, P111, DOI 10.1083/jcb.200312034
   Summerford C, 1998, J VIROL, V72, P1438, DOI 10.1128/JVI.72.2.1438-1445.1998
   Zincarelli C, 2008, MOL THER, V16, P1073, DOI 10.1038/mt.2008.76
NR 32
TC 393
Z9 539
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 108
EP +
DI 10.1038/nature16465
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500042
PM 26814968
DA 2026-03-09
ER

PT J
AU Kherdjemil, Y
   Lalonde, RL
   Sheth, R
   Dumouchel, A
   de Martino, G
   Pineault, KM
   Wellik, DM
   Stadler, HS
   Akimenko, MA
   Kmita, M
AF Kherdjemil, Yacine
   Lalonde, Robert L.
   Sheth, Rushikesh
   Dumouchel, Annie
   de Martino, Gemma
   Pineault, Kyriel M.
   Wellik, Deneen M.
   Stadler, H. Scott
   Akimenko, Marie-Andree
   Kmita, Marie
TI Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state
SO NATURE
LA English
DT Article
ID gene-expression; tetrapod limb; pectoral fin; origin; zebrafish; transcription; fish; conservation; appendages; mechanism
AB The fin-to-limb transition represents one of the major vertebrate morphological innovations associated with the transition from aquatic to terrestrial life and is an attractive model for gaining insights into the mechanisms of morphological diversity between species(1). One of the characteristic features of limbs is the presence of digits at their extremities. Although most tetrapods have limbs with five digits (pentadactyl limbs), palaeontological data indicate that digits emerged in lobed fins of early tetrapods, which were polydactylous(2). How the transition to pentadactyl limbs occurred remains unclear. Here we show that the mutually exclusive expression of the mouse genes Hoxa11 and Hoxa13, which were previously proposed to be involved in the origin of the tetrapod limb(1-6), is required for the pentadactyl state. We further demonstrate that the exclusion of Hoxa11 from the Hoxa13 domain relies on an enhancer that drives antisense transcription at the Hoxa11 locus after activation by HOXA13 and HOXD13. Finally, we show that the enhancer that drives antisense transcription of the mouse Hoxa11 gene is absent in zebrafish, which, together with the largely overlapping expression of hoxa11 and hoxa13 genes reported in fish(3-7), suggests that this enhancer emerged in the course of the fin-to-limb transition. On the basis of the polydactyly that we observed after expression of Hoxa11 in distal limbs, we propose that the evolution of Hoxa11 regulation contributed to the transition from polydactyl limbs in stem-group tetrapods to pentadactyl limbs in extant tetrapods.
C1 [Kherdjemil, Yacine; Sheth, Rushikesh; Dumouchel, Annie; de Martino, Gemma; Kmita, Marie] Clin Res Inst Montreal, Genet & Dev Res Unit, Montreal, PQ H2W 1R7, Canada.
   [Kherdjemil, Yacine; Kmita, Marie] Univ Montreal, Dept Med, Programme Biol Mol, Montreal, PQ H3T 1J4, Canada.
   [Lalonde, Robert L.; Akimenko, Marie-Andree] Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada.
   [Lalonde, Robert L.; Akimenko, Marie-Andree] Univ Ottawa, CAREG, Ottawa, ON K1N 6N5, Canada.
   [Pineault, Kyriel M.; Wellik, Deneen M.] Univ Michigan, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA.
   [Stadler, H. Scott] Shriners Hosp Children, Portland, OR 97239 USA.
   [Kmita, Marie] McGill Univ, Dept Expt Med, Montreal, PQ H3A 1A3, Canada.
   [de Martino, Gemma] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
C3 Institut de Recherche Clinique de Montreal (IRCM); Universite de Montreal; Universite de Montreal; University of Ottawa; University of Ottawa; University of Michigan System; University of Michigan; McGill University; McGill University
RP Kmita, M (corresponding author), Clin Res Inst Montreal, Genet & Dev Res Unit, Montreal, PQ H2W 1R7, Canada.; Kmita, M (corresponding author), Univ Montreal, Dept Med, Programme Biol Mol, Montreal, PQ H3T 1J4, Canada.; Kmita, M (corresponding author), McGill Univ, Dept Expt Med, Montreal, PQ H3A 1A3, Canada.
EM marie.kmita@ircm.qc.ca
FU Canadian Institute for Health Research [MOP-115127]; Canada Research Chair program [RCHS0192]; Natural Sciences and Engineering Research Council of Canada [155817-2012]; Shriners Hospital Research grant [85400]; Molecular Biology program of the Universite de Montreal; IRCM fellowship Michel-Belanger; Canadian Institute for Health Research; NIH NIAMS [AR061402]; NIH [T32 DE007057]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR061402] Funding Source: NIH RePORTER; National Institute of Dental and Craniofacial Research [T32DE007057] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020572] Funding Source: NIH RePORTER
NR 38
TC 57
Z9 67
U1 0
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 89
EP +
DI 10.1038/nature19813
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100035
PM 27706137
DA 2026-03-09
ER

PT J
AU Loayza-Puch, F
   Rooijers, K
   Buil, LCM
   Zijlstra, J
   Vrielink, JFO
   Lopes, R
   Ugalde, AP
   van Breugel, P
   Hofland, I
   Wesseling, J
   van Tellingen, O
   Bex, A
   Agami, R
AF Loayza-Puch, Fabricio
   Rooijers, Koos
   Buil, Levi C. M.
   Zijlstra, Jelle
   Vrielink, Joachim F. Oude
   Lopes, Rui
   Ugalde, Alejandro Pineiro
   van Breugel, Pieter
   Hofland, Ingrid
   Wesseling, Jelle
   van Tellingen, Olaf
   Bex, Axel
   Agami, Reuven
TI Tumour-specific proline vulnerability uncovered by differential ribosome codon reading
SO NATURE
LA English
DT Article
ID genome-wide analysis; reveals; translation; deprivation; alignment
AB Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive(1-4). In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia(5). However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling(6) for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production(7), suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment.
C1 [Loayza-Puch, Fabricio; Rooijers, Koos; Zijlstra, Jelle; Vrielink, Joachim F. Oude; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Agami, Reuven] Netherlands Canc Inst, Div Biol Stress Response, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Buil, Levi C. M.; van Tellingen, Olaf] Netherlands Canc Inst, Mouse Canc Clin, Dept Biopharmacol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Hofland, Ingrid] Netherlands Canc Inst, Core Facil Mol Pathol & Biobanking, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Wesseling, Jelle] Netherlands Canc Inst, Mol Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Bex, Axel] Netherlands Canc Inst, Dept Urol, Div Surg Oncol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Agami, Reuven] Erasmus Univ, Med Ctr, Dept Genet, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands.
C3 Netherlands Cancer Institute; Netherlands Cancer Institute; Netherlands Cancer Institute; Netherlands Cancer Institute; Netherlands Cancer Institute; Erasmus University Rotterdam; Erasmus MC
RP Agami, R (corresponding author), Netherlands Canc Inst, Div Biol Stress Response, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.; Agami, R (corresponding author), Erasmus Univ, Med Ctr, Dept Genet, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands.
EM r.agami@nki.nl
FU Human Frontier Science Program [LT000640/2013]; European Research Council [ERC-PoC EEG-CEC / EU665317]; Netherlands Organization for Scientific Research [NWO-VICI 918.11.601]; Dutch Cancer Society [KWF NKI-2013-5814]
NR 30
TC 215
Z9 250
U1 2
U2 60
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 490
EP +
DI 10.1038/nature16982
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800038
PM 26878238
DA 2026-03-09
ER

PT J
AU Huchard, E
   English, S
   Bell, MBV
   Thavarajah, N
   Clutton-Brock, T
AF Huchard, Elise
   English, Sinead
   Bell, Matt B. V.
   Thavarajah, Nathan
   Clutton-Brock, Tim
TI Competitive growth in a cooperative mammal
SO NATURE
LA English
DT Article
ID meerkats; female; size; dominance; dispersal
AB In many animal societies where hierarchies govern access to reproduction, the social rank of individuals is related to their age and weight(1-5) and slow-growing animals may lose their place in breeding queues to younger 'challengers' that grow faster(5,6). The threat of being displaced might be expected to favour the evolution of competitive growth strategies, where individuals increase their own rate of growth in response to increases in the growth of potential rivals. Although growth rates have been shown to vary in relation to changes in the social environment in several vertebrates including fish(2,3,7) and mammals(8), it is not yet known whether individuals increase their growth rates in response to increases in the growth of particular reproductive rivals. Here we show that, in wild Kalahari meerkats (Suricata suricatta), subordinates of both sexes respond to experimentally induced increases in the growth of same-sex rivals by raising their own growth rate and food intake. In addition, when individuals acquire dominant status, they show a secondary period of accelerated growth whose magnitude increases if the difference between their own weight and that of the heaviest subordinate of the same sex in their group is small. Our results show that individuals adjust their growth to the size of their closest competitor and raise the possibility that similar plastic responses to the risk of competition may occur in other social mammals, including domestic animals and primates.
C1 [Huchard, Elise; English, Sinead; Bell, Matt B. V.; Clutton-Brock, Tim] Univ Cambridge, Dept Zool, Large Anim Res Grp, Downing St, Cambridge CB2 3EJ, England.
   [Huchard, Elise] Univ Montpellier, CNRS, CEFE UMR 5175, 1919 Route Mende, F-34293 Montpellier 5, France.
   [Thavarajah, Nathan; Clutton-Brock, Tim] Univ Pretoria, Mammal Res Inst, Dept Zool & Entomol, ZA-0002 Pretoria, Gauteng, South Africa.
   [English, Sinead] Univ Cambridge, Dept Zool, Behav Ecol Grp, Downing St, Cambridge CB2 3EJ, England.
   [Bell, Matt B. V.] Univ Edinburgh, Inst Evolutionary Biol, W Mains Rd, Edinburgh EH9 3JT, Midlothian, Scotland.
C3 University of Cambridge; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Montpellier; University of Pretoria; University of Cambridge; University of Edinburgh
RP Huchard, E (corresponding author), Univ Cambridge, Dept Zool, Large Anim Res Grp, Downing St, Cambridge CB2 3EJ, England.; Huchard, E (corresponding author), Univ Montpellier, CNRS, CEFE UMR 5175, 1919 Route Mende, F-34293 Montpellier 5, France.
EM ehuchard@gmail.com
FU Animal Ethics Committee of the University of Pretoria [EC010-13]; University of Cambridge; University of Zurich; Natural Environment Research Council [NE/G006822/1]; European Research Council [294494]; Natural Environment Research Council [NE/G006822/1] Funding Source: researchfish; NERC [NE/G006822/1] Funding Source: UKRI
NR 28
TC 91
Z9 102
U1 1
U2 109
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 532
EP +
DI 10.1038/nature17986
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100040
PM 27225127
DA 2026-03-09
ER

PT J
AU Cinner, JE
   Huchery, C
   MacNeil, MA
   Graham, NAJ
   McClanahan, TR
   Maina, J
   Maire, E
   Kittinger, JN
   Hicks, CC
   Mora, C
   Allison, EH
   D'Agata, S
   Hoey, A
   Feary, DA
   Crowder, L
   Williams, ID
   Kulbicki, M
   Vigliola, L
   Wantiez, L
   Edgar, G
   Stuart-Smith, RD
   Sandin, SA
   Green, AL
   Hardt, MJ
   Beger, M
   Friedlander, A
   Campbell, SJ
   Holmes, KE
   Wilson, SK
   Brokovich, E
   Brooks, AJ
   Cruz-Motta, JJ
   Booth, DJ
   Chabanet, P
   Gough, C
   Tupper, M
   Ferse, SCA
   Sumaila, UR
   Mouillot, D
AF Cinner, Joshua E.
   Huchery, Cindy
   MacNeil, M. Aaron
   Graham, Nicholas A. J.
   McClanahan, Tim R.
   Maina, Joseph
   Maire, Eva
   Kittinger, John N.
   Hicks, Christina C.
   Mora, Camilo
   Allison, Edward H.
   D'Agata, Stephanie
   Hoey, Andrew
   Feary, David A.
   Crowder, Larry
   Williams, Ivor D.
   Kulbicki, Michel
   Vigliola, Laurent
   Wantiez, Laurent
   Edgar, Graham
   Stuart-Smith, Rick D.
   Sandin, Stuart A.
   Green, Alison L.
   Hardt, Marah J.
   Beger, Maria
   Friedlander, Alan
   Campbell, Stuart J.
   Holmes, Katherine E.
   Wilson, Shaun K.
   Brokovich, Eran
   Brooks, Andrew J.
   Cruz-Motta, Juan J.
   Booth, David J.
   Chabanet, Pascale
   Gough, Charlie
   Tupper, Mark
   Ferse, Sebastian C. A.
   Sumaila, U. Rashid
   Mouillot, David
TI Bright spots among the world's coral reefs
SO NATURE
LA English
DT Article
ID gravity; management; distance
AB Ongoing declines in the structure and function of the world's coral reefs(1,2) require novel approaches to sustain these ecosystems and the millions of people who depend on them(3). A presently unexplored approach that draws on theory and practice in human health and rural development(4,5) is to systematically identify and learn from the 'outliers'-places where ecosystems are substantially better ('bright spots') or worse ('dark spots') than expected, given the environmental conditions and socioeconomic drivers they are exposed to. Here we compile data from more than 2,500 reefs worldwide and develop a Bayesian hierarchical model to generate expectations of how standing stocks of reef fish biomass are related to 18 socioeconomic drivers and environmental conditions. We identify 15 bright spots and 35 dark spots among our global survey of coral reefs, defined as sites that have biomass levels more than two standard deviations from expectations. Importantly, bright spots are not simply comprised of remote areas with low fishing pressure; they include localities where human populations and use of ecosystem resources is high, potentially providing insights into how communities have successfully confronted strong drivers of change. Conversely, dark spots are not necessarily the sites with the lowest absolute biomass and even include some remote, uninhabited locations often considered near pristine(6). We surveyed local experts about social, institutional, and environmental conditions at these sites to reveal that bright spots are characterized by strong sociocultural institutions such as customary taboos and marine tenure, high levels of local engagement in management, high dependence on marine resources, and beneficial environmental conditions such as deep-water refuges. Alternatively, dark spots are characterized by intensive capture and storage technology and a recent history of environmental shocks. Our results suggest that investments in strengthening fisheries governance, particularly aspects such as participation and property rights, could facilitate innovative conservation actions that help communities defy expectations of global reef degradation.
C1 [Cinner, Joshua E.; Huchery, Cindy; MacNeil, M. Aaron; Graham, Nicholas A. J.; Maire, Eva; Hicks, Christina C.; Hoey, Andrew; Mouillot, David] James Cook Univ, Australian Res Council Ctr Excellence Coral Reef, Townsville, Qld 4811, Australia.
   [MacNeil, M. Aaron] Australian Inst Marine Sci, PMB 3, Townsville, Qld 4810, Australia.
   [MacNeil, M. Aaron] Dalhousie Univ, Dept Math & Stat, Halifax, NS B3H 3J5, Canada.
   [Graham, Nicholas A. J.; Hicks, Christina C.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [McClanahan, Tim R.; Maina, Joseph; D'Agata, Stephanie; Campbell, Stuart J.; Holmes, Katherine E.] Wildlife Conservat Soc, Global Marine Program, Bronx, NY 10460 USA.
   [Maina, Joseph; Beger, Maria] Univ Queensland, Ctr Biodivers & Conservat Sci, Australian Res Council Ctr Excellence Environm De, St Lucia, Qld 4074, Australia.
   [Maina, Joseph; D'Agata, Stephanie] Macquarie Univ, Dept Environm Sci, N Ryde, NSW 2109, Australia.
   [Maire, Eva; Mouillot, David] Univ Montpellier, IRD CNRS UM IFREMER, UMR 9190, MARBEC, F-34095 Montpellier, France.
   [Kittinger, John N.; Hicks, Christina C.; Crowder, Larry] Stanford Univ, Ctr Ocean Solut, Stanford, CA 94305 USA.
   [Kittinger, John N.] Conservat Int Hawaii Betty & Gordon Moore Ctr Sci, 7192 Kalaniana Ole Hwy,Suite G230, Honolulu, HI 96825 USA.
   [Mora, Camilo] Univ Hawaii Manoa, Dept Geog, Honolulu, HI 96822 USA.
   [Allison, Edward H.] Univ Washington, Sch Marine & Environm Affairs, Seattle, WA 98102 USA.
   [D'Agata, Stephanie; Vigliola, Laurent] Inst Res Dev, UMR IRD UR CNRS ENTROPIE, Lab Excellence LABEX CORAIL, BP A5, Noumea 98848, New Caledonia.
   [Feary, David A.] Univ Nottingham, Sch Life Sci, Ecol & Evolut Grp, Univ Pk, Nottingham NG7 2RD, England.
   [Williams, Ivor D.] NOAA Pacific Islands Fisheries Sci Ctr, Coral Reef Ecosyst Div, Honolulu, HI 96818 USA.
   [Kulbicki, Michel] Univ Perpignan, Labex Corail IRD, UMR Entropie, F-66000 Perpignan, France.
   [Wantiez, Laurent] Univ New Caledonia, LIVE EA4243, BPR4, Noumea 98851, New Caledonia.
   [Edgar, Graham; Stuart-Smith, Rick D.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas 7001, Australia.
   [Sandin, Stuart A.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Green, Alison L.] Nature Conservancy, Brisbane, Qld 4101, Australia.
   [Hardt, Marah J.] Future Fish, 7315 Wisconsin Ave,Suite 1000W, Bethesda, MD 20814 USA.
   [Friedlander, Alan] Univ Hawaii, Dept Biol, Fisheries Ecol Res Lab, Honolulu, HI 96822 USA.
   [Friedlander, Alan] Natl Geog Soc, Pristine Seas Program, 1145 17th St NW, Washington, DC 20036 USA.
   [Wilson, Shaun K.] Dept Pk & Wildlife, Perth, WA 6151, Australia.
   [Wilson, Shaun K.] Univ Western Australia, Oceans Inst, Crawley, WA 6009, Australia.
   [Brokovich, Eran] Israeli Soc Ecol & Environm Sci, Kehilat New York 19, Tel Aviv, Israel.
   [Brooks, Andrew J.] Univ Calif Santa Barbara, Inst Marine Sci, Santa Barbara, CA 93106 USA.
   [Cruz-Motta, Juan J.] Univ Puerto Rico, Recinto Univ Mayaguez, Dept Ciencias Marinas, San Juan, PR 00680 USA.
   [Booth, David J.] Univ Technol Sydney, Sch Life Sci, Sydney, NSW 2007, Australia.
   [Chabanet, Pascale] Inst Rech Dev, UMR ENTROPIE, Lab Excellence LABEX CORAIL, CS 41095, St Clothilde 97495, Reunion, France.
   [Gough, Charlie] Blue Ventures Conservat, 39-41 North Rd, London N7 9DP, England.
   [Tupper, Mark] Coastal Resources Assoc, St Joseph St, Surigao City 8400, Surigao Del Nor, Philippines.
   [Ferse, Sebastian C. A.] Leibniz Ctr Trop Marine Ecol ZMT, Fahrenheitstr 6, D-28359 Bremen, Germany.
   [Sumaila, U. Rashid] Univ British Columbia, Fisheries Econ Res Unit, 2202 Main Mall, Vancouver, BC V6T 1Z4, Canada.
C3 James Cook University; Australian Institute of Marine Science; Dalhousie University; Lancaster University; Wildlife Conservation Society; University of Queensland; Macquarie University; Ifremer; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Stanford University; University of Hawaii System; University of Hawaii Manoa; University of Washington; University of Washington Seattle; University of Nottingham; Universite Perpignan Via Domitia; Universite Nouvelle Caledonie; University of Tasmania; University of California System; University of California San Diego; Scripps Institution of Oceanography; Nature Conservancy; University of Hawaii System; National Geographic Society; University of Western Australia; University of California System; University of California Santa Barbara; University of Puerto Rico; University of Technology Sydney; Institut de Recherche pour le Developpement (IRD); Leibniz Association; Leibniz Zentrum fur Marine Tropenforschung (ZMT); University of British Columbia
RP Cinner, JE (corresponding author), James Cook Univ, Australian Res Council Ctr Excellence Coral Reef, Townsville, Qld 4811, Australia.
EM Joshua.cinner@jcu.edu.au
FU ARC Centre of Excellence for Coral Reef Studies, Stanford University; University of Montpellier; J.E.C.'s Pew Fellowship in Marine Conservation; ARC Australian Research Fellowship; Directorate For Geosciences [1236905] Funding Source: National Science Foundation; Division Of Ocean Sciences [1236905] Funding Source: National Science Foundation
NR 55
TC 427
Z9 489
U1 10
U2 353
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 416
EP +
DI 10.1038/nature18607
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200039
PM 27309809
DA 2026-03-09
ER

PT J
AU Kato, N
   Comer, E
   Sakata-Kato, T
   Sharma, A
   Sharma, M
   Maetani, M
   Bastien, J
   Brancucci, NM
   Bittker, JA
   Corey, V
   Clarke, D
   Derbyshire, ER
   Dornan, GL
   Duffy, S
   Eckley, S
   Itoe, MA
   Koolen, KMJ
   Lewis, TA
   Lui, PS
   Lukens, AK
   Lund, E
   March, S
   Meibalan, E
   Meier, BC
   McPhail, JA
   Mitasev, B
   Moss, EL
   Sayes, M
   Van Gessel, Y
   Wawer, MJ
   Yoshinaga, T
   Zeeman, AM
   Avery, VM
   Bhatia, SN
   Burke, JE
   Catteruccia, F
   Clardy, JC
   Clemons, PA
   Dechering, KJ
   Duvall, JR
   Foley, MA
   Gusovsky, F
   Kocken, CHM
   Marti, M
   Morningstar, ML
   Munoz, B
   Neafsey, DE
   Sharma, A
   Winzeler, EA
   Wirth, DF
   Scherer, CA
   Schreiber, SL
AF Kato, Nobutaka
   Comer, Eamon
   Sakata-Kato, Tomoyo
   Sharma, Arvind
   Sharma, Manmohan
   Maetani, Micah
   Bastien, Jessica
   Brancucci, Nicolas M.
   Bittker, Joshua A.
   Corey, Victoria
   Clarke, David
   Derbyshire, Emily R.
   Dornan, Gillian L.
   Duffy, Sandra
   Eckley, Sean
   Itoe, Maurice A.
   Koolen, Karin M. J.
   Lewis, Timothy A.
   Lui, Ping S.
   Lukens, Amanda K.
   Lund, Emily
   March, Sandra
   Meibalan, Elamaran
   Meier, Bennett C.
   McPhail, Jacob A.
   Mitasev, Branko
   Moss, Eli L.
   Sayes, Morgane
   Van Gessel, Yvonne
   Wawer, Mathias J.
   Yoshinaga, Takashi
   Zeeman, Anne-Marie
   Avery, Vicky M.
   Bhatia, Sangeeta N.
   Burke, John E.
   Catteruccia, Flaminia
   Clardy, Jon C.
   Clemons, Paul A.
   Dechering, Koen J.
   Duvall, Jeremy R.
   Foley, Michael A.
   Gusovsky, Fabian
   Kocken, Clemens H. M.
   Marti, Matthias
   Morningstar, Marshall L.
   Munoz, Benito
   Neafsey, Daniel E.
   Sharma, Amit
   Winzeler, Elizabeth A.
   Wirth, Dyann F.
   Scherer, Christina A.
   Schreiber, Stuart L.
TI Diversity-oriented synthesis yields novel multistage antimalarial inhibitors
SO NATURE
LA English
DT Article
ID transfer-rna synthetase; plasmodium-falciparum; drug discovery; hepatic stages; malaria; targets; model; assay; lead; identification
AB Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.
C1 [Kato, Nobutaka; Comer, Eamon; Maetani, Micah; Bastien, Jessica; Bittker, Joshua A.; Derbyshire, Emily R.; Lewis, Timothy A.; Lukens, Amanda K.; March, Sandra; Meier, Bennett C.; Moss, Eli L.; Sayes, Morgane; Wawer, Mathias J.; Bhatia, Sangeeta N.; Clardy, Jon C.; Clemons, Paul A.; Duvall, Jeremy R.; Foley, Michael A.; Morningstar, Marshall L.; Munoz, Benito; Neafsey, Daniel E.; Wirth, Dyann F.; Scherer, Christina A.; Schreiber, Stuart L.] Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.
   [Sakata-Kato, Tomoyo; Brancucci, Nicolas M.; Clarke, David; Itoe, Maurice A.; Lui, Ping S.; Lukens, Amanda K.; Lund, Emily; Meibalan, Elamaran; Catteruccia, Flaminia; Marti, Matthias; Wirth, Dyann F.] Harvard TH Chan Sch Publ Hlth, 665 Huntington Ave Boston, Boston, MA 02115 USA.
   [Sharma, Arvind; Sharma, Manmohan; Sharma, Amit] Int Ctr Genet Engn & Biotechnol, Mol Med Grp, Aruna Asaf Ali Rd, New Delhi 110067, India.
   [Maetani, Micah; Meier, Bennett C.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.
   [Corey, Victoria; Winzeler, Elizabeth A.] Univ Calif San Diego, Sch Med, 9500 Gilman Dr 0760, La Jolla, CA 92093 USA.
   [Derbyshire, Emily R.; Clardy, Jon C.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA.
   [Derbyshire, Emily R.] Duke Univ, Dept Chem, 124 Sci Dr, Durham, NC 27708 USA.
   [Derbyshire, Emily R.] Duke Univ, Dept Mol Genet & Microbiol, 124 Sci Dr, Durham, NC 27708 USA.
   [Dornan, Gillian L.; McPhail, Jacob A.; Burke, John E.] Univ Victoria, Dept Biochem & Microbiol, 270 Petch Hall, Victoria, BC V8P 5C2, Canada.
   [Duffy, Sandra; Avery, Vicky M.] Griffith Univ, Eskitis Inst Drug Discovery, Nathan Campus, Brisbane, Qld 4111, Australia.
   [Eckley, Sean; Mitasev, Branko; Van Gessel, Yvonne; Gusovsky, Fabian] Eisai Inc, 4 Corp Dr, Andover, MA 01810 USA.
   [Koolen, Karin M. J.; Dechering, Koen J.] TropIQ Hlth Sci, Geert Grootepl 28,Huispost 268, NL-6525 GA Nijmegen, Netherlands.
   [March, Sandra; Bhatia, Sangeeta N.] MIT, Dept Elect Engn & Comp Sci, 500 Main St, Cambridge, MA 02142 USA.
   [Yoshinaga, Takashi] Eisai & Co Ltd, 5-1-3 Tokodai, Tsukuba, Ibaraki 3002635, Japan.
   [Zeeman, Anne-Marie; Kocken, Clemens H. M.] Biochem Primate Res Ctr, Dept Parasitol, NL-2280 GH Rijswijk, Netherlands.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard T.H. Chan School of Public Health; Department of Biotechnology (DBT) India; International Center for Genetic Engineering & Biotechnology (ICGEB); International Center for Genetic Engineering & Biotechnology (ICGEB), New Delhi; Harvard University; University of California System; University of California San Diego; Harvard University; Harvard Medical School; Duke University; Duke University; University of Victoria; Griffith University; Eisai Co Ltd; Massachusetts Institute of Technology (MIT); Eisai Co Ltd
RP Schreiber, SL (corresponding author), Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.; Schreiber, SL (corresponding author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.
EM stuart_schreiber@harvard.edu
FU Bill and Melinda Gates Foundation [OPP1032518, OPP1054480, OPP1023607]; Global Health Innovative Technology Fund [G2014-107]; Medicines for Malaria Venture; Wellcome Trust [WT078285]; Canadian Institute of Health Research [FRN 142393]; Medicines for Malaria Venture [12-2400]; National Science Foundation [DGE1144152]; Bill and Melinda Gates Foundation [OPP1032518, OPP1023607] Funding Source: Bill and Melinda Gates Foundation; National Institute of General Medical Sciences [T32GM008666] Funding Source: NIH RePORTER
NR 72
TC 211
Z9 248
U1 0
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 344
EP +
DI 10.1038/nature19804
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100031
PM 27602946
DA 2026-03-09
ER

PT J
AU Hamann, E
   Gruber-Vodicka, H
   Kleiner, M
   Tegetmeyer, HE
   Riedel, D
   Littmann, S
   Chen, JW
   Milucka, J
   Viehweger, B
   Becker, KW
   Dong, XL
   Stairs, CW
   Hinrichs, KU
   Brown, MW
   Roger, AJ
   Strous, M
AF Hamann, Emmo
   Gruber-Vodicka, Harald
   Kleiner, Manuel
   Tegetmeyer, Halina E.
   Riedel, Dietmar
   Littmann, Sten
   Chen, Jianwei
   Milucka, Jana
   Viehweger, Bernhard
   Becker, Kevin W.
   Dong, Xiaoli
   Stairs, Courtney W.
   Hinrichs, Kai-Uwe
   Brown, Matthew W.
   Roger, Andrew J.
   Strous, Marc
TI Environmental Breviatea harbour mutualistic Arcobacter epibionts
SO NATURE
LA English
DT Article
ID shotgun proteomics; read alignment; genome reveals; protein; identification; improvements; physiology; algorithm; abundance; invasion
AB Breviatea form a lineage of free living, unicellular protists, distantly related to animals and fungi(1,2). This lineage emerged almost one billion years ago, when the oceanic oxygen content was low, and extant Breviatea have evolved or retained an anaerobic lifestyle(3,4). Here we report the cultivation of Lenisia limosa, gen. et sp. nov., a newly discovered breviate colonized by relatives of animal-associated Arcobacter. Physiological experiments show that the association of L. limosa with Arcobacter is driven by the transfer of hydrogen and is mutualistic, providing benefits to both partners. With whole-genome sequencing and differential proteomics, we show that an experimentally observed fitness gain of L. limosa could be explained by the activity of a so far unknown type of NAD(P) H-accepting hydrogenase, which is expressed in the presence, but not in the absence, of Arcobacter. Differential proteomics further reveal that the presence of Lenisia stimulates expression of known 'virulence' factors by Arcobacter. These proteins typically enable colonization of animal cells during infection(5), but may in the present case act for mutual benefit. Finally, re-investigation of two currently available transcriptomic data sets of other Breviatea(4) reveals the presence and activity of related hydrogen-consuming Arcobacter, indicating that mutualistic interaction between these two groups of microbes might be pervasive. Our results support the notion that molecular mechanisms involved in virulence can also support mutualism(6), as shown here for Arcobacter and Breviatea.
C1 [Hamann, Emmo; Tegetmeyer, Halina E.; Chen, Jianwei; Strous, Marc] Max Planck Inst Marine Microbiol, Microbial Fitness Grp, Celsiusstr 1, D-28359 Bremen, Germany.
   [Hamann, Emmo; Kleiner, Manuel; Chen, Jianwei; Dong, Xiaoli; Strous, Marc] Univ Calgary, Dept Geosci, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.
   [Gruber-Vodicka, Harald] Max Planck Inst Marine Microbiol, Symbiosis Dept, Celsiusstr 1, D-28359 Bremen, Germany.
   [Tegetmeyer, Halina E.; Strous, Marc] Univ Bielefeld, Inst Genome Res & Syst Biol, Ctr Biotechnol, Univ Str 25, D-3615 Bielefeld, Germany.
   [Riedel, Dietmar] Max Planck Inst Biophys Chem, Fassberg 11, D-37077 Gottingen, Germany.
   [Littmann, Sten; Milucka, Jana] Max Planck Inst Marine Microbiol, Biogeochem Dept, Celsiusstr 1, D-28359 Bremen, Germany.
   [Viehweger, Bernhard; Becker, Kevin W.; Hinrichs, Kai-Uwe] Univ Bremen, MARUM Ctr Marine Environm Sci, Bibliothekstr 1, D-28359 Bremen, Germany.
   [Roger, Andrew J.] Dalhousie Univ, Dept Biochem & Mol Biol, Ctr Comparat Genom & Evolutionary Bioinformat, 6299 South St, Halifax, NS B3H 4R2, Canada.
   [Brown, Matthew W.] Mississippi State Univ, Dept Biol Sci, Mississippi State, MS 39762 USA.
C3 Max Planck Society; University of Calgary; Max Planck Society; University of Bielefeld; Max Planck Society; Max Planck Society; University of Bremen; Dalhousie University; Mississippi State University
RP Hamann, E; Strous, M (corresponding author), Max Planck Inst Marine Microbiol, Microbial Fitness Grp, Celsiusstr 1, D-28359 Bremen, Germany.; Hamann, E; Strous, M (corresponding author), Univ Calgary, Dept Geosci, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.; Strous, M (corresponding author), Univ Bielefeld, Inst Genome Res & Syst Biol, Ctr Biotechnol, Univ Str 25, D-3615 Bielefeld, Germany.
EM emmohamann@gmail.com; mstrous@ucalgary.ca
FU European Research Council [MASEM 242635]; Campus Alberta Innovation Chair Program; Canadian Foundation for Innovation; Alberta Small Equipment Grant Program; German Federal State Nordrhein-Westfalen; Max Planck Society; Natural Sciences and Engineering Research Council of Canada; National Institute of General Medical Sciences [P20GM103476] Funding Source: NIH RePORTER
NR 50
TC 63
Z9 65
U1 2
U2 53
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 254
EP +
DI 10.1038/nature18297
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100042
PM 27279223
DA 2026-03-09
ER

PT J
AU Petroutsos, D
   Tokutsu, R
   Maruyama, S
   Flori, S
   Greiner, A
   Magneschi, L
   Cusant, L
   Kottke, T
   Mittag, M
   Hegemann, P
   Finazzi, G
   Minagawa, J
AF Petroutsos, Dimitris
   Tokutsu, Ryutaro
   Maruyama, Shinichiro
   Flori, Serena
   Greiner, Andre
   Magneschi, Leonardo
   Cusant, Loic
   Kottke, Tilman
   Mittag, Maria
   Hegemann, Peter
   Finazzi, Giovanni
   Minagawa, Jun
TI A blue-light photoreceptor mediates the feedback regulation of photosynthesis
SO NATURE
LA English
DT Article
ID electron-transport; energy-dissipation; messenger-rna; chlamydomonas; protein; phosphorylation; evolution; identification; supercomplex; chlorophyll
AB In plants and algae, light serves both as the energy source for photosynthesis and a biological signal that triggers cellular responses via specific sensory photoreceptors. Red light is perceived by bilin-containing phytochromes and blue light by the flavincontaining cryptochromes and/or phototropins (PHOTs)(1), the latter containing two photosensory light, oxygen, or voltage (LOV) domains2. Photoperception spans several orders of light intensity(3), ranging from far below the threshold for photosynthesis to values beyond the capacity of photosynthetic CO2 assimilation. Excess light may cause oxidative damage and cell death, processes prevented by enhanced thermal dissipation via high-energy quenching (qE), a key photoprotective response(4). Here we show the existence of a molecular link between photoreception, photosynthesis, and photoprotection in the green alga Chlamydomonas reinhardtii. We show that PHOT controls qE by inducing the expression of the qE effector protein LHCSR3 (light-harvesting complex stress-related protein 3) in high light intensities. This control requires blue-light perception by LOV domains on PHOT, LHCSR3 induction through PHOT kinase, and light dissipation in photosystem II via LHCSR3. Mutants deficient in the PHOT gene display severely reduced fitness under excessive light conditions, indicating that the sensing, utilization, and dissipation of light is a concerted process that plays a vital role in microalgal acclimation to environments of variable light intensities.
C1 [Petroutsos, Dimitris; Flori, Serena; Magneschi, Leonardo; Cusant, Loic; Finazzi, Giovanni] Univ Grenoble Alpes, CEA Grenoble,Commissariat Energie Atom & Energies, Inst Natl Rech Agron,Inst Biosci & Biotechnol Gre, Lab Physiol Cellulaire & Vegetale,CNRS,UMR 5168, F-38054 Grenoble 9, France.
   [Tokutsu, Ryutaro; Minagawa, Jun] Natl Inst Basic Biol, Div Environm Photobiol, Nishigonaka 38, Okazaki, Aichi 4448585, Japan.
   [Tokutsu, Ryutaro; Minagawa, Jun] Grad Univ Adv Studies, Sch Life Sci, Dept Basic Biol, Okazaki, Aichi 4448585, Japan.
   [Tokutsu, Ryutaro; Minagawa, Jun] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan.
   [Maruyama, Shinichiro] Tohoku Univ, Grad Sch Life Sci, Dept Environm Life Sci, Sendai, Miyagi 9808578, Japan.
   [Greiner, Andre; Hegemann, Peter] Humboldt Univ, Inst Biol, Expt Biophys, Invalidenstr 42, D-10115 Berlin, Germany.
   [Magneschi, Leonardo] Univ Munster, Inst Plant Biol & Biotechnol, D-48143 Munster, Germany.
   [Kottke, Tilman] Univ Bielefeld, Phys & Biophys Chem, D-33615 Bielefeld, Germany.
   [Mittag, Maria] Univ Jena, Inst Gen Bot & Plant Physiol, D-07743 Jena, Germany.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); INRAE; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB); Graduate University for Advanced Studies - Japan; Japan Science & Technology Agency (JST); Tohoku University; Humboldt University of Berlin; University of Munster; University of Bielefeld; Friedrich Schiller University of Jena
RP Petroutsos, D; Finazzi, G (corresponding author), Univ Grenoble Alpes, CEA Grenoble,Commissariat Energie Atom & Energies, Inst Natl Rech Agron,Inst Biosci & Biotechnol Gre, Lab Physiol Cellulaire & Vegetale,CNRS,UMR 5168, F-38054 Grenoble 9, France.; Minagawa, J (corresponding author), Natl Inst Basic Biol, Div Environm Photobiol, Nishigonaka 38, Okazaki, Aichi 4448585, Japan.; Minagawa, J (corresponding author), Grad Univ Adv Studies, Sch Life Sci, Dept Basic Biol, Okazaki, Aichi 4448585, Japan.; Minagawa, J (corresponding author), Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan.
EM dimitris.petroutsos@cea.fr; giovanni.finazzi@cea.fr; minagawa@nibb.ac.jp
FU Agence Nationale de la Recherche [ANR-12-BIME-0005, ANR-10-LABX-49-01]; Marie Curie Initial Training Network Accliphot [316427]; CNRS Defi (ENRS); CEA Bioenergies program; HFSP [HFSP0052]; NIBB Cooperative Research Program for the Okazaki Large Spectrograph [13-514, 14-508, 15-609, 16-705]; JSPS KAKENHI [JP15H05599, JP26251033, JP16H06553]; NEDO [P07015]; MEXT (through the Network of Centres of Carbon Dioxide Resource Studies in Plants); German Research Foundation, DFG [FOR1261]; Heisenberg fellowship; Alexander von Humboldt Stiftung/Foundation; Grants-in-Aid for Scientific Research [15H05599, 16H06553, 15K18562, 26251033] Funding Source: KAKEN; Agence Nationale de la Recherche (ANR) [ANR-12-BIME-0005] Funding Source: Agence Nationale de la Recherche (ANR)
NR 42
TC 190
Z9 213
U1 9
U2 405
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 563
EP +
DI 10.1038/nature19358
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900059
PM 27626383
DA 2026-03-09
ER

PT J
AU Pontzer, H
   Brown, MH
   Raichlen, DA
   Dunsworth, H
   Hare, B
   Walker, K
   Luke, A
   Dugas, LR
   Durazo-Arvizu, R
   Schoeller, D
   Plange-Rhule, J
   Bovet, P
   Forrester, TE
   Lambert, EV
   Thompson, ME
   Shumaker, RW
   Ross, SR
AF Pontzer, Herman
   Brown, Mary H.
   Raichlen, David A.
   Dunsworth, Holly
   Hare, Brian
   Walker, Kara
   Luke, Amy
   Dugas, Lara R.
   Durazo-Arvizu, Ramon
   Schoeller, Dale
   Plange-Rhule, Jacob
   Bovet, Pascal
   Forrester, Terrence E.
   Lambert, Estelle V.
   Thompson, Melissa Emery
   Shumaker, Robert W.
   Ross, Stephen R.
TI Metabolic acceleration and the evolution of human brain size and life history
SO NATURE
LA English
DT Article
ID total-energy expenditure; respiratory metabolism; adaptation; energetics
AB Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity(1). This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.
C1 [Pontzer, Herman] CUNY Hunter Coll, Dept Anthropol, 695 Pk Ave, New York, NY 10065 USA.
   [Pontzer, Herman] New York Consortium Evolutionary Primatol, New York, NY 10065 USA.
   [Brown, Mary H.; Ross, Stephen R.] Lincoln Pk Zoo, Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL 60614 USA.
   [Raichlen, David A.] Univ Arizona, Sch Anthropol, 1099 E South Campus Dr, Tucson, AZ 85716 USA.
   [Dunsworth, Holly] Univ Rhode Isl, Dept Sociol & Anthropol, 45 Upper Coll Rd, Kingston, RI 02881 USA.
   [Hare, Brian; Walker, Kara] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA.
   [Luke, Amy; Dugas, Lara R.; Durazo-Arvizu, Ramon] Loyola Univ Chicago, Stritch Sch Med, Publ Hlth Sci, 2160 South First Ave, Maywood, IL 60153 USA.
   [Schoeller, Dale] Univ Wisconsin, Nutr Sci Biotechnol Ctr, 425 Henry Mall, Madison, WI 53705 USA.
   [Plange-Rhule, Jacob] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ghana.
   [Bovet, Pascal] Univ Lausanne Hosp, Inst Social & Prevent Med, Rue Corniche 10, CH-1010 Lausanne, Switzerland.
   [Bovet, Pascal] Minist Hlth, POB 52, Victoria, Mahe, Seychelles.
   [Forrester, Terrence E.] Univ W Indies, UWI Solut Developing Countries, 25 West Rd,UWI Mona Campus, Kingston 7, Jamaica.
   [Lambert, Estelle V.] Univ Cape Town, Res Unit Exercise Sci & Sports Med, POB 115, ZA-7725 Cape Town, South Africa.
   [Thompson, Melissa Emery] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA.
   [Shumaker, Robert W.] Indianapolis Zoo, 1200 W Washington St, Indianapolis, IN 46222 USA.
   [Shumaker, Robert W.] Indiana Univ, Dept Anthropol, 701 E Kirkwood Ave, Bloomington, IN 47405 USA.
   [Shumaker, Robert W.] Indiana Univ, Ctr Integrated Study Anim Behav, 701 E Kirkwood Ave, Bloomington, IN 47405 USA.
   [Shumaker, Robert W.] George Mason Univ, Krasnow Inst Adv Study, 4400 Univ Dr, Fairfax, VA 22030 USA.
C3 City University of New York (CUNY) System; Hunter College (CUNY); University of Arizona; University of Rhode Island; Duke University; Loyola University Chicago; University of Wisconsin System; University of Wisconsin Madison; Kwame Nkrumah University Science & Technology; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University West Indies Mona Jamaica; University of Cape Town; University of New Mexico; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; George Mason University
RP Pontzer, H (corresponding author), CUNY Hunter Coll, Dept Anthropol, 695 Pk Ave, New York, NY 10065 USA.
EM hpontzer@hunter.cuny.edu
FU US National Science Foundation [BCS-1317170]; National Institutes of Health [R01DK080763]; L.S.B. Leakey Foundation; Wenner-Gren Foundation [Gr. 8670]; University of Arizona; Hunter College
NR 27
TC 202
Z9 245
U1 7
U2 260
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 390
EP +
DI 10.1038/nature17654
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300047
PM 27144364
DA 2026-03-09
ER

PT J
AU Roux, S
   Brum, JR
   Dutilh, BE
   Sunagawa, S
   Duhaime, MB
   Loy, A
   Poulos, BT
   Solonenko, N
   Lara, E
   Poulain, J
   Pesant, S
   Kandels-Lewis, S
   Dimier, C
   Picheral, M
   Searson, S
   Cruaud, C
   Alberti, A
   Duarte, CM
   Gasol, JM
   Vaqué, D
   Bork, P
   Acinas, SG
   Wincker, P
   Sullivan, MB
AF Roux, Simon
   Brum, Jennifer R.
   Dutilh, Bas E.
   Sunagawa, Shinichi
   Duhaime, Melissa B.
   Loy, Alexander
   Poulos, Bonnie T.
   Solonenko, Natalie
   Lara, Elena
   Poulain, Julie
   Pesant, Stephane
   Kandels-Lewis, Stefanie
   Dimier, Celine
   Picheral, Marc
   Searson, Sarah
   Cruaud, Corinne
   Alberti, Adriana
   Duarte, Carlos M.
   Gasol, Josep M.
   Vaque, Dolors
   Bork, Peer
   Acinas, Silvia G.
   Wincker, Patrick
   Sullivan, Matthew B.
TI Ecogenomics and potential biogeochemical impacts of globally abundant ocean viruses
SO NATURE
LA English
DT Article
ID signal-transduction proteins; genome sequences; interactive tree; marine virus; phage; bacteriophage; alignment; tool; recognition; diversity
AB Ocean microbes drive biogeochemical cycling on a global scale(1). However, this cycling is constrained by viruses that affect community composition, metabolic activity, and evolutionary trajectories(2,3). Owing to challenges with the sampling and cultivation of viruses, genome-level viral diversity remains poorly described and grossly understudied, with less than 1% of observed surface-ocean viruses known(4). Here we assemble complete genomes and large genomic fragments from both surface-and deep-ocean viruses sampled during the Tara Oceans and Malaspina research expeditions(5,6), and analyse the resulting 'global ocean virome' dataset to present a global map of abundant, double-stranded DNA viruses complete with genomic and ecological contexts. A total of 15,222 epipelagic and mesopelagic viral populations were identified, comprising 867 viral clusters (defined as approximately genus-level groups(7,8)). This roughly triples the number of known ocean viral populations(4) and doubles the number of candidate bacterial and archaeal virus genera(8), providing a near-complete sampling of epipelagic communities at both the population and viral-cluster level. We found that 38 of the 867 viral clusters were locally or globally abundant, together accounting for nearly half of the viral populations in any global ocean virome sample. While two-thirds of these clusters represent newly described viruses lacking any cultivated representative, most could be computationally linked to dominant, ecologically relevant microbial hosts. Moreover, we identified 243 viral-encoded auxiliary metabolic genes, of which only 95 were previously known. Deeper analyses of four of these auxiliary metabolic genes (dsrC, soxYZ, P-II (also known as glnB) and amoC) revealed that abundant viruses may directly manipulate sulfur and nitrogen cycling throughout the epipelagic ocean. This viral catalog and functional analyses provide a necessary foundation for the meaningful integration of viruses into ecosystem models where they act as key players in nutrient cycling and trophic networks.
C1 [Roux, Simon; Brum, Jennifer R.; Sullivan, Matthew B.] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.
   [Dutilh, Bas E.] Univ Utrecht, Theoret Biol & Bioinformat, NL-3584 CH Utrecht, Netherlands.
   [Dutilh, Bas E.] Radboud Univ Nijmegen Med Ctr, Ctr Mol & Biomol Informat, NL-6525 GA Nijmegen, Netherlands.
   [Dutilh, Bas E.] Univ Fed Rio de Janeiro, Dept Marine Biol, BR-21941902 Rio De Janeiro, Brazil.
   [Sunagawa, Shinichi; Kandels-Lewis, Stefanie; Bork, Peer] European Mol Biol Lab, Struct & Computat Biol, D-69117 Heidelberg, Germany.
   [Duhaime, Melissa B.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [Loy, Alexander] Univ Vienna, Div Microbial Ecol, Dept Microbiol & Ecosyst Sci, Res Network Chem Meets Microbiol, Waehringer Guertel 18, A-1090 Vienna, Austria.
   [Loy, Alexander] Austrian Polar Res Inst, A-1090 Vienna, Austria.
   [Poulos, Bonnie T.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [Lara, Elena; Gasol, Josep M.; Vaque, Dolors; Acinas, Silvia G.] CSIC, ICM, Dept Marine Biol & Oceanog, E-0800 Barcelona, Spain.
   [Lara, Elena] CNR, Inst Marine Sci CNR ISMAR, I-30122 Venice, Italy.
   [Poulain, Julie; Cruaud, Corinne; Alberti, Adriana; Wincker, Patrick] GENOSCOPE, CEA Inst Genom, F-91057 Evry, France.
   [Pesant, Stephane] Univ Bremen, Data Publisher Earth & Environm Sci, PANGAEA, D-28359 Bremen, Germany.
   [Pesant, Stephane] Univ Bremen, MARUM, D-28359 Bremen, Germany.
   [Kandels-Lewis, Stefanie] European Mol Biol Lab, Directors Res, D-69117 Heidelberg, Germany.
   [Dimier, Celine] CNRS, UMR 7144, EPEP, Stn Biol Roscoff, F-29680 Roscoff, France.
   [Dimier, Celine] Univ Paris 06, Sorbonne Univ, UMR 7144, Stn Biol Roscoff, F-29680 Roscoff, France.
   [Dimier, Celine] Paris Sci & Lettres Res Univ, Ecole Normale Super, Inst Biol, CNRS,INSERM,UMR 8197,U1024, F-75005 Paris, France.
   [Picheral, Marc; Searson, Sarah] Observ Oceanol, Lab Oceanog Villefranche, CNRS, UMR 7093, F-06230 Villefranche Sur Mer, France.
   [Picheral, Marc; Searson, Sarah] Univ Paris 06, Sorbonne Univ, Observ Oceanol, UMR 7093, F-06230 Villefranche Sur Mer, France.
   [Duarte, Carlos M.] CSIC UiB, Mediterranean Inst Adv Studies, Mallorca 2107190, Spain.
   [Duarte, Carlos M.] King Abdullah Univ Sci & Technol, Red Sea Res Ctr, Thuwal 239556900, Saudi Arabia.
   [Bork, Peer] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
   [Wincker, Patrick] CNRS, UMR 8030, F-91057 Evry, France.
   [Wincker, Patrick] Univ Evry, UMR 8030, F-91057 Evry, France.
   [Sullivan, Matthew B.] Ohio State Univ, Dept Civil Environm & Geodet Engn, Columbus, OH 43210 USA.
   [Sunagawa, Shinichi] ETH, Inst Microbiol, Dept Biol, CH-8093 Zurich, Switzerland.
C3 University System of Ohio; Ohio State University; Utrecht University; Radboud University Nijmegen; Universidade Federal do Rio de Janeiro; European Molecular Biology Laboratory (EMBL); University of Michigan System; University of Michigan; University of Vienna; University of Arizona; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienze Marine (ISMAR-CNR); CEA; Universite Paris Saclay; University of Bremen; University of Bremen; European Molecular Biology Laboratory (EMBL); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Consejo Superior de Investigaciones Cientificas (CSIC); ATTITUS Educacao; University of Barcelona; King Abdullah University of Science & Technology; Helmholtz Association; Max Delbruck Center for Molecular Medicine; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); University System of Ohio; Ohio State University; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Sullivan, MB (corresponding author), Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.; Sullivan, MB (corresponding author), Ohio State Univ, Dept Civil Environm & Geodet Engn, Columbus, OH 43210 USA.
EM mbsulli@gmail.com
FU National Science Foundation [1536989]; Gordon and Betty Moore Foundation [3790, 2631]; French Ministry of Research and Government through the 'Investissements d'Avene' program OCEANOMICS [ANR-11-BTBR-0008]; France Genomique [ANR-10-INBS-09-08]; Water, Environmental and Energy Solutions Initiative; Ecosystem Genomics Institute; Netherlands Organization for Scientific Research Vidi [864.14.004]; CAPES, BRASIL; Austrian Science Fund [P25111-B22]; Austrian Science Fund (FWF) [P25111] Funding Source: Austrian Science Fund (FWF); Grants-in-Aid for Scientific Research [16KT0020] Funding Source: KAKEN; Directorate For Geosciences; Division Of Ocean Sciences [1536989] Funding Source: National Science Foundation; Austrian Science Fund (FWF) [P 25111] Funding Source: researchfish
NR 85
TC 600
Z9 696
U1 20
U2 599
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 689
EP +
DI 10.1038/nature19366
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700052
PM 27654921
DA 2026-03-09
ER

PT J
AU Patil, DP
   Chen, CK
   Pickering, BF
   Chow, A
   Jackson, C
   Guttman, M
   Jaffrey, SR
AF Patil, Deepak P.
   Chen, Chun-Kan
   Pickering, Brian F.
   Chow, Amy
   Jackson, Constanza
   Guttman, Mitchell
   Jaffrey, Samie R.
TI m6A RNA methylation promotes XIST-mediated transcriptional repression
SO NATURE
LA English
DT Article
ID x-chromosome inactivation; messenger-rna; nucleotide-resolution; protein interactions; nuclear-rna; reveals; interacts; n-6-methyladenosine; n6-methyladenosine; methyltransferase
AB The long non-coding RNA X-inactive specific transcript (XIST) mediates the transcriptional silencing of genes on the X chromosome. Here we show that, in human cells, XIST is highly methylated with at least 78 N-6-methyladenosine (m(6)A) residues-a reversible base modification of unknown function in long non-coding RNAs. We show that m(6)A formation in XIST, as well as in cellular mRNAs, is mediated by RNA-binding motif protein 15 (RBM15) and its paralogue RBM15B, which bind the m(6)A-methylation complex and recruit it to specific sites in RNA. This results in the methylation of adenosine nucleotides in adjacent m(6)A consensus motifs. Furthermore, we show that knockdown of RBM15 and RBM15B, or knockdown of methyltransferase like 3 (METTL3), an m(6)A methyltransferase, impairs XIST-mediated gene silencing. A systematic comparison of m(6)A-binding proteins shows that YTH domain containing 1 (YTHDC1) preferentially recognizes m(6)A residues on XIST and is required for XIST function. Additionally, artificial tethering of YTHDC1 to XIST rescues XIST-mediated silencing upon loss of m(6)A. These data reveal a pathway of m(6)A formation and recognition required for XIST-mediated transcriptional repression.
C1 [Patil, Deepak P.; Pickering, Brian F.; Jaffrey, Samie R.] Cornell Univ, Dept Pharmacol, Weill Cornell Med Coll, New York, NY 10065 USA.
   [Chen, Chun-Kan; Chow, Amy; Jackson, Constanza; Guttman, Mitchell] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
C3 Cornell University; Weill Cornell Medicine; California Institute of Technology
RP Jaffrey, SR (corresponding author), Cornell Univ, Dept Pharmacol, Weill Cornell Med Coll, New York, NY 10065 USA.
EM srj2003@med.cornell.edu
FU NIH [R01CA186702, T32CA062948, T32GM07616, DP5OD012190]; Rose Hills Foundation; Edward Mallinckrodt Foundation; Sontag Foundation; Searle Scholars Program; Pew-Stewart Scholars program; California Institute of Technology; National Cancer Institute [T32CA062948, R01CA186702] Funding Source: NIH RePORTER
NR 52
TC 1442
Z9 1680
U1 3
U2 274
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 369
EP +
DI 10.1038/nature19342
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000047
PM 27602518
DA 2026-03-09
ER

PT J
AU Roop, JI
   Chang, KC
   Brem, RB
AF Roop, Jeremy I.
   Chang, Kyu Chul
   Brem, Rachel B.
TI Polygenic evolution of a sugar specialization trade-off in yeast
SO NATURE
LA English
DT Article
ID saccharomyces; adaptation; drosophila; genetics; genomics; system; dna
AB The evolution of novel traits can involve many mutations scattered throughout the genome(1,2). Detecting and validating such a suite of alleles, particularly if they arose long ago, remains a key challenge in evolutionary genetics(1-3). Here we dissect an evolutionary trade-off of unprecedented genetic complexity between long-diverged species. When cultured in 1% glucose medium supplemented with galactose, Saccharomyces cerevisiae, but not S. bayanus or other Saccharomyces species, delayed commitment to galactose metabolism until glucose was exhausted. Promoters of seven galactose (GAL) metabolic genes from S. cerevisiae, when introduced together into S. bayanus, largely recapitulated the delay phenotype in 1% glucose-galactose medium, and most had partial effects when tested in isolation. Variation in GAL coding regions also contributed to the delay when tested individually in 1% glucose-galactose medium. When combined, S. cerevisiae GAL coding regions gave rise to profound growth defects in the S. bayanus background. In medium containing 2.5% glucose supplemented with galactose, wild-type S. cerevisiae repressed GAL gene expression and had a robust growth advantage relative to S. bayanus; transgenesis of S. cerevisiae GAL promoter alleles or GAL coding regions was sufficient for partial reconstruction of these phenotypes. S. cerevisiae GAL genes thus encode a regulatory program of slow induction and avid repression, and a fitness detriment during the glucose-galactose transition but a benefit when glucose is in excess. Together, these results make clear that genetic mapping of complex phenotypes is within reach, even in deeply diverged species.
C1 [Roop, Jeremy I.; Brem, Rachel B.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Chang, Kyu Chul] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
   [Chang, Kyu Chul; Brem, Rachel B.] Buck Inst Res Aging, Novato, CA 94945 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; Buck Institute for Research on Aging
RP Brem, RB (corresponding author), Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.; Brem, RB (corresponding author), Buck Inst Res Aging, Novato, CA 94945 USA.
EM rbrem@buckinstitute.org
FU NIGMS NIH HHS [R01 GM087432, GM087432] Funding Source: Medline
NR 26
TC 52
Z9 61
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 336
EP +
DI 10.1038/nature16938
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100037
PM 26863195
DA 2026-03-09
ER

PT J
AU Nguyen, THD
   Galej, WP
   Bai, XC
   Oubridge, C
   Newman, AJ
   Scheres, SHW
   Nagai, K
AF Thi Hoang Duong Nguyen
   Galej, Wojciech P.
   Bai, Xiao-chen
   Oubridge, Chris
   Newman, Andrew J.
   Scheres, Sjors H. W.
   Nagai, Kiyoshi
TI Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution
SO NATURE
LA English
DT Article
ID pre-messenger-rna; group-ii intron; u5 snrnp; splicing factor; saccharomyces-cerevisiae; spliceosome activation; crystal-structure; active-site; electron cryomicroscopy; conformational-changes
AB U4/U6.U5 tri-snRNP represents a substantial part of the spliceosome before activation. A cryo-electron microscopy structure of Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at 3.7 angstrom resolution led to an essentially complete atomic model comprising 30 proteins plus U4/U6 and U5 small nuclear RNAs (snRNAs). The structure reveals striking interweaving interactions of the protein and RNA components, including extended polypeptides penetrating into subunit interfaces. The invariant ACAGAGA sequence of U6 snRNA, which base-pairs with the 5'-splice site during catalytic activation, forms a hairpin stabilized by Dib1 and Prp8 while the adjacent nucleotides interact with the exon binding loop 1 of U5 snRNA. Snu114 harbours GTP, but its putative catalytic histidine is held away from the gamma-phosphate by hydrogen bonding to a tyrosine in the amino-terminal domain of Prp8. Mutation of this histidine to alanine has no detectable effect on yeast growth. The structure provides important new insights into the spliceosome activation process leading to the formation of the catalytic centre.
C1 [Thi Hoang Duong Nguyen; Galej, Wojciech P.; Bai, Xiao-chen; Oubridge, Chris; Newman, Andrew J.; Scheres, Sjors H. W.; Nagai, Kiyoshi] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Nguyen, THD; Galej, WP; Nagai, K (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM knguyen@mrc-lmb.cam.ac.uk; wgalej@mrc-lmb.cam.ac.uk; kn@mrc-lmb.cam.ac.uk
FU Medical Research Council [MC_UP_A025_1013, MC_U105184330] Funding Source: researchfish; MRC [MC_U105184330, MC_UP_A025_1013] Funding Source: UKRI; Medical Research Council [MC_U105184330, MC_UP_A025_1013] Funding Source: Medline
NR 66
TC 175
Z9 203
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 298
EP +
DI 10.1038/nature16940
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100029
PM 26829225
DA 2026-03-09
ER

PT J
AU Chu, JCK
   Rovis, T
AF Chu, John C. K.
   Rovis, Tomislav
TI Amide-directed photoredox-catalysed C-C bond formation at unactivated sp3 C-H bonds
SO NATURE
LA English
DT Article
ID coupled electron-transfer; alpha-amino-acids; functionalization; radicals; pyrrolidines; olefination; activation; generation; arylation; oxidation
AB Carbon-carbon (C-C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C-C bond formation. Strategies that allow C-C bond formation at inert carbon-hydrogen (C-H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules(1,2). Here we report a method for the formation of C-C bonds by directed cleavage of traditionally non-reactive C-H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C-C bond formation at unactivated sp(3) C-H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen-hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C-H bonds through a strategy involving hydrogen-atom transfer.
C1 [Chu, John C. K.; Rovis, Tomislav] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA.
   [Rovis, Tomislav] Columbia Univ, Dept Chem, New York, NY 10027 USA.
C3 Colorado State University System; Colorado State University Fort Collins; Columbia University
RP Rovis, T (corresponding author), Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA.; Rovis, T (corresponding author), Columbia Univ, Dept Chem, New York, NY 10027 USA.
EM tr2504@columbia.edu
FU NIGMS [GM80442]; Croucher Foundation (Hong Kong); National Institute of General Medical Sciences [R01GM080442] Funding Source: NIH RePORTER
NR 25
TC 486
Z9 544
U1 7
U2 338
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 272
EP 275
DI 10.1038/nature19810
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500041
PM 27732580
DA 2026-03-09
ER

PT J
AU Hekstra, DR
   White, KI
   Socolich, MA
   Henning, RW
   Srajer, V
   Ranganathan, R
AF Hekstra, Doeke R.
   White, K. Ian
   Socolich, Michael A.
   Henning, Robert W.
   Srajer, Vukica
   Ranganathan, Rama
TI Electric-field-stimulated protein mechanics
SO NATURE
LA English
DT Article
ID pdz domain; energy landscape; ligand migration; molecular movie; gating charge; dynamics; recognition; binding; crystallography; photocycle
AB The internal mechanics of proteins-the coordinated motions of amino acids and the pattern of forces constraining these motions-connects protein structure to function. Here we describe a new method combining the application of strong electric field pulses to protein crystals with time-resolved X-ray crystallography to observe conformational changes in spatial and temporal detail. Using a human PDZ domain (LNX2(PDZ2)) as a model system, we show that protein crystals tolerate electric field pulses strong enough to drive concerted motions on the sub-microsecond timescale. The induced motions are subtle, involve diverse physical mechanisms, and occur throughout the protein structure. The global pattern of electric-field-induced motions is consistent with both local and allosteric conformational changes naturally induced by ligand binding, including at conserved functional sites in the PDZ domain family. This work lays the foundation for comprehensive experimental study of the mechanical basis of protein function.
C1 [Hekstra, Doeke R.; White, K. Ian; Socolich, Michael A.; Ranganathan, Rama] UT Southwestern Med Ctr, Green Ctr Syst Biol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
   [Henning, Robert W.; Srajer, Vukica] Univ Chicago, Ctr Adv Radiat Sources, 929 East 57th St, Chicago, IL 60637 USA.
   [Ranganathan, Rama] UT Southwestern Med Ctr, Dept Biophys, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
   [Ranganathan, Rama] UT Southwestern Med Ctr, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
   [Hekstra, Doeke R.] Harvard Univ, Dept Mol & Cellular Biol, 52 Oxford St, Cambridge, MA 02138 USA.
   [Hekstra, Doeke R.] Harvard Univ, Sch Engn & Appl Sci, 52 Oxford St, Cambridge, MA 02138 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Chicago; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Harvard University
RP Ranganathan, R (corresponding author), UT Southwestern Med Ctr, Green Ctr Syst Biol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.; Ranganathan, R (corresponding author), UT Southwestern Med Ctr, Dept Biophys, 6001 Forest Pk Rd, Dallas, TX 75390 USA.; Ranganathan, R (corresponding author), UT Southwestern Med Ctr, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
EM rama.ranganathan@utsouthwestern.edu
FU National Institutes of Health (NIH) [R01GM123456]; Robert A. Welch Foundation [I-1366]; Lyda Hill Endowment for Systems Biology; Green Center for Systems Biology; NIH [R24GM111072, P41GM103393]; US Department of Energy [DE-AC02-76SF00515]
NR 52
TC 163
Z9 195
U1 0
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 400
EP +
DI 10.1038/nature20571
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800035
PM 27926732
DA 2026-03-09
ER

PT J
AU Pehrsson, EC
   Tsukayama, P
   Patel, S
   Mejía-Bautista, M
   Sosa-Soto, G
   Navarrete, KM
   Alderon, MC
   Abrera, LC
   Hoyos-Arango, W
   Bertoli, MT
   Berg, DE
   Gilman, RH
   Dantas, G
AF Pehrsson, Erica C.
   Tsukayama, Pablo
   Patel, Sanket
   Mejia-Bautista, Melissa
   Sosa-Soto, Giordano
   Navarrete, Karla M.
   Alderon, Maritza C.
   Abrera, Lilia C.
   Hoyos-Arango, William
   Teresita Bertoli, M.
   Berg, Douglas E.
   Gilman, Robert H.
   Dantas, Gautam
TI Interconnected microbiomes and resistomes in low-income human habitats
SO NATURE
LA English
DT Article
ID antibiotic-resistance genes; water; community; sanitation; bacteria
AB Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities. We found that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but identified key resistance genes that cross habitat boundaries and determined their association with mobile genetic elements. We also assessed the effectiveness of widely used excreta management strategies in reducing faecal bacteria and resistance genes in these settings representative of low- and middle-income countries. Our results lay the foundation for quantitative risk assessment and surveillance of resistance gene dissemination across interconnected habitats in settings representing over two-thirds of the world's population.
C1 [Pehrsson, Erica C.; Tsukayama, Pablo; Patel, Sanket; Mejia-Bautista, Melissa; Sosa-Soto, Giordano; Dantas, Gautam] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.
   [Patel, Sanket; Dantas, Gautam] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Mejia-Bautista, Melissa; Sosa-Soto, Giordano; Navarrete, Karla M.; Hoyos-Arango, William; Teresita Bertoli, M.] Univ Dr Jose Matias Delgado, Fac Ciencias Salud Dr Luis Edmundo Vasquez, Antiguo Cuscatlan, El Salvador.
   [Alderon, Maritza C.; Gilman, Robert H.] Univ Peruana Cayetano Heredia, Labs Invest & Desarrollo, Lima 31, Peru.
   [Abrera, Lilia C.; Gilman, Robert H.] Asociac Benef PRISMA, Lima 32, Peru.
   [Berg, Douglas E.; Dantas, Gautam] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Berg, Douglas E.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Gilman, Robert H.] Johns Hopkins Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
   [Dantas, Gautam] Washington Univ, Dept Biomed Engn, St Louis, MO 63105 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Universidad Peruana Cayetano Heredia; Washington University (WUSTL); University of California System; University of California San Diego; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Washington University (WUSTL)
RP Dantas, G (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.; Dantas, G (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.; Dantas, G (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.; Dantas, G (corresponding author), Washington Univ, Dept Biomed Engn, St Louis, MO 63105 USA.
EM dantas@wustl.edu
FU Edward Mallinckrodt, Jr. Foundation; Children's Discovery Institute [MD-II-2011-117]; National Institute of General Medical Sciences of the National Institutes of Health [R01-GM099538]; Department of Defense (DoD) through the National Defense Science and Engineering Graduate (NDSEG) Fellowship; MRC [MR/K007467/1] Funding Source: UKRI; Medical Research Council [MR/K007467/1] Funding Source: researchfish
NR 55
TC 437
Z9 525
U1 7
U2 345
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 212
EP +
DI 10.1038/nature17672
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200042
PM 27172044
DA 2026-03-09
ER

PT J
AU Nuber, S
   Zabel, U
   Lorenz, K
   Nuber, A
   Milligan, G
   Tobin, AB
   Lohse, MJ
   Hoffmann, C
AF Nuber, Susanne
   Zabel, Ulrike
   Lorenz, Kristina
   Nuber, Andreas
   Milligan, Graeme
   Tobin, Andrew B.
   Lohse, Martin J.
   Hoffmann, Carsten
TI β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle
SO NATURE
LA English
DT Article
ID g-protein; conformational-changes; crystal-structure; 48-kda protein; activation; binding; rhodopsin; energy; specificity; complex
AB (beta-) Arrestins are important regulators of G-protein-coupled receptors (GPCRs)(1-3). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins(3,)4, trigger internalization of GPCRs via interaction with the clathrin machinery(5-7) and mediate signalling via 'non-classical' pathways(1,2). In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) beta-arrestin proteins (beta-arrestin1 and beta-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs)(1,3,4). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (beta-) arrestins that have recently been solved by X-ray crystallography(8-10). Here we investigate both the interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based beta-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in beta-arrestin2 that occur rapidly after the receptor-beta-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and beta-arrestins. They further indicate that beta-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of beta-arrestins, which permits their active signalling.
C1 [Nuber, Susanne; Zabel, Ulrike; Lorenz, Kristina; Nuber, Andreas; Lohse, Martin J.; Hoffmann, Carsten] Univ Wurzburg, Inst Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany.
   [Nuber, Susanne; Zabel, Ulrike; Lohse, Martin J.; Hoffmann, Carsten] Univ Wurzburg, Rudolf Virchow Ctr, Versbacher Str 9, D-97078 Wurzburg, Germany.
   [Lorenz, Kristina; Lohse, Martin J.] Univ Wurzburg, Comprehens Heart Failure Ctr, Versbacher Str 9, D-97078 Wurzburg, Germany.
   [Milligan, Graeme] Univ Glasgow, Inst Mol Cell & Syst Biol, Coll Med Vet & Life Sci, Mol Pharmacol Grp, Glasgow G12 8QQ, Lanark, Scotland.
   [Tobin, Andrew B.] Univ Leicester, MRC Toxicol Unit, Hodgkin Bldg,Lancaster Rd, Leicester LE1 9HN, Leics, England.
   [Lorenz, Kristina] Leibniz Inst Analyt Sci ISAS, Bunsen Kirchhoff Str 11, D-44139 Dortmund, Germany.
   [Lohse, Martin J.] Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13092 Berlin, Germany.
C3 University of Wurzburg; University of Wurzburg; University of Wurzburg; University of Glasgow; University of Leicester; Dortmund University of Technology; Leibniz Association; Leibniz Institut fur Analytische Wissenschaften (ISAS); Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Lohse, MJ; Hoffmann, C (corresponding author), Univ Wurzburg, Inst Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany.; Lohse, MJ; Hoffmann, C (corresponding author), Univ Wurzburg, Rudolf Virchow Ctr, Versbacher Str 9, D-97078 Wurzburg, Germany.; Lohse, MJ (corresponding author), Univ Wurzburg, Comprehens Heart Failure Ctr, Versbacher Str 9, D-97078 Wurzburg, Germany.; Lohse, MJ (corresponding author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13092 Berlin, Germany.
EM lohse@toxi.uni-wuerzburg.de; c.hoffmann@toxi.uni-wuerzburg.de
FU Deutsche Forschungsgemeinschaft [SFB-487 TPA1, SFB-TR166]; Bundesministerium fur Bildung und Forschung grant OptiMAR; ERC; NIH [1 R01 DA038882]; Biotechnology and Biological Sciences Research Council [BB/K019864/1]; BBSRC [BB/K019864/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K019864/1] Funding Source: researchfish
NR 38
TC 173
Z9 193
U1 0
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 661
EP +
DI 10.1038/nature17198
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400043
PM 27007855
DA 2026-03-09
ER

PT J
AU Semenov, SN
   Kraft, LJ
   Ainla, A
   Zhao, M
   Baghbanzadeh, M
   Campbell, VE
   Kang, K
   Fox, JM
   Whitesides, GM
AF Semenov, Sergey N.
   Kraft, Lewis J.
   Ainla, Alar
   Zhao, Mengxia
   Baghbanzadeh, Mostafa
   Campbell, Victoria E.
   Kang, Kyungtae
   Fox, Jerome M.
   Whitesides, George M.
TI Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions
SO NATURE
LA English
DT Article
ID thiol-disulfide interchange; cycle; cell; mechanisms; protein; system; model; rates
AB Networks of organic chemical reactions are important in life and probably played a central part in its origin(1-3). Network dynamics regulate cell division(4-6), circadian rhythms(7), nerve impulses(8) and chemotaxis(9), and guide the development of organisms(10). Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics(11) such as spontaneous pattern formation, bistability and periodic oscillations(12-14), the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes(15) and DNA(16,17)) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov-Zhabotinskii-type reactions)(18,19), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.
C1 [Semenov, Sergey N.; Kraft, Lewis J.; Ainla, Alar; Zhao, Mengxia; Baghbanzadeh, Mostafa; Campbell, Victoria E.; Kang, Kyungtae; Fox, Jerome M.; Whitesides, George M.] Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.
   [Whitesides, George M.] Harvard Univ, Sch Engn & Appl Sci, Kavli Inst Bionano Inspired Sci & Technol, 29 Oxford St, Cambridge, MA 02138 USA.
   [Whitesides, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, 60 Oxford St, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University
RP Whitesides, GM (corresponding author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.; Whitesides, GM (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Kavli Inst Bionano Inspired Sci & Technol, 29 Oxford St, Cambridge, MA 02138 USA.; Whitesides, GM (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, 60 Oxford St, Cambridge, MA 02138 USA.
EM gwhitesides@gmwgroup.harvard.edu
FU Simons Foundation [290364]; Templeton Foundation [48423]; Swedish Research Council (VR)
NR 37
TC 270
Z9 302
U1 6
U2 246
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 656
EP +
DI 10.1038/nature19776
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700045
PM 27680939
DA 2026-03-09
ER

PT J
AU Ayyer, K
   Yefanov, OM
   Oberthür, D
   Roy-Chowdhury, S
   Galli, L
   Mariani, V
   Basu, S
   Coe, J
   Conrad, CE
   Fromme, R
   Schaffer, A
   Dröner, K
   James, D
   Kupitz, C
   Metz, M
   Nelson, G
   Xavier, PL
   Beyerlein, KR
   Schmidt, M
   Sarrou, I
   Spence, JCH
   Weierstall, U
   White, TA
   Yang, JH
   Zhao, Y
   Liang, MN
   Aquila, A
   Hunter, MS
   Robinson, JS
   Koglin, JE
   Boutet, S
   Fromme, P
   Barty, A
   Chapman, HN
AF Ayyer, Kartik
   Yefanov, Oleksandr M.
   Oberthuer, Dominik
   Roy-Chowdhury, Shatabdi
   Galli, Lorenzo
   Mariani, Valerio
   Basu, Shibom
   Coe, Jesse
   Conrad, Chelsie E.
   Fromme, Raimund
   Schaffer, Alexander
   Droener, Katerina
   James, Daniel
   Kupitz, Christopher
   Metz, Markus
   Nelson, Garrett
   Xavier, Paulraj Lourdu
   Beyerlein, Kenneth R.
   Schmidt, Marius
   Sarrou, Iosifina
   Spence, John C. H.
   Weierstall, Uwe
   White, Thomas A.
   Yang, Jay-How
   Zhao, Yun
   Liang, Mengning
   Aquila, Andrew
   Hunter, Mark S.
   Robinson, Joseph S.
   Koglin, Jason E.
   Boutet, Sebastien
   Fromme, Petra
   Barty, Anton
   Chapman, Henry N.
TI Macromolecular diffractive imaging using imperfect crystals
SO NATURE
LA English
DT Article
ID x-ray scattering; diffuse-scattering; phase retrieval; resolution; crystallography; reconstruction; complex; object; model
AB The three-dimensional structures of macromolecules and their complexes are mainly elucidated by X-ray protein crystallography. A major limitation of this method is access to high-quality crystals, which is necessary to ensure X-ray diffraction extends to sufficiently large scattering angles and hence yields information of sufficiently high resolution with which to solve the crystal structure. The observation that crystals with reduced unit-cell volumes and tighter macromolecular packing often produce higher-resolution Bragg peaks(1,2) suggests that crystallographic resolution for some macromolecules may be limited not by their heterogeneity, but by a deviation of strict positional ordering of the crystalline lattice. Such displacements of molecules from the ideal lattice give rise to a continuous diffraction pattern that is equal to the incoherent sum of diffraction from rigid individual molecular complexes aligned along several discrete crystallographic orientations and that, consequently, contains more information than Bragg peaks alone(3). Although such continuous diffraction patterns have long been observed-and are of interest as a source of information about the dynamics of proteins(4)-they have not been used for structure determination. Here we show for crystals of the integral membrane protein complex photosystem II that lattice disorder increases the information content and the resolution of the diffraction pattern well beyond the 4.5-angstrom limit of measurable Bragg peaks, which allows us to phase(5) the pattern directly. Using the molecular envelope conventionally determined at 4.5 angstroms as a constraint, we obtain a static image of the photosystem II dimer at a resolution of 3.5 angstroms. This result shows that continuous diffraction can be used to overcome what have long been supposed to be the resolution limits of macromolecular crystallography, using a method that exploits commonly encountered imperfect crystals and enables modelfree phasing(6,7).
C1 [Ayyer, Kartik; Yefanov, Oleksandr M.; Galli, Lorenzo; Mariani, Valerio; Droener, Katerina; Xavier, Paulraj Lourdu; Beyerlein, Kenneth R.; White, Thomas A.; Barty, Anton; Chapman, Henry N.] DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Oberthuer, Dominik; Galli, Lorenzo; Metz, Markus; Xavier, Paulraj Lourdu; Chapman, Henry N.] Univ Hamburg, Dept Phys, D-22761 Hamburg, Germany.
   [Roy-Chowdhury, Shatabdi; Basu, Shibom; Coe, Jesse; Conrad, Chelsie E.; Fromme, Raimund; Schaffer, Alexander; Droener, Katerina; Kupitz, Christopher; Yang, Jay-How; Fromme, Petra] Arizona State Univ, Sch Mol Sci, Tempe, AZ 85287 USA.
   [Roy-Chowdhury, Shatabdi; Basu, Shibom; Coe, Jesse; Conrad, Chelsie E.; Fromme, Raimund; Schaffer, Alexander; James, Daniel; Nelson, Garrett; Spence, John C. H.; Weierstall, Uwe; Yang, Jay-How; Zhao, Yun; Fromme, Petra] Arizona State Univ, Biodesign Inst, Ctr Appl Struct Discovery, Tempe, AZ 85287 USA.
   [James, Daniel; Nelson, Garrett; Spence, John C. H.; Weierstall, Uwe; Zhao, Yun] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Kupitz, Christopher; Schmidt, Marius] Univ Wisconsin, Dept Phys, Milwaukee, WI 53211 USA.
   [Sarrou, Iosifina] Fdn Res & Technol, Inst Mol Biol & Biotechnol, GR-70013 Iraklion, Greece.
   [Liang, Mengning; Aquila, Andrew; Hunter, Mark S.; Robinson, Joseph S.; Koglin, Jason E.; Boutet, Sebastien] SLAC, Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
   [Chapman, Henry N.] Ctr Ultrafast Imaging, D-22607 Hamburg, Germany.
C3 Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Hamburg; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; University of Wisconsin System; University of Wisconsin Milwaukee; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Chapman, HN (corresponding author), DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
EM henry.chapman@desy.de
FU Helmholtz Association; Virtual Institute "Dynamic Pathways in Multidimensional Landscapes"; DFG through the Gottfried Wilhelm Leibniz Program; European Research Council under the European Union's Seventh Framework Programme ERC Synergy Grant [609920]; Marie Curie FP7-PEOPLE-ITN [317079]; BMBF [05E13GU1]; Graduate College at the University of Hamburg [GRK 1355]; International Max Planck Research School UFAST; BioXFEL Science Technology Center [1231306]; US National Institutes of Health (NIH); National Institute of General Medical Sciences [R01 GM095583, U54 GM094599, R01 GM097463]; NIH [P41GM103393, P41RR001209]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]; National Institute of General Medical Sciences [R01GM095583] Funding Source: NIH RePORTER; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0952643] Funding Source: National Science Foundation
NR 47
TC 107
Z9 125
U1 0
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 202
EP +
DI 10.1038/nature16949
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700035
PM 26863980
DA 2026-03-09
ER

PT J
AU Bozyigit, D
   Yazdani, N
   Yarema, M
   Yarema, O
   Lin, WMM
   Volk, S
   Vuttivorakulchai, K
   Luisier, M
   Juranyi, F
   Wood, V
AF Bozyigit, Deniz
   Yazdani, Nuri
   Yarema, Maksym
   Yarema, Olesya
   Lin, Weyde Matteo Mario
   Volk, Sebastian
   Vuttivorakulchai, Kantawong
   Luisier, Mathieu
   Juranyi, Fanni
   Wood, Vanessa
TI Soft surfaces of nanomaterials enable strong phonon interactions
SO NATURE
LA English
DT Article
ID quantum dots; raman-scattering; pbse; thermodynamics; nanocrystals; relaxation; dynamics
AB Phonons and their interactions with other phonons, electrons or photons drive energy gain, loss and transport in materials. Although the phonon density of states has been measured and calculated in bulk crystalline semiconductors(1), phonons remain poorly understood in nanomaterials(2-5), despite the increasing prevalence of bottom-up fabrication of semiconductors from nanomaterials and the integration of nanometre-sized components into devices(6-8). Here we quantify the phononic properties of bottom-up fabricated semiconductors as a function of crystallite size using inelastic neutron scattering measurements and ab initio molecular dynamics simulations. We show that, unlike in microcrystalline semiconductors, the phonon modes of semiconductors with nanocrystalline domains exhibit both reduced symmetry and low energy owing to mechanical softness at the surface of those domains. These properties become important when phonons couple to electrons in semiconductor devices. Although it was initially believed that the coupling between electrons and phonons is suppressed in nanocrystalline materials owing to the scarcity of electronic states and their large energy separation(9), it has since been shown that the electron-phonon coupling is large and allows high energy-dissipation rates exceeding one electronvolt per picosecond (refs 10-13). Despite detailed investigations into the role of phonons in exciton dynamics, leading to a variety of suggestions as to the origins of these fast transition rates(14,15) and including attempts to numerically calculate them(12,13,16), fundamental questions surrounding electron-phonon interactions in nanomaterials remain unresolved. By combining the microscopic and thermodynamic theories of phonons(1,17-19) and our findings on the phononic properties of nanomaterials, we are able to explain and then experimentally confirm the strong electron-phonon coupling and fast multi-phonon transition rates of charge carriers to trap states. This improved understanding of phonon processes permits the rational selection of nanomaterials, their surface treatments, and the design of devices incorporating them.
C1 [Bozyigit, Deniz; Yazdani, Nuri; Yarema, Maksym; Yarema, Olesya; Lin, Weyde Matteo Mario; Volk, Sebastian; Wood, Vanessa] ETH, Dept Informat Technol & Elect Engn, Lab Nanoelect, CH-8092 Zurich, Switzerland.
   [Vuttivorakulchai, Kantawong; Luisier, Mathieu] ETH, Dept Informat Technol & Elect Engn, Nano TCAD Grp, CH-8092 Zurich, Switzerland.
   [Juranyi, Fanni] Paul Scherrer Inst, Lab Neutron Scattering & Imaging, CH-5232 Villigen, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute
RP Bozyigit, D; Wood, V (corresponding author), ETH, Dept Informat Technol & Elect Engn, Lab Nanoelect, CH-8092 Zurich, Switzerland.
EM denizb@iis.ee.ethz.ch; vwood@ethz.ch
FU Swiss National Science Foundation through the NCCR Quantum Science and Technology; ETH Research Grant; SNF TORNAD [149454]; Swiss National Supercomputing Centre (CSCS) [s579]
NR 33
TC 148
Z9 170
U1 5
U2 222
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 618
EP 622
DI 10.1038/nature16977
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400034
PM 26958836
DA 2026-03-09
ER

PT J
AU Gächter, S
   Schulz, JF
AF Gaechter, Simon
   Schulz, Jonathan F.
TI Intrinsic honesty and the prevalence of rule violations across societies
SO NATURE
LA English
DT Article
ID cultural transmission; unethical behavior; corruption; institutions; dishonesty; evolution
AB Deception is common in nature and humans are no exception(1). Modern societies have created institutions to control cheating, but many situations remain where only intrinsic honesty keeps people from cheating and violating rules. Psychological(2), sociological(3) and economic theories(4) suggest causal pathways to explain how the prevalence of rule violations in people's social environment, such as corruption, tax evasion or political fraud, can compromise individual intrinsic honesty. Here we present cross-societal experiments from 23 countries around the world that demonstrate a robust link between the prevalence of rule violations and intrinsic honesty. We developed an index of the 'prevalence of rule violations' (PRV) based on country-level data from the year 2003 of corruption, tax evasion and fraudulent politics. We measured intrinsic honesty in an anonymous die-rolling experiment(5). We conducted the experiments with 2,568 young participants (students) who, due to their young age in 2003, could not have influenced PRV in 2003. We find individual intrinsic honesty is stronger in the subject pools of low PRV countries than those of high PRV countries. The details of lying patterns support psychological theories of honesty(6,7). The results are consistent with theories of the cultural co-evolution of institutions and values(8), and show that weak institutions and cultural legacies(9-11) that generate rule violations not only have direct adverse economic consequences, but might also impair individual intrinsic honesty that is crucial for the smooth functioning of society.
C1 [Gaechter, Simon; Schulz, Jonathan F.] Univ Nottingham, Univ Pk, Nottingham NG7 2RD, England.
   [Gaechter, Simon] CESifo, Schackstr 4, D-80539 Munich, Germany.
   [Gaechter, Simon] IZA, Schaumburg Lippe Str 5-9, D-53113 Bonn, Germany.
   [Schulz, Jonathan F.] Yale Univ, 1 Prospect St, New Haven, CT 06510 USA.
C3 University of Nottingham; Leibniz Association; Ifo Institut; IZA Institute Labor Economics; Yale University
RP Gächter, S; Schulz, JF (corresponding author), Univ Nottingham, Univ Pk, Nottingham NG7 2RD, England.; Gächter, S (corresponding author), CESifo, Schackstr 4, D-80539 Munich, Germany.; Gächter, S (corresponding author), IZA, Schaumburg Lippe Str 5-9, D-53113 Bonn, Germany.; Schulz, JF (corresponding author), Yale Univ, 1 Prospect St, New Haven, CT 06510 USA.
EM simon.gaechter@nottingham.ac.uk; jonathan.schulz@yale.edu
FU ERC-AdG [295707 COOPERATION]; ESRC Network on Integrated Behavioural Science (NIBS) [ES/K002201/1]; ESRC [ES/K002201/1] Funding Source: UKRI; Economic and Social Research Council [ES/K002201/1] Funding Source: researchfish
NR 30
TC 347
Z9 435
U1 11
U2 261
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 496
EP +
DI 10.1038/nature17160
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300039
PM 26958830
DA 2026-03-09
ER

PT J
AU Baker, DJ
   Childs, BG
   Durik, M
   Wijers, ME
   Sieben, CJ
   Zhong, J
   Saltness, RA
   Jeganathan, KB
   Verzosa, GC
   Pezeshki, A
   Khazaie, K
   Miller, JD
   van Deursen, JM
AF Baker, Darren J.
   Childs, Bennett G.
   Durik, Matej
   Wijers, Melinde E.
   Sieben, Cynthia J.
   Zhong, Jian
   Saltness, Rachel A.
   Jeganathan, Karthik B.
   Verzosa, Grace Casaclang
   Pezeshki, Abdulmohammad
   Khazaie, Khashayarsha
   Miller, Jordan D.
   van Deursen, Jan M.
TI Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
SO NATURE
LA English
DT Article
ID senescent cells; cellular senescence; body-weight; in-vivo; age; expression; mice; growth; restriction; biomarkers
AB Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective K-ATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.
C1 [Baker, Darren J.; Durik, Matej; Wijers, Melinde E.; Zhong, Jian; Saltness, Rachel A.; Jeganathan, Karthik B.; van Deursen, Jan M.] Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
   [Childs, Bennett G.; Sieben, Cynthia J.; van Deursen, Jan M.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [Verzosa, Grace Casaclang; Miller, Jordan D.] Mayo Clin, Coll Med, Div Cardiovasc Surg, Rochester, MN 55905 USA.
   [Pezeshki, Abdulmohammad; Khazaie, Khashayarsha] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA.
C3 Mayo Clinic; Mayo Clinic; Mayo Clinic; Mayo Clinic
RP Baker, DJ (corresponding author), Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
EM baker.darren@mayo.edu
FU National Institutes of Health [AG041122, R01CA96985, HL111121]; Paul F. Glenn Foundation; Ellison Medical Foundation; Noaber Foundation; Children's Research Center; Robert and Arlene Kogod Center on Aging; National Cancer Institute [R01CA096985, P30CA015083] Funding Source: NIH RePORTER; National Institute on Aging [R37AG013925] Funding Source: NIH RePORTER
NR 48
TC 2155
Z9 2495
U1 26
U2 381
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 184
EP +
DI 10.1038/nature16932
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700031
PM 26840489
DA 2026-03-09
ER

PT J
AU Sing, DK
   Fortney, JJ
   Nikolov, N
   Wakeford, HR
   Kataria, T
   Evans, TM
   Aigrain, S
   Ballester, GE
   Burrows, AS
   Deming, D
   Désert, JM
   Gibson, NP
   Henry, GW
   Huitson, CM
   Knutson, HA
   des Etangs, AL
   Pont, F
   Showman, AP
   Vidal-Madjar, A
   Williamson, MH
   Wilson, PA
AF Sing, David K.
   Fortney, Jonathan J.
   Nikolov, Nikolay
   Wakeford, Hannah R.
   Kataria, Tiffany
   Evans, Thomas M.
   Aigrain, Suzanne
   Ballester, Gilda E.
   Burrows, Adam S.
   Deming, Drake
   Desert, Jean-Michel
   Gibson, Neale P.
   Henry, Gregory W.
   Huitson, Catherine M.
   Knutson, Heather A.
   des Etangs, Alain Lecavelier
   Pont, Frederic
   Showman, Adam P.
   Vidal-Madjar, Alfred
   Williamson, Michael H.
   Wilson, Paul A.
TI A continuum from clear to cloudy hot-Jupiter exoplanets without primordial water depletion
SO NATURE
LA English
DT Article
ID transmission spectral survey; hd 189733b; brown dwarfs; atmospheric chemistry; giant planets; hubble; stars; spectroscopy; nitrogen; carbon
AB Thousands of transiting exoplanets have been discovered, but spectral analysis of their atmospheres has so far been dominated by a small number of exoplanets and data spanning relatively narrow wavelength ranges (such as 1.1-1.7 micrometres). Recent studies show that some hot-Jupiter exoplanets have much weaker water absorption features in their near-infrared spectra than predicted(1-5). The low amplitude of water signatures could be explained by very low water abundances(6-8), which may be a sign that water was depleted in the protoplanetary disk at the planet's formation location9, but it is unclear whether this level of depletion can actually occur. Alternatively, these weak signals could be the result of obscuration by clouds or hazes(1-4), as found in some optical spectra(3,4,10,11). Here we report results from a comparative study of ten hot Jupiters covering the wavelength range 0.3-5 micrometres, which allows us to resolve both the optical scattering and infrared molecular absorption spectroscopically. Our results reveal a diverse group of hot Jupiters that exhibit a continuum from clear to cloudy atmospheres. We find that the difference between the planetary radius measured at optical and infrared wavelengths is an effective metric for distinguishing different atmosphere types. The difference correlates with the spectral strength of water, so that strong water absorption lines are seen in clear-atmosphere planets and the weakest features are associated with clouds and hazes. This result strongly suggests that primordial water depletion during formation is unlikely and that clouds and hazes are the cause of weaker spectral signatures.
C1 [Sing, David K.; Nikolov, Nikolay; Wakeford, Hannah R.; Kataria, Tiffany; Evans, Thomas M.; Pont, Frederic] Univ Exeter, Sch Phys, Astrophys Grp, Stocker Rd, Exeter EX4 4QL, Devon, England.
   [Fortney, Jonathan J.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Aigrain, Suzanne] Univ Oxford, Dept Phys, Keble Rd, Oxford OX1 3RH, England.
   [Ballester, Gilda E.; Showman, Adam P.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Burrows, Adam S.] Princeton Univ, Dept Astrophys Sci, Peyton Hall, Princeton, NJ 08544 USA.
   [Deming, Drake] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Desert, Jean-Michel; Huitson, Catherine M.] Univ Colorado, Dept Astrophys & Planetary Sci, Boulder, CO 80309 USA.
   [Gibson, Neale P.] European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
   [Henry, Gregory W.; Williamson, Michael H.] Tennessee State Univ, Ctr Excellence Informat Syst, Nashville, TN 37209 USA.
   [Knutson, Heather A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [des Etangs, Alain Lecavelier; Vidal-Madjar, Alfred; Wilson, Paul A.] CNRS, Inst Astrophys Paris, UMR 7095, 98 Bis Blvd Arago, F-75014 Paris, France.
C3 University of Exeter; University of California System; University of California Santa Cruz; University of Oxford; University of Arizona; Princeton University; University System of Maryland; University of Maryland College Park; University of Colorado System; University of Colorado Boulder; European Southern Observatory; Tennessee State University; California Institute of Technology; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite
RP Sing, DK (corresponding author), Univ Exeter, Sch Phys, Astrophys Grp, Stocker Rd, Exeter EX4 4QL, Devon, England.
EM sing@astro.ex.ac.uk
FU European Research Council under the European Union's Seventh Framework Programme (FP7)/ERC [336792]; STFC [ST/J0016/1]; NASA from the STScI [HST-GO-12473]; CNES; French Agence Nationale de la Recherche (ANR) [ANR-12-BS05-0012]; UK Science and Technology Facilities Council (STFC); NASA; NSF; Tennessee State University; State of Tennessee through its Centers of Excellence programme; Science and Technology Facilities Council [ST/J001627/1, ST/G002266/1, ST/M003515/1, ST/K00106X/1, ST/L000709/1, ST/N000919/1] Funding Source: researchfish; UK Space Agency [ST/G002266/2] Funding Source: researchfish; STFC [ST/M003515/1, ST/L000709/1, ST/K00106X/1, ST/G002266/1, ST/N000919/1, ST/J001627/1] Funding Source: UKRI
NR 55
TC 772
Z9 869
U1 2
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 59
EP +
DI 10.1038/nature16068
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900025
PM 26675732
DA 2026-03-09
ER

PT J
AU Westermann, AJ
   Förstner, KU
   Amman, F
   Barquist, L
   Chao, YJ
   Schulte, LN
   Müller, L
   Reinhardt, R
   Stadler, PF
   Vogel, J
AF Westermann, Alexander J.
   Foerstner, Konrad U.
   Amman, Fabian
   Barquist, Lars
   Chao, Yanjie
   Schulte, Leon N.
   Mueller, Lydia
   Reinhardt, Richard
   Stadler, Peter F.
   Vogel, Joerg
TI Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions
SO NATURE
LA English
DT Article
ID salmonella-typhimurium; gene-expression; transcriptional regulator; epithelial-cells; protein; hfq; infection; virulence; pcr; information
AB Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.
C1 [Westermann, Alexander J.; Foerstner, Konrad U.; Barquist, Lars; Chao, Yanjie; Schulte, Leon N.; Vogel, Joerg] Univ Wurzburg, RNA Biol Grp, Inst Mol Infect Biol, Josef Schneider Str 2-D15, D-97080 Wurzburg, Germany.
   [Foerstner, Konrad U.] Univ Wurzburg, Core Unit Syst Med, Josef Schneider Str 2-D15, D-97080 Wurzburg, Germany.
   [Amman, Fabian; Mueller, Lydia; Stadler, Peter F.] Univ Leipzig, Dept Comp Sci, Hartelstr 16-18, D-04107 Leipzig, Germany.
   [Amman, Fabian; Mueller, Lydia; Stadler, Peter F.] Univ Leipzig, Interdisciplinary Ctr Bioinformat, Hartelstr 16-18, D-04107 Leipzig, Germany.
   [Amman, Fabian; Stadler, Peter F.] Univ Vienna, Inst Theoret Chem, Theoret Biochem Grp, Wahringer Str 17, A-1090 Vienna, Austria.
   [Reinhardt, Richard] Max Planck Genome Ctr Cologne, Max Planck Inst Plant Breeding Res, Carl von Linne Weg 10, D-50829 Cologne, Germany.
   [Stadler, Peter F.] Max Planck Inst Math Sci, Inselstr 22, D-04103 Leipzig, Germany.
   [Stadler, Peter F.] Santa Fe Inst, 1399 Hyde Pk Rd, Santa Fe, NM 87501 USA.
   [Vogel, Joerg] Univ Wurzburg, Res Ctr Infect Dis ZINF, D-97070 Wurzburg, Germany.
C3 University of Wurzburg; University of Wurzburg; Leipzig University; Leipzig University; University of Vienna; Max Planck Society; Max Planck Society; The Santa Fe Institute; University of Wurzburg
RP Vogel, J (corresponding author), Univ Wurzburg, RNA Biol Grp, Inst Mol Infect Biol, Josef Schneider Str 2-D15, D-97080 Wurzburg, Germany.; Vogel, J (corresponding author), Univ Wurzburg, Res Ctr Infect Dis ZINF, D-97070 Wurzburg, Germany.
EM joerg.vogel@uni-wuerzburg.de
FU Elite Advancement Ph.D. stipend from the Universitat Bayern e.V., Germany; Alexander von Humboldt Stiftung/Foundation; Bavarian BioSysNet program; BMBF (Bundesministerium fur Bildung und Forschung); BMBF; EGI-Engage project (Horizon) [654142]
NR 84
TC 378
Z9 442
U1 6
U2 296
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 496
EP +
DI 10.1038/nature16547
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800030
PM 26789254
DA 2026-03-09
ER

PT J
AU Park, RS
   Konopliv, AS
   Bills, BG
   Rambaux, N
   Castillo-Rogez, JC
   Raymond, CA
   Vaughan, AT
   Ermakov, AI
   Zuber, MT
   Fu, RR
   Toplis, MJ
   Russell, CT
   Nathues, A
   Preusker, F
AF Park, R. S.
   Konopliv, A. S.
   Bills, B. G.
   Rambaux, N.
   Castillo-Rogez, J. C.
   Raymond, C. A.
   Vaughan, A. T.
   Ermakov, A. I.
   Zuber, M. T.
   Fu, R. R.
   Toplis, M. J.
   Russell, C. T.
   Nathues, A.
   Preusker, F.
TI A partially differentiated interior for (1) Ceres deduced from its gravity field and shape
SO NATURE
LA English
DT Article
ID moment; inertia; origin
AB Remote observations of the asteroid (1) Ceres from ground-and space-based telescopes have provided its approximate density and shape, leading to a range of models for the interior of Ceres, from homogeneous to fully differentiated(1-6). A previously missing parameter that can place a strong constraint on the interior of Ceres is its moment of inertia, which requires the measurement of its gravitational variation(1,7) together with either precession rate(8,9) or a validated assumption of hydrostatic equilibrium(10). However, Earthbased remote observations cannot measure gravity variations and the magnitude of the precession rate is too small to be detected(9). Here we report gravity and shape measurements of Ceres obtained from the Dawn spacecraft, showing that it is in hydrostatic equilibrium with its inferred normalized mean moment of inertia of 0.37. These data show that Ceres is a partially differentiated body, with a rocky core overlaid by a volatile-rich shell, as predicted in some studies(1,4,6). Furthermore, we show that the gravity signal is strongly suppressed compared to that predicted by the topographic variation. This indicates that Ceres is isostatically compensated(11), such that topographic highs are supported by displacement of a denser interior. In contrast to the asteroid (4) Vesta(8,12), this strong compensation points to the presence of a lower-viscosity layer at depth, probably reflecting a thermal rather than compositional gradient(1,4). To further investigate the interior structure, we assume a two-layer model for the interior of Ceres with a core density of 2,460-2,900 kilograms per cubic metre (that is, composed of CI and CM chondrites(13)), which yields an outer-shell thickness of 70-190 kilometres. The density of this outer shell is 1,6801,950 kilograms per cubic metre, indicating a mixture of volatiles and denser materials such as silicates and salts(14). Although the gravity and shape data confirm that the interior of Ceres evolved thermally(1,4,6,) its partially differentiated interior indicates an evolution more complex than has been envisioned for mid-sized (less than 1,000 kilometres across) ice-rich rocky bodies.
C1 [Park, R. S.; Konopliv, A. S.; Bills, B. G.; Castillo-Rogez, J. C.; Raymond, C. A.; Vaughan, A. T.] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
   [Rambaux, N.] Sorbonne Univ, Univ Paris 06, Univ Lille 1, IMCCE,Observ Paris,PSL Res Univ,CNRS, 77 Ave Denfert Rochereau, F-75014 Paris, France.
   [Ermakov, A. I.; Zuber, M. T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Fu, R. R.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Toplis, M. J.] Univ Toulouse, UPS, CNRS, Inst Rech Astrophys & Planetol, Toulouse, France.
   [Russell, C. T.] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA.
   [Nathues, A.] Max Planck Inst Solar Syst Res, Gottingen, Germany.
   [Preusker, F.] DLR, Inst Planetary Res, Dept Planetary Geodesy, Rutherfordstr 2, D-12489 Berlin, Germany.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite de Lille; Universite PSL; Observatoire de Paris; Massachusetts Institute of Technology (MIT); Columbia University; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California Los Angeles; Max Planck Society; Helmholtz Association; German Aerospace Centre (DLR)
RP Park, RS (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM Ryan.S.Park@jpl.nasa.gov
FU National Aeronautics and Space Administration; MESR; French National Programme of Planetology (PNP); CNES
NR 30
TC 185
Z9 199
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 515
EP +
DI 10.1038/nature18955
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900048
PM 27487219
DA 2026-03-09
ER

PT J
AU Kaletsky, R
   Lakhina, V
   Arey, R
   Williams, A
   Landis, J
   Ashraf, J
   Murphy, CT
AF Kaletsky, Rachel
   Lakhina, Vanisha
   Arey, Rachel
   Williams, April
   Landis, Jessica
   Ashraf, Jasmine
   Murphy, Coleen T.
TI The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators
SO NATURE
LA English
DT Article
ID life-span; tgf-beta; protein; regeneration; daf-16; genes; expression; longevity; behavior; 3-kinase
AB Insulin/insulin-like growth factor signalling (IIS) is a critical regulator of an organism's most important biological decisions from growth, development, and metabolism to reproduction and longevity. It primarily does so through the activity of the DAF-16 transcription factor (forkhead box O (FOXO) homologue), whose global targets were identified in Caenorhabditis elegans using whole-worm transcriptional analyses more than a decade ago(1). IIS and FOXO also regulate important neuronal and adult behavioural phenotypes, such as the maintenance of memory(2) and axon regeneration(3) with age, in both mammals(4) and C. elegans, but the neuron-specific IIS/FOXO targets that regulate these functions are still unknown. By isolating adult C. elegans neurons for transcriptional profiling, we identified both the wild-type and IIS/FOXO mutant adult neuronal transcriptomes for the first time. IIS/FOXO neuron-specific targets are distinct from canonical IIS/FOXO-regulated longevity and metabolism targets, and are required for extended memory in IIS daf-2 mutants. The activity of the forkhead transcription factor FKH-9 in neurons is required for the ability of daf-2 mutants to regenerate axons with age, and its activity in non-neuronal tissues is required for the long lifespan of daf-2 mutants. Together, neuron-specific and canonical IIS/FOXO-regulated targets enable the coordinated extension of neuronal activities, metabolism, and longevity under low-insulin signalling conditions.
C1 [Kaletsky, Rachel; Lakhina, Vanisha; Arey, Rachel; Williams, April; Landis, Jessica; Ashraf, Jasmine; Murphy, Coleen T.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Kaletsky, Rachel; Lakhina, Vanisha; Arey, Rachel; Williams, April; Landis, Jessica; Ashraf, Jasmine; Murphy, Coleen T.] Princeton Univ, LSI Genom, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University
RP Murphy, CT (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.; Murphy, CT (corresponding author), Princeton Univ, LSI Genom, Princeton, NJ 08544 USA.
EM ctmurphy@princeton.edu
FU Keck Scholars Program fellowship; National Institutes of Health Cognitive Aging R01; Ruth L. Kirschstein National Research Service Awards; National Science Foundation; New Jersey Commission on Brain Injury Research fellowships; National Human Genome Research Institute [T32HG003284] Funding Source: NIH RePORTER
NR 33
TC 175
Z9 255
U1 2
U2 86
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 92
EP +
DI 10.1038/nature16483
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900033
PM 26675724
DA 2026-03-09
ER

PT J
AU Reich, PB
   Sendall, KM
   Stefanski, A
   Wei, XR
   Rich, RL
   Montgomery, RA
AF Reich, Peter B.
   Sendall, Kerrie M.
   Stefanski, Artur
   Wei, Xiaorong
   Rich, Roy L.
   Montgomery, Rebecca A.
TI Boreal and temperate trees show strong acclimation of respiration to warming
SO NATURE
LA English
DT Article
ID leaf respiration; thermal-acclimation; plant respiration; climate; photosynthesis; nitrogen; vegetation; feedbacks; canopy; sugars
AB Plant respiration results in an annual flux of carbon dioxide (CO2) to the atmosphere that is six times as large as that due to the emissions from fossil fuel burning, so changes in either will impact future climate. As plant respiration responds positively to temperature, a warming world may result in additional respiratory CO2 release, and hence further atmospheric warming(1,2). Plant respiration can acclimate to altered temperatures, however, weakening the positive feedback of plant respiration to rising global air temperature(3-7), but a lack of evidence on long-term (weeks to years) acclimation to climate warming in field settings currently hinders realistic predictions of respiratory release of CO2 under future climatic conditions. Here we demonstrate strong acclimation of leaf respiration to both experimental warming and seasonal temperature variation for juveniles of ten North American tree species growing for several years in forest conditions. Plants grown and measured at 3.4 degrees C above ambient temperature increased leaf respiration by an average of 5% compared to plants grown and measured at ambient temperature; without acclimation, these increases would have been 23%. Thus, acclimation eliminated 80% of the expected increase in leaf respiration of non-acclimated plants. Acclimation of leaf respiration per degree temperature change was similar for experimental warming and seasonal temperature variation. Moreover, the observed increase in leaf respiration per degree increase in temperature was less than half as large as the average reported for previous studies(4,7), which were conducted largely over shorter time scales in laboratory settings. If such dampening effects of leaf thermal acclimation occur generally, the increase in respiration rates of terrestrial plants in response to climate warming may be less than predicted, and thus may not raise atmospheric CO2 concentrations as much as anticipated.
C1 [Reich, Peter B.; Sendall, Kerrie M.; Stefanski, Artur; Wei, Xiaorong; Rich, Roy L.; Montgomery, Rebecca A.] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Reich, Peter B.] Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2753, Australia.
   [Wei, Xiaorong] Northwest A&F Univ, State Key Lab Soil Eros & Dryland Farming Loess P, Yangling 712100, Peoples R China.
   [Rich, Roy L.] Smithsonian Environm Res Ctr, Edgewater, MD 20137 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; Western Sydney University; Northwest A&F University - China; Smithsonian Institution; Smithsonian Environmental Research Center
RP Reich, PB (corresponding author), Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.; Reich, PB (corresponding author), Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2753, Australia.
EM preich@umn.edu
FU US Department of Energy, Office of Science, Office of Biological and Environmental Research award [DE-FG02-07ER64456]; Minnesota Agricultural Experiment Station [MIN-42-030, MIN-42-060]; Minnesota Department of Natural Resources; College of Food, Agricultural, and Natural Resources Sciences; Wilderness Research Foundation; University of Minnesota
NR 31
TC 228
Z9 268
U1 14
U2 359
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 633
EP +
DI 10.1038/nature17142
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400037
PM 26982730
DA 2026-03-09
ER

PT J
AU Lv, JA
   Liu, YY
   Wei, J
   Chen, EQ
   Qin, L
   Yu, YL
AF Lv, Jiu-An
   Liu, Yuyun
   Wei, Jia
   Chen, Erqiang
   Qin, Lang
   Yu, Yanlei
TI Photocontrol of fluid slugs in liquid crystal polymer microactuators
SO NATURE
LA English
DT Article
ID chemical-synthesis; light; surface; driven; microfluidics; transport; actuators; networks; droplet; motion
AB The manipulation of small amounts of liquids has applications ranging from biomedical devices to liquid transfer. Direct light-driven manipulation of liquids, especially when triggered by light-induced capillary forces, is of particular interest because light can provide contactless spatial and temporal control. However, existing light-driven technologies suffer from an inherent limitation in that liquid motion is strongly resisted by the effect of contact-line pinning. Here we report a strategy to manipulate fluid slugs by photo-induced asymmetric deformation of tubular microactuators, which induces capillary forces for liquid propulsion. Microactuators with various shapes (straight, 'Y'-shaped, serpentine and helical) are fabricated from a mechanically robust linear liquid crystal polymer. These microactuators are able to exert photocontrol of a wide diversity of liquids over a long distance with controllable velocity and direction, and hence to mix multiphase liquids, to combine liquids and even to make liquids run uphill. We anticipate that this photodeformable microactuator will find use in micro-reactors, in laboratory-on-a-chip settings and in micro-optomechanical systems.
C1 [Lv, Jiu-An; Liu, Yuyun; Wei, Jia; Qin, Lang; Yu, Yanlei] Fudan Univ, Dept Mat Sci, State Key Lab Mol Engn Polymers, 220 Handan Rd, Shanghai 200433, Peoples R China.
   [Chen, Erqiang] Peking Univ, Beijing Natl Lab Mol Sci, Key Lab Polymer Chem & Phys, Minist Educ, Beijing 100871, Peoples R China.
C3 Fudan University; Chinese Academy of Sciences; Peking University
RP Yu, YL (corresponding author), Fudan Univ, Dept Mat Sci, State Key Lab Mol Engn Polymers, 220 Handan Rd, Shanghai 200433, Peoples R China.
EM ylyu@fudan.edu.cn
FU National Natural Science Foundation of China [51225304, 21134003, 21273048]; Shanghai Outstanding Academic Leaders Plan [15XD1500600]
NR 51
TC 947
Z9 1027
U1 42
U2 1674
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 179
EP +
DI 10.1038/nature19344
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100037
PM 27604946
DA 2026-03-09
ER

PT J
AU Halter, DP
   Heinemann, FW
   Bachmann, J
   Meyer, K
AF Halter, Dominik P.
   Heinemann, Frank W.
   Bachmann, Julien
   Meyer, Karsten
TI Uranium-mediated electrocatalytic dihydrogen production from water
SO NATURE
LA English
DT Article
ID hydrogen generation; crystal-structure; complex; reduction; h-2; coordination; dinitrogen; mechanism
AB Depleted uranium is a mildly radioactive waste product that is stockpiled worldwide. The chemical reactivity of uranium complexes is well documented, including the stoichiometric activation of small molecules of biological and industrial interest such as H2O, CO2, CO, or N-2 (refs 1-11), but catalytic transformations with actinides remain underexplored in comparison to transition-metal catalysis(12-14). For reduction of water to H-2, complexes of low-valent uranium show the highest potential, but are known to react violently and uncontrollably forming stable bridging oxo or uranyl species(15). As a result, only a few oxidations of uranium with water have been reported so far; all stoichiometric(2,3,16,17). Catalytic H-2 production, however, requires the reductive recovery of the catalyst via a challenging cleavage of the uranium-bound oxygen-containing ligand. Here we report the electrocatalytic water reduction observed with a trisaryloxide U(iii) complex [(((ArO)-Ar-Ad,Me)(3)mes)U] (refs 18 and 19)-the first homogeneous uranium catalyst for H-2 production from H2O. The catalytic cycle involves rare terminal U(iv)-OH and U(v)= O complexes, which have been isolated, characterized, and proven to be integral parts of the catalytic mechanism. The recognition of uranium compounds as potentially useful catalysts suggests new applications for such light actinides. The development of uranium-based catalysts provides new perspectives on nuclear waste management strategies, by suggesting that mildly radioactive depleted uranium-an abundant waste product of the nuclear power industry-could be a valuable resource.
C1 [Halter, Dominik P.; Heinemann, Frank W.; Bachmann, Julien; Meyer, Karsten] Univ Erlangen Nurnberg, Dept Chem & Pharm, Inorgan Chem, Egerlandstr 1, D-91053 Erlangen, Germany.
C3 University of Erlangen Nuremberg
RP Meyer, K (corresponding author), Univ Erlangen Nurnberg, Dept Chem & Pharm, Inorgan Chem, Egerlandstr 1, D-91053 Erlangen, Germany.
EM karsten.meyer@fau.de
NR 37
TC 165
Z9 194
U1 2
U2 372
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 317
EP +
DI 10.1038/nature16530
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100033
PM 26808900
DA 2026-03-09
ER

PT J
AU Nakamura, T
   Gehrke, AR
   Lemberg, J
   Zymaszek, JS
   Shubin, NH
AF Nakamura, Tetsuya
   Gehrke, Andrew R.
   Lemberg, Justin
   Zymaszek, Julie S.
   Shubin, Neil H.
TI Digits and fin rays share common developmental histories
SO NATURE
LA English
DT Article
ID trunk neural crest; gene-expression; limb transition; paired fins; hox-genes; zebrafish; origin; evolution; fish; appendages
AB Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology(1). The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically(2,3). Moreover, comparisons of fins with limbs have been limited by a relative paucity of data on the cellular and molecular processes underlying the development of the fin skeleton. Here, we provide a functional analysis, using CRISPR/Cas9 and fate mapping, of 5' hox genes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods(4,5). We show that cells marked by the activity of an autopodial hoxa13 enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. In hox13 knockout fish, we find that a marked reduction and loss of fin rays is associated with an increased number of endochondral distal radials. These discoveries reveal a cellular and genetic connection between the fin rays of fish and the digits of tetrapods and suggest that digits originated via the transition of distal cellular fates.
C1 [Nakamura, Tetsuya; Gehrke, Andrew R.; Lemberg, Justin; Zymaszek, Julie S.; Shubin, Neil H.] Univ Chicago, Dept Organismal Biol & Anat, 1025 E 57Th St, Chicago, IL 60637 USA.
C3 University of Chicago
RP Shubin, NH (corresponding author), Univ Chicago, Dept Organismal Biol & Anat, 1025 E 57Th St, Chicago, IL 60637 USA.
EM nshubin@uchicago.edu
FU Uehara Memorial Foundation; Japan Society for the Promotion of Science; Marine Biological Laboratory Research Award; National Institutes of Health [T32 HD055164]; National Science Foundation [1311436]; Brinson Foundation; University of Chicago Biological Sciences Division; Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD055164] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Environmental Biology [1311436] Funding Source: National Science Foundation
NR 33
TC 110
Z9 134
U1 1
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 225
EP +
DI 10.1038/nature19322
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100046
PM 27533041
DA 2026-03-09
ER

PT J
AU Meng, FK
   Li, XB
   Torker, S
   Shi, Y
   Shen, X
   Hoveyda, AH
AF Meng, Fanke
   Li, Xiben
   Torker, Sebastian
   Shi, Ying
   Shen, Xiao
   Hoveyda, Amir H.
TI Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups
SO NATURE
LA English
DT Article
ID conjugate allylation; asymmetric 1,6-addition; organic-synthesis; aldehydes; reagents; ligands; iridium
AB Conjugate (or 1,4-) additions of carbanionic species to alpha,beta-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates(1). Nonetheless, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic alpha,beta,gamma,delta-doubly unsaturated acceptors are unknown(2). Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable because the resulting products could then be subjected to further modifications. However, such reactions, especially when dienoates contain two equally substituted olefins, are scarce(3) and are confined to reactions promoted by a phosphine-copper catalyst (with an alkyl Grignard reagent(4,5), dialkylzinc or trialkylaluminium compounds(6,7)), a diene-iridium catalyst (with arylboroxines)(8,9), or a bisphosphine-cobalt catalyst (with monosilyl-acetylenes)(10). 1,6-Conjugate additions are otherwise limited to substrates where there is full substitution at the C4 position(11). It is unclear why certain catalysts favour bond formation at C6, and-although there are a small number of catalytic enantioselective conjugate allyl additions(12-15)-related 1,6-additions and processes involving a propargyl unit are non-existent. Here we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenyl-boron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 per cent yield, >98:2 diastereomeric ratio (for allyl additions) and 99:1 enantiomeric ratio. We elucidate the mechanistic details, including the origins of high site selectivity (1,6-versus 1,4-) and enantioselectivity as a function of the catalyst structure and reaction type, by means of density functional theory calculations. The utility of the approach is highlighted by an application towards enantioselective synthesis of the anti-HIV agent (-)-equisetin.
C1 [Meng, Fanke; Li, Xiben; Torker, Sebastian; Shi, Ying; Shen, Xiao; Hoveyda, Amir H.] Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
C3 Boston College
RP Hoveyda, AH (corresponding author), Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU United States National Institutes of Health, Institute of General Medical Sciences [GM-47480]; National Science Foundation [CHE-1362763]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1362763] Funding Source: National Science Foundation
NR 30
TC 112
Z9 125
U1 1
U2 173
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 387
EP 393
DI 10.1038/nature19063
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000051
PM 27479320
DA 2026-03-09
ER

PT J
AU Mansoor, SE
   Lü, W
   Oosterheert, W
   Shekhar, M
   Tajkhorshid, E
   Gouaux, E
AF Mansoor, Steven E.
   Lu, Wei
   Oosterheert, Wout
   Shekhar, Mrinal
   Tajkhorshid, Emad
   Gouaux, Eric
TI X-ray structures define human P2X3 receptor gating cycle and antagonist action
SO NATURE
LA English
DT Article
ID molecular-dynamics; ion-channel; p2x(2/3) receptors; crystal-structure; amino-terminus; atp-binding; desensitization; identification; domain; rationalization
AB P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X(3) receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the 'cytoplasmic cap', which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents.
C1 [Mansoor, Steven E.; Lu, Wei; Oosterheert, Wout; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Mansoor, Steven E.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA.
   [Shekhar, Mrinal; Tajkhorshid, Emad] Univ Illinois, Dept Biochem, Ctr Biophys & Quantitat Biol, Urbana, IL 61801 USA.
   [Shekhar, Mrinal; Tajkhorshid, Emad] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
   [Oosterheert, Wout] Univ Utrecht, Bijvoet Ctr Biomol Res, Crystal & Struct Chem, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
C3 Oregon Health & Science University; Oregon Health & Science University; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Oregon Health & Science University; Howard Hughes Medical Institute; Utrecht University
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.; Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU National Institutes of General Medical Sciences [U54-GM087519, P41-GM104601]; National Institute of General Medical Sciences [5F32GM108391, R01GM100400]; National Institute of General Medical Sciences [P41GM104601] Funding Source: NIH RePORTER
NR 72
TC 212
Z9 229
U1 1
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 66
EP +
DI 10.1038/nature19367
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900034
PM 27626375
DA 2026-03-09
ER

PT J
AU Im, SJ
   Hashimoto, M
   Gerner, MY
   Lee, J
   Kissick, HT
   Urger, MCB
   Shan, Q
   Hale, JS
   Lee, J
   Nasti, TH
   Sharpe, AH
   Freeman, GJ
   Germain, RN
   Nakaya, HI
   Xue, HH
   Ahmed, R
AF Im, Se Jin
   Hashimoto, Masao
   Gerner, Michael Y.
   Lee, Junghwa
   Kissick, Haydn T.
   Urger, Matheus C. B.
   Shan, Qiang
   Hale, J. Scott
   Lee, Judong
   Nasti, Tahseen H.
   Sharpe, Arlene H.
   Freeman, Gordon J.
   Germain, Ronald N.
   Nakaya, Helder I.
   Xue, Hai-Hui
   Ahmed, Rafi
TI Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy
SO NATURE
LA English
DT Article
ID chronic viral-infection; lymphocytic choriomeningitis virus; transcription factor; lymphoid organs; memory; persistence; effector; fh; differentiation; exhaustion
AB Chronic viral infections are characterized by a state of CD8(+) T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor(1-4). A better understanding of the mechanisms that regulate CD8(+) T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8(+) T cells. Here we identify a population of virus-specific CD8(+) T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8(+) T cells expressed the PD-1 inhibitory receptor, but also expressed several costimulatory molecules such as ICOS and CD28. This CD8(+) T-cell subset was characterized by a unique gene signature that was related to that of CD4(+) T follicular helper (T-FH) cells, CD8(+) T cell memory precursors and haematopoietic stem cell progenitors, but that was distinct from that of CD4(+) T(H)1 cells and CD8(+) terminal effectors. This CD8(+) T-cell population was found only in lymphoid tissues and resided predominantly in the T-cell zones along with naive CD8(+) T cells. These PD-1(+) CD8(+) T cells resembled stem cells during chronic LCMV infection, undergoing self-renewal and also differentiating into the terminally exhausted CD8(+) T cells that were present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade came almost exclusively from this CD8(+) T-cell subset. Notably, the transcription factor TCF1 had a cell-intrinsic and essential role in the generation of this CD8(+) T-cell subset. These findings provide a better understanding of T-cell exhaustion and have implications in the optimization of PD-1-directed immunotherapy in chronic infections and cancer.
C1 [Im, Se Jin; Hashimoto, Masao; Lee, Junghwa; Kissick, Haydn T.; Hale, J. Scott; Lee, Judong; Nasti, Tahseen H.; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Im, Se Jin; Hashimoto, Masao; Lee, Junghwa; Kissick, Haydn T.; Hale, J. Scott; Lee, Judong; Nasti, Tahseen H.; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
   [Gerner, Michael Y.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Gerner, Michael Y.] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98109 USA.
   [Kissick, Haydn T.] Emory Univ, Dept Urol, Sch Med, Atlanta, GA 30322 USA.
   [Urger, Matheus C. B.; Nakaya, Helder I.] Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508 Sao Paulo, Brazil.
   [Shan, Qiang; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA.
   [Sharpe, Arlene H.] Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA 02115 USA.
   [Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
   [Freeman, Gordon J.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Dept Med, Boston, MA 02115 USA.
   [Xue, Hai-Hui] Univ Iowa, Carver Coll Med, Interdisciplinary Immunol Grad Program, Iowa City, IA 52242 USA.
C3 Emory University; Emory University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Washington; University of Washington Seattle; Emory University; Universidade de Sao Paulo; University of Iowa; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Iowa
RP Ahmed, R (corresponding author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.; Ahmed, R (corresponding author), Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
FU National Institutes of Health [R01 AI30048, P01 AI056299, R01 AI112579, R01 AI121080]; Intramural Research Program of NIAID, NIH; Prostate Cancer Foundation; Swim Across America; CNPq; National Cancer Institute [P30CA086862] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI121080, P01AI056299, R01AI112579, ZIAAI001034, R01AI030048] Funding Source: NIH RePORTER
NR 37
TC 1597
Z9 1896
U1 11
U2 201
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 417
EP +
DI 10.1038/nature19330
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000057
PM 27501248
DA 2026-03-09
ER

PT J
AU Mevissen, TET
   Kulathu, Y
   Mulder, MPC
   Geurink, PP
   Maslen, SL
   Gersch, M
   Elliott, PR
   Burke, JE
   van Tol, BDM
   Akutsu, M
   El Oualid, F
   Kawasaki, M
   Freund, SMV
   Ovaa, H
   Komander, D
AF Mevissen, Tycho E. T.
   Kulathu, Yogesh
   Mulder, Monique P. C.
   Geurink, Paul P.
   Maslen, Sarah L.
   Gersch, Malte
   Elliott, Paul R.
   Burke, John E.
   van Tol, Bianca D. M.
   Akutsu, Masato
   El Oualid, Farid
   Kawasaki, Masato
   Freund, Stefan M. V.
   Ovaa, Huib
   Komander, David
TI Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne
SO NATURE
LA English
DT Article
ID ubiquitin chains; a20; inflammation; suppression; inhibition; activation; mechanism; binding; domain; e2
AB The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein(1). Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin(2), and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system. Here we reveal how the deubiquitinase Cezanne (also known as OTUD7B) specifically targets Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked diubiquitin, in combination with hydrogen-deuterium exchange mass spectrometry, enable us to reconstruct the enzymatic cycle in great detail. An intricate mechanism of ubiquitin-assisted conformational changes activates the enzyme, and while all chain types interact with the enzymatic S1 site, only Lys11-linked chains can bind productively across the active site and stimulate catalytic turnover. Our work highlights the plasticity of deubiquitinases and indicates that new conformational states can occur when a true substrate, such as diubiquitin, is bound at the active site.
C1 [Mevissen, Tycho E. T.; Kulathu, Yogesh; Maslen, Sarah L.; Gersch, Malte; Elliott, Paul R.; Burke, John E.; Akutsu, Masato; Freund, Stefan M. V.; Komander, David] MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
   [Mulder, Monique P. C.; Geurink, Paul P.; van Tol, Bianca D. M.; El Oualid, Farid; Ovaa, Huib] Netherlands Canc Inst, Div Cell Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Kawasaki, Masato] High Energy Accelerator Res Org KEK, Inst Mat Struct Sci, Photon Factory, Struct Biol Res Ctr, Tsukuba, Ibaraki 3050801, Japan.
   [Kulathu, Yogesh] MRC, Prot Phosphorylat & Ubiquitylat Unit, Dow St, Dundee DD1 5EH, Scotland.
   [Mulder, Monique P. C.; Geurink, Paul P.; Ovaa, Huib] Leiden Univ, Med Ctr, Chem Immunol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
   [Burke, John E.] Univ Victoria, Dept Biochem & Microbiol, 270 Petch Hall, Victoria, BC, Canada.
   [Akutsu, Masato] Goethe Univ, Buchmann Inst Mol Life Sci, D-60438 Frankfurt, Germany.
   [El Oualid, Farid] UbiQ Bio BV, Sci Pk 408, NL-1098 XH Amsterdam, Netherlands.
C3 MRC Laboratory Molecular Biology; Netherlands Cancer Institute; High Energy Accelerator Research Organization (KEK); Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); University of Victoria; Goethe University Frankfurt
RP Komander, D (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
EM dk@mrc-lmb.cam.ac.uk
FU EU [283570]; Medical Research Council [U105192732]; European Research Council [309756, 281699]; Lister Institute for Preventive Medicine; British Heart Foundation [PG11/109/29247]; Netherlands Organization for Scientific Research VICI [724.013.002]; Marie Curie ITN UPStream; Marie Curie Fellowship; EMBO; British Heart Foundation [PG/11/109/29247] Funding Source: researchfish; Medical Research Council [MC_U105192732, MC_U105184308] Funding Source: researchfish; European Research Council (ERC) [281699] Funding Source: European Research Council (ERC); MRC [MC_U105192732, MC_U105184308] Funding Source: UKRI
NR 25
TC 128
Z9 158
U1 3
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 402
EP +
DI 10.1038/nature19836
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100043
PM 27732584
DA 2026-03-09
ER

PT J
AU Pedersen, HK
   Gudmundsdottir, V
   Nielsen, HB
   Hyotylainen, T
   Nielsen, T
   Jensen, BAH
   Forslund, K
   Hildebrand, F
   Prifti, E
   Falony, G
   Le Chatelier, E
   Levenez, F
   Doré, J
   Mattila, I
   Plichta, DR
   Pöhö, P
   Hellgren, LI
   Arumugam, M
   Sunagawa, S
   Vieira-Silva, S
   Jorgensen, T
   Holm, JB
   Trost, K
   Kristiansen, K
   Brix, S
   Raes, J
   Wang, J
   Hansen, T
   Bork, P
   Brunak, S
   Oresic, M
   Ehrlich, SD
   Pedersen, O
AF Pedersen, Helle Krogh
   Gudmundsdottir, Valborg
   Nielsen, Henrik Bjorn
   Hyotylainen, Tuulia
   Nielsen, Trine
   Jensen, Benjamin A. H.
   Forslund, Kristoffer
   Hildebrand, Falk
   Prifti, Edi
   Falony, Gwen
   Le Chatelier, Emmanuelle
   Levenez, Florence
   Dore, Joel
   Mattila, Ismo
   Plichta, Damian R.
   Poho, Paivi
   Hellgren, Lars I.
   Arumugam, Manimozhiyan
   Sunagawa, Shinichi
   Vieira-Silva, Sara
   Jorgensen, Torben
   Holm, Jacob Bak
   Trost, Kajetan
   Kristiansen, Karsten
   Brix, Susanne
   Raes, Jeroen
   Wang, Jun
   Hansen, Torben
   Bork, Peer
   Brunak, Soren
   Oresic, Matej
   Ehrlich, S. Dusko
   Pedersen, Oluf
TI Human gut microbes impact host serum metabolome and insulin sensitivity
SO NATURE
LA English
DT Article
ID saturated fatty-acids; chain amino-acids; resistance; glucose; association; metagenome; adipocyte; abundance; profiles; genm
AB Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
C1 [Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjorn; Plichta, Damian R.; Hellgren, Lars I.; Brix, Susanne; Brunak, Soren] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Hyotylainen, Tuulia] Univ Orebro, SE-70281 Orebro, Sweden.
   [Hyotylainen, Tuulia; Oresic, Matej] Univ Turku, Turku Ctr Biotechnol, FI-20520 Turku, Finland.
   [Hyotylainen, Tuulia; Oresic, Matej] Abo Akad Univ, FI-20520 Turku, Finland.
   [Hyotylainen, Tuulia; Mattila, Ismo; Poho, Paivi; Oresic, Matej] VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland.
   [Nielsen, Trine; Arumugam, Manimozhiyan; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Jensen, Benjamin A. H.; Holm, Jacob Bak; Kristiansen, Karsten; Wang, Jun] Univ Copenhagen, Dept Biol, Lab Genom & Mol Biomed, DK-2100 Copenhagen, Denmark.
   [Forslund, Kristoffer; Hildebrand, Falk; Sunagawa, Shinichi; Bork, Peer] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Hildebrand, Falk; Raes, Jeroen] Vrije Univ Brussel, Dept Biosci Engn, B-1050 Brussels, Belgium.
   [Hildebrand, Falk; Falony, Gwen; Vieira-Silva, Sara; Raes, Jeroen] VIB, Ctr Biol Dis, B-3000 Louvain, Belgium.
   [Prifti, Edi; Le Chatelier, Emmanuelle; Levenez, Florence; Dore, Joel; Ehrlich, S. Dusko] Univ Paris Saclay, INRA, MGP MetaGenoPolis, F-78350 Jouy En Josas, France.
   [Prifti, Edi] Inst Cardiometab & Nutr ICAN, F-75013 Paris, France.
   [Falony, Gwen; Vieira-Silva, Sara; Raes, Jeroen] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, B-3000 Louvain, Belgium.
   [Dore, Joel] Univ Paris Saclay, INRA, AgroParisTech, Micalis Inst, F-78350 Jouy En Josas, France.
   [Mattila, Ismo; Trost, Kajetan; Oresic, Matej] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
   [Poho, Paivi] Univ Helsinki, Fac Pharm, FI-00014 Helsinki, Finland.
   [Sunagawa, Shinichi] ETH, Inst Microbiol, CH-8092 Zurich, Switzerland.
   [Jorgensen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
   [Jorgensen, Torben] Glostrup Cty Hosp, Capital Reg, Ctr Hlth, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.
   [Kristiansen, Karsten; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Wang, Jun] King Abdulaziz Univ, Princess Al Jawhara Albrahim Ctr Excellence Res H, Jeddah, Saudi Arabia.
   [Wang, Jun] Macau Univ Sci & Technol, Ave Wai Long, Taipa, Macau, Peoples R China.
   [Wang, Jun] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
   [Wang, Jun] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China.
   [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark.
   [Bork, Peer] Heidelberg Univ, Mol Med Partnership Unit, D-69120 Heidelberg, Germany.
   [Bork, Peer] European Mol Biol Lab, D-69120 Heidelberg, Germany.
   [Bork, Peer] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Bork, Peer] Univ Wurzburg, Dept Bioinformat, D-97074 Wurzburg, Germany.
   [Brunak, Soren] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res Dis Syst Biol, DK-2200 Copenhagen, Denmark.
   [Ehrlich, S. Dusko] Kings Coll London, Ctr Host Microbiome Interact, Dent Inst Cent Off, Guys Hosp, London SE1 9RT, England.
C3 Technical University of Denmark; Orebro University; University of Turku; Abo Akademi University; VTT Technical Research Center Finland; University of Copenhagen; Novo Nordisk Foundation; University of Copenhagen; European Molecular Biology Laboratory (EMBL); Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); INRAE; Universite Paris Saclay; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); KU Leuven; AgroParisTech; Universite Paris Saclay; INRAE; Steno Diabetes Center; University of Helsinki; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Copenhagen; University of Copenhagen; Beijing Genomics Institute (BGI); King Abdulaziz University; Macau University of Science & Technology; University of Hong Kong; University of Hong Kong; University of Southern Denmark; Ruprecht Karls University Heidelberg; European Molecular Biology Laboratory (EMBL); Helmholtz Association; Max Delbruck Center for Molecular Medicine; University of Wurzburg; University of Copenhagen; Novo Nordisk Foundation; Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London
RP Brunak, S (corresponding author), Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.; Oresic, M (corresponding author), Univ Turku, Turku Ctr Biotechnol, FI-20520 Turku, Finland.; Oresic, M (corresponding author), Abo Akad Univ, FI-20520 Turku, Finland.; Oresic, M (corresponding author), VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland.; Pedersen, O (corresponding author), Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.; Ehrlich, SD (corresponding author), Univ Paris Saclay, INRA, MGP MetaGenoPolis, F-78350 Jouy En Josas, France.; Oresic, M (corresponding author), Steno Diabet Ctr, DK-2820 Gentofte, Denmark.; Pedersen, O (corresponding author), Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.; Brunak, S (corresponding author), Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res Dis Syst Biol, DK-2200 Copenhagen, Denmark.; Ehrlich, SD (corresponding author), Kings Coll London, Ctr Host Microbiome Interact, Dent Inst Cent Off, Guys Hosp, London SE1 9RT, England.
EM soren.brunak@cpr.ku.dk; matej.oresic@gmail.com; dusko.ehrlich@jouy.inra.fr; oluf@sund.ku.dk
FU European Community [HEALTH-F4-2007-201052]; Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp), Metagenopolis grant [ANR-11-DPBS-0001, HEALTH-F4-2012-305312]; Rega institute for Medical Research, KU Leuven; Agency for Innovation by Science and Technology (IWT) [267139]; Fund for Scientific Research Flanders (FWO); Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; EU FP7 Project TORNADO [222720]; European Union [600375]; Innovative Medicines Initiative Joint Undertaking from the European Union [115317]; Lundbeck Foundation [R155-2013-14070] Funding Source: researchfish; NNF Center for Basic Metabolic Research [Grarup Group, Hansen Group] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Søren Brunak] Funding Source: researchfish
NR 75
TC 1623
Z9 1839
U1 19
U2 793
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 376
EP +
DI 10.1038/nature18646
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200031
PM 27409811
DA 2026-03-09
ER

PT J
AU Levasseur, A
   Bekliz, M
   Chabrière, E
   Pontarotti, P
   La Scola, B
   Raoult, D
AF Levasseur, Anthony
   Bekliz, Meriem
   Chabriere, Eric
   Pontarotti, Pierre
   La Scola, Bernard
   Raoult, Didier
TI MIMIVIRE is a defence system in mimivirus that confers resistance to virophage
SO NATURE
LA English
DT Article
ID crispr-cas systems; giant virus; evolutionary network; rna-interference; prokaryotes; immunity; amebas; classification; bacteria; elements
AB Since their discovery, giant viruses have revealed several unique features that challenge the conventional definition of a virus, such as their large and complex genomes, their infection by virophages and their presence of transferable short element transpovirons(1-5). Here we investigate the sensitivity of mimivirus to virophage infection in a collection of 59 viral strains and demonstrate lineage specificity in the resistance of mimivirus to Zamilon(6), a unique virophage that can infect lineages B and C of mimivirus but not lineage A. We hypothesized that mimiviruses harbour a defence mechanism resembling the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system that is widely present in bacteria and archaea(7-10). We performed de novo sequencing of 45 new mimivirus strains and searched for sequences specific to Zamilon in a total of 60 mimivirus genomes. We found that lineage A strains are resistant to Zamilon and contain the insertion of a repeated Zamilon sequence within an operon, here named the 'mimivirus virophage resistance element' (MIMIVIRE). Further analyses of the surrounding sequences showed that this locus is reminiscent of a defence mechanism related to the CRISPR-Cas system. Silencing the repeated sequence and the MIMIVIRE genes restores mimivirus susceptibility to Zamilon. The MIMIVIRE proteins possess the typical functions (nuclease and helicase) involved in the degradation of foreign nucleic acids. The viral defence system, MIMIVIRE, represents a nucleic-acid-based immunity against virophage infection.
C1 [Levasseur, Anthony; Bekliz, Meriem; Chabriere, Eric; La Scola, Bernard; Raoult, Didier] Aix Marseille Univ, URMITE, INSERM, UM63,CNRS 7278,IRD 198,U1095, Marseille, France.
   [Levasseur, Anthony; Bekliz, Meriem; Chabriere, Eric; La Scola, Bernard; Raoult, Didier] IHU Mediterranee Infect, Assistance Publ Hop Marseille, Fac Med, 27 Blvd Jean Moulin, F-13005 Marseille, France.
   [Pontarotti, Pierre] Aix Marseille Univ, CNRS, Cent Marseille, I2M,UMR7373,FR 4213,FR Eccorev 3098,Equipe EBM, F-13331 Marseille, France.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut de Recherche pour le Developpement (IRD); Aix-Marseille Universite; Assistance Publique-Hopitaux de Marseille; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Mathematical Sciences (INSMI); Aix-Marseille Universite
RP La Scola, B; Raoult, D (corresponding author), Aix Marseille Univ, URMITE, INSERM, UM63,CNRS 7278,IRD 198,U1095, Marseille, France.; La Scola, B; Raoult, D (corresponding author), IHU Mediterranee Infect, Assistance Publ Hop Marseille, Fac Med, 27 Blvd Jean Moulin, F-13005 Marseille, France.
EM bernard.la-scola@univ-amu.fr; didier.raoult@gmail.com
NR 22
TC 89
Z9 104
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 249
EP +
DI 10.1038/nature17146
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100045
PM 26934229
DA 2026-03-09
ER

PT J
AU Wu, JY
   Huang, B
   Chen, H
   Yin, QZ
   Liu, Y
   Xiang, YL
   Zhang, BJ
   Liu, BF
   Wang, QJ
   Xia, WK
   Li, WZ
   Li, YY
   Ma, J
   Peng, X
   Zheng, H
   Ming, J
   Zhang, WH
   Zhang, J
   Tian, G
   Xu, F
   Chang, Z
   Na, J
   Yang, XR
   Xie, W
AF Wu, Jingyi
   Huang, Bo
   Chen, He
   Yin, Qiangzong
   Liu, Yang
   Xiang, Yunlong
   Zhang, Bingjie
   Liu, Bofeng
   Wang, Qiujun
   Xia, Weikun
   Li, Wenzhi
   Li, Yuanyuan
   Ma, Jing
   Peng, Xu
   Zheng, Hui
   Ming, Jia
   Zhang, Wenhao
   Zhang, Jing
   Tian, Geng
   Xu, Feng
   Chang, Zai
   Na, Jie
   Yang, Xuerui
   Xie, Wei
TI The landscape of accessible chromatin in mammalian preimplantation embryos
SO NATURE
LA English
DT Article
ID gene-expression; mouse embryo; stem-cells; rna-seq; visceral endoderm; transcription; differentiation; dynamics; reveals; genome
AB In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development.
C1 [Wu, Jingyi; Yin, Qiangzong; Xiang, Yunlong; Zhang, Bingjie; Liu, Bofeng; Wang, Qiujun; Xia, Weikun; Li, Yuanyuan; Ma, Jing; Zheng, Hui; Zhang, Wenhao; Xie, Wei] Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Stem Cell Biol & Regenerat Med, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China.
   [Wu, Jingyi; Liu, Yang; Yang, Xuerui; Xie, Wei] Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China.
   [Huang, Bo] Peking Univ, Acad Adv Interdisciplinary Studies, PKU THU Ctr Life Sci, Beijing 100871, Peoples R China.
   [Chen, He] Peking Univ, Coll Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100871, Peoples R China.
   [Liu, Yang; Yang, Xuerui] Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Synthet & Syst Biol, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China.
   [Li, Wenzhi; Ming, Jia; Na, Jie] Tsinghua Univ, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Beijing 100084, Peoples R China.
   [Peng, Xu; Xu, Feng] ASTAR, Singapore Inst Clin Sci, Singapore 117609, Singapore.
   [Zhang, Jing; Chang, Zai] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
   [Tian, Geng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Xu, Feng] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
C3 Tsinghua University; National Institute of Biological Sciences, Beijing; Tsinghua University; Peking University; National Institute of Biological Sciences, Beijing; Peking University; Tsinghua University; Tsinghua University; Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Institute for Clinical Sciences (SICS); Tsinghua University; Tsinghua University; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB)
RP Xie, W (corresponding author), Tsinghua Univ, MOE Key Lab Bioinformat, Ctr Stem Cell Biol & Regenerat Med, THU PKU Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China.; Xie, W (corresponding author), Tsinghua Univ, Sch Life Sci, Joint Grad Program Peking Tsinghua NIBS, Beijing 100084, Peoples R China.
EM xiewei121@tsinghua.edu.cn
FU National Basic Research Program of China (973 program) [2015CB856201]; National Natural Science Foundation of China [31422031, 31171381, 81472855]; National Basic Research Program of China [2012CB966701]; Beijing Natural Science Foundation [5152014]; Tsinghua University Initiative Scientific Research Program [20131089278, 2014z21046]; THU-PKU Center for Life Sciences; Youth Thousand Scholar Program of China
NR 50
TC 553
Z9 630
U1 7
U2 311
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 652
EP +
DI 10.1038/nature18606
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000029
PM 27309802
DA 2026-03-09
ER

PT J
AU Prieto-Godino, LL
   Rytz, R
   Bargeton, B
   Abuin, L
   Arguello, JR
   Dal Peraro, M
   Benton, R
AF Prieto-Godino, Lucia L.
   Rytz, Raphael
   Bargeton, Benoite
   Abuin, Liliane
   Arguello, J. Roman
   Dal Peraro, Matteo
   Benton, Richard
TI Olfactory receptor pseudo-pseudogenes
SO NATURE
LA English
DT Article
ID ionotropic glutamate receptors; genetic reference panel; stop codon readthrough; drosophila-melanogaster; saccharomyces-cerevisiae; nonsense mutations; sequence; genome; architecture; evolution
AB Pseudogenes are generally considered to be non-functional DNA sequences that arise through nonsense or frame-shift mutations of protein-coding genes(1). Although certain pseudogene-derived RNAs have regulatory roles(2), and some pseudogene fragments are translated(3), no clear functions for pseudogene-derived proteins are known. Olfactory receptor families contain many pseudogenes, which reflect low selection pressures on loci no longer relevant to the fitness of a species(4). Here we report the characterization of a pseudogene in the chemosensory variant ionotropic glutamate receptor repertoire(5,6) of Drosophila sechellia, an insect endemic to the Seychelles that feeds almost exclusively on the ripe fruit of Morinda citrifolia(7). This locus, D. sechellia Ir75a, bears a premature termination codon (PTC) that appears to be fixed in the population. However, D. sechellia Ir75a encodes a functional receptor, owing to efficient translational read-through of the PTC. Read-through is detected only in neurons and is independent of the type of termination codon, but depends on the sequence downstream of the PTC. Furthermore, although the intact Drosophila melanogaster Ir75a orthologue detects acetic acid-a chemical cue important for locating fermenting food8,9 found only at trace levels in Morinda fruit(10)-D. sechellia Ir75a has evolved distinct odour-tuning properties through amino-acid changes in its ligand-binding domain. We identify functional PTC-containing loci within different olfactory receptor repertoires and species, suggesting that such 'pseudo-pseudogenes' could represent a widespread phenomenon. [GRAPHICS] .
C1 [Prieto-Godino, Lucia L.; Rytz, Raphael; Bargeton, Benoite; Abuin, Liliane; Arguello, J. Roman; Benton, Richard] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Dal Peraro, Matteo] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland.
   [Dal Peraro, Matteo] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Rytz, Raphael] Fed Off Publ Hlth, CH-3003 Bern, Switzerland.
C3 University of Lausanne; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Institute of Bioinformatics
RP Benton, R (corresponding author), Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
EM richard.benton@unil.ch
FU FEBS long-term fellowship; Roche Research Foundation fellowship; Novartis Foundation [12A14]; SNSF; ERC Starting Independent Researcher and Consolidator Grants [205202, 615094]; HFSP Young Investigator Award [RGY0073/2011]; SNSF Nano-Tera Envirobot project [20NA21_143082]
NR 50
TC 111
Z9 131
U1 0
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 93
EP +
DI 10.1038/nature19824
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100036
PM 27776356
DA 2026-03-09
ER

PT J
AU Badro, J
   Siebert, J
   Nimmo, F
AF Badro, James
   Siebert, Julien
   Nimmo, Francis
TI An early geodynamo driven by exsolution of mantle components from Earth's core
SO NATURE
LA English
DT Article
ID differentiation; convection; accretion; evolution; dynamo; equilibration; conductivity; mechanisms; moon; iron
AB Recent palaeomagnetic observations(1) report the existence of a magnetic field on Earth that is at least 3.45 billion years old. Compositional buoyancy caused by inner-core growth(2) is the primary driver of Earth's present-day geodynamo(3-5), but the inner core is too young(6) to explain the existence of a magnetic field before about one billion years ago. Theoretical models(7) propose that the exsolution of magnesium oxide-the major constituent of Earth's mantle-from the core provided a major source of the energy required to drive an early dynamo, but experimental evidence for the incorporation of mantle components into the core has been lacking. Indeed, terrestrial core formation occurred in the early molten Earth by gravitational segregation of immiscible metal and silicate melts, transporting iron-loving (siderophile) elements from the silicate mantle to the metallic core(8-10) and leaving rock-loving (lithophile) mantle components behind. Here we present experiments showing that magnesium oxide dissolves in core-forming iron melt at very high temperatures. Using core-formation models(11), we show that extreme events during Earth's accretion (such as the Moon-forming giant impact(12)) could have contributed large amounts of magnesium to the early core. As the core subsequently cooled, exsolution(7) of buoyant magnesium oxide would have taken place at the core-mantle boundary, generating a substantial amount of gravitational energy as a result of compositional buoyancy. This amount of energy is comparable to, if not more than, that produced by inner-core growth, resolving the conundrum posed by the existence of an ancient magnetic field prior to the formation of the inner core.
C1 [Badro, James; Siebert, Julien] Univ Paris Diderot, Univ Paris 04, Inst Phys Globe Paris, F-75005 Paris, France.
   [Badro, James] Ecole Polytech Fed Lausanne, Earth & Planetary Sci Lab, CH-1015 Lausanne, Switzerland.
   [Nimmo, Francis] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
C3 Sorbonne Universite; Universite Paris Cite; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of California System; University of California Santa Cruz
RP Badro, J (corresponding author), Univ Paris Diderot, Univ Paris 04, Inst Phys Globe Paris, F-75005 Paris, France.; Badro, J (corresponding author), Ecole Polytech Fed Lausanne, Earth & Planetary Sci Lab, CH-1015 Lausanne, Switzerland.
EM badro@ipgp.fr
FU European Research Council under the European Community [207467]; UnivEarthS Labex programme at Sorbonne Paris Cite [ANR-10-LABX-0023, ANR-11-IDEX-0005-02]; IPGP multidisciplinary programme PARI; Paris-IdF region SESAME grant [12015908]; French National Research Agency (ANR project VolTerre) [ANR-14-CE33-0017-01]
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NR 41
TC 151
Z9 165
U1 0
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 326
EP +
DI 10.1038/nature18594
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900034
PM 27437583
DA 2026-03-09
ER

PT J
AU Johnson, TC
   Werne, JP
   Brown, ET
   Abbott, A
   Berke, M
   Steinman, BA
   Halbur, J
   Contreras, S
   Grosshuesch, S
   Deino, A
   Lyons, RP
   Scholz, CA
   Schouten, S
   Damsté, JSS
AF Johnson, T. C.
   Werne, J. P.
   Brown, E. T.
   Abbott, A.
   Berke, M.
   Steinman, B. A.
   Halbur, J.
   Contreras, S.
   Grosshuesch, S.
   Deino, A.
   Lyons, R. P.
   Scholz, C. A.
   Schouten, S.
   Damste, J. S. Sinninghe
TI A progressively wetter climate in southern East Africa over the past 1.3 million years
SO NATURE
LA English
DT Article
ID sea-surface temperatures; tetraether lipids; tex86 paleothermometer; lake; record; variability; equatorial; megadroughts; calibration; evolution
AB African climate is generally considered to have evolved towards progressively drier conditions over the past few million years, with increased variability as glacial-interglacial change intensified worldwide(1-3). Palaeoclimate records derived mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle overprinted on a pronounced 20,000-year (precession) beat, driven by orbital forcing of summer insolation, global ice volume and long-lived atmospheric greenhouse gases(4). Here we present a 1.3-million-year-long climate history from the Lake Malawi basin (10 degrees-14 degrees S in eastern Africa), which displays strong 100,000-year (eccentricity) cycles of temperature and rainfall following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial periods were relatively warm and moist, while ice ages were cool and dry. The Malawi record shows limited evidence for precessional variability, which we attribute to the opposing effects of austral summer insolation and the temporal/spatial pattern of sea surface temperature in the Indian Ocean. The temperature history of the Malawi basin, at least for the past 500,000 years, strongly resembles past changes in atmospheric carbon dioxide and terrigenous dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in this sector of eastern Africa (unlike northern Africa) evolved from a predominantly arid environment with high-frequency variability to generally wetter conditions with more prolonged wet and dry intervals.
C1 [Johnson, T. C.; Brown, E. T.; Steinman, B. A.; Halbur, J.; Grosshuesch, S.] Univ Minnesota, Large Lakes Observ, Duluth, MN 55812 USA.
   [Johnson, T. C.; Brown, E. T.; Steinman, B. A.; Halbur, J.; Grosshuesch, S.] Univ Minnesota, Dept Earth & Environm Sci, Duluth, MN 55812 USA.
   [Johnson, T. C.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
   [Werne, J. P.] Univ Pittsburgh, Dept Geol & Planetary Sci, Pittsburgh, PA 15260 USA.
   [Abbott, A.] Macquarie Univ, Fac Sci & Engn, Dept Earth & Planetary Sci, Sydney, NSW 2109, Australia.
   [Berke, M.] Univ Notre Dame, Dept Civil & Environm Engn & Earth Sci, 257 Fitzpatrick Hall, Notre Dame, IN 46556 USA.
   [Contreras, S.] Univ Catolica Santisima Concepcion, Dept Quim Ambiental, Casilla 297, Concepcion, Chile.
   [Contreras, S.] Univ Catolica Santisima Concepcion, CIBAS, Casilla 297, Concepcion, Chile.
   [Deino, A.] Berkeley Geochronol Ctr, 2455 Ridge Rd, Berkeley, CA 94709 USA.
   [Lyons, R. P.; Scholz, C. A.] Syracuse Univ, Dept Earth Sci, Heroy Geol Lab 011a, Syracuse, NY 13244 USA.
   [Schouten, S.; Damste, J. S. Sinninghe] NIOZ Netherlands Inst Sea Res, Dept Marine Microbiol & Biogeochem, POB 59, NL-1790 AB Den Burg, Netherlands.
   [Schouten, S.; Damste, J. S. Sinninghe] Univ Utrecht, POB 59, NL-1790 AB Den Burg, Netherlands.
   [Schouten, S.; Damste, J. S. Sinninghe] Univ Utrecht, Dept Earth Sci, Fac Geosci, POB 80-021, NL-3508 TA Utrecht, Netherlands.
   [Lyons, R. P.] Chevron Corp, 1400 Smith St, Houston, TX 77002 USA.
C3 University of Minnesota System; University of Minnesota Duluth; Large Lakes Observatory; University of Minnesota System; University of Minnesota Duluth; University of Massachusetts System; University of Massachusetts Amherst; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Macquarie University; University of Notre Dame; Universidad Catolica de la Santisima Concepcion; Universidad Catolica de la Santisima Concepcion; Berkeley Geochronolgy Center; Syracuse University; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Utrecht University; Utrecht University; Chevron
RP Johnson, TC (corresponding author), Univ Minnesota, Large Lakes Observ, Duluth, MN 55812 USA.; Johnson, TC (corresponding author), Univ Minnesota, Dept Earth & Environm Sci, Duluth, MN 55812 USA.
EM tcj@d.umn.edu
FU US National Science Foundation EAR; US National Science Foundation P2C2; International Continental Scientific Drilling Program; Netherlands Earth System Science Centre (NESSC); Dutch Ministry of Education, Culture and Science (OCW); Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1322017] Funding Source: National Science Foundation; Directorate For Geosciences [1462347] Funding Source: National Science Foundation; Division Of Earth Sciences [1462347] Funding Source: National Science Foundation
NR 48
TC 90
Z9 102
U1 1
U2 110
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 220
EP +
DI 10.1038/nature19065
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100045
PM 27509851
DA 2026-03-09
ER

PT J
AU Slessarev, EW
   Lin, Y
   Bingham, NL
   Johnson, JE
   Dai, Y
   Schimel, JP
   Chadwick, OA
AF Slessarev, E. W.
   Lin, Y.
   Bingham, N. L.
   Johnson, J. E.
   Dai, Y.
   Schimel, J. P.
   Chadwick, O. A.
TI Water balance creates a threshold in soil pH at the global scale
SO NATURE
LA English
DT Article
ID data set; evaporation; vegetation; climate; brazil; flux
AB Soil pH regulates the capacity of soils to store and supply nutrients, and thus contributes substantially to controlling productivity in terrestrial ecosystems(1). However, soil pH is not an independent regulator of soil fertility-rather, it is ultimately controlled by environmental forcing. In particular, small changes in water balance cause a steep transition from alkaline to acid soils across natural climate gradients(2,3). Although the processes governing this threshold in soil pH are well understood, the threshold has not been quantified at the global scale, where the influence of climate may be confounded by the effects of topography and mineralogy. Here we evaluate the global relationship between water balance and soil pH by extracting a spatially random sample (n = 20,000) from an extensive compilation of 60,291 soil pH measurements. We show that there is an abrupt transition from alkaline to acid soil pH that occurs at the point where mean annual precipitation begins to exceed mean annual potential evapotranspiration. We evaluate deviations from this global pattern, showing that they may result from seasonality, climate history, erosion and mineralogy. These results demonstrate that climate creates a nonlinear pattern in soil solution chemistry at the global scale; they also reveal conditions under which soils maintain pH out of equilibrium with modern climate.
C1 [Slessarev, E. W.; Schimel, J. P.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Lin, Y.] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA.
   [Bingham, N. L.; Chadwick, O. A.] Univ Calif Santa Barbara, Dept Geog, Santa Barbara, CA 93106 USA.
   [Johnson, J. E.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ USA.
   [Dai, Y.] Sun Yat Sen Univ, Sch Atmospher Sci, Guangzhou, Guangdong, Peoples R China.
   [Johnson, J. E.] Carnegie Inst Sci, Dept Global Ecol, Stanford, CA USA.
C3 University of California System; University of California Santa Barbara; University of California System; University of California Berkeley; University of California System; University of California Santa Barbara; University of Arizona; Sun Yat Sen University; Carnegie Institution for Science
RP Slessarev, EW (corresponding author), Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
EM eric.slessarev@lifesci.ucsb.edu
FU United States National Science Foundation
NR 60
TC 465
Z9 533
U1 38
U2 580
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 567
EP +
DI 10.1038/nature20139
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500048
PM 27871089
DA 2026-03-09
ER

PT J
AU Gao, W
   Emaminejad, S
   Nyein, HYY
   Challa, S
   Chen, KV
   Peck, A
   Fahad, HM
   Ota, H
   Shiraki, H
   Kiriya, D
   Lien, DH
   Brooks, GA
   Davis, RW
   Javey, A
AF Gao, Wei
   Emaminejad, Sam
   Nyein, Hnin Yin Yin
   Challa, Samyuktha
   Chen, Kevin
   Peck, Austin
   Fahad, Hossain M.
   Ota, Hiroki
   Shiraki, Hiroshi
   Kiriya, Daisuke
   Lien, Der-Hsien
   Brooks, George A.
   Davis, Ronald W.
   Javey, Ali
TI Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis
SO NATURE
LA English
DT Article
ID sweat composition; skin; lactate; exercise; electronics; polymer; devices; dehydration; biosensors; pressure
AB Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health(1-12). Sampling human sweat, which is rich in physiological information(13), could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state(14-18). Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.
C1 [Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Chen, Kevin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Javey, Ali] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.
   [Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Chen, Kevin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Javey, Ali] Univ Calif Berkeley, Berkeley Sensor & Actuator Ctr, Berkeley, CA 94720 USA.
   [Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Chen, Kevin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Javey, Ali] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Emaminejad, Sam; Challa, Samyuktha; Davis, Ronald W.] Stanford Genome Technol Ctr, Stanford Sch Med, Palo Alto, CA 94304 USA.
   [Peck, Austin; Brooks, George A.] Univ Calif Berkeley, Integrat Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Stanford University; University of California System; University of California Berkeley
RP Javey, A (corresponding author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.; Javey, A (corresponding author), Univ Calif Berkeley, Berkeley Sensor & Actuator Ctr, Berkeley, CA 94720 USA.; Javey, A (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
EM ajavey@eecs.berkeley.edu
FU Berkeley Sensor and Actuator Center; National Institutes of Health [P01 HG000205]; Office of Science, Office of Basic Energy Sciences, Material Sciences and Engineering Division of the US Department of Energy [DE-AC02-05CH11231]; NSF Nanomanufacturing Systems for mobile Computing and Energy Technologies (NASCENT) Center; Japan Society for the Promotion of Science (JSPS) Fellowship; Directorate For Engineering [1068017] Funding Source: National Science Foundation; Div Of Industrial Innovation & Partnersh [1068017] Funding Source: National Science Foundation
NR 39
TC 4129
Z9 4714
U1 274
U2 6477
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 509
EP +
DI 10.1038/nature16521
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800033
PM 26819044
DA 2026-03-09
ER

PT J
AU Qiu, JZ
   Sheedlo, MJ
   Yu, KW
   Tan, YH
   Nakayasu, ES
   Das, C
   Liu, XY
   Luo, ZQ
AF Qiu, Jiazhang
   Sheedlo, Michael J.
   Yu, Kaiwen
   Tan, Yunhao
   Nakayasu, Ernesto S.
   Das, Chittaranjan
   Liu, Xiaoyun
   Luo, Zhao-Qing
TI Ubiquitination independent of E1 and E2 enzymes by bacterial effectors
SO NATURE
LA English
DT Article
ID legionella-pneumophila; endoplasmic-reticulum; substrate recognition; structural basis; cell biology; protein; system; family; phagosome; replication
AB Signalling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalysed by the E1, E2 and E3 three-enzyme cascade(1), which links the carboxy terminus of ubiquitin to the e-amino group of, in most cases, a lysine of the substrate via an isopeptide bond. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents(2). For example, many bacterial pathogens exploit ubiquitin signalling using virulence factors that function as E3 ligases, deubiquitinases3 or as enzymes that directly attack ubiquitin(4). The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a permissive niche for its replication in phagocytes(5). Here we demonstrate that members of the SidE effector family of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum. Moreover, we show that these proteins are capable of catalysing ubiquitination without the need for the E1 and E2 enzymes. A putative mono-ADP-ribosyltransferase motif critical for the ubiquitination activity is also essential for the role of the SidE family in intracellular bacterial replication in a protozoan host. The E1/E2-independent ubiquitination catalysed by these enzymes is energized by nicotinamide adenine dinucleotide, which activates ubiquitin by the formation of ADP-ribosylated ubiquitin. These results establish that ubiquitination can be catalysed by a single enzyme, the activity of which does not require ATP.
C1 [Qiu, Jiazhang; Tan, Yunhao; Luo, Zhao-Qing] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
   [Qiu, Jiazhang; Tan, Yunhao; Luo, Zhao-Qing] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Sheedlo, Michael J.; Das, Chittaranjan] Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
   [Yu, Kaiwen; Liu, Xiaoyun] Peking Univ, Inst Analyt Chem, Coll Chem & Mol Engn, Beijing 100871, Peoples R China.
   [Yu, Kaiwen; Liu, Xiaoyun] Peking Univ, Synthet & Funct Biomol Ctr, Coll Chem & Mol Engn, Beijing 100871, Peoples R China.
   [Nakayasu, Ernesto S.] Pacific NW Natl Lab, Biol Sci Div, Richland, WA 99352 USA.
   [Tan, Yunhao] Harvard Univ, Sch Med, Div Gastroenterol, Boston Childrens Hosp, Boston, MA 02115 USA.
C3 Purdue University System; Purdue University; Purdue University System; Purdue University; Purdue University System; Purdue University; Peking University; Peking University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Luo, ZQ (corresponding author), Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.; Luo, ZQ (corresponding author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM luoz@purdue.edu
FU National Institutes of Health [R56AI103168, K02AI085403, R21AI105714, 2R01GM103401]; National Natural Science Foundation of China [21305006, 21475005]; National Cancer Institute [P30CA023168] Funding Source: NIH RePORTER
NR 40
TC 292
Z9 371
U1 1
U2 132
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 120
EP +
DI 10.1038/nature17657
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900051
PM 27049943
DA 2026-03-09
ER

PT J
AU Zipperer, A
   Konnerth, MC
   Laux, C
   Berscheid, A
   Janek, D
   Weidenmaier, C
   Burian, M
   Schilling, NA
   Slavetinsky, C
   Marschal, M
   Willmann, M
   Kalbacher, H
   Schittek, B
   Brötz-Oesterhelt, H
   Grond, S
   Peschel, A
   Krismer, B
AF Zipperer, Alexander
   Konnerth, Martin C.
   Laux, Claudia
   Berscheid, Anne
   Janek, Daniela
   Weidenmaier, Christopher
   Burian, Marc
   Schilling, Nadine A.
   Slavetinsky, Christoph
   Marschal, Matthias
   Willmann, Matthias
   Kalbacher, Hubert
   Schittek, Birgit
   Broetz-Oesterhelt, Heike
   Grond, Stephanie
   Peschel, Andreas
   Krismer, Bernhard
TI Human commensals producing a novel antibiotic impair pathogen colonization
SO NATURE
LA English
DT Article
AB The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.
C1 [Zipperer, Alexander; Laux, Claudia; Janek, Daniela; Slavetinsky, Christoph; Peschel, Andreas; Krismer, Bernhard] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, D-72076 Tubingen, Germany.
   [Zipperer, Alexander; Laux, Claudia; Janek, Daniela; Weidenmaier, Christopher; Slavetinsky, Christoph; Willmann, Matthias; Broetz-Oesterhelt, Heike; Peschel, Andreas; Krismer, Bernhard] German Ctr Infect Res DZIF, D-72076 Tubingen, Germany.
   [Konnerth, Martin C.; Schilling, Nadine A.; Grond, Stephanie] Univ Tubingen, Inst Organ Chem, D-72076 Tubingen, Germany.
   [Berscheid, Anne; Broetz-Oesterhelt, Heike] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Microbial Bioact Cpds, D-72076 Tubingen, Germany.
   [Weidenmaier, Christopher; Marschal, Matthias; Willmann, Matthias] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Med Microbial, D-72076 Tubingen, Germany.
   [Burian, Marc; Schittek, Birgit] Univ Tubingen, Dept Dermatol, Div Dermatooncol, D-72076 Tubingen, Germany.
   [Schilling, Nadine A.; Kalbacher, Hubert] Univ Tubingen, Interfac Inst Bioch, D-72076 Tubingen, Germany.
   Boehringer Ingelheim GmbH & Co KG, Stockholm, Sweden.
C3 Eberhard Karls University of Tubingen; German Center for Infection Research; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Boehringer Ingelheim
RP Peschel, A (corresponding author), Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, D-72076 Tubingen, Germany.
EM andreas.peschel@uni-tuebingen.de
FU German Research Council [GRK1708, TRR156, Schi510/8-1, PE805/5-1, TRR34, SFB766]; German Center for Infection Research (DZIF)
NR 59
TC 688
Z9 835
U1 8
U2 260
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 511
EP 516
DI 10.1038/nature18634
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600041
PM 27466123
DA 2026-03-09
ER

PT J
AU Tsuchiya, H
   Doki, S
   Takemoto, M
   Ikuta, T
   Higuchi, T
   Fukui, K
   Usuda, Y
   Tabuchi, E
   Nagatoishi, S
   Tsumoto, K
   Nishizawa, T
   Ito, K
   Dohmae, N
   Ishitani, R
   Nureki, O
AF Tsuchiya, Hirotoshi
   Doki, Shintaro
   Takemoto, Mizuki
   Ikuta, Tatsuya
   Higuchi, Takashi
   Fukui, Keita
   Usuda, Yoshihiro
   Tabuchi, Eri
   Nagatoishi, Satoru
   Tsumoto, Kouhei
   Nishizawa, Tomohiro
   Ito, Koichi
   Dohmae, Naoshi
   Ishitani, Ryuichiro
   Nureki, Osamu
TI Structural basis for amino acid export by DMT superfamily transporter YddG
SO NATURE
LA English
DT Article
ID size-exclusion chromatography; membrane-proteins; escherichia-coli; molecular-dynamics; efflux; evolution; family; mechanism; systems; simulation
AB The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites(1). YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis(2,3). Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudosymmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.
C1 [Tsuchiya, Hirotoshi; Doki, Shintaro; Takemoto, Mizuki; Ikuta, Tatsuya; Higuchi, Takashi; Nishizawa, Tomohiro; Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 2-11-16 Yayoi, Tokyo 1130032, Japan.
   [Fukui, Keita] Ajinomoto Co Inc, Res Inst Biosci Prod & Fine Chem, Kawasaki Ku, 1-1 Suzuki Cho, Kawasaki, Kanagawa 2108681, Japan.
   [Usuda, Yoshihiro; Tabuchi, Eri] Ajinomoto Co Inc, Inst Innovat, Kawasaki Ku, 1-1 Suzuki Cho, Kawasaki, Kanagawa 2108681, Japan.
   [Nagatoishi, Satoru; Tsumoto, Kouhei] Univ Tokyo, Sch Engn, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
   [Ito, Koichi] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan.
   [Dohmae, Naoshi] RIKEN, Ctr Sustainable Resource Sci, Biomol Characterizat Unit, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
   [Ishitani, Ryuichiro] RIKEN, Theoret Mol Sci Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
C3 University of Tokyo; Ajinomoto Co Inc; Ajinomoto Co Inc; University of Tokyo; University of Tokyo; RIKEN; RIKEN
RP Ishitani, R; Nureki, O (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 2-11-16 Yayoi, Tokyo 1130032, Japan.; Ishitani, R (corresponding author), RIKEN, Theoret Mol Sci Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM ishitani@bs.s.u-tokyo.ac.jp; nureki@bs.s.u-tokyo.ac.jp
FU Platform for Drug Discovery, Informatics and Structural Life Science by the Ministry of Education, Culture, Sports, Science and Technology (MEXT); JSPS KAKENHI [24227004, 25291011, 26711003]; FIRST program; Grants-in-Aid for Scientific Research [16H02420, 16H06294, 26410190, 15J08129, 26711003, 16H04710, 15K17882] Funding Source: KAKEN
NR 43
TC 68
Z9 81
U1 2
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 417
EP +
DI 10.1038/nature17991
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800042
PM 27281193
DA 2026-03-09
ER

PT J
AU Nimmo, F
   Hamilton, DP
   McKinnon, WB
   Schenk, PM
   Binzel, RP
   Bierson, CJ
   Beyer, RA
   Moore, JM
   Stern, SA
   Weaver, HA
   Olkin, CB
   Young, LA
   Smith, KE
AF Nimmo, F.
   Hamilton, D. P.
   McKinnon, W. B. .
   Schenk, P. M.
   Binzel, R. P.
   Bierson, C. J.
   Beyer, R. A.
   Moore, J. M.
   Stern, S. A.
   Weaver, H. A.
   Olkin, C. B.
   Young, L. A.
   Smith, K. E.
TI Reorientation of Sputnik Planitia implies a subsurface ocean on Pluto
SO NATURE
LA English
DT Article
ID impact basin relaxation; kuiper-belt objects; topography; convection; horizons; europa
AB The deep nitrogen-covered basin on Pluto, informally named Sputnik Planitia, is located very close to the longitude of Pluto's tidal axis(1) and may be an impact feature(2), by analogy with other large basins in the Solar System(3,4). Reorientation(5-7) of Sputnik Planitia arising from tidal and rotational torques can explain the basin's present-day location, but requires the feature to be a positive gravity anomaly(7), despite its negative topography. Here we argue that if Sputnik Planitia did indeed form as a result of an impact and if Pluto possesses a subsurface ocean, the required positive gravity anomaly would naturally result because of shell thinning and ocean uplift, followed by later modest nitrogen deposition. Without a subsurface ocean, a positive gravity anomaly requires an implausibly thick nitrogen layer (exceeding 40 kilometres). To prolong the lifetime of such a subsurface ocean to the present day(8) and to maintain ocean uplift, a rigid, conductive water-ice shell is required. Because nitrogen deposition is latitude-dependent(9), nitrogen loading and reorientation may have exhibited complex feedbacks(7).
C1 [Nimmo, F.; Bierson, C. J.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Hamilton, D. P.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [McKinnon, W. B. .] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [McKinnon, W. B. .] Washington Univ, McDonnell Ctr Space Sci, St Louis, MO 63130 USA.
   [Schenk, P. M.] Lunar & Planetary Inst, Houston, TX 77058 USA.
   [Binzel, R. P.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Beyer, R. A.; Moore, J. M.; Smith, K. E.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Stern, S. A.; Olkin, C. B.; Young, L. A.] Southwest Res Inst, Boulder, CO 80302 USA.
   [Weaver, H. A.] Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
C3 University of California System; University of California Santa Cruz; University System of Maryland; University of Maryland College Park; Washington University (WUSTL); Washington University (WUSTL); Massachusetts Institute of Technology (MIT); National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Southwest Research Institute; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory
RP Nimmo, F (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
EM fnimmo@es.ucsc.edu
NR 37
TC 97
Z9 112
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 94
EP +
DI 10.1038/nature20148
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600054
PM 27851735
DA 2026-03-09
ER

PT J
AU Tang, L
   El-Din, TMG
   Swanson, TM
   Pryde, DC
   Scheuer, T
   Zheng, N
   Catterall, WA
AF Tang, Lin
   El-Din, Tamer M. Gamal
   Swanson, Teresa M.
   Pryde, David C.
   Scheuer, Todd
   Zheng, Ning
   Catterall, William A.
TI Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs
SO NATURE
LA English
DT Article
ID calcium-channels; sodium-channel; crystal-structure; skeletal-muscle; dihydropyridine binding; molecular determinants; receptor; subunit; pharmacology; mechanism
AB Ca2+ antagonist drugs are widely used in therapy of cardiovascular disorders(1,2). Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on Ca(v)1.2 channels, the most prominent voltage-gated Ca2+ (Ca-v) channel type in myocytes in cardiac and vascular smooth muscle'. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca2+ channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore(1,2). The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model Cav channel Ca(v)Ab, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca2+ interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on Cav channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.
C1 [Tang, Lin; El-Din, Tamer M. Gamal; Swanson, Teresa M.; Scheuer, Todd; Zheng, Ning; Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Tang, Lin; Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Pryde, David C.] Curadev Pharma, Discovery Pk, Sandwich CT14 9FF, Kent, England.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Tang, L (corresponding author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.; Tang, L (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
FU National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health [R01 HL112808]; National Research Service Award [T32 GM008268]; Howard Hughes Medical Institute; National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health [R01 NS26254]; Neusentis; Pfizer Inc., Cambridge, UK; National Heart Lung and Blood Institute [R01HL112808] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008268] Funding Source: NIH RePORTER
NR 30
TC 160
Z9 180
U1 2
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 117
EP 121
DI 10.1038/nature19102
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900050
PM 27556947
DA 2026-03-09
ER

PT J
AU Yu, RP
   Hesk, D
   Rivera, N
   Pelczer, I
   Chirik, PJ
AF Yu, Renyuan Pony
   Hesk, David
   Rivera, Nelo
   Pelczer, Istvan
   Chirik, Paul J.
TI Iron-catalysed tritiation of pharmaceuticals
SO NATURE
LA English
DT Article
ID radiolabeled compounds; h/d exchange; discovery; hydrogenation; complexes; tritium; deuteration; antagonist; deuterium
AB A thorough understanding of the pharmacokinetic and pharmacodynamic properties of a drug in animal models is a critical component of drug discovery and development(1-6). Such studies are performed in vivo and in vitro at various stages of the development process-ranging from preclinical absorption, distribution, metabolism and excretion (ADME) studies to late-stage human clinical trials-to elucidate a drug molecule's metabolic profile and to assess its toxicity(2). Radiolabelled compounds, typically those that contain C-14 or H-3 isotopes, are one of the most powerful and widely deployed diagnostics for these studies(4,5). The introduction of radiolabels using synthetic chemistry enables the direct tracing of the drug molecule without substantially altering its structure or function. The ubiquity of C-H bonds in drugs and the relative ease and low cost associated with tritium (H-3) make it an ideal radioisotope with which to conduct ADME studies early in the drug development process(2,4,6). Here we describe an iron-catalysed method for the direct H-3 labelling of pharmaceuticals by hydrogen isotope exchange, using tritium gas as the source of the radioisotope. The site selectivity of the iron catalyst is orthogonal to currently used iridium catalysts and allows isotopic labelling of complementary positions in drug molecules, providing a new diagnostic tool in drug development.
C1 [Yu, Renyuan Pony; Pelczer, Istvan; Chirik, Paul J.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Hesk, David; Rivera, Nelo] Merck Res Labs, Rahway, NJ 07065 USA.
C3 Princeton University; Merck & Company
RP Chirik, PJ (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
EM pchirik@princeton.edu
FU Merck; Intellectual Property Accelerator Fund at Princeton University
NR 30
TC 328
Z9 373
U1 4
U2 184
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 195
EP 199
DI 10.1038/nature16464
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700033
PM 26762456
DA 2026-03-09
ER

PT J
AU Hamm, G
   Mitchell, P
   Arnold, LJ
   Prideaux, GJ
   Questiaux, D
   Spooner, NA
   Levchenko, VA
   Foley, EC
   Worthy, TH
   Stephenson, B
   Coulthard, V
   Coulthard, C
   Wilton, S
   Johnston, D
AF Hamm, Giles
   Mitchell, Peter
   Arnold, Lee J.
   Prideaux, Gavin J.
   Questiaux, Daniele
   Spooner, Nigel A.
   Levchenko, Vladimir A.
   Foley, Elizabeth C.
   Worthy, Trevor H.
   Stephenson, Birgitta
   Coulthard, Vincent
   Coulthard, Clifford
   Wilton, Sophia
   Johnston, Duncan
TI Cultural innovation and megafauna interaction in the early settlement of arid Australia
SO NATURE
LA English
DT Article
ID late pleistocene; single grains; luminescence; quartz; extinction; loess; holocene; south; osl; distributions
AB Elucidating the material culture of early people in arid Australia and the nature of their environmental interactions is essential for understanding the adaptability of populations and the potential causes of megafaunal extinctions 50-40 thousand years ago (ka). Humans colonized the continent by 50 ka(1,2), but an apparent lack of cultural innovations compared to people in Europe and Africa(3,4) has been deemed a barrier to early settlement in the extensive arid zone(2,3). Here we present evidence from Warratyi rock shelter in the southern interior that shows that humans occupied arid Australia by around 49 ka, 10 thousand years (kyr) earlier than previously reported(2). The site preserves the only reliably dated, stratified evidence of extinct Australian megafauna(5,6), including the giant marsupial Diprotodon optatum, alongside artefacts more than 46 kyr old. We also report on the earliest-known use of ochre in Australia and Southeast Asia (at or before 49-46 ka), gypsum pigment (40-33 ka), bone tools (40-38 ka), hafted tools (38-35 ka), and backed artefacts (30-24 ka), each up to 10 kyr older than any other known occurrence(7,8). Thus, our evidence shows that people not only settled in the arid interior within a few millennia of entering the continent(9), but also developed key technologies much earlier than previously recorded for Australia and Southeast Asia(8).
C1 [Hamm, Giles; Foley, Elizabeth C.] La Trobe Univ, Dept Archaeol & Hist, Melbourne, Vic 3083, Australia.
   [Mitchell, Peter] Geomorph Consultant Gladesville, Sydney, NSW 2111, Australia.
   [Arnold, Lee J.] Univ Adelaide, Inst Environm, Sch Phys Sci, Adelaide, SA 5005, Australia.
   [Arnold, Lee J.] Univ Adelaide, Inst Photon & Adv Sensing, Adelaide, SA 5005, Australia.
   [Prideaux, Gavin J.; Worthy, Trevor H.] Flinders Univ S Australia, Sch Biol Sci, Adelaide, SA 5001, Australia.
   [Questiaux, Daniele; Spooner, Nigel A.] Univ Adelaide, Sch Phys Sci, Inst Photon & Adv Sensing, Adelaide, SA 5005, Australia.
   [Spooner, Nigel A.] Def Sci & Technol Grp, Adelaide, SA 5111, Australia.
   [Levchenko, Vladimir A.] Australian Nucl Sci & Technol Org, Sydney, NSW 2234, Australia.
   [Stephenson, Birgitta] Groove Anal Pty Ltd, Brisbane, Qld 4068, Australia.
   [Stephenson, Birgitta] Univ Queensland, Sch Social Sci, Brisbane, Qld 4072, Australia.
   [Coulthard, Vincent; Coulthard, Clifford; Wilton, Sophia; Johnston, Duncan] Adnyamathanha Tradit Lands Assoc, Port Augusta, SA 5700, Australia.
C3 La Trobe University; Adelaide University; University of Adelaide; Adelaide University; University of Adelaide; Flinders University; Adelaide University; University of Adelaide; Defence Science & Technology; Australian Nuclear Science & Technology Organisation; University of Queensland
RP Hamm, G (corresponding author), La Trobe Univ, Dept Archaeol & Hist, Melbourne, Vic 3083, Australia.
EM A.R.A.S@bigpond.com
FU Australian Research Council [FT130100195, FT130101728]; Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS); Australian Research Council [FT130101728, FT130100195] Funding Source: Australian Research Council
NR 67
TC 104
Z9 116
U1 2
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 280
EP +
DI 10.1038/nature20125
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500043
PM 27806378
DA 2026-03-09
ER

PT J
AU Sciacovelli, M
   Gonçalves, E
   Johnson, TI
   Zecchini, VR
   da Costa, ASH
   Gaude, E
   Drubbel, AV
   Theobald, SJ
   Abbo, SR
   Tran, MGB
   Rajeeve, V
   Cardaci, S
   Foster, S
   Yun, HY
   Cutillas, P
   Warren, A
   Gnanapragasam, V
   Gottlieb, E
   Franze, K
   Huntly, B
   Maher, ER
   Maxwell, PH
   Saez-Rodriguez, J
   Frezza, C
AF Sciacovelli, Marco
   Goncalves, Emanuel
   Johnson, Timothy Isaac
   Zecchini, Vincent Roberto
   da Costa, Ana Sofia Henriques
   Gaude, Edoardo
   Drubbel, Alizee Vercauteren
   Theobald, Sebastian Julian
   Abbo, Sandra Riekje
   Tran, Maxine Gia Binh
   Rajeeve, Vinothini
   Cardaci, Simone
   Foster, Sarah
   Yun, Haiyang
   Cutillas, Pedro
   Warren, Anne
   Gnanapragasam, Vincent
   Gottlieb, Eyal
   Franze, Kristian
   Huntly, Brian
   Maher, Eamonn Richard
   Maxwell, Patrick Henry
   Saez-Rodriguez, Julio
   Frezza, Christian
TI Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition
SO NATURE
LA English
DT Article
ID enrichment analysis; expression; cancer; mutations; succinate; tet; demethylases; glutathione; inhibition; hereditary
AB Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer(1). Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome2. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a bona fide oncometabolite(3). Fumarate has been shown to inhibit a-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation(4,5). However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis(6). We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster(6) mir-200ba429, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.
C1 [Sciacovelli, Marco; Johnson, Timothy Isaac; Zecchini, Vincent Roberto; da Costa, Ana Sofia Henriques; Gaude, Edoardo; Drubbel, Alizee Vercauteren; Theobald, Sebastian Julian; Abbo, Sandra Riekje; Frezza, Christian] Univ Cambridge, MRC, Canc Unit, Cambridge CB2 0XZ, England.
   [Goncalves, Emanuel; Saez-Rodriguez, Julio] EBI, EMBL, Cambridge CB10 1SD, England.
   [Tran, Maxine Gia Binh] Univ Cambridge, Urooncol Res Grp, Dept Oncol, Cambridge CB2 0QL, England.
   [Rajeeve, Vinothini; Cutillas, Pedro] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, Integrat Cell Signalling & Prote,John Vane Sci Ct, Charterhouse Sq, London EC1M 6BQ, England.
   [Cardaci, Simone; Gottlieb, Eyal] Cancer Res UK, Beatson Inst, Glasgow G61 1BD, Lanark, Scotland.
   [Foster, Sarah; Franze, Kristian] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England.
   [Yun, Haiyang; Huntly, Brian] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
   [Yun, Haiyang; Huntly, Brian] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 0XY, England.
   [Yun, Haiyang; Huntly, Brian] Univ Cambridge, Wellcome Trust Med Res Council, Cambridge Stem Cell Inst, Cambridge CB2 0XY, England.
   [Warren, Anne] Univ Cambridge, Dept Pathol, Cambridge CB2 0QQ, England.
   [Gnanapragasam, Vincent] Univ Cambridge, Acad Urol Grp, Dept Surg, Cambridge CB2 0QQ, England.
   [Maher, Eamonn Richard] Univ Cambridge, Dept Med Genet, Cambridge CB2 0QQ, England.
   [Maher, Eamonn Richard] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England.
   [Maxwell, Patrick Henry] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Saez-Rodriguez, Julio] Rhein Westfal TH Aachen, Joint Res Ctr Computat Biomed, Fac Med, D-52074 Aachen, Germany.
   [Tran, Maxine Gia Binh] Royal Free Hosp, Renal Canc Ctr, UCL Div Surg & Intervent Sci, Pond St, London NW3 2QG, England.
C3 University of Cambridge; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Cambridge; University of London; Queen Mary University London; Beatson Institute; University of Cambridge; University of Cambridge; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge; University of Cambridge; University of Cambridge; University of Cambridge; University of Cambridge; RWTH Aachen University; University of London; University College London; UCL Medical School; Royal Free London NHS Foundation Trust
RP Frezza, C (corresponding author), Univ Cambridge, MRC, Canc Unit, Cambridge CB2 0XZ, England.
EM cf366@mrc-cu.cam.ac.uk
FU Medical Research Council (UK); Herchel Smith Research Studentship; MRC; ERC [323004-ONCOTREAT]; Wellcome Trust; NIHR; NIHR Cambridge Biomedical Research Centre; MRC [G1100312, MR/M010392/1, MC_UU_12022/6] Funding Source: UKRI; Cancer Research UK [18278] Funding Source: researchfish; Medical Research Council [MC_UU_12022/6, G1100312, MR/M010392/1, MC_PC_12009] Funding Source: researchfish; National Institute for Health Research [NF-SI-0514-10122] Funding Source: researchfish; Wellcome Trust [096956/Z/11/Z] Funding Source: researchfish
NR 40
TC 462
Z9 525
U1 3
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 544
EP +
DI 10.1038/nature19353
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900055
PM 27580029
DA 2026-03-09
ER

PT J
AU Zhang, BJ
   Zheng, H
   Huang, B
   Li, WZ
   Xiang, YL
   Peng, X
   Ming, J
   Wu, XT
   Zhang, Y
   Xu, QH
   Liu, WQ
   Kou, XC
   Zhao, YH
   He, WT
   Li, C
   Chen, B
   Li, YY
   Wang, QJ
   Ma, J
   Yin, QZ
   Kee, K
   Meng, AM
   Gao, SR
   Xu, F
   Na, J
   Xie, W
AF Zhang, Bingjie
   Zheng, Hui
   Huang, Bo
   Li, Wenzhi
   Xiang, Yunlong
   Peng, Xu
   Ming, Jia
   Wu, Xiaotong
   Zhang, Yu
   Xu, Qianhua
   Liu, Wenqiang
   Kou, Xiaochen
   Zhao, Yanhong
   He, Wenteng
   Li, Chong
   Chen, Bo
   Li, Yuanyuan
   Wang, Qiujun
   Ma, Jing
   Yin, Qiangzong
   Kee, Kehkooi
   Meng, Anming
   Gao, Shaorong
   Xu, Feng
   Na, Jie
   Xie, Wei
TI Allelic reprogramming of the histone modification H3K4me3 in early mammalian development
SO NATURE
LA English
DT Article
ID embryonic stem-cells; dna methylation; mouse genome; chip-seq; rna-seq; gene-expression; oocyte growth; mice; specification; spermatozoa
AB Histone modifications are fundamental epigenetic regulators that control many crucial cellular processes(1) . However, whether these marks can be passed on from mammalian gametes to the next generation is a long-standing question that remains unanswered. Here, by developing a highly sensitive approach, STAR ChIP-seq, we provide a panoramic view of the landscape of H3K4me3, a histone hallmark for transcription initiation(2), from developing gametes to post-implantation embryos. We find that upon fertilization, extensive reprogramming occurs on the paternal genome, as H3K4me3 peaks are depleted in zygotes but are readily observed after major zygotic genome activation at the late two-cell stage. On the maternal genome, we unexpectedly find a non-canonical form of H3K4me3 (ncH3K4me3) in full-grown and mature oocytes, which exists as broad peaks at promoters and a large number of distal loci. Such broad H3K4me3 peaks are in contrast to the typical sharp H3K4me3 peaks restricted to CpG-rich regions of promoters. Notably, ncH3K4me3 in oocytes overlaps almost exclusively with partially methylated DNA domains. It is then inherited in preimplantation embryos, before being erased in the late two-cell embryos, when canonical H3K4me3 starts to be established. The removal of ncH3K4me3 requires zygotic transcription but is independent of DNA replication-mediated passive dilution. Finally, downregulation of H3K4me3 in full-grown oocytes by overexpression of the H3K4me3 demethylase KDM5B is associated with defects in genome silencing. Taken together, these data unveil inheritance and highly dynamic reprogramming of the epigenome in early mammalian development.
C1 [Zhang, Bingjie; Zheng, Hui; Huang, Bo; Xiang, Yunlong; Zhang, Yu; Xu, Qianhua; Li, Yuanyuan; Wang, Qiujun; Ma, Jing; Yin, Qiangzong; Xie, Wei] Tsinghua Univ, Sch Life Sci, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat,THU PKU Ctr Life Sci, Beijing 100084, Peoples R China.
   [Huang, Bo] Peking Univ, Acad Adv Interdisciplinary Studies, PKU THU Ctr Life Sci, Beijing 100871, Peoples R China.
   [Li, Wenzhi; Ming, Jia; Chen, Bo; Kee, Kehkooi; Na, Jie] Tsinghua Univ, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Beijing 100084, Peoples R China.
   [Peng, Xu; Xu, Feng] ASTAR, Singapore Inst Clin Sci, Singapore 117609, Singapore.
   [Wu, Xiaotong; Meng, Anming] Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Engn, Beijing 100084, Peoples R China.
   [Liu, Wenqiang; Kou, Xiaochen; Zhao, Yanhong; He, Wenteng; Li, Chong; Gao, Shaorong] Tongji Univ, Clin & Translat Res Ctr, Sch Life Sci & Technol, Shanghai Matern & Infant Hosp 1, Shanghai 200092, Peoples R China.
   [Xu, Feng] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
C3 Tsinghua University; Peking University; Tsinghua University; Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Institute for Clinical Sciences (SICS); Tsinghua University; Tongji University; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB)
RP Xie, W (corresponding author), Tsinghua Univ, Sch Life Sci, Ctr Stem Cell Biol & Regenerat Med, MOE Key Lab Bioinformat,THU PKU Ctr Life Sci, Beijing 100084, Peoples R China.; Na, J (corresponding author), Tsinghua Univ, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Beijing 100084, Peoples R China.
EM jie.na@tsinghua.edu.cn; xiewei121@tsinghua.edu.cn
FU National Basic Research Program of China [2016YFC0900301, 2015CB856201, 2012CB966701]; National Natural Science Foundation of China [31422031, 91519326, 31171381]; Beijing Natural Science Foundation [5152014]; Tsinghua University Initiative Scientific Research Program [20161080043]; THU-PKU Center for Life Sciences; Youth Thousand Scholar Program of China
NR 40
TC 544
Z9 624
U1 24
U2 290
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 553
EP +
DI 10.1038/nature19361
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900057
PM 27626382
DA 2026-03-09
ER

PT J
AU Wehner, M
   Truby, RL
   Fitzgerald, DJ
   Mosadegh, B
   Whitesides, GM
   Lewis, JA
   Wood, RJ
AF Wehner, Michael
   Truby, Ryan L.
   Fitzgerald, Daniel J.
   Mosadegh, Bobak
   Whitesides, George M.
   Lewis, Jennifer A.
   Wood, Robert J.
TI An integrated design and fabrication strategy for entirely soft, autonomous robots
SO NATURE
LA English
DT Article
ID logic; flow
AB Soft robots possess many attributes that are difficult, if not impossible, to achieve with conventional robots composed of rigid materials(1,2). Yet, despite recent advances, soft robots must still be tethered to hard robotic control systems and power sources(3-10). New strategies for creating completely soft robots, including soft analogues of these crucial components, are needed to realize their full potential. Here we report the untethered operation of a robot composed solely of soft materials. The robot is controlled with microfluidic logic(11) that autonomously regulates fluid flow and, hence, catalytic decomposition of an on-board monopropellant fuel supply. Gas generated from the fuel decomposition inflates fluidic networks downstream of the reaction sites, resulting in actuation(12). The body and microfluidic logic of the robot are fabricated using moulding and soft lithography, respectively, and the pneumatic actuator networks, on-board fuel reservoirs and catalytic reaction chambers needed for movement are patterned within the body via a multi-material, embedded 3D printing technique(13,14). The fluidic and elastomeric architectures required for function span several orders of magnitude from the microscale to the macroscale. Our integrated design and rapid fabrication approach enables the programmable assembly of multiple materials within this architecture, laying the foundation for completely soft, autonomous robots.
C1 [Wehner, Michael; Truby, Ryan L.; Fitzgerald, Daniel J.; Lewis, Jennifer A.; Wood, Robert J.] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Wehner, Michael; Truby, Ryan L.; Fitzgerald, Daniel J.; Whitesides, George M.; Lewis, Jennifer A.; Wood, Robert J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
   [Mosadegh, Bobak] Weill Cornell Med, Dalio Inst Cardiovasc Imaging, New York, NY 10021 USA.
   [Mosadegh, Bobak] New York Presbyterian Hosp, New York, NY 10021 USA.
   [Mosadegh, Bobak] Weill Cornell Med, Dept Radiol, New York, NY 10021 USA.
   [Whitesides, George M.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital; Cornell University; Weill Cornell Medicine; Harvard University
RP Lewis, JA; Wood, RJ (corresponding author), Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.; Lewis, JA; Wood, RJ (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
EM jalewis@seas.harvard.edu; rjwood@seas.harvard.edu
FU National Science Foundation through Harvard MRSEC [DMR-1420570]; Wyss Institute for Biologically Inspired Engineering; National Science Foundation [1541959]; National Security Science and Engineering Faculty Fellowship
NR 35
TC 1822
Z9 2199
U1 106
U2 2953
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 451
EP +
DI 10.1038/nature19100
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600040
PM 27558065
DA 2026-03-09
ER

PT J
AU Chen, WF
   Hill, H
   Christie, A
   Kim, MS
   Holloman, E
   Pavia-Jimenez, A
   Homayoun, F
   Ma, YQ
   Patel, N
   Yell, P
   Hao, GY
   Yousuf, Q
   Joyce, A
   Pedrosa, I
   Geiger, H
   Zhang, H
   Chang, J
   Gardner, KH
   Bruick, RK
   Reeves, C
   Hwang, TH
   Courtney, K
   Frenkel, E
   Sun, XK
   Zojwalla, N
   Wong, T
   Rizzi, JP
   Wallace, EM
   Josey, JA
   Xie, Y
   Xie, XJ
   Kapur, P
   McKay, RM
   Brugarolas, J
AF Chen, Wenfang
   Hill, Haley
   Christie, Alana
   Kim, Min Soo
   Holloman, Eboni
   Pavia-Jimenez, Andrea
   Homayoun, Farrah
   Ma, Yuanqing
   Patel, Nirav
   Yell, Paul
   Hao, Guiyang
   Yousuf, Qurratulain
   Joyce, Allison
   Pedrosa, Ivan
   Geiger, Heather
   Zhang, He
   Chang, Jenny
   Gardner, Kevin H.
   Bruick, Richard K.
   Reeves, Catherine
   Hwang, Tae Hyun
   Courtney, Kevin
   Frenkel, Eugene
   Sun, Xiankai
   Zojwalla, Naseem
   Wong, Tai
   Rizzi, James P.
   Wallace, Eli M.
   Josey, John A.
   Xie, Yang
   Xie, Xian-Jin
   Kapur, Payal
   McKay, Renee M.
   Brugarolas, James
TI Targeting renal cell carcinoma with a HIF-2 antagonist
SO NATURE
LA English
DT Article
ID hypoxia-inducible factor-2; pas-b domain; transcription factor; hif-2-alpha; inhibition; hif2-alpha; rna; expression; gene; dna
AB Clear cell renal cell carcinoma (ccRCC) is characterized by inactivation of the von Hippel-Lindau tumour suppressor gene (VHL)(1,2). Because no other gene is mutated as frequently in ccRCC and VHL mutations are truncal(3), VHL inactivation is regarded as the governing event(4). VHL loss activates the HIF-2 transcription factor, and constitutive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells(5). HIF-2 has been implicated in angiogenesis and multiple other processes(6-9), but angiogenesis is the main target of drugs such as the tyrosine kinase inhibitor sunitinib(10). HIF-2 has been regarded as undruggable(11). Here we use a tumourgraft/patient-derived xenograft platform(12,13) to evaluate PT2399, a selective HIF-2 antagonist that was identified using a structure-based design approach. PT2399 dissociated HIF-2 (an obligatory heterodimer of HIF-2 alpha-HIF-1 beta)(14) in human ccRCC cells and suppressed tumorigenesis in 56% (10 out of 18) of such lines. PT2399 had greater activity than sunitinib, was active in sunitinib-progressing tumours, and was better tolerated. Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399. Resistance occurred despite HIF-2 dissociation in tumours and evidence of Hif-2 inhibition in the mouse, as determined by suppression of circulating erythropoietin, a HIF-2 target(15) and possible pharmacodynamic marker. We identified a HIF-2-dependent gene signature in sensitive tumours. Gene expression was largely unaffected by PT2399 in resistant tumours, illustrating the specificity of the drug. Sensitive tumours exhibited a distinguishing gene expression signature and generally higher levels of HIF-2 alpha. Prolonged PT2399 treatment led to resistance. We identified binding site and second site suppressor mutations in HIF-2 alpha and HIF-1 beta, respectively. Both mutations preserved HIF-2 dimers despite treatment with PT2399. Finally, an extensively pretreated patient whose tumour had given rise to a sensitive tumourgraft showed disease control for more than 11 months when treated with a close analogue of PT2399, PT2385. We validate HIF-2 as a target in ccRCC, show that some ccRCCs are HIF-2 independent, and set the stage for biomarker-driven clinical trials.
C1 [Chen, Wenfang; Hill, Haley; Christie, Alana; Kim, Min Soo; Holloman, Eboni; Pavia-Jimenez, Andrea; Homayoun, Farrah; Ma, Yuanqing; Patel, Nirav; Yousuf, Qurratulain; Joyce, Allison; Pedrosa, Ivan; Zhang, He; Chang, Jenny; Bruick, Richard K.; Hwang, Tae Hyun; Courtney, Kevin; Frenkel, Eugene; Sun, Xiankai; Xie, Yang; Xie, Xian-Jin; Kapur, Payal; McKay, Renee M.; Brugarolas, James] Univ Texas Southwestern Med Ctr Dallas, Simmons Comprehens Canc Ctr, Kidney Canc Program, Dallas, TX 75390 USA.
   [Chen, Wenfang; Hill, Haley; Holloman, Eboni; Pavia-Jimenez, Andrea; Homayoun, Farrah; Ma, Yuanqing; Patel, Nirav; Yousuf, Qurratulain; Joyce, Allison; Courtney, Kevin; Frenkel, Eugene; McKay, Renee M.; Brugarolas, James] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Chen, Wenfang] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China.
   [Kim, Min Soo; Zhang, He; Hwang, Tae Hyun; Xie, Yang; Xie, Xian-Jin] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Yell, Paul] Parkland Hlth & Hosp Syst, Dallas, TX 75235 USA.
   [Hao, Guiyang; Pedrosa, Ivan; Sun, Xiankai] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA.
   [Geiger, Heather; Reeves, Catherine] New York Genome Ctr, New York, NY 10013 USA.
   [Gardner, Kevin H.] CUNY, Adv Sci Res Ctr, Struct Biol Initiat, New York, NY 10031 USA.
   [Gardner, Kevin H.] CUNY, Dept Chem & Biochem, New York, NY 10031 USA.
   [Gardner, Kevin H.] CUNY, Grad Ctr, Biochem Chem & Biol PhD Programs, New York, NY 10016 USA.
   [Bruick, Richard K.] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Zojwalla, Naseem; Wong, Tai; Rizzi, James P.; Wallace, Eli M.; Josey, John A.] Peloton Therapeut Inc, Dallas, TX 75235 USA.
   [Kapur, Payal] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Sun Yat Sen University; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; City University of New York (CUNY) System; City University of New York (CUNY) System; City University of New York (CUNY) System; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Brugarolas, J (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Simmons Comprehens Canc Ctr, Kidney Canc Program, Dallas, TX 75390 USA.; Brugarolas, J (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
EM james.brugarolas@utsouthwestern.edu
FU Peloton Therapeutics, Inc. [OTD-105466]; CPRIT [RP160440, RP150596, RP110771, RP130603, RP130513]; National Natural Science Foundation of China [811011934]; Science and Technology Program of Guangzhou, China [2012J5100031]; NIH [R01CA154475, P50CA196516, R01CA175754, P30CA142543]; National Center for Advancing Translational Sciences (Center for Translational Medicine) [UL1TR001105]; National Cancer Institute [P30CA142543, P50CA196516, R01CA154475] Funding Source: NIH RePORTER
NR 37
TC 575
Z9 654
U1 5
U2 177
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 112
EP +
DI 10.1038/nature19796
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100040
PM 27595394
DA 2026-03-09
ER

PT J
AU Aragonès, AC
   Haworth, NL
   Darwish, N
   Ciampi, S
   Bloomfield, NJ
   Wallace, GG
   Diez-Perez, I
   Coote, ML
AF Aragones, Albert C.
   Haworth, Naomi L.
   Darwish, Nadim
   Ciampi, Simone
   Bloomfield, Nathaniel J.
   Wallace, Gordon G.
   Diez-Perez, Ismael
   Coote, Michelle L.
TI Electrostatic catalysis of a Diels-Alder reaction
SO NATURE
LA English
DT Article
ID distonic radical-anions; external electric-field; somo-homo conversion; norbornylogous bridges; molecular junctions; valence-bond; selectivity; rulers
AB It is often thought that the ability to control reaction rates with an applied electrical potential gradient is unique to redox systems. However, recent theoretical studies suggest that oriented electric fields could affect the outcomes of a range of chemical reactions, regardless of whether a redox system is involved(1-4). This possibility arises because many formally covalent species can be stabilized via minor charge-separated resonance contributors. When an applied electric field is aligned in such a way as to electrostatically stabilize one of these minor forms, the degree of resonance increases, resulting in the overall stabilization of the molecule or transition state. This means that it should be possible to manipulate the kinetics and thermodynamics of non-redox processes using an external electric field, as long as the orientation of the approaching reactants with respect to the field stimulus can be controlled. Here, we provide experimental evidence that the formation of carboncarbon bonds is accelerated by an electric field. We have designed a surface model system to probe the Diels-Alder reaction, and coupled it with a scanning tunnelling microscopy break-junction approach(5-7). This technique, performed at the single-molecule level, is perfectly suited to deliver an electric-field stimulus across approaching reactants. We find a fivefold increase in the frequency of formation of single-molecule junctions, resulting from the reaction that occurs when the electric field is present and aligned so as to favour electron flow from the dienophile to the diene. Our results are qualitatively consistent with those predicted by quantum-chemical calculations in a theoretical model of this system, and herald a new approach to chemical catalysis.
C1 [Aragones, Albert C.; Darwish, Nadim; Diez-Perez, Ismael] Univ Barcelona, Dept Quim Fis, Diagonal 645, E-08028 Barcelona, Catalonia, Spain.
   [Aragones, Albert C.; Darwish, Nadim; Diez-Perez, Ismael] Inst Bioengn Catalunya IBEC, Baldiri Reixac 15-21, Barcelona 08028, Catalonia, Spain.
   [Aragones, Albert C.; Diez-Perez, Ismael] Ctr Invest Biomed Red CIBER BBN, Campus Rio Ebro Edificio I D, Zaragoza 50018, Spain.
   [Haworth, Naomi L.; Bloomfield, Nathaniel J.; Coote, Michelle L.] Australian Natl Univ, Res Sch Chem, ARC Ctr Excellence Electromat Sci, Canberra, ACT 2601, Australia.
   [Ciampi, Simone; Wallace, Gordon G.] Univ Wollongong, Intelligent Polymer Res Inst, ARC Ctr Excellence Electromat Sci, Wollongong, NSW 2500, Australia.
C3 University of Barcelona; Barcelona Institute of Science & Technology; Institut de Bioenginyeria de Catalunya; CIBER - Centro de Investigacion Biomedica en Red; CIBERBBN; Australian National University; University of Wollongong; ARC Centre of Excellence for Electromaterials Science
RP Darwish, N; Diez-Perez, I (corresponding author), Univ Barcelona, Dept Quim Fis, Diagonal 645, E-08028 Barcelona, Catalonia, Spain.; Darwish, N; Diez-Perez, I (corresponding author), Inst Bioengn Catalunya IBEC, Baldiri Reixac 15-21, Barcelona 08028, Catalonia, Spain.; Diez-Perez, I (corresponding author), Ctr Invest Biomed Red CIBER BBN, Campus Rio Ebro Edificio I D, Zaragoza 50018, Spain.; Coote, ML (corresponding author), Australian Natl Univ, Res Sch Chem, ARC Ctr Excellence Electromat Sci, Canberra, ACT 2601, Australia.; Ciampi, S (corresponding author), Univ Wollongong, Intelligent Polymer Res Inst, ARC Ctr Excellence Electromat Sci, Wollongong, NSW 2500, Australia.
EM ndarwish@ibecbarcelona.eu; sciampi@uow.edu.au; isma_diez@ub.edu; michelle.coote@anu.edu.au
FU MINECO Spanish National Project [CTQ2012-36090]; EU Reintegration Grant [FP7-PEOPLE-2010-RG-277182]; Australian Government; European Union; Ramon y Cajal program (MINECO) [RYC-2011-07951]; University of Wollongong; Australian National Fabrication Facility; Spanish Ministerio de Educacion; Australian Research Council (ARC); ARC; ARC Centre of Excellence Scheme [CE 140100012]
NR 30
TC 611
Z9 695
U1 15
U2 642
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 88
EP 91
DI 10.1038/nature16989
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900045
PM 26935697
DA 2026-03-09
ER

PT J
AU Lee, ASY
   Kranzusch, PJ
   Doudna, JA
   Cate, JHD
AF Lee, Amy S. Y.
   Kranzusch, Philip J.
   Doudna, Jennifer A.
   Cate, Jamie H. D.
TI eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation
SO NATURE
LA English
DT Article
ID dependent translation; c-jun; mechanism; model; phosphorylation
AB Eukaryotic mRNAs contain a 5' cap structure that is crucial for recruitment of the translation machinery and initiation of protein synthesis. mRNA recognition is thought to require direct interactions between eukaryotic initiation factor 4E (eIF4E) and the mRNA cap. However, translation of numerous capped mRNAs remains robust during cellular stress, early development, and cell cycle progression(1) despite inactivation of eIF4E. Here we describe a cap-dependent pathway of translation initiation in human cells that relies on a previously unknown cap-binding activity of eIF3d, a subunit of the 800-kilodalton eIF3 complex. A 1.4 angstrom crystal structure of the eIF3d cap-binding domain reveals unexpected homology to endonucleases involved in RNA turnover, and allows modelling of cap recognition by eIF3d. eIF3d makes specific contacts with the cap, as exemplified by cap analogue competition, and these interactions are essential for assembly of translation initiation complexes on eIF3-specialized mRNAs(2) such as the cell proliferation regulator c-Jun (also known as JUN). The c-Jun mRNA further encodes an inhibitory RNA element that blocks eIF4E recruitment, thus enforcing alternative cap recognition by eIF3d. Our results reveal a mechanism of cap-dependent translation that is independent of eIF4E, and illustrate how modular RNA elements work together to direct specialized forms of translation initiation.
C1 [Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
   [Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA.
   [Kranzusch, Philip J.; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.; Cate, Jamie H. D.] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA.
   [Lee, Amy S. Y.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
   [Kranzusch, Philip J.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.
   [Kranzusch, Philip J.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Brandeis University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School
RP Cate, JHD (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.; Cate, JHD (corresponding author), Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA.; Cate, JHD (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Cate, JHD (corresponding author), Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
EM jcate@lbl.gov
FU UC Office of the President, Multicampus Research Programs and Initiatives grant [MR-15-328599]; Program for Breakthrough Biomedical Research; Sandler Foundation; NIH [S10RR025622]; NIGMS Center for RNA Systems Biology [P50-GM201706]
NR 34
TC 283
Z9 363
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 96
EP +
DI 10.1038/nature18954
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200037
PM 27462815
DA 2026-03-09
ER

PT J
AU Wenzel, S
   Cox, PM
   Eyring, V
   Friedlingstein, P
AF Wenzel, Sabrina
   Cox, Peter M.
   Eyring, Veronika
   Friedlingstein, Pierre
TI Projected land photosynthesis constrained by changes in the seasonal cycle of atmospheric CO2
SO NATURE
LA English
DT Article
ID northern ecosystems; elevated co2; carbon; climate; cmip5; models
AB Uncertainties in the response of vegetation to rising atmospheric CO2 concentrations(1,2) contribute to the large spread in projections of future climate change(3,4). Climate-carbon cycle models generally agree that elevated atmospheric CO2 concentrations will enhance terrestrial gross primary productivity (GPP). However, the magnitude of this CO2 fertilization effect varies from a 20 per cent to a 60 per cent increase in GPP for a doubling of atmospheric CO2 concentrations in model studies(5-7). Here we demonstrate emergent constraints(8-11) on large-scale CO2 fertilization using observed changes in the amplitude of the atmospheric CO2 seasonal cycle that are thought to be the result of increasing terrestrial GPP(12-14). Our comparison of atmospheric CO2 measurements from Point Barrow in Alaska and Cape Kumukahi in Hawaii with historical simulations of the latest climate-carbon cycle models demonstrates that the increase in the amplitude of the CO2 seasonal cycle at both measurement sites is consistent with increasing annual mean GPP, driven in part by climate warming, but with differences in CO2 fertilization controlling the spread among the model trends. As a result, the relationship between the amplitude of the CO2 seasonal cycle and the magnitude of CO2 fertilization of GPP is almost linear across the entire ensemble of models. When combined with the observed trends in the seasonal CO2 amplitude, these relationships lead to consistent emergent constraints on the CO2 fertilization of GPP. Overall, we estimate a GPP increase of 37 +/- 9 per cent for high-latitude ecosystems and 32 +/- 9 per cent for extratropical ecosystems under a doubling of atmospheric CO2 concentrations on the basis of the Point Barrow and Cape Kumukahi records, respectively.
C1 [Wenzel, Sabrina; Eyring, Veronika] Deutsches Zentrum Luft & Raumfahrt DLR, Inst Atmospher Phys, Oberpfaffenhofen, Germany.
   [Cox, Peter M.; Friedlingstein, Pierre] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QE, Devon, England.
C3 Helmholtz Association; German Aerospace Centre (DLR); University of Exeter
RP Wenzel, S (corresponding author), Deutsches Zentrum Luft & Raumfahrt DLR, Inst Atmospher Phys, Oberpfaffenhofen, Germany.
EM Sabrina.wenzel@dlr.de
FU Horizon European Union's Framework Programme for Research and Innovation [641816]; Coordinated Research in Earth Systems and Climate: Experiments, kNowledge, Dissemination and Outreach (CRESCENDO) project; DLR Klimarelevanz von atmospharischen Spurengasen; Aerosolen und Wolken: Auf dem Weg zu EarthCARE und MERLIN (KliSAW) project
NR 19
TC 157
Z9 173
U1 3
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 499
EP +
DI 10.1038/nature19772
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400055
PM 27680704
DA 2026-03-09
ER

PT J
AU Lahr, MM
   Rivera, F
   Power, RK
   Mounier, A
   Copsey, B
   Crivellaro, F
   Edung, JE
   Fernandez, JMM
   Kiarie, C
   Lawrence, J
   Leakey, A
   Mbua, E
   Miller, H
   Muigai, A
   Mukhongo, DM
   Van Baelen, A
   Wood, R
   Schwenninger, JL
   Grün, R
   Achyuthan, H
   Wilshaw, A
   Foley, RA
AF Lahr, M. Mirazon
   Rivera, F.
   Power, R. K.
   Mounier, A.
   Copsey, B.
   Crivellaro, F.
   Edung, J. E.
   Maillo Fernandez, J. M.
   Kiarie, C.
   Lawrence, J.
   Leakey, A.
   Mbua, E.
   Miller, H.
   Muigai, A.
   Mukhongo, D. M.
   Van Baelen, A.
   Wood, R.
   Schwenninger, J. -L.
   Gruen, R.
   Achyuthan, H.
   Wilshaw, A.
   Foley, R. A.
TI Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya
SO NATURE
LA English
DT Article
ID single-aliquot; fracture patterns; lethal aggression; lake turkana; quartz; luminescence; injury; trauma; warfare; bone
AB The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies(1,2). Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore(3). Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers.
C1 [Lahr, M. Mirazon; Rivera, F.; Power, R. K.; Mounier, A.; Copsey, B.; Crivellaro, F.; Lawrence, J.; Miller, H.; Mukhongo, D. M.; Van Baelen, A.; Wilshaw, A.; Foley, R. A.] Univ Cambridge, Dept Archaeol & Anthropol, Leverhulme Ctr Human Evolutionary Studies, Cambridge CB2 1QH, England.
   [Lahr, M. Mirazon; Kiarie, C.; Leakey, A.; Foley, R. A.] Turkana Basin Inst, Nairobi, Kenya.
   [Edung, J. E.] Natl Museums Kenya, Lodwar, Kenya.
   [Maillo Fernandez, J. M.] UNED, Dept Prehist & Arqueol, Madrid 28040, Spain.
   [Mbua, E.] Natl Museums Kenya, Nairobi, Kenya.
   [Muigai, A.] Jomo Kenyatta Univ Agr & Technol, Nairobi, Kenya.
   [Wood, R.; Gruen, R.] Australian Natl Univ, Res Sch Earth Sci, Acton, ACT 2601, Australia.
   [Schwenninger, J. -L.] Univ Oxford, Res Lab Archaeol & Hist Art, Oxford OX1 3QY, England.
   [Gruen, R.] Griffith Univ, Res Ctr Human Evolut, Environm Futures Res Inst, Nathan, Qld 4111, Australia.
   [Achyuthan, H.] Anna Univ, Dept Geol, Madras 600025, Tamil Nadu, India.
C3 University of Cambridge; Universidad Nacional de Educacion a Distancia (UNED); Jomo Kenyatta University of Agriculture & Technology; Australian National University; University of Oxford; Griffith University; Anna University; Anna University Chennai
RP Lahr, MM (corresponding author), Univ Cambridge, Dept Archaeol & Anthropol, Leverhulme Ctr Human Evolutionary Studies, Fitzwilliam St, Cambridge CB2 1QH, England.
EM mbml1@cam.ac.uk; raf10@cam.ac.uk
FU European Research Council (IN-AFRICA) [ERC 295907]; Newby Trust; McDonald Institute for Archaeological Research, University of Cambridge
NR 88
TC 154
Z9 187
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 394
EP +
DI 10.1038/nature16477
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800046
PM 26791728
DA 2026-03-09
ER

PT J
AU Raccuglia, P
   Elbert, KC
   Adler, PDF
   Falk, C
   Wenny, MB
   Mollo, A
   Zeller, M
   Friedler, SA
   Schrier, J
   Norquist, AJ
AF Raccuglia, Paul
   Elbert, Katherine C.
   Adler, Philip D. F.
   Falk, Casey
   Wenny, Malia B.
   Mollo, Aurelio
   Zeller, Matthias
   Friedler, Sorelle A.
   Schrier, Joshua
   Norquist, Alexander J.
TI Machine-learning-assisted materials discovery using failed experiments
SO NATURE
LA English
DT Article
ID metal-organic frameworks; crystal-structure; selenites; solids
AB Inorganic-organic hybrid materials(1-3) such as organically templated metal oxides(1), metal-organic frameworks (MOFs)(2) and organohalide perovskites(4) have been studied for decades, and hydrothermal and (non-aqueous) solvothermal syntheses have produced thousands of new materials that collectively contain nearly all the metals in the periodic table(5-9). Nevertheless, the formation of these compounds is not fully understood, and development of new compounds relies primarily on exploratory syntheses. Simulation-and data-driven approaches (promoted by efforts such as the Materials Genome Initiative(10)) provide an alternative to experimental trial-and-error. Three major strategies are: simulation-based predictions of physical properties (for example, charge mobility(11), photovoltaic properties(12), gas adsorption capacity(13) or lithium-ion intercalation(14)) to identify promising target candidates for synthetic efforts(11,15); determination of the structure-property relationship from large bodies of experimental data(16,17), enabled by integration with high-throughput synthesis and measurement tools(18); and clustering on the basis of similar crystallographic structure (for example, zeolite structure classification(19,20) or gas adsorption properties(21)). Here we demonstrate an alternative approach that uses machine-learning algorithms trained on reaction data to predict reaction outcomes for the crystallization of templated vanadium selenites. We used information on 'dark' reactions-failed or unsuccessful hydrothermal syntheses-collected from archived laboratory notebooks from our laboratory, and added physicochemical property descriptions to the raw notebook information using cheminformatics techniques. We used the resulting data to train a machine-learning model to predict reaction success. When carrying out hydrothermal synthesis experiments using previously untested, commercially available organic building blocks, our machine-learning model outperformed traditional human strategies, and successfully predicted conditions for new organically templated inorganic product formation with a success rate of 89 per cent. Inverting the machine-learning model reveals new hypotheses regarding the conditions for successful product formation.
C1 [Raccuglia, Paul; Elbert, Katherine C.; Adler, Philip D. F.; Falk, Casey; Wenny, Malia B.; Mollo, Aurelio; Friedler, Sorelle A.; Schrier, Joshua; Norquist, Alexander J.] Haverford Coll, 370 Lancaster Ave, Haverford, PA 19041 USA.
   [Zeller, Matthias] Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
C3 Haverford College; Purdue University System; Purdue University
RP Friedler, SA; Schrier, J; Norquist, AJ (corresponding author), Haverford Coll, 370 Lancaster Ave, Haverford, PA 19041 USA.
EM sorelle@cs.haverford.edu; jschrier@haverford.edu; anorquis@haverford.edu
FU Ohio Board of Reagents [CAP-491]; Youngstown State University; National Science Foundation [DMR-1307801]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1662030] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Materials Research [1337296] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [1307801] Funding Source: National Science Foundation
NR 39
TC 1184
Z9 1430
U1 58
U2 2054
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 73
EP +
DI 10.1038/nature17439
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900041
PM 27147027
DA 2026-03-09
ER

PT J
AU Stokes, CR
   Margold, M
   Clark, CD
   Tarasov, L
AF Stokes, C. R.
   Margold, M.
   Clark, C. D.
   Tarasov, L.
TI Ice stream activity scaled to ice sheet volume during Laurentide Ice Sheet deglaciation
SO NATURE
LA English
DT Article
ID sea-level rise; glacial lineations; collapse; instability; flow; reorganization; identification; surface; bed
AB The contribution of the Greenland and West Antarctic ice sheets to sea level has increased in recent decades, largely owing to the thinning and retreat of outlet glaciers and ice streams(1-4). This dynamic loss is a serious concern, with some modelling studies suggesting that the collapse of a major ice sheet could be imminent(5,6) or potentially underway(7) in West Antarctica, but others predicting a more limited response(8). A major problem is that observations used to initialize and calibrate models typically span only a few decades, and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves over longer timescales. This represents one of the largest sources of uncertainty when predicting the contributions of ice sheets to sea-level rise(8-10). A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing(5-10). Here we reconstruct the activity of 117 ice streams that operated at various times during deglaciation of the Laurentide Ice Sheet (from about 22,000 to 7,000 years ago) and show that as they activated and deactivated in different locations, their overall number decreased, they occupied a progressively smaller percentage of the ice sheet perimeter and their total discharge decreased. The underlying geology and topography clearly influenced ice stream activity, but-at the ice-sheet scale-their drainage network adjusted and was linked to changes in ice sheet volume. It is unclear whether these findings can be directly translated to modern ice sheets. However, contrary to the view that sees ice streams as unstable entities that can accelerate ice-sheet deglaciation, we conclude that ice streams exerted progressively less influence on ice sheet mass balance during the retreat of the Laurentide Ice Sheet.
C1 [Stokes, C. R.; Margold, M.] Univ Durham, Dept Geog, Durham, England.
   [Clark, C. D.] Univ Sheffield, Dept Geog, Sheffield S10 2TN, S Yorkshire, England.
   [Tarasov, L.] Mem Univ Newfoundland, Dept Phys & Phys Oceanog, St John, NF, Canada.
   [Margold, M.] Stockholm Univ, Dept Phys Geog, S-10691 Stockholm, Sweden.
C3 Durham University; University of Sheffield; Memorial University Newfoundland; Stockholm University
RP Stokes, CR (corresponding author), Univ Durham, Dept Geog, Durham, England.
EM c.r.stokes@durham.ac.uk
FU NERC [NE/J00782X/1, NE/J007455/1] Funding Source: UKRI; Natural Environment Research Council [NE/J00782X/1, NE/J007455/1] Funding Source: researchfish
NR 55
TC 97
Z9 107
U1 0
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 322
EP +
DI 10.1038/nature16947
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100034
PM 26887494
DA 2026-03-09
ER

PT J
AU Khakimov, RI
   Henson, BM
   Shin, DK
   Hodgman, SS
   Dall, RG
   Baldwin, KGH
   Truscott, AG
AF Khakimov, R. I.
   Henson, B. M. .
   Shin, D. K.
   Hodgman, S. S.
   Dall, R. G.
   Baldwin, K. G. H.
   Truscott, A. G.
TI Ghost imaging with atoms
SO NATURE
LA English
DT Article
ID diffraction; quantum; light; waves
AB Ghost imaging is a counter-intuitive phenomenon-first realized in quantum optics(1,2)-that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recover a 'ghost' image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms(3), which originate from s-wave scattering of two colliding Bose-Einstein condensates(4,5). We use higher-order Kapitza-Dirac scattering(6-8) to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference(9), and enable tests of Einstein-Podolsky-Rosen entanglement(9) and Bell's inequalities(10) with atoms.
C1 [Khakimov, R. I.; Henson, B. M. .; Shin, D. K.; Hodgman, S. S.; Dall, R. G.; Baldwin, K. G. H.; Truscott, A. G.] Australian Natl Univ, Res Sch Phys & Engn, Canberra, ACT 2601, Australia.
C3 Australian National University
RP Truscott, AG (corresponding author), Australian Natl Univ, Res Sch Phys & Engn, Canberra, ACT 2601, Australia.
EM andrew.truscott@anu.edu.au
FU Australian Research Council (ARC) [FT100100468, DP120101390]; ARC through the DECRA [DE150100315]; Australian Research Council [FT100100468, DE150100315] Funding Source: Australian Research Council
NR 33
TC 169
Z9 192
U1 1
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 100
EP +
DI 10.1038/nature20154
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600056
PM 27905444
DA 2026-03-09
ER

PT J
AU Yin, ZQ
   Shi, K
   Banerjee, S
   Pandey, KK
   Bera, S
   Grandgenett, DP
   Aihara, H
AF Yin, Zhiqi
   Shi, Ke
   Banerjee, Surajit
   Pandey, Krishan K.
   Bera, Sibes
   Grandgenett, Duane P.
   Aihara, Hideki
TI Crystal structure of the Rous sarcoma virus intasome
SO NATURE
LA English
DT Article
ID target dna recognition; murine leukemia-virus; retroviral integration; synaptic complex; type-1 integrase; hiv-1 integrase; pol gene; protein; domain; determinants
AB Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome1. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino-and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase-DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers(2-5), the architecture of a canonical three-domain integrase bound to DNA remained elusive. Here we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein-DNA and protein-protein contacts that show both conserved and distinct features compared with those observed for prototype foamy virus integrase. Our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.
C1 [Yin, Zhiqi; Shi, Ke; Aihara, Hideki] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
   [Yin, Zhiqi; Shi, Ke; Aihara, Hideki] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
   [Yin, Zhiqi; Shi, Ke; Aihara, Hideki] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Banerjee, Surajit] Cornell Univ, Northeastern Collaborat Access Team, Adv Photon Source, Lemont, IL 60439 USA.
   [Pandey, Krishan K.; Bera, Sibes; Grandgenett, Duane P.] St Louis Univ, Hlth Sci Ctr, Inst Mol Virol, St Louis, MO 63104 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; United States Department of Energy (DOE); Argonne National Laboratory; Saint Louis University
RP Aihara, H (corresponding author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.; Aihara, H (corresponding author), Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.; Aihara, H (corresponding author), Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
EM aihar001@umn.edu
FU National Institutes of Health [GM109770, AI087098, AI100682];  [DE-AC02-06CH11357]; National Institute of General Medical Sciences [R35GM118047] Funding Source: NIH RePORTER
NR 41
TC 70
Z9 78
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 362
EP +
DI 10.1038/nature16950
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100043
PM 26887497
DA 2026-03-09
ER

PT J
AU Granvik, M
   Morbidelli, A
   Jedicke, R
   Bolin, B
   Bottke, WF
   Beshore, E
   Vokrouhlicky, D
   Delbò, M
   Michel, P
AF Granvik, Mikael
   Morbidelli, Alessandro
   Jedicke, Robert
   Bolin, Bryce
   Bottke, William F.
   Beshore, Edward
   Vokrouhlicky, David
   Delbo, Marco
   Michel, Patrick
TI Super-catastrophic disruption of asteroids at small perihelion distances
SO NATURE
LA English
DT Article
ID near-earth objects; population; origin
AB Most near-Earth objects came from the asteroid belt and drifted via non-gravitational thermal forces into resonant escape routes that, in turn, pushed them onto planet-crossing orbits(1-3). Models predict that numerous asteroids should be found on orbits that closely approach the Sun, but few have been seen. In addition, even though the near-Earth-object population in general is an even mix of low-albedo (less than ten per cent of incident radiation is reflected) and high-albedo (more than ten per cent of incident radiation is reflected) asteroids, the characterized asteroids near the Sun typically have high albedos(4). Here we report a quantitative comparison of actual asteroid detections and a near-Earth-object model (which accounts for observational selection effects). We conclude that the deficit of low-albedo objects near the Sun arises from the super-catastrophic breakup (that is, almost complete disintegration) of a substantial fraction of asteroids when they achieve perihelion distances of a few tens of solar radii. The distance at which destruction occurs is greater for smaller asteroids, and their temperatures during perihelion passages are too low for evaporation to explain their disappearance. Although both bright and dark (high-and low-albedo) asteroids eventually break up, we find that low-albedo asteroids are more likely to be destroyed farther from the Sun, which explains the apparent excess of high-albedo near-Earth objects and suggests that low-albedo asteroids break up more easily as a result of thermal effects.
C1 [Granvik, Mikael] Univ Helsinki, Dept Phys, POB 64, FIN-00014 Helsinki, Finland.
   [Granvik, Mikael] Finnish Geospatial Res Inst, POB 15, Masala 02430, Finland.
   [Morbidelli, Alessandro; Bolin, Bryce; Delbo, Marco; Michel, Patrick] Observ Cote Azur, Blvd Observ, F-06304 Nice 4, France.
   [Jedicke, Robert] Univ Hawaii, Inst Astron, 2680 Woodlawn Dr, Honolulu, HI 96822 USA.
   [Bottke, William F.] Southwest Res Inst, 1050 Walnut St,Suite 300, Boulder, CO 80302 USA.
   [Beshore, Edward] Univ Arizona, 933 North Cherry Ave, Tucson, AZ 85721 USA.
   [Vokrouhlicky, David] Charles Univ Prague, Inst Astron, V Holesovickach 2, CZ-18000 Prague 8, Czech Republic.
C3 University of Helsinki; The National Land Survey of Finland; Finnish Geospatial Research Institute (FGI); Universite Cote d'Azur; Observatoire de la Cote d'Azur; University of Hawaii System; Southwest Research Institute; University of Arizona; Charles University Prague
RP Granvik, M (corresponding author), Univ Helsinki, Dept Phys, POB 64, FIN-00014 Helsinki, Finland.; Granvik, M (corresponding author), Finnish Geospatial Res Inst, POB 15, Masala 02430, Finland.
EM mgranvik@iki.fi
NR 22
TC 204
Z9 219
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 303
EP 306
DI 10.1038/nature16934
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100030
PM 26887492
DA 2026-03-09
ER

PT J
AU Liu, JQ
   Hanne, J
   Britton, BM
   Bennett, J
   Kim, D
   Lee, JB
   Fishel, R
AF Liu, Jiaquan
   Hanne, Jeungphill
   Britton, Brooke M.
   Bennett, Jared
   Kim, Daehyung
   Lee, Jong-Bong
   Fishel, Richard
TI Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair
SO NATURE
LA English
DT Article
ID escherichia-coli muts; proteins; recognition; reveals; ribonucleotides; visualization; hydrolysis; mechanisms; switches; signals
AB Mismatched nucleotides arise from polymerase misincorporation errors, recombination between heteroallelic parents and chemical or physical DNA damage(1). Highly conserved MutS (MSH) and MutL (MLH/PMS) homologues initiate mismatch repair and, in higher eukaryotes, act as DNA damage sensors that can trigger apoptosis(2). Defects in human mismatch repair genes cause Lynch syndrome or hereditary non-polyposis colorectal cancer and 10-40% of related sporadic tumours(3). However, the collaborative mechanics of MSH and MLH/PMS proteins have not been resolved in any organism. We visualized Escherichia coli (Ec) ensemble mismatch repair and confirmed that EcMutS mismatch recognition results in the formation of stable ATP-bound sliding clamps that randomly diffuse along the DNA with intermittent backbone contact. The EcMutS sliding clamps act as a platform to recruit EcMutL onto the mismatched DNA, forming an EcMutS-EcMutL search complex that then closely follows the DNA backbone. ATP binding by EcMutL establishes a second long-lived DNA clamp that oscillates between the principal EcMutS-EcMutL search complex and unrestricted EcMutS and EcMutL sliding clamps. The EcMutH endonuclease that targets mismatch repair excision only binds clamped EcMutL, increasing its DNA association kinetics by more than 1,000-fold. The assembly of an EcMutS-EcMutL-EcMutH search complex illustrates how sequential stable sliding clamps can modulate one-dimensional diffusion mechanics along the DNA to direct mismatch repair.
C1 [Liu, Jiaquan; Hanne, Jeungphill; Britton, Brooke M.; Bennett, Jared; Fishel, Richard] Ohio State Univ, Wexner Med Ctr, Dept Canc Biol & Genet, Columbus, OH 43210 USA.
   [Kim, Daehyung; Lee, Jong-Bong] Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, Kyungbuk, South Korea.
   [Lee, Jong-Bong] POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, Kyungbuk, South Korea.
   [Fishel, Richard] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; Pohang University of Science & Technology (POSTECH); Pohang University of Science & Technology (POSTECH); University System of Ohio; Ohio State University
RP Fishel, R (corresponding author), Ohio State Univ, Wexner Med Ctr, Dept Canc Biol & Genet, Columbus, OH 43210 USA.; Lee, JB (corresponding author), Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, Kyungbuk, South Korea.; Lee, JB (corresponding author), POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, Kyungbuk, South Korea.; Fishel, R (corresponding author), Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
EM jblee@postech.ac.kr; fishel.7@osu.edu
FU NRF of Korea [2011-001309]; NIH [CA67007]; National Cancer Institute [P30CA016058, R01CA067007] Funding Source: NIH RePORTER
NR 40
TC 90
Z9 106
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 583
EP +
DI 10.1038/nature20562
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600048
PM 27851738
DA 2026-03-09
ER

PT J
AU Okamura, M
   Kondo, M
   Kuga, R
   Kurashige, Y
   Yanai, T
   Hayami, S
   Praneeth, VKK
   Yoshida, M
   Yoneda, K
   Kawata, S
   Masaoka, S
AF Okamura, Masaya
   Kondo, Mio
   Kuga, Reiko
   Kurashige, Yuki
   Yanai, Takeshi
   Hayami, Shinya
   Praneeth, Vijayendran K. K.
   Yoshida, Masaki
   Yoneda, Ko
   Kawata, Satoshi
   Masaoka, Shigeyuki
TI A pentanuclear iron catalyst designed for water oxidation
SO NATURE
LA English
DT Article
ID hydrogen evolution; photosystem-ii; complexes; electrocatalyst; resolution; angstrom; ligand; cycle; core
AB Although the oxidation of water is efficiently catalysed by the oxygen-evolving complex in photosystem II (refs 1 and 2), it remains one of the main bottlenecks when aiming for synthetic chemical fuel production powered by sunlight or electricity. Consequently, the development of active and stable water oxidation catalysts is crucial, with heterogeneous systems(3,4) considered more suitable for practical use and their homogeneous counterparts more suitable for targeted, molecular-level design guided by mechanistic understanding(5-19). Research into the mechanism of water oxidation has resulted in a range of synthetic molecular catalysts, yet there remains much interest in systems that use abundant, inexpensive and environmentally benign metals such as iron (the most abundant transition metal in the Earth's crust and found in natural(20,21) and synthetic(22) oxidation catalysts). Water oxidation catalysts based on mononuclear iron complexes have been explored(9,12,16,18), but they often deactivate rapidly and exhibit relatively low activities. Here we report a pentanuclear iron complex that efficiently and robustly catalyses water oxidation with a turnover frequency of 1,900 per second, which is about three orders of magnitude larger than that of other iron-based catalysts. Electrochemical analysis confirms the redox flexibility of the system, characterized by six different oxidation states between Fe-5(II) and Fe-5(III); the Fe-5(III) state is active for oxidizing water. Quantum chemistry calculations indicate that the presence of adjacent active sites facilitates O-O bond formation with a reaction barrier of less than ten kilocalories per mole. Although the need for a high overpotential and the inability to operate in water-rich solutions limit the practicality of the present system, our findings clearly indicate that efficient water oxidation catalysts based on iron complexes can be created by ensuring that the system has redox flexibility and contains adjacent water-activation sites.
C1 [Okamura, Masaya; Kondo, Mio; Kuga, Reiko; Praneeth, Vijayendran K. K.; Yoshida, Masaki; Masaoka, Shigeyuki] Inst Mol Sci, Dept Life & Coordinat Complex Mol Sci, Higashiyama 5-1, Okazaki, Aichi 4448787, Japan.
   [Okamura, Masaya; Kondo, Mio; Kurashige, Yuki; Yanai, Takeshi; Masaoka, Shigeyuki] SOKENDAI Grad Univ Adv Studies, Hayama, Kanagawa 2400193, Japan.
   [Kondo, Mio; Masaoka, Shigeyuki] Inst Mol Sci, Res Ctr Integrat Mol Syst, Nishigo Naka 38, Okazaki, Aichi 4448585, Japan.
   [Kondo, Mio] Japan Sci & Technol Agcy, Adv Catalyt Transformat Program Carbon Utilizat, Honcho 4-1-8, Kawaguchi, Saitama 3320012, Japan.
   [Kurashige, Yuki; Yanai, Takeshi] Inst Mol Sci, Dept Theoret & Computat Mol Sci, Nishigo naka 38, Okazaki, Aichi 4448585, Japan.
   [Kurashige, Yuki] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Hayami, Shinya] Kumamoto Univ, Grad Sch Sci & Technol, Dept Chem, Kurokami 2-39-1, Kumamoto 8608555, Japan.
   [Yoneda, Ko] Saga Univ, Grad Sch Sci & Engn, Dept Chem & Appl Chem, Honjo Machi 1, Saga 8408502, Japan.
   [Kawata, Satoshi] Fukuoka Univ, Dept Chem, Fac Sci, Jonan Ku 8-19-1, Fukuoka 8140180, Japan.
C3 National Institutes of Natural Sciences (NINS) - Japan; Institute for Molecular Science (IMS); Graduate University for Advanced Studies - Japan; National Institutes of Natural Sciences (NINS) - Japan; Institute for Molecular Science (IMS); Japan Science & Technology Agency (JST); National Institutes of Natural Sciences (NINS) - Japan; Institute for Molecular Science (IMS); Japan Science & Technology Agency (JST); Kumamoto University; Saga University; Fukuoka University
RP Masaoka, S (corresponding author), Inst Mol Sci, Dept Life & Coordinat Complex Mol Sci, Higashiyama 5-1, Okazaki, Aichi 4448787, Japan.; Masaoka, S (corresponding author), SOKENDAI Grad Univ Adv Studies, Hayama, Kanagawa 2400193, Japan.; Masaoka, S (corresponding author), Inst Mol Sci, Res Ctr Integrat Mol Syst, Nishigo Naka 38, Okazaki, Aichi 4448585, Japan.
EM masaoka@ims.ac.jp
FU MEXT/JSPS [25708011, 15H05480, 26620160, 15H00889, 25107526, 15H01097, 26104538, 254037, 25288013, 25410030]; JST ACT-C; JST PRESTO; NINS Program for Cross-Disciplinary Study; Morino Foundation for Molecular Science; Grants-in-Aid for Scientific Research [15H00889, 15K17827, 26104538, 25288013, 13J04037, 25410078, 15H05480, 25410030, 15H01097, 25107526, 26620160, 25708011] Funding Source: KAKEN
NR 30
TC 464
Z9 496
U1 10
U2 614
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 465
EP 468
DI 10.1038/nature16529
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800032
PM 26863188
DA 2026-03-09
ER

PT J
AU Tarazona, OA
   Slota, LA
   Lopez, DH
   Zhang, GJ
   Cohn, MJ
AF Tarazona, Oscar A.
   Slota, Leslie A.
   Lopez, Davys H.
   Zhang, GuangJun
   Cohn, Martin J.
TI The genetic program for cartilage development has deep homology within Bilateria
SO NATURE
LA English
DT Article
ID ii collagen; chondrocyte differentiation; neural crest; evolution; sox9; expression; sequence; insights; animals; limulus
AB The evolution of novel cell types led to the emergence of new tissues and organs during the diversification of animals(1). The origin of the chondrocyte, the cell type that synthesizes cartilage matrix, was central to the evolution of the vertebrate endoskeleton. Cartilage-like tissues also exist outside the vertebrates, although their relationship to vertebrate cartilage is enigmatic. Here we show that protostome and deuterostome cartilage share structural and chemical properties, and that the mechanisms of cartilage development are extensively conserved-from induction of chondroprogenitor cells by Hedgehog and beta-catenin signalling, to chondrocyte differentiation and matrix synthesis by SoxE and SoxD regulation of clade A fibrillar collagen (ColA) genes-suggesting that the chondrogenic gene regulatory network evolved in the common ancestor of Bilateria. These results reveal deep homology of the genetic program for cartilage development in Bilateria and suggest that activation of this ancient core chondrogenic network underlies the parallel evolution of cartilage tissues in Ecdysozoa, Lophotrochozoa and Deuterostomia.
C1 [Tarazona, Oscar A.; Cohn, Martin J.] Univ Florida, UF Genet Inst, Howard Hughes Med Inst, POB 103610, Gainesville, FL 32610 USA.
   [Tarazona, Oscar A.; Zhang, GuangJun; Cohn, Martin J.] Univ Florida, Dept Biol, POB 103610, Gainesville, FL 32610 USA.
   [Slota, Leslie A.; Lopez, Davys H.; Cohn, Martin J.] Univ Florida, Dept Mol Genet & Microbiol, Coll Med, POB 103610, Gainesville, FL 32610 USA.
   [Zhang, GuangJun] Purdue Univ, Coll Vet Med, Dept Comparat Pathobiol, 625 Harrison St, W Lafayette, IN 47907 USA.
C3 Howard Hughes Medical Institute; State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; Purdue University System; Purdue University
RP Cohn, MJ (corresponding author), Univ Florida, UF Genet Inst, Howard Hughes Med Inst, POB 103610, Gainesville, FL 32610 USA.; Cohn, MJ (corresponding author), Univ Florida, Dept Biol, POB 103610, Gainesville, FL 32610 USA.; Cohn, MJ (corresponding author), Univ Florida, Dept Mol Genet & Microbiol, Coll Med, POB 103610, Gainesville, FL 32610 USA.
EM mjcohn@ufl.edu
FU Howard Hughes Medical Institute
NR 44
TC 48
Z9 60
U1 0
U2 47
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 86
EP +
DI 10.1038/nature17398
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900044
PM 27111511
DA 2026-03-09
ER

PT J
AU McKinnon, WB
   Nimmo, F
   Wong, T
   Schenk, PM
   White, OL
   Roberts, JH
   Moore, JM
   Spencer, JR
   Howard, AD
   Umurhan, OM
   Stern, SA
   Weaver, HA
   Olkin, CB
   Young, LA
   Smith, KE
AF McKinnon, William B.
   Nimmo, Francis
   Wong, Teresa
   Schenk, Paul M.
   White, Oliver L.
   Roberts, J. H.
   Moore, J. M.
   Spencer, J. R.
   Howard, A. D.
   Umurhan, O. M.
   Stern, S. A.
   Weaver, H. A.
   Olkin, C. B.
   Young, L. A.
   Smith, K. E.
TI Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour
SO NATURE
LA English
DT Article
ID viscosity; rheology; impact; relaxation; surface; mantle; onset
AB The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity(1,2). Composed of molecular nitrogen, methane, and carbon monoxide ices(3), but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection(1,2). Here we report, on the basis of available rheological measurements(4), that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated presentday heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime(5), a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum(2). Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.
C1 [McKinnon, William B.; Wong, Teresa] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [McKinnon, William B.; Wong, Teresa] Washington Univ, McDonnell Ctr Space Sci, St Louis, MO 63130 USA.
   [Nimmo, Francis] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Schenk, Paul M.] Lunar & Planetary Inst, 3303 NASA Rd 1, Houston, TX 77058 USA.
   [White, Oliver L.; Moore, J. M.; Umurhan, O. M.; Smith, K. E.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Roberts, J. H.; Weaver, H. A.] Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
   [Spencer, J. R.; Stern, S. A.; Olkin, C. B.; Young, L. A.] SW Res Inst, Boulder, CO 80302 USA.
   [Howard, A. D.] Univ Virginia, Dept Environm Sci, Charlottesville, VA 22904 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California Santa Cruz; National Aeronautics & Space Administration (NASA); National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; University of Virginia
RP McKinnon, WB (corresponding author), Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.; McKinnon, WB (corresponding author), Washington Univ, McDonnell Ctr Space Sci, St Louis, MO 63130 USA.
EM mckinnon@wustl.edu
FU NASA's New Horizons project
NR 40
TC 99
Z9 109
U1 4
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 82
EP +
DI 10.1038/nature18289
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300037
PM 27251279
DA 2026-03-09
ER

PT J
AU Thackeray, SJ
   Henrys, PA
   Hemming, D
   Bell, JR
   Botham, MS
   Burthe, S
   Helaouet, P
   Johns, DG
   Jones, ID
   Leech, DI
   Mackay, EB
   Massimino, D
   Atkinson, S
   Bacon, PJ
   Brereton, TM
   Carvalho, L
   Clutton-Brock, TH
   Duck, C
   Edwards, M
   Elliott, JM
   Hall, SJG
   Harrington, R
   Pearce-Higgins, JW
   Hoye, TT
   Kruuk, LEB
   Pemberton, JM
   Sparks, TH
   Thompson, PM
   White, I
   Winfield, IJ
   Wanless, S
AF Thackeray, Stephen J.
   Henrys, Peter A.
   Hemming, Deborah
   Bell, James R.
   Botham, Marc S.
   Burthe, Sarah
   Helaouet, Pierre
   Johns, David G.
   Jones, Ian D.
   Leech, David I.
   Mackay, Eleanor B.
   Massimino, Dario
   Atkinson, Sian
   Bacon, Philip J.
   Brereton, Tom M.
   Carvalho, Laurence
   Clutton-Brock, Tim H.
   Duck, Callan
   Edwards, Martin
   Elliott, J. Malcolm
   Hall, Stephen J. G.
   Harrington, Richard
   Pearce-Higgins, James W.
   Hoye, Toke T.
   Kruuk, Loeske E. B.
   Pemberton, Josephine M.
   Sparks, Tim H.
   Thompson, Paul M.
   White, Ian
   Winfield, Ian J.
   Wanless, Sarah
TI Phenological sensitivity to climate across taxa and trophic levels
SO NATURE
LA English
DT Article
ID fresh-water; spring phytoplankton; responses; constraints; stream; shifts
AB Differences in phenological responses to climate change among species can desynchronise ecological interactions and thereby threaten ecosystem function. To assess these threats, we must quantify the relative impact of climate change on species at different trophic levels. Here, we apply a Climate Sensitivity Profile approach to 10,003 terrestrial and aquatic phenological data sets, spatially matched to temperature and precipitation data, to quantify variation in climate sensitivity. The direction, magnitude and timing of climate sensitivity varied markedly among organisms within taxonomic and trophic groups. Despite this variability, we detected systematic variation in the direction and magnitude of phenological climate sensitivity. Secondary consumers showed consistently lower climate sensitivity than other groups. We used mid-century climate change projections to estimate that the timing of phenological events could change more for primary consumers than for species in other trophic levels (6.2 versus 2.5-2.9 days earlier on average), with substantial taxonomic variation (1.1-14.8 days earlier on average).
C1 [Thackeray, Stephen J.; Henrys, Peter A.; Jones, Ian D.; Mackay, Eleanor B.; Winfield, Ian J.] Lancaster Environm Ctr, Ctr Ecol & Hydrol, Lib Ave, Lancaster LA1 4AP, England.
   [Hemming, Deborah] Met Off, FitzRoy Rd, Exeter EX1 3PB, Devon, England.
   [Bell, James R.; Harrington, Richard] Rothamsted Res, Harpenden AL5 2JQ, Herts, England.
   [Botham, Marc S.] Ctr Ecol & Hydrol, Maclean Bldg,Benson Lane, Wallingford OX10 8BB, Oxon, England.
   [Burthe, Sarah; Carvalho, Laurence; Wanless, Sarah] Ctr Ecol & Hydrol, Bush Estate, Penicuik EH26 0QB, Midlothian, Scotland.
   [Helaouet, Pierre; Johns, David G.; Edwards, Martin] Sir Alister Hardy Fdn Ocean Sci, The Lab, Citadel Hill, Plymouth PL1 2PB, Devon, England.
   [Leech, David I.; Massimino, Dario; Pearce-Higgins, James W.] British Trust Ornithol, The Nunnery, Thetford IP24 2PU, Norfolk, England.
   [Atkinson, Sian] Woodland Trust, Kempton Way, Grantham NG31 6LL, Lincolnshire, England.
   [Bacon, Philip J.] Futtie Pk, Aberdeen AB31 4RX, Scotland.
   [Brereton, Tom M.] Butterfly Conservat, Wareham BH20 5QP, Dorset, England.
   [Clutton-Brock, Tim H.] Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
   [Duck, Callan] Univ St Andrews, Scottish Oceans Inst, Sea Mammal Res Unit, St Andrews KY16 8LB, Fife, Scotland.
   [Elliott, J. Malcolm] Freshwater Biol Assoc, Ambleside LA22 0LP, Cumbria, England.
   [Hall, Stephen J. G.] Lincoln Univ, Riseholme Hall,Riseholme Pk, Lincoln LN2 2LG, Lincolnshire, England.
   [Hoye, Toke T.] Aarhus Univ, Aarhus Inst Adv Studies, Dept Biosci, Hoegh Guldbergs Gade 6B, Aarhus, Denmark.
   [Hoye, Toke T.] Aarhus Univ, Arctic Res Ctr, Hoegh Guldbergs Gade 6B, DK-8000 Aarhus C, Denmark.
   [Kruuk, Loeske E. B.; Pemberton, Josephine M.] Univ Edinburgh, Sch Biol Sci, Inst Evolutionary Biol, Edinburgh EH9 3FL, Midlothian, Scotland.
   [Kruuk, Loeske E. B.] Australian Natl Univ, Res Sch Biol, Canberra, ACT 2612, Australia.
   [Sparks, Tim H.] Coventry Univ, Fac Engn & Comp, Priory St, Coventry CV1 5FB, W Midlands, England.
   [Sparks, Tim H.] Poznan Univ Life Sci, Inst Zool, Wojska Polskiego 71C, PL-60625 Poznan, Poland.
   [Thompson, Paul M.] Univ Aberdeen, George St, Cromarty IV11 8YJ, Ross Shire, Scotland.
   [White, Ian] Peoples Trust Endangered Species, 15 Cloisters House,8 Battersea Pk Rd, London SW8 4BG, England.
C3 UK Centre for Ecology & Hydrology (UKCEH); Lancaster University; Met Office - UK; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; UK Centre for Ecology & Hydrology (UKCEH); UK Centre for Ecology & Hydrology (UKCEH); British Trust for Ornithology; University of Cambridge; University of St Andrews; Freshwater Biological Association (FBA); University of Lincoln; Aarhus University; Aarhus University; University of Edinburgh; Australian National University; Coventry University; Poznan University of Life Sciences; University of Aberdeen
RP Thackeray, SJ (corresponding author), Lancaster Environm Ctr, Ctr Ecol & Hydrol, Lib Ave, Lancaster LA1 4AP, England.
EM sjtr@ceh.ac.uk
FU Natural Environment Research Council (NERC) [NE/J02080X/1]; BBSRC; BBSRC [BBS/E/C/00005191, BBS/E/C/00005195] Funding Source: UKRI; NERC [NE/J020362/1, NE/I030062/1, NE/M003035/1, NE/J02080X/1, NE/I024925/1, SAH01001, ceh020002, NE/J020451/1, NE/L00688X/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/C/00005195, BBS/E/C/00005191] Funding Source: researchfish; Natural Environment Research Council [smru10001, NE/I024925/1, ceh020002, NE/J02080X/1, NE/J020451/1, NE/M003035/1, NE/I030062/1, SAH01001, NE/L00688X/1, NE/J020362/1] Funding Source: researchfish; Division Of Ocean Sciences; Directorate For Geosciences [1154661] Funding Source: National Science Foundation
NR 41
TC 764
Z9 874
U1 15
U2 668
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 241
EP U94
DI 10.1038/nature18608
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600048
PM 27362222
DA 2026-03-09
ER

PT J
AU Murray, DH
   Jahnel, M
   Lauer, J
   Avellaneda, MJ
   Brouilly, N
   Cezanne, A
   Morales-Navarrete, H
   Perini, ED
   Ferguson, C
   Lupas, AN
   Kalaidzidis, Y
   Parton, RG
   Grill, SW
   Zerial, M
AF Murray, David H.
   Jahnel, Marcus
   Lauer, Janelle
   Avellaneda, Mario J.
   Brouilly, Nicolas
   Cezanne, Alice
   Morales-Navarrete, Hernan
   Perini, Enrico D.
   Ferguson, Charles
   Lupas, Andrei N.
   Kalaidzidis, Yannis
   Parton, Robert G.
   Grill, Stephan W.
   Zerial, Marino
TI An endosomal tether undergoes an entropic collapse to bring vesicles together
SO NATURE
LA English
DT Article
ID membrane-fusion; coiled coils; eea1; rab; conversion; complexes; transport; proteins; docking; binding
AB An early step in intracellular transport is the selective recognition of a vesicle by its appropriate target membrane, a process regulated by Rab GTPases via the recruitment of tethering effectors(1-4). Membrane tethering confers higher selectivity and efficiency to membrane fusion than the pairing of SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) alone(5-7). Here we address the mechanism whereby a tethered vesicle comes closer towards its target membrane for fusion by reconstituting an endosomal asymmetric tethering machinery consisting of the dimeric coiled-coil protein EEA1 (refs 6, 7) recruited to phosphatidylinositol 3-phosphate membranes and binding vesicles harbouring Rab5. Surprisingly, structural analysis reveals that Rab5:GTP induces an allosteric conformational change in EEA1, from extended to flexible and collapsed. Through dynamic analysis by optical tweezers, we confirm that EEA1 captures a vesicle at a distance corresponding to its extended conformation, and directly measure its flexibility and the forces induced during the tethering reaction. Expression of engineered EEA1 variants defective in the conformational change induce prominent clusters of tethered vesicles in vivo. Our results suggest a new mechanism in which Rab5 induces a change in flexibility of EEA1, generating an entropic collapse force that pulls the captured vesicle towards the target membrane to initiate docking and fusion.
C1 [Murray, David H.; Jahnel, Marcus; Lauer, Janelle; Avellaneda, Mario J.; Brouilly, Nicolas; Cezanne, Alice; Morales-Navarrete, Hernan; Perini, Enrico D.; Kalaidzidis, Yannis; Grill, Stephan W.; Zerial, Marino] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
   [Jahnel, Marcus; Avellaneda, Mario J.; Perini, Enrico D.; Grill, Stephan W.] Tech Univ Dresden, Ctr Biotechnol, Tatzberg 47-49, D-01307 Dresden, Germany.
   [Jahnel, Marcus; Grill, Stephan W.] Max Planck Inst Phys Komplexer Syst, Nothnitzerstr 38, D-01187 Dresden, Germany.
   [Ferguson, Charles; Parton, Robert G.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
   [Lupas, Andrei N.] Max Planck Inst Dev Biol, Dept Prot Evolut, D-72076 Tubingen, Germany.
   [Parton, Robert G.] Univ Queensland, Ctr Microscopy & Microanal, St Lucia, Qld 4072, Australia.
   [Avellaneda, Mario J.] FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
C3 Max Planck Society; Technische Universitat Dresden; Max Planck Society; University of Queensland; Max Planck Society; University of Queensland; AMOLF
RP Murray, DH (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
FU Bohringer Ingelheim Fonds; La Caixa; Deutscher Akademischer Austauschdienst scholarship; National Health and Medical Research Council of Australia [APP1037320, 569452]; Australian Research Council Centre of Excellence [CE140100036]; Deutsche Forschungsgemeinschaft [SPP 1782, GSC 97, GR 3271/2, GR 3271/3, GR 3271/4, Transregio 83]; European Research Council [281903]; Human Frontier Science Program [RGP0023/2014]; Max Planck Society; European Research Council (ERC) [281903] Funding Source: European Research Council (ERC)
NR 29
TC 109
Z9 130
U1 1
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 107
EP 111
DI 10.1038/nature19326
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900048
PM 27556945
DA 2026-03-09
ER

PT J
AU Silver, D
   Huang, A
   Maddison, CJ
   Guez, A
   Sifre, L
   van den Driessche, G
   Schrittwieser, J
   Antonoglou, I
   Panneershelvam, V
   Lanctot, M
   Dieleman, S
   Grewe, D
   Nham, J
   Kalchbrenner, N
   Sutskever, I
   Lillicrap, T
   Leach, M
   Kavukcuoglu, K
   Graepel, T
   Hassabis, D
AF Silver, David
   Huang, Aja
   Maddison, Chris J.
   Guez, Arthur
   Sifre, Laurent
   van den Driessche, George
   Schrittwieser, Julian
   Antonoglou, Ioannis
   Panneershelvam, Veda
   Lanctot, Marc
   Dieleman, Sander
   Grewe, Dominik
   Nham, John
   Kalchbrenner, Nal
   Sutskever, Ilya
   Lillicrap, Timothy
   Leach, Madeleine
   Kavukcuoglu, Koray
   Graepel, Thore
   Hassabis, Demis
TI Mastering the game of Go with deep neural networks and tree search
SO NATURE
LA English
DT Article
ID computer; chess
AB The game of Go has long been viewed as the most challenging of classic games for artificial intelligence owing to its enormous search space and the difficulty of evaluating board positions and moves. Here we introduce a new approach to computer Go that uses 'value networks' to evaluate board positions and 'policy networks' to select moves. These deep neural networks are trained by a novel combination of supervised learning from human expert games, and reinforcement learning from games of self-play. Without any lookahead search, the neural networks play Go at the level of state-of-the-art Monte Carlo tree search programs that simulate thousands of random games of self-play. We also introduce a new search algorithm that combines Monte Carlo simulation with value and policy networks. Using this search algorithm, our program AlphaGo achieved a 99.8% winning rate against other Go programs, and defeated the human European Go champion by 5 games to 0. This is the first time that a computer program has defeated a human professional player in the full-sized game of Go, a feat previously thought to be at least a decade away.
C1 [Silver, David; Huang, Aja; Maddison, Chris J.; Guez, Arthur; Sifre, Laurent; van den Driessche, George; Schrittwieser, Julian; Antonoglou, Ioannis; Panneershelvam, Veda; Lanctot, Marc; Dieleman, Sander; Grewe, Dominik; Kalchbrenner, Nal; Lillicrap, Timothy; Leach, Madeleine; Kavukcuoglu, Koray; Graepel, Thore; Hassabis, Demis] Google DeepMind, 5 New St Sq, London EC4A 3TW, England.
   [Nham, John; Sutskever, Ilya] Google, 1600 Amphitheatre Pkwy, Mountain View, CA 94043 USA.
C3 Alphabet Inc.; Google Incorporated; DeepMind; Alphabet Inc.; Google Incorporated
RP Silver, D; Hassabis, D (corresponding author), Google DeepMind, 5 New St Sq, London EC4A 3TW, England.
EM davidsilver@google.com; demishassabis@google.com
NR 61
TC 11285
Z9 14663
U1 177
U2 5659
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 484
EP +
DI 10.1038/nature16961
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800028
PM 26819042
DA 2026-03-09
ER

PT J
AU Walls, AC
   Tortorici, MA
   Bosch, BJ
   Frenz, B
   Rottier, PJM
   DiMaio, F
   Rey, FA
   Veesler, D
AF Walls, Alexandra C.
   Tortorici, M. Alejandra
   Bosch, Berend-Jan
   Frenz, Brandon
   Rottier, Peter J. M.
   DiMaio, Frank
   Rey, Felix A.
   Veesler, David
TI Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer
SO NATURE
LA English
DT Article
ID respiratory syndrome coronavirus; em structure determination; particle cryo-em; crystal-structure; murine coronavirus; fusion protein; electron cryomicroscopy; membrane-fusion; human receptor; s2 domain
AB The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions(1). S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins(2,3), implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.
C1 [Walls, Alexandra C.; Frenz, Brandon; DiMaio, Frank; Veesler, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Tortorici, M. Alejandra; Rey, Felix A.] Inst Pasteur, Unite Virol Struct, F-75015 Paris, France.
   [Tortorici, M. Alejandra; Rey, Felix A.] CNRS UMR 3569 Virol, F-75015 Paris, France.
   [Bosch, Berend-Jan; Rottier, Peter J. M.] Univ Utrecht, Div Virol, Dept Infect Dis & Immunol, Fac Vet Med, NL-3584 CL Utrecht, Netherlands.
C3 University of Washington; University of Washington Seattle; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Utrecht University
RP Veesler, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.; Rey, FA (corresponding author), Inst Pasteur, Unite Virol Struct, F-75015 Paris, France.; Rey, FA (corresponding author), CNRS UMR 3569 Virol, F-75015 Paris, France.
EM felix.rey@pasteur.fr; dveesler@uw.edu
FU National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) [T32GM008268]; National Resource for Automated Molecular Microscopy [GM103310]; National Institute of General Medical Sciences [P41GM103310, T32GM008268] Funding Source: NIH RePORTER
NR 53
TC 396
Z9 485
U1 1
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 114
EP +
DI 10.1038/nature16988
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900051
PM 26855426
DA 2026-03-09
ER

PT J
AU Wu, TP
   Wang, T
   Seetin, MG
   Lai, YQ
   Zhu, SJ
   Lin, KX
   Liu, YF
   Byrum, SD
   Mackintosh, SG
   Zhong, M
   Tackett, A
   Wang, GL
   Hon, LS
   Fang, G
   Swenberg, JA
   Xiao, AZ
AF Wu, Tao P.
   Wang, Tao
   Seetin, Matthew G.
   Lai, Yongquan
   Zhu, Shijia
   Lin, Kaixuan
   Liu, Yifei
   Byrum, Stephanie D.
   Mackintosh, Samuel G.
   Zhong, Mei
   Tackett, Alan
   Wang, Guilin
   Hon, Lawrence S.
   Fang, Gang
   Swenberg, James A.
   Xiao, Andrew Z.
TI DNA methylation on N6-adenine in mammalian embryonic stem cellse
SO NATURE
LA English
DT Article
ID x-chromosome inactivation; chip-seq data; single-molecule; repeat hypothesis; histone variants; rna-seq; adenine; line-1; mouse; differentiation
AB It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N-6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N-6-methyladenine. An increase of N-6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N-6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (<1.5 million years old) but not old (>6 million years old) L1 elements. The deposition of N-6-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N-6-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N-6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes.
C1 [Wu, Tao P.; Wang, Tao; Lin, Kaixuan; Liu, Yifei; Xiao, Andrew Z.] Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA.
   [Wu, Tao P.; Wang, Tao; Lin, Kaixuan; Liu, Yifei; Zhong, Mei; Xiao, Andrew Z.] Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA.
   [Seetin, Matthew G.; Hon, Lawrence S.] Pacific Biosci, 1380 Willow Rd, Menlo Pk, CA 94025 USA.
   [Lai, Yongquan; Swenberg, James A.] Univ N Carolina, Environm Sci & Engn, Chapel Hill, NC 27599 USA.
   [Zhu, Shijia; Fang, Gang] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Zhu, Shijia; Fang, Gang] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.
   [Byrum, Stephanie D.; Mackintosh, Samuel G.; Tackett, Alan] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA.
   [Zhong, Mei] Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA.
   [Wang, Guilin] Yale Univ, Sch Med, Yale Ctr Genome Anal, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA.
C3 Yale University; Yale University; University of North Carolina; University of North Carolina Chapel Hill; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Arkansas System; University of Arkansas Medical Sciences; Yale University; Yale University
RP Xiao, AZ (corresponding author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA.; Xiao, AZ (corresponding author), Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06520 USA.
EM Andrew.Xiao@Yale.edu
FU CT Stem Cell Foundation [11SCA34]; National Institutes of Environmental Health Sciences (NIEHS) Superfund Basic Research Program [P42 ES005948]; NIEHS Center for Environmental Health and Susceptibility [P30 ES010126]; [R01GM114205-01];  [R01 GM114472-01]; National Cancer Institute [P30CA016359] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001863] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [P30ES010126] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P20GM103429] Funding Source: NIH RePORTER
NR 41
TC 504
Z9 604
U1 1
U2 176
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 329
EP +
DI 10.1038/nature17640
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700025
PM 27027282
DA 2026-03-09
ER

PT J
AU Meeske, AJ
   Riley, EP
   Robins, WP
   Uehara, T
   Mekalanos, JJ
   Kahne, D
   Walker, S
   Kruse, AC
   Bernhardt, TG
   Rudner, DZ
AF Meeske, Alexander J.
   Riley, Eammon P.
   Robins, William P.
   Uehara, Tsuyoshi
   Mekalanos, John J.
   Kahne, Daniel
   Walker, Suzanne
   Kruse, Andrew C.
   Bernhardt, Thomas G.
   Rudner, David Z.
TI SEDS proteins are a widespread family of bacterial cell wall polymerases
SO NATURE
LA English
DT Article
ID penicillin-binding proteins; beta-lactam resistance; bacillus-subtilis; peptidoglycan synthesis; division; gene; biosynthesis; precursors; dynamics; flippase
AB Elongation of rod-shaped bacteria is mediated by a dynamic peptidoglycan-synthetizing machinery called the Rod complex. Here we report that, in Bacillus subtilis, this complex is functional in the absence of all known peptidoglycan polymerases. Cells lacking these enzymes survive by inducing an envelope stress response that increases the expression of RodA, a widely conserved core component of the Rod complex. RodA is a member of the SEDS (shape, elongation, division and sporulation) family of proteins, which have essential but ill-defined roles in cell wall biogenesis during growth, division and sporulation. Our genetic and biochemical analyses indicate that SEDS proteins constitute a family of peptidoglycan polymerases. Thus, B. subtilis and probably most bacteria use two distinct classes of polymerase to synthesize their exoskeleton. Our findings indicate that SEDS family proteins are core cell wall synthases of the cell elongation and division machinery, and represent attractive targets for antibiotic development.
C1 [Meeske, Alexander J.; Riley, Eammon P.; Robins, William P.; Uehara, Tsuyoshi; Mekalanos, John J.; Walker, Suzanne; Bernhardt, Thomas G.; Rudner, David Z.] Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
   [Kahne, Daniel; Walker, Suzanne; Kruse, Andrew C.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA.
   [Kahne, Daniel; Walker, Suzanne] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University
RP Bernhardt, TG; Rudner, DZ (corresponding author), Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM thomas@hms.harvard.edu; rudner@hms.harvard.edu
FU National Institute of Health [GM073831, RC2 GM092616, AI083365, AI099144]; Center for Excellence in Translational Research [U19 AI109764]; National Institute of Allergy and Infectious Diseases [R01AI083365, R37AI018045, T32AI007061] Funding Source: NIH RePORTER
NR 47
TC 369
Z9 461
U1 3
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 634
EP +
DI 10.1038/nature19331
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700040
PM 27525505
DA 2026-03-09
ER

PT J
AU Annett, J
   Cross, GLW
AF Annett, James
   Cross, Graham L. W.
TI Self-assembly of graphene ribbons by spontaneous self-tearing and peeling from a substrate
SO NATURE
LA English
DT Article
ID layer graphene; adhesion; membranes
AB Graphene and related two-dimensional materials have shown unusual and exceptional mechanical properties(1-3), with similarities to origami-like paper folding(4,5) and kirigami-like cutting(6,7) demonstrated. For paper analogues, a critical difference between macroscopic sheets and a two-dimensional solid is the molecular scale of the thin dimension of the latter, allowing the thermal activation of considerable out-of-plane motion. So far thermal activity has been shown to produce local wrinkles in a free graphene sheet that help in theoretically understanding its stability(8), for example, and give rise to unexpected long-range bending stiffness(6). Here we show that thermal activation can have a more marked effect on the behaviour of two-dimensional solids, leading to spontaneous and self-driven sliding, tearing and peeling from a substrate on scales approaching the macroscopic. We demonstrate that scalable nanoimprint-style contact techniques can nucleate and direct the parallel self-assembly of graphene ribbons of controlled shape in ambient conditions. We interpret our observations through a simple fracture-mechanics model that shows how thermodynamic forces drive the formation of the graphene-graphene interface in lieu of substrate contact with sufficient strength to peel and tear multilayer graphene sheets. Our results show how weak physical surface forces can be harnessed and focused by simple folded configurations of graphene to tear the strongest covalent bond. This effect may hold promise for the patterning and mechanical actuating of devices based on two-dimensional materials.
C1 [Annett, James; Cross, Graham L. W.] Trinity Coll Dublin, Ctr Res Adapt Nanostruct & Nanodevices, Dublin 2, Ireland.
   [Annett, James; Cross, Graham L. W.] Trinity Coll Dublin, Adv Mat & BioEngn Res, Dublin 2, Ireland.
   [Annett, James; Cross, Graham L. W.] Trinity Coll Dublin, Sch Phys, Dublin 2, Ireland.
C3 Trinity College Dublin; Trinity College Dublin; Trinity College Dublin
RP Cross, GLW (corresponding author), Trinity Coll Dublin, Ctr Res Adapt Nanostruct & Nanodevices, Dublin 2, Ireland.; Cross, GLW (corresponding author), Trinity Coll Dublin, Adv Mat & BioEngn Res, Dublin 2, Ireland.; Cross, GLW (corresponding author), Trinity Coll Dublin, Sch Phys, Dublin 2, Ireland.
EM graham.cross@tcd.ie
FU Science Foundation of Ireland (SFI) [CRANN CSET 08/CE/11432, PI 08/IN/I1932]
NR 32
TC 170
Z9 189
U1 4
U2 504
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 271
EP +
DI 10.1038/nature18304
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600054
PM 27411633
DA 2026-03-09
ER

PT J
AU Cugola, FR
   Fernandes, IR
   Russo, FB
   Freitas, BC
   Dias, JLM
   Guimaraes, KP
   Benazzato, C
   Almeida, N
   Pignatari, GC
   Romero, S
   Polonio, CM
   Cunha, I
   Freitas, CL
   Brandao, WN
   Rossato, C
   Andrade, DG
   Faria, DD
   Garcez, AT
   Buchpigel, CA
   Braconi, CT
   Mendes, E
   Sall, AA
   Zanotto, PMD
   Peron, JPS
   Muotri, AR
   Beltrao-Braga, PCB
AF Cugola, Fernanda R.
   Fernandes, Isabella R.
   Russo, Fabiele B.
   Freitas, Beatriz C.
   Dias, Joao L. M.
   Guimaraes, Katia P.
   Benazzato, Cecilia
   Almeida, Nathalia
   Pignatari, Graciela C.
   Romero, Sarah
   Polonio, Carolina M.
   Cunha, Isabela
   Freitas, Carla L.
   Brandao, Wesley N.
   Rossato, Cristiano
   Andrade, David G.
   Faria, Daniele de P.
   Garcez, Alexandre T.
   Buchpigel, Carlos A.
   Braconi, Carla T.
   Mendes, Erica
   Sall, Amadou A.
   Zanotto, Paolo M. de A.
   Peron, Jean Pierre S.
   Muotri, Alysson R.
   Beltrao-Braga, Patricia C. B.
TI The Brazilian Zika virus strain causes birth defects in experimental models
SO NATURE
LA English
DT Article
ID infection; brain; growth
AB Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel rhesus monkeys(1). Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on Yap Island in Micronesia(2). Patients experienced fever, skin rash, arthralgia and conjunctivitis(2). From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America3. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barre syndrome(4,5). Despite clinical evidence, direct experimental evidence showing that the Brazilian ZIKV (ZIKVBR) strain causes birth defects remains absent(6). Here we demonstrate that ZIKVBR infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells in vitro, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKVBR crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKVBR outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKVBR in human neurodevelopment.
C1 [Cugola, Fernanda R.; Fernandes, Isabella R.; Russo, Fabiele B.; Dias, Joao L. M.; Guimaraes, Katia P.; Benazzato, Cecilia; Almeida, Nathalia; Pignatari, Graciela C.; Beltrao-Braga, Patricia C. B.] Univ Sao Paulo, Dept Surg, Stem Cell Lab, BR-05508270 Sao Paulo, Brazil.
   [Fernandes, Isabella R.; Freitas, Beatriz C.; Romero, Sarah; Muotri, Alysson R.] Univ Calif San Diego, Dept Cellular & Mol Med, Rady Childrens Hosp San Diego, Sch Med,Dept Pediat,Stem Cell Program, La Jolla, CA 92037 USA.
   [Russo, Fabiele B.; Pignatari, Graciela C.] Tismoo, BR-01401000 Sao Paulo, Brazil.
   [Polonio, Carolina M.; Cunha, Isabela; Freitas, Carla L.; Brandao, Wesley N.; Rossato, Cristiano; Andrade, David G.; Peron, Jean Pierre S.] Univ Sao Paulo, Dept Immunol, Neuroimmune Interact Lab, BR-05508000 Sao Paulo, Brazil.
   [Faria, Daniele de P.; Garcez, Alexandre T.; Buchpigel, Carlos A.] Univ Sao Paulo, USP Sch Med, Dept Radiol & Oncol, BR-05403010 Sao Paulo, Brazil.
   [Braconi, Carla T.; Mendes, Erica; Zanotto, Paolo M. de A.] Univ Sao Paulo, Inst Microbiol Sci, Dept Microbiol, Lab Mol Evolut & Bioinformat, BR-05508000 Sao Paulo, Brazil.
   [Sall, Amadou A.] Inst Pasteur, Dakar 220, Senegal.
   [Beltrao-Braga, Patricia C. B.] Univ Sao Paulo, Sch Arts Sci & Humanities, Dept Obstet, BR-03828000 Sao Paulo, Brazil.
C3 Universidade de Sao Paulo; Rady Childrens Hospital San Diego; University of California System; University of California San Diego; Universidade de Sao Paulo; Universidade de Sao Paulo; Universidade de Sao Paulo; Pasteur Network; Institut Pasteur Dakar; Universidade de Sao Paulo
RP Beltrao-Braga, PCB (corresponding author), Univ Sao Paulo, Dept Surg, Stem Cell Lab, BR-05508270 Sao Paulo, Brazil.; Muotri, AR (corresponding author), Univ Calif San Diego, Dept Cellular & Mol Med, Rady Childrens Hosp San Diego, Sch Med,Dept Pediat,Stem Cell Program, La Jolla, CA 92037 USA.; Peron, JPS (corresponding author), Univ Sao Paulo, Dept Immunol, Neuroimmune Interact Lab, BR-05508000 Sao Paulo, Brazil.; Beltrao-Braga, PCB (corresponding author), Univ Sao Paulo, Sch Arts Sci & Humanities, Dept Obstet, BR-03828000 Sao Paulo, Brazil.
EM jeanpierre@usp.br; muotri@ucsd.edu; patriciacbbbraga@usp.br
FU Zika Network FAPESP [2011/18703-2, 2014/17766-9]; NGO 'The Tooth Fairy Project'; National Institutes of Health [U19MH107367, R01MH094753]; NARSAD Independent Investigator Grant; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [14/17766-9, 11/18703-2] Funding Source: FAPESP
NR 36
TC 1003
Z9 1189
U1 1
U2 329
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 267
EP +
DI 10.1038/nature18296
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100045
PM 27279226
DA 2026-03-09
ER

PT J
AU Hebert-Chatelain, E
   Desprez, T
   Serrat, R
   Bellocchio, L
   Soria-Gomez, E
   Busquets-Garcia, A
   Zottola, ACP
   Delamarre, A
   Cannich, A
   Vincent, P
   Varilh, M
   Robin, LM
   Terral, G
   García-Fernández, MD
   Colavita, M
   Mazier, W
   Drago, F
   Puente, N
   Reguero, L
   Elezgarai, I
   Dupuy, JW
   Cota, D
   Lopez-Rodriguez, ML
   Barreda-Gómez, G
   Massa, F
   Grandes, P
   Bénard, G
   Marsicano, G
AF Hebert-Chatelain, Etienne
   Desprez, Tifany
   Serrat, Roman
   Bellocchio, Luigi
   Soria-Gomez, Edgar
   Busquets-Garcia, Arnau
   Zottola, Antonio Christian Pagano
   Delamarre, Anna
   Cannich, Astrid
   Vincent, Peggy
   Varilh, Marjorie
   Robin, Laurie M.
   Terral, Geoffrey
   Dolores Garcia-Fernandez, M.
   Colavita, Michelangelo
   Mazier, Wilfrid
   Drago, Filippo
   Puente, Nagore
   Reguero, Leire
   Elezgarai, Izaskun
   Dupuy, Jean-William
   Cota, Daniela
   Lopez-Rodriguez, Maria-Luz
   Barreda-Gomez, Gabriel
   Massa, Federico
   Grandes, Pedro
   Benard, Giovanni
   Marsicano, Giovanni
TI A cannabinoid link between mitochondria and memory
SO NATURE
LA English
DT Article
ID soluble adenylyl-cyclase; endocannabinoid system; oxidative-phosphorylation; subcellular-localization; catalytic subunit; brain; proteins; neurons; metabolism; receptors
AB Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP(1-4). Acute cannabinoid intoxication induces amnesia in humans and animals(5,6), and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB(1)) can directly alter mitochondrial energetic activity(7-9). Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established(1,2), the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB(1) receptors. Genetic exclusion of CB1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB(1) receptors signal through intra-mitochondrial G alpha(i) protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB(1) receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.
C1 [Hebert-Chatelain, Etienne; Desprez, Tifany; Serrat, Roman; Bellocchio, Luigi; Soria-Gomez, Edgar; Busquets-Garcia, Arnau; Zottola, Antonio Christian Pagano; Delamarre, Anna; Cannich, Astrid; Vincent, Peggy; Varilh, Marjorie; Robin, Laurie M.; Terral, Geoffrey; Colavita, Michelangelo; Mazier, Wilfrid; Cota, Daniela; Massa, Federico; Benard, Giovanni; Marsicano, Giovanni] NeuroCtr Magendie, INSERM U1215, F-33077 Bordeaux, France.
   [Hebert-Chatelain, Etienne; Desprez, Tifany; Serrat, Roman; Bellocchio, Luigi; Soria-Gomez, Edgar; Busquets-Garcia, Arnau; Zottola, Antonio Christian Pagano; Delamarre, Anna; Cannich, Astrid; Vincent, Peggy; Varilh, Marjorie; Robin, Laurie M.; Terral, Geoffrey; Colavita, Michelangelo; Mazier, Wilfrid; Cota, Daniela; Massa, Federico; Benard, Giovanni; Marsicano, Giovanni] Univ Bordeaux, NeuroCtr Magendie, F-33077 Bordeaux, France.
   [Hebert-Chatelain, Etienne] Univ Moncton, Dept Biol, Moncton, NB E1A 3E9, Canada.
   [Bellocchio, Luigi] Univ Complutense, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain.
   [Dolores Garcia-Fernandez, M.; Barreda-Gomez, Gabriel] IMG Pharma Biotech SL, Dept Res & Dev, Derio 48160, Spain.
   [Dolores Garcia-Fernandez, M.] Univ Basque Country UPV EHU, Fac Med & Dent, Dept Pharmacol, Leioa 48940, Spain.
   [Colavita, Michelangelo; Drago, Filippo] Univ Catania, Pharmacol Sect, Dept Biomed & Biotechnol Sci, I-95124 Catania, Italy.
   [Puente, Nagore; Reguero, Leire; Elezgarai, Izaskun; Grandes, Pedro] Univ Basque Country UPV EHU, Fac Med & Nursing, Dept Neurosci, Leioa 48940, Spain.
   [Puente, Nagore; Reguero, Leire; Elezgarai, Izaskun; Grandes, Pedro] Achucarro Basque Ctr Neurosci, Bizkaia Sci & Technol Pk,Bldg 205, Zamudio 48170, Spain.
   [Dupuy, Jean-William] Univ Bordeaux, Ctr Genom Fonct, Plateforme Proteome, F-33077 Bordeaux, France.
   [Lopez-Rodriguez, Maria-Luz] Univ Complutense, Dept Organ Chem, E-28040 Madrid, Spain.
   [Grandes, Pedro] Univ Victoria, Div Med Sci, Victoria, BC V8W 2Y2, Canada.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Moncton; Complutense University of Madrid; University of Basque Country; University of Catania; University of Basque Country; Universite de Bordeaux; Complutense University of Madrid; University of Victoria
RP Marsicano, G (corresponding author), NeuroCtr Magendie, INSERM U1215, F-33077 Bordeaux, France.; Marsicano, G (corresponding author), Univ Bordeaux, NeuroCtr Magendie, F-33077 Bordeaux, France.
EM giovanni.marsicano@inserm.fr
FU INSERM; EU-Fp7 (PAINCAGE [HEALTH-603191, FP7-PEOPLE-2013-1EF-623638]; European Research Council (Endofood) [ERC-2010-StG-260515, ERC-2014-PoC-640923]; Fondation pour la Recherche Medicate [DRM20101220445, SPF20121226369, ARF20140129235]; Fondation pour la Recherche en Psychiatrie et en Sante Mentale (FRPSM); Human Frontiers Science Program [RGP0036/2014]; Region Aquitaine; AFM Telethon Trampoline Grant [16474]; Agence Nationale de la Recherche (ANR Blanc NeuroNutriSens) [ANR-13-BSV4-0006]; BRAIN [ANR-10-LABX-0043, ANR-10-IDEX-03-02]; Dulbecco Telethon Institute post-doc fellowship; NSERC [RGPIN-2015-05880]; Fyssen Foundation; EMBO post-doc fellowship; CONACyT; Zabalduz pre-doc fellowship; Basque Government [11764-13]; MINECO/FEDER [SAF2015-65034-R]; University of the Basque Country [UPV/EHU UF111/41]; Red de Trastornos Adictivos Instituto de Salud Carlos III [RD12/0028/0004, RD16/0017/0012]
NR 48
TC 332
Z9 364
U1 0
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 555
EP +
DI 10.1038/nature20127
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600042
PM 27828947
DA 2026-03-09
ER

PT J
AU Oswald, C
   Rappas, M
   Kean, J
   Doré, AS
   Errey, JC
   Bennett, K
   Eflorian, FD
   Christopher, JA
   Jazayeri, A
   Mason, JS
   Congreve, M
   Cooke, RM
   Marshall, FH
AF Oswald, Christine
   Rappas, Mathieu
   Kean, James
   Dore, Andrew S.
   Errey, James C.
   Bennett, Kirstie
   Eflorian, Francesca D.
   Christopher, John A.
   Jazayeri, Ali
   Mason, Jonathan S.
   Congreve, Miles
   Cooke, Robert M.
   Marshall, Fiona H.
TI Intracellular allosteric antagonism of the CCR9 receptor
SO NATURE
LA English
DT Article
ID chemokine receptor; binding-site; crystal-structure; refinement; gpcr; activation
AB Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells(1). They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases(2,3). Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization4. The high failure rate may in part be due to limited understanding of the mechanism of action of chemokine antagonists and an inability to optimize compounds in the absence of structural information(5). CC chemokine receptor type 9 (CCR9) activation by CCL25 plays a key role in leukocyte recruitment to the gut and represents a therapeutic target in inflammatory bowel disease(6). The selective CCR9 antagonist vercirnon progressed to phase 3 clinical trials in Crohn's disease but efficacy was limited, with the need for very high doses to block receptor activation(6). Here we report the crystal structure of the CCR9 receptor in complex with vercirnon at 2.8 angstrom resolution. Remarkably, vercirnon binds to the intracellular side of the receptor, exerting allosteric antagonism and preventing G-protein coupling. This binding site explains the need for relatively lipophilic ligands and describes another example of an allosteric site on G-protein-coupled receptors(7) that can be targeted for drug design, not only at CCR9, but potentially extending to other chemokine receptors.
C1 [Oswald, Christine; Rappas, Mathieu; Kean, James; Dore, Andrew S.; Errey, James C.; Bennett, Kirstie; Eflorian, Francesca D.; Christopher, John A.; Jazayeri, Ali; Mason, Jonathan S.; Congreve, Miles; Cooke, Robert M.; Marshall, Fiona H.] Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
C3 Heptares Therapeutics Ltd.
RP Marshall, FH (corresponding author), Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
EM fiona.marshall@heptares.com
NR 41
TC 202
Z9 243
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 462
EP +
DI 10.1038/nature20606
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800048
PM 27926729
DA 2026-03-09
ER

PT J
AU van Houte, S
   Ekroth, AKE
   Broniewski, JM
   Chabas, H
   Ashby, B
   Bondy-Denomy, J
   Gandon, S
   Boots, M
   Paterson, S
   Buckling, A
   Westra, ER
AF van Houte, Stineke
   Ekroth, Alice K. E.
   Broniewski, Jenny M.
   Chabas, Helene
   Ashby, Ben
   Bondy-Denomy, Joseph
   Gandon, Sylvain
   Boots, Mike
   Paterson, Steve
   Buckling, Angus
   Westra, Edze R.
TI The diversity-generating benefits of a prokaryotic adaptive immune system
SO NATURE
LA English
DT Article
ID host-parasite coevolution; genetic diversity; crispr-cas; red queen; resistance; evolution; dynamics; virus; drives
AB Prokaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity(1,2). This frequently results in high within-population spacer diversity(3-6), but it is unclear if and why this is important. Here we show that, as a result of this spacer diversity, viruses can no longer evolve to overcome CRISPR-Cas by point mutation, which results in rapid virus extinction. This effect arises from synergy between spacer diversity and the high specificity of infection, which greatly increases overall population resistance. We propose that the resulting short-lived nature of CRISPR-dependent bacteria-virus coevolution has provided strong selection for the evolution of sophisticated virus-encoded anti-CRISPR mechanisms(7).
C1 [van Houte, Stineke; Ekroth, Alice K. E.; Broniewski, Jenny M.; Chabas, Helene; Buckling, Angus; Westra, Edze R.] Univ Exeter, Biosci, ESI, Cornwall Campus, Penryn TR10 9EZ, England.
   [van Houte, Stineke; Ekroth, Alice K. E.; Broniewski, Jenny M.; Chabas, Helene; Ashby, Ben; Boots, Mike; Buckling, Angus; Westra, Edze R.] Univ Exeter, Biosci, CEC, Cornwall Campus, Penryn TR10 9EZ, England.
   [Chabas, Helene; Gandon, Sylvain] Univ Montpellier, Univ Paul Valery Montpellier, CEFE,UMR 5175, CNRS,EPHE, 1919 Route de Mende, F-34293 Montpellier 5, France.
   [Ashby, Ben; Boots, Mike] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Bondy-Denomy, Joseph] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA.
   [Paterson, Steve] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England.
C3 University of Exeter; University of Exeter; Universite PSL; Ecole Pratique des Hautes Etudes (EPHE); Institut Agro; Institut Agro Montpellier; CIRAD; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Paul-Valery; Universite de Montpellier; University of California System; University of California Berkeley; University of California System; University of California San Francisco; University of Liverpool
RP van Houte, S; Buckling, A; Westra, ER (corresponding author), Univ Exeter, Biosci, ESI, Cornwall Campus, Penryn TR10 9EZ, England.; van Houte, S; Buckling, A; Westra, ER (corresponding author), Univ Exeter, Biosci, CEC, Cornwall Campus, Penryn TR10 9EZ, England.
EM vanhoute.stineke@gmail.com; A.J.Buckling@exeter.ac.uk; westra.edze@gmail.com
FU European Union [660039, 327606]; Natural Environment Research Council; Biotechnology and Biological Sciences Research Council; Royal Society; Leverhulme Trust; Wellcome Trust; AXA; University of California San Francisco Program for Breakthrough in Biomedical Research; Sandler Foundation; National Institutes of Health Director's Early Independence Award [DP5-OD021344]; Erasmus+ programme (European Union); Explora'Sup programme (Region Rhone-Alpes); Centre Regional des OEuvres Universitaires et Scolaires (CROUS; French State); Marie Curie Actions (MSCA) [660039] Funding Source: Marie Curie Actions (MSCA); BBSRC [1622146] Funding Source: UKRI; NERC [NE/M018350/1, NE/K014617/1, NBAF010002, NE/J021806/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [1622146] Funding Source: researchfish; Natural Environment Research Council [NE/K014617/1, NBAF010002, NE/M018350/1, NE/J021806/1] Funding Source: researchfish
NR 30
TC 198
Z9 239
U1 2
U2 91
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 385
EP +
DI 10.1038/nature17436
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700035
PM 27074511
DA 2026-03-09
ER

PT J
AU Fonfara, I
   Richter, H
   Bratovic, M
   Le Rhun, A
   Charpentier, E
AF Fonfara, Ines
   Richter, Hagen
   Bratovic, Majda
   Le Rhun, Anais
   Charpentier, Emmanuelle
TI The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA
SO NATURE
LA English
DT Article
ID integrative genomics viewer; crystal-structure; cas immunity; thermus-thermophilus; guided endonuclease; target dna; complex; recognition; systems; protein
AB CRISPR-Cas systems that provide defence against mobile genetic elements in bacteria and archaea have evolved a variety of mechanisms to target and cleave RNA or DNA(1). The well-studied types I, II and III utilize a set of distinct CRISPR-associated ( Cas) proteins for production of mature CRISPR RNAs (crRNAs) and interference with invading nucleic acids. In types I and III, Cas6 or Cas5d cleaves precursor crRNA (pre-crRNA)(2-5) and the mature crRNAs then guide a complex of Cas proteins ( Cascade-Cas3, type I; Csm or Cmr, type III) to target and cleave invading DNA or RNA(6-12). In type II systems, RNase III cleaves pre-crRNA base-paired with trans-activating crRNA (tracrRNA) in the presence of Cas9 (refs 13, 14). The mature tracrRNA-crRNA duplex then guides Cas9 to cleave target DNA15. Here, we demonstrate a novel mechanism in CRISPR-Cas immunity. We show that type V-A Cpf1 from Francisella novicida is a dual-nuclease that is specific to crRNA biogenesis and target DNA interference. Cpf1 cleaves pre-crRNA upstream of a hairpin structure formed within the CRISPR repeats and thereby generates intermediate crRNAs that are processed further, leading to mature crRNAs. After recognition of a 5'-YTN- 3' protospacer adjacent motif on the non-target DNA strand and subsequent probing for an eight-nucleotide seed sequence, Cpf1, guided by the single mature repeat-spacer crRNA, introduces double-stranded breaks in the target DNA to generate a 5' overhang(16). The RNase and DNase activities of Cpf1 require sequence- and structure-specific binding to the hairpin of crRNA repeats. Cpf1 uses distinct active domains for both nuclease reactions and cleaves nucleic acids in the presence of magnesium or calcium. This study uncovers a new family of enzymes with specific dual endoribonuclease and endonuclease activities, and demonstrates that type V- A constitutes the most minimalistic of the CRISPR- Cas systems so far described.
C1 [Fonfara, Ines; Le Rhun, Anais; Charpentier, Emmanuelle] Umea Univ, Dept Mol Biol, UCMR, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden.
   [Fonfara, Ines; Richter, Hagen; Bratovic, Majda; Le Rhun, Anais; Charpentier, Emmanuelle] Helmholtz Ctr Infect Res, Dept Regulat Infect Biol, D-38124 Braunschweig, Germany.
   [Fonfara, Ines; Richter, Hagen; Bratovic, Majda; Le Rhun, Anais; Charpentier, Emmanuelle] Max Planck Inst Infect Biol, Dept Regulat Infect Biol, D-10117 Berlin, Germany.
   [Bratovic, Majda; Charpentier, Emmanuelle] Hannover Med Sch, D-30625 Hannover, Germany.
C3 Umea University; Helmholtz Association; Helmholtz-Center for Infection Research; Max Planck Society; Hannover Medical School
RP Charpentier, E (corresponding author), Umea Univ, Dept Mol Biol, UCMR, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden.; Charpentier, E (corresponding author), Helmholtz Ctr Infect Res, Dept Regulat Infect Biol, D-38124 Braunschweig, Germany.; Charpentier, E (corresponding author), Max Planck Inst Infect Biol, Dept Regulat Infect Biol, D-10117 Berlin, Germany.; Charpentier, E (corresponding author), Hannover Med Sch, D-30625 Hannover, Germany.
EM charpentier@mpiib-berlin.mpg.de
FU Alexander von Humboldt Foundation (AvH Professorship); German Federal Ministry for Education and Research; Helmholtz Association; German Research Foundation; Max Planck Society; Goran Gustafsson Foundation (Goran Gustafsson Prize from the Royal Swedish Academy of Sciences); Swedish Research Council; Umea University; Helmholtz Postdoc Programme
NR 43
TC 755
Z9 1014
U1 21
U2 543
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 517
EP +
DI 10.1038/nature17945
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900051
PM 27096362
DA 2026-03-09
ER

PT J
AU Strilic, B
   Yang, LD
   Albarrán-Juárez, J
   Wachsmuth, L
   Han, K
   Müller, UC
   Pasparakis, M
   Offermanns, S
AF Strilic, Boris
   Yang, Lida
   Albarran-Juarez, Julian
   Wachsmuth, Laurens
   Han, Kang
   Mueller, Ulrike C.
   Pasparakis, Manolis
   Offermanns, Stefan
TI Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
SO NATURE
LA English
DT Article
ID amyloid precursor protein; lung metastasis; migration; dr6; inflammation; activation; insights
AB Metastasis is the leading cause of cancer-related death in humans. It is a complex multistep process during which individual tumour cells spread primarily through the circulatory system to colonize distant organs(1-3). Once in the circulation, tumour cells remain vulnerable, and their metastatic potential largely depends on a rapid and efficient way to escape from the blood stream by passing the endothelial barrier(4-9). Evidence has been provided that tumour cell extravasation resembles leukocyte transendothelial migration(7-9). However, it remains unclear how tumour cells interact with endothelial cells during extravasation and how these processes are regulated on a molecular level. Here we show that human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis. Treatment of mice with the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-inhibitor necrostatin-1 or endothelial-cell-specific deletion of RIPK3 reduced tumour-cell-induced endothelial necroptosis, tumour cell extravasation and metastasis. In contrast, pharmacological caspase inhibition or endothelial-cell-specific loss of caspase-8 promoted these processes. We furthermore show in vitro and in vivo that tumour-cell-induced endothelial necroptosis leading to extravasation and metastasis requires amyloid precursor protein expressed by tumour cells and its receptor, death receptor 6 (DR6), on endothelial cells as the primary mediators of these effects. Our data identify a new mechanism underlying tumour cell extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic signalling pathways as targets for anti-metastatic therapies.
C1 [Strilic, Boris; Yang, Lida; Albarran-Juarez, Julian; Offermanns, Stefan] Max Planck Inst Heart & Lung Res, Dept Pharmacol, Ludwigstr 43, D-61231 Bad Nauheim, Germany.
   [Wachsmuth, Laurens; Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, Joseph Stelzmann Str 26, D-50931 Cologne, Germany.
   [Wachsmuth, Laurens; Pasparakis, Manolis] Cologne Excellence Cluster Cellular Stress Respon, Joseph Stelzmann Str 26, D-50931 Cologne, Germany.
   [Han, Kang; Mueller, Ulrike C.] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Dept Bioinformat & Funct Gen, Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
   [Offermanns, Stefan] JW Goethe Univ Frankfurt, Fac Med, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
C3 Max Planck Society; University of Cologne; University of Cologne; Ruprecht Karls University Heidelberg; Goethe University Frankfurt
RP Strilic, B; Offermanns, S (corresponding author), Max Planck Inst Heart & Lung Res, Dept Pharmacol, Ludwigstr 43, D-61231 Bad Nauheim, Germany.; Offermanns, S (corresponding author), JW Goethe Univ Frankfurt, Fac Med, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM boris.strilic@mpi-bn.mpg.de; stefan.offermanns@mpi-bn.mpg.de
FU German Cancer Aid; Max Planck Society; China Scholarship Council; Deutsche Forschungsgemeinschaft [MU 1457/9-2, SFB670, SFB829]; European Research Council [323040]; Worldwide Cancer Research [15-0228]; Helmholtz Alliance Preclinical Comprehensive Cancer Center; European Research Council (ERC) [323040] Funding Source: European Research Council (ERC)
NR 36
TC 421
Z9 482
U1 3
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 215
EP +
DI 10.1038/nature19076
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100037
PM 27487218
DA 2026-03-09
ER

PT J
AU Okazaki, K
   Hirth, G
AF Okazaki, Keishi
   Hirth, Greg
TI Dehydration of lawsonite could directly trigger earthquakes in subducting oceanic crust
SO NATURE
LA English
DT Article
ID high-pressure; antigorite dehydration; thermal structure; high-temperature; deformation; serpentine; stability; kinetics; release; creep
AB Intermediate-depth earthquakes in cold subduction zones are observed within the subducting oceanic crust, as well as the mantle(1,2). In contrast, intermediate-depth earthquakes in hot subduction zones predominantly occur just below the Mohorovicic discontinuity(1). These observations have stimulated interest in relationships between blueschist-facies metamorphism and seismicity, particularly through dehydration reactions involving the mineral lawsonite(1,2). Here we conducted deformation experiments on lawsonite, while monitoring acoustic emissions, in a Griggs-type deformation apparatus. The temperature was increased above the thermal stability of lawsonite, while the sample was deforming, to test whether the lawsonite dehydration reaction induces unstable fault slip. In contrast to similar tests on antigorite, unstable fault slip (that is, stick-slip) occurred during dehydration reactions in the lawsonite and acoustic emission signals were continuously observed. Microstructural observations indicate that strain is highly localized along the fault (R-1 and B shears), and that the fault surface develops slickensides (very smooth fault surfaces polished by frictional sliding). The unloading slope during the unstable slip follows the stiffness of the apparatus at all experimental conditions, regardless of the strain rate and temperature ramping rate. A thermomechanical scaling factor(3) for the experiments is within the range estimated for natural subduction zones, indicating the potential for unstable frictional sliding within natural lawsonite layers.
C1 [Okazaki, Keishi; Hirth, Greg] Brown Univ, Dept Earth Environm & Planetary Sci, 324 Brook St,Box 1846, Providence, RI 02906 USA.
C3 Brown University
RP Okazaki, K (corresponding author), Brown Univ, Dept Earth Environm & Planetary Sci, 324 Brook St,Box 1846, Providence, RI 02906 USA.
EM keishi_okazaki@brown.edu
FU US National Science Foundation [EAR-1049582, EAR-1315784]
NR 34
TC 124
Z9 143
U1 2
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 81
EP +
DI 10.1038/nature16501
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500036
PM 26842057
DA 2026-03-09
ER

PT J
AU Krause, S
   Bon, V
   Senkovska, I
   Stoeck, U
   Wallacher, D
   Többens, DM
   Zander, S
   Pillai, RS
   Maurin, G
   Coudert, FX
   Kaskel, S
AF Krause, Simon
   Bon, Volodymyr
   Senkovska, Irena
   Stoeck, Ulrich
   Wallacher, Dirk
   Toebbens, Daniel M.
   Zander, Stefan
   Pillai, Renjith S.
   Maurin, Guillaume
   Coudert, Francois-Xavier
   Kaskel, Stefan
TI A pressure-amplifying framework material with negative gas adsorption transitions
SO NATURE
LA English
DT Article
ID metal-organic framework; porous coordination polymers; co2; sorption; flexibility; selectivity; separation; membranes
AB Adsorption-based phenomena are important in gas separations(1,2), such as the treatment of greenhouse-gas(3) and toxic-gas(4) pollutants, and in water-adsorption-based heat pumps(5) for solar cooling systems. The ability to tune the pore size, shape and functionality of crystalline porous coordination polymers-or metal-organic frameworks (MOFs)-has made them attractive materials for such adsorption-based applications(3,6-8). The flexibility and guest-molecule-dependent response(9,10) of MOFs give rise to unexpected and often desirable adsorption phenomena(11-14). Common to all isothermal gas adsorption phenomena, however, is increased gas uptake with increased pressure. Here we report adsorption transitions in the isotherms of a MOF (DUT-49) that exhibits a negative gas adsorption; that is, spontaneous desorption of gas (methane and n-butane) occurs during pressure increase in a defined temperature and pressure range. A combination of in situ powder X-ray diffraction, gas adsorption experiments and simulations shows that this adsorption behaviour is controlled by a sudden hysteretic structural deformation and pore contraction of the MOF, which releases guest molecules. These findings may enable technologies using frameworks capable of negative gas adsorption for pressure amplification in micro-and macroscopic system engineering. Negative gas adsorption extends the series of counterintuitive phenomena such as negative thermal expansion(15,16) and negative refractive indices(17) and may be interpreted as an adsorptive analogue of force-amplifying negative compressibility transitions proposed for metamaterials(18).
C1 [Krause, Simon; Bon, Volodymyr; Senkovska, Irena; Stoeck, Ulrich; Kaskel, Stefan] Tech Univ Dresden, Dept Inorgan Chem, Bergstr 66, D-01062 Dresden, Germany.
   [Wallacher, Dirk] Helmholtz Zentrum Berlin Mat & Energie, Dept Sample Environm, Hahn Meitner Pl 1, D-14109 Berlin, Germany.
   [Toebbens, Daniel M.; Zander, Stefan] Helmholtz Zentrum Berlin Mat & Energie, Dept Struct & Dynam Energy Mat, Hahn Meitner Pl 1, D-14109 Berlin, Germany.
   [Pillai, Renjith S.; Maurin, Guillaume] Univ Montpellier, Inst Charles Gerhardt Montpellier UMR CNRS UM ENS, F-34095 Montpellier 05, France.
   [Coudert, Francois-Xavier] PSL Res Univ, Chim ParisTech, CNRS, Inst Rech Chim Paris, F-75005 Paris, France.
   [Stoeck, Ulrich] Leibniz Inst Solid State & Mat Res IFW Dresden, Inst Complex Mat, Helmholtzstr 20, D-01069 Dresden, Germany.
C3 Technische Universitat Dresden; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); Universite de Montpellier; Ecole nationale superieure de chimie de Montpellier; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Chimie ParisTech; Leibniz Association; Leibniz Institute for Solid State & Materials Research Dresden
RP Kaskel, S (corresponding author), Tech Univ Dresden, Dept Inorgan Chem, Bergstr 66, D-01062 Dresden, Germany.
EM stefan.kaskel@chemie.tu-dresden.de
FU German Federal Ministry for education and research (project BMBF) [05K13OD3]; Helmholtz-Zentrum Berlin; GENCI [x2015087069]
NR 30
TC 523
Z9 548
U1 35
U2 985
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 348
EP 352
DI 10.1038/nature17430
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700028
PM 27049950
DA 2026-03-09
ER

PT J
AU Horn, EJ
   Rosen, BR
   Chen, Y
   Tang, JZ
   Chen, K
   Eastgate, MD
   Baran, PS
AF Horn, Evan J.
   Rosen, Brandon R.
   Chen, Yong
   Tang, Jiaze
   Chen, Ke
   Eastgate, Martin D.
   Baran, Phil S.
TI Scalable and sustainable electrochemical allylic C-H oxidation
SO NATURE
LA English
DT Article
ID phthalimide-n-oxyl; anodic electrochemistry; hydroxyphthalimide; functionalization; catalysis; mediator; olefins; enones
AB New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials(1). The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials(2). Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics"(3). Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium)(2). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.
C1 [Horn, Evan J.; Rosen, Brandon R.; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Chen, Yong; Tang, Jiaze] Tianjin Econ Technol Dev Zone, Asymchem Life Sci Tianjin, Tianjin 300457, Peoples R China.
   [Chen, Ke; Eastgate, Martin D.] Bristol Myers Squibb Co, Chem Dev, New Brunswick, NJ 08903 USA.
C3 Scripps Research Institute; Bristol-Myers Squibb
RP Baran, PS (corresponding author), Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
EM pbaran@scripps.edu
FU NSF; National Institute of General Medical Sciences [GM-097444]; Asymchem; Bristol-Myers Squibb; National Institute of General Medical Sciences [R35GM118176] Funding Source: NIH RePORTER
NR 30
TC 606
Z9 669
U1 14
U2 535
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 77
EP 81
DI 10.1038/nature17431
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900042
PM 27096371
DA 2026-03-09
ER

PT J
AU Peters, IR
   Majumdar, S
   Jaeger, HM
AF Peters, Ivo R.
   Majumdar, Sayantan
   Jaeger, Heinrich M.
TI Direct observation of dynamic shear jamming in dense suspensions
SO NATURE
LA English
DT Article
ID fronts
AB Liquid-like at rest, dense suspensions of hard particles can undergo striking transformations in behaviour when agitated or sheared(1). These phenomena include solidification during rapid impact(2,3), as well as strong shear thickening characterized by discontinuous, orders-of-magnitude increases in suspension viscosity(4-8). Much of this highly non-Newtonian behaviour has recently been interpreted within the framework of a jamming transition. However, although jamming indeed induces solid-like rigidity(9-11), even a strongly shear-thickened state still flows and thus cannot be fully jammed(12,13). Furthermore, although suspensions are incompressible, the onset of rigidity in the standard jamming scenario requires an increase in particle density(9,10,14). Finally, whereas shear thickening occurs in the steady state, impact-induced solidification is transient(2,15-17). As a result, it has remained unclear how these dense suspension phenomena are related and how they are connected to jamming. Here we resolve this by systematically exploring both the steady-state and transient regimes with the same experimental system. We demonstrate that a fully jammed, solid-like state can be reached without compression and instead purely with shear, as recently proposed for dry granular systems(18,19). This state is created by transient shear-jamming fronts, which we track directly. We also show that shear stress, rather than shear rate, is the key control parameter. From these findings we map out a state diagram with particle density and shear stress as variables. We identify discontinuous shear thickening with a marginally jammed regime just below the onset of full, solid-like jamming(20). This state diagram provides a unifying framework, compatible with prior experimental and simulation results on dense suspensions, that connects steady-state and transient behaviour in terms of a dynamic shear-jamming process.
C1 [Peters, Ivo R.; Majumdar, Sayantan; Jaeger, Heinrich M.] Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
   [Peters, Ivo R.] Univ Southampton, Engn & Environm, Southampton SO17 1BJ, Hants, England.
C3 University of Chicago; University of Southampton
RP Peters, IR (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM i.r.peters@soton.ac.uk
FU US Army Research Office [W911NF-12-1-0182]; Chicago Materials Research Science and Engineering Center; NSF [DMR-1420709]; Kadanoff-Rice fellowship
NR 31
TC 285
Z9 337
U1 11
U2 365
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 214
EP +
DI 10.1038/nature17167
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100035
PM 27042934
DA 2026-03-09
ER

PT J
AU Votteler, J
   Ogohara, C
   Yi, S
   Hsia, Y
   Nattermann, U
   Belnap, DM
   King, NP
   Sundquist, WI
AF Votteler, Jorg
   Ogohara, Cassandra
   Yi, Sue
   Hsia, Yang
   Nattermann, Una
   Belnap, David M.
   King, Neil P.
   Sundquist, Wesley I.
TI Designed proteins induce the formation of nanocage-containing extracellular vesicles
SO NATURE
LA English
DT Article
ID computational design; virus; dna; fusion; image; visualization
AB Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids(1,2) or proteins(3-5), but strategies for engineering hybrid biological materials are only beginning to emerge(6,7). Here we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses. We refer to these hybrid biomaterials as 'enveloped protein nanocages' (EPNs). Robust EPN biogenesis requires protein sequence elements that encode three distinct functions: membrane binding, self-assembly, and recruitment of the endosomal sorting complexes required for transport (ESCRT) machinery(8). A variety of synthetic proteins with these functional elements induce EPN biogenesis, highlighting the modularity and generality of the design strategy. Biochemical analyses and cryo-electron microscopy reveal that one design, EPN-01, comprises small (similar to 100 nm) vesicles containing multiple protein nanocages that closely match the structure of the designed 60-subunit self-assembling scaffold(9). EPNs that incorporate the vesicular stomatitis viral glycoprotein can fuse with target cells and deliver their contents, thereby transferring cargoes from one cell to another. These results show how proteins can be programmed to direct the formation of hybrid biological materials that perform complex tasks, and establish EPNs as a class of designed, modular, genetically-encoded nanomaterials that can transfer molecules between cells.
C1 [Votteler, Jorg; Belnap, David M.; Sundquist, Wesley I.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA.
   [Ogohara, Cassandra; Yi, Sue; Hsia, Yang; Nattermann, Una; King, Neil P.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Ogohara, Cassandra; Yi, Sue; Hsia, Yang; Nattermann, Una; King, Neil P.] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
   [Hsia, Yang; Nattermann, Una] Univ Washington, Grad Program Biol Phys Struct & Design, Seattle, WA 98195 USA.
   [Belnap, David M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Utah System of Higher Education; University of Utah
RP Sundquist, WI (corresponding author), Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA.; King, NP (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.; King, NP (corresponding author), Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
EM neilking@uw.edu; wes@biochem.utah.edu
FU Deutsche Forschungsgemeinschaft (DFG) Fellowship [VO 1836/1-1]; NIH Molecular Biology Training Grant [T32GM008268]; PHS National Research Service Award from NIGMS [T32GM007270]; Bill & Melinda Gates Foundation [OPP1118840]; Defense Advanced Research Projects Agency [W911NF-14-1-0162, W911NF-15-1-0645]; NIH [RO1 AI 51174, P50 082545]; National Institute of General Medical Sciences [T32GM008268] Funding Source: NIH RePORTER; Bill and Melinda Gates Foundation [OPP1118840] Funding Source: Bill and Melinda Gates Foundation
NR 46
TC 121
Z9 154
U1 1
U2 185
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 292
EP +
DI 10.1038/nature20607
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700062
PM 27919066
DA 2026-03-09
ER

PT J
AU Moyes, DL
   Wilson, D
   Richardson, JP
   Mogavero, S
   Tang, SX
   Wernecke, J
   Höfs, S
   Gratacap, RL
   Robbins, J
   Runglall, M
   Murciano, C
   Blagojevic, M
   Thavaraj, S
   Förster, TM
   Hebecker, B
   Kasper, L
   Vizcay, G
   Iancu, SI
   Kichik, N
   Häder, A
   Kurzai, O
   Luo, T
   Krüger, T
   Kniemeyer, O
   Cota, E
   Bader, O
   Wheeler, RT
   Gutsmann, T
   Hube, B
   Naglik, JR
AF Moyes, David L.
   Wilson, Duncan
   Richardson, Jonathan P.
   Mogavero, Selene
   Tang, Shirley X.
   Wernecke, Julia
   Hoefs, Sarah
   Gratacap, Remi L.
   Robbins, Jon
   Runglall, Manohursingh
   Murciano, Celia
   Blagojevic, Mariana
   Thavaraj, Selvam
   Foerster, Toni M.
   Hebecker, Betty
   Kasper, Lydia
   Vizcay, Gema
   Iancu, Simona I.
   Kichik, Nessim
   Haeder, Antje
   Kurzai, Oliver
   Luo, Ting
   Krueger, Thomas
   Kniemeyer, Olaf
   Cota, Ernesto
   Bader, Oliver
   Wheeler, Robert T.
   Gutsmann, Thomas
   Hube, Bernhard
   Naglik, Julian R.
TI Candidalysin is a fungal peptide toxin critical for mucosal infection
SO NATURE
LA English
DT Article
ID protein-kinase homolog; saccharomyces-cerevisiae; hyphal development; epithelial-cells; oropharyngeal candidiasis; pathogenicity mechanisms; transcription factor; beta-mannosylation; filamentous growth; albicans encodes
AB Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.
C1 [Moyes, David L.; Richardson, Jonathan P.; Tang, Shirley X.; Runglall, Manohursingh; Murciano, Celia; Blagojevic, Mariana; Thavaraj, Selvam; Iancu, Simona I.; Kichik, Nessim; Naglik, Julian R.] Kings Coll London, Inst Dent, Mucosal & Salivary Biol Div, London SE1 1UL, England.
   [Wilson, Duncan; Mogavero, Selene; Hoefs, Sarah; Foerster, Toni M.; Hebecker, Betty; Kasper, Lydia; Hube, Bernhard] Hans Knoell Inst, Dept Microbial Pathogen Mech, D-07745 Jena, Germany.
   [Wernecke, Julia; Gutsmann, Thomas] Res Ctr Borstel, Div Biophys, D-23845 Borstel, Germany.
   [Wernecke, Julia] Deutsch Elektronen Synchrotron DESY, D-22607 Hamburg, Germany.
   [Gratacap, Remi L.; Wheeler, Robert T.] Univ Maine, Dept Mol & Biomed Sci, Orono, ME 04469 USA.
   [Robbins, Jon] Kings Coll London, Wolfson CARD, Guys Campus, London SE1 1UL, England.
   [Hebecker, Betty] Hans Knoell Inst, Res Grp Microbial Immunol, D-07745 Jena, Germany.
   [Vizcay, Gema] Kings Coll London, Ctr Ultrastruct Imaging, London SE1 1UL, England.
   [Kichik, Nessim; Cota, Ernesto] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
   [Haeder, Antje; Kurzai, Oliver] Hans Knoell Inst, Sept Res Ctr, D-07745 Jena, Germany.
   [Haeder, Antje; Kurzai, Oliver] Univ Jena, D-07745 Jena, Germany.
   [Luo, Ting; Krueger, Thomas; Kniemeyer, Olaf] Hans Knoell Inst, Dept Mol & Appl Microbiol, D-07745 Jena, Germany.
   [Bader, Oliver] Univ Med Ctr Gottingen, Inst Med Microbiol, D-37075 Gottingen, Germany.
   [Hube, Bernhard] Univ Jena, D-07737 Jena, Germany.
   [Hube, Bernhard] Integrated Res & Treatment Ctr, Ctr Sepsis Control & Care, D-07747 Jena, Germany.
   [Wilson, Duncan] Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Fungal Grp, Aberdeen AB25 2ZD, Scotland.
   [Runglall, Manohursingh] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 1UL, England.
   [Murciano, Celia] Univ Valencia, ERI Biotecmed & Microbiol & Ecol Dept, E-46100 Valencia, Spain.
C3 University of London; King's College London; Leibniz Association; Hans Knoll Institute (HKI); Leibniz Association; Forschungszentrum Borstel; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Maine System; University of Maine Orono; University of London; King's College London; Leibniz Association; Hans Knoll Institute (HKI); University of London; King's College London; Imperial College London; Leibniz Association; Hans Knoll Institute (HKI); Friedrich Schiller University of Jena; Leibniz Association; Hans Knoll Institute (HKI); University of Gottingen; University of Gottingen Hospital; Friedrich Schiller University of Jena; University of Aberdeen; Guy's & St Thomas' NHS Foundation Trust; University of Valencia
RP Hube, B (corresponding author), Hans Knoell Inst, Dept Microbial Pathogen Mech, D-07745 Jena, Germany.; Hube, B (corresponding author), Univ Jena, D-07737 Jena, Germany.; Hube, B (corresponding author), Integrated Res & Treatment Ctr, Ctr Sepsis Control & Care, D-07747 Jena, Germany.
EM bernhard.hube@leibniz-hki.de
FU Medical Research Council [MR/J008303/1, MR/M011372/1]; Biotechnology & Biological Sciences Research Council [BB/J015261/1]; FP7-PEOPLE-Initial Training Network [606786]; Wellcome Trust [097377/Z/11/Z, 102549/Z/13/Z]; Royal Society [102549/Z/13/Z]; Deutsche Forschungsgemeinschaft [CRC/TR124, SPP 1580 (Hu 528/17-1)]; CSCC, German Federal Ministry of Education and Health (BMBF) [01E01002]; Cluster of Excellence 'Inflammation at interfaces' and Deutsche Forschungsgemeinschaft [SPP1580, GU 568/5-1]; National Institutes of Health [R15AI094406]; Burroughs Wellcome Fund; Biotechnology and Biological Sciences Research Council [BB/J015261/1, BB/N014677/1, BB/K003887/1] Funding Source: researchfish; Medical Research Council [MR/M011372/1, MR/J008303/1] Funding Source: researchfish; Wellcome Trust [097377/Z/11/Z, 102549/Z/13/Z] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [606786] Funding Source: National Health and Medical Research Council (NHMRC); Wellcome Trust [102549/Z/13/Z] Funding Source: Wellcome Trust; BBSRC [BB/J015261/1, BB/K003887/1, BB/N014677/1] Funding Source: UKRI; MRC [MR/J008303/1, MR/M011372/1] Funding Source: UKRI
NR 98
TC 720
Z9 843
U1 5
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 64
EP +
DI 10.1038/nature17625
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500033
PM 27027296
DA 2026-03-09
ER

PT J
AU Zheng, Y
   Qin, L
   Zacarias, NVO
   de Vries, H
   Han, GW
   Gustavsson, M
   Dabros, M
   Zhao, CX
   Cherney, RJ
   Carter, P
   Stamos, D
   Abagyan, R
   Cherezov, V
   Stevens, RC
   Ijzerman, AP
   Heitman, LH
   Tebben, A
   Kufareva, I
   Handel, TM
AF Zheng, Yi
   Qin, Ling
   Zacarias, Natalia V. Ortiz
   de Vries, Henk
   Han, Gye Won
   Gustavsson, Martin
   Dabros, Marta
   Zhao, Chunxia
   Cherney, Robert J.
   Carter, Percy
   Stamos, Dean
   Abagyan, Ruben
   Cherezov, Vadim
   Stevens, Raymond C.
   Ijzerman, Adriaan P.
   Heitman, Laura H.
   Tebben, Andrew
   Kufareva, Irina
   Handel, Tracy M.
TI Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists
SO NATURE
LA English
DT Article
ID crystal-structure; small-molecule; binding-site; membrane-proteins; discovery; potent; activation; complex; reveal; cxcr4
AB CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases(2) including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer(3). These disease associations have motivated numerous preclinical studies and clinical trials(4) (see http://www.clinicaltrials.gov) in search of therapies that target the CCR2-chemokine axis. To aid drug discovery efforts(5), here we solve a structure of CCR2 in a ternary complex with an orthosteric (BMS-681 (ref. 6)) and allosteric (CCR2-RA-[R](7)) antagonist. BMS-681 inhibits chemokine binding by occupying the orthosteric pocket of the receptor in a previously unseen binding mode. CCR2-RA-[R] binds in a novel, highly druggable pocket that is the most intracellular allosteric site observed in class A G-protein-coupled receptors so far; this site spatially overlaps the G-protein-binding site in homologous receptors. CCR2-RA-[R] inhibits CCR2 non-competitively by blocking activation-associated conformational changes and formation of the G-protein-binding interface. The conformational signature of the conserved microswitch residues observed in double-antagonist-bound CCR2 resembles the most inactive G-protein-coupled receptor structures solved so far. Like other protein-protein interactions, receptor-chemokine complexes are considered challenging therapeutic targets for small molecules, and the present structure suggests diverse pocket epitopes that can be exploited to overcome obstacles in drug design.
C1 [Zheng, Yi; Qin, Ling; Gustavsson, Martin; Zhao, Chunxia; Abagyan, Ruben; Kufareva, Irina; Handel, Tracy M.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Zacarias, Natalia V. Ortiz; de Vries, Henk; Ijzerman, Adriaan P.; Heitman, Laura H.] Leiden Univ, LACDR, Div Med Chem, NL-2333 CC Leiden, Netherlands.
   [Han, Gye Won; Cherezov, Vadim; Stevens, Raymond C.] Univ Southern Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA.
   [Han, Gye Won; Cherezov, Vadim] Univ Southern Calif, Bridge Inst, Dept Phys & Astron, Los Angeles, CA 90089 USA.
   [Dabros, Marta; Cherney, Robert J.; Carter, Percy; Tebben, Andrew] Bristol Myers Squibb Co, Princeton, NJ 08543 USA.
   [Stamos, Dean] Vertex Pharmaceut Inc, 11010 Torreyana Rd, San Diego, CA 92121 USA.
   [Stevens, Raymond C.] Univ Southern Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA.
C3 University of California System; University of California San Diego; Leiden University - Excl LUMC; Leiden University; University of Southern California; University of Southern California; Bristol-Myers Squibb; Vertex Pharmaceuticals; University of Southern California
RP Kufareva, I; Handel, TM (corresponding author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr, La Jolla, CA 92093 USA.; Heitman, LH (corresponding author), Leiden Univ, LACDR, Div Med Chem, NL-2333 CC Leiden, Netherlands.
EM l.h.heitman@lacdr.leidenuniv.nl; ikufareva@ucsd.edu; thandel@ucsd.edu
FU National Institutes of Health [R01 GM071872, U54 GM094618, R01 AI118985, R21 AI121918, R21 AI122211]; National Cancer Institute [ACB-12002]; National Institute of General Medical Sciences [AGM-12006]; DOE Office of Science [DE-AC02-06CH11357]
NR 42
TC 236
Z9 279
U1 0
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 458
EP +
DI 10.1038/nature20605
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800047
PM 27926736
DA 2026-03-09
ER

PT J
AU Cuylen, S
   Blaukopf, C
   Politi, AZ
   Müller-Reichert, T
   Neumann, B
   Poser, I
   Ellenberg, J
   Hyman, AA
   Gerlich, DW
AF Cuylen, Sara
   Blaukopf, Claudia
   Politi, Antonio Z.
   Mueller-Reichert, Thomas
   Neumann, Beate
   Poser, Ina
   Ellenberg, Jan
   Hyman, Anthony A.
   Gerlich, Daniel W.
TI Ki-67 acts as a biological surfactant to disperse mitotic chromosomes
SO NATURE
LA English
DT Article
ID cell-proliferation; protein; antigen; organization; microscopy; anaphase; genome; domain; genes
AB Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis(1-3). This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes(4) and the discovery of proteins at the chromosome surface(3,5,6), the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization.
C1 [Cuylen, Sara; Blaukopf, Claudia; Gerlich, Daniel W.] Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria.
   [Politi, Antonio Z.; Ellenberg, Jan] EMBL, Cell Biol & Biophys Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany.
   [Mueller-Reichert, Thomas] Tech Univ Dresden, Med Fac Carl Gustav Carus, Expt Ctr, Fetscherstr 74, D-01307 Dresden, Germany.
   [Neumann, Beate] EMBL, Adv Light Microscopy Facil, Meyerhofstr 1, D-69117 Heidelberg, Germany.
   [Poser, Ina; Hyman, Anthony A.] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); European Molecular Biology Laboratory (EMBL); Technische Universitat Dresden; Carl Gustav Carus University Hospital; European Molecular Biology Laboratory (EMBL); Max Planck Society
RP Cuylen, S (corresponding author), Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria.
FU European Community [241548, 258068, 330114]; ERC [281198]; Austrian Science Fund (FWF) project [SFB F34-06]; Human Frontier Science Program Long-Term Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG) [MU 1423/3-2, MU 1423/8-1]; European Research Council (ERC) [281198] Funding Source: European Research Council (ERC)
NR 33
TC 421
Z9 485
U1 1
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 308
EP +
DI 10.1038/nature18610
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600062
PM 27362226
DA 2026-03-09
ER

PT J
AU Anderson, KM
   Anderson, DM
   McAnally, JR
   Shelton, JM
   Bassel-Duby, R
   Olson, EN
AF Anderson, Kelly M.
   Anderson, Douglas M.
   McAnally, John R.
   Shelton, John M.
   Bassel-Duby, Rhonda
   Olson, Eric N.
TI Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development
SO NATURE
LA English
DT Article
ID response element; dhand; enhancer; activation; morphogenesis; promoters; landscape; chromatin; disease; muscle
AB HAND2 is an ancestral regulator of heart development and one of four transcription factors that control the reprogramming of fibroblasts into cardiomyocytes(1-4). Deletion of Hand2 in mice results in right ventricle hypoplasia and embryonic lethality(1,5). Hand2 expression is tightly regulated by upstream enhancers(6,7) that reside within a super-enhancer delineated by histone 113 acetyl Lys27 (H3K27ac) modifications(8). Here we show that transcription of a Hand2-associated long non-coding RNA, which we named upperhand (Uph), is required to maintain the super-enhancer signature and elongation of RNA polymerase II through the Hand2 enhancer locus. Blockade of Uph transcription, but not knockdown of the mature transcript, abolished Hand2 expression, causing right ventricular hypoplasia and embryonic lethality in mice. Given the substantial number of uncharacterized promoter-associated long non-coding RNAs encoded by the mammalian genome(9), the Uph-Hand2 regulatory partnership offers a mechanism by which divergent non-coding transcription can establish a permissive chromatin environment.
C1 [Anderson, Kelly M.; Anderson, Douglas M.; McAnally, John R.; Bassel-Duby, Rhonda; Olson, Eric N.] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Anderson, Kelly M.; Anderson, Douglas M.; McAnally, John R.; Bassel-Duby, Rhonda; Olson, Eric N.] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA.
   [Shelton, John M.] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Olson, EN (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.; Olson, EN (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA.
EM eric.olson@utsouthwestern.edu
FU National Institutes of Health [HL-077439, AR-067294, HL-130253, DK-099653, U01-HL-100401]; Fondation Leducq Networks of Excellence; Cancer Prevention and Research Institute of Texas; Robert A. Welch Foundation [1-0025]; American Heart Association [14PRE19830031]; Muscular Dystrophy Association [MDA377340]; American Heart Association (AHA) [14PRE19830031] Funding Source: American Heart Association (AHA); National Heart Lung and Blood Institute [R01HL130253] Funding Source: NIH RePORTER
NR 30
TC 282
Z9 335
U1 2
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 433
EP 436
DI 10.1038/nature20128
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700055
PM 27783597
DA 2026-03-09
ER

PT J
AU Wu, JP
   Yan, Z
   Li, ZQ
   Qian, XY
   Lu, S
   Dong, MQ
   Zhou, Q
   Yan, NE
AF Wu, Jianping
   Yan, Zhen
   Li, Zhangqiang
   Qian, Xingyang
   Lu, Shan
   Dong, Mengqiu
   Zhou, Qiang
   Yan, Nieng
TI Structure of the voltage-gated calcium channel Cav1.1 at 3.6 Å resolution
SO NATURE
LA English
DT Article
ID ca2+ channel; crystal-structure; skeletal-muscle; sodium-channel; beta-subunit; alpha(2)delta subunits; accurate determination; receptor; inactivation; restoration
AB The voltage-gated calcium (Ca-v) channels convert membrane electrical signals to intracellular Ca2+-mediated events. Among the ten subtypes of Ca-v channel in mammals, Ca(v)1.1 is specified for the excitation-contraction coupling of skeletal muscles. Here we present the cryo-electron microscopy structure of the rabbit Ca(v)1.1 complex at a nominal resolution of 3.6 angstrom. The inner gate of the ion-conducting alpha 1-subunit is closed and all four voltage-sensing domains adopt an 'up' conformation, suggesting a potentially inactivated state. The extended extracellular loops of the pore domain, which are stabilized by multiple disulfide bonds, form a windowed dome above the selectivity filter. One side of the dome provides the docking site for the angstrom 2 delta-1-subunit, while the other side may attract cations through its negative surface potential. The intracellular I-II and III-IV linker helices interact with the beta(1a)-subunit and the carboxy-terminal domain of alpha 1, respectively. Classification of the particles yielded two additional reconstructions that reveal pronounced displacement of beta(1a) and adjacent elements in alpha 1. The atomic model of the Ca(v)1.1 complex establishes a foundation for mechanistic understanding of excitation-contraction coupling and provides a three-dimensional template for molecular interpretations of the functions and disease mechanisms of Ca-v and Na-v channels.
C1 [Wu, Jianping; Yan, Zhen; Li, Zhangqiang; Zhou, Qiang; Yan, Nieng] Tsinghua Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.
   [Wu, Jianping; Yan, Zhen; Li, Zhangqiang; Zhou, Qiang; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Wu, Jianping; Yan, Zhen; Li, Zhangqiang; Zhou, Qiang; Yan, Nieng] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Beijing 100084, Peoples R China.
   [Wu, Jianping; Li, Zhangqiang; Qian, Xingyang; Yan, Nieng] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
   [Lu, Shan; Dong, Mengqiu] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; National Institute of Biological Sciences, Beijing
RP Yan, NE (corresponding author), Tsinghua Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.; Yan, NE (corresponding author), Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.; Yan, NE (corresponding author), Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Beijing 100084, Peoples R China.; Yan, NE (corresponding author), Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2015CB9101012014, 2016YFA0500402, ZX09507003006]; National Natural Science Foundation of China [31321062]; International Early Career Scientist grant from the Howard Hughes Medical Institute; Bayer Healthcare
NR 70
TC 385
Z9 463
U1 8
U2 230
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 191
EP +
DI 10.1038/nature19321
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100039
PM 27580036
DA 2026-03-09
ER

PT J
AU Haussmann, IU
   Bodi, Z
   Sanchez-Moran, E
   Mongan, NP
   Archer, N
   Fray, RG
   Soller, M
AF Haussmann, Irmgard U.
   Bodi, Zsuzsanna
   Sanchez-Moran, Eugenio
   Mongan, Nigel P.
   Archer, Nathan
   Fray, Rupert G.
   Soller, Matthias
TI m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination
SO NATURE
LA English
DT Article
ID gene; expression; identification; specificity; methylase; virilizer; reveals; complex; protein
AB N-6-methyladenosine (m(6)A) is the most common internal modification of eukaryotic messenger RNA (mRNA) and is decoded by YTH domain proteins(1-7). The mammalian mRNA m(6)A methylosome is a complex of nuclear proteins that includes METTL3 (methyltransferase-like 3), METTL14, WTAP (Wilms tumour 1-associated protein) and KIAA1429. Drosophila has corresponding homologues named Ime4 and KAR4 (Inducer of meiosis 4 and Karyogamy protein 4), and Female-lethal (2) d (Fl(2) d) and Virilizer (Vir)(8-12). In Drosophila, fl(2) d and vir are required for sex-dependent regulation of alternative splicing of the sex determination factor Sex lethal (Sxl)(13). However, the functions of m(6)A in introns in the regulation of alternative splicing remain uncertain(3). Here we show that m6A is absent in the mRNA of Drosophila lacking Ime4. In contrast to mouse and plant knockout models(5,7,14), Drosophila Ime4-null mutants remain viable, though flightless, and show a sex bias towards maleness. This is because m6A is required for female-specific alternative splicing of Sxl, which determines female physiognomy, but also translationally represses male-specific lethal 2 (msl-2) to prevent dosage compensation in females. We further show that the m(6)A reader protein YT521-B decodes m(6)A in the sex-specifically spliced intron of Sxl, as its absence phenocopies Ime4 mutants. Loss of m(6)A also affects alternative splicing of additional genes, predominantly in the 5' untranslated region, and has global effects on the expression of metabolic genes. The requirement of m(6)A and its reader YT521-B for female-specific Sxl alternative splicing reveals that this hitherto enigmatic mRNA modification constitutes an ancient and specific mechanism to adjust levels of gene expression.
C1 [Haussmann, Irmgard U.; Sanchez-Moran, Eugenio; Soller, Matthias] Univ Birmingham, Coll Life & Environm Sci, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
   [Haussmann, Irmgard U.] Coventry Univ, Sch Life Sci, Fac Hlth & Life Sci, Coventry CV1 5FB, W Midlands, England.
   [Bodi, Zsuzsanna; Archer, Nathan; Fray, Rupert G.] Univ Nottingham, Plant Sci Div, Sch Biosci, Loughborough LE12 5RD, Leics, England.
   [Mongan, Nigel P.] Univ Nottingham, Sch Vet Med & Sci, Loughborough LE12 5RD, Leics, England.
C3 University of Birmingham; Coventry University; University of Nottingham; University of Nottingham
RP Soller, M (corresponding author), Univ Birmingham, Coll Life & Environm Sci, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
EM m.soller@bham.ac.uk
FU BBSRC [BB/M008606/1]; Biotechnology and Biological Sciences Research Council [976176, BB/C513369/1, BB/M010066/1, BB/M008606/1] Funding Source: researchfish; BBSRC [BB/M010066/1, BB/M008606/1] Funding Source: UKRI
NR 42
TC 496
Z9 590
U1 5
U2 257
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 301
EP +
DI 10.1038/nature20577
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700064
PM 27919081
DA 2026-03-09
ER

PT J
AU Halbertal, D
   Cuppens, J
   Ben Shalom, M
   Embon, L
   Shadmi, N
   Anahory, Y
   Naren, HR
   Sarkar, J
   Uri, A
   Ronen, Y
   Myasoedov, Y
   Levitov, LS
   Joselevich, E
   Geim, AK
   Zeldov, E
AF Halbertal, D.
   Cuppens, J.
   Ben Shalom, M.
   Embon, L.
   Shadmi, N.
   Anahory, Y.
   Naren, H. R.
   Sarkar, J.
   Uri, A.
   Ronen, Y.
   Myasoedov, Y.
   Levitov, L. S.
   Joselevich, E.
   Geim, A. K.
   Zeldov, E.
TI Nanoscale thermal imaging of dissipation in quantum systems
SO NATURE
LA English
DT Article
ID thermometry; temperature
AB Energy dissipation is a fundamental process governing the dynamics of physical, chemical and biological systems. It is also one of the main characteristics that distinguish quantum from classical phenomena. In particular, in condensed matter physics, scattering mechanisms, loss of quantum information or breakdown of topological protection are deeply rooted in the intricate details of how and where the dissipation occurs. Yet the microscopic behaviour of a system is usually not formulated in terms of dissipation because energy dissipation is not a readily measurable quantity on the micrometre scale. Although nanoscale thermometry has gained much recent interest(1-15), existing thermal imaging methods are not sensitive enough for the study of quantum systems and are also unsuitable for the low-temperature operation that is required. Here we report a nano-thermometer based on a superconducting quantum interference device with a diameter of less than 50 nanometres that resides at the apex of a sharp pipette: it provides scanning cryogenic thermal sensing that is four orders of magnitude more sensitive than previous devices-below 1 mu K Hz(-1/2). This non contact, non-invasive thermometry allows thermal imaging of very low intensity, nanoscale energy dissipation down to the fundamental Landauer limit(16-18) of 40 femtowatts for continuous readout of a single qubit at one gigahertz at 4.2 kelvin. These advances enable the observation of changes in dissipation due to single-electron charging of individual quantum dots in carbon nanotubes. They also reveal a dissipation mechanism attributable to resonant localized states in graphene encapsulated within hexagonal boron nitride, opening the door to direct thermal imaging of nanoscale dissipation processes in quantum matter.
C1 [Halbertal, D.; Cuppens, J.; Embon, L.; Anahory, Y.; Naren, H. R.; Sarkar, J.; Uri, A.; Ronen, Y.; Myasoedov, Y.; Zeldov, E.] Weizmann Inst Sci, Dept Condensed Matter Phys, IL-7610001 Rehovot, Israel.
   [Cuppens, J.] CSIC, ICN2, Campus UAB, Barcelona 08193, Spain.
   [Cuppens, J.] Barcelona Inst Sci & Technol, Campus UAB, Barcelona 08193, Spain.
   [Ben Shalom, M.; Geim, A. K.] Univ Manchester, Natl Graphene Inst, Booth St East, Manchester M13 9PL, Lancs, England.
   [Ben Shalom, M.; Geim, A. K.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Shadmi, N.; Joselevich, E.] Weizmann Inst Sci, Dept Mat & Interfaces, IL-7610001 Rehovot, Israel.
   [Levitov, L. S.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Embon, L.] Columbia Univ, Dept Phys, 538 W 120th St, New York, NY 10027 USA.
C3 Weizmann Institute of Science; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); Barcelona Institute of Science & Technology; Catalan Institute of Nanoscience & Nanotechnology (ICN2); Autonomous University of Barcelona; Barcelona Institute of Science & Technology; University of Manchester; University of Manchester; Weizmann Institute of Science; Massachusetts Institute of Technology (MIT); Columbia University
RP Halbertal, D; Zeldov, E (corresponding author), Weizmann Inst Sci, Dept Condensed Matter Phys, IL-7610001 Rehovot, Israel.
EM dorri.halbertal@weizmann.ac.il; eli.zeldov@weizmann.ac.il
FU European Research Council (ERC) under the European Union [655416]; Minerva Foundation; Federal German Ministry of Education and Research; Rosa and Emilio Segre Research Award; MISTI MIT-Israel Seed Fund; EPSRC [EP/K005014/1, EP/N010345/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/N010345/1, EP/K005014/1] Funding Source: researchfish; European Research Council (ERC) [655416] Funding Source: European Research Council (ERC)
NR 33
TC 182
Z9 205
U1 2
U2 242
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 407
EP 410
DI 10.1038/nature19843
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700049
PM 27786173
DA 2026-03-09
ER

PT J
AU Watts, J
   Sheehan, O
   Atkinson, QD
   Bulbulia, J
   Gray, RD
AF Watts, Joseph
   Sheehan, Oliver
   Atkinson, Quentin D.
   Bulbulia, Joseph
   Gray, Russell D.
TI Ritual human sacrifice promoted and sustained the evolution of stratified societies
SO NATURE
LA English
DT Article
AB Evidence for human sacrifice is found throughout the archaeological record of early civilizations(1), the ethnographic records of indigenous world cultures(2-5), and the texts of the most prolific contemporary religions(6). According to the social control hypothesis(2,7,8), human sacrifice legitimizes political authority and social class systems, functioning to stabilize such social stratification. Support for the social control hypothesis is largely limited to historical anecdotes of human sacrifice(2,8), where the causal claims have not been subject to rigorous quantitative cross-cultural tests. Here we test the social control hypothesis by applying Bayesian phylogenetic methods to a geographically and socially diverse sample of 93 traditional Austronesian cultures. We find strong support for models in which human sacrifice stabilizes social stratification once stratification has arisen, and promotes a shift to strictly inherited class systems. Whilst evolutionary theories of religion have focused on the functionality of prosocial and moral beliefs(9,10), our results reveal a darker link between religion and the evolution of modern hierarchical societies(11,12).
C1 [Watts, Joseph; Sheehan, Oliver; Atkinson, Quentin D.; Gray, Russell D.] Univ Auckland, Sch Psychol, Auckland 1142, New Zealand.
   [Sheehan, Oliver; Atkinson, Quentin D.; Gray, Russell D.] Max Planck Inst Sci Human Hist, D-07743 Jena, Germany.
   [Bulbulia, Joseph] Victoria Univ Wellington, Sch Art Hist Class & Religious Studies, Wellington 6014, New Zealand.
   [Gray, Russell D.] Australian Natl Univ, Res Sch Social Sci, GPO Box 4, Canberra, ACT 2601, Australia.
   [Gray, Russell D.] Allan Wilson Ctr Mol Ecol & Evolut, Palmerston North 4442, New Zealand.
C3 University of Auckland; Victoria University Wellington; Australian National University; Massey University
RP Watts, J (corresponding author), Univ Auckland, Sch Psychol, Auckland 1142, New Zealand.
EM me@josephwatts.org
FU John Templeton Foundation [28745]; Templeton World Charity Foundation [0077]; Rutherford Discovery Fellowship [RDF-OUA1101]; University of Auckland; Marsden Fund [UOA1104, VUW1321]
NR 42
TC 121
Z9 143
U1 1
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 228
EP +
DI 10.1038/nature17159
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100038
PM 27042932
DA 2026-03-09
ER

PT J
AU Faber, F
   Tran, L
   Byndloss, MX
   Lopez, CA
   Velazquez, EM
   Kerrinnes, T
   Nuccio, SP
   Wangdi, T
   Fiehn, O
   Tsolis, RM
   Baumler, AJ
AF Faber, Franziska
   Tran, Lisa
   Byndloss, Mariana X.
   Lopez, Christopher A.
   Velazquez, Eric M.
   Kerrinnes, Tobias
   Nuccio, Sean-Paul
   Wangdi, Tamding
   Fiehn, Oliver
   Tsolis, Renee M.
   Baumler, Andreas J.
TI Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion
SO NATURE
LA English
DT Article
ID enterica serotype typhimurium; salmonella-typhimurium; escherichia-coli; nitric-oxide; resistance; growth; microbiota; infection
AB Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars(1), increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse(2,3). These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel(4). However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion.
C1 [Faber, Franziska; Tran, Lisa; Byndloss, Mariana X.; Lopez, Christopher A.; Velazquez, Eric M.; Kerrinnes, Tobias; Nuccio, Sean-Paul; Wangdi, Tamding; Tsolis, Renee M.; Baumler, Andreas J.] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, One Shields Ave, Davis, CA 95616 USA.
   [Fiehn, Oliver] Univ Calif Davis, Genome Ctr, One Shields Ave, Davis, CA 95616 USA.
   [Fiehn, Oliver] King Abdulaziz Univ, Dept Biochem, Jeddah 21412, Saudi Arabia.
C3 University of California System; University of California Davis; University of California System; University of California Davis; King Abdulaziz University
RP Baumler, AJ (corresponding author), Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, One Shields Ave, Davis, CA 95616 USA.
EM ajbaumler@ucdavis.edu
FU Public Health Service [OD010931, AI060555, AI096528, AI09799, AI112241, AI112258, AI112445, U24 DK097154 (01), AI112949, AI114922]; National Institute of Allergy and Infectious Diseases [R01AI112445, R01AI112949, R01AI109799, R01AI096528, T32AI060555] Funding Source: NIH RePORTER; NIH Office of the Director [T35OD010956] Funding Source: NIH RePORTER
NR 30
TC 150
Z9 183
U1 2
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 697
EP +
DI 10.1038/nature18597
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000039
PM 27309805
DA 2026-03-09
ER

PT J
AU Zheng, ZG
   Li, YN
   Bisoyi, HK
   Wang, L
   Bunning, TJ
   Li, Q
AF Zheng, Zhi-gang
   Li, Yannian
   Bisoyi, Hari Krishna
   Wang, Ling
   Bunning, Timothy J.
   Li, Quan
TI Three-dimensional control of the helical axis of a chiral nematic liquid crystal by light
SO NATURE
LA English
DT Article
ID diffraction gratings; handedness inversion; polymer
AB Chiral nematic liquid crystals-otherwise referred to as cholesteric liquid crystals (CLCs)-are self-organized helical superstructures that find practical application in, for example, thermography(1), reflective displays(2), tuneable colour filters(3,4) and mirrorless lasing(5,6). Dynamic, remote and three-dimensional control over the helical axis of CLCs is desirable, but challenging(7,8). For example, the orientation of the helical axis relative to the substrate can be changed from perpendicular to parallel by applying an alternating-current electric field(9), by changing the anchoring conditions of the substrate, or by altering the topography of the substrate's surface(10-16); separately, in-plane rotation of the helical axis parallel to the substrate can be driven by a direct-current field(17-19). Here we report three-dimensional manipulation of the helical axis of a CLC, together with inversion of its handedness, achieved solely with a light stimulus. We use this technique to carry out light-activated, wide-area, reversible two-dimensional beam steering-previously accomplished using complex integrated systems(20) and optical phased arrays(21). During the three-dimensional manipulation by light, the helical axis undergoes, in sequence, a reversible transition from perpendicular to parallel, followed by in-plane rotation on the substrate surface. Such reversible manipulation depends on experimental parameters such as cell thickness, surface anchoring condition, and pitch length. Because there is no thermal relaxation, the system can be driven either forwards or backwards from any light-activated intermediate state. We also describe reversible photocontrol between a two-dimensional diffraction state, a one-dimensional diffraction state and a diffraction 'off' state in a bilayer cell.
C1 [Zheng, Zhi-gang; Li, Yannian; Bisoyi, Hari Krishna; Wang, Ling; Li, Quan] Kent State Univ, Inst Liquid Crystal, Kent, OH 44242 USA.
   [Zheng, Zhi-gang; Li, Yannian; Bisoyi, Hari Krishna; Wang, Ling; Li, Quan] Kent State Univ, Chem Phys Interdisciplinary Program, Kent, OH 44242 USA.
   [Bunning, Timothy J.] US Air Force, Mat & Mfg Directorate, Res Lab, Wright Patterson AFB, OH 45433 USA.
C3 University System of Ohio; Kent State University; Kent State University Kent; Kent State University Salem; University System of Ohio; Kent State University; Kent State University Salem; Kent State University Kent; United States Department of Defense; United States Air Force
RP Li, Q (corresponding author), Kent State Univ, Inst Liquid Crystal, Kent, OH 44242 USA.; Li, Q (corresponding author), Kent State Univ, Chem Phys Interdisciplinary Program, Kent, OH 44242 USA.
EM qli1@kent.edu
FU Air Force Office of Scientific Research (AFOSR) [FA9950-09-1-0193]; Air Force Research Laboratory; China Scholarship Council; Materials and Manufacturing Directorate; AFOSR
NR 29
TC 508
Z9 546
U1 27
U2 763
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 352
EP +
DI 10.1038/nature17141
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300049
PM 26950601
DA 2026-03-09
ER

PT J
AU Sarkisyan, KS
   Bolotin, DA
   Meer, MV
   Usmanova, DR
   Mishin, AS
   Sharonov, GV
   Ivankov, DN
   Bozhanova, NG
   Baranov, MS
   Soylemez, O
   Bogatyreva, NS
   Vlasov, PK
   Egorov, ES
   Logacheva, MD
   Kondrashov, AS
   Chudakov, DM
   Putintseva, EV
   Mamedov, IZ
   Tawfik, DS
   Lukyanov, KA
   Kondrashov, FA
AF Sarkisyan, Karen S.
   Bolotin, Dmitry A.
   Meer, Margarita V.
   Usmanova, Dinara R.
   Mishin, Alexander S.
   Sharonov, George V.
   Ivankov, Dmitry N.
   Bozhanova, Nina G.
   Baranov, Mikhail S.
   Soylemez, Onuralp
   Bogatyreva, Natalya S.
   Vlasov, Peter K.
   Egorov, Evgeny S.
   Logacheva, Maria D.
   Kondrashov, Alexey S.
   Chudakov, Dmitry M.
   Putintseva, Ekaterina V.
   Mamedov, Ilgar Z.
   Tawfik, Dan S.
   Lukyanov, Konstantin A.
   Kondrashov, Fyodor A.
TI Local fitness landscape of the green fluorescent protein
SO NATURE
LA English
DT Article
ID sequence space; evolution; selection; epistasis; mutations; domain
AB Fitness landscapes(1,2) depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology(2-7), yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness(2,4), experimentally assessing the effect on function of single mutations and their combinations in a specific sequence(2,5,8-15) or in different sequences(2,3,5,16-18). However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported. Here we visualize an extensive region of the local fitness landscape of the green fluorescent protein from Aequorea victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands of derivative genotypes of avGFP. We show that the fitness landscape of avGFP is narrow, with 3/4 of the derivatives with a single mutation showing reduced fluorescence and half of the derivatives with four mutations being completely non-fluorescent. The narrowness is enhanced by epistasis, which was detected in up to 30% of genotypes with multiple mutations and mostly occurred through the cumulative effect of slightly deleterious mutations causing a threshold-like decrease in protein stability and a concomitant loss of fluorescence. A model of orthologous sequence divergence spanning hundreds of millions of years predicted the extent of epistasis in our data, indicating congruence between the fitness landscape properties at the local and global scales. The characterization of the local fitness landscape of avGFP has important implications for several fields including molecular evolution, population genetics and protein design.
C1 [Sarkisyan, Karen S.; Bolotin, Dmitry A.; Mishin, Alexander S.; Sharonov, George V.; Bozhanova, Nina G.; Baranov, Mikhail S.; Egorov, Evgeny S.; Chudakov, Dmitry M.; Putintseva, Ekaterina V.; Mamedov, Ilgar Z.; Lukyanov, Konstantin A.] Shemyakin Ovchinnikov Inst Bioorgan Chem, Miklukho Maklaya 16-10, Moscow 117997, Russia.
   [Sarkisyan, Karen S.; Mishin, Alexander S.; Lukyanov, Konstantin A.] Nizhny Novgorod State Med Acad, Minin Sq 10-1, Nizhnii Novgorod 603005, Russia.
   [Sarkisyan, Karen S.; Bolotin, Dmitry A.; Chudakov, Dmitry M.; Putintseva, Ekaterina V.; Mamedov, Ilgar Z.] Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic.
   [Sarkisyan, Karen S.; Meer, Margarita V.; Usmanova, Dinara R.; Ivankov, Dmitry N.; Soylemez, Onuralp; Bogatyreva, Natalya S.; Vlasov, Peter K.; Kondrashov, Fyodor A.] Barcelona Inst Sci & Technol, CRG, Bioinformat & Genom Programme, 88 Dr Aiguader, Barcelona 08003, Spain.
   [Sarkisyan, Karen S.; Meer, Margarita V.; Usmanova, Dinara R.; Ivankov, Dmitry N.; Soylemez, Onuralp; Bogatyreva, Natalya S.; Vlasov, Peter K.; Kondrashov, Fyodor A.] UPF, Barcelona 08003, Spain.
   [Usmanova, Dinara R.] Moscow Inst Phys & Technol, Inst Pereulok 9, G Dolgoprudny 141700, Russia.
   [Sharonov, George V.] Moscow MV Lomonosov State Univ, Fac Med, Lomonosov Ave 31-5, Moscow 119192, Russia.
   [Ivankov, Dmitry N.; Bogatyreva, Natalya S.] Russian Acad Sci, Inst Prot Res, Lab Prot Phys, 4 Inst Skaya Str, Pushchino 142290, Moscow Region, Russia.
   [Baranov, Mikhail S.; Logacheva, Maria D.] Pirogov Russian Natl Res Med Univ, Ostrovitianov 1, Moscow 117997, Russia.
   [Logacheva, Maria D.] Russian Acad Sci, AA Kharkevich Inst Informat Transmiss Problems, Moscow 127051, Russia.
   [Logacheva, Maria D.; Kondrashov, Alexey S.] Moscow MV Lomonosov State Univ, Dept Bioinformat & Bioengn, Moscow 119234, Russia.
   [Kondrashov, Alexey S.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [Tawfik, Dan S.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Kondrashov, Fyodor A.] ICREA, 23 Pg Lluis Companys, Barcelona 08010, Spain.
C3 Russian Academy of Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Privolzhsky Research Medical University; Masaryk University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Moscow Institute of Physics & Technology; Lomonosov Moscow State University; Russian Academy of Sciences; Pirogov Russian National Research Medical University; Kharkevich Institute for Information Transmission Problems of the RAS; Russian Academy of Sciences; Lomonosov Moscow State University; University of Michigan System; University of Michigan; Weizmann Institute of Science; ICREA
RP Kondrashov, FA (corresponding author), Barcelona Inst Sci & Technol, CRG, Bioinformat & Genom Programme, 88 Dr Aiguader, Barcelona 08003, Spain.; Kondrashov, FA (corresponding author), UPF, Barcelona 08003, Spain.; Kondrashov, FA (corresponding author), ICREA, 23 Pg Lluis Companys, Barcelona 08010, Spain.
EM fyodor.kondrashov@crg.es
FU Russian Science Foundation [14-50-00150, 14-25-00129]; HHMI International Early Career Scientist Program [55007424]; EMBO Young Investigator Programme; MINECO [BFU2012-31329]; Spanish Ministry of Economy and Competitiveness Centro de Excelencia Severo Ochoa [SEV-2012-0208]; Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat's AGAUR program [2014 SGR 0974]; European Research Council under the European Union's Seventh Framework Programme (ERC) [335980_EinME]; Russian Science Foundation [14-25-00129] Funding Source: Russian Science Foundation; ICREA Funding Source: Custom
NR 30
TC 369
Z9 480
U1 5
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 397
EP +
DI 10.1038/nature17995
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300049
PM 27193686
DA 2026-03-09
ER

PT J
AU Delling, M
   Indzhykulian, AA
   Liu, X
   Li, Y
   Xie, T
   Corey, DP
   Clapham, DE
AF Delling, M.
   Indzhykulian, A. A.
   Liu, X.
   Li, Y.
   Xie, T.
   Corey, D. P.
   Clapham, D. E.
TI Primary cilia are not calcium-responsive mechanosensors
SO NATURE
LA English
DT Article
ID left-right asymmetry; nodal flow; mouse embryos; fluid-flow; channels; ca2+; polycystin-1; dynamics; breaking; mice
AB Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium(1). This Ca2+-responsive mechanosensor hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers(2,3). Here we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. We developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca2+ influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signalling.
C1 [Delling, M.; Liu, X.; Clapham, D. E.] Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA.
   [Indzhykulian, A. A.; Li, Y.; Corey, D. P.; Clapham, D. E.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
   [Xie, T.] Harvard Univ, Sch Med, IDAC, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Clapham, DE (corresponding author), Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA.; Corey, DP; Clapham, DE (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
EM dcorey@hms.harvard.edu; dclapham@enders.tch.harvard.edu
FU Mouse Gene Manipulation Facility of the Boston Children's Hospital Intellectual and Developmental Disabilities Research Center (IDDRC) [NIHP30-HD 18655]; National Institutes of Health (NIH) [5R01 DC000304]; Kaplan Family
NR 45
TC 285
Z9 347
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 656
EP +
DI 10.1038/nature17426
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400042
PM 27007841
DA 2026-03-09
ER

PT J
AU Hosten, O
   Engelsen, NJ
   Krishnakumar, R
   Kasevich, MA
AF Hosten, Onur
   Engelsen, Nils J.
   Krishnakumar, Rajiv
   Kasevich, Mark A.
TI Measurement noise 100 times lower than the quantum-projection limit using entangled atoms
SO NATURE
LA English
DT Article
ID interferometry; states
AB Quantum metrology uses quantum entanglement-correlations in the properties of microscopic systems-to improve the statistical precision of physical measurements(1). When measuring a signal, such as the phase shift of a light beam or an atomic state, a prominent limitation to achievable precision arises from the noise associated with the counting of uncorrelated probe particles. This noise, commonly referred to as shot noise or projection noise, gives rise to the standard quantum limit (SQL) to phase resolution. However, it can be mitigated down to the fundamental Heisenberg limit by entangling the probe particles. Despite considerable experimental progress in a variety of physical systems, a question that persists is whether these methods can achieve performance levels that compare favourably with optimized conventional (non-entangled) systems. Here we demonstrate an approach that achieves unprecedented levels of metrological improvement using half a million Rb-87 atoms in their 'clock' states. The ensemble is 20.1 +/- 0.3 decibels (100-fold) spin-squeezed via an optical-cavity-based measurement. We directly resolve small microwave-induced rotations 18.5 +/- 0.3 decibels (70-fold) beyond the SQL. The single-shot phase resolution of 147 microradians achieved by the apparatus is better than that achieved by the best engineered cold atom sensors despite lower atom numbers(2,3). We infer entanglement of more than 680 +/- 35 particles in the atomic ensemble. Applications include atomic clocks(4), inertial sensors(5), and fundamental physics experiments such as tests of general relativity(6) or searches for electron electric dipole moment(7). To this end, we demonstrate an atomic clock measurement with a quantum enhancement of 10.5 +/- 0.3 decibels (11-fold), limited by the phase noise of our microwave source.
C1 [Hosten, Onur; Engelsen, Nils J.; Krishnakumar, Rajiv; Kasevich, Mark A.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
C3 Stanford University
RP Kasevich, MA (corresponding author), Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
EM kasevich@stanford.edu
FU DTRA; NSSEFF fellowship; ONR
NR 30
TC 440
Z9 514
U1 0
U2 158
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 505
EP +
DI 10.1038/nature16176
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800032
PM 26751056
DA 2026-03-09
ER

PT J
AU Meadows, AL
   Hawkins, KM
   Tsegaye, Y
   Antipov, E
   Kim, Y
   Raetz, L
   Dahl, RH
   Tai, A
   Mahatdejkul-Meadows, T
   Xu, L
   Zhao, LS
   Dasika, MS
   Murarka, A
   Lenihan, J
   Eng, D
   Leng, JS
   Liu, CL
   Wenger, JW
   Jiang, HX
   Chao, LL
   Westfall, P
   Lai, J
   Ganesan, S
   Jackson, P
   Mans, R
   Platt, D
   Reeves, CD
   Saija, PR
   Wichmann, G
   Holmes, VF
   Benjamin, K
   Hill, PW
   Gardner, TS
   Tsong, AE
AF Meadows, Adam L.
   Hawkins, Kristy M.
   Tsegaye, Yoseph
   Antipov, Eugene
   Kim, Youngnyun
   Raetz, Lauren
   Dahl, Robert H.
   Tai, Anna
   Mahatdejkul-Meadows, Tina
   Xu, Lan
   Zhao, Lishan
   Dasika, Madhukar S.
   Murarka, Abhishek
   Lenihan, Jacob
   Eng, Diana
   Leng, Joshua S.
   Liu, Chi-Li
   Wenger, Jared W.
   Jiang, Hanxiao
   Chao, Lily
   Westfall, Patrick
   Lai, Jefferson
   Ganesan, Savita
   Jackson, Peter
   Mans, Robert
   Platt, Darren
   Reeves, Christopher D.
   Saija, Poonam R.
   Wichmann, Gale
   Holmes, Victor F.
   Benjamin, Kirsten
   Hill, Paul W.
   Gardner, Timothy S.
   Tsong, Annie E.
TI Rewriting yeast central carbon metabolism for industrial isoprenoid production
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; phosphoketolase pathway; phosphorolytic cleavage; escherichia-coli; acetyl-coenzyme; genome; stress; growth; fructose-6-phosphate; conservation
AB A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments(1). Adapting these strains for biosynthesis of other isoprenoids such as beta-farnesene (C15H24), a plant sesquiterpene with versatile industrial applications(2-5), is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO2-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained(6). Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.
C1 [Meadows, Adam L.; Hawkins, Kristy M.; Tsegaye, Yoseph; Antipov, Eugene; Kim, Youngnyun; Raetz, Lauren; Dahl, Robert H.; Tai, Anna; Mahatdejkul-Meadows, Tina; Xu, Lan; Zhao, Lishan; Dasika, Madhukar S.; Murarka, Abhishek; Lenihan, Jacob; Eng, Diana; Leng, Joshua S.; Liu, Chi-Li; Wenger, Jared W.; Jiang, Hanxiao; Chao, Lily; Westfall, Patrick; Lai, Jefferson; Ganesan, Savita; Jackson, Peter; Mans, Robert; Platt, Darren; Reeves, Christopher D.; Saija, Poonam R.; Wichmann, Gale; Holmes, Victor F.; Benjamin, Kirsten; Hill, Paul W.; Gardner, Timothy S.; Tsong, Annie E.] Amyris, 5885 Hollis St,Suite 100, Emeryville, CA 94608 USA.
RP Tsong, AE (corresponding author), Amyris, 5885 Hollis St,Suite 100, Emeryville, CA 94608 USA.
EM tsong@amyris.com
NR 56
TC 528
Z9 629
U1 15
U2 603
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 694
EP +
DI 10.1038/nature19769
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700053
PM 27654918
DA 2026-03-09
ER

PT J
AU Hu, QY
   Kim, DY
   Yang, WG
   Yang, LX
   Meng, Y
   Zhang, L
   Mao, HK
AF Hu, Qingyang
   Kim, Duck Young
   Yang, Wenge
   Yang, Liuxiang
   Meng, Yue
   Zhang, Li
   Mao, Ho-Kwang
TI FeO2 and FeOOH under deep lower-mantle conditions and Earth's oxygen-hydrogen cycles
SO NATURE
LA English
DT Article
ID generalized gradient approximation; raman-spectroscopy; high-pressures; (mg,fe)sio3 perovskite; stability; fe2o3; complexity; state; crust; h-2
AB The distribution, accumulation and circulation of oxygen and hydrogen in Earth's interior dictate the geochemical evolution of the hydrosphere, atmosphere and biosphere(1). The oxygen-rich atmosphere and iron-rich core represent two end-members of the oxygen-iron (O-Fe) system, overlapping with the entire pressure-temperature-composition range of the planet. The extreme pressure and temperature conditions of the deep interior alter the oxidation states(1), spin states(2) and phase stabilities(3,4) of iron oxides, creating new stoichiometries, such as Fe4O5 (ref. 5) and Fe5O6 (ref. 6). Such interactions between O and Fe dictate Earth's formation, the separation of the core and mantle, and the evolution of the atmosphere. Iron, in its multiple oxidation states, controls the oxygen fugacity and oxygen budget, with hydrogen having a key role in the reaction of Fe and O (causing iron to rust in humid air). Here we use first-principles calculations and experiments to identify a highly stable, pyrite-structured iron oxide (FeO2) at 76 gigapascals and 1,800 kelvin that holds an excessive amount of oxygen. We show that the mineral goethite, FeOOH, which exists ubiquitously as 'rust' and is concentrated in bog iron ore, decomposes under the deep lower-mantle conditions to form FeO2 and release H-2. The reaction could cause accumulation of the heavy FeO2-bearing patches in the deep lower mantle, upward migration of hydrogen, and separation of the oxygen and hydrogen cycles. This process provides an alternative interpretation for the origin of seismic and geochemical anomalies in the deep lower mantle, as well as a sporadic O-2 source for the Great Oxidation Event over two billion years ago that created the present oxygen-rich atmosphere.
C1 [Hu, Qingyang; Kim, Duck Young; Yang, Wenge; Yang, Liuxiang; Zhang, Li; Mao, Ho-Kwang] Ctr High Pressure Sci & Technol Adv Res HPSTAR, Shanghai 201203, Peoples R China.
   [Hu, Qingyang; Kim, Duck Young; Zhang, Li; Mao, Ho-Kwang] Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
   [Yang, Wenge; Yang, Liuxiang] Carnegie Inst, Geophys Lab, High Pressure Synerget Consortium HPSynC, Argonne, IL 60439 USA.
   [Meng, Yue] Carnegie Inst, Geophys Lab, High Pressure Collaborat Access Team HPCAT, Argonne, IL 60439 USA.
C3 Carnegie Institution for Science; Carnegie Institution for Science; Carnegie Institution for Science
RP Mao, HK (corresponding author), Ctr High Pressure Sci & Technol Adv Res HPSTAR, Shanghai 201203, Peoples R China.; Mao, HK (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
EM hmao@gl.ciw.edu
FU DOE-NNSA [DE-NA0001974]; DOE-BES [DE-FG02-99ER45775, DE-AC02-06CH11357]; NSF; COMPRES through the Partnership for Extreme Crystallography (PX2) project under NSF [EAR 11-57758]; NSF [EAR-1345112, EAR-1447438]; Foundation of President of China Academy of Engineering Physics [201402032]; National Natural Science Foundation of China [41574080, U1530402]; Division Of Earth Sciences; Directorate For Geosciences [1345112] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1447438] Funding Source: National Science Foundation
NR 42
TC 273
Z9 328
U1 18
U2 542
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 241
EP +
DI 10.1038/nature18018
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100039
PM 27279220
DA 2026-03-09
ER

PT J
AU Osberger, TJ
   Rogness, DC
   Kohrt, JT
   Stepan, AF
   White, MC
AF Osberger, Thomas J.
   Rogness, Donald C.
   Kohrt, Jeffrey T.
   Stepan, Antonia F.
   White, M. Christina
TI Oxidative diversification of amino acids and peptides by small-molecule iron catalysis
SO NATURE
LA English
DT Article
ID diversity-oriented synthesis; nonribosomal peptides; functionalization; selectivity; discovery; strategy; enzymes; bonds
AB Secondary metabolites synthesized by non-ribosomal peptide synthetases display diverse and complex topologies and possess a range of biological activities(1,2). Much of this diversity derives from a synthetic strategy that entails pre-3 and post-assembly(2) oxidation of both the chiral amino acid building blocks and the assembled peptide scaffolds. The vancomycin biosynthetic pathway is an excellent example of the range of oxidative transformations that can be performed by the iron-containing enzymes involved in its biosynthesis(4). However, because of the challenges associated with using such oxidative enzymes to carry out chemical transformations in vitro, chemical syntheses guided by these principles have not been fully realized in the laboratory(5). Here we report that two small-molecule iron catalysts are capable of facilitating the targeted C-H oxidative modification of amino acids and peptides with preservation of a-centre chirality. Oxidation of proline to 5-hydroxyproline furnishes a versatile intermediate that can be transformed to rigid arylated derivatives or flexible linear carboxylic acids, alcohols, olefins and amines in both monomer and peptide settings. The value of this C-H oxidation strategy is demonstrated in its capacity for generating diversity: four 'chiral pool' amino acids are transformed to twenty-one chiral unnatural amino acids representing seven distinct functional group arrays; late-stage C-H functionalizations of a single proline-containing tripeptide furnish eight tripeptides, each having different unnatural amino acids. Additionally, a macrocyclic peptide containing a proline turn element is transformed via late-stage C-H oxidation to one containing a linear unnatural amino acid.
C1 [Osberger, Thomas J.; Rogness, Donald C.; White, M. Christina] Univ Illinois, Dept Chem, Roger Adams Lab, Urbana, IL 61801 USA.
   [Kohrt, Jeffrey T.] Groton Labs, Pfizer Worldwide Res & Dev, Eastern Point Rd, Groton, CT 06340 USA.
   [Stepan, Antonia F.] Pfizer Worldwide Res & Dev, Worldwide Med Chem, Cambridge, MA 02139 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; Pfizer; Pfizer USA; Pfizer; Pfizer USA
RP White, MC (corresponding author), Univ Illinois, Dept Chem, Roger Adams Lab, Urbana, IL 61801 USA.
EM mcwhite7@illinois.edu
FU NIH/National Institute of General Medical Sciences [GM112492]; Pfizer
NR 30
TC 219
Z9 246
U1 5
U2 228
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 214
EP 219
DI 10.1038/nature18941
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100044
PM 27479323
DA 2026-03-09
ER

PT J
AU Katayama, Y
   Nishiyama, M
   Shoji, H
   Ohkawa, Y
   Kawamura, A
   Sato, T
   Suyama, M
   Takumi, T
   Miyakawa, T
   Nakayama, KI
AF Katayama, Yuta
   Nishiyama, Masaaki
   Shoji, Hirotaka
   Ohkawa, Yasuyuki
   Kawamura, Atsuki
   Sato, Tetsuya
   Suyama, Mikita
   Takumi, Toru
   Miyakawa, Tsuyoshi
   Nakayama, Keiichi I.
TI CHD8 haploinsufficiency results in autistic-like phenotypes in mice
SO NATURE
LA English
DT Article
ID histone h1 recruitment; de-novo mutations; behavioral phenotypes; binding protein; chromatin; genetics; genes; rest; abnormality; networks
AB Autism spectrum disorder (ASD) comprises a range of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as by restricted and repetitive behaviours(1). ASD has a strong genetic component with high heritability. Exome sequencing analysis has recently identified many de novo mutations in a variety of genes in individuals with ASD(2,3), with CHD8, a gene encoding a chromatin remodeller, being most frequently affected(4-8). Whether CHD8 mutations are causative for ASD and how they might establish ASD traits have remained unknown. Here we show that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. Our results are thus consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment.
C1 [Katayama, Yuta; Nishiyama, Masaaki; Kawamura, Atsuki; Nakayama, Keiichi I.] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.
   [Shoji, Hirotaka; Miyakawa, Tsuyoshi] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Syst Med Sci, Toyoake, Aichi 4701192, Japan.
   [Ohkawa, Yasuyuki] Kyushu Univ, Med Inst Bioregulat, Div Transcript, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.
   [Sato, Tetsuya; Suyama, Mikita] Kyushu Univ, Med Inst Bioregulat, Div Bioinformat, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.
   [Takumi, Toru] RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan.
C3 Kyushu University; Fujita Health University; Kyushu University; Kyushu University; RIKEN
RP Nishiyama, M; Nakayama, KI (corresponding author), Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan.
EM nishiyam@bioreg.kyushu-u.ac.jp; nakayak1@bioreg.kyushu-u.ac.jp
FU Center for Advanced Instrumental and Educational Support, Faculty of Agriculture, Kyushu University; KAKENHI; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Grants-in-Aid for Scientific Research [15H01291, 16K13110, 16H06316, 16H06462, 15K06835, 16H06463, 16H01341, 16H06276, 25242078, 15H01516] Funding Source: KAKEN
NR 46
TC 252
Z9 305
U1 7
U2 64
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 675
EP +
DI 10.1038/nature19357
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700049
PM 27602517
DA 2026-03-09
ER

PT J
AU Hu, Y
   Bürgmann, R
   Banerjee, P
   Feng, LJ
   Hill, EM
   Ito, T
   Tabei, T
   Wang, KL
AF Hu, Yan
   Buergmann, Roland
   Banerjee, Paramesh
   Feng, Lujia
   Hill, Emma M.
   Ito, Takeo
   Tabei, Takao
   Wang, Kelin
TI Asthenosphere rheology inferred from observations of the 2012 Indian Ocean earthquake
SO NATURE
LA English
DT Article
ID m-w 8.6; viscoelastic relaxation; postseismic deformation; wharton basin; mantle; resolution; melt; tomography; subduction; viscosity
AB The concept of a weak asthenospheric layer underlying Earth's mobile tectonic plates is fundamental to our understanding of mantle convection and plate tectonics. However, little is known about the mechanical properties of the asthenosphere (the part of the upper mantle below the lithosphere) underlying the oceanic crust, which covers about 60 per cent of Earth's surface. Great earthquakes cause large coseismic crustal deformation in areas hundreds of kilometres away from and below the rupture area. Subsequent relaxation of the earthquake-induced stresses in the viscoelastic upper mantle leads to prolonged postseismic crustal deformation that may last several decades and can be recorded with geodetic methods(1-3). The observed postseismic deformation helps us to understand the rheological properties of the upper mantle, but so far such measurements have been limited to continental-plate boundary zones. Here we consider the postseismic deformation of the very large (moment magnitude 8.6) 2012 Indian Ocean earthquake(4-6) to provide by far the most direct constraint on the structure of oceanic mantle rheology. In the first three years after the Indian Ocean earthquake, 37 continuous Global Navigation Satellite Systems stations in the region underwent horizontal northeastward displacements of up to 17 centimetres in a direction similar to that of the coseismic offsets. However, a few stations close to the rupture area that had experienced subsidence of up to about 4 centimetres during the earthquake rose by nearly 7 centimetres after the earthquake. Our three-dimensional viscoelastic finite-element models of the post-earthquake deformation show that a thin (30-200 kilometres), low-viscosity (having a steady-state Maxwell viscosity of (0.5-10) x 10(18) pascal seconds) asthenospheric layer beneath the elastic oceanic lithosphere is required to produce the observed postseismic uplift.
C1 [Hu, Yan; Buergmann, Roland] Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
   [Hu, Yan; Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Hu, Yan] Univ Sci & Technol China, Sch Earth & Space Sci, Mengcheng Natl Geophys Observ, Hefei 230026, Peoples R China.
   [Banerjee, Paramesh; Feng, Lujia; Hill, Emma M.] Nanyang Technol Univ, Earth Observ Singapore, Asian Sch Environm, Singapore, Singapore.
   [Ito, Takeo] Nagoya Univ, Grad Sch Environm Studies, Nagoya, Aichi 4648601, Japan.
   [Tabei, Takao] Kochi Univ, Dept Appl Sci, Akebono Cho 2-5-1, Kochi 7808520, Japan.
   [Wang, Kelin] Nat Resources Canada, Geol Survey Canada, Pacific Geosci Ctr, Sidney, BC, Canada.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Nanyang Technological University; Nagoya University; Kochi University; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada
RP Hu, Y (corresponding author), Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.; Hu, Y (corresponding author), Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.; Hu, Y (corresponding author), Univ Sci & Technol China, Sch Earth & Space Sci, Mengcheng Natl Geophys Observ, Hefei 230026, Peoples R China.
EM yhu@seismo.berkeley.edu
FU NSF [EAR-1246850]; Miller Institute for Basic Research in Science; Singapore National Research Foundation [NRF-NRFF2010-064]; Grants-in-Aid for Scientific Research [16H06474] Funding Source: KAKEN
NR 41
TC 91
Z9 100
U1 2
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 368
EP +
DI 10.1038/nature19787
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100036
PM 27723742
DA 2026-03-09
ER

PT J
AU Shiba, Y
   Gomibuchi, T
   Seto, T
   Wada, Y
   Ichimura, H
   Tanaka, Y
   Ogasawara, T
   Okada, K
   Shiba, N
   Sakamoto, K
   Ido, D
   Shiina, T
   Ohkura, M
   Nakai, J
   Uno, N
   Kazuki, Y
   Oshimura, M
   Minami, I
   Ikeda, U
AF Shiba, Yuji
   Gomibuchi, Toshihito
   Seto, Tatsuichiro
   Wada, Yuko
   Ichimura, Hajime
   Tanaka, Yuki
   Ogasawara, Tatsuki
   Okada, Kenji
   Shiba, Naoko
   Sakamoto, Kengo
   Ido, Daisuke
   Shiina, Takashi
   Ohkura, Masamichi
   Nakai, Junichi
   Uno, Narumi
   Kazuki, Yasuhiro
   Oshimura, Mitsuo
   Minami, Itsunari
   Ikeda, Uichi
TI Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; major histocompatibility complex; cardiac differentiation; t-cells; model; polymorphism; integration
AB Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy(1), few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.
C1 [Shiba, Yuji] Shinshu Univ, Inst Biomed Sci, Matsumoto, Nagano 3908621, Japan.
   [Shiba, Yuji; Ikeda, Uichi] Shinshu Univ, Sch Med, Dept Cardiovasc Med, Matsumoto, Nagano 3908621, Japan.
   [Gomibuchi, Toshihito; Seto, Tatsuichiro; Wada, Yuko; Ichimura, Hajime; Tanaka, Yuki; Ogasawara, Tatsuki; Okada, Kenji] Shinshu Univ, Sch Med, Dept Cardiovasc Surg, Matsumoto, Nagano 3908621, Japan.
   [Shiba, Naoko] Shinshu Univ, Sch Med, Dept Pediat, Matsumoto, Nagano 3908621, Japan.
   [Sakamoto, Kengo; Ido, Daisuke] Ina Res Inc, Ina, Saitama 3994501, Japan.
   [Shiina, Takashi] Tokai Univ, Sch Med, Dept Mol Life Sci, Isehara, Kanagawa 2591193, Japan.
   [Ohkura, Masamichi; Nakai, Junichi] Saitama Univ, Brain Sci Inst, Saitama 3388570, Japan.
   [Ohkura, Masamichi; Nakai, Junichi] Saitama Univ, Grad Sch Sci & Engn, Saitama 3388570, Japan.
   [Uno, Narumi; Kazuki, Yasuhiro; Oshimura, Mitsuo] Tottori Univ, Chromosome Engn Res Ctr, Yonago, Tottori 6838503, Japan.
   [Minami, Itsunari] Kyoto Univ, Inst Integrated Cell Mat Sci WPI iCeMS, Kyoto 6068501, Japan.
C3 Shinshu University; Shinshu University; Shinshu University; Shinshu University; Ina Research Inc.; Tokai University; Saitama University; Saitama University; Tottori University; Kyoto University
RP Shiba, Y (corresponding author), Shinshu Univ, Inst Biomed Sci, Matsumoto, Nagano 3908621, Japan.; Shiba, Y (corresponding author), Shinshu Univ, Sch Med, Dept Cardiovasc Med, Matsumoto, Nagano 3908621, Japan.
EM yshiba@shinshu-u.ac.jp
FU Japan Society for the Promotion of Science KAKENHI [26293182]; Japan Agency for Medical Research and Development; Takeda Science Foundation; Astellas Foundation for Research on Metabolic Disorders; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Japan Heart Association; Ministry of Education, Culture, Sports, Science and Technology (MEXT) [26115504, 25116504]; Regional Innovation Cluster Program (City Area Type, Central Saitama Area); Grants-in-Aid for Scientific Research [16H06502, 15H05723, 26461062, 25116504, 26282217, 15H01275, 26115504, 16H01378, 16K14552, 26293182, 15K08270] Funding Source: KAKEN
NR 26
TC 626
Z9 752
U1 4
U2 238
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 388
EP +
DI 10.1038/nature19815
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100040
PM 27723741
DA 2026-03-09
ER

PT J
AU Kremkow, J
   Jin, JZ
   Wang, YS
   Alonso, JM
AF Kremkow, Jens
   Jin, Jianzhong
   Wang, Yushi
   Alonso, Jose M.
TI Principles underlying sensory map topography in primary visual cortex
SO NATURE
LA English
DT Article
ID cell orientation selectivity; monkey striate cortex; receptive-fields; directional selectivity; ordered arrangement; response property; linear mechanisms; ocular dominance; single neurons; on-center
AB The primary visual cortex contains a detailed map of the visual scene, which is represented according to multiple stimulus dimensions including spatial location, ocular dominance and stimulus orientation. The maps for spatial location and ocular dominance arise from the spatial arrangement of thalamic afferent axons in the cortex. However, the origins of the other maps remain unclear. Here we show that the cortical maps for orientation, direction and retinal disparity in the cat (Felis catus) are all strongly related to the organization of the map for spatial location of light (ON) and dark (OFF) stimuli, an organization that we show is OFF-dominated, OFF-centric and runs orthogonal to ocular dominance columns. Because this ON-OFF organization originates from the clustering of ON and OFF thalamic afferents in the visual cortex, we conclude that all main features of visual cortical topography, including orientation, direction and retinal disparity, follow a common organizing principle that arranges thalamic axons with similar retinotopy and ON-OFF polarity in neighbouring cortical regions.
C1 [Kremkow, Jens; Jin, Jianzhong; Wang, Yushi; Alonso, Jose M.] SUNY Coll Optometry, Grad Ctr Vis Res, 33 West 42nd St, New York, NY 10036 USA.
   [Kremkow, Jens] Humboldt Univ, Inst Theoret Biol, Dept Biol, Philippstr 13, D-10115 Berlin, Germany.
C3 State University of New York (SUNY) System; SUNY Optometry; Humboldt University of Berlin
RP Alonso, JM (corresponding author), SUNY Coll Optometry, Grad Ctr Vis Res, 33 West 42nd St, New York, NY 10036 USA.
EM jalonso@sunyopt.edu
FU US National Institutes of Health [EY005253]; DFG [KR 4062/1-1]; Humboldt-Universitat zu Berlin in the framework of the Excellence Initiative of the BMBF; Humboldt-Universitat zu Berlin in the framework of the Excellence Initiative of DFG; National Eye Institute [R01EY005253] Funding Source: NIH RePORTER
NR 45
TC 104
Z9 118
U1 1
U2 32
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 52
EP +
DI 10.1038/nature17936
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900037
PM 27120164
DA 2026-03-09
ER

PT J
AU Jaubert, J
   Verheyden, S
   Genty, D
   Soulier, M
   Cheng, H
   Blamart, D
   Burlet, C
   Camus, H
   Delaby, S
   Deldicque, D
   Dwards, RLE
   Ferrier, C
   Lacrampe-Cuyaubère, F
   Lévêque, F
   Maksud, F
   Mora, P
   Muth, X
   Régnier, E
   Rouzaud, JN
   Santos, F
AF Jaubert, Jacques
   Verheyden, Sophie
   Genty, Dominique
   Soulier, Michel
   Cheng, Hai
   Blamart, Dominique
   Burlet, Christian
   Camus, Hubert
   Delaby, Serge
   Deldicque, Damien
   Dwards, R. Lawrence E.
   Ferrier, Catherine
   Lacrampe-Cuyaubere, Francois
   Leveque, Francois
   Maksud, Frederic
   Mora, Pascal
   Muth, Xavier
   Regnier, Edouard
   Rouzaud, Jean-Noel
   Santos, Frederic
TI Early Neanderthal constructions deep in Bruniquel Cave in southwestern France
SO NATURE
LA English
DT Article
ID origin; paintings; hearths; fire
AB Very little is known about Neanderthal cultures(1), particularly early ones. Other than lithic implements and exceptional bone tools(2), very few artefacts have been preserved. While those that do remain include red and black pigments(3) and burial sites(4), these indications of modernity are extremely sparse and few have been precisely dated, thus greatly limiting our knowledge of these predecessors of modern humans(5). Here we report the dating of annular constructions made of broken stalagmites found deep in Bruniquel Cave in southwest France. The regular geometry of the stalagmite circles, the arrangement of broken stalagmites and several traces of fire demonstrate the anthropogenic origin of these constructions. Uranium-series dating of stalagmite regrowths on the structures and on burnt bone, combined with the dating of stalagmite tips in the structures, give a reliable and replicated age of 176.5 thousand years (+/-2.1 thousand years), making these edifices among the oldest known well-dated constructions made by humans. Their presence at 336 metres from the entrance of the cave indicates that humans from this period had already mastered the underground environment, which can be considered a major step in human modernity.
C1 [Jaubert, Jacques; Ferrier, Catherine; Santos, Frederic] Univ Bordeaux, PACEA, UMR 5199, CNRS,MCC, F-33615 Pessac, France.
   [Verheyden, Sophie; Burlet, Christian] Royal Belgian Inst Nat Sci, Earth & Hist Life, B-1000 Brussels, Belgium.
   [Verheyden, Sophie] Vrije Univ Brussel, AMGC, B-1050 Brussels, Belgium.
   [Genty, Dominique; Blamart, Dominique; Regnier, Edouard] UVSQ, CEA, CNRS, LSCE,UMR 8212, F-91400 Gif Sur Yvette, France.
   [Soulier, Michel] Soc Speleol & Archeol Caussade, 5 Rue Bourdelle, F-82300 Caussade, France.
   [Cheng, Hai] Xi An Jiao Tong Univ, Inst Global Environm Change, Xian 710049, Peoples R China.
   [Cheng, Hai; Dwards, R. Lawrence E.] Univ Minnesota, Earth Sci, Minneapolis, MN 55455 USA.
   [Camus, Hubert] Protee Expert Sas, F-30250 Sommieres, France.
   [Delaby, Serge] Univ Mons, Fac Polytech, B-7000 Mons, Belgium.
   [Deldicque, Damien; Rouzaud, Jean-Noel] Ecole Normale Super, Lab Geol, UMR 8538, CNRS, F-75000 Paris, France.
   [Lacrampe-Cuyaubere, Francois] Archeosphere, F-11500 Quirbajou, France.
   [Lacrampe-Cuyaubere, Francois; Muth, Xavier] Get Situ, CH-1091 Bourg En Lavaux, Switzerland.
   [Leveque, Francois] Univ La Rochelle, CNRS, UMR 7266, LIENSs, F-17000 La Rochelle, France.
   [Maksud, Frederic] Minist Culture, Reg Archaeol Serv Midi Pyrenees, F-31080 Toulouse, France.
   [Mora, Pascal] SHS 3D, Archeostransfert, Archeovis, UMS 3657, F-33007 Pessac, France.
C3 Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Royal Belgian Institute of Natural Sciences; Vrije Universiteit Brussel; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); CEA; Xi'an Jiaotong University; University of Minnesota System; University of Minnesota Twin Cities; University of Mons; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Ecole Normale Superieure (ENS); La Rochelle Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social Sciences (INSHS)
RP Jaubert, J (corresponding author), Univ Bordeaux, PACEA, UMR 5199, CNRS,MCC, F-33615 Pessac, France.; Verheyden, S (corresponding author), Royal Belgian Inst Nat Sci, Earth & Hist Life, B-1000 Brussels, Belgium.; Verheyden, S (corresponding author), Vrije Univ Brussel, AMGC, B-1050 Brussels, Belgium.; Genty, D (corresponding author), UVSQ, CEA, CNRS, LSCE,UMR 8212, F-91400 Gif Sur Yvette, France.
EM jacques.jaubert@u-bordeaux.fr; sophie.verheyden@naturalsciences.be; dominique.genty@lsce.ipsl.fr
FU French MCC (DRAC-SRA Midi-Pyrenees, Toulouse); Belgian Science Policy Office
NR 49
TC 169
Z9 200
U1 0
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 111
EP +
DI 10.1038/nature18291
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300044
PM 27251286
DA 2026-03-09
ER

PT J
AU Keestra-Gounder, AM
   Byndloss, MX
   Seyffert, N
   Young, BM
   Chávez-Arroyo, A
   Tsai, AY
   Cevallos, SA
   Winter, MG
   Pham, OH
   Tiffany, CR
   de Jong, MF
   Kerrinnes, T
   Ravindran, R
   Luciw, PA
   McSorley, SJ
   Baumler, AJ
   Tsolis, RM
AF Keestra-Gounder, A. Marijke
   Byndloss, Mariana X.
   Seyffert, Nubia
   Young, Briana M.
   Chavez-Arroyo, Alfredo
   Tsai, April Y.
   Cevallos, Stephanie A.
   Winter, Maria G.
   Pham, Oanh H.
   Tiffany, Connor R.
   de Jong, Maarten F.
   Kerrinnes, Tobias
   Ravindran, Resmi
   Luciw, Paul A.
   McSorley, Stephen J.
   Baumler, Andreas J.
   Tsolis, Renee M.
TI NOD1/NOD2 signaling links ER stress with inflammation
SO NATURE
LA English
DT Article
ID nf-kappa-b; endoplasmic-reticulum stress; iv secretion system; activation; kinase; ire1; mice; infection; responses; pathogen
AB Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn's disease and type 2 diabetes(1,2). ER stress induces the unfolded protein response (UPR), which involves activation of three transmembrane receptors, ATF6 (activating transcription factor 6), PERK (protein kinase RNA-like endoplasmic reticulum kinase) and IRE1 alpha (inositol-requiring enzyme 1 alpha)(3) (Extended Data figure 1 alpha). Once activated, IRE1a recruits TRAF2 (TNF receptor-associated factor 2) to the ER membrane to initiate inflammatory responses via the nuclear factor kappa B (NF-kappa B) pathway(4). Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) or nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), detect tissue damage or microbial infection. However, it is not clear which PRRs play a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NLR family of PRRs, are important mediators of ER stress-induced inflammation. The ER stress inducers thapsigargin and dithiothreitol (DTT) triggered production of the pro-inflammatory cytokine interleukin (IL)-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system (T4SS) effector protein VceC into host cells(5), was TRAF2, NOD1/2 and RIP2-dependent and could be blunted by treatment with the ER-stress inhibitor tauroursodeoxycholate (TUDCA) or an IRE1 alpha kinase inhibitor. The association of NOD1 and NOD2 with pro-inflammatory responses induced by the IRE1 alpha/TRAF2 signaling pathway provides a novel link between innate immunity and ER stress-induced inflammation.
C1 [Keestra-Gounder, A. Marijke; Byndloss, Mariana X.; Seyffert, Nubia; Young, Briana M.; Chavez-Arroyo, Alfredo; Tsai, April Y.; Cevallos, Stephanie A.; Winter, Maria G.; Tiffany, Connor R.; de Jong, Maarten F.; Kerrinnes, Tobias; Baumler, Andreas J.; Tsolis, Renee M.] Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, One Shields Ave, Davis, CA 95616 USA.
   [Pham, Oanh H.; Ravindran, Resmi; Luciw, Paul A.; McSorley, Stephen J.] Univ Calif Davis, Ctr Comparat Med, Sch Med, One Shields Ave, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis
RP Tsolis, RM (corresponding author), Univ Calif Davis, Dept Med Microbiol & Immunol, Sch Med, One Shields Ave, Davis, CA 95616 USA.
EM rmtsolis@ucdavis.edu
FU NIAID NIH HHS [R01 AI076246, R21 AI112258, R21 AI117303, R37 AI044170, R01 AI044170, R01 AI096528, AI044170, AI076278, R01 AI103422, AI076246, R01 AI109799, R01 AI076278, AI096528, AI109799, AI112258, AI117303] Funding Source: Medline; NIGMS NIH HHS [GM056765, R25 GM056765, R25 GM086262] Funding Source: Medline; National Institute of Allergy and Infectious Diseases [R01AI109799, R01AI096528, R01AI044170] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R25GM086262] Funding Source: NIH RePORTER
NR 29
TC 427
Z9 496
U1 8
U2 174
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 394
EP 397
DI 10.1038/nature17631
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EJ2HW
UT WOS:000393031700001
PM 27007849
DA 2026-03-09
ER

PT J
AU Barends, R
   Shabani, A
   Lamata, L
   Kelly, J
   Mezzacapo, A
   Heras, UL
   Babbush, R
   Fowler, AG
   Campbell, B
   Chen, Y
   Chen, Z
   Chiaro, B
   Dunsworth, A
   Jeffrey, E
   Lucero, E
   Megrant, A
   Mutus, JY
   Neeley, M
   Neill, C
   O'Malley, PJJ
   Quintana, C
   Roushan, P
   Sank, D
   Vainsencher, A
   Wenner, J
   White, TC
   Solano, E
   Neven, H
   Martinis, JM
AF Barends, R.
   Shabani, A.
   Lamata, L.
   Kelly, J.
   Mezzacapo, A.
   Heras, U. Las
   Babbush, R.
   Fowler, A. G.
   Campbell, B.
   Chen, Yu
   Chen, Z.
   Chiaro, B.
   Dunsworth, A.
   Jeffrey, E.
   Lucero, E.
   Megrant, A.
   Mutus, J. Y.
   Neeley, M.
   Neill, C.
   O'Malley, P. J. J.
   Quintana, C.
   Roushan, P.
   Sank, D.
   Vainsencher, A.
   Wenner, J.
   White, T. C.
   Solano, E.
   Neven, H.
   Martinis, John M.
TI Digitized adiabatic quantum computing with a superconducting circuit
SO NATURE
LA English
DT Article
ID computation; simulation
AB Quantum mechanics can help to solve complex problems in physics(1) and chemistry(2), provided they can be programmed in a physical device. In adiabatic quantum computing(3-5), a system is slowly evolved from the ground state of a simple initial Hamiltonian to a final Hamiltonian that encodes a computational problem. The appeal of this approach lies in the combination of simplicity and generality; in principle, any problem can be encoded. In practice, applications are restricted by limited connectivity, available interactions and noise. A complementary approach is digital quantum computing(6), which enables the construction of arbitrary interactions and is compatible with error correction(7,8), but uses quantum circuit algorithms that are problem-specific. Here we combine the advantages of both approaches by implementing digitized adiabatic quantum computing in a superconducting system. We tomographically probe the system during the digitized evolution and explore the scaling of errors with system size. We then let the full system find the solution to random instances of the one-dimensional Ising problem as well as problem Hamiltonians that involve more complex interactions. This digital quantum simulation(9-12) of the adiabatic algorithm consists of up to nine qubits and up to 1,000 quantum logic gates. The demonstration of digitized adiabatic quantum computing in the solid state opens a path to synthesizing long-range correlations and solving complex computational problems. When combined with fault-tolerance, our approach becomes a general-purpose algorithm that is scalable.
C1 [Barends, R.; Kelly, J.; Fowler, A. G.; Chen, Yu; Jeffrey, E.; Lucero, E.; Mutus, J. Y.; Neeley, M.; Roushan, P.; Sank, D.; Martinis, John M.] Google Inc, Santa Barbara, CA 93117 USA.
   [Shabani, A.; Babbush, R.; Neven, H.] Google Inc, Venice, CA 90291 USA.
   [Lamata, L.; Mezzacapo, A.; Heras, U. Las; Solano, E.] Univ Basque Country UPV EHU, Dept Phys Chem, Apartado 644, E-48080 Bilbao, Spain.
   [Campbell, B.; Chen, Z.; Chiaro, B.; Dunsworth, A.; Megrant, A.; Neill, C.; O'Malley, P. J. J.; Quintana, C.; Vainsencher, A.; Wenner, J.; White, T. C.; Martinis, John M.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Solano, E.] Basque Fdn Sci, Ikerbasque, Maria Diaz Haro 3, Bilbao 48013, Spain.
   [Mezzacapo, A.] IBM TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA.
C3 Alphabet Inc.; Google Incorporated; Alphabet Inc.; Google Incorporated; University of Basque Country; University of California System; University of California Santa Barbara; Basque Foundation for Science; International Business Machines (IBM); IBM USA
RP Barends, R (corresponding author), Google Inc, Santa Barbara, CA 93117 USA.; Shabani, A (corresponding author), Google Inc, Venice, CA 90291 USA.
EM barends@google.com; shabani@google.com
FU Spanish MINECO [FIS2012-36673-C03-02]; Ramon y Cajal [RYC-2012-11391]; Basque Government [IT472-10]; UPV/EHU PhD grant; PROMISCE EU project; SCALEQIT EU project; NSF;  [UPV/EHU UFI 11/55];  [EHUA14/04]
NR 29
TC 378
Z9 435
U1 3
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 222
EP 226
DI 10.1038/nature17658
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100035
PM 27279216
DA 2026-03-09
ER

PT J
AU Okbay, A
   Beauchamp, JP
   Fontana, MA
   Lee, JJ
   Pers, TH
   Rietveld, CA
   Turley, P
   Chen, GB
   Emilsson, V
   Meddens, SFW
   Oskarsson, S
   Pickrell, JK
   Thom, K
   Timshel, P
   de Vlaming, R
   Abdellaoui, A
   Ahluwalia, TS
   Bacelis, J
   Baumbach, C
   Bjornsdottir, G
   Brandsma, JH
   Concas, MP
   Derringer, J
   Furlotte, NA
   Galesloot, TE
   Girotto, G
   Gupta, R
   Hall, LM
   Harris, SE
   Hofer, E
   Horikoshi, M
   Huffman, JE
   Kaasik, K
   Kalafati, IP
   Karlsson, R
   Kong, A
   Lahti, J
   van der Lee, SJ
   de Leeuw, C
   Lind, PA
   Lindgren, KO
   Liu, T
   Mangino, M
   Marten, J
   Mihailov, E
   Miller, MB
   van der Most, PJ
   Oldmeadow, C
   Payton, A
   Pervjakova, N
   Peyrot, WJ
   Qian, Y
   Raitakari, O
   Rueedi, R
   Salvi, E
   Schmidt, B
   Schraut, KE
   Shi, JX
   Smith, AV
   Poot, RA
   St Pourcain, B
   Teumer, A
   Thorleifsson, G
   Verweij, N
   Vuckovic, D
   Wellmann, J
   Westra, HJ
   Yang, JY
   Zhao, W
   Zhu, ZH
   Alizadeh, BZ
   Amin, N
   Bakshi, A
   Baumeister, SE
   Biino, G
   Bonnelykke, K
   Boyle, PA
   Campbell, H
   Cappuccio, FP
   Davies, G
   De Neve, JE
   Deloukas, P
   Demuth, I
   Ding, J
   Eibich, P
   Eisele, L
   Eklund, N
   Evans, DM
   Faul, JD
   Feitosa, MF
   Forstner, AJ
   Gandin, I
   Gunnarsson, B
   Halldórsson, BV
   Harris, TB
   Heath, AC
   Hocking, LJ
   Holliday, EG
   Homuth, G
   Horan, MA
   Hottenga, JJ
   de Jager, PL
   Joshi, PK
   Jugessur, A
   Kaakinen, MA
   Kähönen, M
   Kanoni, S
   Keltigangas-Järvinen, L
   Kiemeney, LALM
   Kolcic, I
   Koskinen, S
   Kraja, AT
   Kroh, M
   Kutalik, Z
   Latvala, A
   Launer, LJ
   Lebreton, MP
   Levinson, DF
   Lichtenstein, P
   Lichtner, P
   Liewald, DCM
   Loukola, A
   Madden, PA
   Mägi, R
   Mäki-Opas, T
   Marioni, RE
   Marques-Vidal, P
   Meddens, GA
   McMahon, G
   Meisinger, C
   Meitinger, T
   Milaneschi, Y
   Milani, L
   Montgomery, GW
   Myhre, R
   Nelson, CP
   Nyholt, DR
   Ollier, WER
   Palotie, A
   Paternoster, L
   Pedersen, NL
   Petrovic, KE
   Porteous, DJ
   Räikkönen, K
   Ring, SM
   Robino, A
   Rostapshova, O
   Rudan, I
   Rustichini, A
   Salomaa, V
   Sanders, AR
   Sarin, AP
   Schmidt, H
   Scott, RJ
   Smith, BH
   Smith, JA
   Staessen, JA
   Steinhagen-Thiessen, E
   Strauch, K
   Terracciano, A
   Tobin, MD
   Ulivi, S
   Vaccargiu, S
   Quaye, L
   van Rooij, FJA
   Venturini, C
   Vinkhuyzen, AAE
   Völker, U
   Völzke, H
   Vonk, JM
   Vozzi, D
   Waage, J
   Ware, EB
   Willemsen, G
   Attia, JR
   Bennett, DA
   Berger, K
   Bertram, L
   Bisgaard, H
   Boomsma, DI
   Borecki, IB
   Bültmann, U
   Chabris, CF
   Cucca, F
   Cusi, D
   Deary, IJ
   Dedoussis, GV
   van Duijn, CM
   Eriksson, JG
   Franke, B
   Franke, L
   Gasparini, P
   Gejman, PV
   Gieger, C
   Grabe, HJ
   Gratten, J
   Groenen, PJF
   Gudnason, V
   van der Harst, P
   Hayward, C
   Hinds, DA
   Hoffmann, W
   Hyppnen, E
   Iacono, WG
   Jacobsson, B
   Järvelin, MR
   Jöckel, KH
   Kaprio, J
   Kardia, SLR
   Lehtimäki, T
   Lehrer, SF
   Magnusson, PKE
   Martin, NG
   McGue, M
   Metspalu, A
   Pendleton, N
   Penninx, BWJH
   Perola, M
   Pirastu, N
   Pirastu, M
   Polasek, O
   Posthuma, D
   Power, C
   Province, MA
   Samani, NJ
   Schlessinger, D
   Schmidt, R
   Sorensen, TIA
   Spector, TD
   Stefansson, K
   Thorsteinsdottir, U
   Thurik, AR
   Timpson, NJ
   Tiemeier, H
   Tung, JY
   Uitterlinden, AG
   Vitart, V
   Vollenweider, P
   Weir, DR
   Wilson, JF
   Wright, AF
   Conley, DC
   Krueger, RF
   Smith, GD
   Hofman, A
   Laibson, DI
   Medland, SE
   Meyer, MN
   Yang, J
   Johannesson, M
   Visscher, PM
   Esko, T
   Koellinger, PD
   Cesarini, D
   Benjamin, DJ
AF Okbay, Aysu
   Beauchamp, Jonathan P.
   Fontana, Mark Alan
   Lee, James J.
   Pers, Tune H.
   Rietveld, Cornelius A.
   Turley, Patrick
   Chen, Guo-Bo
   Emilsson, Valur
   Meddens, S. Fleur W.
   Oskarsson, Sven
   Pickrell, Joseph K.
   Thom, Kevin
   Timshel, Pascal
   de Vlaming, Ronald
   Abdellaoui, Abdel
   Ahluwalia, Tarunveer S.
   Bacelis, Jonas
   Baumbach, Clemens
   Bjornsdottir, Gyda
   Brandsma, Johannes H.
   Concas, Maria Pina
   Derringer, Jaime
   Furlotte, Nicholas A.
   Galesloot, Tessel E.
   Girotto, Giorgia
   Gupta, Richa
   Hall, Leanne M.
   Harris, Sarah E.
   Hofer, Edith
   Horikoshi, Momoko
   Huffman, Jennifer E.
   Kaasik, Kadri
   Kalafati, Ioanna P.
   Karlsson, Robert
   Kong, Augustine
   Lahti, Jari
   van der Lee, Sven J.
   de Leeuw, Christiaan
   Lind, Penelope A.
   Lindgren, Karl-Oskar
   Liu, Tian
   Mangino, Massimo
   Marten, Jonathan
   Mihailov, Evelin
   Miller, Michael B.
   van der Most, Peter J.
   Oldmeadow, Christopher
   Payton, Antony
   Pervjakova, Natalia
   Peyrot, Wouter J.
   Qian, Yong
   Raitakari, Olli
   Rueedi, Rico
   Salvi, Erika
   Schmidt, Brge
   Schraut, Katharina E.
   Shi, Jianxin
   Smith, Albert V.
   Poot, Raymond A.
   St Pourcain, Beate
   Teumer, Alexander
   Thorleifsson, Gudmar
   Verweij, Niek
   Vuckovic, Dragana
   Wellmann, Juergen
   Westra, Harm-Jan
   Yang, Jingyun
   Zhao, Wei
   Zhu, Zhihong
   Alizadeh, Behrooz Z.
   Amin, Najaf
   Bakshi, Andrew
   Baumeister, Sebastian E.
   Biino, Ginevra
   Bonnelykke, Klaus
   Boyle, Patricia A.
   Campbell, Harry
   Cappuccio, Francesco P.
   Davies, Gail
   De Neve, Jan-Emmanuel
   Deloukas, Panos
   Demuth, Ilja
   Ding, Jun
   Eibich, Peter
   Eisele, Lewin
   Eklund, Niina
   Evans, David M.
   Faul, Jessica D.
   Feitosa, Mary F.
   Forstner, Andreas J.
   Gandin, Ilaria
   Gunnarsson, Bjarni
   Halldorsson, Bjarni V.
   Harris, Tamara B.
   Heath, Andrew C.
   Hocking, Lynne J.
   Holliday, Elizabeth G.
   Homuth, Georg
   Horan, Michael A.
   Hottenga, Jouke-Jan
   de Jager, Philip L.
   Joshi, Peter K.
   Jugessur, Astanand
   Kaakinen, Marika A.
   Kahonen, Mika
   Kanoni, Stavroula
   Keltigangas-Jarvinen, Liisa
   Kiemeney, Lambertus A. L. M.
   Kolcic, Ivana
   Koskinen, Seppo
   Kraja, Aldi T.
   Kroh, Martin
   Kutalik, Zoltan
   Latvala, Antti
   Launer, Lenore J.
   Lebreton, Mael P.
   Levinson, Douglas F.
   Lichtenstein, Paul
   Lichtner, Peter
   Liewald, David C. M.
   Loukola, Anu
   Madden, Pamela A.
   Magi, Reedik
   Maki-Opas, Tomi
   Marioni, Riccardo E.
   Marques-Vidal, Pedro
   Meddens, Gerardus A.
   McMahon, George
   Meisinger, Christa
   Meitinger, Thomas
   Milaneschi, Yusplitri
   Milani, Lili
   Montgomery, Grant W.
   Myhre, Ronny
   Nelson, Christopher P.
   Nyholt, Dale R.
   Ollier, William E. R.
   Palotie, Aarno
   Paternoster, Lavinia
   Pedersen, Nancy L.
   Petrovic, Katja E.
   Porteous, David J.
   Raikkonen, Katri
   Ring, Susan M.
   Robino, Antonietta
   Rostapshova, Olga
   Rudan, Igor
   Rustichini, Aldo
   Salomaa, Veikko
   Sanders, Alan R.
   Sarin, Antti-Pekka
   Schmidt, Helena
   Scott, Rodney J.
   Smith, Blair H.
   Smith, Jennifer A.
   Staessen, Jan A.
   Steinhagen-Thiessen, Elisabeth
   Strauch, Konstantin
   Terracciano, Antonio
   Tobin, Martin D.
   Ulivi, Sheila
   Vaccargiu, Simona
   Quaye, Lydia
   van Rooij, Frank J. A.
   Venturini, Cristina
   Vinkhuyzen, Anna A. E.
   Volker, Uwe
   Volzke, Henry
   Vonk, Judith M.
   Vozzi, Diego
   Waage, Johannes
   Ware, Erin B.
   Willemsen, Gonneke
   Attia, John R.
   Bennett, David A.
   Berger, Klaus
   Bertram, Lars
   Bisgaard, Hans
   Boomsma, Dorret I.
   Borecki, Ingrid B.
   Bultmann, Ute
   Chabris, Christopher F.
   Cucca, Francesco
   Cusi, Daniele
   Deary, Ian J.
   Dedoussis, George V.
   van Duijn, Cornelia M.
   Eriksson, Johan G.
   Franke, Barbara
   Franke, Lude
   Gasparini, Paolo
   Gejman, Pablo V.
   Gieger, Christian
   Grabe, Hans-Jorgen
   Gratten, Jacob
   Groenen, Patrick J. F.
   Gudnason, Vilmundur
   van der Harst, Pim
   Hayward, Caroline
   Hinds, David A.
   Hoffmann, Wolfgang
   Hyppnen, Elina
   Iacono, William G.
   Jacobsson, Bo
   Jarvelin, Marjo-Riitta
   Jockel, Karl-Heinz
   Kaprio, Jaakko
   Kardia, Sharon L. R.
   Lehtimaki, Terho
   Lehrer, Steven F.
   Magnusson, Patrik K. E.
   Martin, Nicholas G.
   McGue, Matt
   Metspalu, Andres
   Pendleton, Neil
   Penninx, Brenda W. J. H.
   Perola, Markus
   Pirastu, Nicola
   Pirastu, Mario
   Polasek, Ozren
   Posthuma, Danielle
   Power, Christine
   Province, Michael A.
   Samani, Nilesh J.
   Schlessinger, David
   Schmidt, Reinhold
   Sorensen, Thorkild I. A.
   Spector, Tim D.
   Stefansson, Kari
   Thorsteinsdottir, Unnur
   Thurik, A. Roy
   Timpson, Nicholas J.
   Tiemeier, Henning
   Tung, Joyce Y.
   Uitterlinden, Andre G.
   Vitart, Veronique
   Vollenweider, Peter
   Weir, David R.
   Wilson, James F.
   Wright, Alan F.
   Conley, Dalton C.
   Krueger, Robert F.
   Smith, George Davey
   Hofman, Albert
   Laibson, David I.
   Medland, Sarah E.
   Meyer, Michelle N.
   Yang, Jian
   Johannesson, Magnus
   Visscher, Peter M.
   Esko, Tonu
   Koellinger, Philipp D.
   Cesarini, David
   Benjamin, Daniel J.
TI Genome-wide association study identifies 74 loci associated with educational attainment
SO NATURE
LA English
DT Article
ID heritability; achievement; iq
AB Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
C1 [Okbay, Aysu; Rietveld, Cornelius A.; de Vlaming, Ronald; Thurik, A. Roy] Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3062 PA Rotterdam, Netherlands.
   [Okbay, Aysu; Rietveld, Cornelius A.; de Vlaming, Ronald; van der Lee, Sven J.; Amin, Najaf; van Rooij, Frank J. A.; van Duijn, Cornelia M.; Tiemeier, Henning; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
   [Okbay, Aysu; Rietveld, Cornelius A.; Meddens, S. Fleur W.; de Vlaming, Ronald; Palotie, Aarno; Thurik, A. Roy; Koellinger, Philipp D.] Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.
   [Beauchamp, Jonathan P.; Turley, Patrick; Rostapshova, Olga; Laibson, David I.] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA.
   [Fontana, Mark Alan; Benjamin, Daniel J.] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90089 USA.
   [Lee, James J.; Miller, Michael B.; Iacono, William G.; McGue, Matt; Krueger, Robert F.] Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN 55455 USA.
   [Pers, Tune H.; Hofman, Albert; Esko, Tonu] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.
   [Pers, Tune H.; Hofman, Albert; Esko, Tonu] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.
   [Pers, Tune H.; Timshel, Pascal; Westra, Harm-Jan; de Jager, Philip L.; Esko, Tonu] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Pers, Tune H.; Ahluwalia, Tarunveer S.; Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.
   [Pers, Tune H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
   [Chen, Guo-Bo; Zhu, Zhihong; Bakshi, Andrew; Marioni, Riccardo E.; Vinkhuyzen, Anna A. E.; Gratten, Jacob; Yang, Jian; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
   [Emilsson, Valur; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
   [Emilsson, Valur] Univ Iceland, Fac Pharmaceut Sci, IS-107 Reykjavik, Iceland.
   [Meddens, S. Fleur W.; de Leeuw, Christiaan; Posthuma, Danielle; Koellinger, Philipp D.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.
   [Meddens, S. Fleur W.; Lebreton, Mael P.; Koellinger, Philipp D.] Univ Amsterdam, Amsterdam Business Sch, NL-1018 TV Amsterdam, Netherlands.
   [Oskarsson, Sven; Lindgren, Karl-Oskar] Uppsala Univ, Dept Govt, S-75120 Uppsala, Sweden.
   [Pickrell, Joseph K.] New York Genome Ctr, New York, NY 10013 USA.
   [Thom, Kevin; Cesarini, David] NYU, Dept Econ, New York, NY 10003 USA.
   [Timshel, Pascal] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark.
   [Abdellaoui, Abdel; Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
   [Ahluwalia, Tarunveer S.; Waage, Johannes; Bisgaard, Hans] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, DK-2820 Copenhagen, Denmark.
   [Ahluwalia, Tarunveer S.; Waage, Johannes] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
   [Bacelis, Jonas; Jacobsson, Bo] Sahlgrens Acad, Inst Clin Sci, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden.
   [Baumbach, Clemens; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
   [Baumbach, Clemens; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
   [Brandsma, Johannes H.; Poot, Raymond A.] Erasmus MC, Dept Cell Biol, NL-3015 CN Rotterdam, Netherlands.
   [Concas, Maria Pina; Pirastu, Mario] Natl Res Council Italy, UOS Sassari, Ist Ric Genet & Biomed, I-07100 Sassari, Italy.
   [Derringer, Jaime] Univ Illinois, Psychol, Champaign, IL 61820 USA.
   [Furlotte, Nicholas A.; Hinds, David A.; Tung, Joyce Y.] 23andMe Inc, Mountain View, CA 94041 USA.
   [Galesloot, Tessel E.; Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands.
   [Girotto, Giorgia; Vuckovic, Dragana; Gandin, Ilaria; Gasparini, Paolo; Pirastu, Nicola] Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy.
   [Gupta, Richa; Latvala, Antti; Loukola, Anu; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland.
   [Hall, Leanne M.; Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
   [Hall, Leanne M.; Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Gen Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
   [Harris, Sarah E.; Davies, Gail; Liewald, David C. M.; Marioni, Riccardo E.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Harris, Sarah E.; Porteous, David J.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Hofer, Edith; Petrovic, Katja E.; Schmidt, Helena; Schmidt, Reinhold] Gen Hosp, Dept Neurol, A-8036 Graz, Austria.
   [Hofer, Edith; Petrovic, Katja E.; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, A-8036 Graz, Austria.
   [Hofer, Edith] Gen Hosp, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
   [Horikoshi, Momoko] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England.
   [Horikoshi, Momoko] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Huffman, Jennifer E.; Marten, Jonathan; Hayward, Caroline; Vitart, Veronique; Wilson, James F.; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Kaasik, Kadri; Lahti, Jari; Keltigangas-Jarvinen, Liisa; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, FIN-00014 Helsinki, Finland.
   [Kalafati, Ioanna P.; Dedoussis, George V.] Harokopio Univ, Nutr & Dietet, Hlth Sci & Educ, Athens 17671, Greece.
   [Karlsson, Robert; Lichtenstein, Paul; Pedersen, Nancy L.; Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
   [Lahti, Jari; Raikkonen, Katri; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki 00014, Finland.
   [de Leeuw, Christiaan] Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 EC Nijmegen, Netherlands.
   [Lind, Penelope A.; Medland, Sarah E.] QIMR Berghofer Med Res Inst, Quantitat Genet, Brisbane, Qld 4029, Australia.
   [Liu, Tian] Max Planck Inst Human Dev, Lifespan Psychol, D-14195 Berlin, Germany.
   [Mangino, Massimo; Quaye, Lydia; Venturini, Cristina; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Mangino, Massimo; Venturini, Cristina] Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 7EH, England.
   [Mihailov, Evelin; Pervjakova, Natalia; Magi, Reedik; Milani, Lili; Metspalu, Andres; Perola, Markus; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
   [van der Most, Peter J.; Alizadeh, Behrooz Z.; Vonk, Judith M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
   [Oldmeadow, Christopher; Holliday, Elizabeth G.; Attia, John R.] Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW 2305, Australia.
   [Oldmeadow, Christopher; Holliday, Elizabeth G.; Scott, Rodney J.] Univ Newcastle, Fac Hlth & Med, Newcastle, NSW 2300, Australia.
   [Payton, Antony; Ollier, William E. R.; Attia, John R.] Univ Manchester, Inst Populat Hlth, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England.
   [Payton, Antony] Univ Manchester, Sch Psychol Sci, Human Commun & Deafness, Manchester M13 9PL, Lancs, England.
   [Pervjakova, Natalia; Eklund, Niina; Koskinen, Seppo; Maki-Opas, Tomi; Salomaa, Veikko; Kaprio, Jaakko; Perola, Markus] THL Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland.
   [Peyrot, Wouter J.; Milaneschi, Yusplitri; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, Psychiat, NL-1081 HL Amsterdam, Netherlands.
   [Peyrot, Wouter J.; Milaneschi, Yusplitri; Penninx, Brenda W. J. H.] GGZ inGeest, NL-1081 HL Amsterdam, Netherlands.
   [Qian, Yong; Ding, Jun; Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
   [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20521, Finland.
   [Rueedi, Rico; Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Rueedi, Rico; Kutalik, Zoltan] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Salvi, Erika; Cusi, Daniele] Univ Milan, Dept Hlth Sci, I-20142 Milan, Italy.
   [Schmidt, Brge; Eisele, Lewin; Jockel, Karl-Heinz] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany.
   [Schraut, Katharina E.; Campbell, Harry; Joshi, Peter K.; Rudan, Igor; Polasek, Ozren; Wilson, James F.] Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Smith, Albert V.] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
   [Smith, Albert V.; Gudnason, Vilmundur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [St Pourcain, Beate; Evans, David M.; McMahon, George; Paternoster, Lavinia; Ring, Susan M.; Sorensen, Thorkild I. A.; Timpson, Nicholas J.; Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
   [St Pourcain, Beate; Bonnelykke, Klaus] Univ Bristol, Sch Oral & Dent Sci, Bristol BS1 2LY, Avon, England.
   [Teumer, Alexander; Baumeister, Sebastian E.; Volzke, Henry; Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
   [Verweij, Niek; Berger, Klaus; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
   [Wellmann, Juergen] Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany.
   [Westra, Harm-Jan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.
   [Westra, Harm-Jan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol,Dept Med, Boston, MA 02115 USA.
   [Westra, Harm-Jan] Partners Ctr Personalized Genet Med, Boston, MA 02115 USA.
   [Yang, Jingyun; Boyle, Patricia A.; Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
   [Yang, Jingyun; Vaccargiu, Simona; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
   [Zhao, Wei; Smith, Jennifer A.; Ware, Erin B.; Kardia, Sharon L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Alizadeh, Behrooz Z.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9713 GZ Groningen, Netherlands.
   [Baumeister, Sebastian E.] Univ Regensburg, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
   [Biino, Ginevra] Natl Res Council Italy, Inst Mol Genet, I-27100 Pavia, Italy.
   [Boyle, Patricia A.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA.
   [Cappuccio, Francesco P.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
   [Davies, Gail; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [De Neve, Jan-Emmanuel] Univ Oxford, Said Business Sch, Oxford OX1 1HP, England.
   [Deloukas, Panos; Kanoni, Stavroula] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.
   [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
   [Demuth, Ilja; Steinhagen-Thiessen, Elisabeth] Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13347 Berlin, Germany.
   [Demuth, Ilja] Charite, Inst Med & Human Genet, D-13353 Berlin, Germany.
   [Eibich, Peter; Kroh, Martin] DIW Berlin, German Socioecon Panel Study, D-10117 Berlin, Germany.
   [Eibich, Peter] Univ Oxford, Nuffield Dept Populat Hlth, Hlth Econ Res Ctr, Oxford OX3 7LF, England.
   [Evans, David M.; Yang, Jian; Visscher, Peter M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia.
   [Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48109 USA.
   [Feitosa, Mary F.; Kraja, Aldi T.; Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63018 USA.
   [Forstner, Andreas J.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
   [Forstner, Andreas J.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
   [Halldorsson, Bjarni V.] Reykjavik Univ, Sch Sci & Engn, Inst Biomed & Neural Engn, IS-101 Reykjavik, Iceland.
   [Harris, Tamara B.] NIA, Lab Epidemiol, Demog, NIH, Bethesda, MD 20892 USA.
   [Heath, Andrew C.; Madden, Pamela A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Hocking, Lynne J.] Univ Aberdeen, Div Appl Hlth Sci, Aberdeen AB25 2ZD, Scotland.
   [Homuth, Georg; Volker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany.
   [Horan, Michael A.] Univ Manchester, Manchester Med Sch, Manchester M13 9PT, Lancs, England.
   [de Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA.
   [de Jager, Philip L.] Brigham & Womens Hosp, Dept Psychiat, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA.
   [de Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Jugessur, Astanand; Myhre, Ronny; Jacobsson, Bo] Norwegian Inst Publ Hlth, Dept Genes & Environm, N-0403 Oslo, Norway.
   [Kaakinen, Marika A.] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London W12 0NN, England.
   [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
   [Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland.
   [Kolcic, Ivana] Univ Split, Sch Med, Publ Hlth, Split 21000, Croatia.
   [Kutalik, Zoltan] Lausanne Univ Hosp CHUV, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.
   [Launer, Lenore J.] NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA.
   [Lebreton, Mael P.] Univ Amsterdam, Amsterdam Brain & Cognit Ctr, NL-1018 XA Amsterdam, Netherlands.
   [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Lichtner, Peter; Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Marioni, Riccardo E.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Marques-Vidal, Pedro; Vollenweider, Peter] Lausanne Univ Hosp CHUV, Dept Internal Med, Internal Med, CH-1011 Lausanne, Switzerland.
   [Meddens, Gerardus A.] Tema BV, NL-2131 HE Hoofddorp, Netherlands.
   [Montgomery, Grant W.; Nyholt, Dale R.] QIMR Berghofer Med Res Inst, Mol Epidemiol, Brisbane, Qld 4029, Australia.
   [Nyholt, Dale R.] Queensland Inst Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia.
   [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Palotie, Aarno] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
   [Sarin, Antti-Pekka; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland.
   [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   [Robino, Antonietta; Ulivi, Sheila; Gasparini, Paolo] Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Med Genet, I-34100 Trieste, Italy.
   [Rostapshova, Olga; Vozzi, Diego] Social Impact, Arlington, VA 22201 USA.
   [Rustichini, Aldo] Univ Minnesota Twin Cities, Dept Econ, Minneapolis, MN 55455 USA.
   [Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL 60201 USA.
   [Sanders, Alan R.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
   [Sarin, Antti-Pekka] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki 00300, Finland.
   [Schmidt, Helena] Gen Hosp, Ctr Mol Med, Inst Mol Biol & Biochem, Res Unit Genet Epidemiol, A-8010 Graz, Austria.
   [Schmidt, Helena] Med Univ, A-8010 Graz, Graz, Austria.
   [Scott, Rodney J.] Hunter Med Res Inst, Informat Based Med Stream, New Lambton, NSW 2305, Australia.
   [Smith, Blair H.] Univ Dundee, Res Inst, Dundee DD1 9SY, Scotland.
   [Staessen, Jan A.] Univ Leuven, Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium.
   [Staessen, Jan A.] Maastricht Univ, R&D VitaK Grp, NL-6229 EV Maastricht, Netherlands.
   [Strauch, Konstantin] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
   [Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.
   [Terracciano, Antonio] Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA.
   [Tobin, Martin D.] Univ Leicester, Dept Hlth Sci & Genet, Leicester LE1 7RH, Leics, England.
   [van Rooij, Frank J. A.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [Ware, Erin B.] Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI 48104 USA.
   [Bertram, Lars] Univ Lubeck, Inst Neurogenet & Integrat & Expt Genom, Platform Genome Analyt, D-23562 Lubeck, Germany.
   [Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Neuroepidemiol & Ageing Res Unit, Sch Publ Hlth, Fac Med, London SW7 2AZ, England.
   [Bultmann, Ute] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci Community & Occupat Med, NL-9713 AV Groningen, Netherlands.
   [Chabris, Christopher F.] Union Coll, Dept Psychol, Schenectady, NY 12308 USA.
   [Cucca, Francesco] Cittadella Univ Monserrato, CNR, IRGB, I-9042 Cagliari, Italy.
   [Cusi, Daniele] Italian Natl Res Council, Inst Biomed Technol, I-20090 Milan, Italy.
   [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland.
   [Franke, Barbara] Donders Ctr Neurosci, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
   [Franke, Barbara] Donders Ctr Neurosci, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands.
   [Franke, Lude; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
   [Gasparini, Paolo] Sidra, Expt Genet Div, Doha 26999, Qatar.
   [Grabe, Hans-Jorgen] Univ Med Greifswald, Dept Psychiat & Psychotherapy, D-17475 Greifswald, Germany.
   [Grabe, Hans-Jorgen] HELIOS Hosp Stralsund, Dept Psychiat & Psychotherapy, D-18437 Stralsund, Germany.
   [Groenen, Patrick J. F.] Erasmus Univ, Erasmus Sch Econ, Econometr Inst, NL-3062 PA Rotterdam, Netherlands.
   [van der Harst, Pim] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-1105 AZ Utrecht, Netherlands.
   [Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, Generat Scotland, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Hyppnen, Elina] Univ S Australia, Sch Hlth Sci, Ctr Populat Hlth Res, Adelaide, SA 5000, Australia.
   [Hyppnen, Elina] Univ S Australia, Sansom Inst, Adelaide, SA 5000, Australia.
   [Hyppnen, Elina] South Australian Hlth & Med Res Inst, Adelaide, SA 5000, Australia.
   [Hyppnen, Elina; Power, Christine] UCL Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England.
   [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Fac Med, Ctr Life Course Epidemiol, Oulu 90014, Finland.
   [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu 90029, Finland.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland.
   [Lehtimaki, Terho] Fimlab Labs, Tampere 33520, Finland.
   [Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
   [Lehrer, Steven F.] NYU Shanghai, Econ, Pudong 200122, Peoples R China.
   [Lehrer, Steven F.] Queens Univ, Policy Studies, Kingston, ON K7L 3N6, Canada.
   [Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld 4029, Australia.
   [Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
   [Pendleton, Neil] Salford Royal Hosp, Inst Brain Behav & Mental Hlth, Ctr Clin & Cognit Neurosci, Manchester M6 8HD, Lancs, England.
   [Pendleton, Neil] Univ Manchester, Manchester Inst Collaborat Res Ageing, Manchester M13 9PL, Lancs, England.
   [Polasek, Ozren] Univ Split, Fac Med, Split 21000, Croatia.
   [Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands.
   [Sorensen, Thorkild I. A.] Bispebjerg Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark.
   [Sorensen, Thorkild I. A.] Frederiksberg Univ Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark.
   [Thurik, A. Roy] Montpellier Business Sch, F-34080 Montpellier, France.
   [Thurik, A. Roy] Panteia, NL-2715 CA Zoetermeer, Netherlands.
   [Tiemeier, Henning] Erasmus MC, Dept Psychiat, NL-3015 GE Rotterdam, Netherlands.
   [Tiemeier, Henning] Erasmus MC, Dept Child & Adolescent Psychiat, NL-3015 GE Rotterdam, Netherlands.
   [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [Conley, Dalton C.] NYU, Dept Sociol, 550 1St Ave, New York, NY 10012 USA.
   [Conley, Dalton C.] NYU, Sch Med, 550 1St Ave, New York, NY 10016 USA.
   [Meyer, Michelle N.] Icahn Sch Med Mt Sinai, Grad Coll, Bioeth Program, Schenectady, NY 12308 USA.
   [Johannesson, Magnus] Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden.
   [Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Cesarini, David] Res Inst Ind Econ, S-10215 Stockholm, Sweden.
C3 Erasmus University Rotterdam; Erasmus University Rotterdam - Excl Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam - Excl Erasmus MC; Erasmus University Rotterdam; Harvard University; University of Southern California; University of Minnesota System; University of Minnesota Twin Cities; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Copenhagen; Novo Nordisk Foundation; Statens Serum Institut; University of Queensland; Icelandic Heart Association; University of Iceland; Vrije Universiteit Amsterdam; University of Amsterdam; Uppsala University; New York University; Technical University of Denmark; Vrije Universiteit Amsterdam; University of Copenhagen; Steno Diabetes Center; University of Gothenburg; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Erasmus University Rotterdam; Erasmus MC; Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); University of Illinois System; University of Illinois Urbana-Champaign; 23andMe, Inc.; Radboud University Nijmegen; University of Trieste; University of Helsinki; University of Leicester; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University of Edinburgh; University of Edinburgh; Medical University of Graz; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; University of Edinburgh; University of Helsinki; Harokopio University Athens; Karolinska Institutet; Folkhalsan Research Center; Radboud University Nijmegen; QIMR Berghofer Medical Research Institute; Max Planck Society; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; University of Tartu; University of Groningen; University of Newcastle; Hunter Medical Research Institute; University of Newcastle; University of Manchester; University of Manchester; Finland National Institute for Health & Welfare; Vrije Universiteit Amsterdam; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Turku; University of Lausanne; Swiss Institute of Bioinformatics; University of Milan; University of Duisburg Essen; University of Edinburgh; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Icelandic Heart Association; University of Iceland; University of Bristol; University of Bristol; Universitat Greifswald; Greifswald Medical School; University of Groningen; University of Munster; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Rush University; Rush University; University of Michigan System; University of Michigan; University of Groningen; University of Regensburg; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR); Rush University; University of Warwick; University of Edinburgh; University of Oxford; University of London; Queen Mary University London; King Abdulaziz University; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Leibniz Association; DIW Berlin - Deutsches Institut fur Wirtschaftsforschung; University of Oxford; University of Queensland; University of Michigan System; University of Michigan; Washington University (WUSTL); University of Bonn; University of Bonn; Reykjavik University; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Washington University (WUSTL); University of Aberdeen; Universitat Greifswald; Greifswald Medical School; University of Manchester; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Norwegian Institute of Public Health (NIPH); Imperial College London; Tampere University; Tampere University Hospital; Tampere University; University of Split; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Amsterdam; Stanford University; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Edinburgh; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); QIMR Berghofer Medical Research Institute; Queensland University of Technology (QUT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Helsinki; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; IRCCS Burlo Garofolo; University of Minnesota System; University of Minnesota Twin Cities; NorthShore University Health System; University of Chicago; Finland National Institute for Health & Welfare; Medical University of Graz; Hunter Medical Research Institute; University of Newcastle; University of Dundee; KU Leuven; Maastricht University; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; State University System of Florida; Florida State University; University of Leicester; Erasmus University Rotterdam; Erasmus MC; University of Michigan System; University of Michigan; University of Lubeck; Imperial College London; University of Groningen; Union College; Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); Consiglio Nazionale delle Ricerche (CNR); Istituto di Tecnologie Biomediche (ITB-CNR); University of Helsinki; University of Groningen; Sidra Medical & Research Center; Universitat Greifswald; Greifswald Medical School; Erasmus University Rotterdam - Excl Erasmus MC; Erasmus University Rotterdam; University of Edinburgh; Adelaide University; University of South Australia; Adelaide University; University of South Australia; South Australian Health & Medical Research Institute (SAHMRI); University of London; University College London; Imperial College London; University of Oulu; University of Oulu; University of Oulu; Tampere University; New York University; NYU Shanghai; Queens University - Canada; QIMR Berghofer Medical Research Institute; University of Tartu; Salford Royal NHS Foundation Trust; Salford Royal Hospital; University of Manchester; University of Split; Vrije Universiteit Amsterdam; Amsterdam University Medical Center; University of Copenhagen; Bispebjerg Hospital; Copenhagen University Hospital; Montpellier Business School; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; New York University; New York University; Icahn School of Medicine at Mount Sinai; Stockholm School of Economics; Harvard University; Harvard Medical School; Research Institute of Industrial Economics (IFN)
RP Koellinger, PD (corresponding author), Erasmus Univ, Inst Behav & Biol, NL-3062 PA Rotterdam, Netherlands.; Benjamin, DJ (corresponding author), Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA 90089 USA.; Visscher, PM (corresponding author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.; Koellinger, PD (corresponding author), Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands.; Koellinger, PD (corresponding author), Univ Amsterdam, Amsterdam Business Sch, NL-1018 TV Amsterdam, Netherlands.; Cesarini, D (corresponding author), NYU, Dept Econ, New York, NY 10003 USA.; Visscher, PM (corresponding author), Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia.; Cesarini, D (corresponding author), Res Inst Ind Econ, S-10215 Stockholm, Sweden.
EM peter.visscher@uq.edu.au; p.d.koellinger@vu.nl; dac12@nyu.edu; daniel.benjamin@gmail.com
FU Social Science Genetic Association Consortium (SSGAC); Ragnar Soderberg Foundation [E9/11]; Swedish Research Council [421-2013-1061]; Jan Wallander and Tom Hedelius Foundation; ERC [647648 EdGe]; Pershing Square Fund of the Foundations of Human Behavior; NIA/NIH [P01-AG005842, P01-AG005842-20S2, P30-AG012810, T32-AG000186-23, R01-AG042568]; National Institute on Aging [ZIAAG000675, R01AG042568, P01AG005842, R01AG017917, U01AG009740, T32AG000186, P30AG012810, ZIAAG000693] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/F022441/1] Funding Source: researchfish; Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish; Economic and Social Research Council [ES/M010341/1] Funding Source: researchfish; Lundbeck Foundation [R190-2014-3904, R163-2013-16235] Funding Source: researchfish; Medical Research Council [1201677, MR/N01104X/1, MC_UU_12013/4, MC_qA137853, MC_UU_12013/1, MC_UU_12013/3, G1001799, MR/J012165/1, MR/K026992/1, MC_PC_U127561128] Funding Source: researchfish; National Institute for Health Research [NF-SI-0514-10027] Funding Source: researchfish; NNF Center for Basic Metabolic Research [Pers Group] Funding Source: researchfish; BBSRC [BB/F022441/1] Funding Source: UKRI; ESRC [ES/M010341/1] Funding Source: UKRI; MRC [MC_UU_12013/3, G1001799, MC_UU_12013/1, MR/J012165/1, MC_UU_12013/4, MR/N01104X/1, MC_PC_U127561128] Funding Source: UKRI
NR 16
TC 883
Z9 988
U1 4
U2 320
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 539
EP +
DI 10.1038/nature17671
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100042
PM 27225129
DA 2026-03-09
ER

PT J
AU Wells, MF
   Wimmer, RD
   Schmitt, LI
   Feng, GP
   Halassa, MM
AF Wells, Michael F.
   Wimmer, Ralf D.
   Schmitt, L. Ian
   Feng, Guoping
   Halassa, Michael M.
TI Thalamic reticular impairment underlies attention deficit in Ptchd1Y/- mice
SO NATURE
LA English
DT Article
ID intellectual disability; gabaergic neurons; sleep spindles; autism; nucleus; architecture; inhibition; disorders; variants; channels
AB Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in similar to 1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post-natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN-restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention.
C1 [Wells, Michael F.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
   [Wells, Michael F.; Feng, Guoping] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA.
   [Wimmer, Ralf D.; Schmitt, L. Ian; Halassa, Michael M.] NYU, Med Ctr, Neurosci Inst, New York, NY 10016 USA.
   [Wimmer, Ralf D.; Schmitt, L. Ian; Halassa, Michael M.] NYU, Langone Med Ctr, Dept Neurosci & Physiol, 550 1St Ave, New York, NY 10016 USA.
   [Feng, Guoping] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Halassa, Michael M.] NYU, Dept Psychiat, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA.
   [Halassa, Michael M.] NYU, Ctr Neural Sci, New York, NY USA.
C3 Duke University; Massachusetts Institute of Technology (MIT); New York University; NYU Langone Medical Center; New York University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; NYU Langone Medical Center; New York University; New York University
RP Feng, GP (corresponding author), MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA.; Feng, GP (corresponding author), Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
EM fengg@mit.edu
FU Simons Foundation Autism Research Initiative (SFARI) [ID: 307913]; NIH (NIH/NIMH) [R01MH097104]; NIH [R01MH107680]; Poitras Center for Affective Disorders Research; Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard; Brain and Behavior Foundation; Sloan Foundation; Klingenstein Foundation; Feldstein Foundation; NIH Ruth L. Kirschstein National Research Service Award [FMH098641A]; Swiss National Science Foundation
NR 50
TC 141
Z9 178
U1 2
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 58
EP +
DI 10.1038/nature17427
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500032
PM 27007844
DA 2026-03-09
ER

PT J
AU Han, CZ
   Juncadella, IJ
   Kinchen, JM
   Buckley, MW
   Klibanov, AL
   Dryden, K
   Onengut-Gumuscu, S
   Erdbrügger, U
   Turner, SD
   Shim, YM
   Tung, KS
   Ravichandran, KS
AF Han, Claudia Z.
   Juncadella, Ignacio J.
   Kinchen, Jason M.
   Buckley, Monica W.
   Klibanov, Alexander L.
   Dryden, Kelly
   Onengut-Gumuscu, Suna
   Erdbruegger, Uta
   Turner, Stephen D.
   Shim, Yun M.
   Tung, Kenneth S.
   Ravichandran, Kodi S.
TI Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation
SO NATURE
LA English
DT Article
ID epithelial-cells; i receptor; growth; requirement; engulfment; expression; inhibitor; potent; vivo
AB Professional phagocytes (such as macrophages(1)) and nonprofessional phagocytes(2-8) (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis(9). Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known(10). Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1-and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.
C1 [Han, Claudia Z.; Juncadella, Ignacio J.; Kinchen, Jason M.; Buckley, Monica W.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA.
   [Han, Claudia Z.; Buckley, Monica W.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA.
   [Klibanov, Alexander L.; Shim, Yun M.; Tung, Kenneth S.] Univ Virginia, Dept Med, Charlottesville, VA 22903 USA.
   [Klibanov, Alexander L.] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22903 USA.
   [Dryden, Kelly] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA.
   [Onengut-Gumuscu, Suna] Univ Virginia, Div Endocrinol & Metab, Dept Med, Charlottesville, VA 22903 USA.
   [Onengut-Gumuscu, Suna] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22903 USA.
   [Erdbruegger, Uta] Univ Virginia, Dept Med, Div Nephrol, Charlottesville, VA 22903 USA.
   [Turner, Stephen D.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22903 USA.
   [Tung, Kenneth S.] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22903 USA.; Ravichandran, KS (corresponding author), Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22903 USA.
EM ravi@virginia.edu
FU NIGMS [GM064709]; NIMH [MH096484]; NHLBI [P01HL120840, HL132287, HL091127]; Center for Cell Signalling at the University of Virginia; NIH [T32 GM008136, T32 AI007496, T32 GM007267];  [K23 HL12610]; National Heart Lung and Blood Institute [P01HL120840] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007496] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007267] Funding Source: NIH RePORTER
NR 41
TC 184
Z9 212
U1 1
U2 90
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 570
EP +
DI 10.1038/nature20141
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600045
PM 27820945
DA 2026-03-09
ER

PT J
AU Meyerson, JR
   Chittori, S
   Merk, A
   Rao, P
   Han, TH
   Serpe, M
   Mayer, ML
   Subramaniam, S
AF Meyerson, Joel R.
   Chittori, Sagar
   Merk, Alan
   Rao, Prashant
   Han, Tae Hee
   Serpe, Mihaela
   Mayer, Mark L.
   Subramaniam, Sriram
TI Structural basis of kainate subtype glutamate receptor desensitization
SO NATURE
LA English
DT Article
ID ligand-binding domain; crystal-structures; ampa; activation; mutations; complexes; dynamics; system; image
AB Glutamate receptors are ligand-gated tetrameric ion channels that mediate synaptic transmission in the central nervous system. They are instrumental in vertebrate cognition and their dysfunction underlies diverse diseases(1,2). In both the resting and desensitized states of AMPA and kainate receptor subtypes, the ion channels are closed, whereas the ligand-binding domains, which are physically coupled to the channels, adopt markedly different conformations(3-6). Without an atomic model for the desensitized state, it is not possible to address a central problem in receptor gating: how the resting and desensitized receptor states both display closed ion channels, although they have major differences in the quaternary structure of the ligand-binding domain. Here, by determining the structure of the kainate receptor GluK2 subtype in its desensitized state by cryo-electron microscopy (cryo-EM) at 3.8 angstrom resolution, we show that desensitization is characterized by the establishment of a ringlike structure in the ligand-binding domain layer of the receptor. Formation of this 'desensitization ring' is mediated by staggered helix contacts between adjacent subunits, which leads to a pseudo-four-fold symmetric arrangement of the ligand-binding domains, illustrating subtle changes in symmetry that are important for the gating mechanism. Disruption of the desensitization ring is probably the key switch that enables restoration of the receptor to its resting state, thereby completing the gating cycle.
C1 [Meyerson, Joel R.; Chittori, Sagar; Merk, Alan; Rao, Prashant; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
   [Chittori, Sagar; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Han, Tae Hee; Serpe, Mihaela] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
   [Meyerson, Joel R.] Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Brandeis University; Howard Hughes Medical Institute
RP Meyerson, JR; Subramaniam, S (corresponding author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.; Mayer, ML (corresponding author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.; Meyerson, JR (corresponding author), Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA.
EM jmeyerson@brandeis.edu; mayerm@mail.nih.gov; ss1@nih.gov
FU NCI; NICHD, NIH; IATAP program at NIH; NIH-FEI Living Laboratory for Structural Biology; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD008914] Funding Source: NIH RePORTER
NR 40
TC 82
Z9 94
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 567
EP +
DI 10.1038/nature19352
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900060
PM 27580033
DA 2026-03-09
ER

PT J
AU Bader, E
   Migliorini, A
   Gegg, M
   Moruzzi, N
   Gerdes, J
   Roscioni, SS
   Bakhti, M
   Brandl, E
   Irmler, M
   Beckers, J
   Aichler, M
   Feuchtinger, A
   Leitzinger, C
   Zischka, H
   Wang-Sattler, R
   Jastroch, M
   Tschöp, M
   Machicao, F
   Staiger, H
   Häring, HU
   Chmelova, H
   Chouinard, JA
   Oskolkov, N
   Korsgren, O
   Speier, S
   Lickert, H
AF Bader, Erik
   Migliorini, Adriana
   Gegg, Moritz
   Moruzzi, Noah
   Gerdes, Jantje
   Roscioni, Sara S.
   Bakhti, Mostafa
   Brandl, Elisabeth
   Irmler, Martin
   Beckers, Johannes
   Aichler, Michaela
   Feuchtinger, Annette
   Leitzinger, Christin
   Zischka, Hans
   Wang-Sattler, Rui
   Jastroch, Martin
   Tschoep, Matthias
   Machicao, Fausto
   Staiger, Harald
   Haering, Hans-Ulrich
   Chmelova, Helena
   Chouinard, Julie A.
   Oskolkov, Nikolay
   Korsgren, Olle
   Speier, Stephan
   Lickert, Heiko
TI Identification of proliferative and mature β-cells in the islets of Langerhans
SO NATURE
LA English
DT Article
ID insulin-secretion; pancreatic-islets; polarity; expression; mouse; line; dedifferentiation; differentiation; communication; heterogeneity
AB Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of beta-cells. Pancreatic beta-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential(1-5); understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene(6), acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature beta-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs(7-9). We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger beta-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for beta-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional beta-cell heterogeneity and induce beta-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional beta-cell mass in diabetic patients.
C1 [Bader, Erik; Migliorini, Adriana; Gegg, Moritz; Moruzzi, Noah; Gerdes, Jantje; Roscioni, Sara S.; Bakhti, Mostafa; Brandl, Elisabeth; Lickert, Heiko] Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.
   [Bader, Erik; Migliorini, Adriana; Gegg, Moritz; Lickert, Heiko] Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
   [Bader, Erik; Wang-Sattler, Rui] Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
   [Moruzzi, Noah] Karolinska Univ Hosp, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.
   [Irmler, Martin; Beckers, Johannes; Jastroch, Martin; Tschoep, Matthias; Machicao, Fausto; Staiger, Harald; Haering, Hans-Ulrich; Chmelova, Helena; Chouinard, Julie A.; Speier, Stephan; Lickert, Heiko] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.
   [Irmler, Martin; Beckers, Johannes] Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.
   [Beckers, Johannes; Lickert, Heiko] Tech Univ Munich, Ismaninger Str 22, D-81675 Munich, Germany.
   [Aichler, Michaela; Feuchtinger, Annette] Helmholtz Zentrum Munchen, Res Unit Analyt Pathol, D-85764 Neuherberg, Germany.
   [Leitzinger, Christin; Zischka, Hans] Helmholtz Zentrum Munchen, Inst Mol Toxicol & Pharmacol, D-85764 Neuherberg, Germany.
   [Jastroch, Martin; Tschoep, Matthias] Helmholtz Zentrum Munchen, Inst Diabet & Obes, D-85764 Neuherberg, Germany.
   [Machicao, Fausto; Staiger, Harald; Haering, Hans-Ulrich] Univ Tubingen, Helmholtz Zentrum Munchen, Inst Diabet Res & Metab Dis, D-72076 Tubingen, Germany.
   [Staiger, Harald; Haering, Hans-Ulrich] Univ Tubingen, Div Endocrinol Diabetol Vasc Dis Nephrol & Clin C, Dept Internal Med, D-72076 Tubingen, Germany.
   [Chmelova, Helena; Chouinard, Julie A.; Speier, Stephan] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Zentrum Munchen, PLID, D-01307 Dresden, Germany.
   [Chmelova, Helena; Chouinard, Julie A.; Speier, Stephan] Tech Univ Dresden, Fac Med, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany.
   [Oskolkov, Nikolay] Lund Univ, Ctr Diabet, Diabet & Endocrinol, S-20502 Malmo, Sweden.
   [Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, S-75105 Uppsala, Sweden.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Karolinska Institutet; Karolinska University Hospital; German Center for Diabetes Research (DZD); Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Eberhard Karls University of Tubingen; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Eberhard Karls University of Tubingen; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technische Universitat Dresden; Carl Gustav Carus University Hospital; Technische Universitat Dresden; Lund University; Uppsala University
RP Lickert, H (corresponding author), Helmholtz Zentrum Munchen, Inst Diabet & Regenerat Res, D-85764 Neuherberg, Germany.; Lickert, H (corresponding author), Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.; Lickert, H (corresponding author), German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.; Lickert, H (corresponding author), Tech Univ Munich, Ismaninger Str 22, D-81675 Munich, Germany.
EM heiko.lickert@helmholtz-muenchen.de
FU Strategic Research Grant from the Swedish Research Council [2009-1039]; Helmholtz post-doctoral fellowship program; Emmy-Noether Fellowship; European Union (ERC starting grant Ciliary Disease); HumEn project from the European Union [602587]; Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases, through the Initiative and Networking Fund of the Helmholtz Association; Helmholtz Society; Helmholtz Portfolio Theme 'Metabolic Dysfunction and Common Disease; German Research Foundation; German Center for Diabetes Research (DZD e.V.); Emmy-Noether Program; Center for Regenerative Therapies Dresden-DFG Research Center for Regenerative Therapies Dresden; Cluster of Excellence (CRTD); DFG-Collaborative Research Center/Transregio [127]; German Ministry for Education and Research; Novo Nordisk Fonden [NNF14OC0010935] Funding Source: researchfish
NR 44
TC 276
Z9 318
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 430
EP +
DI 10.1038/nature18624
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200042
PM 27398620
DA 2026-03-09
ER

PT J
AU O'Donoghue, J
   Moore, L
   Stallard, TS
   Melin, H
AF O'Donoghue, J.
   Moore, L.
   Stallard, T. S.
   Melin, H.
TI Heating of Jupiter's upper atmosphere above the Great Red Spot
SO NATURE
LA English
DT Article
ID giant planet ionospheres; jovian thermosphere; acoustic-waves; gravity-waves; h-3(+); magnetosphere; temperature; dissipation; telescope; dynamics
AB The temperatures of giant-planet upper atmospheres at mid-to low latitudes are measured to be hundreds of degrees warmer than simulations based on solar heating alone can explain(1-4). Modelling studies that focus on additional sources of heating have been unable to resolve this major discrepancy. Equatorward transport of energy from the hot auroral regions was expected to heat the low latitudes, but models have demonstrated that auroral energy is trapped at high latitudes, a consequence of the strong Coriolis forces on rapidly rotating planets(3-5). Wave heating, driven from below, represents another potential source of upper-atmospheric heating, though initial calculations have proven inconclusive for Jupiter, largely owing to a lack of observational constraints on wave parameters(6,7). Here we report that the upper atmosphere above Jupiter's Great Red Spot-the largest storm in the Solar System-is hundreds of degrees hotter than anywhere else on the planet. This hotspot, by process of elimination, must be heated from below, and this detection is therefore strong evidence for coupling between Jupiter's lower and upper atmospheres, probably the result of upwardly propagating acoustic or gravity waves.
C1 [O'Donoghue, J.; Moore, L.] Boston Univ, Ctr Space Phys, Boston, MA 02215 USA.
   [Stallard, T. S.; Melin, H.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
C3 Boston University; University of Leicester
RP O'Donoghue, J (corresponding author), Boston Univ, Ctr Space Phys, Boston, MA 02215 USA.
EM jameso@bu.edu
FU National Aeronautics and Space Administration (NASA) [NNH14CK55B]; NASA [9500303356]; UK Science and Technology Facilities Council (STFC) [ST/N000749/1]; Royal Astronomical Society; STFC [ST/G002223/1, ST/L001306/1, ST/K001000/1, ST/N001524/1, ST/N000749/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/N001524/1, ST/K001000/1, ST/L001306/1, ST/G002223/1, ST/N000749/1] Funding Source: researchfish
NR 28
TC 33
Z9 42
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 190
EP +
DI 10.1038/nature18940
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100031
PM 27462811
DA 2026-03-09
ER

PT J
AU Tovote, P
   Esposito, MS
   Botta, P
   Haudun, FC
   Fadok, JP
   Markovic, M
   Wolff, SBE
   Ramakrishnan, C
   Fenno, L
   Deisseroth, K
   Herry, C
   Arber, S
   Lüthi, A
AF Tovote, Philip
   Esposito, Maria Soledad
   Botta, Paolo
   Haudun, Fabrice C.
   Fadok, Jonathan P.
   Markovic, Milica
   Wolff, Steffen B. E.
   Ramakrishnan, Charu
   Fenno, Lief
   Deisseroth, Karl
   Herry, Cyril
   Arber, Silvia
   Luthi, Andreas
TI Midbrain circuits for defensive behaviour
SO NATURE
LA English
DT Article
ID ventrolateral periaqueductal gray; contextual conditioned fear; amino-acid microinjection; neuronal organization; in-vivo; anxiety; rat; amygdala; nucleus; projections
AB Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.
C1 [Tovote, Philip; Esposito, Maria Soledad; Botta, Paolo; Fadok, Jonathan P.; Markovic, Milica; Wolff, Steffen B. E.; Arber, Silvia; Luthi, Andreas] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
   [Esposito, Maria Soledad; Arber, Silvia] Univ Basel, Dept Cell Biol, Biozentrum, CH-4056 Basel, Switzerland.
   [Haudun, Fabrice C.; Herry, Cyril] INSERM, Neuroctr Magendie, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.
   [Ramakrishnan, Charu; Fenno, Lief; Deisseroth, Karl] Stanford Univ, 318 Campus Dr West,Clark Ctr W080, Stanford, CA 94305 USA.
   [Botta, Paolo] Champalimaud Ctr Unknown, Ave Brasilia, P-1400038 Lisbon, Portugal.
   [Wolff, Steffen B. E.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm); Stanford University; Fundacao Champalimaud; Harvard University
RP Tovote, P; Lüthi, A (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM philip.tovote@fmi.ch; andreas.luthi@fmi.ch
FU Novartis Research Foundation; National Center of Competences in Research; Swiss National Science Foundation; European Research Council; Kanton Basel-Stadt; NARSAD Young Investigator Grants by the Brain and Behavior Foundation; Human Frontier Science Program; Synapsis Foundation; European Research Council (ERC) under the European Union [281168]; Fondation pour la Recherche Medicale; European Research Council (ERC) [281168] Funding Source: European Research Council (ERC)
NR 50
TC 528
Z9 638
U1 3
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 206
EP +
DI 10.1038/nature17996
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100032
PM 27279213
DA 2026-03-09
ER

PT J
AU Landig, R
   Hruby, L
   Dogra, N
   Landini, M
   Mottl, R
   Donner, T
   Esslinger, T
AF Landig, Renate
   Hruby, Lorenz
   Dogra, Nishant
   Landini, Manuele
   Mottl, Rafael
   Donner, Tobias
   Esslinger, Tilman
TI Quantum phases from competing short- and long-range interactions in an optical lattice
SO NATURE
LA English
DT Article
ID polar-molecules; ultracold atoms; mott insulator; cold atoms; gas; transition; superfluid; cavity; bosons
AB Insights into complex phenomena in quantum matter can be gained from simulation experiments with ultracold atoms, especially in cases where theoretical characterization is challenging. However, these experiments are mostly limited to short-range collisional interactions; recently observed perturbative effects of long-range interactions were too weak to reach new quantum phases(1,2). Here we experimentally realize a bosonic lattice model with competing short-and long-range interactions, and observe the appearance of four distinct quantum phases-a superfluid, a supersolid, a Mott insulator and a charge density wave. Our system is based on an atomic quantum gas trapped in an optical lattice inside a high-finesse optical cavity. The strength of the short-range on-site interactions is controlled by means of the optical lattice depth. The long (infinite)-range interaction potential is mediated by a vacuum mode of the cavity(3,4) and is independently controlled by tuning the cavity resonance. When probing the phase transition between the Mott insulator and the charge density wave in real time, we observed a behaviour characteristic of a first-order phase transition. Our measurements have accessed a regime for quantum simulation of many-body systems where the physics is determined by the intricate competition between two different types of interactions and the zero point motion of the particles.
C1 [Landig, Renate; Hruby, Lorenz; Dogra, Nishant; Landini, Manuele; Mottl, Rafael; Donner, Tobias; Esslinger, Tilman] Swiss Fed Inst Technol, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Donner, T (corresponding author), Swiss Fed Inst Technol, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM donner@phys.ethz.ch
FU Synthetic Quantum Many-Body Systems (European Research Council); EU Collaborative Project TherMiQ [618074]; SBFI; SNF
NR 34
TC 358
Z9 392
U1 2
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 476
EP +
DI 10.1038/nature17409
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900041
PM 27064902
DA 2026-03-09
ER

PT J
AU Bouvier, A
   Boyet, M
AF Bouvier, A.
   Boyet, M.
TI Primitive Solar System materials and Earth share a common initial 142Nd abundance
SO NATURE
LA English
DT Article
ID sm-146 half-life; isotopic heterogeneity; chondritic composition; terrestrial planets; allende meteorite; bulk composition; neodymium; samarium; nebula; moon
AB The early evolution of planetesimals and planets can be constrained using variations in the abundance of neodymium-142 (Nd-142), which arise from the initial distribution of Nd-142 within the protoplanetary disk and the radioactive decay of the short-lived samarium-146 isotope (Sm-146)(1,2). The apparent offset in Nd-142 abundance found previously between chondritic meteorites and Earth(1,2) has been interpreted either as a possible consequence of nucleosynthetic variations within the protoplanetary disk(2-4) or as a function of the differentiation of Earth very early in its history(5). Here we report high-precision Sm and Nd stable and radiogenic isotopic compositions of four calcium-aluminium-rich refractory inclusions (CAIs) from three CV-type carbonaceous chondrites, and of three whole-rock samples of unequilibrated enstatite chondrites. The CAIs, which are the first solids formed by condensation from the nebular gas, provide the best constraints for the isotopic evolution of the early Solar System. Using the mineral isochron method for individual CAIs, we find that CAIs without isotopic anomalies in Nd compared to the terrestrial composition share a Sm-146/Sm-144-Nd-142/Nd-144 isotopic evolution with Earth. The average Nd-142/Nd-144 composition for pristine enstatite chondrites that we calculate coincides with that of the accessible silicate layers of Earth. This relationship between CAIs, enstatite chondrites and Earth can only be a result of Earth having inherited the same initial abundance of Nd-142 and chondritic proportions of Sm and Nd. Consequently, Nd-142 isotopic heterogeneities found in other CAIs and among chondrite groups may arise from extrasolar grains that were present in the disk and incorporated in different proportions into these planetary objects. Our finding supports a chondritic Sm/Nd ratio for the bulk silicate Earth and, as a consequence, chondritic abundances for other refractory elements. It also removes the need for a hidden reservoir or for collisional erosion scenarios(5,6) to explain the Nd-142/Nd-144 composition of Earth.
C1 [Bouvier, A.] Univ Western Ontario, Dept Earth Sci, Ctr Planetary Sci & Explorat, London, ON N6A 3K7, Canada.
   [Boyet, M.] Univ Clermont Ferrand, Clermont Univ, Lab Magmas & Volcans, UMR CNRS 6524, Campus Univ Cezeaux,6 Ave Blaise Pascal, F-63178 Aubiere, France.
C3 Western University (University of Western Ontario)
RP Bouvier, A (corresponding author), Univ Western Ontario, Dept Earth Sci, Ctr Planetary Sci & Explorat, London, ON N6A 3K7, Canada.
EM audrey.bouvier@uwo.ca
FU NSF; NASA; National Science Foundation [NSF/EAR 1119135]; France-Canada Research Fund; NSERC Canada; French Government [ANR-10-LABX-0006]; Region Auvergne; European Regional Development Fund; INSU Programme National de Planetologie
NR 44
TC 96
Z9 108
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 399
EP +
DI 10.1038/nature19351
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000053
PM 27629644
DA 2026-03-09
ER

PT J
AU Warren, TK
   Jordan, R
   Lo, MK
   Ray, AS
   Mackman, RL
   Soloveva, V
   Siegel, D
   Perron, M
   Bannister, R
   Hui, HC
   Larson, N
   Strickley, R
   Wells, J
   Stuthman, KS
   Van Tongeren, SA
   Garza, NL
   Donnelly, G
   Shurtleff, AC
   Retterer, CJ
   Gharaibeh, D
   Zamani, R
   Kenny, T
   Eaton, BP
   Grimes, E
   Welch, LS
   Gomba, L
   Wilhelmsen, CL
   Nichols, DK
   Nuss, JE
   Nagle, ER
   Kugelman, JR
   Palacios, G
   Doerffler, E
   Neville, S
   Carra, E
   Clarke, MO
   Zhang, LJ
   Lew, W
   Ross, B
   Wang, Q
   Chun, K
   Wolfe, L
   Babusis, D
   Park, Y
   Stray, KM
   Trancheva, I
   Feng, JY
   Barauskas, O
   Xu, YL
   Wong, P
   Braun, MR
   Flint, M
   McMullan, LK
   Chen, SS
   Fearns, R
   Swaminathan, S
   Mayers, DL
   Spiropoulou, CF
   Lee, WA
   Nichol, ST
   Cihlar, T
   Bavari, S
AF Warren, Travis K.
   Jordan, Robert
   Lo, Michael K.
   Ray, Adrian S.
   Mackman, Richard L.
   Soloveva, Veronica
   Siegel, Dustin
   Perron, Michel
   Bannister, Roy
   Hui, Hon C.
   Larson, Nate
   Strickley, Robert
   Wells, Jay
   Stuthman, Kelly S.
   Van Tongeren, Sean A.
   Garza, Nicole L.
   Donnelly, Ginger
   Shurtleff, Amy C.
   Retterer, Cary J.
   Gharaibeh, Dima
   Zamani, Rouzbeh
   Kenny, Tara
   Eaton, Brett P.
   Grimes, Elizabeth
   Welch, Lisa S.
   Gomba, Laura
   Wilhelmsen, Catherine L.
   Nichols, Donald K.
   Nuss, Jonathan E.
   Nagle, Elyse R.
   Kugelman, Jeffrey R.
   Palacios, Gustavo
   Doerffler, Edward
   Neville, Sean
   Carra, Ernest
   Clarke, Michael O.
   Zhang, Lijun
   Lew, Willard
   Ross, Bruce
   Wang, Queenie
   Chun, Kwon
   Wolfe, Lydia
   Babusis, Darius
   Park, Yeojin
   Stray, Kirsten M.
   Trancheva, Iva
   Feng, Joy Y.
   Barauskas, Ona
   Xu, Yili
   Wong, Pamela
   Braun, Molly R.
   Flint, Mike
   McMullan, Laura K.
   Chen, Shan-Shan
   Fearns, Rachel
   Swaminathan, Swami
   Mayers, Douglas L.
   Spiropoulou, Christina F.
   Lee, William A.
   Nichol, Stuart T.
   Cihlar, Tomas
   Bavari, Sina
TI Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys
SO NATURE
LA English
DT Article
ID infected nonhuman-primates; antiviral activity; t-705 favipiravir; high-throughput; polymerase; inhibitor; model; protection; macaques; promoter
AB The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.
C1 [Warren, Travis K.; Soloveva, Veronica; Wells, Jay; Stuthman, Kelly S.; Van Tongeren, Sean A.; Garza, Nicole L.; Donnelly, Ginger; Shurtleff, Amy C.; Retterer, Cary J.; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P.; Grimes, Elizabeth; Welch, Lisa S.; Gomba, Laura; Wilhelmsen, Catherine L.; Nichols, Donald K.; Nuss, Jonathan E.; Nagle, Elyse R.; Kugelman, Jeffrey R.; Palacios, Gustavo; Mayers, Douglas L.; Bavari, Sina] US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
   [Warren, Travis K.; Soloveva, Veronica; Gomba, Laura; Nuss, Jonathan E.; Bavari, Sina] US Army, Med Res Inst Infect Dis, Therapeut Dev Ctr, Ft Detrick, MD 21702 USA.
   [Jordan, Robert; Ray, Adrian S.; Mackman, Richard L.; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C.; Larson, Nate; Strickley, Robert; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O.; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M.; Trancheva, Iva; Feng, Joy Y.; Barauskas, Ona; Xu, Yili; Wong, Pamela; Chen, Shan-Shan; Swaminathan, Swami; Lee, William A.; Cihlar, Tomas] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
   [Lo, Michael K.; Flint, Mike; McMullan, Laura K.; Spiropoulou, Christina F.; Nichol, Stuart T.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
   [Braun, Molly R.; Fearns, Rachel] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Welch, Lisa S.] LOKET Consulting, Clarksburg, MD 20871 USA.
   [Mayers, Douglas L.] Cocrystal Pharma, Tucker, GA 30084 USA.
C3 Gilead Sciences; Centers for Disease Control & Prevention - USA; Boston University
RP Bavari, S (corresponding author), US Army, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.; Bavari, S (corresponding author), US Army, Med Res Inst Infect Dis, Therapeut Dev Ctr, Ft Detrick, MD 21702 USA.; Cihlar, T (corresponding author), Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
EM tomas.cihlar@gilead.com; sina.bavari.civ@mail.mil
FU Joint Science and Technology Office for Chemical and Biological Defense (JSTO-CBD) of the Defense Threat Reduction Agency (DTRA) [CB10218]; NIH [R01AI113321]
NR 37
TC 1140
Z9 1340
U1 6
U2 391
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 381
EP +
DI 10.1038/nature17180
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300055
PM 26934220
DA 2026-03-09
ER

PT J
AU Emmanuel, MA
   Greenberg, NR
   Oblinsky, DG
   Hyster, TK
AF Emmanuel, Megan A.
   Greenberg, Norman R.
   Oblinsky, Daniel G.
   Hyster, Todd K.
TI Accessing non-natural reactivity by irradiating nicotinamide-dependent enzymes with light
SO NATURE
LA English
DT Article
ID alcohol-dehydrogenase; photoredox catalysis; radical cations; visible-light; ketones; debromination; biocatalysis; mechanisms; reduction; esters
AB Enzymes are ideal for use in asymmetric catalysis by the chemical industry, because their chemical compositions can be tailored to a specific substrate and selectivity pattern while providing efficiencies and selectivities that surpass those of classical synthetic methods(1). However, enzymes are limited to reactions that are found in nature and, as such, facilitate fewer types of transformation than do other forms of catalysis(2). Thus, a longstanding challenge in the field of biologically mediated catalysis has been to develop enzymes with new catalytic functions(3). Here we describe a method for achieving catalytic promiscuity that uses the photoexcited state of nicotinamide co-factors (molecules that assist enzyme-mediated catalysis). Under irradiation with visible light, the nicotinamide-dependent enzyme known as ketoreductase can be transformed from a carbonyl reductase into an initiator of radical species and a chiral source of hydrogen atoms. We demonstrate this new reactivity through a highly enantioselective radical dehalogenation of lactones-a challenging transformation for small-molecule catalysts(4-7). Mechanistic experiments support the theory that a radical species acts as an intermediate in this reaction, with NADH and NADPH (the reduced forms of nicotinamide adenine nucleotide and nicotinamide adenine dinucleotide phosphate, respectively) serving as both a photoreductant and the source of hydrogen atoms. To our knowledge, this method represents the first example of photo-induced enzyme promiscuity, and highlights the potential for accessing new reactivity from existing enzymes simply by using the excited states of common biological co-factors. This represents a departure from existing light-driven biocatalytic techniques, which are typically explored in the context of co-factor regeneration(8,9).
C1 [Emmanuel, Megan A.; Greenberg, Norman R.; Oblinsky, Daniel G.; Hyster, Todd K.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University
RP Hyster, TK (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
EM thyster@princeton.edu
FU Princeton University; Natural Sciences and Engineering Research Council of Canada (NSERC)
NR 30
TC 318
Z9 377
U1 16
U2 373
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 414
EP +
DI 10.1038/nature20569
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800038
PM 27974767
DA 2026-03-09
ER

PT J
AU Tu, S
   Narendra, V
   Yamaji, M
   Vidal, SE
   Rojas, LA
   Wang, XS
   Kim, SY
   Garcia, BA
   Tuschl, T
   Stadtfeld, M
   Reinberg, D
AF Tu, Shengjiang
   Narendra, Varun
   Yamaji, Masashi
   Vidal, Simon E.
   Rojas, Luis Alejandro
   Wang, Xiaoshi
   Kim, Sang Yong
   Garcia, Benjamin A.
   Tuschl, Thomas
   Stadtfeld, Matthias
   Reinberg, Danny
TI Co-repressor CBFA2T2 regulates pluripotency and germline development
SO NATURE
LA English
DT Article
ID embryonic stem-cells; acute myeloid-leukemia; mice; prdm14; specification; lineage; genes; rna; methylation; complexes
AB Developmental specification of germ cells lies at the heart of inheritance, as germ cells contain all of the genetic and epigenetic information transmitted between generations. The critical developmental event distinguishing germline from somatic lineages is the differentiation of primordial germ cells (PGCs)(1,2), precursors of sex-specific gametes that produce an entire organism upon fertilization. Germ cells toggle between uni- and pluripotent states as they exhibit their own 'latent' form of pluripotency. For example, PGCs express a number of transcription factors in common with embryonic stem (ES) cells, including OCT4 (encoded by Pou5f1), SOX2, NANOG and PRDM14 (refs 2-4). A biochemical mechanism by which these transcription factors converge on chromatin to produce the dramatic rearrangements underlying ES-cell-and PGC-specific transcriptional programs remains poorly understood. Here we identify a novel co-repressor protein, CBFA2T2, that regulates pluripotency and germline specification in mice. Cbfa2t2(-/-) mice display severe defects in PGC maturation and epigenetic reprogramming. CBFA2T2 forms a biochemical complex with PRDM14, a germline-specific transcription factor. Mechanistically, CBFA2T2 oligomerizes to form a scaffold upon which PRDM14 and OCT4 are stabilized on chromatin. Thus, in contrast to the traditional 'passenger' role of a co-repressor, CBFA2T2 functions synergistically with transcription factors at the crossroads of the fundamental developmental plasticity between uni- and pluripotency.
C1 [Tu, Shengjiang; Narendra, Varun; Rojas, Luis Alejandro; Reinberg, Danny] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Tu, Shengjiang; Narendra, Varun; Rojas, Luis Alejandro; Reinberg, Danny] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [Yamaji, Masashi; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
   [Vidal, Simon E.; Stadtfeld, Matthias] NYU, Sch Med, Skirball Inst Biomol Med, Dept Cell Biol, New York, NY 10016 USA.
   [Vidal, Simon E.; Stadtfeld, Matthias] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Wang, Xiaoshi; Garcia, Benjamin A.] Univ Penn, Dept Biochem & Biophys, Epigenet Program, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Kim, Sang Yong] NYU, Sch Med, Rodent Genet Engn Core, New York, NY 10016 USA.
C3 New York University; Howard Hughes Medical Institute; New York University; Rockefeller University; Howard Hughes Medical Institute; New York University; New York University; University of Pennsylvania; New York University
RP Reinberg, D (corresponding author), NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.; Reinberg, D (corresponding author), NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
EM danny.reinberg@nyumc.org
FU Howard Hughes Medical Institute (HHMI); National Institutes of Health (NIH) [RO1GM064844-12, R01GM110174]; Starr Foundation; Tri-Institutional Stem Cell Initiative; Japan Society for the Promotion of Science (JSPS); National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 41
TC 54
Z9 62
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 387
EP +
DI 10.1038/nature18004
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800036
PM 27281218
DA 2026-03-09
ER

PT J
AU Díaz, S
   Kattge, J
   Cornelissen, JHC
   Wright, IJ
   Lavorel, S
   Dray, S
   Reu, B
   Kleyer, M
   Wirth, C
   Prentice, IC
   Garnier, E
   Bönisch, G
   Westoby, M
   Poorter, H
   Reich, PB
   Moles, AT
   Dickie, J
   Gillison, AN
   Zanne, AE
   Chave, J
   Wright, SJ
   Sheremet'ev, SN
   Jactel, H
   Baraloto, C
   Cerabolini, B
   Pierce, S
   Shipley, B
   Kirkup, D
   Casanoves, F
   Joswig, JS
   Günther, A
   Falczuk, V
   Rüger, N
   Mahecha, MD
   Gorné, LD
AF Diaz, Sandra
   Kattge, Jens
   Cornelissen, Johannes H. C.
   Wright, Ian J.
   Lavorel, Sandra
   Dray, Stephane
   Reu, Bjoern
   Kleyer, Michael
   Wirth, Christian
   Prentice, I. Colin
   Garnier, Eric
   Boenisch, Gerhard
   Westoby, Mark
   Poorter, Hendrik
   Reich, Peter B.
   Moles, Angela T.
   Dickie, John
   Gillison, Andrew N.
   Zanne, Amy E.
   Chave, Jerome
   Wright, S. Joseph
   Sheremet'ev, Serge N.
   Jactel, Herve
   Baraloto, Christopher
   Cerabolini, Bruno
   Pierce, Simon
   Shipley, Bill
   Kirkup, Donald
   Casanoves, Fernando
   Joswig, Julia S.
   Guenther, Angela
   Falczuk, Valeria
   Rueger, Nadja
   Mahecha, Miguel D.
   Gorne, Lucas D.
TI The global spectrum of plant form and function
SO NATURE
LA English
DT Article
ID hawaiian metrosideros-polymorpha; trait-environment relationships; foliar nitrogen isotopes; leaf economics spectrum; relative growth-rate; dry-matter content; seed size; photosynthetic capacity; wide-range; trade-offs
AB Earth is home to a remarkable diversity of plant forms and life histories, yet comparatively few essential trait combinations have proved evolutionarily viable in today's terrestrial biosphere. By analysing worldwide variation in six major traits critical to growth, survival and reproduction within the largest sample of vascular plant species ever compiled, we found that occupancy of six-dimensional trait space is strongly concentrated, indicating coordination and trade-offs. Three-quarters of trait variation is captured in a two-dimensional global spectrum of plant form and function. One major dimension within this plane reflects the size of whole plants and their parts; the other represents the leaf economics spectrum, which balances leaf construction costs against growth potential. The global plant trait spectrum provides a backdrop for elucidating constraints on evolution, for functionally qualifying species and ecosystems, and for improving models that predict future vegetation based on continuous variation in plant form and function.
C1 [Diaz, Sandra; Falczuk, Valeria; Gorne, Lucas D.] Univ Nacl Cordoba, CONICET, Inst Multidisciplinario Biol Vegetal IMBIV, Casilla Correo 495, RA-5000 Cordoba, Argentina.
   [Diaz, Sandra; Falczuk, Valeria; Gorne, Lucas D.] Univ Nacl Cordoba, FCEFyN, RA-5000 Cordoba, Argentina.
   [Kattge, Jens; Wirth, Christian; Boenisch, Gerhard; Joswig, Julia S.; Guenther, Angela; Mahecha, Miguel D.] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Kattge, Jens; Wirth, Christian; Rueger, Nadja; Mahecha, Miguel D.] German Ctr Integrat Biodivers Res iDiv, D-04103 Leipzig, Germany.
   [Cornelissen, Johannes H. C.] Vrije Univ, Dept Ecol Sci, Syst Ecol, NL-1081 HV Amsterdam, Netherlands.
   [Wright, Ian J.; Prentice, I. Colin; Westoby, Mark] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [Lavorel, Sandra] Univ Grenoble Alpes, CNRS, UMR 5553, Lab Ecol Alpine, F-38041 Grenoble 9, France.
   [Dray, Stephane] Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut, UMR5558, F-69622 Villeurbanne, France.
   [Reu, Bjoern] Univ Leipzig, Inst Biol, D-04103 Leipzig, Germany.
   [Reu, Bjoern] Univ Ind Santander, Escuela Biol, Bucaramanga 680002, Colombia.
   [Kleyer, Michael] Carl von Ossietzky Univ Oldenburg, Inst Biol & Environm Sci, Landscape Ecol Grp, D-26111 Oldenburg, Germany.
   [Wirth, Christian] Univ Leipzig, Dept Systemat Bot & Funct Biodivers, D-04103 Leipzig, Germany.
   [Prentice, I. Colin] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, AXA Chair Biosphere & Climate Impacts, Grand Challenges Ecosyst, Ascot SL5 7PY, Berks, England.
   [Prentice, I. Colin] Univ London Imperial Coll Sci Technol & Med, Environm & Grantham Inst, Climate Change & Environm, Ascot SL5 7PY, Berks, England.
   [Garnier, Eric] Univ Montpellier, Univ Paul Valery Montpellier, Ctr Ecol Fonct & Evolut,UMR 5175, CNRS,EPHE, F-34293 Montpellier 5, France.
   [Poorter, Hendrik] Forschungszentrum Julich GmbH, Plant Sci IBG 2, D-52425 Julich, Germany.
   [Reich, Peter B.] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Reich, Peter B.] Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2751, Australia.
   [Moles, Angela T.] UNSW Australia, Sch Biol Earth & Environm Sci, Evolut & Ecol Res Ctr, Sydney, NSW 2052, Australia.
   [Dickie, John] Collections, Ardingly RH17 6TN, W Sussex, England.
   [Gillison, Andrew N.] Ctr Biodivers Management, Yungaburra, Qld 4884, Australia.
   [Zanne, Amy E.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
   [Zanne, Amy E.] Missouri Bot Garden, Ctr Conservat & Sustainable Dev, St Louis, MO 63121 USA.
   [Chave, Jerome] CNRS, Lab Evolut & Divers Biol, UMR 5174, F-31062 Toulouse, France.
   [Chave, Jerome] Univ Toulouse 3, F-31062 Toulouse, France.
   [Wright, S. Joseph; Rueger, Nadja] Smithsonian Trop Res Inst, Balboa, Ancon, Panama.
   [Sheremet'ev, Serge N.] Komarov Bot Inst, St Petersburg 197376, Russia.
   [Jactel, Herve] INRA, UMR1202, BIOGECO, F-33610 Cestas, France.
   [Jactel, Herve] Univ Bordeaux, BIOGECO, UMR 1202, F-33600 Pessac, France.
   [Baraloto, Christopher] Florida Int Univ, Dept Biol Sci, Int Ctr Trop Bot, Miami, FL 33199 USA.
   [Baraloto, Christopher] INRA, UMR Ecol Forets Guyane, Kourou 97310, French Guiana.
   [Cerabolini, Bruno] Univ Insubria, Dept Theoret & Appl Sci, I-21100 Varese, Italy.
   [Pierce, Simon] Univ Milan, Dept Agr & Environm Sci DiSAA, I-20133 Milan, Italy.
   [Shipley, Bill] Univ Sherbrooke, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada.
   [Kirkup, Donald] Royal Bot Gardens Kew, Biodivers Informat & Spatial Anal, Richmond TW9 3AB, Surrey, England.
   [Casanoves, Fernando] Ctr Agron Trop Invest & Ensenanza CATIE, Unidad Bioestadist, Turrialba 30501, Costa Rica.
C3 National University of Cordoba; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); National University of Cordoba; Max Planck Society; German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); Vrije Universiteit Amsterdam; Macquarie University; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universite Savoie Mont Blanc; VetAgro Sup; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Leipzig University; Universidad Industrial de Santander; Carl von Ossietzky Universitat Oldenburg; Leipzig University; Imperial College London; Imperial College London; Universite PSL; Ecole Pratique des Hautes Etudes (EPHE); Institut Agro; Institut Agro Montpellier; CIRAD; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Paul-Valery; Universite de Montpellier; Helmholtz Association; Julich Research Centre; University of Minnesota System; University of Minnesota Twin Cities; Western Sydney University; University of New South Wales Sydney; George Washington University; Missouri Botanical Gardens; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Ecole Nationale Formation Agronomique (ENSFEA); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Smithsonian Institution; Smithsonian Tropical Research Institute; Russian Academy of Sciences; Komarov Botanical Institute, Russian Academy of Sciences; INRAE; Universite de Bordeaux; State University System of Florida; Florida International University; INRAE; University of Insubria; University of Milan; University of Sherbrooke; Royal Botanic Gardens, Kew; CATIE - Centro Agronomico Tropical de Investigacion y Ensenanza
RP Díaz, S (corresponding author), Univ Nacl Cordoba, CONICET, Inst Multidisciplinario Biol Vegetal IMBIV, Casilla Correo 495, RA-5000 Cordoba, Argentina.
EM sandra.diaz@unc.edu.ar
FU TRY initiative on plant traits; DIVERSITAS/Future Earth; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig; BACI [ID 640176]; Universidad Nacional de Cordoba; CONICET; FONCyT [PICT 554]; SECyT (Argentina); Leverhulme Trust, UK; Inter-American Institute for Global Change Research (IAI) [SGP-CRA2015]; US National Science Foundation [GEO-1138881]; Direct For Biological Sciences; Division Of Environmental Biology [1234162, 1242531] Funding Source: National Science Foundation
NR 263
TC 2541
Z9 2855
U1 149
U2 2607
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 167
EP +
DI 10.1038/nature16489
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700027
PM 26700811
DA 2026-03-09
ER

PT J
AU Nadeau, NJ
   Pardo-Diaz, C
   Whibley, A
   Supple, MA
   Saenko, SV
   Wallbank, RWR
   Wu, GC
   Maroja, L
   Ferguson, L
   Hanly, JJ
   Hines, H
   Salazar, C
   Merrill, RM
   Dowling, AJ
   Ffrench-Constant, RH
   Llaurens, V
   Joron, M
   McMillan, WO
   Jiggins, CD
AF Nadeau, Nicola J.
   Pardo-Diaz, Carolina
   Whibley, Annabel
   Supple, Megan A.
   Saenko, Suzanne V.
   Wallbank, Richard W. R.
   Wu, Grace C.
   Maroja, Luana
   Ferguson, Laura
   Hanly, Joseph J.
   Hines, Heather
   Salazar, Camilo
   Merrill, Richard M.
   Dowling, Andrea J.
   Ffrench-Constant, Richard H.
   Llaurens, Violaine
   Joron, Mathieu
   McMillan, W. Owen
   Jiggins, Chris D.
TI The gene cortex controls mimicry and crypsis in butterflies and moths
SO NATURE
LA English
DT Article
ID genomic sequence; warning-color; hybrid zones; heliconius; evolution; quantification; divergence; expression; generation; speciation
AB The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection(1,2). Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators(3), suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia)(4), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects.
C1 [Nadeau, Nicola J.] Univ Sheffield, Dept Anim & Plant Sci, Western Bank, Sheffield S10 2TN, S Yorkshire, England.
   [Nadeau, Nicola J.; Supple, Megan A.; Wallbank, Richard W. R.; Hanly, Joseph J.; Merrill, Richard M.; McMillan, W. Owen; Jiggins, Chris D.] Smithsonian Trop Res Inst, Apartado Postal 0843-00153, Panama City, Panama.
   [Pardo-Diaz, Carolina; Salazar, Camilo] Univ Rosario, Fac Nat Sci & Math, Biol Program, Cra 24 63C-69, Bogota 111221, Colombia.
   [Whibley, Annabel; Saenko, Suzanne V.; Llaurens, Violaine; Joron, Mathieu] Univ Paris 06, Sorbonne Univ, Inst Systemat Evolut & Biodivers,UMR 7205, CNRS,MNHN,EPHE, CP50,57 Rue Cuvier, F-75005 Paris, France.
   [Whibley, Annabel] John Innes Ctr, Cell & Dev Biol, Norwich NR4 7UH, Norfolk, England.
   [Supple, Megan A.] Australian Natl Univ, Res Sch Biol, 134 Linnaeus Way, Acton0, ACT 2601, Australia.
   [Wallbank, Richard W. R.; Hanly, Joseph J.; Merrill, Richard M.; Jiggins, Chris D.] Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
   [Wu, Grace C.] Univ Calif Berkeley, Energy & Resources Grp, Berkeley, CA 94720 USA.
   [Maroja, Luana] Williams Coll, Dept Biol, Williamstown, MA 01267 USA.
   [Ferguson, Laura] Univ Oxford, Dept Zool, South Parks Rd, Oxford OX1 3PS, England.
   [Hines, Heather] Penn State Univ, 517 Mueller, University Pk, PA 16802 USA.
   [Dowling, Andrea J.; Ffrench-Constant, Richard H.] Univ Exeter Cornwall, Sch Biosci, Penryn TR10 9FE, Cornwall, England.
   [Joron, Mathieu] Univ Montpellier, Univ Paul Valery Montpellier, Ctr Ecol Fonctionnelle & Evolut, CEFE,UMR 5175,CNRS,EPHE, 1919 Route de Mende, F-34293 Montpellier, France.
C3 University of Sheffield; Smithsonian Institution; Smithsonian Tropical Research Institute; Universidad del Rosario; Universite PSL; Ecole Pratique des Hautes Etudes (EPHE); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Museum National d'Histoire Naturelle (MNHN); UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Australian National University; University of Cambridge; University of California System; University of California Berkeley; Williams College; University of Oxford; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Exeter; Universite PSL; Ecole Pratique des Hautes Etudes (EPHE); Institut Agro; Institut Agro Montpellier; CIRAD; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Paul-Valery; Universite de Montpellier; CNRS - Institute of Ecology & Environment (INEE)
RP Nadeau, NJ (corresponding author), Univ Sheffield, Dept Anim & Plant Sci, Western Bank, Sheffield S10 2TN, S Yorkshire, England.; Nadeau, NJ; Jiggins, CD (corresponding author), Smithsonian Trop Res Inst, Apartado Postal 0843-00153, Panama City, Panama.; Jiggins, CD (corresponding author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
EM n.nadeau@sheffield.ac.uk; c.jiggins@zoo.cam.ac.uk
FU Leverhulme Trust [RPG-2014-167]; BBSRC [H01439X/1]; ERC (SpeciationGenetics) [339873]; NERC [MGF 280, NE/K008498/1]; NSF [DEB 1257689, IOS 1052541]; ERC [StG-243179]; French National Agency for Research (ANR) [ANR-12-JSV7-0005, ANR-13-JSV7-0003-01]; BBSRC [BB/H01439X/1, BB/H014268/1, BB/E006191/1] Funding Source: UKRI; NERC [NE/K008498/1, NE/D000114/2] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H01439X/1, BB/H014268/1, BB/E006191/1] Funding Source: researchfish; Natural Environment Research Council [NE/K008498/1, NE/D000114/2] Funding Source: researchfish; European Research Council (ERC) [339873] Funding Source: European Research Council (ERC); Agence Nationale de la Recherche (ANR) [ANR-12-JSV7-0005, ANR-13-JSV7-0003] Funding Source: Agence Nationale de la Recherche (ANR)
NR 58
TC 162
Z9 197
U1 6
U2 253
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 106
EP +
DI 10.1038/nature17961
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300043
PM 27251285
DA 2026-03-09
ER

PT J
AU Wang, T
   Naredla, RR
   Thompson, SK
   Hoye, TR
AF Wang, Teng
   Naredla, Rajasekhar Reddy
   Thompson, Severin K.
   Hoye, Thomas R.
TI The pentadehydro-Diels-Alder reaction
SO NATURE
LA English
DT Article
ID stepwise mechanisms; thermal generation; cycloaromatization; cyclization; system; (z)-1,2,4-heptatrien-6-yne; alpha,3-dehydrotoluene; substituents; nucleophiles; diradicals
AB In the classic Diels-Alder [4 + 2] cycloaddition reaction(1), the overall degree of unsaturation (or oxidation state) of the 4 pi (diene) and 2 pi (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced(2) by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA)(3-7) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate(8,9) can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4 pi + 2 pi cycloaddition reaction that generates a different, highly reactive intermediate known as an alpha,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, alpha,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC equivalent to N), although non-participants in aza-HDDA reactions, readily function as the 2 pi component in PDDA cyclizations to produce, via trapping of the alpha,3-(5-aza) dehydrotoluene intermediates, pyridine-containing products.
C1 [Wang, Teng; Naredla, Rajasekhar Reddy; Thompson, Severin K.; Hoye, Thomas R.] Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Hoye, TR (corresponding author), Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA.
EM hoye@umn.edu
FU National Institute of General Medical Sciences [GM65597]; National Cancer Institute of the US Department of Health and Human Services [CA76497]; NIH [S10OD011952]
NR 30
TC 65
Z9 82
U1 3
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 484
EP 488
DI 10.1038/nature17429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900043
PM 27088605
DA 2026-03-09
ER

PT J
AU von der Ecken, J
   Heissler, SM
   Pathan-Chhatbar, S
   Manstein, DJ
   Raunser, S
AF von der Ecken, Julian
   Heissler, Sarah M.
   Pathan-Chhatbar, Salma
   Manstein, Dietmar J.
   Raunser, Stefan
TI Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution
SO NATURE
LA English
DT Article
ID heavy-chain gene; familial hypertrophic cardiomyopathy; dictyostelium myosin-ii; actin-binding site; beta-myosin; functional-characterization; dilated cardiomyopathy; muscle-contraction; missense mutation; atpase activity
AB The interaction of myosin with actin filaments is the central feature of muscle contraction(1) and cargo movement along actin filaments of the cytoskeleton(2). The energy for these movements is generated during a complex mechanochemical reaction cycle(3,4). Crystal structures of myosin in different states have provided important structural insights into the myosin motor cycle when myosin is detached from F-actin(5-7). The difficulty of obtaining diffracting crystals, however, has prevented structure determination by crystallography of actomyosin complexes. Thus, although structural models exist of F-actin in complex with various myosins(8-11), a high-resolution structure of the F-actin-myosin complex is missing. Here, using electron cryomicroscopy, we present the structure of a human rigor actomyosin complex at an average resolution of 3.9 angstrom. The structure reveals details of the actomyosin interface, which is mainly stabilized by hydrophobic interactions. The negatively charged amino (N) terminus of actin interacts with a conserved basic motif in loop 2 of myosin, promoting cleft closure in myosin. Surprisingly, the overall structure of myosin is similar to rigor-like myosin structures in the absence of F-actin, indicating that F-actin binding induces only minimal conformational changes in myosin. A comparison with pre-powerstroke and intermediate (P-i-release)(7) states of myosin allows us to discuss the general mechanism of myosin binding to F-actin. Our results serve as a strong foundation for the molecular understanding of cytoskeletal diseases, such as autosomal dominant hearing loss and diseases affecting skeletal and cardiac muscles, in particular nemaline myopathy and hypertrophic cardiomyopathy.
C1 [von der Ecken, Julian; Raunser, Stefan] Max Planck Inst Mol Physiol, Dept Struct Biochem, D-44227 Dortmund, Germany.
   [Heissler, Sarah M.; Pathan-Chhatbar, Salma; Manstein, Dietmar J.] Hannover Med Sch, Inst Biophys Chem, D-30625 Hannover, Germany.
   [Manstein, Dietmar J.] Hannover Med Sch, Div Struct Anal, D-30625 Hannover, Germany.
   [Heissler, Sarah M.] NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA.
C3 Max Planck Society; Hannover Medical School; Hannover Medical School; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Raunser, S (corresponding author), Max Planck Inst Mol Physiol, Dept Struct Biochem, D-44227 Dortmund, Germany.
EM stefan.raunser@mpi-dortmund.mpg.de
FU Max Planck Society; European Research Council under the European Union [615984]; Behrens-Weise foundation; German Research Foundation (DFG) [MA 1081/21-1]
NR 78
TC 186
Z9 219
U1 3
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 724
EP +
DI 10.1038/nature18295
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000045
PM 27324845
DA 2026-03-09
ER

PT J
AU Choueiri, RM
   Galati, E
   Thérien-Aubin, H
   Klinkova, A
   Larin, EM
   Querejeta-Fernández, A
   Han, LL
   Xin, HL
   Gang, O
   Zhulina, EB
   Rubinstein, M
   Kumacheva, E
AF Choueiri, Rachelle M.
   Galati, Elizabeth
   Therien-Aubin, Heloise
   Klinkova, Anna
   Larin, Egor M.
   Querejeta-Fernandez, Ana
   Han, Lili
   Xin, Huolin L.
   Gang, Oleg
   Zhulina, Ekaterina B.
   Rubinstein, Michael
   Kumacheva, Eugenia
TI Surface patterning of nanoparticles with polymer patches
SO NATURE
LA English
DT Article
ID ligand shell; solvents; colloids; brushes; chains
AB Patterning of colloidal particles with chemically or topographically distinct surface domains (patches) has attracted intense research interest(1-3). Surface-patterned particles act as colloidal analogues of atoms and molecules(4,5), serve as model systems in studies of phase transitions in liquid systems(6), behave as 'colloidal surfactants'(7) and function as templates for the synthesis of hybrid particles(8). The generation of micrometre- and submicrometre-sized patchy colloids is now efficient(9-11), but surface patterning of inorganic colloidal nanoparticles with dimensions of the order of tens of nanometres is uncommon. Such nanoparticles exhibit size-and shape-dependent optical, electronic and magnetic properties, and their assemblies show new collective properties(12). At present, nanoparticle patterning is limited to the generation of two-patch nanoparticles(13-15), and nanoparticles with surface ripples(16) or a 'raspberry' surface morphology(17). Here we demonstrate nanoparticle surface patterning, which utilizes thermodynamically driven segregation of polymer ligands from a uniform polymer brush into surface-pinned micelles following a change in solvent quality. Patch formation is reversible but can be permanently preserved using a photocrosslinking step. The methodology offers the ability to control the dimensions of patches, their spatial distribution and the number of patches per nanoparticle, in agreement with a theoretical model. The versatility of the strategy is demonstrated by patterning nanoparticles with different dimensions, shapes and compositions, tethered with various types of polymers and subjected to different external stimuli. These patchy nanocolloids have potential applications in fundamental research, the self-assembly of nanomaterials, diagnostics, sensing and colloidal stabilization.
C1 [Choueiri, Rachelle M.; Galati, Elizabeth; Therien-Aubin, Heloise; Klinkova, Anna; Larin, Egor M.; Querejeta-Fernandez, Ana; Kumacheva, Eugenia] Univ Toronto, Dept Chem, 80 St George St, Toronto, ON M5S 3H6, Canada.
   [Han, Lili; Xin, Huolin L.; Gang, Oleg] Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA.
   [Han, Lili] Tianjin Univ, Inst New Energy Mat, Sch Mat Sci & Engn, Tianjin 300072, Peoples R China.
   [Zhulina, Ekaterina B.] Russian Acad Sci, Inst Macromol Cpds, St Petersburg 199004, Russia.
   [Zhulina, Ekaterina B.] St Petersburg Natl Univ Informat Technol Mech & O, St Petersburg 197101, Russia.
   [Rubinstein, Michael] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
   [Kumacheva, Eugenia] Univ Toronto, Inst Biomat & Biomed Engn, 4 Taddle Creek Rd, Toronto, ON M5S 3G9, Canada.
   [Kumacheva, Eugenia] Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada.
   [Gang, Oleg] Columbia Univ, Dept Chem Engn, New York, NY 10027 USA.
   [Gang, Oleg] Columbia Univ, Dept Appl Phys & Appl Math, New York, NY 10027 USA.
C3 University of Toronto; United States Department of Energy (DOE); Brookhaven National Laboratory; Tianjin University; Russian Academy of Sciences; Institute of Macromolecular Compounds of the Russian Academy of Sciences; ITMO University; University of North Carolina; University of North Carolina Chapel Hill; University of Toronto; University of Toronto; Columbia University; Columbia University
RP Kumacheva, E (corresponding author), Univ Toronto, Dept Chem, 80 St George St, Toronto, ON M5S 3H6, Canada.; Kumacheva, E (corresponding author), Univ Toronto, Inst Biomat & Biomed Engn, 4 Taddle Creek Rd, Toronto, ON M5S 3G9, Canada.; Kumacheva, E (corresponding author), Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada.
EM ekumache@chem.utoronto.ca
FU Connaught Foundation; National Science and Engineering Research Council of Canada; Russian Foundation for Basic Research [14-03-00372a]; Government of Russian Federation [074-U01]; National Science Foundation [DMR-1309892, DMR-1436201, DMR-1121107]; National Institutes of Health [P01-HL108808, 1UH2HL123645]; Cystic Fibrosis Foundation; US Department of Energy, Office of Basic Energy Sciences [DE-SC0012704]; Natural Sciences and Engineering Research Council of Canada; Division Of Materials Research; Direct For Mathematical & Physical Scien [1309892] Funding Source: National Science Foundation; National Heart Lung and Blood Institute [P01HL108808] Funding Source: NIH RePORTER
NR 32
TC 274
Z9 302
U1 14
U2 797
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 79
EP 83
DI 10.1038/nature19089
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900037
PM 27556943
DA 2026-03-09
ER

PT J
AU Tang, CC
   Ang, MCY
   Choo, KK
   Keerthi, V
   Tan, JK
   Syafiqah, MN
   Kugler, T
   Burroughes, JH
   Png, RQ
   Chua, LL
   Ho, PKH
AF Tang, Cindy C.
   Ang, Mervin C. Y.
   Choo, Kim-Kian
   Keerthi, Venu
   Tan, Jun-Kai
   Syafiqah, Mazlan Nur
   Kugler, Thomas
   Burroughes, Jeremy H.
   Png, Rui-Qi
   Chua, Lay-Lay
   Ho, Peter K. H.
TI Doped polymer semiconductors with ultrahigh and ultralow work functions for ohmic contacts
SO NATURE
LA English
DT Article
ID field-effect transistors; organic semiconductors; conducting-polymer; solar-cells; charge injection; highly efficient; hole-injection; devices; recombination; electronics
AB To make high-performance semiconductor devices, a good ohmic contact between the electrode and the semiconductor layer is required to inject the maximum current density across the contact. Achieving ohmic contacts requires electrodes with high and low work functions to inject holes and electrons respectively, where the work function is the minimum energy required to remove an electron from the Fermi level of the electrode to the vacuum level. However, it is challenging to produce electrically conducting films with sufficiently high or low work functions, especially for solution-processed semiconductor devices. Hole-doped polymer organic semiconductors are available in a limited work-function range(1,2), but hole-doped materials with ultrahigh work functions and, especially, electron-doped materials with low to ultralow work functions are not yet available. The key challenges are stabilizing the thin films against de-doping and suppressing dopant migration(3,4). Here we report a general strategy to overcome these limitations and achieve solution-processed doped films over a wide range of work functions (3.0-5.8 electronvolts), by charge-doping of conjugated polyelectrolytes(5-7) and then internal ion-exchange to give self-compensated heavily doped polymers. Mobile carriers on the polymer backbone in these materials are compensated by covalently bonded counter-ions. Although our self-compensated doped polymers superficially resemble self-doped polymers(8,9), they are generated by separate charge-carrier doping and compensation steps, which enables the use of strong dopants to access extreme work functions. We demonstrate solution-processed ohmic contacts for high-performance organic light-emitting diodes, solar cells, photodiodes and transistors, including ohmic injection of both carrier types into polyfluorene-the benchmark wide-bandgap blue-light-emitting polymer organic semiconductor. We also show that metal electrodes can be transformed into highly efficient hole-and electron-injection contacts via the self-assembly of these doped polyelectrolytes. This consequently allows ambipolar field-effect transistors to be transformed into high-performance p-and n-channel transistors. Our strategy provides a method for producing ohmic contacts not only for organic semiconductors, but potentially for other advanced semiconductors as well, including perovskites, quantum dots, nanotubes and two-dimensional materials.
C1 [Tang, Cindy C.; Tan, Jun-Kai; Png, Rui-Qi; Chua, Lay-Lay; Ho, Peter K. H.] Natl Univ Singapore, Dept Phys, Lower Kent Ridge Rd, S-117550 Singapore, Singapore.
   [Tang, Cindy C.; Ang, Mervin C. Y.; Tan, Jun-Kai; Png, Rui-Qi; Chua, Lay-Lay; Ho, Peter K. H.] Natl Univ Singapore, SERIS, 7 Engn Dr 1, S-117574 Singapore, Singapore.
   [Ang, Mervin C. Y.; Choo, Kim-Kian; Keerthi, Venu; Syafiqah, Mazlan Nur; Chua, Lay-Lay] Natl Univ Singapore, Dept Chem, Lower Kent Ridge Rd, S-117552 Singapore, Singapore.
   [Kugler, Thomas; Burroughes, Jeremy H.] Cambridge Display Technol Ltd, Bldg 2020,Cambourne Business Pk, Cambridge CB3 6DW, England.
C3 National University of Singapore; National University of Singapore; National University of Singapore
RP Png, RQ; Chua, LL; Ho, PKH (corresponding author), Natl Univ Singapore, Dept Phys, Lower Kent Ridge Rd, S-117550 Singapore, Singapore.; Png, RQ; Chua, LL; Ho, PKH (corresponding author), Natl Univ Singapore, SERIS, 7 Engn Dr 1, S-117574 Singapore, Singapore.; Chua, LL (corresponding author), Natl Univ Singapore, Dept Chem, Lower Kent Ridge Rd, S-117552 Singapore, Singapore.
EM phypngrq@nus.edu.sg; chmcll@nus.edu.sg; phyhop@nus.edu.sg
FU National Research Foundation, Prime Minister's Office, Singapore under its Competitive Research Programme (CRP Award) [NRF-CRP 11-2012-03: R-144-000-339-281, R-143-000-608-281]; Ministry of Education, Singapore [R-144-000-324-112]; National University of Singapore; Singapore's National Research Foundation through the Singapore Economic Development Board
NR 35
TC 225
Z9 245
U1 6
U2 699
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 536
EP +
DI 10.1038/nature20133
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600038
PM 27882976
DA 2026-03-09
ER

PT J
AU Murakami, K
   Günesdogan, U
   Zylicz, JJ
   Tang, WWC
   Sengupta, R
   Kobayashi, T
   Kim, S
   Butler, R
   Dietmann, S
   Surani, MA
AF Murakami, Kazuhiro
   Guenesdogan, Ufuk
   Zylicz, Jan J.
   Tang, Walfred W. C.
   Sengupta, Roopsha
   Kobayashi, Toshihiro
   Kim, Shinseog
   Butler, Richard
   Dietmann, Sabine
   Surani, M. Azim
TI NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; ground-state; mouse embryo; self-renewal; specification; mice; expression; dynamics; lineage; fate
AB Nanog, a core pluripotency factor in the inner cell mass of blastocysts, is also expressed in unipotent primordial germ cells (PGCs) in mice(1), where its precise role is yet unclear(2-4). We investigated this in an in vitro model, in which naive pluripotent embryonic stem (ES) cells cultured in basic fibroblast growth factor (bFGF) and activin A develop as epiblast-like cells (EpiLCs) and gain competence for a PGC-like fate(5). Consequently, bone morphogenetic protein 4 (BMP4), or ectopic expression of key germline transcription factors Prdm1, Prdm14 and Tfap2c, directly induce PGC-like cells (PGCLCs) in EpiLCs, but not in ES cells(6-8). Here we report an unexpected discovery that Nanog alone can induce PGCLCs in EpiLCs, independently of BMP4. We propose that after the dissolution of the naive ES-cell pluripotency network during establishment of EpiLCs(9,10), the epigenome is reset for cell fate determination. Indeed, we found genome-wide changes in NANOG-binding patterns between ES cells and EpiLCs, indicating epigenetic resetting of regulatory elements. Accordingly, we show that NANOG can bind and activate enhancers of Prdm1 and Prdm14 in EpiLCs in vitro; BLIMP1 (encoded by Prdm1) then directly induces Tfap2c. Furthermore, while SOX2 and NANOG promote the pluripotent state in ES cells, they show contrasting roles in EpiLCs, as Sox2 specifically represses PGCLC induction by Nanog. This study demonstrates a broadly applicable mechanistic principle for how cells acquire competence for cell fate determination, resulting in the context-dependent roles of key transcription factors during development.
C1 [Murakami, Kazuhiro; Guenesdogan, Ufuk; Zylicz, Jan J.; Tang, Walfred W. C.; Sengupta, Roopsha; Kobayashi, Toshihiro; Kim, Shinseog; Butler, Richard; Surani, M. Azim] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Murakami, Kazuhiro; Guenesdogan, Ufuk; Zylicz, Jan J.; Tang, Walfred W. C.; Sengupta, Roopsha; Kobayashi, Toshihiro; Kim, Shinseog; Surani, M. Azim] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England.
   [Murakami, Kazuhiro; Guenesdogan, Ufuk; Zylicz, Jan J.; Tang, Walfred W. C.; Sengupta, Roopsha; Kobayashi, Toshihiro; Kim, Shinseog; Dietmann, Sabine; Surani, M. Azim] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1QR, England.
   [Murakami, Kazuhiro] RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Murakami, Kazuhiro] Hokkaido Univ, Fac Adv Life Sci, Lab Mol & Cellular Biol, Kita Ku, Sapporo, Hokkaido 0010021, Japan.
C3 University of Cambridge; University of Cambridge; University of Cambridge; RIKEN; Hokkaido University
RP Surani, MA (corresponding author), Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM a.surani@gurdon.cam.ac.uk
FU Japan Society for the Promotion of Science (JSPS); Marie Sklodowska-Curie and a Newton Trust/Leverhulme Trust Early Career fellowship; Wellcome Trust [RG44593, WT096738]; JSPS; Gurdon Institute core grants from the Wellcome Trust [092096]; Cancer Research UK [C6946/A14492]; Medical Research Council [MC_PC_12009] Funding Source: researchfish; Grants-in-Aid for Scientific Research [15K18539] Funding Source: KAKEN
NR 39
TC 140
Z9 155
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 403
EP +
DI 10.1038/nature16480
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800048
PM 26751055
DA 2026-03-09
ER

PT J
AU Bjerkeli, P
   van der Wiel, MHD
   Harsono, D
   Ramsey, JP
   Jorgensen, JK
AF Bjerkeli, Per
   van der Wiel, Matthijs H. D.
   Harsono, Daniel
   Ramsey, Jon P.
   Jorgensen, Jes K.
TI Resolved images of a protostellar outflow driven by an extended disk wind
SO NATURE
LA English
DT Article
ID young stars; rotation; jet; envelope; tauri; transition; chondrules; flows; co
AB Young stars are associated with prominent outflows of molecular gas(1,2). The ejection of gas is believed to remove angular momentum from the protostellar system, permitting young stars to grow by the accretion of material from the protostellar disk(2). The underlying mechanism for outflow ejection is not yet understood(2), but is believed to be closely linked to the protostellar disk(3). Various models have been proposed to explain the outflows, differing mainly in the region where acceleration of material takes place: close to the protostar itself ('X-wind'(4,5), or stellar wind(6)), in a larger region throughout the protostellar disk (disk wind(7-9)), or at the interface between the two(10). Outflow launching regions have so far been probed only by indirect extrapolation(11-13) because of observational limits. Here we report resolved images of carbon monoxide towards the outflow associated with the TMC1A protostellar system. These data show that gas is ejected from a region extending up to a radial distance of 25 astronomical units from the central protostar, and that angular momentum is removed from an extended region of the disk. This demonstrates that the outflowing gas is launched by an extended disk wind from a Keplerian disk.
C1 [Bjerkeli, Per; van der Wiel, Matthijs H. D.; Ramsey, Jon P.; Jorgensen, Jes K.] Univ Copenhagen, Niels Bohr Inst, Ctr Star & Planet Format, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
   [Bjerkeli, Per; van der Wiel, Matthijs H. D.; Ramsey, Jon P.; Jorgensen, Jes K.] Univ Copenhagen, Nat Hist Museum Denmark, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
   [Bjerkeli, Per] Chalmers Univ Technol, Onsala Space Observ, Dept Earth & Space Sci, S-43992 Onsala, Sweden.
   [van der Wiel, Matthijs H. D.] Netherlands Inst Radio Astron, ASTRON, Postbus 2, NL-7990 AA Dwingeloo, Netherlands.
   [Harsono, Daniel] Heidelberg Univ, Inst Theoret Astrophys, Ctr Astron, Albert Ueberle Str 2, D-69120 Heidelberg, Germany.
C3 University of Copenhagen; Niels Bohr Institute; University of Copenhagen; Chalmers University of Technology; Ruprecht Karls University Heidelberg
RP Bjerkeli, P (corresponding author), Univ Copenhagen, Niels Bohr Inst, Ctr Star & Planet Format, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.; Bjerkeli, P (corresponding author), Univ Copenhagen, Nat Hist Museum Denmark, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.; Bjerkeli, P (corresponding author), Chalmers Univ Technol, Onsala Space Observ, Dept Earth & Space Sci, S-43992 Onsala, Sweden.
EM per.bjerkeli@bjerkeli.se
FU Swedish Research Council [637-2013-472]; Lundbeck Foundation Junior Group Leader Fellowship; European Research Council (ERC) under the European Union [646908]; ERC Consolidator Grant 'S4F'; Danish National Research Foundation; Deutsche Forschungsgemeinschaft Schwerpunktprogramm [DFG SPP 1385]; Lundbeck Foundation [R52-2010-4810] Funding Source: researchfish
NR 38
TC 133
Z9 142
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 406
EP +
DI 10.1038/nature20600
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800036
PM 27974756
DA 2026-03-09
ER

PT J
AU Wang, K
   Jacobsen, SB
AF Wang, Kun
   Jacobsen, Stein B.
TI Potassium isotopic evidence for a high-energy giant impact origin of the Moon
SO NATURE
LA English
DT Article
ID oxygen isotopes; solar; cosmochemistry; fractionation; evaporation; depletion
AB The Earth-Moon system has unique chemical and isotopic signatures compared with other planetary bodies(1-3); any successful model for the origin of this system therefore has to satisfy these chemical and isotopic constraints. The Moon is substantially depleted in volatile elements such as potassium compared with the Earth and the bulk solar composition(4), and it has long been thought to be the result of a catastrophic Moon-forming giant impact event(5). Volatile-element-depleted bodies such as the Moon were expected to be enriched in heavy potassium isotopes during the loss of volatiles; however such enrichment was never found(6). Here we report new high-precision potassium isotope data for the Earth, the Moon and chondritic meteorites. We found that the lunar rocks are significantly (>2 sigma) enriched in the heavy isotopes of potassium compared to the Earth and chondrites (by around 0.4 parts per thousand). The enrichment of the heavy isotope of potassium in lunar rocks compared with those of the Earth and chondrites can be best explained as the result of the incomplete condensation of a bulk silicate Earth vapour at an ambient pressure that is higher than 10 bar. We used these coupled constraints of the chemical loss and isotopic fractionation of K to compare two recent dynamic models that were used to explain the identical non-mass-dependent isotope composition of the Earth and the Moon. Our K isotope result is inconsistent with the low-energy disk equilibration model(7), but supports the high-energy, high-angular-momentum giant impact model(8) for the origin of the Moon. High-precision potassium isotope data can also be used as a 'palaeo-barometer' to reveal the physical conditions during the Moon-forming event.
C1 [Wang, Kun; Jacobsen, Stein B.] Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
   [Wang, Kun] Washington Univ, Dept Earth & Planetary Sci, One Brookings Dr, St Louis, MO 63130 USA.
   [Wang, Kun] Washington Univ, McDonnell Ctr Space Sci, One Brookings Dr, St Louis, MO 63130 USA.
C3 Harvard University; Washington University (WUSTL); Washington University (WUSTL)
RP Wang, K (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.; Wang, K (corresponding author), Washington Univ, Dept Earth & Planetary Sci, One Brookings Dr, St Louis, MO 63130 USA.; Wang, K (corresponding author), Washington Univ, McDonnell Ctr Space Sci, One Brookings Dr, St Louis, MO 63130 USA.
EM wangkun@wustl.edu
FU NASA Emerging Worlds program [NNX15AH66G]; Harvard Origins of Life Initiative Postdoctoral Fellowship; Emerging Frontiers & Multidisciplinary Activities; Directorate For Engineering [1542741] Funding Source: National Science Foundation
NR 35
TC 682
Z9 830
U1 8
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 487
EP +
DI 10.1038/nature19341
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400052
PM 27617635
DA 2026-03-09
ER

PT J
AU Kawamura, S
   Chu, H
   Felding, J
   Baran, PS
AF Kawamura, Shuhei
   Chu, Hang
   Felding, Jakob
   Baran, Phil S.
TI Nineteen-step total synthesis of (+)-phorbol
SO NATURE
LA English
DT Article
ID c-h oxidation; tumor promoters; part 14; phorbol
AB Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to its intriguing chemical structure and the medicinal potential of phorbol esters(1). Access to useful quantities of phorbol and related analogues has relied on isolation from natural sources and semisynthesis. Despite efforts spanning 40 years, chemical synthesis has been unable to compete with these strategies, owing to its complexity and unusual placement of oxygen atoms. Purely synthetic enantiopure phorbol has remained elusive, and biological synthesis has not led to even the simplest members of this terpene family. Recently, the chemical syntheses of eudesmanes(2), germacrenes(3), taxanes(4,5) and ingenanes(6-8) have all benefited from a strategy inspired by the logic of two-phase terpene biosynthesis in which powerful C-C bond constructions and C-H bond oxidations go hand in hand. Here we implement a two-phase terpene synthesis strategy to achieve enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene. The purpose of this synthesis route is not to displace isolation or semisynthesis as a means of generating the natural product per se, but rather to enable access to analogues containing unique placements of oxygen atoms that are otherwise inaccessible.
C1 [Kawamura, Shuhei; Chu, Hang; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Felding, Jakob] LEO Pharma AS, Front End Innovat, Ind Pk 55, DK-2750 Ballerup, Denmark.
C3 Scripps Research Institute; LEO Pharma
RP Baran, PS (corresponding author), Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
EM pbaran@scripps.edu
FU LEO Pharma; Uehara Memorial Foundation; National Institute of General Medical Sciences [GM-097444]; National Institute of General Medical Sciences [R35GM118176] Funding Source: NIH RePORTER
NR 30
TC 192
Z9 233
U1 5
U2 315
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 90
EP 93
DI 10.1038/nature17153
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500039
PM 27007853
DA 2026-03-09
ER

PT J
AU Shihoya, W
   Nishizawa, T
   Okuta, A
   Tani, K
   Dohmae, N
   Fujiyoshi, Y
   Nureki, O
   Doi, T
AF Shihoya, Wataru
   Nishizawa, Tomohiro
   Okuta, Akiko
   Tani, Kazutoshi
   Dohmae, Naoshi
   Fujiyoshi, Yoshinori
   Nureki, Osamu
   Doi, Tomoko
TI Activation mechanism of endothelin ETB receptor by endothelin-1
SO NATURE
LA English
DT Article
ID g-protein; crystal-structure; b receptor; peptide; binding; thermostabilization; pharmacology; selectivity; antagonists; affinity
AB Endothelin, a 21-amino-acid peptide, participates in various physiological processes, such as regulation of vascular tone, humoral homeostasis, neural crest cell development and neurotransmission. Endothelin and its G-protein-coupled receptor are involved in the development of various diseases, such as pulmonary arterial hypertension, and thus are important therapeutic targets. Here we report crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1. The structures and mutation analysis reveal the mechanism for the isopeptide selectivity between endothelin-1 and -3. Transmembrane helices 1, 2, 6 and 7 move and envelop the entire endothelin peptide, in a virtually irreversible manner. The agonist-induced conformational changes are propagated to the receptor core and the cytoplasmic G-protein coupling interface, and probably induce conformational flexibility in TM6. A comparison with the M2 muscarinic receptor suggests a shared mechanism for signal transduction in class A G-protein-coupled receptors.
C1 [Shihoya, Wataru; Fujiyoshi, Yoshinori] Nagoya Univ, Grad Sch Pharmaceut Sci, Dept Basic Med Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Shihoya, Wataru; Okuta, Akiko; Tani, Kazutoshi; Fujiyoshi, Yoshinori] Nagoya Univ, Cellular & Struct Physiol Inst, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Shihoya, Wataru; Nishizawa, Tomohiro; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.
   [Nishizawa, Tomohiro] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan.
   [Dohmae, Naoshi] RIKEN Ctr Sustainable Resource Sci, Biomol Characterizat Unit, Wako, Saitama 3510198, Japan.
   [Doi, Tomoko] Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto 6068502, Japan.
C3 Nagoya University; Nagoya University; University of Tokyo; Japan Science & Technology Agency (JST); RIKEN; Kyoto University
RP Nureki, O (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.; Doi, T (corresponding author), Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto 6068502, Japan.
EM nureki@bs.s.u-tokyo.ac.jp; doi@mb.biophys.kyoto-u.ac.jp
FU Japan Society for the Promotion of Science KAKENHI [15J09780, 22227004, 24227004, 25650019, 26440024, 26640102]; Core Research for Evolutional Science and Technology Program; Platform for Drug Discovery, Information, and Structural Life Science from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; Japan New Energy and Industrial Technology Development Organization (NEDO); Japan Agency for Medical Research and Development (AMED); National Institute of Biomedical Innovation; Grants-in-Aid for Scientific Research [22227004, 15H05775, 16H06294, 26440024, 26640102, 15J09780, 25650019, 16K07172] Funding Source: KAKEN
NR 65
TC 134
Z9 153
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 363
EP +
DI 10.1038/nature19319
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000046
PM 27595334
DA 2026-03-09
ER

PT J
AU Headley, MB
   Bins, A
   Nip, A
   Roberts, EW
   Looney, MR
   Gerard, A
   Krummel, MF
AF Headley, Mark B.
   Bins, Adriaan
   Nip, Alyssa
   Roberts, Edward W.
   Looney, Mark R.
   Gerard, Audrey
   Krummel, Matthew F.
TI Visualization of immediate immune responses to pioneer metastatic cells in the lung
SO NATURE
LA English
DT Article
ID t-cell; reporter mouse; antigen; differentiation; expression; monocytes; exosm; growth; mice
AB Lung metastasis is the lethal determinant in many cancers(1,2) and a number of lines of evidence point to monocytes and macrophages having key roles in its development(3-5). Yet little is known about the immediate fate of incoming tumour cells as they colonize this tissue, and even less known about how they make first contact with the immune system. Primary tumours liberate circulating tumour cells (CTCs) into the blood and we have developed a stable intravital two-photon lung imaging model in mice(6) for direct observation of the arrival of CTCs and subsequent host interaction. Here we show dynamic generation of tumour microparticles in shear flow in the capillaries within minutes of CTC entry. Rather than dispersing under flow, many of these microparticles remain attached to the lung vasculature or independently migrate along the inner walls of vessels. Using fluorescent lineage reporters and flow cytometry, we observed 'waves' of distinct myeloid cell subsets that load differentially and sequentially with this CTC-derived material. Many of these tumour-ingesting myeloid cells collectively accumulated in the lung interstitium along with the successful metastatic cells and, as previously understood, promote the development of successful metastases from surviving tumour cells(3). Although the numbers of these cells rise globally in the lung with metastatic exposure and ingesting myeloid cells undergo phenotypic changes associated with microparticle ingestion, a consistently sparse population of resident conventional dendritic cells, among the last cells to interact with CTCs, confer anti-metastatic protection. This work reveals that CTC fragmentation generates immune-interacting intermediates, and defines a competitive relationship between phagocyte populations for tumour loading during metastatic cell seeding.
C1 [Headley, Mark B.; Bins, Adriaan; Nip, Alyssa; Roberts, Edward W.; Gerard, Audrey; Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, 513 Parnassus Ave,HSW512, San Francisco, CA 94143 USA.
   [Bins, Adriaan] Acad Med Ctr Amsterdam, Dept Med Oncol, Meibergdreef 9, NL-91105 AZ Amsterdam, Netherlands.
   [Looney, Mark R.] Univ Calif San Francisco, Dept Med, 513 Parnassus Ave,HSW512, San Francisco, CA 94143 USA.
   [Looney, Mark R.] Univ Calif San Francisco, Dept Lab Med, 513 Parnassus Ave,HSW512, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of Amsterdam; Academic Medical Center Amsterdam; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Krummel, MF (corresponding author), Univ Calif San Francisco, Dept Pathol, 513 Parnassus Ave,HSW512, San Francisco, CA 94143 USA.
EM matthew.krummel@ucsf.edu
FU Department of Defense [W81XWH-13-1-0009]; NIH [U54 CA163123, P01 HL024136, R21CA167601]; National Institute of Allergy and Infectious Diseases [T32AI007334] Funding Source: NIH RePORTER
NR 28
TC 350
Z9 419
U1 4
U2 200
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 513
EP +
DI 10.1038/nature16985
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300043
PM 26982733
DA 2026-03-09
ER

PT J
AU Blanco, S
   Bandiera, R
   Popis, M
   Hussain, S
   Lombard, P
   Aleksic, J
   Sajini, A
   Tanna, H
   Cortés-Garrido, R
   Gkatza, N
   Dietmann, S
   Frye, M
AF Blanco, Sandra
   Bandiera, Roberto
   Popis, Martyna
   Hussain, Shobbir
   Lombard, Patrick
   Aleksic, Jelena
   Sajini, Abdulrahim
   Tanna, Hinal
   Cortes-Garrido, Rosana
   Gkatza, Nikoletta
   Dietmann, Sabine
   Frye, Michaela
TI Stem cell function and stress response are controlled by protein synthesis
SO NATURE
LA English
DT Article
ID open reading frames; methyltransferase misu nsun2; rna methyltransferase; gene-expression; messenger-rna; translational regulation; tgf-beta; in-vivo; methylation; identification
AB Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.
C1 [Blanco, Sandra; Bandiera, Roberto; Popis, Martyna; Lombard, Patrick; Aleksic, Jelena; Sajini, Abdulrahim; Cortes-Garrido, Rosana; Gkatza, Nikoletta; Dietmann, Sabine; Frye, Michaela] Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Dept Genet, Cambridge CB2 1QR, England.
   [Hussain, Shobbir] Univ Bath, Dept Biol & Biochem, Claverton Down, Bath BA2 7AY, Avon, England.
   [Tanna, Hinal] Univ Cambridge, CR UK, Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England.
C3 University of Cambridge; University of Bath; University of Cambridge; CRUK Cambridge Institute
RP Frye, M (corresponding author), Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Dept Genet, Cambridge CB2 1QR, England.
EM mf364@cam.ac.uk
FU Cancer Research UK; Worldwide Cancer Research; Medical Research Council (MRC); European Research Council; EMBO; Wellcome Trust; MRC; MRC [MR/M01939X/1, G0801904] Funding Source: UKRI; Cancer Research UK [15181] Funding Source: researchfish; Medical Research Council [MC_PC_12009, G0801904, MR/M01939X/1] Funding Source: researchfish
NR 60
TC 377
Z9 423
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 335
EP +
DI 10.1038/nature18282
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800025
PM 27306184
DA 2026-03-09
ER

PT J
AU McDermott, JH
   Schultz, AF
   Undurraga, EA
   Godoy, RA
AF McDermott, Josh H.
   Schultz, Alan F.
   Undurraga, Eduardo A.
   Godoy, Ricardo A.
TI Indifference to dissonance in native Amazonians reveals cultural variation in music perception
SO NATURE
LA English
DT Article
ID tonal consonance; preference; fluctuations; foundations; complexes; infants; bolivia; hearing; chords; tones
AB Music is present in every culture, but the degree to which it is shaped by biology remains debated. One widely discussed phenomenon is that some combinations of notes are perceived by Westerners as pleasant, or consonant, whereas others are perceived as unpleasant, or dissonant(1). The contrast between consonance and dissonance is central to Western music(2,3), and its origins have fascinated scholars since the ancient Greeks(4-10). Aesthetic responses to consonance are commonly assumed by scientists to have biological roots(11-14), and thus to be universally present in humans(15,16). Ethnomusicologists(17) and composers(8), in contrast, have argued that consonance is a creation of Western musical culture(6). The issue has remained unresolved, partly because little is known about the extent of cross-cultural variation in consonance preferences(18). Here we report experiments with the Tsimane'-a native Amazonian society with minimal exposure to Western culture-and comparison populations in Bolivia and the United States that varied in exposure to Western music. Participants rated the pleasantness of sounds. Despite exhibiting Western-like discrimination abilities and Western-like aesthetic responses to familiar sounds and acoustic roughness, the Tsimane' rated consonant and dissonant chords and vocal harmonies as equally pleasant. By contrast, Bolivian city-and town-dwellers exhibited significant preferences for consonance, albeit to a lesser degree than US residents. The results indicate that consonance preferences can be absent in cultures sufficiently isolated from Western music, and are thus unlikely to reflect innate biases or exposure to harmonic natural sounds. The observed variation in preferences is presumably determined by exposure to musical harmony, suggesting that culture has a dominant role in shaping aesthetic responses to music.
C1 [McDermott, Josh H.] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
   [Schultz, Alan F.] Baylor Univ, Dept Anthropol, Waco, TX 76798 USA.
   [Undurraga, Eduardo A.; Godoy, Ricardo A.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02453 USA.
   [Undurraga, Eduardo A.] Pontificia Univ Catolica Chile, Ctr Intercultural & Indigenous Res, Santiago 7820436, Region Metropol, Chile.
C3 Massachusetts Institute of Technology (MIT); Baylor University; Brandeis University; Pontificia Universidad Catolica de Chile
RP McDermott, JH (corresponding author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
EM jhm@mit.edu
FU National Science Foundation; McDonnell Scholar Award; TAPS
NR 41
TC 226
Z9 256
U1 4
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 547
EP +
DI 10.1038/nature18635
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600028
PM 27409816
DA 2026-03-09
ER

PT J
AU Ma, ZG
   Stork, T
   Bergles, DE
   Freeman, MR
AF Ma, Zhiguo
   Stork, Tobias
   Bergles, Dwight E.
   Freeman, Marc R.
TI Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour
SO NATURE
LA English
DT Article
ID drosophila-melanogaster; tyramine-receptor; calcium waves; mechanical stimulation; cortical astrocytes; neuronal-activity; glutamate; networks; gliotransmitters; oscillations
AB Astrocytes associate with synapses throughout the brain and express receptors for neurotransmitters that can increase intracellular calcium (Ca2+)(1-3). Astrocytic Ca2+ signalling has been proposed to modulate neural circuit activity(4), but the pathways that regulate these events are poorly defined and in vivo evidence linking changes in astrocyte Ca2+ levels to alterations in neurotransmission or behaviour is limited. Here we show that Drosophila astrocytes exhibit activity-regulated Ca2+ signalling in vivo. Tyramine and octopamine released from neurons expressing tyrosine decarboxylase 2 (Tdc2) signal directly to astrocytes to stimulate Ca2+ increases through the octopamine/tyramine receptor (Oct-TyrR) and the transient receptor potential (TRP) channel Water witch (Wtrw), and astrocytes in turn modulate downstream dopaminergic neurons. Application of tyramine or octopamine to live preparations silenced dopaminergic neurons and this inhibition required astrocytic Oct-TyrR and Wtrw. Increasing astrocyte Ca2+ signalling was sufficient to silence dopaminergic neuron activity, which was mediated by astrocyte endocytic function and adenosine receptors. Selective disruption of Oct-TyrR or Wtrw expression in astrocytes blocked astrocytic Ca2+ signalling and profoundly altered olfactory-driven chemotaxis and touch-induced startle responses. Our work identifies Oct-TyrR and Wtrw as key components of the astrocytic Ca2+ signalling machinery, provides direct evidence that octopamine- and tyramine-based neuromodulation can be mediated by astrocytes, and demonstrates that astrocytes are essential for multiple sensory-driven behaviours in Drosophila.
C1 [Ma, Zhiguo; Stork, Tobias; Freeman, Marc R.] Univ Massachusetts, Dept Neurobiol, Sch Med, Worcester, MA 01605 USA.
   [Ma, Zhiguo; Stork, Tobias; Freeman, Marc R.] Univ Massachusetts, Howard Hughes Med Inst, Sch Med, Worcester, MA 01605 USA.
   [Bergles, Dwight E.] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.
   [Freeman, Marc R.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester; Johns Hopkins University; Oregon Health & Science University
RP Freeman, MR (corresponding author), Univ Massachusetts, Dept Neurobiol, Sch Med, Worcester, MA 01605 USA.; Freeman, MR (corresponding author), Univ Massachusetts, Howard Hughes Med Inst, Sch Med, Worcester, MA 01605 USA.; Freeman, MR (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
EM freemmar@ohsu.edu
FU NINDS [R01 NS053538]; National Institute of Neurological Disorders and Stroke [R37NS053538, R01NS053538] Funding Source: NIH RePORTER
NR 29
TC 196
Z9 240
U1 2
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 428
EP 432
DI 10.1038/nature20145
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700054
PM 27828941
DA 2026-03-09
ER

PT J
AU Quick, J
   Loman, NJ
   Duraffour, S
   Simpson, JT
   Ettore, S
   Cowley, L
   Bore, JA
   Koundouno, R
   Dudas, G
   Mikhail, A
   Ouédraogo, N
   Afrough, B
   Bah, A
   Baum, JHJ
   Becker-Ziaja, B
   Boettcher, JP
   Cabeza-Cabrerizo, M
   Camino-Sánchez, A
   Carter, LL
   Doerrbecker, J
   Enkirch, T
   García-Dorival, I
   Hetzelt, N
   Hinzmann, J
   Holm, T
   Kafetzopoulou, LE
   Koropogui, M
   Kosgey, A
   Kuisma, E
   Logue, CH
   Mazzarelli, A
   Meisel, S
   Mertens, M
   Michel, J
   Ngabo, D
   Nitzsche, K
   Pallasch, E
   Patrono, LV
   Portmann, J
   Repits, JG
   Rickett, NY
   Sachse, A
   Singethan, K
   Vitoriano, I
   Emanaberhan, RLY
   Zekeng, EG
   Racine, T
   Bello, A
   Sall, AA
   Faye, O
   Faye, O
   Magassouba, N
   Williams, CV
   Amburgey, V
   Winona, L
   Davis, E
   Gerlach, J
   Washington, F
   Monteil, V
   Jourdain, M
   Bererd, M
   Camara, A
   Somlare, H
   Camara, A
   Gerard, M
   Bado, G
   Baillet, B
   Delaune, D
   Nebie, KY
   Diarra, A
   Savane, Y
   Pallawo, RB
   Gutierrez, GJ
   Milhano, N
   Roger, I
   Williams, CJ
   Yattara, F
   Lewandowski, K
   Taylor, J
   Rachwal, P
   Turner, DJ
   Pollakis, G
   Hiscox, JA
   Matthews, DA
   O'Shea, MK
   Johnston, AM
   Wilson, D
   Hutley, E
   Smit, E
   DiCaro, A
   Wölfel, R
   Stoecker, K
   Fleischmann, E
   Gabriel, M
   Weller, SA
   Koivogui, L
   Diallo, B
   Keïta, S
   Rambaut, A
   Formenty, P
   Günther, S
   Carroll, MW
AF Quick, Joshua
   Loman, Nicholas J.
   Duraffour, Sophie
   Simpson, Jared T.
   Severi, Ettore
   Cowley, Lauren
   Bore, Joseph Akoi
   Koundouno, Raymond
   Dudas, Gytis
   Mikhail, Amy
   Ouedraogo, Nobila
   Afrough, Babak
   Bah, Amadou
   Baum, Jonathan H. J.
   Becker-Ziaja, Beate
   Boettcher, Jan Peter
   Cabeza-Cabrerizo, Mar
   Camino-Sanchez, Alvaro
   Carter, Lisa L.
   Doerrbecker, Juliane
   Enkirch, Theresa
   Garcia-Dorival, Isabel
   Hetzelt, Nicole
   Hinzmann, Julia
   Holm, Tobias
   Kafetzopoulou, Liana Eleni
   Koropogui, Michel
   Kosgey, Abigael
   Kuisma, Eeva
   Logue, Christopher H.
   Mazzarelli, Antonio
   Meisel, Sarah
   Mertens, Marc
   Michel, Janine
   Ngabo, Didier
   Nitzsche, Katja
   Pallasch, Elisa
   Patrono, Livia Victoria
   Portmann, Jasmine
   Repits, Johanna Gabriella
   Rickett, Natasha Y.
   Sachse, Andreas
   Singethan, Katrin
   Vitoriano, Ines
   Emanaberhan, Rahel L. Y.
   Zekeng, Elsa G.
   Racine, Trina
   Bello, Alexander
   Sall, Amadou Alpha
   Faye, Ousmane
   Faye, Oumar
   Magassouba, N'Faly
   Williams, Cecelia V.
   Amburgey, Victoria
   Winona, Linda
   Davis, Emily
   Gerlach, Jon
   Washington, Frank
   Monteil, Vanessa
   Jourdain, Marine
   Bererd, Marion
   Camara, Alimou
   Somlare, Hermann
   Camara, Abdoulaye
   Gerard, Marianne
   Bado, Guillaume
   Baillet, Bernard
   Delaune, Deborah
   Nebie, Koumpingnin Yacouba
   Diarra, Abdoulaye
   Savane, Yacouba
   Pallawo, Raymond Bernard
   Gutierrez, Giovanna Jaramillo
   Milhano, Natacha
   Roger, Isabelle
   Williams, Christopher J.
   Yattara, Facinet
   Lewandowski, Kuiama
   Taylor, James
   Rachwal, Phillip
   Turner, Daniel J.
   Pollakis, Georgios
   Hiscox, Julian A.
   Matthews, David A.
   O'Shea, Matthew K.
   Johnston, Andrew McD
   Wilson, Duncan
   Hutley, Emma
   Smit, Erasmus
   DiCaro, Antonino
   Woelfel, Roman
   Stoecker, Kilian
   Fleischmann, Erna
   Gabriel, Martin
   Weller, Simon A.
   Koivogui, Lamine
   Diallo, Boubacar
   Keita, Sakoba
   Rambaut, Andrew
   Formenty, Pierre
   Guenther, Stephan
   Carroll, Miles W.
TI Real-time, portable genome sequencing for Ebola surveillance
SO NATURE
LA English
DT Article
ID virus; transmission; outbreak; evolution; dynamics
AB The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths(1). Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 x 10(-3) and 1.42 x 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic(2-7). Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions(8). Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities(9). To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.
C1 [Quick, Joshua; Loman, Nicholas J.; Boettcher, Jan Peter; Garcia-Dorival, Isabel] Univ Birmingham, Inst Microbiol & Infect, Birmingham B15 2TT, W Midlands, England.
   [Duraffour, Sophie; Bore, Joseph Akoi; Koundouno, Raymond; Afrough, Babak; Bah, Amadou; Baum, Jonathan H. J.; Becker-Ziaja, Beate; Boettcher, Jan Peter; Cabeza-Cabrerizo, Mar; Camino-Sanchez, Alvaro; Carter, Lisa L.; Doerrbecker, Juliane; Enkirch, Theresa; Garcia-Dorival, Isabel; Hetzelt, Nicole; Hinzmann, Julia; Holm, Tobias; Kafetzopoulou, Liana Eleni; Koropogui, Michel; Kosgey, Abigael; Kuisma, Eeva; Logue, Christopher H.; Mazzarelli, Antonio; Meisel, Sarah; Mertens, Marc; Michel, Janine; Ngabo, Didier; Nitzsche, Katja; Pallasch, Elisa; Patrono, Livia Victoria; Portmann, Jasmine; Repits, Johanna Gabriella; Rickett, Natasha Y.; Sachse, Andreas; Singethan, Katrin; Vitoriano, Ines; Emanaberhan, Rahel L. Y.; Zekeng, Elsa G.; DiCaro, Antonino; Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Gabriel, Martin; Guenther, Stephan; Carroll, Miles W.] Bernhard Nocht Inst Trop Med, European Mobile Lab Consortium, D-20359 Hamburg, Germany.
   [Duraffour, Sophie; Baum, Jonathan H. J.; Becker-Ziaja, Beate; Cabeza-Cabrerizo, Mar; Doerrbecker, Juliane; Holm, Tobias; Meisel, Sarah; Nitzsche, Katja; Pallasch, Elisa; Patrono, Livia Victoria; Emanaberhan, Rahel L. Y.; Gabriel, Martin; Guenther, Stephan] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany.
   [Simpson, Jared T.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Simpson, Jared T.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada.
   [Severi, Ettore; Milhano, Natacha; Williams, Christopher J.] European Ctr Dis Prevent & Control ECDC, S-17165 Solna, Sweden.
   [Cowley, Lauren; Mikhail, Amy] Publ Hlth England, Natl Infect Serv, London NW9 5EQ, England.
   [Dudas, Gytis; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 2FL, Midlothian, Scotland.
   [Ouedraogo, Nobila] Robert Koch Inst, PAE, German FETP, D-13302 Berlin, Germany.
   [Afrough, Babak; Kuisma, Eeva; Logue, Christopher H.; Ngabo, Didier; Vitoriano, Ines; Lewandowski, Kuiama; Carroll, Miles W.] Publ Hlth England, Natl Infect Serv, Porton Down SP4 0JG, Wilts, England.
   [Bah, Amadou] Swiss Trop & Publ Hlth Inst, CH-4002 Basel, Switzerland.
   [Boettcher, Jan Peter; Hetzelt, Nicole; Hinzmann, Julia; Michel, Janine; Sachse, Andreas] Robert Koch Inst, D-13302 Berlin, Germany.
   [Carter, Lisa L.] UCL, London WC1E 6BT, England.
   [Enkirch, Theresa] Paul Ehrlich Inst, Div Vet Med, D-63225 Langen, Germany.
   [Garcia-Dorival, Isabel; Rickett, Natasha Y.; Zekeng, Elsa G.; Pollakis, Georgios; Hiscox, Julian A.] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 7BE, Merseyside, England.
   [Kafetzopoulou, Liana Eleni] Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, B-3000 Louvain, Belgium.
   [Koropogui, Michel; Yattara, Facinet; Keita, Sakoba] Minist Hlth Guinea, Conakry, Guinea.
   [Kosgey, Abigael] Kenya Govt Med Res Ctr, Nairobi 00200, Kenya.
   [Mazzarelli, Antonio; DiCaro, Antonino] Natl Inst Infect Dis L Spallanzani, I-00149 Rome, Italy.
   [Mertens, Marc] Friedrich Loeffler Inst, D-17493 Greifswald, Germany.
   [Portmann, Jasmine] Fed Off Civil Protect, Spiez Lab, CH-3700 Spiez, Switzerland.
   [Repits, Johanna Gabriella] Janssen Cilag, S-19207 Stockholm, Sweden.
   [Rickett, Natasha Y.; Zekeng, Elsa G.; Pollakis, Georgios; Hiscox, Julian A.] Univ Liverpool, NIHR Hlth Protect Res Unit Emerging & Zoonot Infe, Liverpool L69 7BE, Merseyside, England.
   [Singethan, Katrin] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany.
   [Racine, Trina; Bello, Alexander] Publ Hlth Agcy Canada, Winnipeg, MB R3E 3R2, Canada.
   [Sall, Amadou Alpha; Faye, Ousmane] Inst Pasteur, Dakar, Senegal.
   [Magassouba, N'Faly] Lab Fievres Hemorrag Guinee, Conakry, Guinea.
   [Williams, Cecelia V.; Amburgey, Victoria; Winona, Linda] Sandia Natl Labs, Albuquerque, NM 87185 USA.
   [Williams, Cecelia V.; Amburgey, Victoria; Winona, Linda; Davis, Emily; Gerlach, Jon; Washington, Frank] Ratoma Ebola Diagnost Ctr, Conakry, Guinea.
   [Davis, Emily; Gerlach, Jon; Washington, Frank] MRIGlobal, Kansas City, MO 64110 USA.
   [Monteil, Vanessa; Jourdain, Marine; Bererd, Marion; Camara, Alimou; Somlare, Hermann; Camara, Abdoulaye; Gerard, Marianne; Bado, Guillaume; Baillet, Bernard] Expertise France, Lab Kplan Forecariah Guinee, F-75006 Paris, France.
   [Delaune, Deborah] Federat Lab HIA Begin, F-94163 St Mande, France.
   [Delaune, Deborah] Ctr Traitement Soignants, Biol Lab, Conakry, Guinea.
   [Nebie, Koumpingnin Yacouba; Diarra, Abdoulaye; Savane, Yacouba; Pallawo, Raymond Bernard; Roger, Isabelle; Diallo, Boubacar; Formenty, Pierre] World Hlth Org, Conakry, Guinea.
   [Gutierrez, Giovanna Jaramillo] London Sch Hyg & Trop Med, London EC1E 7HT, England.
   [Milhano, Natacha] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
   [Williams, Christopher J.] Publ Hlth Wales, Cardiff CF11 9LJ, S Glam, Wales.
   [Taylor, James; Rachwal, Phillip; Weller, Simon A.] Dstl Porton Down, Salisbury SP4 0JQ, Wilts, England.
   [Turner, Daniel J.] Oxford Nanopore Technol, Oxford OX4 4GA, England.
   [Matthews, David A.] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England.
   [O'Shea, Matthew K.; Johnston, Andrew McD; Wilson, Duncan] Royal Ctr Def Med, Acad Dept Mil Med, Birmingham B15 2TH, W Midlands, England.
   [Hutley, Emma] Royal Ctr Def Med, Ctr Def Pathol, Birmingham B15 2TH, W Midlands, England.
   [Smit, Erasmus] Queen Elizabeth Hosp, Birmingham B12 2TH, W Midlands, England.
   [Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna] Bundeswehr Inst Microbiol, D-80937 Munich, Germany.
   [Koivogui, Lamine] Inst Natl St Publ, Conakry, Guinea.
   [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 2FL, Midlothian, Scotland.
   [Carroll, Miles W.] Univ Southampton, South Gen Hosp, Southampton SO16 6YD, Hants, England.
   [Carroll, Miles W.] NIHR Hlth Protect Res, Res Unit Emerging & Zoonot Infect, PHE Porton Down, London, England.
C3 University of Birmingham; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; University of Toronto; Ontario Institute for Cancer Research; University of Toronto; European Centre for Disease Prevention & Control; Public Health England; University of Edinburgh; Robert Koch Institute; Public Health England; Swiss School of Public Health (SSPH+); University of Basel; Swiss Tropical & Public Health Institute; Robert Koch Institute; University of London; University College London; Paul Ehrlich Institute; University of Liverpool; KU Leuven; Kenya Medical Research Institute; IRCCS Lazzaro Spallanzani; Friedrich Loeffler Institute; Johnson & Johnson; Johnson & Johnson Sweden; University of Liverpool; Technical University of Munich; Public Health Agency of Canada; Pasteur Network; Institut Pasteur Dakar; United States Department of Energy (DOE); Sandia National Laboratories; World Health Organization; University of London; London School of Hygiene & Tropical Medicine; Norwegian Institute of Public Health (NIPH); Defence Science & Technology Laboratory; Oxford Nanopore Technologies; University of Bristol; Royal Centre for Defence Medicine; Royal Centre for Defence Medicine; University of Birmingham; Bundeswehr Institute of Microbiology (IMB); National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC); University of Edinburgh; University of Southampton
RP Loman, NJ (corresponding author), Univ Birmingham, Inst Microbiol & Infect, Birmingham B15 2TT, W Midlands, England.
EM n.j.loman@bham.ac.uk
FU European Union [666100]; Directorate-General for International Cooperation and Development [IFS/2011/272-372]; NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC); Medical Research Council; Ontario Institute for Cancer Research through Government of Ontario; UK Ministry of Defence (MOD); EU [278433-PREDEMICS]; ERC [260864]; MRC [MR/J014370/1, MR/L015080/1, MR/M501621/1] Funding Source: UKRI; Medical Research Council [MR/J014370/1, MR/M501621/1, MR/L015080/1] Funding Source: researchfish
NR 33
TC 1035
Z9 1226
U1 8
U2 457
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 228
EP +
DI 10.1038/nature16996
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700041
PM 26840485
DA 2026-03-09
ER

PT J
AU Buitink, S
   Corstanje, A
   Falcke, H
   Hörandel, JR
   Huege, T
   Nelles, A
   Rachen, JP
   Rossetto, L
   Schellart, P
   Scholten, O
   ter Veen, S
   Thoudam, S
   Trinh, TNG
   Anderson, J
   Asgekar, A
   Avruch, IM
   Bell, ME
   Bentum, MJ
   Bernardi, G
   Best, P
   Bonafede, A
   Breitling, F
   Broderick, JW
   Brouw, WN
   Brüggen, M
   Buteher, HR
   Carbone, D
   Ciardi, B
   Conway, JE
   de Gasperin, E
   de Geus, E
   Deller, A
   Dettmar, RJ
   van Diepen, G
   Duscha, S
   Eislöffel, J
   Engels, D
   Enriquez, JE
   Fallows, RA
   Fender, R
   Ferrari, C
   Frieswijk, W
   Garrett, MA
   Griessmeier, JM
   Gunst, AW
   van Haarlem, MP
   Hassall, TE
   Heald, G
   Hessels, JWT
   Hoeft, M
   Horneffer, A
   Iaeobelli, M
   Intema, H
   Juette, E
   Karastergiou, A
   Kondratiev, VI
   Kramer, M
   Kuniyoshi, M
   Kuper, G
   van Lecuwen, J
   Loose, GM
   Maat, P
   Nann, G
   Markoff, S
   McFadden, R
   McKay-Bukowski, D
   McKean, JP
   Mevius, M
   Mulcahy, DD
   Munk, H
   Norden, MJ
   Orru, E
   Paas, H
   Pandey-Pommier, M
   Pandey, VN
   Pietka, M
   Pizzo, R
   Polatidis, AG
   Reich, W
   Rötgering, HJA
   Scaife, AMM
   Schwarz, DJ
   Serylak, M
   Sluman, J
   Smirnov, O
   Stappers, BW
   Steinmetz, M
   Stewart, A
   Swinbank, J
   Tagger, M
   Tang, Y
   Tasse, C
   Toribio, MC
   Vermeulen, R
   Vocks, C
   Vogt, C
   van Weeren, RJ
   Wijers, RAMJ
   Wijnholds, SJ
   Wise, MW
   Wucknitz, O
   Yatawatta, S
   Zarka, P
   Zensuss, JA
AF Buitink, S.
   Corstanje, A.
   Falcke, H.
   Hoerandel, J. R.
   Huege, T.
   Nelles, A.
   Rachen, J. P.
   Rossetto, L.
   Schellart, P.
   Scholten, O.
   ter Veen, S.
   Thoudam, S.
   Trinh, T. N. G.
   Anderson, J.
   Asgekar, A.
   Avruch, I. M.
   Bell, M. E.
   Bentum, M. J.
   Bernardi, G.
   Best, P.
   Bonafede, A.
   Breitling, F.
   Broderick, J. W.
   Brouw, W. N.
   Brueggen, M.
   Buteher, H. R.
   Carbone, D.
   Ciardi, B.
   Conway, J. E.
   de Gasperin, E.
   de Geus, E.
   Deller, A.
   Dettmar, R. -J.
   van Diepen, G.
   Duscha, S.
   Eisloeffel, J.
   Engels, D.
   Enriquez, J. E.
   Fallows, R. A.
   Fender, R.
   Ferrari, C.
   Frieswijk, W.
   Garrett, M. A.
   Griessmeier, J. M.
   Gunst, A. W.
   van Haarlem, M. P.
   Hassall, T. E.
   Heald, G.
   Hessels, J. W. T.
   Hoeft, M.
   Horneffer, A.
   Iaeobelli, M.
   Intema, H.
   Juette, E.
   Karastergiou, A.
   Kondratiev, V. I.
   Kramer, M.
   Kuniyoshi, M.
   Kuper, G.
   van Lecuwen, J.
   Loose, G. M.
   Maat, P.
   Nann, G.
   Markoff, S.
   McFadden, R.
   McKay-Bukowski, D.
   McKean, J. P.
   Mevius, M.
   Mulcahy, D. D.
   Munk, H.
   Norden, M. J.
   Orru, E.
   Paas, H.
   Pandey-Pommier, M.
   Pandey, V. N.
   Pietka, M.
   Pizzo, R.
   Polatidis, A. G.
   Reich, W.
   Roetgering, H. J. A.
   Scaife, A. M. M.
   Schwarz, D. J.
   Serylak, M.
   Sluman, J.
   Smirnov, O.
   Stappers, B. W.
   Steinmetz, M.
   Stewart, A.
   Swinbank, J.
   Tagger, M.
   Tang, Y.
   Tasse, C.
   Toribio, M. C.
   Vermeulen, R.
   Vocks, C.
   Vogt, C.
   van Weeren, R. J.
   Wijers, R. A. M. J.
   Wijnholds, S. J.
   Wise, M. W.
   Wucknitz, O.
   Yatawatta, S.
   Zarka, P.
   Zensuss, J. A.
TI A large light-mass component of cosmic rays at 1017-1017.5 electronvolts from radio observations
SO NATURE
LA English
DT Article
ID air-showers; energy-spectrum; emission; lofar; pulses
AB Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal1 comes from accelerators capable of producing cosmic rays of these energies(2). Cosmic rays initiate air showers-cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum3 (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground(4). Current measurements(5) have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays(6-8) is a rapidly developing technique(9) for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front(6,12). Here we report radio measurements of X-max with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 1017-1017.5 electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.
C1 [Buitink, S.] Vrije Univ Brussel, Inst Astrophys, Pleinlaan 2, B-1050 Brussels, Belgium.
   [Buitink, S.; Corstanje, A.; Falcke, H.; Hoerandel, J. R.; Nelles, A.; Rachen, J. P.; Rossetto, L.; Schellart, P.; Thoudam, S.] Radboud Univ Nijmegen, IMAPP, Dept Astrophys, POB 9010, NL-6500 GL Nijmegen, Netherlands.
   [Falcke, H.; ter Veen, S.; Asgekar, A.; Bentum, M. J.; Brouw, W. N.; de Geus, E.; Deller, A.; van Diepen, G.; Duscha, S.; Enriquez, J. E.; Fallows, R. A.; Frieswijk, W.; Garrett, M. A.; Gunst, A. W.; van Haarlem, M. P.; Heald, G.; Hessels, J. W. T.; Iaeobelli, M.; Kondratiev, V. I.; Kuper, G.; van Lecuwen, J.; Loose, G. M.; Maat, P.; McFadden, R.; McKean, J. P.; Mevius, M.; Munk, H.; Norden, M. J.; Orru, E.; Pandey, V. N.; Pizzo, R.; Polatidis, A. G.; Sluman, J.; Tang, Y.; Toribio, M. C.; Vermeulen, R.; Vogt, C.; Wijnholds, S. J.; Wise, M. W.; Yatawatta, S.] Netherlands Inst Radio Astron, ASTRON, Postbus 2, NL-7990 AA Dwingeloo, Netherlands.
   [Falcke, H.; Hoerandel, J. R.] Nikhef, Sci Pk Amsterdam, NL-1098 XG Amsterdam, Netherlands.
   [Falcke, H.; Horneffer, A.; Kramer, M.; Reich, W.; Wucknitz, O.; Zensuss, J. A.] Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
   [Huege, T.] Karlsruhe Inst Technol, Inst Nucl Phys IKP, Postfach 3640, D-76021 Karlsruhe, Germany.
   [Nelles, A.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Scholten, O.; Trinh, T. N. G.] Univ Groningen, KVI Ctr Adv Radiat Technol, NL-9747 AA Groningen, Netherlands.
   [Scholten, O.] Vrije Univ Brussel, Dienst ELEM, B-1050 Brussels, Belgium.
   [Anderson, J.] Helmholtz Zentrum Potsdam, Deutsch GeoForschungsZentrum GEZ, Dept 1, Geodesy & Remote Sensing, Telegrafenberg A17, D-14473 Potsdam, Germany.
   [Asgekar, A.] Shell Technol Ctr, Bangalore 560048, Karnataka, India.
   [Avruch, I. M.] SRON Netherlands Inst Space Res, POB 800, NL-9700 AV Groningen, Netherlands.
   [Avruch, I. M.; Brouw, W. N.; Heald, G.; McKean, J. P.; Mevius, M.] Univ Groningen, Kapteyn Astron Inst, POB 800, NL-9700 AV Groningen, Netherlands.
   [Bell, M. E.] CSIRO Australia Telescope Natl Facil, POB 76, Epping, NSW 1710, Australia.
   [Bell, M. E.] Univ Twente, POB 217, NL-7500 AE Enschede, Netherlands.
   [Bernardi, G.; van Weeren, R. J.] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
   [Bernardi, G.; Smirnov, O.] SKA South Africa, 3rd Floor,Pk Rd, ZA-7405 Pinelands, South Africa.
   [Best, P.] Univ Edinburgh, Royal Observ Edinburgh, Inst Astron, Blackford Hill, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Bonafede, A.; Brueggen, M.; de Gasperin, E.] Univ Hamburg, Gojenbergsweg 112, D-21029 Hamburg, Germany.
   [Breitling, F.; Nann, G.; Steinmetz, M.; Vocks, C.] Leibniz Inst Astrophys Potsdam AIP, Sternwarte 16, D-14482 Potsdam, Germany.
   [Broderick, J. W.; Hassall, T. E.; Mulcahy, D. D.; Scaife, A. M. M.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Buteher, H. R.] Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2611, Australia.
   [Carbone, D.; Hessels, J. W. T.; van Lecuwen, J.; Markoff, S.; Swinbank, J.; Wijers, R. A. M. J.; Wise, M. W.] Univ Amsterdam, Anton Pannekoek Inst Astron, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
   [Ciardi, B.] Max Planck Inst Astrophys, Karl Schwarzschild Str 1, D-85741 Garching, Germany.
   [Conway, J. E.] Chalmers Univ Technol, Dept Earth & Space Sci, Onsala Space Observ, SE-43992 Onsala, Sweden.
   [de Geus, E.] SmarterVision BV, Oostersingel 5, NL-9401 JX Assen, Netherlands.
   [Dettmar, R. -J.; Juette, E.] Ruhr Univ Bochum, Astron Inst, Univ Str 150, D-44780 Bochum, Germany.
   [Eisloeffel, J.; Hoeft, M.] Thuringer Landessternwarte, Sternwarte 5, D-07778 Tautenburg, Germany.
   [Engels, D.] Elamburger Sternwarte, Gojenbergsweg 112, D-21029 Hamburg, Germany.
   [Fender, R.; Karastergiou, A.; Pietka, M.; Serylak, M.; Stewart, A.] Univ Oxford, Dept Astrophys, Denys Wilkinson Bldg,Keble Rd, Oxford OX1 3RH, England.
   [Ferrari, C.] Univ Cote Azur, Observ Cote Azur, CNRS, Lab Lagrange, Blvd Observ,CS 34229, F-06304 Nice 4, France.
   [Garrett, M. A.; Intema, H.; Roetgering, H. J. A.; Toribio, M. C.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Griessmeier, J. M.; Tagger, M.] Univ Orleans, CNRS, LPC2E, F-45071 Orleans 2, France.
   [Griessmeier, J. M.] Univ Orleans, OSUC, Stn Radioastron Nancay, Observ Paris,CNRS,INSU,USR 704, Route Souesmes, F-18330 Nancay, France.
   [Intema, H.] Natl Radio Astron Observ, 1003 Lopezville Rd, Socorro, NM 87801 USA.
   [Kondratiev, V. I.] Ctr Astro Space, Lebeclev Phys Inst, Profsoyuznayast 84-32, Moscow 117997, Russia.
   [Kramer, M.; Stappers, B. W.] Univ Manchester, Sch Phys & Astron, Jodrell Bank Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Kuniyoshi, M.] Natl Astron Observ Japan, Mitaka, Tokyo 1818588, Japan.
   [McKay-Bukowski, D.] Univ Oulu, Sodankyla Geophys Observ, Tahtelantie 62, Sodankyla 99600, Finland.
   [McKay-Bukowski, D.] STFC Rutherford Appleton Lab, Harwell Sci & Innovation Campus, Didcot OX11 0QX, Oxon, England.
   [Paas, H.] Univ Groningen, CIT, POB 72, NL-9700 AB Groningen, Netherlands.
   [Pandey-Pommier, M.] Observ Lyon, Ctr Rech Astrophys Lyon, 9 Ave Charles Andre, F-69561 St Gems Laval, France.
   [Schwarz, D. J.] Univ Bielefeld, Fak Phys, Postfach 100131, D-33501 Bielefeld, Germany.
   [Smirnov, O.; Tasse, C.] Rhodes Univ, Dept Phys & Elect, POB 94, ZA-6140 Grahamstown, South Africa.
   [Swinbank, J.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Tasse, C.] Univ Paris Diderot, CNRS, Observ Paris, GEPI, 5 Pl Jules Janssen, F-92190 Meudon, France.
   [Zarka, P.] UPMC, Univ Paris Diderot, CNRS, LESIA,Observ Paris, 5 Pl Jules Janssen, F-92190 Meudon, France.
C3 Vrije Universiteit Brussel; Radboud University Nijmegen; FOM National Institute for Subatomic Physics; Max Planck Society; Helmholtz Association; Karlsruhe Institute of Technology; University of California System; University of California Irvine; University of Groningen; Vrije Universiteit Brussel; Helmholtz Association; GFZ Helmholtz Centre for Geosciences; Royal Dutch Shell; University of Groningen; Kapteyn Astronomical Institute; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility; University of Twente; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; SKA South Africa; University of Edinburgh; University of Hamburg; Leibniz Association; Leibniz Institut fur Astrophysik Potsdam (AIP); University of Southampton; Australian National University; University of Amsterdam; Max Planck Society; Chalmers University of Technology; Ruhr University Bochum; University of Oxford; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Leiden University; Leiden University - Excl LUMC; Centre National de la Recherche Scientifique (CNRS); Universite de Orleans; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Orleans; National Radio Astronomy Observatory (NRAO); University of Manchester; Jodrell Bank Centre for Astrophysics; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); University of Oulu; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of Groningen; Universite Lyon 1; University of Bielefeld; Rhodes University; Princeton University; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; Universite Paris Cite; Sorbonne Universite
RP Buitink, S (corresponding author), Vrije Univ Brussel, Inst Astrophys, Pleinlaan 2, B-1050 Brussels, Belgium.; Buitink, S (corresponding author), Radboud Univ Nijmegen, IMAPP, Dept Astrophys, POB 9010, NL-6500 GL Nijmegen, Netherlands.
EM Stijn.Buitink@vub.ac.be
FU Netherlands Organization for Scientific Research (NWO), VENI grant [639-041-130]; Netherlands Research School for Astronomy (NOVA); Samenwerkingsverband Noord-Nederland (SNN); Foundation for Fundamental Research on Matter (FOM); European Research Council under the European Union [227610, 640130]; STFC [ST/L000768/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/M001229/1, ST/L000768/1] Funding Source: researchfish; European Research Council (ERC) [640130] Funding Source: European Research Council (ERC)
NR 39
TC 129
Z9 140
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 70
EP +
DI 10.1038/nature16976
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900041
PM 26935696
DA 2026-03-09
ER

PT J
AU Kim, K
   Lee, T
   Kwon, Y
   Seo, Y
   Song, J
   Park, JK
   Lee, H
   Park, JY
   Ihee, H
   Cho, SJ
   Ryoo, R
AF Kim, Kyoungsoo
   Lee, Taekyoung
   Kwon, Yonghyun
   Seo, Yongbeom
   Song, Jongchan
   Park, Jung Ki
   Lee, Hyunsoo
   Park, Jeong Young
   Ihee, Hyotcherl
   Cho, Sung June
   Ryoo, Ryong
TI Lanthanum-catalysed synthesis of microporous 3D graphene-like carbons in a zeolite template
SO NATURE
LA English
DT Article
ID hydrogen storage; replicas
AB Three-dimensional graphene architectures with periodic nanopores-reminiscent of zeolite frameworks-are of topical interest because of the possibility of combining the characteristics of graphene with a three-dimensional porous structure(1-6). Lately, the synthesis of such carbons has been approached by using zeolites as templates and small hydrocarbon molecules that can enter the narrow pore apertures(7-15). However, pyrolytic carbonization of the hydrocarbons (a necessary step in generating pure carbon) requires high temperatures and results in non-selective carbon deposition outside the pores. Here, we demonstrate that lanthanum ions embedded in zeolite pores can lower the temperature required for the carbonization of ethylene or acetylene. In this way, a graphene-like carbon structure can be selectively formed inside the zeolite template, without carbon being deposited at the external surfaces. X-ray diffraction data from zeolite single crystals after carbonization indicate that electron densities corresponding to carbon atoms are generated along the walls of the zeolite pores. After the zeolite template is removed, the carbon framework exhibits an electrical conductivity that is two orders of magnitude higher than that of amorphous mesoporous carbon. Lanthanum catalysis allows a carbon framework to form in zeolite pores with diameters of less than 1 nanometre; as such, microporous carbon nanostructures can be reproduced with various topologies corresponding to different zeolite pore sizes and shapes. We demonstrate carbon synthesis for large-pore zeolites (FAU, EMT and beta), a one-dimensional medium-pore zeolite (LTL), and even small-pore zeolites (MFI and LTA). The catalytic effect is a common feature of lanthanum, yttrium and calcium, which are all carbide-forming metal elements. We also show that the synthesis can be readily scaled up, which will be important for practical applications such as the production of lithium-ion batteries and zeolite-like catalyst supports.
C1 [Kim, Kyoungsoo; Lee, Taekyoung; Kwon, Yonghyun; Seo, Yongbeom; Lee, Hyunsoo; Park, Jeong Young; Ihee, Hyotcherl; Ryoo, Ryong] Inst for Basic Sci Korea, Ctr Nanomat & Chem React, Daejeon 305701, South Korea.
   [Lee, Taekyoung; Kwon, Yonghyun; Ihee, Hyotcherl; Ryoo, Ryong] Korea Adv Inst Sci & Technol, Dept Chem, Daejeon 34141, South Korea.
   [Song, Jongchan; Park, Jung Ki] Korea Adv Inst Sci & Technol, Dept Chem & Biomol Engn, Daejeon 34141, South Korea.
   [Park, Jeong Young] Korea Adv Inst Sci & Technol, Grad Sch EEWS, Daejeon 34141, South Korea.
   [Cho, Sung June] Chonnam Natl Univ, Clean Energy Technol Lab, Gwangju 61186, South Korea.
   [Cho, Sung June] Chonnam Natl Univ, Dept Chem Engn, Gwangju 61186, South Korea.
C3 Institute for Basic Science - Korea (IBS); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Chonnam National University; Chonnam National University
RP Ryoo, R (corresponding author), Inst for Basic Sci Korea, Ctr Nanomat & Chem React, Daejeon 305701, South Korea.; Ryoo, R (corresponding author), Korea Adv Inst Sci & Technol, Dept Chem, Daejeon 34141, South Korea.
EM rryoo@kaist.ac.kr
FU IBS-R004-D1
NR 41
TC 285
Z9 309
U1 13
U2 998
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 131
EP +
DI 10.1038/nature18284
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600038
PM 27362224
DA 2026-03-09
ER

PT J
AU Levin, M
   Anavy, L
   Cole, AG
   Winter, E
   Mostov, N
   Khair, S
   Senderovich, N
   Kovalev, E
   Silver, DH
   Feder, M
   Fernandez-Valverde, SL
   Nakanishi, N
   Simmons, D
   Simakov, O
   Larsson, T
   Liu, SY
   Jerafi-Vider, A
   Yaniv, K
   Ryan, JF
   Martindale, MQ
   Rink, JC
   Arendt, D
   Degnan, SM
   Degnan, BM
   Hashimshony, T
   Yanai, I
AF Levin, Michal
   Anavy, Leon
   Cole, Alison G.
   Winter, Eitan
   Mostov, Natalia
   Khair, Sally
   Senderovich, Naftalie
   Kovalev, Ekaterina
   Silver, David H.
   Feder, Martin
   Fernandez-Valverde, Selene L.
   Nakanishi, Nagayasu
   Simmons, David
   Simakov, Oleg
   Larsson, Tomas
   Liu, Shang-Yun
   Jerafi-Vider, Ayelet
   Yaniv, Karina
   Ryan, Joseph F.
   Martindale, Mark Q.
   Rink, Jochen C.
   Arendt, Detlev
   Degnan, Sandie M.
   Degnan, Bernard M.
   Hashimshony, Tamar
   Yanai, Itai
TI The mid-developmental transition and the evolution of animal body plans
SO NATURE
LA English
DT Article
ID gene-expression; rna-seq; alignment; origin
AB Animals are grouped into similar to 35 'phyla' based upon the notion of distinct body plans(1-4). Morphological and molecular analyses have revealed that a stage in the middle of development-known as the phylotypic period-is conserved among species within some phyla(5-9). Although these analyses provide evidence for their existence, phyla have also been criticized as lacking an objective definition, and consequently based on arbitrary groupings of animals(10). Here we compare the developmental transcriptomes of ten species, each annotated to a different phylum, with a wide range of life histories and embryonic forms. We find that in all ten species, development comprises the coupling of early and late phases of conserved gene expression. These phases are linked by a divergent 'mid-developmental transition' that uses species-specific suites of signalling pathways and transcription factors. This mid-developmental transition overlaps with the phylotypic period that has been defined previously for three of the ten phyla, suggesting that transcriptional circuits and signalling mechanisms active during this transition are crucial for defining the phyletic body plan and that the mid-developmental transition may be used to define phylotypic periods in other phyla. Placing these observations alongside the reported conservation of mid-development within phyla, we propose that a phylum may be defined as a collection of species whose gene expression at the mid-developmental transition is both highly conserved among them, yet divergent relative to other species.
C1 [Levin, Michal; Anavy, Leon; Cole, Alison G.; Winter, Eitan; Mostov, Natalia; Khair, Sally; Senderovich, Naftalie; Kovalev, Ekaterina; Silver, David H.; Feder, Martin; Hashimshony, Tamar; Yanai, Itai] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
   [Fernandez-Valverde, Selene L.; Nakanishi, Nagayasu; Degnan, Sandie M.; Degnan, Bernard M.] Univ Queensland, Sch Biol Sci, Brisbane, Qld, Australia.
   [Simmons, David; Ryan, Joseph F.; Martindale, Mark Q.] Univ Florida, Whitney Lab Marine Biosci, 9505 N Ocean Shore Blvd, St Augustine, FL 32080 USA.
   [Simakov, Oleg; Larsson, Tomas; Arendt, Detlev] European Mol Biol Lab, Dev Biol Unit, Heidelberg, Germany.
   [Liu, Shang-Yun; Rink, Jochen C.] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
   [Jerafi-Vider, Ayelet; Yaniv, Karina] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Levin, Michal] Univ Med Ctr Mainz, CTH, Mainz, Germany.
   [Fernandez-Valverde, Selene L.] IPN, Ctr Invest Estudios Avanzados, Lab Nacl Genom Biodiversidad, Guanajuato, Mexico.
   [Nakanishi, Nagayasu] Univ Florida, Whitney Lab Marine Biosci, 9505 N,Ocean Shore Blvd, St Augustine, FL 32080 USA.
C3 Technion Israel Institute of Technology; University of Queensland; State University System of Florida; University of Florida; European Molecular Biology Laboratory (EMBL); Max Planck Society; Weizmann Institute of Science; Johannes Gutenberg University of Mainz; Instituto Politecnico Nacional - Mexico; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; State University System of Florida; University of Florida
RP Yanai, I (corresponding author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
EM yanai@technion.ac.il
FU European Research Council grant (EvoDevoPaths); EMBO Young Investigator Program; Australian Research Council
NR 52
TC 192
Z9 216
U1 0
U2 91
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 637
EP +
DI 10.1038/nature16994
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400038
PM 26886793
DA 2026-03-09
ER

PT J
AU Lin, PYP
   Gaherty, JB
   Jin, G
   Collins, JA
   Lizarralde, D
   Evans, RL
   Hirth, G
AF Lin, Pei-Ying Patty
   Gaherty, James B.
   Jin, Ge
   Collins, John A.
   Lizarralde, Daniel
   Evans, Rob. L.
   Hirth, Greg
TI High-resolution seismic constraints on flow dynamics in the oceanic asthenosphere
SO NATURE
LA English
DT Article
ID pacific upper-mantle; azimuthal anisotropy; dependent viscosity; net-rotation; plate; tomography; convection; deformation; lithosphere; beneath
AB Convective flow in the mantle and the motions of tectonic plates produce deformation of Earth's interior, and the rock fabric produced by this deformation can be discerned using the anisotropy of the seismic wavespeed(1-3). This deformation is commonly inferred close to lithospheric boundaries beneath the ocean in the uppermost mantle, including near seafloor-spreading centres as new plates are formed via corner flow(4), and within a weak asthenosphere that lubricates large-scale plate-driven flow and accommodates smaller-scale convection(5,6). Seismic models of oceanic upper mantle differ as to the relative importance of these deformation processes: seafloor-spreading fabric is very strong just beneath the crust-mantle boundary (the Mohorovicic discontinuity, or Moho) at relatively local scales(7,8), but at the global and ocean-basin scales, oceanic lithosphere typically appears weakly anisotropic when compared to the asthenosphere(9,10). Here we use Rayleigh waves, recorded across an ocean-bottom seismograph array in the central Pacific Ocean (the NoMelt Experiment), to provide unique localized constraints on seismic anisotropy within the oceanic lithosphere-asthenosphere system in the middle of a plate. We find that azimuthal anisotropy is strongest within the high-seismic-velocity lid, with the fast direction coincident with seafloor spreading. A minimum in the magnitude of azimuthal anisotropy occurs within the middle of the seismic low-velocity zone, and then increases with depth below the weakest portion of the asthenosphere. At no depth does the fast direction correlate with the apparent plate motion. Our results suggest that the highest strain deformation in the shallow oceanic mantle occurs during corner flow at the ridge axis, and via pressure-driven or buoyancy-driven flow within the asthenosphere. Shear associated with motion of the plate over the underlying asthenosphere, if present, is weak compared to these other processes.
C1 [Lin, Pei-Ying Patty; Gaherty, James B.; Jin, Ge] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY USA.
   [Collins, John A.; Lizarralde, Daniel; Evans, Rob. L.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
   [Hirth, Greg] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Lin, Pei-Ying Patty] Taiwan Ocean Res Inst, Natl Appl Res Labs, Kaohsiung, Taiwan.
C3 Columbia University; Woods Hole Oceanographic Institution; Brown University; National Applied Research Laboratories - Taiwan
RP Lin, PYP (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY USA.; Lin, PYP (corresponding author), Taiwan Ocean Res Inst, Natl Appl Res Labs, Kaohsiung, Taiwan.
EM pylin.patty@gmail.com
FU Scripps Institution of Oceanography's facility as part of the US Ocean Bottom Seismograph Instrument Pool; US National Science Foundation; Institute of Earth Science, Academia Sinica, Taipei, Taiwan; Institute of Undersea Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; Directorate For Geosciences; Division Of Ocean Sciences [0928663] Funding Source: National Science Foundation
NR 45
TC 97
Z9 112
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 538
EP +
DI 10.1038/nature18012
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600026
PM 27383792
DA 2026-03-09
ER

PT J
AU Costa, KM
   McManus, JF
   Anderson, RF
   Ren, H
   Sigman, DM
   Winckler, G
   Fleisher, MQ
   Marcantonio, F
   Ravelo, AC
AF Costa, K. M.
   McManus, J. F.
   Anderson, R. F.
   Ren, H.
   Sigman, D. M.
   Winckler, G.
   Fleisher, M. Q.
   Marcantonio, F.
   Ravelo, A. C.
TI No iron fertilization in the equatorial Pacific Ocean during the last ice age
SO NATURE
LA English
DT Article
ID glacial-interglacial variability; deep-sea; sediment; th-230; dust; denitrification; nutrient; pa-231; ratio; opal
AB The equatorial Pacific Ocean is one of the major high-nutrient, low-chlorophyll regions in the global ocean. In such regions, the consumption of the available macro-nutrients such as nitrate and phosphate is thought to be limited in part by the low abundance of the critical micro-nutrient iron(1). Greater atmospheric dust deposition(2) could have fertilized the equatorial Pacific with iron during the last ice age-the Last Glacial Period (LGP)-but the effect of increased ice-age dust fluxes on primary productivity in the equatorial Pacific remains uncertain(3-6). Here we present meridional transects of dust (derived from the Th-232 proxy), phytoplankton productivity (using opal, Pa-231/Th-230 and excess Ba), and the degree of nitrate consumption (using foraminifera-bound delta N-15) from six cores in the central equatorial Pacific for the Holocene (0-10,000 years ago) and the LGP (17,000-27,000 years ago). We find that, although dust deposition in the central equatorial Pacific was two to three times greater in the LGP than in the Holocene, productivity was the same or lower, and the degree of nitrate consumption was the same. These biogeochemical findings suggest that the relatively greater ice-age dust fluxes were not large enough to provide substantial iron fertilization to the central equatorial Pacific. This may have been because the absolute rate of dust deposition in the LGP (although greater than the Holocene rate) was very low. The lower productivity coupled with unchanged nitrate consumption suggests that the subsurface major nutrient concentrations were lower in the central equatorial Pacific during the LGP. As these nutrients are today dominantly sourced from the Subantarctic Zone of the Southern Ocean, we propose that the central equatorial Pacific data are consistent with more nutrient consumption in the Subantarctic Zone, possibly owing to iron fertilization as a result of higher absolute dust fluxes in this region(7,8). Thus, ice-age iron fertilization in the Subantarctic Zone would have ultimately worked to lower, not raise, equatorial Pacific productivity.
C1 [Costa, K. M.; McManus, J. F.; Anderson, R. F.; Winckler, G.; Fleisher, M. Q.] Columbia Univ, Lamont Doherty Geol Observ, Palisades, NY 10964 USA.
   [Costa, K. M.; McManus, J. F.; Anderson, R. F.; Winckler, G.] Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
   [Ren, H.] Natl Taiwan Univ, Dept Geosci, Taipei 106, Taiwan.
   [Sigman, D. M.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Marcantonio, F.] Texas A&M Univ, Dept Geol & Geophys, College Stn, TX 77843 USA.
   [Ravelo, A. C.] Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
C3 Columbia University; Columbia University; National Taiwan University; Princeton University; Texas A&M University System; Texas A&M University College Station; University of California System; University of California Santa Cruz
RP Costa, KM (corresponding author), Columbia Univ, Lamont Doherty Geol Observ, Palisades, NY 10964 USA.; Costa, KM (corresponding author), Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
EM kcosta@ldeo.columbia.edu
FU NSF [AGS 15-02889, OCE-1060947, OCE-1003374, OCE-1159053, OCE-1158886]; Grand Challenges Program of Princeton University; Comer Science and Education Foundation; MOST, Taiwan [103-2116-M-002-032-MY2]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1502889] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1502962] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1060947] Funding Source: National Science Foundation
NR 64
TC 82
Z9 108
U1 1
U2 110
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 519
EP +
DI 10.1038/nature16453
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800035
PM 26819045
DA 2026-03-09
ER

PT J
AU Kaur, A
   Webster, MR
   Marchbank, K
   Behera, R
   Ndoye, A
   Kugel, CH
   Dang, VM
   Appleton, J
   O'Connell, MP
   Cheng, P
   Valiga, AA
   Morissette, R
   McDonnell, NB
   Ferrucci, L
   Kossenkov, AV
   Meeth, K
   Tang, HY
   Yin, XF
   Wood, WH
   Lehrmann, E
   Becker, KG
   Flaherty, KT
   Frederick, DT
   Wargo, JA
   Cooper, ZA
   Tetzlaff, MT
   Hudgens, C
   Aird, KM
   Zhang, RG
   Xu, XW
   Liu, Q
   Bartlett, E
   Karakousis, G
   Eroglu, Z
   Lo, RS
   Chan, M
   Menzies, AM
   Long, GV
   Johnson, DB
   Sosman, J
   Schilling, B
   Schadendorf, D
   Speicher, DW
   Bosenberg, M
   Ribas, A
   Weeraratna, AT
AF Kaur, Amanpreet
   Webster, Marie R.
   Marchbank, Katie
   Behera, Reeti
   Ndoye, Abibatou
   Kugel, Curtis H., III
   Dang, Vanessa M.
   Appleton, Jessica
   O'Connell, Michael P.
   Cheng, Phil
   Valiga, Alexander A.
   Morissette, Rachel
   McDonnell, Nazli B.
   Ferrucci, Luigi
   Kossenkov, Andrew V.
   Meeth, Katrina
   Tang, Hsin-Yao
   Yin, Xiangfan
   Wood, William H., III
   Lehrmann, Elin
   Becker, Kevin G.
   Flaherty, Keith T.
   Frederick, Dennie T.
   Wargo, Jennifer A.
   Cooper, Zachary A.
   Tetzlaff, Michael T.
   Hudgens, Courtney
   Aird, Katherine M.
   Zhang, Rugang
   Xu, Xiaowei
   Liu, Qin
   Bartlett, Edmund
   Karakousis, Giorgos
   Eroglu, Zeynep
   Lo, Roger S.
   Chan, Matthew
   Menzies, Alexander M.
   Long, Georgina V.
   Johnson, Douglas B.
   Sosman, Jeffrey
   Schilling, Bastian
   Schadendorf, Dirk
   Speicher, David W.
   Bosenberg, Marcus
   Ribas, Antoni
   Weeraratna, Ashani T.
TI sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance
SO NATURE
LA English
DT Article
ID beta-catenin; oxidative stress; cells; tumor; growth; braf(v600e); progression; phenotype; mitf
AB Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression(1-4), we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy. Here we find that aged fibroblasts secrete a Wnt antagonist, sFRP2, which activates a multi-step signalling cascade in melanoma cells that results in a decrease in beta-catenin and microphthalmia-associated transcription factor (MITF), and ultimately the loss of a key redox effector, APE1. Loss of APE1 attenuates the response of melanoma cells to DNA damage induced by reactive oxygen species, rendering the cells more resistant to targeted therapy (vemurafenib). Age-related increases in sFRP2 also augment both angiogenesis and metastasis of melanoma cells. These data provide an integrated view of how fibroblasts in the aged microenvironment contribute to tumour progression, offering new possibilities for the design of therapy for the elderly.
C1 [Kaur, Amanpreet; Webster, Marie R.; Marchbank, Katie; Behera, Reeti; Ndoye, Abibatou; Kugel, Curtis H., III; Dang, Vanessa M.; Appleton, Jessica; O'Connell, Michael P.; Valiga, Alexander A.; Kossenkov, Andrew V.; Tang, Hsin-Yao; Yin, Xiangfan; Aird, Katherine M.; Zhang, Rugang; Liu, Qin; Speicher, David W.; Weeraratna, Ashani T.] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
   [Kaur, Amanpreet] Univ Sci, Philadelphia, PA 19104 USA.
   [Cheng, Phil] Univ Zurich, Dept Dermatol, CH-8006 Zurich, Switzerland.
   [Morissette, Rachel; McDonnell, Nazli B.; Ferrucci, Luigi; Wood, William H., III; Lehrmann, Elin; Becker, Kevin G.] NIA, NIH, Baltimore, MD 21224 USA.
   [Meeth, Katrina; Bosenberg, Marcus] Yale Univ, Dept Dermatol & Pathol, New Haven, CT 06511 USA.
   [Flaherty, Keith T.; Frederick, Dennie T.] Massachusetts Gen Hosp, Ctr Canc, Dev Therapeut, Boston, MA 02114 USA.
   [Wargo, Jennifer A.; Cooper, Zachary A.; Tetzlaff, Michael T.; Hudgens, Courtney] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
   [Xu, Xiaowei; Bartlett, Edmund; Karakousis, Giorgos] Univ Penn, Dept Surg, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
   [Xu, Xiaowei; Bartlett, Edmund; Karakousis, Giorgos] Univ Penn, Dept Pathol, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
   [Eroglu, Zeynep] City Hope Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA.
   [Lo, Roger S.; Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
   [Chan, Matthew] Westmead Hosp, Crown Princess Mary Canc Ctr, Westmead, NSW 2145, Australia.
   [Menzies, Alexander M.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW 2000, Australia.
   [Menzies, Alexander M.; Long, Georgina V.] Univ Sydney, Sydney, NSW 2000, Australia.
   [Johnson, Douglas B.; Sosman, Jeffrey] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA.
   [Schilling, Bastian; Schadendorf, Dirk] Univ Duesburg Essen, Dept Dermatol, Univ Hosp, West German Canc Ctr, Essen, Germany.
   [Schilling, Bastian; Schadendorf, Dirk] German Canc Consortium DKTK, D-45127 Heidelberg, Germany.
C3 The Wistar Institute; University of Zurich; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Yale University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Texas System; UTMD Anderson Cancer Center; University of Pennsylvania; University of Pennsylvania; City of Hope; University of California System; University of California Los Angeles; NSW Health; Westmead Hospital; University of Sydney; Melanoma Institute Australia; University of Sydney; Vanderbilt University; University of Duisburg Essen; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Weeraratna, AT (corresponding author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM aweeraratna@wistar.org
FU National Institute on Aging, Baltimore, Maryland; Harry J. Lloyd Foundation; ACS-IRG; Melanoma Research Foundation; Cancer Center Support Grant [P30 CA010815];  [P01 CA 114046-06];  [T32 CA 9171-36];  [RO1 CA174746-01]; National Cancer Institute [R50CA211199, T32CA009171, P30CA010815, P01CA114046, R01CA160331] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007324] Funding Source: NIH RePORTER; National Institute on Aging [ZICAG000616] Funding Source: NIH RePORTER
NR 29
TC 339
Z9 387
U1 1
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 250
EP +
DI 10.1038/nature17392
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100043
PM 27042933
DA 2026-03-09
ER

PT J
AU Glorevski, N
   Sachs, N
   Manfrin, A
   Giger, S
   Bragina, ME
   Ordóñez-Morán, P
   Clevers, H
   Lutolf, MP
AF Glorevski, Nikolce
   Sachs, Norman
   Manfrin, Andrea
   Giger, Sonja
   Bragina, Maiia E.
   Ordonez-Moran, Paloma
   Clevers, Hans
   Lutolf, Matthias P.
TI Designer matrices for intestinal stem cell and organoid culture
SO NATURE
LA English
DT Article
ID laminin alpha-1 chain; differential expression; in-vitro; extracellular-matrix; growth; epithelium; hydrogels; cancer; fate; yap
AB Epithelial organoids recapitulate multiple aspects of real organs, making them promising models of organ development, function and disease1-3. However, the full potential of organoids in research and therapy has remained unrealized, owing to the poorly defined animal-derived matrices in which they are grown(4). Here we used modular synthetic hydrogel networks(5,6) to define the key extracellular matrix (ECM) parameters that govern intestinal stem cell (ISC) expansion and organoid formation, and show that separate stages of the process require different mechanical environments and ECM components. In particular, fibronectin-based adhesion was sufficient for ISC survival and proliferation. High matrix stiffness significantly enhanced ISC expansion through a yes-associated protein 1 (YAP)-dependent mechanism. ISC differentiation and organoid formation, on the other hand, required a soft matrix and laminin-based adhesion. We used these insights to build a fully defined culture system for the expansion of mouse and human ISCs. We also produced mechanically dynamic matrices that were initially optimal for ISC expansion and subsequently permissive to differentiation and intestinal organoid formation, thus creating well-defined alternatives to animal-derived matrices for the culture of mouse and human stem-cell-derived organoids. Our approach overcomes multiple limitations of current organoid cultures and greatly expands their applicability in basic and clinical research. The principles presented here can be extended to identify designer matrices that are optimal for long-term culture of other types of stem cells and organoids.
C1 [Glorevski, Nikolce; Manfrin, Andrea; Giger, Sonja; Bragina, Maiia E.; Lutolf, Matthias P.] Ecole Polytech Fed Lausanne EPFL, Inst Bioengn, Sch Life Sci SV, Lab Stem Cell Bioengn, Lausanne, Switzerland.
   [Glorevski, Nikolce; Manfrin, Andrea; Giger, Sonja; Bragina, Maiia E.; Lutolf, Matthias P.] Ecole Polytech Fed Lausanne EPFL, Sch Engn STI, Lausanne, Switzerland.
   [Sachs, Norman; Clevers, Hans] Hubrecht Inst, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
   [Sachs, Norman; Clevers, Hans] Univ Med Ctr Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
   [Ordonez-Moran, Paloma] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, Lausanne, Switzerland.
   [Lutolf, Matthias P.] Ecole Polytech Fed Lausanne EPFL, Sch Basic Sci, Inst Chem Sci & Engn, Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Institute Experimental Cancer Research; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Lutolf, MP (corresponding author), Ecole Polytech Fed Lausanne EPFL, Inst Bioengn, Sch Life Sci SV, Lab Stem Cell Bioengn, Lausanne, Switzerland.; Lutolf, MP (corresponding author), Ecole Polytech Fed Lausanne EPFL, Sch Engn STI, Lausanne, Switzerland.; Lutolf, MP (corresponding author), Ecole Polytech Fed Lausanne EPFL, Sch Basic Sci, Inst Chem Sci & Engn, Lausanne, Switzerland.
EM matthias.lutolf@epfl.ch
FU EMBO Long-Term Postdoctoral Fellowship; Ecole Polytechnique Federale de Lausanne (EPFL); NWO Translational Adult Stem Cell Research Grant [40-41400-98-1108]; NWO VENI Grant [916.15.182]
NR 43
TC 779
Z9 952
U1 26
U2 751
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 560
EP +
DI 10.1038/nature20168
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600043
PM 27851739
DA 2026-03-09
ER

PT J
AU Colletier, JP
   Sawaya, MR
   Gingery, M
   Rodriguez, JA
   Cascio, D
   Brewster, AS
   Michels-Clark, T
   Hice, RH
   Coquelle, N
   Boutet, S
   Williams, GJ
   Messerschmidt, M
   DePonte, DP
   Sierra, RG
   Laksmono, H
   Koglin, JE
   Hunter, MS
   Park, HW
   Uervirojnangkoorn, M
   Bideshi, DK
   Brunger, AT
   Federici, BA
   Sauter, NK
   Eisenberg, DS
AF Colletier, Jacques-Philippe
   Sawaya, Michael R.
   Gingery, Mari
   Rodriguez, Jose A.
   Cascio, Duilio
   Brewster, Aaron S.
   Michels-Clark, Tara
   Hice, Robert H.
   Coquelle, Nicolas
   Boutet, Sebastien
   Williams, Garth J.
   Messerschmidt, Marc
   DePonte, Daniel P.
   Sierra, Raymond G.
   Laksmono, Hartawan
   Koglin, Jason E.
   Hunter, Mark S.
   Park, Hyun-Woo
   Uervirojnangkoorn, Monarin
   Bideshi, Dennis K.
   Brunger, Axel T.
   Federici, Brian A.
   Sauter, Nicholas K.
   Eisenberg, David S.
TI De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure
SO NATURE
LA English
DT Article
ID bacillus-sphaericus; crystal-structure; toxin; pore; binding; crystallography; complementarity; identification; thuringiensis; sporulation
AB BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine-and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.
C1 [Colletier, Jacques-Philippe; Coquelle, Nicolas] Univ Grenoble Alpes, CEA, CNRS, IBS, F-38044 Grenoble, France.
   [Sawaya, Michael R.; Gingery, Mari; Rodriguez, Jose A.; Cascio, Duilio; Eisenberg, David S.] Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Sawaya, Michael R.; Eisenberg, David S.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Michels-Clark, Tara; Hice, Robert H.; Sauter, Nicholas K.] Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA.
   [Hice, Robert H.; Park, Hyun-Woo; Bideshi, Dennis K.; Federici, Brian A.] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
   [Hice, Robert H.; Park, Hyun-Woo; Bideshi, Dennis K.; Federici, Brian A.] Univ Calif Riverside, Grad Program Cell Mol & Dev Biol, Riverside, CA 92521 USA.
   [Boutet, Sebastien; Williams, Garth J.; Messerschmidt, Marc; DePonte, Daniel P.; Sierra, Raymond G.; Laksmono, Hartawan; Koglin, Jason E.; Hunter, Mark S.] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
   [Park, Hyun-Woo; Bideshi, Dennis K.] Calif Baptist Univ, Dept Biol Sci, Riverside, CA 92504 USA.
   [Uervirojnangkoorn, Monarin; Brunger, Axel T.] Stanford Univ, Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Uervirojnangkoorn, Monarin; Brunger, Axel T.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California Los Angeles; United States Department of Energy (DOE); Howard Hughes Medical Institute; University of California System; University of California Los Angeles; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Riverside; University of California System; University of California Riverside; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; California Baptist University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Colletier, JP (corresponding author), Univ Grenoble Alpes, CEA, CNRS, IBS, F-38044 Grenoble, France.; Eisenberg, DS (corresponding author), Univ Calif Los Angeles, UCLA DOE Inst Genom & Prote, Dept Biol Chem, Los Angeles, CA 90095 USA.; Eisenberg, DS (corresponding author), Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
EM colletier@ibs.fr; david@mbi.ucla.edu
FU W.M. Keck Foundation [2843398]; NIH [AG-029430, GM095887, GM102520, AI45817]; National Science Foundation [MCB 0958111]; DOE [DE-FC02-02ER63421]; France Alzheimer Foundation [FA-AAP-2013-65-101349]; Agence Nationale de la Recherche [ANR-12-BS07-0008-03]; CNRS [PEPS-SASLELX-2013, PEPS-SASLELX-2014]; US Department of Energy, Office of Science, and Office of Basic Energy Sciences [DE-AC02-76SF00515]; Linac Coherent Light Source Ultrafast Science Instruments project; DOE Office of Basic Energy Sciences; National Institutes of Health [P41GM103393, P41RR001209]; Agence Nationale de la Recherche (ANR) [ANR-12-BS07-0008] Funding Source: Agence Nationale de la Recherche (ANR)
NR 60
TC 90
Z9 98
U1 2
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 43
EP +
DI 10.1038/nature19825
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100025
PM 27680699
DA 2026-03-09
ER

PT J
AU Wang, J
   Krejci, R
   Giangrandel, S
   Kuang, C
   Barbosa, HMJ
   Brito, J
   Carbone, S
   Chi, XG
   Comstock, J
   Ditas, F
   Lavric, J
   Manninen, HE
   Mei, F
   Moran-Zuloaga, D
   Pöhlker, C
   Pöhlker, ML
   Saturno, J
   Schmid, B
   Souza, RAF
   Springston, SR
   Tomlinson, JM
   Toto, T
   Walter, D
   Wimmer, D
   Smith, JN
   Kulmala, M
   Machado, LAT
   Artaxo, P
   Andreae, MO
   Petäjä, T
   Martin, ST
AF Wang, Jian
   Krejci, Radovan
   Giangrandel, Scott
   Kuang, Chongai
   Barbosa, Henrique M. J.
   Brito, Joel
   Carbone, Samara
   Chi, Xuguang
   Comstock, Jennifer
   Ditas, Florian
   Lavric, Jost
   Manninen, Hanna E.
   Mei, Fan
   Moran-Zuloaga, Daniel
   Poehlker, Christopher
   Poehlker, Mira L.
   Saturno, Jorge
   Schmid, Beat
   Souza, Rodrigo A. F.
   Springston, Stephen R.
   Tomlinson, Jason M.
   Toto, Tami
   Walter, David
   Wimmer, Daniela
   Smith, James N.
   Kulmala, Markku
   Machado, Luiz A. T.
   Artaxo, Paulo
   Andreae, Meinrat O.
   Petaja, Tuukka
   Martin, Scot T.
TI Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall
SO NATURE
LA English
DT Article
ID atmospheric aerosols; free troposphere; wet season; tall tower; nucleation; forest; nuclei; ccn
AB The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere(1). Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions(3-5), but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear(6-8). Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.
C1 [Wang, Jian; Giangrandel, Scott; Kuang, Chongai; Springston, Stephen R.; Toto, Tami] Brookhaven Natl Lab, Environm & Climate Sci Dept, Upton, NY 11973 USA.
   [Krejci, Radovan] Stockholm Univ, Dept Appl Environm Sci & Analyt Chem, S-10691 Stockholm, Sweden.
   [Barbosa, Henrique M. J.; Brito, Joel; Carbone, Samara; Artaxo, Paulo] Univ Sao Paulo, BR-05508900 Sao Paulo, Brazil.
   [Chi, Xuguang; Ditas, Florian; Moran-Zuloaga, Daniel; Poehlker, Christopher; Poehlker, Mira L.; Saturno, Jorge; Walter, David; Andreae, Meinrat O.] Max Planck Inst Chem, Biogeochem & Multiphase Chem Dept, D-55128 Mainz, Germany.
   [Chi, Xuguang] Nanjing Univ, Sch Atmospher Sci, Nanjing 210023, Jiangsu, Peoples R China.
   [Chi, Xuguang] Collaborat Innovat Ctr Climate Change, Nanjing 210023, Jiangsu, Peoples R China.
   [Comstock, Jennifer; Mei, Fan; Schmid, Beat; Tomlinson, Jason M.] Pacific Northwest Natl Lab, Atmospher Sci & Global Change Div, Richland, WA 99352 USA.
   [Lavric, Jost] Max Planck Inst Biogeochem, Dept Biogeochem Syst, D-07745 Jena, Germany.
   [Manninen, Hanna E.; Wimmer, Daniela; Kulmala, Markku; Petaja, Tuukka] Univ Helsinki, Dept Phys, POB 64, FI-00014 Helsinki, Finland.
   [Souza, Rodrigo A. F.] Amazonas State Univ, BR-69050020 Manaus, Amazonas, Brazil.
   [Smith, James N.] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
   [Machado, Luiz A. T.] Natl Inst Space Res, BR-12227010 Sao Jose Dos Campos, SP, Brazil.
   [Andreae, Meinrat O.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Martin, Scot T.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Martin, Scot T.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory; Stockholm University; Universidade de Sao Paulo; Max Planck Society; Nanjing University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Max Planck Society; University of Helsinki; Universidade do Estado do Amazonas; University of California System; University of California Irvine; Instituto Nacional de Pesquisas Espaciais (INPE); University of California System; University of California San Diego; Scripps Institution of Oceanography; Harvard University; Harvard University
RP Wang, J (corresponding author), Brookhaven Natl Lab, Environm & Climate Sci Dept, Upton, NY 11973 USA.
EM jian@bnl.gov
FU Office of Biological and Environmental Research; Atmospheric System Research (ASR) programme (Office of Biological and Environmental Research of US DOE) [DE-AC02-98CH10886]; Amazonas State Research Foundation (FAPEAM-GoAmazon); Sao Paulo Research Foundation (FAPESP) [2013/50510-5, 2013/05014-0, CHUVA 2009/15235-8]; Brazil Scientific Mobility Program (CsF/CAPES-CNPq); Brazilian Ministry of Science, Technology, and Innovation (MCTI/FINEP) [01.11.01248.00]; German Max Planck Society (MPG); German Federal Ministry of Education and Research (BMBF) [01LB1001A]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/50510-5, 09/15235-8] Funding Source: FAPESP
NR 30
TC 117
Z9 137
U1 5
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 416
EP 419
DI 10.1038/nature19819
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700051
PM 27776357
DA 2026-03-09
ER

PT J
AU Gossner, MM
   Lewinsohn, TM
   Kahl, T
   Grassein, F
   Boch, S
   Prati, D
   Birkhofer, K
   Renner, SC
   Sikorski, J
   Wubet, T
   Arndt, H
   Baumgartner, V
   Blaser, S
   Blüthgen, N
   Börschig, C
   Buscot, F
   Diekötter, T
   Jorge, LR
   Jung, K
   Keyel, AC
   Klein, AM
   Klemmer, S
   Krauss, J
   Lange, M
   Müller, J
   Overmann, J
   Pasalic, E
   Penone, C
   Perovic, DJ
   Purschke, O
   Schall, P
   Socher, SA
   Sonnemann, I
   Tschapka, M
   Tscharntke, T
   Türke, M
   Venter, PC
   Weiner, CN
   Werner, M
   Wolters, V
   Wurst, S
   Westphal, C
   Fischer, M
   Weisser, WW
   Allan, E
AF Gossner, Martin M.
   Lewinsohn, Thomas M.
   Kahl, Tiemo
   Grassein, Fabrice
   Boch, Steffen
   Prati, Daniel
   Birkhofer, Klaus
   Renner, Swen C.
   Sikorski, Johannes
   Wubet, Tesfaye
   Arndt, Hartmut
   Baumgartner, Vanessa
   Blaser, Stefan
   Bluethgen, Nico
   Boerschig, Carmen
   Buscot, Francois
   Diekoetter, Tim
   Jorge, Leonardo Re
   Jung, Kirsten
   Keyel, Alexander C.
   Klein, Alexandra-Maria
   Klemmer, Sandra
   Krauss, Jochen
   Lange, Markus
   Mueller, Joerg
   Overmann, Joerg
   Pasalic, Esther
   Penone, Caterina
   Perovic, David J.
   Purschke, Oliver
   Schall, Peter
   Socher, Stephanie A.
   Sonnemann, Ilja
   Tschapka, Marco
   Tscharntke, Teja
   Tuerke, Manfred
   Venter, Paul Christiaan
   Weiner, Christiane N.
   Werner, Michael
   Wolters, Volkmar
   Wurst, Susanne
   Westphal, Catrin
   Fischer, Markus
   Weisser, Wolfgang W.
   Allan, Eric
TI Land-use intensification causes multitrophic homogenization of grassland communities
SO NATURE
LA English
DT Article
ID biotic homogenization; beta-diversity; use intensity; microbial community; species-diversity; plant; forest; biodiversity; fertilization; echolocation
AB Land-use intensification is a major driver of biodiversity loss(1,2). Alongside reductions in local species diversity, biotic homogenization at larger spatial scales is of great concern for conservation. Biotic homogenization means a decrease in beta-diversity (the compositional dissimilarity between sites). Most studies have investigated losses in local (alpha)-diversity(1,3) and neglected biodiversity loss at larger spatial scales. Studies addressing beta-diversity have focused on single or a few organism groups (for example, ref. 4), and it is thus unknown whether land-use intensification homogenizes communities at different trophic levels, above-and belowground. Here we show that even moderate increases in local land-use intensity (LUI) cause biotic homogenization across microbial, plant and animal groups, both above- and belowground, and that this is largely independent of changes in alpha-diversity. We analysed a unique grassland biodiversity dataset, with abundances of more than 4,000 species belonging to 12 trophic groups. LUI, and, in particular, high mowing intensity, had consistent effects on beta-diversity across groups, causing a homogenization of soil microbial, fungal pathogen, plant and arthropod communities. These effects were nonlinear and the strongest declines in beta-diversity occurred in the transition from extensively managed to intermediate intensity grassland. LUI tended to reduce local alpha-diversity in aboveground groups, whereas the alpha-diversity increased in belowground groups. Correlations between the alpha-diversity of different groups, particularly between plants and their consumers, became weaker at high LUI. This suggests a loss of specialist species and is further evidence for biotic homogenization. The consistently negative effects of LUI on landscape-scale biodiversity underscore the high value of extensively managed grasslands for conserving multitrophic biodiversity and ecosystem service provision. Indeed, biotic homogenization rather than local diversity loss could prove to be the most substantial consequence of land-use intensification.
C1 [Gossner, Martin M.; Lewinsohn, Thomas M.; Lange, Markus; Pasalic, Esther; Tuerke, Manfred; Weisser, Wolfgang W.] Tech Univ Munich, Sch Life Sci Weihenstephan, Dept Ecol & Ecosyst Management, Terr Ecol Res Grp, Hans Carl von Carlowitz Pl 2, D-85354 Freising Weihenstephan, Germany.
   [Gossner, Martin M.; Lange, Markus; Pasalic, Esther; Tuerke, Manfred; Weisser, Wolfgang W.] Friedrich Schiller Univ Jena, Inst Ecol, Dornburger Str 159, D-07743 Jena, Germany.
   [Gossner, Martin M.] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Lewinsohn, Thomas M.; Jorge, Leonardo Re] Univ Estadual Campinas, IB, Dept Anim Biol, BR-13083970 Sao Paulo, Brazil.
   [Kahl, Tiemo] Univ Freiburg, Fac Environm & Nat Resources, Chair Silviculture, Tennenbacherstr 4, D-79106 Freiburg, Germany.
   [Kahl, Tiemo] Biosphere Reserve Vessertal Thuringian Forest, Brunnenstr 1, D-98711 Schmiedefeld, Germany.
   [Grassein, Fabrice; Boch, Steffen; Prati, Daniel; Blaser, Stefan; Penone, Caterina; Fischer, Markus; Allan, Eric] Univ Bern, Inst Plant Sci, Altenbergrain 21, CH-3013 Bern, Switzerland.
   [Birkhofer, Klaus] Lund Univ, Dept Biol Biodivers & Conservat Sci, Solvegatan 37, S-22362 Lund, Sweden.
   [Birkhofer, Klaus] BTU Cottbus Senftenberg, Fac Environm & Nat Sci, Chair Ecol, Grossenhainer Str 57, D-01968 Senftenberg, Germany.
   [Renner, Swen C.] Univ Nat Resources & Life Sci, Inst Zool, A-1180 Vienna, Austria.
   [Renner, Swen C.; Jung, Kirsten; Tschapka, Marco] Univ Ulm, Inst Evolutionary Ecol & Conservat Genom, D-89069 Ulm, Germany.
   [Sikorski, Johannes; Baumgartner, Vanessa; Overmann, Joerg] Leibniz Inst DSMZ German Collect Microorganisms &, Inhoffenstr 7B, D-38302 Braunschweig, Germany.
   [Wubet, Tesfaye; Buscot, Francois; Klemmer, Sandra] UFZ Helmholtz Ctr Environm Res, Dept Soil Ecol, D-06120 Halle, Germany.
   [Wubet, Tesfaye; Buscot, Francois; Tuerke, Manfred] Univ Leipzig, Inst Biol, Johannisallee 21, D-04103 Leipzig, Germany.
   [Arndt, Hartmut; Venter, Paul Christiaan] Univ Cologne, Inst Zool, Bioctr, Gen Ecol, Zuelpicher Str 47b, D-50674 Cologne, Germany.
   [Bluethgen, Nico; Weiner, Christiane N.; Werner, Michael] Tech Univ Darmstadt, Dept Biol, Ecol Networks, Schnittspahnstr 3, D-64287 Darmstadt, Germany.
   [Boerschig, Carmen; Krauss, Jochen] Univ Wurzburg, Dept Anim Ecol & Trop Biol, Bioctr, D-97074 Wurzburg, Germany.
   [Diekoetter, Tim; Wolters, Volkmar] Univ Giessen, Anim Ecol, Heinrich Buff Ring 26-32, D-35392 Giessen, Germany.
   [Diekoetter, Tim] Univ Kiel, Inst Nat Resource Conservat, Landscape Ecol, Olshausenstr 75, D-24118 Kiel, Germany.
   [Keyel, Alexander C.] Univ Gottingen, Dept Ecosyst Modelling, Busgenweg 4, D-37077 Gottingen, Germany.
   [Klein, Alexandra-Maria] Univ Freiburg, Fac Environm & Nat Resources, Chair Nat Conservat & Landscape Ecol, Tennenbacherstr 4, D-79106 Freiburg, Germany.
   [Klemmer, Sandra; Purschke, Oliver; Tuerke, Manfred] German Ctr Integrat Biodivers Res iDiv, Deutsch Pl 5e, D-04103 Leipzig, Germany.
   [Lange, Markus] Max Planck Inst Biogeochem, Hans Knoell Str 10, D-07745 Jena, Germany.
   [Mueller, Joerg] Univ Potsdam, Inst Biochem & Biol, Maulbeerallee 1, D-14469 Potsdam, Germany.
   [Perovic, David J.] Fujian Agr & Forestry Univ, Inst Appl Ecol, Fuzhou, Peoples R China.
   [Perovic, David J.; Tscharntke, Teja; Westphal, Catrin] Univ Gottingen, Dept Crop Sci, Agroecol, D-37077 Gottingen, Germany.
   [Purschke, Oliver] Univ Halle Wittenberg, Dept Comp Sci, D-06120 Halle, Saale, Germany.
   [Purschke, Oliver] Univ Halle Wittenberg, Geobot, Inst Biol, D-06108 Halle, Saale, Germany.
   [Purschke, Oliver] Univ Halle Wittenberg, Bot Garden, Inst Biol, D-06108 Halle, Saale, Germany.
   [Schall, Peter] Univ Gottingen, Dept Silviculture & Forest Ecol Temperate Zones, D-37077 Gottingen, Germany.
   [Socher, Stephanie A.] Salzburg Univ, Dept Ecol & Evolut, Bot Garden, Hellbrunnerstr 34, A-5020 Salzburg, Austria.
   [Sonnemann, Ilja; Wurst, Susanne] Free Univ Berlin, Inst Biol, Funct Biodivers, Konigin Luise Str 1-3, D-14195 Berlin, Germany.
   [Allan, Eric] Univ Bern, Ctr Dev & Environm, Hallerstr 10, CH-3012 Bern, Switzerland.
C3 Technical University of Munich; Friedrich Schiller University of Jena; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Universidade Estadual de Campinas; University of Freiburg; University of Bern; Lund University; Brandenburg University of Technology Cottbus; BOKU University; Ulm University; Leibniz Association; Leibniz Institut fur Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ); Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); Leipzig University; University of Cologne; Technical University of Darmstadt; University of Wurzburg; Justus Liebig University Giessen; University of Kiel; University of Gottingen; University of Freiburg; German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); Max Planck Society; University of Potsdam; Fujian Agriculture & Forestry University; University of Gottingen; Martin Luther University Halle Wittenberg; Martin Luther University Halle Wittenberg; Martin Luther University Halle Wittenberg; University of Gottingen; Salzburg University; Free University of Berlin; University of Bern
RP Gossner, MM (corresponding author), Tech Univ Munich, Sch Life Sci Weihenstephan, Dept Ecol & Ecosyst Management, Terr Ecol Res Grp, Hans Carl von Carlowitz Pl 2, D-85354 Freising Weihenstephan, Germany.; Gossner, MM (corresponding author), Friedrich Schiller Univ Jena, Inst Ecol, Dornburger Str 159, D-07743 Jena, Germany.; Gossner, MM (corresponding author), Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
EM martin.gossner@wsl.ch
FU DFG Priority Program 1374 'Infrastructure-Biodiversity-Exploratories'
NR 69
TC 520
Z9 562
U1 29
U2 878
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 266
EP +
DI 10.1038/nature20575
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700056
PM 27919075
DA 2026-03-09
ER

PT J
AU Archer, SK
   Shirokikh, NE
   Beilharz, TH
   Preiss, T
AF Archer, Stuart K.
   Shirokikh, Nikolay E.
   Beilharz, Traude H.
   Preiss, Thomas
TI Dynamics of ribosome scanning and recycling revealed by translation complex profiling
SO NATURE
LA English
DT Article
ID start codon recognition; messenger-rna; eukaryotic translation; protein-synthesis; gene-expression; initiation complex; yeast; termination; mechanism; promotes
AB Regulation of messenger RNA translation is central to eukaryotic gene expression control(1). Regulatory inputs are specified by the mRNA untranslated regions (UTRs) and often target translation initiation. Initiation involves binding of the 40S ribosomal small subunit (SSU) and associated eukaryotic initiation factors (eIFs) near the mRNA 5' cap; the SSU then scans in the 3' direction until it detects the start codon and is joined by the 60S ribosomal large subunit (LSU)(2-5) to form the 80S ribosome. Scanning and other dynamic aspects of the initiation model have remained as conjectures because methods to trap early intermediates were lacking. Here we uncover the dynamics of the complete translation cycle in live yeast cells using translation complex profile sequencing (TCP-seq), a method developed from the ribosome profiling(6) approach. We document scanning by observing SSU footprints along 5' UTRs. Scanning SSU have 5'-extended footprints (up to similar to 75 nucleotides), indicative of additional interactions with mRNA emerging from the exit channel, promoting forward movement. We visualized changes in initiation complex conformation as SSU footprints coalesced into three major sizes at start codons (19, 29 and 37 nucleotides). These share the same 5' start site but differ at the 3' end, reflecting successive changes at the entry channel from an open to a closed state following start codon recognition. We also observe SSU 'lingering' at stop codons after LSU departure. Our results underpin mechanistic models of translation initiation and termination, built on decades of biochemical and structural investigation, with direct genome-wide in vivo evidence. Our approach captures ribosomal complexes at all phases of translation and will aid in studying translation dynamics in diverse cellular contexts. Dysregulation of translation is common in disease and, for example, SSU scanning is a target of anti-cancer drug development(7). TCP-seq will prove useful in discerning differences in mRNA-specific initiation in pathologies and their response to treatment.
C1 [Archer, Stuart K.; Shirokikh, Nikolay E.; Preiss, Thomas] Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Sci, EMBL Australia Collaborating Grp, Canberra, ACT 2601, Australia.
   [Archer, Stuart K.] Monash Univ, Monash Bioinformat Platform, Melbourne, Vic 3800, Australia.
   [Shirokikh, Nikolay E.] Moscow Reg State Inst Humanities & Social Studies, Kolomna 140410, Russia.
   [Beilharz, Traude H.] Monash Univ, Monash Biomed Discovery Inst, Dev & Stem Cells Program, Melbourne, Vic 3800, Australia.
   [Beilharz, Traude H.] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3800, Australia.
   [Preiss, Thomas] Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia.
C3 Australian National University; John Curtin School of Medical Research; Monash University; Monash University; Monash University; Victor Chang Cardiac Research Institute
RP Preiss, T (corresponding author), Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Sci, EMBL Australia Collaborating Grp, Canberra, ACT 2601, Australia.; Preiss, T (corresponding author), Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia.
EM thomas.preiss@anu.edu.au
FU ARC [DP1300101928]; NHMRC [514904]; Go8 European Fellowship; National Health and Medical Research Council (NHMRC) [514904] Funding Source: National Health and Medical Research Council (NHMRC)
NR 45
TC 165
Z9 206
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 570
EP +
DI 10.1038/nature18647
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600033
PM 27437580
DA 2026-03-09
ER

PT J
AU Nishikawa, JL
   Boeszoermenyi, A
   Vale-Silva, LA
   Torelli, R
   Posteraro, B
   Sohn, YJ
   Ji, F
   Gelev, V
   Sanglard, D
   Sanguinetti, M
   Sadreyev, RI
   Mukherjee, G
   Bhyravabhotla, J
   Buhrlage, SJ
   Gray, NS
   Wagner, G
   Näär, AM
   Arthanari, H
AF Nishikawa, Joy L.
   Boeszoermenyi, Andras
   Vale-Silva, Luis A.
   Torelli, Riccardo
   Posteraro, Brunella
   Sohn, Yoo-Jin
   Ji, Fei
   Gelev, Vladimir
   Sanglard, Dominique
   Sanguinetti, Maurizio
   Sadreyev, Ruslan I.
   Mukherjee, Goutam
   Bhyravabhotla, Jayaram
   Buhrlage, Sara J.
   Gray, Nathanael S.
   Wagner, Gerhard
   Naeaer, Anders M.
   Arthanari, Haribabu
TI Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction
SO NATURE
LA English
DT Article
ID candida-glabrata; protein; pdr1
AB Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex(1,2). Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of detailed molecular knowledge of the mechanisms of gene activation by disease-associated transcription activators. We previously identified an activator-targeted three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11/Med15 Mediator subunits in fungi(3,4). The Gal11/Med15 KIX domain engages pleiotropic drug resistance transcription factor (Pdr1) orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae and in the clinically important human pathogen Candida glabrata(5,6). The prevalence of C. glabrata is rising, partly owing to its low intrinsic susceptibility to azoles, the most widely used antifungal agent(7,8). Drug-resistant clinical isolates of C. glabrata most commonly contain point mutations in Pdr1 that render it constitutively active(9-14), suggesting that this transcriptional activation pathway represents a linchpin in C. glabrata multidrug resistance. Here we perform sequential biochemical and in vivo high-throughput screens to identify small-molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Determining the NMR structure of the C. glabrata Gal11A KIX domain provides a detailed understanding of the molecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1. We have demonstrated the feasibility of small-molecule targeting of a transcription factor-binding site in Mediator as a novel therapeutic strategy in fungal infectious disease.
C1 [Nishikawa, Joy L.; Sohn, Yoo-Jin; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
   [Nishikawa, Joy L.; Sohn, Yoo-Jin; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Boeszoermenyi, Andras; Buhrlage, Sara J.; Gray, Nathanael S.; Wagner, Gerhard; Arthanari, Haribabu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Vale-Silva, Luis A.; Sanglard, Dominique] Univ Lausanne Hosp, Inst Microbiol, CH-1011 Lausanne, Switzerland.
   [Vale-Silva, Luis A.; Sanglard, Dominique] Univ Hosp Ctr, CH-1011 Lausanne, Switzerland.
   [Torelli, Riccardo; Sanguinetti, Maurizio] Univ Cattolica Sacro Cuore, Inst Microbiol, I-00168 Rome, Italy.
   [Posteraro, Brunella] Univ Cattolica Sacro Cuore, Inst Publ Hlth, I-00168 Rome, Italy.
   [Ji, Fei; Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Ji, Fei] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Gelev, Vladimir] Univ Sofia, Fac Chem & Pharm, Sofia 1164, Bulgaria.
   [Sadreyev, Ruslan I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Sadreyev, Ruslan I.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Mukherjee, Goutam; Bhyravabhotla, Jayaram] Indian Inst Technol Delhi, Dept Chem, New Delhi 110016, India.
   [Mukherjee, Goutam; Bhyravabhotla, Jayaram] Indian Inst Technol Delhi, Supercomp Facil Bioinformat & Computat Biol, New Delhi 110016, India.
   [Bhyravabhotla, Jayaram] Indian Inst Technol Delhi, Kusuma Sch Biol Sci, New Delhi 110016, India.
   [Buhrlage, Sara J.; Gray, Nathanael S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Sofia; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Delhi; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Delhi; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Delhi; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Näär, AM (corresponding author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.; Näär, AM (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.; Wagner, G; Arthanari, H (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM gerhard_wagner@hms.harvard.edu; naar@helix.mgh.harvard.edu; hari_arthanari@hms.harvard.edu
FU National Institute of Health [GM047467, EB002026]; NSERC fellowship; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561] Funding Source: NIH RePORTER
NR 25
TC 126
Z9 155
U1 0
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 485
EP +
DI 10.1038/nature16963
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800037
PM 26886795
DA 2026-03-09
ER

PT J
AU Weigelt, P
   Steinbauer, MJ
   Cabral, JS
   Kreft, H
AF Weigelt, Patrick
   Steinbauer, Manuel Jonas
   Cabral, Juliano Sarmento
   Kreft, Holger
TI Late Quaternary climate change shapes island biodiversity
SO NATURE
LA English
DT Article
ID species-area relationship; spatial autocorrelation; insular biogeography; distribution models; global patterns; vegetation; richness; ecology; driven; scale
AB Island biogeographical models consider islands either as geologically static with biodiversity resulting from ecologically neutral immigration-extinction dynamics(1), or as geologically dynamic with biodiversity resulting from immigration-speciation-extinction dynamics influenced by changes in island characteristics over millions of years(2). Present climate and spatial arrangement of islands, however, are rather exceptional compared to most of the Late Quaternary, which is characterized by recurrent cooler and drier glacial periods. These climatic oscillations over short geological timescales strongly affected sea levels(3,4) and caused massive changes in island area, isolation and connectivity(5), orders of magnitude faster than the geological processes of island formation, subsidence and erosion considered in island theory(2,6). Consequences of these oscillations for present biodiversity remain unassessed(5,7). Here we analyse the effects of present and Last Glacial Maximum (LGM) island area, isolation, elevation and climate on key components of angiosperm diversity on islands worldwide. We find that post-LGM changes in island characteristics, especially in area, have left a strong imprint on present diversity of endemic species. Specifically, the number and proportion of endemic species today is significantly higher on islands that were larger during the LGM. Native species richness, in turn, is mostly determined by present island characteristics. We conclude that an appreciation of Late Quaternary environmental change is essential to understand patterns of island endemism and its underlying evolutionary dynamics.
C1 [Weigelt, Patrick; Cabral, Juliano Sarmento; Kreft, Holger] Univ Gottingen, Biodivers Macroecol & Conservat Biogeog Grp, D-37077 Gottingen, Germany.
   [Weigelt, Patrick] Univ Gottingen, Syst Conservat Biol, D-37073 Gottingen, Germany.
   [Steinbauer, Manuel Jonas] Aarhus Univ, Dept Biosci, Sect Ecoinformat & Biodivers, DK-8000 Aarhus, Denmark.
   [Steinbauer, Manuel Jonas] Univ Bayreuth, BayCEER, Dept Biogeog, POB 101251, D-95440 Bayreuth, Germany.
   [Cabral, Juliano Sarmento] German Ctr Integrat Biodivers Res iDiv, Synth Ctr, D-04103 Leipzig, Germany.
C3 University of Gottingen; University of Gottingen; Aarhus University; University of Bayreuth; German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv)
RP Weigelt, P; Kreft, H (corresponding author), Univ Gottingen, Biodivers Macroecol & Conservat Biogeog Grp, D-37077 Gottingen, Germany.; Weigelt, P (corresponding author), Univ Gottingen, Syst Conservat Biol, D-37073 Gottingen, Germany.
EM pweigel@uni-goettingen.de; hkreft@uni-goettingen.de
FU German Research Council (DFG) Free Floater Program in the Excellence Initiative at the University of Gottingen; BEFmate project from the Ministry of Science and Culture of Lower Saxony; Danish Carlsbergfondet [CF14-0148]
NR 101
TC 200
Z9 210
U1 4
U2 236
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 99
EP +
DI 10.1038/nature17443
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500041
PM 27027291
DA 2026-03-09
ER

PT J
AU Kaneda, MM
   Messer, KS
   Ralainirina, N
   Li, HY
   Leem, CJ
   Gorjestani, S
   Woo, G
   Nguyen, AV
   Figueiredo, CC
   Foubert, P
   Schmid, MC
   Pink, M
   Winkler, DG
   Rausch, M
   Palombella, VJ
   Kutok, J
   McGovern, K
   Frazer, KA
   Wu, XF
   Karin, M
   Sasik, R
   Cohen, EEW
   Varner, JA
AF Kaneda, Megan M.
   Messer, Karen S.
   Ralainirina, Natacha
   Li, Hongying
   Leem, Christopher J.
   Gorjestani, Sara
   Woo, Gyunghwi
   Nguyen, Abraham V.
   Figueiredo, Camila C.
   Foubert, Philippe
   Schmid, Michael C.
   Pink, Melissa
   Winkler, David G.
   Rausch, Matthew
   Palombella, Vito J.
   Kutok, Jeffery
   McGovern, Karen
   Frazer, Kelly A.
   Wu, Xuefeng
   Karin, Michael
   Sasik, Roman
   Cohen, Ezra E. W.
   Varner, Judith A.
TI PI3Kγ is a molecular switch that controls immune suppression
SO NATURE
LA English
DT Article
ID macrophage; polarization; inhibition; activation; discovery; kinases; pathway; cancer; cells
AB Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer(1-5). In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors(1-7). Here we show that macrophage PI 3-kinase gamma controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3K gamma signalling through Akt and mTOR inhibits NF kappa B activation while stimulating C/EBP beta activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3K gamma stimulates and prolongs NF kappa B activation and inhibits C/EBP beta activation, thus promoting an immunostimulatory transcriptional program that restores CD8(+). T cell activation and cytotoxicity. PI3K gamma synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3K gamma-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders.
C1 [Kaneda, Megan M.; Messer, Karen S.; Ralainirina, Natacha; Li, Hongying; Leem, Christopher J.; Gorjestani, Sara; Woo, Gyunghwi; Nguyen, Abraham V.; Figueiredo, Camila C.; Foubert, Philippe; Schmid, Michael C.; Cohen, Ezra E. W.; Varner, Judith A.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
   [Messer, Karen S.; Li, Hongying] Univ Calif San Diego, Div Biostat & Bioinformat, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
   [Figueiredo, Camila C.] Univ Estado Rio De Janeiro, Dept Biol Celular, BR-20550013 Rio De Janeiro, Brazil.
   [Pink, Melissa; Winkler, David G.; Rausch, Matthew; Palombella, Vito J.; Kutok, Jeffery; McGovern, Karen] Infin Pharmaceut, Cambridge, MA 02139 USA.
   [Frazer, Kelly A.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [Frazer, Kelly A.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
   [Wu, Xuefeng; Karin, Michael] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Sasik, Roman] Univ Calif San Diego, Inst Genom Med, Ctr Computat Biol & Bioinformat, La Jolla, CA 92093 USA.
   [Cohen, Ezra E. W.; Varner, Judith A.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Varner, Judith A.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Universidade do Estado do Rio de Janeiro; Infinity Pharmaceuticals, Inc.; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Varner, JA (corresponding author), Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.; Varner, JA (corresponding author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.; Varner, JA (corresponding author), Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
EM jvarner@ucsd.edu
FU NIH [R01CA126820, T32HL098062, T32CA009523, T32CA121938]; CAPES Foundation; Ministry of Education of Brazil; Immunotherapy Foundation; National Cancer Institute [R01CA167426, T32CA009523, T32CA121938, P30CA023100] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001442] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL134632] Funding Source: NIH RePORTER
NR 26
TC 965
Z9 1097
U1 6
U2 331
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 437
EP 442
DI 10.1038/nature19834
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700056
PM 27642729
DA 2026-03-09
ER

PT J
AU Khare, S
   Nagle, AS
   Biggart, A
   Lai, YH
   Liang, F
   Davis, LC
   Barnes, SW
   Mathison, CJN
   Myburgh, E
   Gao, MY
   Gillespie, JR
   Liu, XZ
   Tan, JL
   Stinson, M
   Rivera, IC
   Ballard, J
   Yeh, V
   Groessl, T
   Federe, G
   Koh, HXY
   Venable, JD
   Bursulaya, B
   Shapiro, M
   Mishra, PK
   Spraggon, G
   Brock, A
   Mottram, JC
   Buckner, FS
   Rao, SPS
   Wen, BG
   Walker, JR
   Tuntland, T
   Molteni, V
   Glynne, RJ
   Supek, F
AF Khare, Shilpi
   Nagle, Advait S.
   Biggart, Agnes
   Lai, Yin H.
   Liang, Fang
   Davis, Lauren C.
   Barnes, S. Whitney
   Mathison, Casey J. N.
   Myburgh, Elmarie
   Gao, Mu-Yun
   Gillespie, J. Robert
   Liu, Xianzhong
   Tan, Jocelyn L.
   Stinson, Monique
   Rivera, Ianne C.
   Ballard, Jaime
   Yeh, Vince
   Groessl, Todd
   Federe, Glenn
   Koh, Hazel X. Y.
   Venable, John D.
   Bursulaya, Badry
   Shapiro, Michael
   Mishra, Pranab K.
   Spraggon, Glen
   Brock, Ansgar
   Mottram, Jeremy C.
   Buckner, Frederick S.
   Rao, Srinivasa P. S.
   Wen, Ben G.
   Walker, John R.
   Tuntland, Tove
   Molteni, Valentina
   Glynne, Richard J.
   Supek, Frantisek
TI Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness
SO NATURE
LA English
DT Article
ID trypanosoma-cruzi; randomized-trial; drug discovery; benznidazole; posaconazole; bortezomib; infection; system; gene; cure
AB Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually(1). The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target(2). However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.
C1 [Khare, Shilpi; Nagle, Advait S.; Biggart, Agnes; Lai, Yin H.; Liang, Fang; Davis, Lauren C.; Barnes, S. Whitney; Mathison, Casey J. N.; Gao, Mu-Yun; Liu, Xianzhong; Tan, Jocelyn L.; Stinson, Monique; Rivera, Ianne C.; Ballard, Jaime; Yeh, Vince; Groessl, Todd; Federe, Glenn; Venable, John D.; Bursulaya, Badry; Shapiro, Michael; Spraggon, Glen; Brock, Ansgar; Wen, Ben G.; Walker, John R.; Tuntland, Tove; Molteni, Valentina; Glynne, Richard J.; Supek, Frantisek] Novartis Res Fdn, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA.
   [Myburgh, Elmarie; Mottram, Jeremy C.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Wellcome Trust Ctr Mol Parasitol, Glasgow G12 8TA, Lanark, Scotland.
   [Myburgh, Elmarie; Mottram, Jeremy C.] Univ York, Dept Biol, Ctr Immunol & Infect, Wentworth Way, York YO10 5DD, N Yorkshire, England.
   [Gillespie, J. Robert; Buckner, Frederick S.] Univ Washington, Dept Med, Seattle, WA 98109 USA.
   [Koh, Hazel X. Y.; Rao, Srinivasa P. S.] Novartis Inst Trop Dis, 10 Biopolis Rd, Singapore 138670, Singapore.
C3 Novartis; Novartis USA; University of Glasgow; University of York - UK; University of Washington; University of Washington Seattle; Novartis; Novartis Singapore
RP Supek, F (corresponding author), Novartis Res Fdn, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA.
EM fsupek@gnf.org
FU Wellcome Trust [091038/Z/09/Z, 104976/Z/14/Z, 104111/15/Z]; NIH [AI106850]; Wellcome Trust [091038/Z/09/Z, 104976/Z/14/Z] Funding Source: Wellcome Trust
NR 46
TC 323
Z9 350
U1 2
U2 108
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 229
EP +
DI 10.1038/nature19339
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100047
PM 27501246
DA 2026-03-09
ER

PT J
AU Fox, RG
   Lytle, NK
   Jaquish, DV
   Park, FD
   Ito, T
   Bajaj, J
   Koechlein, CS
   Zimdahl, B
   Yano, M
   Kopp, JL
   Kritzik, M
   Sicklick, JK
   Sander, M
   Grandgenett, PM
   Hollingsworth, MA
   Shibata, S
   Pizzo, D
   Valasek, MA
   Sasik, R
   Scadeng, M
   Okano, H
   Kim, Y
   MacLeod, AR
   Lowy, AM
   Reya, T
AF Fox, Raymond G.
   Lytle, Nikki K.
   Jaquish, Dawn V.
   Park, Frederick D.
   Ito, Takahiro
   Bajaj, Jeevisha
   Koechlein, Claire S.
   Zimdahl, Bryan
   Yano, Masato
   Kopp, Janel L.
   Kritzik, Marcie
   Sicklick, Jason K.
   Sander, Maike
   Grandgenett, Paul M.
   Hollingsworth, Michael A.
   Shibata, Shinsuke
   Pizzo, Donald
   Valasek, Mark A.
   Sasik, Roman
   Scadeng, Miriam
   Okano, Hideyuki
   Kim, Youngsoo
   MacLeod, A. Robert
   Lowy, Andrew M.
   Reya, Tannishtha
TI Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma
SO NATURE
LA English
DT Article
ID cancer stem-cells; antisense oligonucleotides; rna; musashi; regulator; microarrays; marker; screen; roles
AB Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance1. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression both in genetic models and in patient-derived xenografts. Specifically, we developed Msi reporter mice that allowed image-based tracking of stem cell signals within cancers, revealing that Msi expression rises as pancreatic intraepithelial neoplasia progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreatic cancer: they preferentially harbour the capacity to propagate adenocarcinoma, are enriched in circulating tumour cells, and are markedly drug resistant. This population could be effectively targeted by deletion of either Msi1 or Msi2, which led to a striking defect in the progression of pancreatic intraepithelial neoplasia to adenocarcinoma and an improvement in overall survival. Msi inhibition also blocked the growth of primary patient-derived tumours, suggesting that this signal is required for human disease. To define the translational potential of this work we developed antisense oligonucleotides against Msi; these showed reliable tumour penetration, uptake and target inhibition, and effectively blocked pancreatic cancer growth. Collectively, these studies highlight Msi reporters as a unique tool to identify therapy resistance, and define Msi signalling as a central regulator of pancreatic cancer.
C1 [Fox, Raymond G.; Lytle, Nikki K.; Park, Frederick D.; Ito, Takahiro; Bajaj, Jeevisha; Koechlein, Claire S.; Zimdahl, Bryan; Kritzik, Marcie; Reya, Tannishtha] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Fox, Raymond G.; Lytle, Nikki K.; Park, Frederick D.; Ito, Takahiro; Bajaj, Jeevisha; Koechlein, Claire S.; Zimdahl, Bryan; Kritzik, Marcie; Reya, Tannishtha] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
   [Fox, Raymond G.; Lytle, Nikki K.; Park, Frederick D.; Ito, Takahiro; Bajaj, Jeevisha; Koechlein, Claire S.; Zimdahl, Bryan; Kritzik, Marcie; Sander, Maike; Reya, Tannishtha] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
   [Fox, Raymond G.; Lytle, Nikki K.; Jaquish, Dawn V.; Park, Frederick D.; Ito, Takahiro; Bajaj, Jeevisha; Koechlein, Claire S.; Zimdahl, Bryan; Kritzik, Marcie; Sicklick, Jason K.; Lowy, Andrew M.; Reya, Tannishtha] Univ Calif San Diego, Sch Med, Moores Canc Ctr, La Jolla, CA 92093 USA.
   [Jaquish, Dawn V.; Sicklick, Jason K.; Lowy, Andrew M.] Univ Calif San Diego, Sch Med, Dept Surg, Div Surg Oncol, La Jolla, CA 92093 USA.
   [Park, Frederick D.] Univ Calif San Diego, Sch Med, Dept Med, Div Gastroenterol, La Jolla, CA 92093 USA.
   [Yano, Masato; Shibata, Shinsuke; Okano, Hideyuki] Keio Univ, Dept Physiol, Sch Med, Tokyo 1608582, Japan.
   [Kopp, Janel L.; Sander, Maike] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Grandgenett, Paul M.; Hollingsworth, Michael A.] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Dept Pathol, Omaha, NE 68198 USA.
   [Pizzo, Donald; Valasek, Mark A.] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA.
   [Sasik, Roman] Univ Calif San Diego, Sch Med, Ctr Computat Biol & Bioinformat, La Jolla, CA 92093 USA.
   [Scadeng, Miriam] Univ Calif San Diego, Sch Med, Dept Radiol, La Jolla, CA 92093 USA.
   [Kim, Youngsoo; MacLeod, A. Robert] Ionis Pharmaceut, Dept Oncol Drug Discovery, Carlsbad, CA 92010 USA.
   [Yano, Masato] Niigata Univ, Div Neurobiol & Anat, Grad Sch Med & Dent Sci, Chuo Ku, Niigata 9518510, Japan.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Keio University; University of California System; University of California San Diego; University of Nebraska System; University of Nebraska Medical Center; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Ionis Pharmaceuticals, Inc.; Niigata University
RP Reya, T (corresponding author), Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.; Reya, T (corresponding author), Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.; Reya, T (corresponding author), Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.; Lowy, AM; Reya, T (corresponding author), Univ Calif San Diego, Sch Med, Moores Canc Ctr, La Jolla, CA 92093 USA.; Lowy, AM (corresponding author), Univ Calif San Diego, Sch Med, Dept Surg, Div Surg Oncol, La Jolla, CA 92093 USA.
EM alowy@ucsd.edu; treya@ucsd.edu
FU California Institute for Regenerative Medicine; National Research Service Award [F31 CA206416]; National Institutes of Health (NIH) [F32CA136124]; Advanced Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation; University of California San Diego Clinical and Translational Research Institute KL2 Award; National Cancer Center; Leukemia and Lymphoma Society Scholar Award; Specialized Program of Research Excellence (SPORE) in Pancreatic Cancer [CA127297]; TMEN Tumor Microenvironment Network [U54]; National Cancer Institute Cancer Center Support Grant [P30 CA36727]; Early Detection Research Network (EDRN) [U01 CA111294]; NIH [DK078803, CA194839, K08CA168999]; Clinical and Translational Research Institute (CTRI) grant [UL1TR001442];  [T32 HL086344];  [T32 CA009523];  [T32 GM007752];  [T32 GM007184-33];  [CA155620];  [DK63031];  [HL097767];  [DP1 CA174422];  [R35 CA197699];  [CA186043]; National Cancer Institute [R01CA155620, R50CA211462, R35CA197699, P30CA036727, T32CA009523] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001442] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL086344] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK078803] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007752] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [16K07247] Funding Source: KAKEN
NR 48
TC 119
Z9 139
U1 0
U2 105
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 407
EP +
DI 10.1038/nature17988
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800040
PM 27281208
DA 2026-03-09
ER

PT J
AU Dalladay-Simpson, P
   Howie, RT
   Gregoryanz, E
AF Dalladay-Simpson, Philip
   Howie, Ross T.
   Gregoryanz, Eugene
TI Evidence for a new phase of dense hydrogen above 325 gigapascals
SO NATURE
LA English
DT Article
ID raman-spectroscopy; solid hydrogen; dissociation; transition; atoms; gpa
AB Almost 80 years ago it was predicted that, under sufficient compression, the H-H bond in molecular hydrogen (H-2) would break, forming a new, atomic, metallic, solid state of hydrogen(1). Reaching this predicted state experimentally has been one of the principal goals in high-pressure research for the past 30 years. Here, using in situ high-pressure Raman spectroscopy, we present evidence that at pressures greater than 325 gigapascals at 300 kelvin, H-2 and hydrogen deuteride (HD) transform to a new phase-phase V. This new phase of hydrogen is characterized by substantial weakening of the vibrational Raman activity, a change in pressure dependence of the fundamental vibrational frequency and partial loss of the low-frequency excitations. We map out the domain in pressure-temperature space of the suggested phase V in H-2 and HD up to 388 gigapascals at 300 kelvin, and up to 465 kelvin at 350 gigapascals; we do not observe phase V in deuterium (D-2). However, we show that the transformation to phase IV' in D-2 occurs above 310 gigapascals and 300 kelvin. These values represent the largest known isotropic shift in pressure, and hence the largest possible pressure difference between the H-2 and D-2 phases, which implies that the appearance of phase V of D-2 must occur at a pressure of above 380 gigapascals. These experimental data provide a glimpse of the physical properties of dense hydrogen above 325 gigapascals and constrain the pressure and temperature conditions at which the new phase exists. We speculate that phase V may be the precursor to the non-molecular (atomic and metallic) state of hydrogen that was predicted 80 years ago.
C1 [Dalladay-Simpson, Philip; Howie, Ross T.; Gregoryanz, Eugene] Univ Edinburgh, Sch Phys, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Dalladay-Simpson, Philip; Howie, Ross T.; Gregoryanz, Eugene] Univ Edinburgh, Ctr Sci Extreme Condit, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Gregoryanz, Eugene] Chinese Acad Sci, Inst Solid State Phys, Key Lab Mat Phys, Hefei 230031, Peoples R China.
   [Howie, Ross T.] Ctr High Pressure Sci & Technol Adv Res, Shanghai 201203, Peoples R China.
C3 University of Edinburgh; University of Edinburgh; Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS
RP Gregoryanz, E (corresponding author), Univ Edinburgh, Sch Phys, Edinburgh EH9 3JZ, Midlothian, Scotland.; Gregoryanz, E (corresponding author), Univ Edinburgh, Ctr Sci Extreme Condit, Edinburgh EH9 3JZ, Midlothian, Scotland.; Gregoryanz, E (corresponding author), Chinese Acad Sci, Inst Solid State Phys, Key Lab Mat Phys, Hefei 230031, Peoples R China.
EM e.gregoryanz@ed.ac.uk
FU UK Engineering and Physical Sciences Research Council (EPSRC) [EP/J003999/1]; EPSRC [EP/G03673X/1]; EPSRC [EP/J003999/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/J003999/1, 1110865] Funding Source: researchfish
NR 29
TC 237
Z9 258
U1 3
U2 223
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 63
EP +
DI 10.1038/nature16164
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900026
PM 26738591
DA 2026-03-09
ER

PT J
AU Sekar, A
   Bialas, AR
   de Rivera, H
   Davis, A
   Hammond, TR
   Kamitaki, N
   Tooley, K
   Presumey, J
   Baum, M
   Van Doren, V
   Genovese, G
   Rose, SA
   Handsaker, RE
   Daly, MJ
   Carroll, MC
   Stevens, B
   McCarroll, SA
AF Sekar, Aswin
   Bialas, Allison R.
   de Rivera, Heather
   Davis, Avery
   Hammond, Timothy R.
   Kamitaki, Nolan
   Tooley, Katherine
   Presumey, Jessy
   Baum, Matthew
   Van Doren, Vanessa
   Genovese, Giulio
   Rose, Samuel A.
   Handsaker, Robert E.
   Daly, Mark J.
   Carroll, Michael C.
   Stevens, Beth
   McCarroll, Steven A.
TI Schizophrenia risk from complex variation of complement component 4
SO NATURE
LA English
DT Article
ID classical pathway complement; cortical pyramidal neurons; dendritic spine density; endogenous retrovirus; prenatal development; synapse elimination; common variants; mhc haplotypes; c4; protein
AB Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
C1 [Sekar, Aswin; de Rivera, Heather; Davis, Avery; Kamitaki, Nolan; Tooley, Katherine; Baum, Matthew; Van Doren, Vanessa; Genovese, Giulio; Handsaker, Robert E.; McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sekar, Aswin; de Rivera, Heather; Davis, Avery; Kamitaki, Nolan; Tooley, Katherine; Baum, Matthew; Genovese, Giulio; Rose, Samuel A.; Handsaker, Robert E.; Daly, Mark J.; Stevens, Beth; McCarroll, Steven A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Sekar, Aswin; Baum, Matthew] Harvard Univ, Sch Med, MD PhD Program, Boston, MA 02115 USA.
   [Bialas, Allison R.; Hammond, Timothy R.; Baum, Matthew; Stevens, Beth] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurol,FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Bialas, Allison R.; Presumey, Jessy; Carroll, Michael C.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP McCarroll, SA (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM mccarroll@genetics.med.harvard.edu
FU Stanley Center for Psychiatric Research;  [R01 HG 006855];  [U01 MH105641];  [R01 MH077139];  [T32 GM007753]; MRC [G0901310, MR/P005748/1, G0800509] Funding Source: UKRI; Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish; Medical Research Council [MR/P005748/1, G0901310, MR/L010305/1, G0800509] Funding Source: researchfish; National Institute for Health Research [PDA/02/06/016] Funding Source: researchfish; National Human Genome Research Institute [R01HG006855] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 56
TC 1760
Z9 2090
U1 5
U2 370
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 177
EP +
DI 10.1038/nature16549
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700030
PM 26814963
DA 2026-03-09
ER

PT J
AU Vermeij, WP
   Dollé, MET
   Reiling, E
   Jaarsma, D
   Payan-Gomez, C
   Bombardieri, CR
   Wu, H
   Roks, AJM
   Botter, SM
   van der Eerden, BC
   Youssef, SA
   Kuiper, RV
   Nagarajah, B
   van Oostrom, CT
   Brandt, RMC
   Barnhoorn, S
   Imholz, S
   Pennings, JLA
   de Bruin, A
   Gyenis, A
   Pothof, J
   Vijg, J
   van Steeg, H
   Hoeijmakers, JHJ
AF Vermeij, W. P.
   Dolle, M. E. T.
   Reiling, E.
   Jaarsma, D.
   Payan-Gomez, C.
   Bombardieri, C. R.
   Wu, H.
   Roks, A. J. M.
   Botter, S. M.
   van der Eerden, B. C.
   Youssef, S. A.
   Kuiper, R. V.
   Nagarajah, B.
   van Oostrom, C. T.
   Brandt, R. M. C.
   Barnhoorn, S.
   Imholz, S.
   Pennings, J. L. A.
   de Bruin, A.
   Gyenis, A.
   Pothof, J.
   Vijg, J.
   van Steeg, H.
   Hoeijmakers, J. H. J.
TI Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice
SO NATURE
LA English
DT Article
ID caloric restriction; nuclear abnormality; cockayne-syndrome; growth; degeneration; component; models; cancer; p53
AB Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1(Delta/-)) show numerous accelerated ageing features that limit their lifespan to 4-6 months(1-4). They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction)(1,5). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg(-/-) (also known as Ercc5(-/-)) mice, a model of Cockayne syndrome(6), responded similarly. The dietary restriction response in Ercc1(Delta/-) mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1(Delta/-) mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of gamma H2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1(Delta/-) mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.
C1 [Vermeij, W. P.; Reiling, E.; Payan-Gomez, C.; Bombardieri, C. R.; Botter, S. M.; Brandt, R. M. C.; Barnhoorn, S.; Gyenis, A.; Pothof, J.; Hoeijmakers, J. H. J.] Erasmus Univ, Dept Mol Genet, Med Ctr Rotterdam, POB 2040, NL-3000 CA Rotterdam, Netherlands.
   [Dolle, M. E. T.; Reiling, E.; Nagarajah, B.; van Oostrom, C. T.; Imholz, S.; Pennings, J. L. A.; van Steeg, H.] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, POB 1, NL-3720 BA Bilthoven, Netherlands.
   [Jaarsma, D.] Erasmus Univ, Med Ctr Rotterdam, Dept Neurosci, POB 2040, NL-3000 CA Rotterdam, Netherlands.
   [Payan-Gomez, C.] Univ Rosario, Fac Ciencias Nat & Matemat, Carrera 24,63C-69, Bogota, Colombia.
   [Wu, H.; Roks, A. J. M.] Erasmus Univ, Div Vasc Med & Pharmacol, Dept Internal Med, Med Ctr Rotterdam, POB 2040, NL-3000 CA Rotterdam, Netherlands.
   [Botter, S. M.] Balgrist Univ Hosp, Lab Orthoped Res, Forchstr 340, CH-8008 Zurich, Switzerland.
   [van der Eerden, B. C.] Erasmus Univ, Dept Internal Med, Med Ctr Rotterdam, POB 2040, NL-3000 CA Rotterdam, Netherlands.
   [Youssef, S. A.; Kuiper, R. V.; de Bruin, A.] Univ Utrecht, Dept Pathobiol, Dutch Mol Pathol Ctr, Fac Vet Med, POB 80125, NL-3508 TC Utrecht, Netherlands.
   [de Bruin, A.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, Div Mol Genet, POB 30001, NL-9700 RB Groningen, Netherlands.
   [Vijg, J.] Albert Einstein Coll Med, Dept Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
   [van Steeg, H.] Leiden Univ, Med Ctr, Dept Human Genet, POB 9600, NL-2300 RC Leiden, Netherlands.
   [Hoeijmakers, J. H. J.] Univ Cologne, CECAD Forschungszentrum, Joseph Stelzmann Str 26, D-50931 Cologne, Germany.
   [Kuiper, R. V.] Karolinska Inst, Dept Lab Med, SE-17177 Stockholm, Sweden.
C3 Erasmus University Rotterdam; Erasmus MC; Netherlands National Institute for Public Health & the Environment; Erasmus University Rotterdam; Erasmus MC; Universidad del Rosario; Erasmus University Rotterdam; Erasmus MC; University of Zurich; Erasmus University Rotterdam; Erasmus MC; Utrecht University; University of Groningen; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); University of Cologne; Karolinska Institutet
RP Hoeijmakers, JHJ (corresponding author), Erasmus Univ, Dept Mol Genet, Med Ctr Rotterdam, POB 2040, NL-3000 CA Rotterdam, Netherlands.; Dollé, MET (corresponding author), Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, POB 1, NL-3720 BA Bilthoven, Netherlands.
EM martijn.dolle@rivm.nl; j.hoeijmakers@erasmusmc.nl
FU National Institute of Health (NIH)/National Institute of Ageing (NIA) [1PO1 AG-17242-02]; National Institute for Public Health and the Environment; Ministry of Health, Welfare and Sport of The Netherlands [S/340005]; European Research Council; European commission [FP7-Health-2008-200880]; DNA Repair [LSHG-CT-2005-512113]; EU ITN Address [GA-316390]; KWO Dutch Cancer Society [5030]; Dutch CAA Foundation; Royal Academy of Arts and Sciences of the Netherlands; European Community [HEALTH-F2-2010-259893]; National Cancer Institute [P30CA013330] Funding Source: NIH RePORTER; National Institute on Aging [P01AG017242] Funding Source: NIH RePORTER
NR 46
TC 238
Z9 272
U1 2
U2 96
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 427
EP +
DI 10.1038/nature19329
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000059
PM 27556946
DA 2026-03-09
ER

PT J
AU Sheyko, A
   Finlay, CC
   Jackson, A
AF Sheyko, Andrey
   Finlay, Christopher C.
   Jackson, Andrew
TI Magnetic reversals from planetary dynamo waves
SO NATURE
LA English
DT Article
ID convection-driven dynamos; simulations; dipolar; transition; frequency; geodynamo; buoyancy; models; flux
AB A striking feature of many natural dynamos is their ability to undergo polarity reversals(1,2). The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history(3,4). The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes place in Earth's core, but the precise mechanism is debated(5). The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines by columnar convection(6). Here we present an example of another class of reversing-geodynamo model, which operates in a regime of comparatively low viscosity and high magnetic diffusivity. This class does not fit into the paradigm of reversal regimes that are dictated by the value of the local Rossby number (the ratio of advection to Coriolis force)(7,8). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin to kinematic dynamo waves(9,10). Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.
C1 [Sheyko, Andrey; Jackson, Andrew] Swiss Fed Inst Technol, Inst Geophys, CH-8092 Zurich, Switzerland.
   [Finlay, Christopher C.] Tech Univ Denmark, DTU Space, Div Geomagnetism, DK-2800 Lyngby, Denmark.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Technical University of Denmark
RP Sheyko, A (corresponding author), Swiss Fed Inst Technol, Inst Geophys, CH-8092 Zurich, Switzerland.
EM andrei.sheiko@erdw.ethz.ch
FU Centro Svizzero di Calcolo Scientifico (CSCS) [s577]; ERC [247303]; Danish Council for Independent Research (DFF) [4002-00366]; European Research Council (ERC) [247303] Funding Source: European Research Council (ERC)
NR 43
TC 29
Z9 31
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 551
EP +
DI 10.1038/nature19842
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600041
PM 27820946
DA 2026-03-09
ER

PT J
AU Petzold, G
   Fischer, ES
   Thomä, NH
AF Petzold, Georg
   Fischer, Eric S.
   Thomae, Nicolas H.
TI Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
SO NATURE
LA English
DT Article
ID thalidomide; complex; target; identification; architecture; validation; activation; cereblon; ikaros; cells
AB Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies(1,2). IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4(CRBN)) E3 ubiquitin ligase(3), and inhibit ubiquitination of endogenous CRL4CRBN substrates(4). Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3)(5-7), and casein kinase 1 alpha (CK1 alpha)(8), which contributes to its clinical efficacy in the treatment of multiple myeloma(5) and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS)(8), respectively. How lenalidomide alters the specificity of the ligase to degrade these proteins remains elusive. Here we present the 2.45 angstrom crystal structure of DDB1-CRBN bound to lenalidomide and CK1 alpha. CRBN and lenalidomide jointly provide the binding interface for a CK1 alpha beta-hairpin-loop located in the kinase N-lobe. We show that CK1 alpha binding to CRL4(CRBN) is strictly dependent on the presence of an IMiD. Binding of IKZF1 to CRBN similarly requires the compound and both, IKZF1 and CK1 alpha, use a related binding mode. Our study provides a mechanistic explanation for the selective efficacy of lenalidomide in del(5q) MDS therapy(8,9). We anticipate that high-affinity protein-protein interactions induced by small molecules will provide opportunities for drug development, particularly for targeted protein degradation.
C1 [Petzold, Georg; Fischer, Eric S.; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
   [Petzold, Georg; Fischer, Eric S.; Thomae, Nicolas H.] Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland.
   [Fischer, Eric S.] Dana Farber Canc Inst, Dept Canc Biol, LC-4312,360 Longwood Ave, Boston, MA 02215 USA.
   [Fischer, Eric S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School
RP Thomä, NH (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.; Thomä, NH (corresponding author), Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland.
EM nicolas.thoma@fmi.ch
FU Novartis Research Foundation; Swiss National Science Foundation [31003A_144020]; European Research Council [ERC-2014-ADG 666068]; European Molecular Biology Organization (EMBO) [ALTF-1350-2013]; Human Frontier Science Program (HFSP) [LT000210/2014]; Swiss National Science Foundation (SNF) [31003A_144020] Funding Source: Swiss National Science Foundation (SNF)
NR 41
TC 461
Z9 531
U1 3
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 127
EP +
DI 10.1038/nature16979
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500047
PM 26909574
DA 2026-03-09
ER

PT J
AU Kadau, H
   Schmitt, M
   Wenzel, M
   Wink, C
   Maier, T
   Ferrier-Barbut, I
   Pfau, T
AF Kadau, Holger
   Schmitt, Matthias
   Wenzel, Matthias
   Wink, Clarissa
   Maier, Thomas
   Ferrier-Barbut, Igor
   Pfau, Tilman
TI Observing the Rosensweig instability of a quantum ferrofluid
SO NATURE
LA English
DT Article
ID bose-einstein condensation; stabilization; helium; gas
AB Ferrofluids exhibit unusual hydrodynamic effects owing to the magnetic nature of their constituents. As magnetization increases, a classical ferrofluid undergoes a Rosensweig instability(1) and creates self-organized, ordered surface structures(2) or droplet crystals(3). Quantum ferrofluids such as Bose-Einstein condensates with strong dipolar interactions also display superfluidity(4). The field of dipolar quantum gases is motivated by the search for new phases of matter that break continuous symmetries(5,6). The simultaneous breaking of continuous symmetries such as the phase invariance in a superfluid state and the translational symmetry in a crystal provides the basis for these new states of matter. However, interaction-induced crystallization in a superfluid has not yet been observed. Here we use in situ imaging to directly observe the spontaneous transition from an unstructured superfluid to an ordered arrangement of droplets in an atomic dysprosium Bose-Einstein condensate(7). By using a Feshbach resonance to control the interparticle interactions, we induce a finite-wavelength instability(8) and observe discrete droplets in a triangular structure, the number of which grows as the number of atoms increases. We find that these structured states are surprisingly long-lived and observe hysteretic behaviour, which is typical for a crystallization process and in close analogy to the Rosensweig instability. Our system exhibits both superfluidity and, as we show here, spontaneous translational symmetry breaking. Although our observations do not probe superfluidity in the structured states, if the droplets establish a common phase via weak links, then our system is a very good candidate for a supersolid ground state(9-11).
C1 [Kadau, Holger; Schmitt, Matthias; Wenzel, Matthias; Wink, Clarissa; Maier, Thomas; Ferrier-Barbut, Igor; Pfau, Tilman] Univ Stuttgart, Phys Inst 5, D-70569 Stuttgart, Germany.
   [Kadau, Holger; Schmitt, Matthias; Wenzel, Matthias; Wink, Clarissa; Maier, Thomas; Ferrier-Barbut, Igor; Pfau, Tilman] Univ Stuttgart, Ctr Integrated Quantum Sci & Technol, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; University of Stuttgart
RP Kadau, H (corresponding author), Univ Stuttgart, Phys Inst 5, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM h.kadau@physik.uni-stuttgart.de; t.pfau@physik.uni-stuttgart.de
FU German Research Foundation (DFG) [SFB/TRR21]; 'Studienstiftung des deutschen Volkes'
NR 30
TC 523
Z9 565
U1 3
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 194
EP +
DI 10.1038/nature16485
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700033
PM 26829224
DA 2026-03-09
ER

PT J
AU Hamo, A
   Benyamini, A
   Shapir, I
   Khivrich, I
   Waissman, J
   Kaasbjerg, K
   Oreg, Y
   von Oppen, F
   Ilani, S
AF Hamo, A.
   Benyamini, A.
   Shapir, I.
   Khivrich, I.
   Waissman, J.
   Kaasbjerg, K.
   Oreg, Y.
   von Oppen, F.
   Ilani, S.
TI Electron attraction mediated by Coulomb repulsion
SO NATURE
LA English
DT Article
ID superconductivity; mechanism; systems
AB One of the defining properties of electrons is their mutual Coulomb repulsion. However, in solids this basic property may change; for example, in superconductors, the coupling of electrons to lattice vibrations makes the electrons attract one another, leading to the formation of bound pairs. Fifty years ago it was proposed(1) that electrons can be made attractive even when all of the degrees of freedom in the solid are electronic, by exploiting their repulsion from other electrons. This attraction mechanism, termed 'excitonic', promised to achieve stronger and more exotic superconductivity(2-6). Yet, despite an extensive search(7), experimental evidence for excitonic attraction has yet to be found. Here we demonstrate this attraction by constructing, from the bottom up, the fundamental building block(8) of the excitonic mechanism. Our experiments are based on quantum devices made from pristine carbon nanotubes, combined with cryogenic precision manipulation. Using this platform, we demonstrate that two electrons can be made to attract each other using an independent electronic system as the 'glue' that mediates attraction. Owing to its tunability, our system offers insights into the underlying physics, such as the dependence of the emergent attraction on the underlying repulsion, and the origin of the pairing energy. We also demonstrate transport signatures of excitonic pairing. This experimental demonstration of excitonic pairing paves the way for the design of exotic states of matter.
C1 [Hamo, A.; Benyamini, A.; Shapir, I.; Khivrich, I.; Waissman, J.; Kaasbjerg, K.; Oreg, Y.; Ilani, S.] Weizmann Inst Sci, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
   [von Oppen, F.] Free Univ Berlin, Dahlem Ctr Complex Quantum Syst, D-14195 Berlin, Germany.
   [von Oppen, F.] Free Univ Berlin, Fachbereich Phys, D-14195 Berlin, Germany.
   [Waissman, J.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Kaasbjerg, K.] Tech Univ Denmark, Dept Micro & Nanotechnol, DK-2800 Lyngby, Denmark.
C3 Weizmann Institute of Science; Free University of Berlin; Free University of Berlin; Harvard University; Technical University of Denmark
RP Ilani, S (corresponding author), Weizmann Inst Sci, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
EM shahal.ilani@weizmann.ac.il
FU Carlsberg Foundation; Minerva; BSF; ERC Adg grant [FP7/2007-2013 340210]; ERC Cog grant [647413];  [SPP 1459];  [SFB 658]; European Research Council (ERC) [647413] Funding Source: European Research Council (ERC)
NR 29
TC 82
Z9 89
U1 0
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 395
EP 400
DI 10.1038/nature18639
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200035
PM 27443742
DA 2026-03-09
ER

PT J
AU Wang, DL
   Kon, N
   Lasso, G
   Jiang, L
   Leng, WC
   Zhu, WG
   Qin, J
   Honig, B
   Gu, W
AF Wang, Donglai
   Kon, Ning
   Lasso, Gorka
   Jiang, Le
   Leng, Wenchuan
   Zhu, Wei-Guo
   Qin, Jun
   Honig, Barry
   Gu, Wei
TI Acetylation-regulated interaction between p53 and SET reveals a widespread regulatory mode
SO NATURE
LA English
DT Article
ID dna-damage response; c-terminal domain; lysine acetylation; tumor suppression; transcription; inhibition; histone; binding; information; activation
AB Although lysine acetylation is now recognized as a general protein modification for both histones and non-histone proteins(1-3), the mechanisms of acetylation-mediated actions are not completely understood. Acetylation of the C-terminal domain (CTD) of p53 (also known as TP53) was an early example of non-histone protein acetylation(4) and its precise role remains unclear. Lysine acetylation often creates binding sites for bromodomain-containing 'reader' proteins(5,6). Here we use a proteomic screen to identify the oncoprotein SET as a major cellular factor whose binding with p53 is dependent on CTD acetylation status. SET profoundly inhibits p53 transcriptional activity in unstressed cells, but SET-mediated repression is abolished by stress-induced acetylation of p53 CTD. Moreover, loss of the interaction with SET activates p53, resulting in tumour regression in mouse xenograft models. Notably, the acidic domain of SET acts as a 'reader' for the unacetylated CTD of p53 and this mechanism of acetylation-dependent regulation is widespread in nature. For example, acetylation of p53 also modulates its interactions with similar acidic domains found in other p53 regulators including VPRBP (also known as DCAF1), DAXX and PELP1 (refs. 7-9), and computational analysis of the proteome has identified numerous proteins with the potential to serve as acidic domain readers and lysine-rich ligands. Unlike bromodomain readers, which preferentially bind the acetylated forms of their cognate ligands, the acidic domain readers specifically recognize the unacetylated forms of their ligands. Finally, the acetylation-dependent regulation of p53 was further validated in vivo by using a knock-in mouse model expressing an acetylation-mimicking form of p53. These results reveal that acidic-domain-containing factors act as a class of acetylation-dependent regulators by targeting p53 and, potentially, other proteins.
C1 [Wang, Donglai; Kon, Ning; Jiang, Le; Gu, Wei] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet,Dept Pathol & Cell Biol, 1130 Nicholas Ave, New York, NY 10032 USA.
   [Lasso, Gorka; Honig, Barry] Columbia Univ, Howard Hughes Med Inst, Ctr Computat Biol & Bioinformat, Dept Biochem & Mol Biophys & Syst Biol, 1130 Nicholas Ave, New York, NY 10032 USA.
   [Leng, Wenchuan; Qin, Jun] PHOENIX Ctr, Natl Ctr Prot Sci, State Key Lab Prote, Beijing 102206, Peoples R China.
   [Zhu, Wei-Guo] Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen 518060, Peoples R China.
   [Qin, Jun] Baylor Coll Med, Dept Mol & Cellular Biol, Verna & Marrs McLean Dept Biochem & Mol Biol, Alkek Ctr Mol Discovery, Houston, TX 77030 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; Shenzhen University; Baylor College of Medicine
RP Gu, W (corresponding author), Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet,Dept Pathol & Cell Biol, 1130 Nicholas Ave, New York, NY 10032 USA.
EM wg8@cumc.columbia.edu
FU National Cancer Institute of the National Institutes of Health [5R01CA193890, 5RO1CA190477, 5RO1CA085533, 2P01CA080058, GM030518, CA121852]; National Cancer Institute [R01CA085533] Funding Source: NIH RePORTER
NR 30
TC 173
Z9 200
U1 2
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 118
EP 122
DI 10.1038/nature19759
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900046
PM 27626385
DA 2026-03-09
ER

PT J
AU Jezouin, S
   Iftikhar, Z
   Anthore, A
   Parmentier, FD
   Gennser, U
   Cavanna, A
   Ouerghi, A
   Levkivskyi, IP
   Idrisov, E
   Sukhorukov, EV
   Glazman, LI
   Pierre, F
AF Jezouin, S.
   Iftikhar, Z.
   Anthore, A.
   Parmentier, F. D.
   Gennser, U.
   Cavanna, A.
   Ouerghi, A.
   Levkivskyi, I. P.
   Idrisov, E.
   Sukhorukov, E. V.
   Glazman, L. I.
   Pierre, F.
TI Controlling charge quantization with quantum fluctuations
SO NATURE
LA English
DT Article
ID coulomb-blockade; oscillations; conductance; dot; coherent; flow
AB In 1909, Millikan showed that the charge of electrically isolated systems is quantized in units of the elementary electron charge e. Today, the persistence of charge quantization in small, weakly connected conductors allows for circuits in which single electrons are manipulated, with applications in, for example, metrology, detectors and thermometry(1-5). However, as the connection strength is increased, the discreteness of charge is progressively reduced by quantum fluctuations. Here we report the full quantum control and characterization of charge quantization. By using semiconductor-based tunable elemental conduction channels to connect a micrometre-scale metallic island to a circuit, we explore the complete evolution of charge quantization while scanning the entire range of connection strengths, from a very weak (tunnel) to a perfect (ballistic) contact. We observe, when approaching the ballistic limit, that charge quantization is destroyed by quantum fluctuations, and scales as the square root of the residual probability for an electron to be reflected across the quantum channel; this scaling also applies beyond the different regimes of connection strength currently accessible to theory(6-8). At increased temperatures, the thermal fluctuations result in an exponential suppression of charge quantization and in a universal square-root scaling, valid for all connection strengths, in agreement with expectations(8). Besides being pertinent for the improvement of single-electron circuits and their applications, and for the metal-semiconductor hybrids relevant to topological quantum computing(9), knowledge of the quantum laws of electricity will be essential for the quantum engineering of future nanoelectronic devices.
C1 [Jezouin, S.; Iftikhar, Z.; Anthore, A.; Parmentier, F. D.; Gennser, U.; Cavanna, A.; Ouerghi, A.; Pierre, F.] Univ Paris Diderot, Univ Paris Saclay, Univ Paris Sud,CNR, Ctr NanoSci & Nanotechnol C2N,Sorbonne Paris Cite, F-91120 Palaiseau, France.
   [Levkivskyi, I. P.] ETH, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
   [Idrisov, E.; Sukhorukov, E. V.] Univ Geneva, Dept Phys Theor, CH-1211 Geneva, Switzerland.
   [Glazman, L. I.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
C3 Universite Paris Cite; Universite Paris Saclay; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Geneva; Yale University
RP Pierre, F (corresponding author), Univ Paris Diderot, Univ Paris Saclay, Univ Paris Sud,CNR, Ctr NanoSci & Nanotechnol C2N,Sorbonne Paris Cite, F-91120 Palaiseau, France.
EM frederic.pierre@lpn.cnrs.fr
FU European Research Council [ERC-2010-StG-20091028, 259033]; French RENATECH network; national French programme 'Investissements d'Avenir' (Labex NanoSaclay) [ANR-10-LABX-0035]; US Department of Energy [DE-FG02-08ER46482]; Swiss National Science Foundation; U.S. Department of Energy (DOE) [DE-FG02-08ER46482] Funding Source: U.S. Department of Energy (DOE); European Research Council (ERC) [259033] Funding Source: European Research Council (ERC)
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NR 43
TC 39
Z9 43
U1 0
U2 59
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 58
EP +
DI 10.1038/nature19072
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200029
PM 27488797
DA 2026-03-09
ER

PT J
AU Marsh, TR
   Gänsicke, BT
   Hümmerich, S
   Hambsch, FJ
   Ernhard, KB
   Lloyd, C
   Breedt, E
   Stanway, ER
   Steeghs, DT
   Parsons, SG
   Toloza, O
   Schreiber, MR
   Jonker, PG
   van Roestel, J
   Kupfer, T
   Pala, AF
   Dhillon, VS
   Hardy, LK
   Littlefair, SP
   Aungwerojwit, A
   Arjyotha, S
   Koester, D
   Bochinski, JJ
   Haswell, CA
   Frank, P
   Wheatley, PJ
AF Marsh, T. R.
   Gansicke, B. T.
   Huemmerich, S.
   Hambsch, F. -J.
   Ernhard, K. B.
   Lloyd, C.
   Breedt, E.
   Stanway, E. R.
   Steeghs, D. T.
   Parsons, S. G.
   Toloza, O.
   Schreiber, M. R.
   Jonker, P. G.
   van Roestel, J.
   Kupfer, T.
   Pala, A. F.
   Dhillon, V. S.
   Hardy, L. K.
   Littlefair, S. P.
   Aungwerojwit, A.
   Arjyotha, S.
   Koester, D.
   Bochinski, J. J.
   Haswell, C. A.
   Frank, P.
   Wheatley, P. J.
TI A radio-pulsing white dwarf binary star
SO NATURE
LA English
DT Article
ID dq herculis stars; ae-aquarii; cataclysmic variables; emission; sky; spectroscopy; period; discovery; propeller; spectrum
AB White dwarfs are compact stars, similar in size to Earth but approximately 200,000 times more massive(1). Isolated white dwarfs emit most of their power from ultraviolet to near-infrared wavelengths, but when in close orbits with less dense stars, white dwarfs can strip material from their companions and the resulting mass transfer can generate atomic line(2) and X-ray(3) emission, as well as near-and mid-infrared radiation if the white dwarf is magnetic(4). However, even in binaries, white dwarfs are rarely detected at far-infrared or radio frequencies. Here we report the discovery of a white dwarf/cool star binary that emits from X-ray to radio wavelengths. The star, AR Scorpii (henceforth AR Sco), was classified in the early 1970s as a delta-Scuti star(5), a common variety of periodic variable star. Our observations reveal instead a 3.56-hour period close binary, pulsing in brightness on a period of 1.97 minutes. The pulses are so intense that AR Sco's optical flux can increase by a factor of four within 30 seconds, and they are also detectable at radio frequencies. They reflect the spin of a magnetic white dwarf, which we find to be slowing down on a 10(7)-year timescale. The spin-down power is an order of magnitude larger than that seen in electromagnetic radiation, which, together with an absence of obvious signs of accretion, suggests that AR Sco is primarily spin-powered. Although the pulsations are driven by the white dwarf's spin, they mainly originate from the cool star. AR Sco's broadband spectrum is characteristic of synchrotron radiation, requiring relativistic electrons. These must either originate from near the white dwarf or be generated in situ at the M star through direct interaction with the white dwarf's magnetosphere.
C1 [Marsh, T. R.; Gansicke, B. T.; Breedt, E.; Stanway, E. R.; Steeghs, D. T.; Toloza, O.; Pala, A. F.; Wheatley, P. J.] Univ Warwick, Dept Phys, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.
   [Huemmerich, S.; Hambsch, F. -J.; Ernhard, K. B.; Frank, P.] Bundesdeutsch Arbeitsgemeinschaft Veranderliche S, Berlin, Germany.
   [Huemmerich, S.; Hambsch, F. -J.; Ernhard, K. B.] AAVSO, Cambridge, MA USA.
   [Hambsch, F. -J.] VVS, Brugge, Belgium.
   [Lloyd, C.] Univ Sussex, Dept Phys & Astron, Brighton BN1 9QH, E Sussex, England.
   [Parsons, S. G.; Schreiber, M. R.] Univ Valparaiso, Inst Fis & Astron, Ave Gran Bretana 1111, Valparaiso, Chile.
   [Jonker, P. G.] SRON Netherlands Inst Space Res, SRON, Sorbonnelaan 2, NL-3584 CA Utrecht, Netherlands.
   [Jonker, P. G.; van Roestel, J.] Radboud Univ Nijmegen, IMAPP, Dept Astrophys, POB 9010, NL-6500 GL Nijmegen, Netherlands.
   [Kupfer, T.] CALTECH, Div Phys Math & Astron, Pasadena, CA 91125 USA.
   [Dhillon, V. S.; Hardy, L. K.; Littlefair, S. P.] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
   [Dhillon, V. S.] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
   [Dhillon, V. S.] Univ La Laguna, Dept Astrofis, E-38205 Tenerife, Spain.
   [Aungwerojwit, A.] Naresuan Univ, Dept Phys, Fac Sci, Phitsanulok 65000, Thailand.
   [Arjyotha, S.] Chiang Rai Rajabhat Univ, Fac Sci & Technol, Program Phys, Chiang Rai 57100, Thailand.
   [Koester, D.] Univ Kiel, Inst Theoret Phys & Astrophys, D-24098 Kiel, Germany.
   [Bochinski, J. J.; Haswell, C. A.] Open Univ, Dept Phys Sci, Milton Keynes, Bucks, England.
C3 University of Warwick; University of Sussex; Universidad de Valparaiso; Radboud University Nijmegen; California Institute of Technology; University of Sheffield; Instituto de Astrofisica de Canarias; Universidad de la Laguna; Naresuan University; Chiang Rai Rajabhat University; University of Kiel; Open University - UK
RP Marsh, TR (corresponding author), Univ Warwick, Dept Phys, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.
EM t.r.marsh@warwick.ac.uk
FU Science and Technology Facilities Council (STFC) [ST/L000733, ST/M001350/1]; European Research Council (ERC) [320964, 647208]; Fondecyt [3140585, 1141269]; Millenium Nucleus (Chilean Ministry of Economy) [RC130007]; Thailand Research Fund [MRG5680152]; National Research Council of Thailand [R2559B034]; European Organisation for Astronomical Research in the Southern Hemisphere [095.D-0489, 095.D-0739, 095.D-0802]; NASA/ ESA Hubble Space Telescope [14470]; Science and Technology Facilities Council [ST/M006492/1, ST/M002012/1, ST/L000776/1, ST/L000733/1, ST/M001350/1] Funding Source: researchfish; STFC [ST/M006492/1, ST/M001350/1, ST/L000733/1, ST/L000776/1, ST/M002012/1] Funding Source: UKRI
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   Pretorius ML, 2014, MON NOT R ASTRON SOC, V442, P2580, DOI 10.1093/mnras/stu990
   Rebassa-Mansergas A, 2007, MON NOT R ASTRON SOC, V382, P1377, DOI 10.1111/j.1365-2966.2007.12288.x
   Renedo I, 2010, ASTROPHYS J, V717, P183, DOI 10.1088/0004-637X/717/1/183
   Revnivtsev M, 2008, ASTRON ASTROPHYS, V489, P1121, DOI 10.1051/0004-6361:200810213
   Satyvaldiev V, 1971, ASTRONOMICHESKIJ TSIRKULYAR, V633, P7
   Skrutskie MF, 2006, ASTRON J, V131, P1163, DOI 10.1086/498708
   Szkody P, 2011, ASTRON J, V142, P0, DOI 10.1088/0004-6256/142/6/181
   Thorstensen JR, 2008, ASTRON J, V136, P2107, DOI 10.1088/0004-6256/136/5/2107
   WADE RA, 1988, ASTROPHYS J, V324, P411, DOI 10.1086/165905
   Werner MW, 2004, ASTROPHYS J SUPPL S, V154, P1, DOI 10.1086/422992
   Wright EL, 2010, ASTRON J, V140, P1868, DOI 10.1088/0004-6256/140/6/1868
   Wynn GA, 1997, MON NOT R ASTRON SOC, V286, P436, DOI 10.1093/mnras/286.2.436
NR 45
TC 168
Z9 178
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 374
EP +
DI 10.1038/nature18620
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000048
PM 27462808
DA 2026-03-09
ER

PT J
AU Errea, I
   Calandra, M
   Pickard, CJ
   Nelson, JR
   Needs, RJ
   Li, YW
   Liu, HY
   Zhang, YW
   Ma, YM
   Mauri, F
AF Errea, Ion
   Calandra, Matteo
   Pickard, Chris J.
   Nelson, Joseph R.
   Needs, Richard J.
   Li, Yinwei
   Liu, Hanyu
   Zhang, Yunwei
   Ma, Yanming
   Mauri, Francesco
TI Quantum hydrogen-bond symmetrization in the superconducting hydrogen sulfide system
SO NATURE
LA English
DT Article
ID bilbao crystallographic server; ab-initio; ice; approximation; phases
AB The quantum nature of the proton can crucially affect the structural and physical properties of hydrogen compounds. For example, in the high-pressure phases(1,2) of H2O, quantum proton fluctuations lead to symmetrization of the hydrogen bond and reduce the boundary between asymmetric and symmetric structures in the phase diagram by 30 gigapascals (ref. 3). Here we show that an analogous quantum symmetrization occurs in the recently discovered(4) sulfur hydride superconductor with a superconducting transition temperature T-c of 203 kelvin at 155 gigapascals-the highest T-c reported for any superconductor so far. Superconductivity occurs via the formation of a compound with chemical formula H3S (sulfur trihydride) with sulfur atoms arranged on a body-centred cubic lattice(5-9). If the hydrogen atoms are treated as classical particles, then for pressures greater than about 175 gigapascals they are predicted to sit exactly halfway between two sulfur atoms in a structure with Im (3) over barm symmetry. At lower pressures, the hydrogen atoms move to an off-centre position, forming a short H-S covalent bond and a longer H center dot center dot center dot S hydrogen bond in a structure with R3m symmetry(5-9). X-ray diffraction experiments confirm the H3S stoichiometry and the sulfur lattice sites, but were unable to discriminate between the two phases(10). Ab initio density-functional-theory calculations show that quantum nuclear motion lowers the symmetrization pressure by 72 gigapascals for H3S and by 60 gigapascals for D3S. Consequently, we predict that the Im (3) over barm phase dominates the pressure range within which the high T-c was measured. The observed pressure dependence of T-c is accurately reproduced in our calculations for the Im (3) over barm phase, but not for the R3m phase. Therefore, the quantum nature of the proton fundamentally changes the superconducting phase diagram of H3S.
C1 [Errea, Ion] Univ Basque Country UPV EHU, EUITI Bilbao, Fis Aplikatua Saila 1, Rafael Moreno Pitxitxi Pasealekua 3, Bilbao 48013, Spain.
   [Errea, Ion] DIPC, Manuel Lardizabal Pasealekua 4, Donostia San Sebastian 20018, Spain.
   [Calandra, Matteo; Mauri, Francesco] Univ Paris 06, Sorbonne Univ, CNRS, IMPMC,UMR 7590,MNHN,IRD, 4 Pl Jussieu, F-75005 Paris, France.
   [Pickard, Chris J.] Univ Cambridge, Dept Mat Sci & Met, 27 Charles Babbage Rd, Cambridge CB3 0FS, England.
   [Nelson, Joseph R.; Needs, Richard J.] Univ Cambridge, Cavendish Lab, Theory Condensed Matter Grp, JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Li, Yinwei] Jiangsu Normal Univ, Sch Phys & Elect Engn, Xuzhou 221116, Peoples R China.
   [Liu, Hanyu] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Zhang, Yunwei; Ma, Yanming] Jilin Univ, State Key Lab Superhard Mat, Changchun 130012, Peoples R China.
   [Mauri, Francesco] Univ Roma La Sapienza, Dipartimento Fis, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
C3 University of Basque Country; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; CNRS - Institute of Physics (INP); Museum National d'Histoire Naturelle (MNHN); University of Cambridge; University of Cambridge; Jiangsu Normal University; Carnegie Institution for Science; Jilin University; Sapienza University Rome
RP Errea, I (corresponding author), Univ Basque Country UPV EHU, EUITI Bilbao, Fis Aplikatua Saila 1, Rafael Moreno Pitxitxi Pasealekua 3, Bilbao 48013, Spain.; Errea, I (corresponding author), DIPC, Manuel Lardizabal Pasealekua 4, Donostia San Sebastian 20018, Spain.; Calandra, M; Mauri, F (corresponding author), Univ Paris 06, Sorbonne Univ, CNRS, IMPMC,UMR 7590,MNHN,IRD, 4 Pl Jussieu, F-75005 Paris, France.; Mauri, F (corresponding author), Univ Roma La Sapienza, Dipartimento Fis, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
EM ion.errea@ehu.eus; matteo.calandra@impmc.upmc.fr; francesco.mauri@uniroma1.it
FU Spanish Ministry of Economy and Competitiveness [FIS2013-48286-C2-2-P]; EPSRC (UK) [EP/J017639/1, EP/K014560/1]; Cambridge Commonwealth Trust; National Natural Science Foundation of China [11204111, 11404148, 11274136, 11534003]; Changjiang Scholars Program of China; Natural Science Foundation of Jiangsu province [BK20130223]; Royal Society through Wolfson Research Merit award; EFree, an Energy Frontier Research Center - DOE, Office of Science, Basic Energy Sciences [DE-SC-0001057]; EPSRC [EP/K014560/1, EP/J017639/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/J017639/1, EP/K014560/1] Funding Source: researchfish
NR 40
TC 270
Z9 298
U1 4
U2 346
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 81
EP +
DI 10.1038/nature17175
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500037
PM 27018657
DA 2026-03-09
ER

PT J
AU Coleman, JA
   Green, EM
   Gouaux, E
AF Coleman, Jonathan A.
   Green, Evan M.
   Gouaux, Eric
TI X-ray structures and mechanism of the human serotonin transporter
SO NATURE
LA English
DT Article
ID high-affinity recognition; binding-site; selective recognition; dopamine transporter; allosteric binding; bacterial homolog; r-citalopram; neurotransmitter; antidepressants; leut
AB The serotonin transporter (SERT) terminates serotonergic signalling through the sodium-and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 A resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.
C1 [Coleman, Jonathan A.; Green, Evan M.; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
   [Green, Evan M.] Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94158 USA.
C3 Oregon Health & Science University; Howard Hughes Medical Institute; Oregon Health & Science University; University of California System; University of California San Francisco
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.; Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU Banting postdoctoral fellowship from the Canadian Institutes of Health Research; National Institutes of Health (NIH) [5R37MH070039]
NR 59
TC 532
Z9 599
U1 2
U2 210
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 334
EP +
DI 10.1038/nature17629
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700026
PM 27049939
DA 2026-03-09
ER

PT J
AU Soliveres, S
   van der Plas, F
   Manning, P
   Prati, D
   Gossner, MM
   Renner, SC
   Alt, F
   Arndt, H
   Baumgartner, V
   Binkenstein, J
   Birkhofer, K
   Blaser, S
   Blüthgen, N
   Boch, S
   Böhm, S
   Börschig, C
   Buscot, F
   Diekötter, T
   Heinze, J
   Hölzel, N
   Jung, K
   Klaus, VH
   Kleinebecker, T
   Klemmer, S
   Krauss, J
   Lange, M
   Morris, EK
   Müller, J
   Oelmann, Y
   Overmann, J
   Pasalic, E
   Rillig, MC
   Schaefer, HM
   Schloter, M
   Schmitt, B
   Schöning, I
   Schrumpf, M
   Sikorski, J
   Socher, SA
   Solly, EF
   Sonnemann, I
   Sorkau, E
   Steckel, J
   Steffan-Dewenter, I
   Stempfhuber, B
   Tschapka, M
   Türke, M
   Venter, PC
   Weiner, CN
   Weisser, WW
   Werner, M
   Westphal, C
   Wilcke, W
   Wolters, V
   Wubet, T
   Wurst, S
   Fischer, M
   Allan, E
AF Soliveres, Santiago
   van der Plas, Fons
   Manning, Peter
   Prati, Daniel
   Gossner, Martin M.
   Renner, Swen C.
   Alt, Fabian
   Arndt, Hartmut
   Baumgartner, Vanessa
   Binkenstein, Julia
   Birkhofer, Klaus
   Blaser, Stefan
   Bluethgen, Nico
   Boch, Steffen
   Boehm, Stefan
   Boerschig, Carmen
   Buscot, Francois
   Diekoetter, Tim
   Heinze, Johannes
   Hoelzel, Norbert
   Jung, Kirsten
   Klaus, Valentin H.
   Kleinebecker, Till
   Klemmer, Sandra
   Krauss, Jochen
   Lange, Markus
   Morris, E. Kathryn
   Mueller, Joerg
   Oelmann, Yvonne
   Overmann, Joerg
   Pasalic, Esther
   Rillig, Matthias C.
   Schaefer, H. Martin
   Schloter, Michael
   Schmitt, Barbara
   Schoening, Ingo
   Schrumpf, Marion
   Sikorski, Johannes
   Socher, Stephanie A.
   Solly, Emily F.
   Sonnemann, Ilja
   Sorkau, Elisabeth
   Steckel, Juliane
   Steffan-Dewenter, Ingolf
   Stempfhuber, Barbara
   Tschapka, Marco
   Tuerke, Manfred
   Venter, Paul C.
   Weiner, Christiane N.
   Weisser, Wolfgang W.
   Werner, Michael
   Westphal, Catrin
   Wilcke, Wolfgang
   Wolters, Volkmar
   Wubet, Tesfaye
   Wurst, Susanne
   Fischer, Markus
   Allan, Eric
TI Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
SO NATURE
LA English
DT Article
ID land-use intensity; plant; diversity; productivity; consequences; herbivore; richness; services; weakens; impact
AB Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend(1,2). However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa(3,4) and that the functional effects of any trophic group may depend on the abundance and diversity of others(5,6). Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above-and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results(7,8) to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
C1 [Soliveres, Santiago; van der Plas, Fons; Manning, Peter; Prati, Daniel; Blaser, Stefan; Boch, Steffen; Schmitt, Barbara; Fischer, Markus; Allan, Eric] Univ Bern, Inst Plant Sci, Altenbergrain 21, CH-3013 Bern, Switzerland.
   [van der Plas, Fons; Manning, Peter; Fischer, Markus] Senckenberg Gesell Nat Forsch Biodivers & Climate, Senckenberganlage 25, D-60325 Frankfurt, Germany.
   [Gossner, Martin M.; Lange, Markus; Pasalic, Esther; Schoening, Ingo; Tuerke, Manfred; Weisser, Wolfgang W.] Univ Jena, Inst Ecol, Dornburger Str 159, D-07743 Jena, Germany.
   [Gossner, Martin M.; Lange, Markus; Pasalic, Esther; Tuerke, Manfred; Weisser, Wolfgang W.] Tech Univ Munich, Terr Ecol Res Grp, Dept Ecol & Ecosyst Management, Sch Life Sci Weihenstephan, Hans Carl von Carlowitz Pl 2, D-85354 Freising Weihenstephan, Germany.
   [Renner, Swen C.; Boehm, Stefan] Univ Nat Resources & Life Sci, Inst Zool, Gregor Mendel Str 33, A-1180 Vienna, Austria.
   [Renner, Swen C.] Natl Zool Pk, Smithsonian Conservat Biol Inst, 1500 Remount Rd, Front Royal, VA 22630 USA.
   [Alt, Fabian; Oelmann, Yvonne; Sorkau, Elisabeth] Univ Tubingen, Geocol, Ruemelinstr 19-23, Tubingen, Germany.
   [Arndt, Hartmut; Venter, Paul C.] Univ Cologne, Inst Zool, Zulpicher Str 47b, D-50674 Cologne, Germany.
   [Baumgartner, Vanessa; Overmann, Joerg; Sikorski, Johannes] Leibniz Inst DSMZ German Collect Microorganisms &, Inhoffenstr 7B, D-38124 Braunschweig, Germany.
   [Binkenstein, Julia] Univ Freiburg, Fac Environm & Nat Resources, Chair Nat Conservat & Landscape Ecol, Tennenbacher Str 4, D-79106 Freiburg, Germany.
   [Birkhofer, Klaus] Lund Univ, Dept Biol, Solvegatan 35, D-22362 Lund, Germany.
   [Bluethgen, Nico; Weiner, Christiane N.] Tech Univ Darmstadt, Biol, Ecol Networks, Schnittspahnstr 3, D-64287 Darmstadt, Germany.
   [Boch, Steffen; Fischer, Markus] Univ Bern, Bot Gardens, Altenbergrain 21, CH-3013 Bern, Switzerland.
   [Boerschig, Carmen; Westphal, Catrin] Univ Gottingen, Dept Crop Sci, Agroecol, Grisebachstr 6, D-37077 Gottingen, Germany.
   [Buscot, Francois; Klemmer, Sandra; Wubet, Tesfaye] UFZ Helmholtz Ctr Environm Res, Dept Soil Ecol, Theodor Lieser Str 4, D-06120 Halle, Saale, Germany.
   [Buscot, Francois; Tuerke, Manfred; Wubet, Tesfaye] German Ctr Integrat Biodivers Res iDiv, Deutsch Pl 5e, D-04103 Leipzig, Germany.
   [Diekoetter, Tim] Univ Kiel, Dept Landscape Ecol, Olshausenstr 75, D-24118 Kiel, Germany.
   [Heinze, Johannes; Mueller, Joerg] Univ Potsdam, Biodivers Res Systemat Bot, Maulbeerallee 1, D-14469 Potsdam, Germany.
   [Heinze, Johannes; Rillig, Matthias C.] Berlin Brandenburg Inst Adv Biodivers Res BBIB, D-14195 Berlin, Germany.
   [Hoelzel, Norbert; Klaus, Valentin H.; Kleinebecker, Till] Univ Munster, Inst Landscape Ecol, D-48149 Munster, Germany.
   [Jung, Kirsten; Tschapka, Marco] Univ Ulm, Inst Evolutionary Ecol & Conservat Genom, Albert Einstein Allee 11, D-89069 Ulm, Germany.
   [Krauss, Jochen; Steckel, Juliane; Steffan-Dewenter, Ingolf; Werner, Michael] Univ Wurzburg, Bioctr, Dept Anim Ecol & Trop Biol, Hubland, D-97074 Wurzburg, Germany.
   [Lange, Markus; Schoening, Ingo; Schrumpf, Marion; Solly, Emily F.] Max Planck Inst Biogeochem, Hans Knoell Str 10, D-07745 Jena, Germany.
   [Morris, E. Kathryn] Xavier Univ, Dept Biol, 3800 Victory Pkwy, Cincinnati, OH 45207 USA.
   [Morris, E. Kathryn; Rillig, Matthias C.] Free Univ Berlin, Inst Biol, Plant Ecol, Altensteinstr 6, D-14195 Berlin, Germany.
   [Schaefer, H. Martin] Univ Freiburg, Fac Biol, Dept Ecol & Evolutionary Biol, D-79104 Freiburg, Germany.
   [Schloter, Michael; Stempfhuber, Barbara] Helmholtz Zentrum Munchen, Res Unit Environm Genom, Ingolstadter Landstr 1, D-85758 Oberschleissheim, Germany.
   [Socher, Stephanie A.] Salzburg Univ, Dept Ecol & Evolut, Hellbrunnerstr 34, A-5020 Salzburg, Austria.
   [Solly, Emily F.] Swiss Fed Inst Forest Snow & Landscape Res WSL, Zurcherstr 111, CH-8903 Birmensdorf, Switzerland.
   [Sonnemann, Ilja; Wurst, Susanne] Free Univ Berlin, Inst Biol, Funct Biodivers, Konigin Luise Str 1-3, D-14195 Berlin, Germany.
   [Tschapka, Marco] Smithsonian Trop Res Inst, Balboa, Panama.
   [Tuerke, Manfred] Univ Leipzig, Inst Biol, Johannisallee 21, D-04103 Leipzig, Germany.
   [Wilcke, Wolfgang] KIT, Inst Geog & Geoecol, Reinhard Baumeister Pl 1, D-76131 Karlsruhe, Germany.
   [Wolters, Volkmar] Univ Giessen, Dept Anim Ecol, Heinrich Buff Ring 26-32, D-35392 Giessen, Germany.
   [Allan, Eric] Univ Bern, Ctr Dev & Environm, Hallerstr 10, CH-3012 Bern, Switzerland.
C3 University of Bern; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Friedrich Schiller University of Jena; Technical University of Munich; BOKU University; Smithsonian Institution; Smithsonian National Zoological Park & Conservation Biology Institute; Eberhard Karls University of Tubingen; University of Cologne; Leibniz Association; Leibniz Institut fur Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ); University of Freiburg; Technical University of Darmstadt; University of Bern; University of Gottingen; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); University of Kiel; University of Potsdam; University of Munster; Ulm University; University of Wurzburg; Max Planck Society; University System of Ohio; Xavier University; Free University of Berlin; University of Freiburg; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Salzburg University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Free University of Berlin; Smithsonian Institution; Smithsonian Tropical Research Institute; Leipzig University; Helmholtz Association; Karlsruhe Institute of Technology; Justus Liebig University Giessen; University of Bern
RP Soliveres, S (corresponding author), Univ Bern, Inst Plant Sci, Altenbergrain 21, CH-3013 Bern, Switzerland.
EM santiago.soliveres@ips.unibe.ch
FU Deutsche Forschungsgemeinschaft [1374]
NR 45
TC 629
Z9 721
U1 72
U2 1559
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 456
EP +
DI 10.1038/nature19092
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600041
PM 27533038
DA 2026-03-09
ER

PT J
AU Wilson, MD
   Benlekbir, S
   Fradet-Turcotte, A
   Sherker, A
   Julien, JP
   McEwan, A
   Noordermeer, SM
   Sicheri, F
   Rubinstein, JL
   Durocher, D
AF Wilson, Marcus D.
   Benlekbir, Samir
   Fradet-Turcotte, Amelie
   Sherker, Alana
   Julien, Jean-Philippe
   McEwan, Andrea
   Noordermeer, Sylvie M.
   Sicheri, Frank
   Rubinstein, John L.
   Durocher, Daniel
TI The structural basis of modified nucleosome recognition by 53BP1
SO NATURE
LA English
DT Article
ID dna-damage; cryo-em; homologous recombination; h2b monoubiquitination; ubiquitin; system; particles; histones; binding
AB DNA double-strand breaks (DSBs) elicit a histone modification cascade that controls DNA repair(1-3). This pathway involves the sequential ubiquitination of histones H1 and H2A by the E3 ubiquitin ligases RNF8 and RNF168, respectively(4-8). RNF168 ubiquitinates H2A on lysine 13 and lysine 15 (refs 7, 8) (yielding H2AK13ub and H2AK15ub, respectively), an event that triggers the recruitment of 53BP1 (also known as TP53BP1) to chromatin flanking DSBs(9,10). 53BP1 binds specifically to H2AK15ubcontaining nucleosomes through a peptide segment termed the ubiquitination-dependent recruitment motif (UDR), which requires the simultaneous engagement of histone H4 lysine 20 dimethylation (H4K20me2) by its tandem Tudor domain(10,11). How 53BP1 interacts with these two histone marks in the nucleosomal context, how it recognizes ubiquitin, and how it discriminates between H2AK13ub and H2AK15ub is unknown. Here we present the electron cryomicroscopy (cryo-EM) structure of a dimerized human 53BP1 fragment bound to a H4K20me2-containing and H2AK15ub-containing nucleosome core particle (NCP-ubme) at 4.5 angstrom resolution. The structure reveals that H4K20me2 and H2AK15ub recognition involves intimate contacts with multiple nucleosomal elements including the acidic patch. Ubiquitin recognition by 53BP1 is unusual and involves the sandwiching of the UDR segment between ubiquitin and the NCP surface. The selectivity for H2AK15ub is imparted by two arginine fingers in the H2A amino-terminal tail, which straddle the nucleosomal DNA and serve to position ubiquitin over the NCP-bound UDR segment. The structure of the complex between NCP-ubme and 53BP1 reveals the basis of 53BP1 recruitment to DSB sites and illuminates how combinations of histone marks and nucleosomal elements cooperate to produce highly specific chromatin responses, such as those elicited following chromosome breaks.
C1 [Wilson, Marcus D.; Fradet-Turcotte, Amelie; Sherker, Alana; McEwan, Andrea; Noordermeer, Sylvie M.; Sicheri, Frank; Durocher, Daniel] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
   [Benlekbir, Samir; Julien, Jean-Philippe; Rubinstein, John L.] Hosp Sick Children, Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 0A4, Canada.
   [Sherker, Alana; Sicheri, Frank; Durocher, Daniel] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
   [Julien, Jean-Philippe; Sicheri, Frank; Rubinstein, John L.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Julien, Jean-Philippe] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
   [Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Fradet-Turcotte, Amelie] Univ Laval, Canc Res Ctr, Oncol Axis CHU Quebec Res Ctr, Hotel Dieu Quebec, Quebec City, PQ G1R 2J6, Canada.
   [Fradet-Turcotte, Amelie] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1R 2J6, Canada.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; University of Toronto; University of Toronto; Laval University; Laval University Hospital; Laval University; Laval University Hospital
RP Sicheri, F; Durocher, D (corresponding author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.; Rubinstein, JL (corresponding author), Hosp Sick Children, Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 0A4, Canada.; Sicheri, F; Durocher, D (corresponding author), Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.; Sicheri, F; Rubinstein, JL (corresponding author), Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.; Rubinstein, JL (corresponding author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
EM sicheri@lunenfeld.ca; john.rubinstein@utoronto.ca; durocher@lunenfeld.ca
FU Human Frontiers Science Program fellowship; Dutch Cancer Foundation (KWF); CIHR [FDN143343, FDN143277, MOP81294]; Krembil Foundation
NR 48
TC 199
Z9 231
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 100
EP +
DI 10.1038/nature18951
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200038
PM 27462807
DA 2026-03-09
ER

PT J
AU Stephenson-Jones, M
   Yu, K
   Ahrens, S
   Tucciarone, JM
   van Huijstee, AN
   Mejia, LA
   Penzo, MA
   Tai, LH
   Wilbrecht, L
   Li, B
AF Stephenson-Jones, Marcus
   Yu, Kai
   Ahrens, Sandra
   Tucciarone, Jason M.
   van Huijstee, Aile N.
   Mejia, Luis A.
   Penzo, Mario A.
   Tai, Lung-Hao
   Wilbrecht, Linda
   Li, Bo
TI A basal ganglia circuit for evaluating action outcomes
SO NATURE
LA English
DT Article
ID rostromedial tegmental nucleus; negative reward signals; lateral habenula; subthalamic nucleus; globus-pallidus; entopeduncular projection; dopamine neurons; mechanisms; behavior; reveal
AB The basal ganglia, a group of subcortical nuclei, play a crucial role in decision-making by selecting actions and evaluating their outcomes(1,2). While much is known about the function of the basal ganglia circuitry in selection(1,3,4), how these nuclei contribute to outcome evaluation is less clear. Here we show that neurons in the habenula-projecting globus pallidus (GPh) in mice are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia. We find in a classical conditioning task that individual mouse GPh neurons bidirectionally encode whether an outcome is better or worse than expected. Mimicking these evaluation signals with optogenetic inhibition or excitation is sufficient to reinforce or discourage actions in a decision-making task. Moreover, cell-type-specific synaptic manipulations reveal that the inhibitory and excitatory inputs to the GPh are necessary for mice to appropriately evaluate positive and negative feedback, respectively. Finally, using rabies-virus-assisted monosynaptic tracing(5), we show that the GPh is embedded in a basal ganglia circuit wherein it receives inhibitory input from both striosomal and matrix compartments of the striatum, and excitatory input from the 'limbic' regions of the subthalamic nucleus. Our results provide evidence that information about the selection and evaluation of actions is channelled through distinct sets of basal ganglia circuits, with the GPh representing a key locus in which information of opposing valence is integrated to determine whether action outcomes are better or worse than expected.
C1 [Stephenson-Jones, Marcus; Yu, Kai; Ahrens, Sandra; Tucciarone, Jason M.; van Huijstee, Aile N.; Mejia, Luis A.; Penzo, Mario A.; Li, Bo] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Tucciarone, Jason M.] SUNY Stony Brook, Med Scientist Training Program, Stony Brook, NY 11790 USA.
   [Tucciarone, Jason M.] SUNY Stony Brook, Program Neurosci, Stony Brook, NY 11790 USA.
   [Tai, Lung-Hao; Wilbrecht, Linda] Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA.
   [Tai, Lung-Hao] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
C3 Cold Spring Harbor Laboratory; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Stephenson-Jones, M; Li, B (corresponding author), Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
EM mstephen@cshl.edu; bli@cshl.edu
FU National Institutes of Health (NIH) [R01MH108924]; Dana Foundation; NARSAD; Louis Feil Trust; Stanley Family Foundation; Simons Foundation; Wodecroft Foundation; EMBO Long-Term Fellowship Award; National Institute of Mental Health [ZIAMH002950, R01MH108924] Funding Source: NIH RePORTER
NR 36
TC 162
Z9 180
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 289
EP +
DI 10.1038/nature19845
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500045
PM 27652894
DA 2026-03-09
ER

PT J
AU Brumm, A
   van den Bergh, GD
   Storey, M
   Kurniawan, I
   Alloway, BV
   Setiawan, R
   Setiyabudi, E
   Grün, R
   Moore, MW
   Yurnaldi, D
   Puspaningrum, MR
   Wibowo, UP
   Insani, H
   Sutisna, I
   Westgate, JA
   Pearce, NJG
   Duval, M
   Meijer, HJM
   Aziz, F
   Sutikna, T
   van der Kaars, S
   Flude, S
   Morwood, MJ
AF Brumm, Adam
   van den Bergh, Gerrit D.
   Storey, Michael
   Kurniawan, Iwan
   Alloway, Brent V.
   Setiawan, Ruly
   Setiyabudi, Erick
   Gruen, Rainer
   Moore, Mark W.
   Yurnaldi, Dida
   Puspaningrum, Mika R.
   Wibowo, Unggul P.
   Insani, Halmi
   Sutisna, Indra
   Westgate, John A.
   Pearce, Nick J. G.
   Duval, Mathieu
   Meijer, Hanneke J. M.
   Aziz, Fachroel
   Sutikna, Thomas
   van der Kaars, Sander
   Flude, Stephanie
   Morwood, Michael J.
TI Age and context of the oldest known hominin fossils from Flores
SO NATURE
LA English
DT Article
ID fission-track ages; stone technology; late pleistocene; southeast-asia; tooth enamel; glass shards; soa basin; liang-bua; indonesia; chronology
AB Recent excavations at the early Middle Pleistocene site of Mata Menge in the So'a Basin of central Flores, Indonesia, have yielded hominin fossils(1) attributed to a population ancestral to Late Pleistocene Homo floresiensis(2). Here we describe the age and context of the Mata Menge hominin specimens and associated archaeological findings. The fluvial sandstone layer from which the in situ fossils were excavated in 2014 was deposited in a small valley stream around 700 thousand years ago, as indicated by 40Ar/39Ar and fission track dates on stratigraphically bracketing volcanic ash and pyroclastic density current deposits, in combination with coupled uranium-series and electron spin resonance dating of fossil teeth. Palaeoenvironmental data indicate a relatively dry climate in the So'a Basin during the early Middle Pleistocene, while various lines of evidence suggest the hominins inhabited a savannah-like open grassland habitat with a wetland component. The hominin fossils occur alongside the remains of an insular fauna and a simple stone technology that is markedly similar to that associated with Late Pleistocene H. floresiensis.
C1 [Brumm, Adam; Gruen, Rainer] Griffith Univ, Res Ctr Human Evolut Environm Futures Res Inst, Nathan, Qld 4111, Australia.
   [Brumm, Adam] Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.
   [van den Bergh, Gerrit D.; Alloway, Brent V.; Setiawan, Ruly; Yurnaldi, Dida; Puspaningrum, Mika R.; Wibowo, Unggul P.; Sutikna, Thomas; Morwood, Michael J.] Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [Storey, Michael] Univ Copenhagen, Quadlab, Nat Hist Museum Denmark, DK-1350 Copenhagen, Denmark.
   [Kurniawan, Iwan; Setiyabudi, Erick; Wibowo, Unggul P.; Insani, Halmi; Sutisna, Indra; Aziz, Fachroel] Geol Museum, Bandung 40122, Indonesia.
   [Alloway, Brent V.] Victoria Univ, Sch Geog Environm & Earth Sci, Wellington 6012, New Zealand.
   [Setiawan, Ruly; Yurnaldi, Dida] Geol Agcy, Ctr Geol Survey, Bandung 40122, Indonesia.
   [Gruen, Rainer] Australian Natl Univ, Res Sch Earth Sci, GPO Box 4, Canberra, ACT 2601, Australia.
   [Moore, Mark W.] Univ New England, Stone Tools & Cognit Hub, Armidale, NSW 2351, Australia.
   [Westgate, John A.] Univ Toronto, Dept Earth Sci, Toronto, ON M5S 3B1, Canada.
   [Pearce, Nick J. G.] Aberystwyth Univ, Dept Geog & Earth Sci, Aberystwyth SY23 3DB, Dyfed, Wales.
   [Duval, Mathieu] Ctr Nacl Invest Evoluc Humana CENIEH, Geochronol, Paseo Atapuerca 3, Burgos 09002, Spain.
   [Meijer, Hanneke J. M.] Univ Bergen, Univ Museum Bergen, N-5007 Bergen, Norway.
   [Sutikna, Thomas] Pusat Penelitian Arkeol Nas ARKENAS, Jakarta 12510, Indonesia.
   [van der Kaars, Sander] Vrije Univ Amsterdam, Fac Earth & Life Sci, Cluster Earth & Climate, NL-1081 HV Amsterdam, Netherlands.
   [van der Kaars, Sander] Monash Univ, Sch Earth Atmosphere & Environm, Clayton, Vic 3800, Australia.
   [Flude, Stephanie] Univ Edinburgh, Sch Geosci, Edinburgh EH8 9AD, Midlothian, Scotland.
C3 Griffith University; University of Wollongong; University of Wollongong; University of Copenhagen; Victoria University Wellington; Australian National University; University of New England; University of Toronto; Aberystwyth University; Centro Nacional de Investigacion de La Evolucion Humana (CENIEH); University of Bergen; Vrije Universiteit Amsterdam; Monash University; University of Edinburgh
RP Brumm, A (corresponding author), Griffith Univ, Res Ctr Human Evolut Environm Futures Res Inst, Nathan, Qld 4111, Australia.; Brumm, A (corresponding author), Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.; van den Bergh, GD (corresponding author), Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
EM a.brumm@griffith.edu.au; gert@uow.edu.au
FU Australian Research Council (ARC) [DP1093342]; Geological Survey Institute (GSI) of Bandung, Indonesia; ARC Future Fellowship [FT100100384]; ARC [DP1096558]; Villum Foundation; EU [PIOF-GA-2013-626474]; Victoria University of Wellington Science Faculty Research Grant [201255]; Villum Fonden [00007408] Funding Source: researchfish; Australian Research Council [DP1096558, DP1093342] Funding Source: Australian Research Council
NR 59
TC 67
Z9 84
U1 2
U2 106
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 249
EP +
DI 10.1038/nature17663
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100041
PM 27279222
DA 2026-03-09
ER

PT J
AU Brown, A
   Fernández, IS
   Gordiyenko, Y
   Ramakrishnan, V
AF Brown, Alan
   Fernandez, Israel S.
   Gordiyenko, Yuliya
   Ramakrishnan, V.
TI Ribosome-dependent activation of stringent control
SO NATURE
LA English
DT Article
ID escherichia-coli; ribonucleic-acid; guanosine tetraphosphate; structural basis; ef-tu; rela; rna; resolution; protein; ppgpp
AB In order to survive, bacteria continually sense, and respond to, environmental fluctuations. Stringent control represents a key bacterial stress response to nutrient starvation(1,2) that leads to rapid and comprehensive reprogramming of metabolic and transcriptional patterns(3). In general, transcription of genes for growth and proliferation is downregulated, while those important for survival and virulence are upregulated(4). Amino acid starvation is sensed by depletion of the aminoacylated tRNA pools(5), and this results in accumulation of ribosomes stalled with non-aminoacylated (uncharged) tRNA in the ribosomal A site(6,7). RelA is recruited to stalled ribosomes and activated to synthesize a hyperphosphorylated guanosine analogue, (p)ppGpp(8), which acts as a pleiotropic secondary messenger. However, structural information about how RelA recognizes stalled ribosomes and discriminates against aminoacylated tRNAs is missing. Here we present the cryo-electron microscopy structure of RelA bound to the bacterial ribosome stalled with uncharged tRNA. The structure reveals that RelA utilizes a distinct binding site compared to the translational factors, with a multi-domain architecture that wraps around a highly distorted A-site tRNA. The TGS (ThrRS, GTPase and SpoT) domain of RelA binds the CCA tail to orient the free 3'hydroxyl group of the terminal adenosine towards a beta-strand, such that an aminoacylated tRNA at this position would be sterically precluded. The structure supports a model in which association of RelA with the ribosome suppresses auto-inhibition to activate synthesis of (p) ppGpp and initiate the stringent response. Since stringent control is responsible for the survival of pathogenic bacteria under stress conditions, and contributes to chronic infections and antibiotic tolerance, RelA represents a good target for the development of novel antibacterial therapeutics.
C1 [Brown, Alan; Fernandez, Israel S.; Gordiyenko, Yuliya; Ramakrishnan, V.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
   [Fernandez, Israel S.] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
C3 MRC Laboratory Molecular Biology; Columbia University
RP Ramakrishnan, V (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM ramak@mrc-lmb.cam.ac.uk
FU UK Medical Research Council [MC_U105184332]; Wellcome Trust [WT096570]; Agouron Institute; Louis-Jeantet Foundation; MRC [MC_U105184332] Funding Source: UKRI; Wellcome Trust [096570/Z/11/Z] Funding Source: Wellcome Trust; Medical Research Council [MC_U105184332] Funding Source: researchfish; Wellcome Trust [096570/Z/11/Z] Funding Source: researchfish
NR 51
TC 169
Z9 190
U1 1
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 277
EP +
DI 10.1038/nature17675
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100047
PM 27279228
DA 2026-03-09
ER

PT J
AU Alfieri, C
   Chang, LF
   Zhang, ZG
   Yang, J
   Maslen, S
   Skehel, M
   Barford, D
AF Alfieri, Claudio
   Chang, Leifu
   Zhang, Ziguo
   Yang, Jing
   Maslen, Sarah
   Skehel, Mark
   Barford, David
TI Molecular basis of APC/C regulation by the spindle assembly checkpoint
SO NATURE
LA English
DT Article
ID anaphase-promoting complex; mitotic checkpoint; protein bubr1; saccharomyces-cerevisiae; recombinant expression; cdc20 binding; ucsf chimera; phosphorylation; mechanism; mad2
AB In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex (APC/C), the E3 ubiquitin ligase responsible for initiating chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), which inhibits the APC/C and delays chromosome segregation. By cryo-electron microscopy, here we determine the near-atomic resolution structure of a human APC/C-MCC complex (APC/C-MCC). Degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit responsible for substrate interactions. BubR1 also obstructs binding of the initiating E2 enzyme UbcH10 to repress APC/C ubiquitination activity. Conformational variability of the complex enables UbcH10 association, and structural analysis shows how the Cdc20 subunit intrinsic to the MCC (Cdc20M(CC)) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced.
C1 [Alfieri, Claudio; Chang, Leifu; Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Barford, D (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM dbarford@mrc-lmb.cam.ac.uk
FU Cancer Research UK [C576/A14109]; Medical Research Council [MRC_UP_1201/6]; Long Term EMBO Fellowship; Cancer Research UK [14109] Funding Source: researchfish; Medical Research Council [MC_UP_1201/6] Funding Source: researchfish; MRC [MC_UP_1201/6] Funding Source: UKRI
NR 74
TC 179
Z9 219
U1 1
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 431
EP +
DI 10.1038/nature19083
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600036
PM 27509861
DA 2026-03-09
ER

PT J
AU Mardinly, AR
   Spiegel, I
   Patrizi, A
   Centofante, E
   Bazinet, JE
   Tzeng, CP
   Mandel-Brehm, C
   Harmin, DA
   Adesnik, H
   Fagiolini, M
   Greenberg, ME
AF Mardinly, A. R.
   Spiegel, I.
   Patrizi, A.
   Centofante, E.
   Bazinet, J. E.
   Tzeng, C. P.
   Mandel-Brehm, C.
   Harmin, D. A.
   Adesnik, H.
   Fagiolini, M.
   Greenberg, M. E.
TI Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons
SO NATURE
LA English
DT Article
ID growth-factor-i; neocortical gabaergic neurons; primary visual-cortex; critical-period; gene-expression; transgenic mice; interneurons; rna; transcription; plasticity
AB Inhibitory neurons regulate the adaptation of neural circuits to sensory experience(1), but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron(2,3) to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons(3-5) and affecting inhibition onto cortical pyramidal neurons.
C1 [Mardinly, A. R.; Adesnik, H.] Univ Calif Berkeley, Dept Mol & Cellular Biol, 205 Life Sci Addit, Berkeley, CA 94720 USA.
   [Spiegel, I.; Bazinet, J. E.; Tzeng, C. P.; Mandel-Brehm, C.; Harmin, D. A.; Greenberg, M. E.] Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
   [Patrizi, A.; Centofante, E.; Fagiolini, M.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, 3 Blackfan Circle, Boston, MA 02115 USA.
C3 University of California System; University of California Berkeley; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Greenberg, ME (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM Michael_Greenberg@hms.harvard.edu
FU Human Frontiers Science Program; Swiss National Science Foundation; National Institute of Health [R01 NS028829, P01 NS047572]; National Institute of Neurological Disorders and Stroke [R01NS028829] Funding Source: NIH RePORTER
NR 36
TC 133
Z9 174
U1 2
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 371
EP +
DI 10.1038/nature17187
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300053
PM 26958833
DA 2026-03-09
ER

PT J
AU Barba-Spaeth, G
   Dejnirattisai, W
   Rouvinski, A
   Vaney, MC
   Medits, I
   Sharma, A
   Simon-Lorière, E
   Sakuntabhai, A
   Cao-Lormeau, VM
   Haouz, A
   England, P
   Stiasny, K
   Mongkolsapaya, J
   Heinz, FX
   Screaton, GR
   Rey, FA
AF Barba-Spaeth, Giovanna
   Dejnirattisai, Wanwisa
   Rouvinski, Alexander
   Vaney, Marie-Christine
   Medits, Iris
   Sharma, Arvind
   Simon-Loriere, Etienne
   Sakuntabhai, Anavaj
   Cao-Lormeau, Van-Mai
   Haouz, Ahmed
   England, Patrick
   Stiasny, Karin
   Mongkolsapaya, Juthathip
   Heinz, Franz X.
   Screaton, Gavin R.
   Rey, Felix A.
TI Structural basis of potent Zika-dengue virus antibody cross-neutralization
SO NATURE
LA English
DT Article
ID reactive antibody; fusion-loop; in-vivo; flavivirus; maturation; infection; enhancement; recognition; dynamics; receptor
AB Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barre syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections.
C1 [Barba-Spaeth, Giovanna; Rouvinski, Alexander; Vaney, Marie-Christine; Sharma, Arvind; Rey, Felix A.] Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France.
   [Barba-Spaeth, Giovanna; Rouvinski, Alexander; Vaney, Marie-Christine; Sharma, Arvind; Rey, Felix A.] CNRS, UMR Virol 3569, F-75724 Paris 15, France.
   [Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Screaton, Gavin R.] Imperial Coll London, Dept Med, Div Immunol & Inflammat, Hammersmith Campus, London W12 0NN, England.
   [Medits, Iris; Stiasny, Karin; Heinz, Franz X.] Med Univ Vienna, Dept Virol, Kinderspitalgasse 15, A-1095 Vienna, Austria.
   [Simon-Loriere, Etienne; Sakuntabhai, Anavaj] Inst Pasteur, Unite Genet Fonct Malad Infect, Dept Genomes & Genet, F-75724 Paris 15, France.
   [Simon-Loriere, Etienne; Sakuntabhai, Anavaj] CNRS, URA 3012, F-75724 Paris 15, France.
   [Cao-Lormeau, Van-Mai] Inst Louis Malarde, Unit Emerging Infect Dis, F-98713 Papeete, Tahiti, France.
   [Haouz, Ahmed] Inst Pasteur, Plateforme Cristallog CiTech, Dept Biol Struct & Chim, F-75724 Paris 15, France.
   [Haouz, Ahmed; England, Patrick] CNRS, UMR 3528, F-75724 Paris 15, France.
   [England, Patrick] Inst Pasteur, Plateforme Biophys Macromol & Leurs Interact, CiTech, Dept Biol Struct & Chim, F-75724 Paris 15, France.
   [Mongkolsapaya, Juthathip] Mahidol Univ, Siriraj Hosp, Dengue Hemorrhag Fever Res Unit, Off Res & Dev,Fac Med, Bangkok 10700, Thailand.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Imperial College London; Medical University of Vienna; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Mahidol University
RP Rey, FA (corresponding author), Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France.; Rey, FA (corresponding author), CNRS, UMR Virol 3569, F-75724 Paris 15, France.; Screaton, GR (corresponding author), Imperial Coll London, Dept Med, Div Immunol & Inflammat, Hammersmith Campus, London W12 0NN, England.; Heinz, FX (corresponding author), Med Univ Vienna, Dept Virol, Kinderspitalgasse 15, A-1095 Vienna, Austria.
EM franz.x.heinz@meduniwien.ac.at; g.screaton@imperial.ac.uk; felix.rey@pasteur.fr
FU European Commission [282 378FP7]; "Integrative Biology of Emerging Infectious Diseases" Labex (Laboratoire d'Excellence (French Government's "Investissements d'Avenir" program) [ANR-10-LABX-62-IBEID]; transnational ANR/FWF grant [FlaviStem/I1378]; Medical Research Council, UK; National Institute for Health Research Biomedical Research Centre, Funding Scheme, UK; NEUTRAVIR grant from Region ile-de-France (DIM-Maladies Infectieuses); Austrian Science Fund (FWF) [I 1378, P 27501] Funding Source: researchfish; Medical Research Council [G0600000, G0801508, G0400720, MR/N012658/1] Funding Source: researchfish; MRC [G0801508, MR/N012658/1, G0400720] Funding Source: UKRI; Austrian Science Fund (FWF) [P27501, I1378] Funding Source: Austrian Science Fund (FWF)
NR 45
TC 433
Z9 517
U1 4
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 48
EP +
DI 10.1038/nature18938
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200027
PM 27338953
DA 2026-03-09
ER

PT J
AU Ndabashimiye, G
   Ghimire, S
   Wu, MX
   Browne, DA
   Schafer, KJ
   Gaarde, MB
   Reis, DA
AF Ndabashimiye, Georges
   Ghimire, Shambhu
   Wu, Mengxi
   Browne, Dana A.
   Schafer, Kenneth J.
   Gaarde, Mette B.
   Reis, David A.
TI Solid-state harmonics beyond the atomic limit
SO NATURE
LA English
DT Article
ID generation; polarization; ellipticity; neon
AB Strong-field laser excitation of solids can produce extremely nonlinear electronic and optical behaviour. As recently demonstrated, this includes the generation of high harmonics extending into the vacuum-ultraviolet and extreme-ultraviolet regions of the electromagnetic spectrum(1-8). High harmonic generation is shown to occur fundamentally differently in solids and in dilute atomic gases(1-6,9-13). How the microscopic mechanisms in the solid and the gas differ remains a topic of intense debate(1-11,14-18). Here we report a direct comparison of high harmonic generation in the solid and gas phases of argon and krypton. Owing to the weak van der Waals interaction, rare (noble)-gas solids are a near-ideal medium in which to study the role of high density and periodicity in the generation process. We find that the high harmonic generation spectra from the rare-gas solids exhibit multiple plateaus extending well beyond the atomic limit of the corresponding gas-phase harmonics measured under similar conditions. The appearance of multiple plateaus indicates strong interband couplings involving multiple single-particle bands. We also compare the dependence of the solid and gas harmonic yield on laser ellipticity and find that they are similar, suggesting the importance of electron-hole recollision in these solids. This implies that gas-phase methods such as polarization gating for attosecond pulse generation and orbital tomography could be realized in solids.
C1 [Ndabashimiye, Georges; Reis, David A.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Ndabashimiye, Georges; Ghimire, Shambhu; Reis, David A.] SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA.
   [Wu, Mengxi; Browne, Dana A.; Schafer, Kenneth J.; Gaarde, Mette B.] Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
C3 Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Louisiana State University System; Louisiana State University
RP Ndabashimiye, G; Reis, DA (corresponding author), Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.; Ndabashimiye, G; Reis, DA (corresponding author), SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA.
EM ndabashi@stanford.edu; dreis@stanford.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences through the AMOS programme within the Chemical Sciences Division; Office of Science Early Career Research Program; National Science Foundation [PHY-1403236]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE AC02-76SF00515]; Division Of Physics; Direct For Mathematical & Physical Scien [1403236] Funding Source: National Science Foundation
NR 29
TC 428
Z9 475
U1 2
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 520
EP +
DI 10.1038/nature17660
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300047
PM 27281195
DA 2026-03-09
ER

PT J
AU Zhao, DY
   Gish, G
   Braunschweig, U
   Li, Y
   Ni, ZY
   Schmitges, FW
   Zhong, GQ
   Liu, K
   Li, WG
   Moffat, J
   Vedadi, M
   Min, JR
   Pawson, TJ
   Blencowe, BJ
   Greenblatt, JF
AF Zhao, Dorothy Yanling
   Gish, Gerald
   Braunschweig, Ulrich
   Li, Yue
   Ni, Zuyao
   Schmitges, Frank W.
   Zhong, Guoqing
   Liu, Ke
   Li, Weiguo
   Moffat, Jason
   Vedadi, Masoud
   Min, Jinrong
   Pawson, Tony J.
   Blencowe, Benjamin J.
   Greenblatt, Jack F.
TI SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination
SO NATURE
LA English
DT Article
ID transcriptional pause sites; spinal muscular-atrophy; protein; methylation; methyltransferase; recruitment; chromatin; complex; tdp-43; als
AB The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA-DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.
C1 [Zhao, Dorothy Yanling; Braunschweig, Ulrich; Li, Yue; Ni, Zuyao; Schmitges, Frank W.; Zhong, Guoqing; Moffat, Jason; Blencowe, Benjamin J.; Greenblatt, Jack F.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Zhao, Dorothy Yanling; Gish, Gerald; Pawson, Tony J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
   [Zhao, Dorothy Yanling; Moffat, Jason; Pawson, Tony J.; Blencowe, Benjamin J.; Greenblatt, Jack F.] Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada.
   [Li, Yue] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada.
   [Liu, Ke; Li, Weiguo; Vedadi, Masoud; Min, Jinrong] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
C3 University of Toronto; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University of Toronto; University of Toronto; Structural Genomics Consortium
RP Greenblatt, JF (corresponding author), Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.; Greenblatt, JF (corresponding author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada.
EM jack.greenblatt@utoronto.ca
FU Ontario Research Fund from the Ontario Ministry of Research and Innovation; CIHR; National Science and Engineering Research Council of Canada Studentship; Ontario Graduate Scholarship; HFSP
NR 56
TC 190
Z9 245
U1 4
U2 63
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 48
EP +
DI 10.1038/nature16469
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900023
PM 26700805
DA 2026-03-09
ER

PT J
AU Lence, T
   Akhtar, J
   Bayer, M
   Schmid, K
   Spindler, L
   Ho, CH
   Kreim, N
   Andrade-Navarro, MA
   Poeck, B
   Helm, M
   Roignant, JY
AF Lence, Tina
   Akhtar, Junaid
   Bayer, Marc
   Schmid, Katharina
   Spindler, Laura
   Ho, Cheuk Hei
   Kreim, Nastasja
   Andrade-Navarro, Miguel A.
   Poeck, Burkhard
   Helm, Mark
   Roignant, Jean-Yves
TI m6A modulates neuronal functions and sex determination in Drosophila
SO NATURE
LA English
DT Article
ID messenger-rna methylation; embryonic stem-cells; nuclear-rna; saccharomyces-cerevisiae; central complex; mammalian rna; gene; n-6-methyladenosine; reveals; expression
AB N-6-methyladenosine RNA (m(6)A) is a prevalent messenger RNA modification in vertebrates. Although its functions in the regulation of post-transcriptional gene expression are beginning to be unveiled, the precise roles of m(6)A during development of complex organisms remain unclear. Here we carry out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex, as well as of the YTH domain-containing nuclear reader protein in Drosophila melanogaster. We identify the member of the split ends protein family, Spenito, as a novel bona fide subunit of the methyltransferase complex. We further demonstrate important roles of this complex in neuronal functions and sex determination, and implicate the nuclear YT521-B protein as a main m(6)A effector in these processes. Altogether, our work substantially extends our knowledge of m(6)A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.
C1 [Lence, Tina; Akhtar, Junaid; Bayer, Marc; Kreim, Nastasja; Andrade-Navarro, Miguel A.; Roignant, Jean-Yves] Inst Mol Biol, D-55128 Mainz, Germany.
   [Schmid, Katharina; Helm, Mark] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, D-55128 Mainz, Germany.
   [Spindler, Laura; Poeck, Burkhard] Johannes Gutenberg Univ Mainz, Inst Zool Neurobiol 3, D-55128 Mainz, Germany.
   [Ho, Cheuk Hei] NYU, Skirball Inst, Dept Cell Biol, Kimmel Ctr Biol & Med,Sch Med, 540 First Ave, New York, NY 10016 USA.
   [Andrade-Navarro, Miguel A.] Johannes Gutenberg Univ Mainz, Fac Biol, D-55128 Mainz, Germany.
C3 Institute of Molecular Biology (IMB); Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; New York University; Johannes Gutenberg University of Mainz
RP Roignant, JY (corresponding author), Inst Mol Biol, D-55128 Mainz, Germany.
EM j.roignant@imb-mainz.de
FU Marie Curie CIG [334288]; Deutsche Forschungsgemeinschaft (DFG) [RO 4681/4-1]; Rhineland-Palatinate program Gene RED; DFG [HE 3397/13-1]
NR 54
TC 456
Z9 529
U1 6
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 242
EP +
DI 10.1038/nature20568
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700051
PM 27919077
DA 2026-03-09
ER

PT J
AU Park, KC
   Kim, P
   Grinthal, A
   He, N
   Fox, D
   Weaver, JC
   Aizenberg, J
AF Park, Kyoo-Chul
   Kim, Philseok
   Grinthal, Alison
   He, Neil
   Fox, David
   Weaver, James C.
   Aizenberg, Joanna
TI Condensation on slippery asymmetric bumps
SO NATURE
LA English
DT Article
ID superhydrophobic surfaces; nanostructured surfaces; water collection; desert beetle; enhanced condensation; dropwise condensation; capture; growth; energy
AB Controlling dropwise condensation is fundamental to water-harvesting systems(1-3), desalination(4), thermal power generation(4-8), air conditioning(9), distillation towers(10), and numerous other applications(4,5,11). For any of these, it is essential to design surfaces that enable droplets to grow rapidly and to be shed as quickly as possible(4-7). However, approaches(4-8,10-21) based on microscale, nanoscale or molecular-scale textures suffer from intrinsic tradeoffs that make it difficult to optimize both growth and transport at once. Here we present a conceptually different design approachbased on principles derived from Namib desert beetles(3,22-24), cacti(25), and pitcher plants(17,26)-that synergistically combines these aspects of condensation and substantially outperforms other synthetic surfaces. Inspired by an unconventional interpretation of the role of the beetle's bumpy surface geometry in promoting condensation, and using theoretical modelling, we show how to maximize vapour diffusion flux(20,27,28) at the apex of convex millimetric bumps by optimizing the radius of curvature and cross-sectional shape. Integrating this apex geometry with a widening slope, analogous to cactus spines, directly couples facilitated droplet growth with fast directional transport, by creating a free-energy profile that drives the droplet down the slope before its growth rate can decrease. This coupling is further enhanced by a slippery, pitcher-plant-inspired nanocoating that facilitates feedback between coalescence-driven growth and capillary-driven motion on the way down. Bumps that are rationally designed to integrate these mechanisms are able to grow and transport large droplets even against gravity and overcome the effect of an unfavourable temperature gradient. We further observe an unprecedented sixfold-higher exponent of growth rate, faster onset, higher steady-state turnover rate, and a greater volume of water collected compared to other surfaces. We envision that this fundamental understanding and rational design strategy can be applied to a wide range of water-harvesting and phase-change heat-transfer applications.
C1 [Park, Kyoo-Chul; Grinthal, Alison; He, Neil; Fox, David; Aizenberg, Joanna] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Park, Kyoo-Chul; Kim, Philseok; Weaver, James C.; Aizenberg, Joanna] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
   [Aizenberg, Joanna] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University
RP Park, KC; Aizenberg, J (corresponding author), Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.; Park, KC; Aizenberg, J (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.; Aizenberg, J (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM kpark@seas.harvard.edu; jaiz@seas.harvard.edu
FU Department of Energy/ARPA-E award [DE-AR0000326]; National Science Foundation [DMR-1420570]
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NR 30
TC 785
Z9 865
U1 25
U2 1339
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 78
EP 82
DI 10.1038/nature16956
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900043
PM 26909575
DA 2026-03-09
ER

PT J
AU Aharonian, F
   Akamatsu, H
   Akimoto, F
   Allen, SW
   Anabuki, N
   Angelini, L
   Arnaud, K
   Audard, M
   Awaki, H
   Axelsson, M
   Bamba, A
   Bautz, M
   Blandford, R
   Brenneman, L
   Brown, GV
   Bulbul, E
   Cackett, E
   Chernyakova, M
   Chiao, M
   Coppi, P
   Costantini, E
   de Plaa, J
   den Herder, JW
   Done, C
   Dotani, T
   Ebisawa, K
   Eckart, M
   Enoto, T
   Ezoe, Y
   Fabian, AC
   Ferrigno, C
   Foster, A
   Fujimoto, R
   Fukazawa, Y
   Furuzawa, A
   Galeazzi, M
   Gallo, L
   Gandhi, P
   Giustini, M
   Goldwurm, A
   Gu, L
   Guainazzi, M
   Haba, Y
   Hagino, K
   Hamaguchi, K
   Harrus, I
   Hatsukade, I
   Hayashi, K
   Hayashi, T
   Hayashida, K
   Hiraga, J
   Hornschemeier, A
   Hoshino, A
   Hughes, J
   Iizuka, R
   Inoue, H
   Inoue, Y
   Ishibashi, K
   Ishida, M
   Ishikawa, K
   Ishisaki, Y
   Itoh, M
   Iyomoto, N
   Kaastra, J
   Kallman, T
   Kamae, T
   Kara, E
   Kataoka, J
   Katsuda, S
   Katsuta, J
   Kawaharada, M
   Kawai, N
   Kelley, R
   Khangulyan, D
   Kilbourne, C
   King, A
   Kitaguchi, T
   Kitamoto, S
   Kitayama, T
   Kohmura, T
   Kokubun, M
   Koyama, S
   Koyama, K
   Kretschmar, P
   Krimm, H
   Kubota, A
   Kunieda, H
   Laurent, P
   Lebrun, F
   Lee, SH
   Leutenegger, M
   Limousin, O
   Loewenstein, M
   Long, KS
   Lumb, D
   Madejski, G
   Maeda, Y
   Maier, D
   Makishima, K
   Markevitch, M
   Matsumoto, H
   Matsushita, K
   McCammon, D
   McNamara, B
   Mehdipour, M
   Miller, E
   Miller, J
   Mineshige, S
   Mitsuda, K
   Mitsuishi, I
   Miyazawa, T
   Mizuno, T
   Mori, H
   Mori, K
   Moseley, H
   Mukai, K
   Murakami, H
   Murakami, T
   Mushotzky, R
   Nagino, R
   Nakagawa, T
   Nakajima, H
   Nakamori, T
   Nakano, T
   Nakashima, S
   Nakazawa, K
   Nobukawa, M
   Noda, H
   Nomachi, M
   O'Dell, S
   Odaka, H
   Ohashi, T
   Ohno, M
   Okajima, T
   Ota, N
   Ozaki, M
   Paerels, F
   Paltani, S
   Parmar, A
   Petre, R
   Pinto, C
   Pohl, M
   Porter, FS
   Pottschmidt, K
   Ramsey, B
   Reynolds, C
   Russell, H
   Safi-Harb, S
   Saito, S
   Sakai, K
   Sameshima, H
   Sato, G
   Sato, K
   Sato, R
   Sawada, M
   Schartel, N
   Serlemitsos, P
   Seta, H
   Shidatsu, M
   Simionescu, A
   Smith, R
   Soong, Y
   Stawarz, L
   Sugawara, Y
   Sugita, S
   Szymkowiak, A
   Tajima, H
   Takahashi, H
   Takahashi, T
   Takeda, S
   Takei, Y
   Tamagawa, T
   Tamura, K
   Tamura, T
   Tanaka, T
   Tanaka, Y
   Tanaka, Y
   Tashiro, M
   Tawara, Y
   Terada, Y
   Terashima, Y
   Tombesi, F
   Tomida, H
   Tsuboi, Y
   Tsujimoto, M
   Tsunemi, H
   Tsuru, T
   Uchida, H
   Uchiyama, H
   Uchiyama, Y
   Ueda, S
   Ueda, Y
   Ueno, S
   Uno, S
   Urry, M
   Ursino, E
   De Vries, C
   Watanabe, S
   Werner, N
   Wik, D
   Wilkins, D
   Williams, B
   Yamada, S
   Yamaguchi, H
   Yamaoka, K
   Yamasaki, NY
   Yamauchi, M
   Yamauchi, S
   Yaqoob, T
   Yatsu, Y
   Yonetoku, D
   Yoshida, A
   Yuasa, T
   Zhuravleva, I
   Zoghbi, A
AF Aharonian, Felix
   Akamatsu, Hiroki
   Akimoto, Fumie
   Allen, Steven W.
   Anabuki, Naohisa
   Angelini, Lorella
   Arnaud, Keith
   Audard, Marc
   Awaki, Hisamitsu
   Axelsson, Magnus
   Bamba, Aya
   Bautz, Marshall
   Blandford, Roger
   Brenneman, Laura
   Brown, Gregory V.
   Bulbul, Esra
   Cackett, Edward
   Chernyakova, Maria
   Chiao, Meng
   Coppi, Paolo
   Costantini, Elisa
   de Plaa, Jelle
   den Herder, Jan-Willem
   Done, Chris
   Dotani, Tadayasu
   Ebisawa, Ken
   Eckart, Megan
   Enoto, Teruaki
   Ezoe, Yuichiro
   Fabian, Andrew C.
   Ferrigno, Carlo
   Foster, Adam
   Fujimoto, Ryuichi
   Fukazawa, Yasushi
   Furuzawa, Akihiro
   Galeazzi, Massimiliano
   Gallo, Luigi
   Gandhi, Poshak
   Giustini, Margherita
   Goldwurm, Andrea
   Gu, Liyi
   Guainazzi, Matteo
   Haba, Yoshito
   Hagino, Kouichi
   Hamaguchi, Kenji
   Harrus, Ilana
   Hatsukade, Isamu
   Hayashi, Katsuhiro
   Hayashi, Takayuki
   Hayashida, Kiyoshi
   Hiraga, Junko
   Hornschemeier, Ann
   Hoshino, Akio
   Hughes, John
   Iizuka, Ryo
   Inoue, Hajime
   Inoue, Yoshiyuki
   Ishibashi, Kazunori
   Ishida, Manabu
   Ishikawa, Kumi
   Ishisaki, Yoshitaka
   Itoh, Masayuki
   Iyomoto, Naoko
   Kaastra, Jelle
   Kallman, Timothy
   Kamae, Tuneyoshi
   Kara, Erin
   Kataoka, Jun
   Katsuda, Satoru
   Katsuta, Junichiro
   Kawaharada, Madoka
   Kawai, Nobuyuki
   Kelley, Richard
   Khangulyan, Dmitry
   Kilbourne, Caroline
   King, Ashley
   Kitaguchi, Takao
   Kitamoto, Shunji
   Kitayama, Tetsu
   Kohmura, Takayoshi
   Kokubun, Motohide
   Koyama, Shu
   Koyama, Katsuji
   Kretschmar, Peter
   Krimm, Hans
   Kubota, Aya
   Kunieda, Hideyo
   Laurent, Philippe
   Lebrun, Francois
   Lee, Shiu-Hang
   Leutenegger, Maurice
   Limousin, Olivier
   Loewenstein, Michael
   Long, Knox S.
   Lumb, David
   Madejski, Grzegorz
   Maeda, Yoshitomo
   Maier, Daniel
   Makishima, Kazuo
   Markevitch, Maxim
   Matsumoto, Hironori
   Matsushita, Kyoko
   McCammon, Dan
   McNamara, Brian
   Mehdipour, Missagh
   Miller, Eric
   Miller, Jon
   Mineshige, Shin
   Mitsuda, Kazuhisa
   Mitsuishi, Ikuyuki
   Miyazawa, Takuya
   Mizuno, Tsunefumi
   Mori, Hideyuki
   Mori, Koji
   Moseley, Harvey
   Mukai, Koji
   Murakami, Hiroshi
   Murakami, Toshio
   Mushotzky, Richard
   Nagino, Ryo
   Nakagawa, Takao
   Nakajima, Hiroshi
   Nakamori, Takeshi
   Nakano, Toshio
   Nakashima, Shinya
   Nakazawa, Kazuhiro
   Nobukawa, Masayoshi
   Noda, Hirofumi
   Nomachi, Masaharu
   O'Dell, Steve
   Odaka, Hirokazu
   Ohashi, Takaya
   Ohno, Masanori
   Okajima, Takashi
   Ota, Naomi
   Ozaki, Masanobu
   Paerels, Frits
   Paltani, Stephane
   Parmar, Arvind
   Petre, Robert
   Pinto, Ciro
   Pohl, Martin
   Porter, F. Scott
   Pottschmidt, Katja
   Ramsey, Brian
   Reynolds, Christopher
   Russell, Helen
   Safi-Harb, Samar
   Saito, Shinya
   Sakai, Kazuhiro
   Sameshima, Hiroaki
   Sato, Goro
   Sato, Kosuke
   Sato, Rie
   Sawada, Makoto
   Schartel, Norbert
   Serlemitsos, Peter
   Seta, Hiromi
   Shidatsu, Megumi
   Simionescu, Aurora
   Smith, Randall
   Soong, Yang
   Stawarz, Lukasz
   Sugawara, Yasuharu
   Sugita, Satoshi
   Szymkowiak, Andrew
   Tajima, Hiroyasu
   Takahashi, Hiromitsu
   Takahashi, Tadayuki
   Takeda, Shin'ichiro
   Takei, Yoh
   Tamagawa, Toru
   Tamura, Keisuke
   Tamura, Takayuki
   Tanaka, Takaaki
   Tanaka, Yasuo
   Tanaka, Yasuyuki
   Tashiro, Makoto
   Tawara, Yuzuru
   Terada, Yukikatsu
   Terashima, Yuichi
   Tombesi, Francesco
   Tomida, Hiroshi
   Tsuboi, Yohko
   Tsujimoto, Masahiro
   Tsunemi, Hiroshi
   Tsuru, Takeshi
   Uchida, Hiroyuki
   Uchiyama, Hideki
   Uchiyama, Yasunobu
   Ueda, Shutaro
   Ueda, Yoshihiro
   Ueno, Shiro
   Uno, Shin'ichiro
   Urry, Meg
   Ursino, Eugenio
   De Vries, Cor
   Watanabe, Shin
   Werner, Norbert
   Wik, Daniel
   Wilkins, Dan
   Williams, Brian
   Yamada, Shinya
   Yamaguchi, Hiroya
   Yamaoka, Kazutaka
   Yamasaki, Noriko Y.
   Yamauchi, Makoto
   Yamauchi, Shigeo
   Yaqoob, Tahir
   Yatsu, Yoichi
   Yonetoku, Daisuke
   Yoshida, Atsumasa
   Yuasa, Takayuki
   Zhuravleva, Irina
   Zoghbi, Abderahmen
TI The quiescent intracluster medium in the core of the Perseus cluster
SO NATURE
LA English
DT Article
ID x-ray spectroscopy; galaxy clusters; xmm-newton; turbulent velocity; ngc 1275; ngc-1275; line; gas; constraints; feedback
AB Clusters of galaxies are the most massive gravitationally bound objects in the Universe and are still forming. They are thus important probes(1) of cosmological parameters and many astrophysical processes. However, knowledge of the dynamics of the pervasive hot gas, the mass of which is much larger than the combined mass of all the stars in the cluster, is lacking. Such knowledge would enable insights into the injection of mechanical energy by the central supermassive black hole and the use of hydrostatic equilibrium for determining cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50-million-kelvin diffuse hot plasma filling its gravitational potential well. The active galactic nucleus of the central galaxy NGC 1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These bubbles probably induce motions in the intracluster medium and heat the inner gas, preventing runaway radiative cooling-a process known as active galactic nucleus feedback(2-6). Here we report X-ray observations of the core of the Perseus cluster, which reveal a remarkably quiescent atmosphere in which the gas has a line-of-sight velocity dispersion of 164 +/- 10 kilometres per second in the region 30-60 kiloparsecs from the central nucleus. A gradient in the line-of-sight velocity of 150 +/- 70 kilometres per second is found across the 60-kiloparsec image of the cluster core. Turbulent pressure support in the gas is four per cent of the thermodynamic pressure, with large-scale shear at most doubling this estimate. We infer that a total cluster mass determined from hydrostatic equilibrium in a central region would require little correction for turbulent pressure.
C1 [Aharonian, Felix; Chernyakova, Maria] Dublin Inst Adv Studies, Astron & Astrophys Sect, Dublin 2, Ireland.
   [Aharonian, Felix] Natl Res Nucl Univ MEPHI, Moscow 115409, Russia.
   [Akamatsu, Hiroki; Costantini, Elisa; de Plaa, Jelle; den Herder, Jan-Willem; Giustini, Margherita; Gu, Liyi; Kaastra, Jelle; Mehdipour, Missagh; De Vries, Cor] SRON Netherlands Inst Space Res, Utrecht, Netherlands.
   [Akimoto, Fumie; Furuzawa, Akihiro; Hayashi, Takayuki; Ishibashi, Kazunori; Kunieda, Hideyo; Mitsuishi, Ikuyuki; Miyazawa, Takuya; Tamura, Keisuke; Tawara, Yuzuru; Yamaoka, Kazutaka] Nagoya Univ, Dept Phys, Nagoya, Aichi 4648602, Japan.
   [Allen, Steven W.; Blandford, Roger; Kamae, Tuneyoshi; King, Ashley; Madejski, Grzegorz; Werner, Norbert; Zhuravleva, Irina] Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
   [Allen, Steven W.; Blandford, Roger; King, Ashley; Werner, Norbert; Zhuravleva, Irina] Stanford Univ, Dept Phys, 382 Via Pueblo Mall, Stanford, CA 94305 USA.
   [Allen, Steven W.; Blandford, Roger; Madejski, Grzegorz] SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA.
   [Anabuki, Naohisa; Hayashida, Kiyoshi; Nagino, Ryo; Nakajima, Hiroshi; Tsunemi, Hiroshi] Osaka Univ, Dept Earth & Space Sci, Osaka 5600043, Japan.
   [Angelini, Lorella; Arnaud, Keith; Chiao, Meng; Eckart, Megan; Hamaguchi, Kenji; Harrus, Ilana; Hornschemeier, Ann; Kallman, Timothy; Kelley, Richard; Kilbourne, Caroline; Krimm, Hans; Leutenegger, Maurice; Loewenstein, Michael; Markevitch, Maxim; Mori, Hideyuki; Moseley, Harvey; Mukai, Koji; Okajima, Takashi; Petre, Robert; Porter, F. Scott; Pottschmidt, Katja; Sakai, Kazuhiro; Serlemitsos, Peter; Soong, Yang; Tombesi, Francesco; Wik, Daniel; Williams, Brian; Yamaguchi, Hiroya; Yaqoob, Tahir] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Arnaud, Keith; Kara, Erin; Loewenstein, Michael; Mushotzky, Richard; Reynolds, Christopher] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Audard, Marc; Ferrigno, Carlo; Paltani, Stephane; Pohl, Martin] Univ Geneva, CH-1211 Geneva 4, Switzerland.
   [Awaki, Hisamitsu; Terashima, Yuichi] Ehime Univ, Dept Phys, Matsuyama, Ehime 7908577, Japan.
   [Axelsson, Magnus; Ezoe, Yuichiro; Ishisaki, Yoshitaka; Ohashi, Takaya; Seta, Hiromi; Yamada, Shinya] Tokyo Metropolitan Univ, Dept Phys, Tokyo 1920397, Japan.
   [Bamba, Aya; Nakazawa, Kazuhiro] Univ Tokyo, Dept Phys, Tokyo 1130033, Japan.
   [Bautz, Marshall; Bulbul, Esra; Miller, Eric] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Brenneman, Laura; Foster, Adam; Smith, Randall] Smithsonian Astrophys Observ, 60 Garden St,MS-4, Cambridge, MA 02138 USA.
   [Brown, Gregory V.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Cackett, Edward; Fabian, Andrew C.; Pinto, Ciro; Russell, Helen] Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
   [Coppi, Paolo; Szymkowiak, Andrew; Urry, Meg] Yale Univ, Yale Ctr Astron & Astrophys, New Haven, CT 06520 USA.
   [Done, Chris] Univ Durham, Dept Phys, Durham DH1 3LE, England.
   [Dotani, Tadayasu; Ebisawa, Ken; Guainazzi, Matteo; Hagino, Kouichi; Hayashi, Katsuhiro; Iizuka, Ryo; Inoue, Hajime; Inoue, Yoshiyuki; Ishida, Manabu; Kokubun, Motohide; Koyama, Shu; Lee, Shiu-Hang; Maeda, Yoshitomo; Mitsuda, Kazuhisa; Nakagawa, Takao; Nakashima, Shinya; Odaka, Hirokazu; Ozaki, Masanobu; Sameshima, Hiroaki; Sato, Goro; Sato, Rie; Simionescu, Aurora; Takahashi, Tadayuki; Takei, Yoh; Tamura, Takayuki; Tanaka, Yasuo; Tomida, Hiroshi; Tsujimoto, Masahiro; Ueda, Shutaro; Ueno, Shiro; Watanabe, Shin; Yamasaki, Noriko Y.] Japan Aerosp Explorat Agcy JAXA, ISAS, Sagamihara, Kanagawa 2525210, Japan.
   [Enoto, Teruaki; Mineshige, Shin; Ueda, Yoshihiro] Kyoto Univ, Dept Astron, Kyoto 6068502, Japan.
   [Enoto, Teruaki] Kyoto Univ, Hakubi Ctr Adv Res, Kyoto 6068302, Japan.
   [Fujimoto, Ryuichi; Murakami, Toshio; Yonetoku, Daisuke] Kanazawa Univ, Fac Math & Phys, Kanazawa, Ishikawa 9201192, Japan.
   [Fukazawa, Yasushi; Katsuta, Junichiro; Kitaguchi, Takao; Mizuno, Tsunefumi; Ohno, Masanori; Takahashi, Hiromitsu; Tanaka, Yasuyuki] Hiroshima Univ, Dept Phys Sci, Hiroshima 7398526, Japan.
   [Galeazzi, Massimiliano; Ursino, Eugenio] Univ Miami, Dept Phys, Miami, FL 33124 USA.
   [Gallo, Luigi; Wilkins, Dan] St Marys Univ, Dept Phys & Astron, Halifax, NS B3H 3C3, Canada.
   [Gandhi, Poshak] Univ Southampton, Dept Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Goldwurm, Andrea; Laurent, Philippe; Lebrun, Francois; Limousin, Olivier; Maier, Daniel] CEA Saclay, IRFU Serv Astrophys, F-91191 Gif Sur Yvette, France.
   [Guainazzi, Matteo; Kretschmar, Peter; Schartel, Norbert] ESAC, ESA, Madrid, Spain.
   [Haba, Yoshito] Aichi Univ Educ, Dept Phys & Astron, Kariya, Aichi 4488543, Japan.
   [Hamaguchi, Kenji; Harrus, Ilana; Mukai, Koji; Pottschmidt, Katja; Yaqoob, Tahir] Univ Maryland Baltimore Cty, Dept Phys, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
   [Hatsukade, Isamu; Mori, Koji; Yamauchi, Makoto] Miyazaki Univ, Dept Appl Phys & Elect Engn, Miyazaki 8892192, Japan.
   [Hiraga, Junko] Kwansei Gakuin Univ, Sch Sci & Technol, Dept Phys, Nishinomiya, Hyogo 6691337, Japan.
   [Hoshino, Akio; Khangulyan, Dmitry; Kitamoto, Shunji; Saito, Shinya; Uchiyama, Yasunobu] Rikkyo Univ, Dept Phys, Tokyo 1718501, Japan.
   [Hughes, John] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Ishikawa, Kumi; Nakano, Toshio; Noda, Hirofumi; Tamagawa, Toru; Yuasa, Takayuki] RIKEN, Nishina Ctr, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
   [Itoh, Masayuki] Kobe Univ, Fac Human Dev, Kobe, Hyogo 6578501, Japan.
   [Iyomoto, Naoko] Kyushu Univ, Fukuoka 8190395, Japan.
   [Kataoka, Jun] Waseda Univ, Res Inst Sci & Engn, Tokyo 1698555, Japan.
   [Katsuda, Satoru; Sugawara, Yasuharu; Tsuboi, Yohko] Chuo Univ, Dept Phys, Tokyo 1128551, Japan.
   [Kawaharada, Madoka] Japan Aerosp Explorat Agcy JAXA, Tsukuba Space Ctr TKSC, Tsukuba, Ibaraki 3058505, Japan.
   [Kawai, Nobuyuki; Sugita, Satoshi; Yatsu, Yoichi] Tokyo Inst Technol, Dept Phys, Tokyo 1528551, Japan.
   [Kitayama, Tetsu] Toho Univ, Dept Phys, Chiba 2748510, Japan.
   [Kohmura, Takayoshi] Tokyo Univ Sci, Dept Phys, Chiba 2788510, Japan.
   [Koyama, Katsuji; Tanaka, Takaaki; Tsuru, Takeshi; Uchida, Hiroyuki] Kyoto Univ, Dept Phys, Kyoto 6068502, Japan.
   [Krimm, Hans] Univ Space Res Assoc, 7178 Columbia Gateway Dr, Columbia, MD 21046 USA.
   [Kubota, Aya] Shibaura Inst Technol, Dept Elect Informat Syst, Saitama 3378570, Japan.
   [Long, Knox S.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Lumb, David; Parmar, Arvind] ESTEC, ESA, NL-2200 AG Noordwijk, Netherlands.
   [Makishima, Kazuo; Shidatsu, Megumi] RIKEN, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
   [Matsumoto, Hironori] Nagoya Univ, Kobayashi Maskawa Inst, Nagoya, Aichi 4648602, Japan.
   [Matsushita, Kyoko; Sato, Kosuke] Tokyo Univ Sci, Dept Phys, Tokyo 1628601, Japan.
   [McCammon, Dan] Univ Wisconsin, Dept Phys, Madison, WI 53706 USA.
   [McNamara, Brian] Univ Waterloo, Waterloo, ON N2L 3G1, Canada.
   [Miller, Jon; Zoghbi, Abderahmen] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Murakami, Hiroshi] Tohoku Gakuin Univ, Fac Liberal Arts, Dept Informat Sci, Sendai, Miyagi 9813193, Japan.
   [Nakamori, Takeshi] Yamagata Univ, Dept Phys, Fac Sci, Yamagata 9908560, Japan.
   [Nobukawa, Masayoshi] Nara Univ Educ, Dept Teacher Training, Takabatake Cho, Nara 6308528, Japan.
   [Nobukawa, Masayoshi] Nara Univ Educ, Sch Educ, Takabatake Cho, Nara 6308528, Japan.
   [Nomachi, Masaharu] Osaka Univ, Res Ctr Nucl Phys Toyonaka, 1-1 Machikaneyama Machi, Toyonaka, Osaka 5600043, Japan.
   [O'Dell, Steve; Ramsey, Brian] NASA, George C Marshall Space Flight Ctr, Huntsville, AL 35812 USA.
   [Ota, Naomi; Yamauchi, Shigeo] Nara Womens Univ, Fac Sci, Dept Phys, Nara 6308506, Japan.
   [Paerels, Frits] Columbia Univ, Dept Astron, New York, NY 10027 USA.
   [Safi-Harb, Samar] Univ Manitoba, Dept Phys & Astron, Winnipeg, MB R3T 2N2, Canada.
   [Sawada, Makoto; Yoshida, Atsumasa] Aoyama Gakuin Univ, Dept Math & Phys, Sagamihara, Kanagawa 2525258, Japan.
   [Stawarz, Lukasz] Jagiellonian Univ, Astron Observ, PL-30244 Krakow, Poland.
   [Tajima, Hiroyasu] Nagoya Univ, Inst Space Earth Environm Res, Nagoya, Aichi 4648601, Japan.
   [Takeda, Shin'ichiro] Grad Univ OIST, Okinawa Inst Sci & Technol, Adv Med Instrumentat Unit, Okinawa 9040495, Japan.
   [Tashiro, Makoto; Terada, Yukikatsu] Saitama Univ, Dept Phys, Saitama 3388570, Japan.
   [Uchiyama, Hideki] Shizuoka Univ, Fac Educ, Sci Educ, Shizuoka 4228529, Japan.
   [Uno, Shin'ichiro] Nihon Fukushi Univ, Fac Hlth Sci, Mihama, Aichi 4750012, Japan.
   [Wik, Daniel] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
C3 Dublin Institute for Advanced Studies; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Nagoya University; Stanford University; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; University of Osaka; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; University of Geneva; Ehime University; Tokyo Metropolitan University; University of Tokyo; Massachusetts Institute of Technology (MIT); Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Cambridge; Yale University; Durham University; Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); Kyoto University; Kyoto University; Kanazawa University; Hiroshima University; University of Miami; Saint Marys University - Canada; University of Southampton; Universite Paris Saclay; CEA; European Space Agency; European Space Astronomy Center; Aichi University Education; University System of Maryland; University of Maryland Baltimore County; University of Miyazaki; Kwansei Gakuin University; Rikkyo University; Rutgers University System; Rutgers University New Brunswick; RIKEN; Kobe University; Kyushu University; Waseda University; Chuo University; Japan Aerospace Exploration Agency (JAXA); Institute of Science Tokyo; Tokyo Institute of Technology; Toho University; Tokyo University of Science; Kyoto University; Universities Space Research Association (USRA); Shibaura Institute of Technology; Space Telescope Science Institute; European Space Agency; European Space Research & Technology Centre; RIKEN; Nagoya University; Tokyo University of Science; University of Wisconsin System; University of Wisconsin Madison; University of Waterloo; University of Michigan System; University of Michigan; Tohoku Gakuin University; Yamagata University; Nara University Education; Nara University Education; University of Osaka; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; Nara Womens University; Columbia University; University of Manitoba; Aoyama Gakuin University; Jagiellonian University; Nagoya University; Okinawa Institute of Science & Technology Graduate University; Saitama University; Shizuoka University; Johns Hopkins University
RP Fabian, AC (corresponding author), Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
EM acf@ast.cam.ac.uk
FU NASA Science Mission Directorate; DoE [DE-AC3-76SF00515]; NASA [NNX15AM19G]; US DoE by LLNL [DE-AC52-07NA27344]; NASA; European Space Agency; CNES; Centre National d'Etudes Spatiales; NWO, the Netherlands Organization for Scientific Research; Swiss Secretariat for Education, Research and Innovation SERI; ESA's PRODEX programme; Canadian Space Agency; JSPS/MEXT KAKENHI [15H02070, 15K05107, 23340071, 26109506, 24103002, 25400236, 25800119, 25400237, 25287042, 24540229, 25105516, 23540280, 25400235, 25247028, 26800095, 25400231, 26220703, 24105007, 23340055, 15H00773, 23000004, 15H02090, 15K17610, 15H05438, 15H00785, 24540232]; NWO via a Veni grant; JSPS; STFC [ST/L00075X/1]; JAXA; UK Science and Technology Funding Council (STFC) [ST/J003697/2]; ERC [340442]; JAXA/ISAS; JAXA/TKSC; NASA/GSFC; Noqsi Aerospace Ltd; Stanford U/KIPAC; ESA (Netherlands); SRON; CSA; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1333514] Funding Source: National Science Foundation; Grants-in-Aid for Scientific Research [23000004, 15H05438, 15H00773, 15J10520, 15F14748, 24540237, 24105007, 16K17672, 24103002, 15K17610, 15K05107, 15H00785, 16K05300, 24105001, 15J02737, 25800119, 26400228, 15H03642, 15H03641, 25105516, 24540232, 26109506, 15H02090, 15H06896, 25247028, 26800095, 26220703, 23540280, 16K17673, 16H03983, 15K17652, 24540229, 26800160, 15H02070, 16K13787, 26800144, 25302003, 16K05296, 15K21679, 16H00949, 16K17667, 16H02198, 23340071, 16K05295, 25287042, 15K17657] Funding Source: KAKEN; Science and Technology Facilities Council [ST/N000927/1, ST/J003697/2, ST/J003697/1, ST/L00075X/1] Funding Source: researchfish; STFC [ST/J003697/1, ST/J003697/2, ST/L00075X/1] Funding Source: UKRI
NR 37
TC 364
Z9 390
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 117
EP +
DI 10.1038/nature18627
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600035
PM 27383985
DA 2026-03-09
ER

PT J
AU Thal, DM
   Sun, BF
   Feng, D
   Nawaratne, V
   Leach, K
   Felder, CC
   Bures, MG
   Evans, DA
   Weis, WI
   Bachhawat, P
   Kobilka, TS
   Sexton, PM
   Kobilka, BK
   Hristopoulos, AC
AF Thal, David M.
   Sun, Bingfa
   Feng, Dan
   Nawaratne, Vindhya
   Leach, Katie
   Felder, Christian C.
   Bures, Mark G.
   Evans, David A.
   Weis, William I.
   Bachhawat, Priti
   Kobilka, Tong Sun
   Sexton, Patrick M.
   Kobilka, Brian K.
   Hristopoulos, Arthur C.
TI Crystal structures of the M1 and M4 muscarinic acetylcholine receptors
SO NATURE
LA English
DT Article
ID 2nd extracellular loop; in-vivo validation; allosteric modulation; evolutionary conservation; swiss-model; binding; activation; proteins; consurf; insights
AB Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.
C1 [Thal, David M.; Nawaratne, Vindhya; Leach, Katie; Sexton, Patrick M.; Hristopoulos, Arthur C.] Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia.
   [Thal, David M.; Nawaratne, Vindhya; Leach, Katie; Sexton, Patrick M.; Hristopoulos, Arthur C.] Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia.
   [Sun, Bingfa; Feng, Dan; Bachhawat, Priti; Kobilka, Tong Sun; Kobilka, Brian K.] ConfometRx, 3070 Kenneth St, Santa Clara, CA 95054 USA.
   [Felder, Christian C.] Eli Lilly & Co, Neurosci, Indianapolis, IN 46285 USA.
   [Bures, Mark G.] Eli Lilly & Co, Computat Chem & Chemoinformat, Indianapolis, IN 46285 USA.
   [Evans, David A.] Eli Lilly & Co, Computat Chem & Chemoinformat, Sunninghill Rd, Windlesham GU20 6PH, Surrey, England.
   [Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA.
C3 Monash University; Monash University; Eli Lilly; Eli Lilly; Eli Lilly; Stanford University; Stanford University
RP Sexton, PM; Hristopoulos, AC (corresponding author), Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia.; Sexton, PM; Hristopoulos, AC (corresponding author), Monash Univ, Monash Inst Pharmaceut Sci, Dept Pharmacol, Parkville, Vic 3052, Australia.; Kobilka, BK (corresponding author), ConfometRx, 3070 Kenneth St, Santa Clara, CA 95054 USA.; Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM patrick.sexton@monash.edu; kobilka@stanford.edu; arthur.christopoulos@monash.edu
FU National Health and Medical Research Council (NHMRC) of Australia [APP1055134]; Lilly Research Award Program; Mathers Foundation; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Science [Y1-GM-1104]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38]
NR 66
TC 273
Z9 318
U1 7
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 335
EP +
DI 10.1038/nature17188
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300045
PM 26958838
DA 2026-03-09
ER

PT J
AU Ludwig, JR
   Zimmerman, PM
   Gianino, JB
   Schindler, CS
AF Ludwig, Jacob R.
   Zimmerman, Paul M.
   Gianino, Joseph B.
   Schindler, Corinna S.
TI Iron(III)-catalysed carbonyl-olefin metathesis
SO NATURE
LA English
DT Article
ID mechanism; alcohols
AB The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries(1). These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism(2). While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
C1 [Ludwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.] Univ Michigan, Dept Chem, Willard Henry Dow Lab, 930 North Univ Ave, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Schindler, CS (corresponding author), Univ Michigan, Dept Chem, Willard Henry Dow Lab, 930 North Univ Ave, Ann Arbor, MI 48109 USA.
EM corinnas@umich.edu
FU Petroleum Research Fund (PRF) [54688-DNI1, 54267-DNI6]; University of Michigan; National Science Foundation; Office of Naval Research [N00014-14-1-0551]
NR 31
TC 185
Z9 224
U1 1
U2 173
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 374
EP 379
DI 10.1038/nature17432
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300044
PM 27120158
DA 2026-03-09
ER

PT J
AU Martinez-Zapien, D
   Ruiz, FX
   Poirson, J
   Mitschler, A
   Ramirez, J
   Forster, A
   Cousido-Siah, A
   Masson, M
   Vande Pol, S
   Podjarny, A
   Travé, G
   Zanier, K
AF Martinez-Zapien, Denise
   Ruiz, Francesc Xavier
   Poirson, Juline
   Mitschler, Andre
   Ramirez, Juan
   Forster, Anne
   Cousido-Siah, Alexandra
   Masson, Murielle
   Vande Pol, Scott
   Podjarny, Alberto
   Trave, Gilles
   Zanier, Katia
TI Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53
SO NATURE
LA English
DT Article
ID human-papillomavirus type-16; e6 oncoprotein; e6-mediated degradation; viral oncoprotein; protein; immortalization; ubiquitination; localization; association; determines
AB The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by 'high-risk' mucosal human papilloma viruses, including human cervical carcinoma and a growing number of head-and-neck cancers(1), p53 is degraded by the viral oncoprotein E6 (ref. 2). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP(3). Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4). Neither E6 nor E6AP are separately able to recruit p53 (refs 3, 5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA-and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus.
C1 [Martinez-Zapien, Denise; Poirson, Juline; Ramirez, Juan; Forster, Anne; Masson, Murielle; Trave, Gilles; Zanier, Katia] Ecole Super Biotechnol Strasbourg, Equipe Labellisee Ligue, Biotechnol & Signalisat Cellulaire UMR 7242, Blvd Sebastien Brant,BP 10413, F-67412 Illkirch Graffenstaden, France.
   [Ruiz, Francesc Xavier; Mitschler, Andre; Cousido-Siah, Alexandra; Podjarny, Alberto] Univ Strasbourg, CNRS UMR 7104, INSERM U964, IGBMC, 1 Rue Laurent Fries,BP 10142, F-67404 Illkirch Graffenstaden, France.
   [Vande Pol, Scott] Univ Virginia, Dept Pathol, POB 800904, Charlottesville, VA 22908 USA.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Virginia
RP Travé, G; Zanier, K (corresponding author), Ecole Super Biotechnol Strasbourg, Equipe Labellisee Ligue, Biotechnol & Signalisat Cellulaire UMR 7242, Blvd Sebastien Brant,BP 10413, F-67412 Illkirch Graffenstaden, France.
EM gilles.trave@unistra.fr; zanier@unistra.fr
FU Ligue contre le Cancer, National Institutes of Health [R01CA134737]; l'Agence Nationale de la Recherche [ANR-13-JSV8-004-01]; Instruct (ESFRI); French Infrastructure for Integrated Structural Biology (FRISBI); Fondation pour La Recherche Medicale
NR 37
TC 388
Z9 462
U1 0
U2 113
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 541
EP +
DI 10.1038/nature16481
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800040
PM 26789255
DA 2026-03-09
ER

PT J
AU Ye, LB
   Van Eps, N
   Zimmer, M
   Ernst, OP
   Prosser, RS
AF Ye, Libin
   Van Eps, Ned
   Zimmer, Marco
   Ernst, Oliver P.
   Prosser, R. Scott
TI Activation of the A2A adenosine G-protein-coupled receptor by conformational selection
SO NATURE
LA English
DT Article
ID beta(2)-adrenergic receptor; crystal-structure; pichia-pastoris; dynamic process; equilibrium; binding; landscapes; rhodopsin; insights; states
AB Conformational selection and induced fit are two prevailing mechanisms(1,2) to explain the molecular basis for ligand-based activation of receptors. G-protein-coupled receptors are the largest class of cell surface receptors and are important drug targets. A molecular understanding of their activation mechanism is critical for drug discovery and design. However, direct evidence that addresses how agonist binding leads to the formation of an active receptor state is scarce(3). Here we use F-19 nuclear magnetic resonance to quantify the conformational landscape occupied by the adenosine A(2A) receptor (A(2A)R), a prototypical class A G-protein-coupled receptor. We find an ensemble of four states in equilibrium: (1) two inactive states in millisecond exchange, consistent with a formed (state S-1) and a broken (state S-2) salt bridge (known as 'ionic lock') between transmembrane helices 3 and 6; and (2) two active states, S-3 and S-3', as identified by binding of a G-protein-derived peptide. In contrast to a recent study of the beta(2)-adrenergic receptor(4), the present approach allowed identification of a second active state for A(2A)R. Addition of inverse agonist (ZM241385) increases the population of the inactive states, while full agonists (UK432097 or NECA) stabilize the active state, S-3', in a manner consistent with conformational selection. In contrast, partial agonist (LUF5834) and an allosteric modulator (HMA) exclusively increase the population of the S-3 state. Thus, partial agonism is achieved here by conformational selection of a distinct active state which we predict will have compromised coupling to the G protein. Direct observation of the conformational equilibria of ligand-dependent G-protein-coupled receptor and deduction of the underlying mechanisms of receptor activation will have wide-reaching implications for our understanding of the function of G-protein-coupled receptor in health and disease.
C1 [Ye, Libin; Prosser, R. Scott] Univ Toronto, Dept Chem, UTM, 3359 Mississauga Rd North, Mississauga, ON L5L 1C6, Canada.
   [Ye, Libin; Van Eps, Ned; Zimmer, Marco; Ernst, Oliver P.; Prosser, R. Scott] Univ Toronto, Dept Biochem, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
   [Zimmer, Marco] Univ Stuttgart, Dept Tech Biochem, 31 Allmandring, D-70569 Stuttgart, Baden Wurttembe, Germany.
   [Ernst, Oliver P.] Univ Toronto, Dept Mol Genet, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University Toronto Mississauga; University of Toronto; University of Stuttgart; University of Toronto
RP Prosser, RS (corresponding author), Univ Toronto, Dept Chem, UTM, 3359 Mississauga Rd North, Mississauga, ON L5L 1C6, Canada.; Ernst, OP; Prosser, RS (corresponding author), Univ Toronto, Dept Biochem, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.; Ernst, OP (corresponding author), Univ Toronto, Dept Mol Genet, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
EM oliver.ernst@utoronto.ca; scott.prosser@utoronto.ca
FU Natural Sciences and Engineering Research Council of Canada [261980]; Canada Excellence Research Chair Program
NR 37
TC 282
Z9 330
U1 0
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 265
EP +
DI 10.1038/nature17668
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200054
PM 27144352
DA 2026-03-09
ER

PT J
AU Jazayeri, A
   Doré, AS
   Lamb, D
   Krishnamurthy, H
   Southall, SM
   Baig, AH
   Bortolato, A
   Koglin, M
   Robertson, NJ
   Errey, JC
   Andrews, SP
   Teobald, I
   Brown, AJH
   Cooke, RM
   Weir, M
   Marshall, FH
AF Jazayeri, Ali
   Dore, Andrew S.
   Lamb, Daniel
   Krishnamurthy, Harini
   Southall, Stacey M.
   Baig, Asma H.
   Bortolato, Andrea
   Koglin, Markus
   Robertson, Nathan J.
   Errey, James C.
   Andrews, Stephen P.
   Teobald, Iryna
   Brown, Alastair J. H.
   Cooke, Robert M.
   Weir, Malcolm
   Marshall, Fiona H.
TI Extra-helical binding site of a glucagon receptor antagonist
SO NATURE
LA English
DT Article
ID protein-coupled receptors; thermostabilization; activation; discovery; insights; family
AB Glucagon is a 29-amino-acid peptide released from the alpha-cells of the islet of Langerhans, which has a key role in glucose homeostasis(1). Glucagon action is transduced by the class B G-protein-coupled glucagon receptor (GCGR), which is located on liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart and pancreas cells, and this receptor has been considered an important drug target in the treatment of diabetes. Administration of recently identified small-molecule GCGR antagonists in patients with type 2 diabetes results in a substantial reduction of fasting and postprandial glucose concentrations(2). Although an X-ray structure of the transmembrane domain of the GCGR(3) has previously been solved, the ligand (NNC0640) was not resolved. Here we report the 2.5 angstrom structure of human GCGR in complex with the antagonist MK-0893 (ref. 4), which is found to bind to an allosteric site outside the seven transmembrane (7TM) helical bundle in a position between TM6 and TM7 extending into the lipid bilayer. Mutagenesis of key residues identified in the X-ray structure confirms their role in the binding of MK-0893 to the receptor. The unexpected position of the binding site for MK-0893, which is structurally similar to other GCGR antagonists, suggests that glucagon activation of the receptor is prevented by restriction of the outward helical movement of TM6 required for G-protein coupling. Structural knowledge of class B receptors is limited, with only one other ligand-binding site defined-for the corticotropin-releasing hormone receptor 1 (CRF1R)-which was located deep within the 7TM bundle(5). We describe a completely novel allosteric binding site for class B receptors, providing an opportunity for structure-based drug design for this receptor class and furthering our understanding of the mechanisms of activation of these receptors.
C1 [Jazayeri, Ali; Dore, Andrew S.; Lamb, Daniel; Krishnamurthy, Harini; Southall, Stacey M.; Baig, Asma H.; Bortolato, Andrea; Koglin, Markus; Robertson, Nathan J.; Errey, James C.; Andrews, Stephen P.; Teobald, Iryna; Brown, Alastair J. H.; Cooke, Robert M.; Weir, Malcolm; Marshall, Fiona H.] Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
C3 Heptares Therapeutics Ltd.
RP Marshall, FH (corresponding author), Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
EM fiona.marshall@heptares.com
CR Ahrén B, 2015, PEPTIDES, V67, P74, DOI 10.1016/j.peptides.2015.03.011
   Bagger JI, 2011, DIABETES OBES METAB, V13, P965, DOI 10.1111/j.1463-1326.2011.01427.x
   Ballesteros JA, 1995, METHODS IN NEUROSCIENCES, V0, PP366, DOI 10.1016/S1043-9471(05)80049-7
   Deupi X, 2011, CURR OPIN STRUC BIOL, V21, P541, DOI 10.1016/j.sbi.2011.06.002
   Hollenstein K, 2014, TRENDS PHARMACOL SCI, V35, P12, DOI 10.1016/j.tips.2013.11.001
   Hollenstein K, 2013, NATURE, V499, P438, DOI 10.1038/nature12357
   Robertson N, 2011, NEUROPHARMACOLOGY, V60, P36, DOI 10.1016/j.neuropharm.2010.07.001
   Serrano-Vega MJ, 2008, P NATL ACAD SCI USA, V105, P877, DOI 10.1073/pnas.0711253105
   Shibata Y, 2009, J MOL BIOL, V390, P262, DOI 10.1016/j.jmb.2009.04.068
   Siu FY, 2013, NATURE, V499, P444, DOI 10.1038/nature12393
   Tehan BG, 2014, PHARMACOL THERAPEUT, V143, P51, DOI 10.1016/j.pharmthera.2014.02.004
   Wootten D, 2013, P NATL ACAD SCI USA, V110, P5211, DOI 10.1073/pnas.1221585110
   Xiong YS, 2012, J MED CHEM, V55, P6137, DOI 10.1021/jm300579z
   Zhang DD, 2015, NATURE, V520, P317, DOI 10.1038/nature14287
NR 14
TC 181
Z9 212
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 274
EP +
DI 10.1038/nature17414
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200056
PM 27111510
DA 2026-03-09
ER

PT J
AU Malaspinas, AS
   Westaway, MC
   Muller, C
   Sousa, VC
   Lao, O
   Alves, I
   Bergström, A
   Athanasiadis, G
   Cheng, JY
   Crawford, JE
   Heupink, TH
   Macholdt, E
   Peischl, S
   Rasmussen, S
   Schiffels, S
   Subramanian, S
   Wright, JL
   Albrechtsen, A
   Barbieri, C
   Dupanloup, I
   Eriksson, A
   Margaryan, A
   Moltke, I
   Pugach, I
   Korneliussen, TS
   Levkivskyi, IP
   Moreno-Mayar, JV
   Ni, S
   Racimo, F
   Sikora, M
   Xue, YL
   Aghakhanian, FA
   Brucato, N
   Brunak, S
   Campos, PF
   Clark, W
   Ellingvåg, S
   Fourmile, G
   Gerbault, P
   Injie, D
   Koki, G
   Leavesley, M
   Logan, B
   Lynch, A
   Matisoo-Smith, EA
   McAllister, PJ
   Mentzer, AJ
   Metspalu, M
   Migliano, AB
   Murgha, L
   Phipps, ME
   Pomat, W
   Reynolds, D
   Ricaut, FX
   Siba, P
   Thomas, MG
   Wales, T
   Wall, CM
   Oppenheimer, SJ
   Tyler-Smith, C
   Durbin, R
   Dortch, J
   Manica, A
   Schierup, MH
   Foley, RA
   Lahr, MM
   Bowern, C
   Wall, JD
   Mailund, T
   Stoneking, M
   Nielsen, R
   Sandhu, MS
   Excoffier, L
   Lambert, DM
   Willerslev, E
AF Malaspinas, Anna-Sapfo
   Westaway, Michael C.
   Muller, Craig
   Sousa, Vitor C.
   Lao, Oscar
   Alves, Isabel
   Bergstrom, Anders
   Athanasiadis, Georgios
   Cheng, Jade Y.
   Crawford, Jacob E.
   Heupink, Tim H.
   Macholdt, Enrico
   Peischl, Stephan
   Rasmussen, Simon
   Schiffels, Stephan
   Subramanian, Sankar
   Wright, Joanne L.
   Albrechtsen, Anders
   Barbieri, Chiara
   Dupanloup, Isabelle
   Eriksson, Anders
   Margaryan, Ashot
   Moltke, Ida
   Pugach, Irina
   Korneliussen, Thorfinn S.
   Levkivskyi, Ivan P.
   Moreno-Mayar, J. Vctor
   Ni, Shengyu
   Racimo, Fernando
   Sikora, Martin
   Xue, Yali
   Aghakhanian, Farhang A.
   Brucato, Nicolas
   Brunak, Soren
   Campos, Paula F.
   Clark, Warren
   Ellingvag, Sturla
   Fourmile, Gudjugudju
   Gerbault, Pascale
   Injie, Darren
   Koki, George
   Leavesley, Matthew
   Logan, Betty
   Lynch, Aubrey
   Matisoo-Smith, Elizabeth A.
   McAllister, Peter J.
   Mentzer, Alexander J.
   Metspalu, Mait
   Migliano, Andrea B.
   Murgha, Les
   Phipps, Maude E.
   Pomat, William
   Reynolds, Doc
   Ricaut, Francois-Xavier
   Siba, Peter
   Thomas, Mark G.
   Wales, Thomas
   Wall, Colleen Ma'run
   Oppenheimer, Stephen J.
   Tyler-Smith, Chris
   Durbin, Richard
   Dortch, Joe
   Manica, Andrea
   Schierup, Mikkel H.
   Foley, Robert A.
   Lahr, Marta Mirazon
   Bowern, Claire
   Wall, Jeffrey D.
   Mailund, Thomas
   Stoneking, Mark
   Nielsen, Rasmus
   Sandhu, Manjinder S.
   Excoffier, Laurent
   Lambert, David M.
   Willerslev, Eske
TI A genomic history of Aboriginal Australia
SO NATURE
LA English
DT Article
ID modern human dispersals; southeast-asia; neanderthal; ancestry; evolution; admixture; sequence; african; cave
AB The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated similar to 10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.
C1 [Malaspinas, Anna-Sapfo; Muller, Craig; Margaryan, Ashot; Korneliussen, Thorfinn S.; Moreno-Mayar, J. Vctor; Sikora, Martin; Campos, Paula F.; Schierup, Mikkel H.; Foley, Robert A.; Lahr, Marta Mirazon; Nielsen, Rasmus; Willerslev, Eske] Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, Oster Voldgacle 5-7, DK-1350 Copenhagen, Denmark.
   [Malaspinas, Anna-Sapfo; Sousa, Vitor C.; Alves, Isabel; Dupanloup, Isabelle; Excoffier, Laurent] Univ Bern, Inst Ecol & Evolut, Baltzerstr 6, CH-3012 Bern, Switzerland.
   [Malaspinas, Anna-Sapfo; Sousa, Vitor C.; Alves, Isabel; Peischl, Stephan; Dupanloup, Isabelle; Excoffier, Laurent] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Westaway, Michael C.; Heupink, Tim H.; Subramanian, Sankar; Wright, Joanne L.; Lambert, David M.] Griffith Univ, Environm Futures Res Inst, Res Ctr Human Evolut, Nathan, Qld 4111, Australia.
   [Lao, Oscar] BIST, Ctr Genom Regulat CRG, CNAG CRG, Baldiri & Reixac 4, Barcelona 08028, Spain.
   [Lao, Oscar] UPF, Barcelona 08003, Spain.
   [Alves, Isabel] Inst Gulbenkian Ciencias, Populat & Conservat Genet Grp, P-2780156 Oeiras, Portugal.
   [Bergstrom, Anders; Xue, Yali; Tyler-Smith, Chris; Durbin, Richard; Sandhu, Manjinder S.; Willerslev, Eske] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.
   [Athanasiadis, Georgios; Cheng, Jade Y.; Mailund, Thomas] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark.
   [Cheng, Jade Y.; Crawford, Jacob E.; Racimo, Fernando] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Crawford, Jacob E.] Verily Life Sci, 2425 Garcia Ave, Mountain View, CA 94043 USA.
   [Macholdt, Enrico; Barbieri, Chiara; Pugach, Irina; Ni, Shengyu; Stoneking, Mark] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Deutsch Pl 6, D-04103 Leipzig, Germany.
   [Peischl, Stephan] Univ Bern, Interfac Bioinformat Unit, Baltzerstr 6, CH-3012 Bern, Switzerland.
   [Rasmussen, Simon] Techn Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, Bldg 208,Denm, DK-2800 Kemitorvet, Kongens Lyngby, Denmark.
   [Schiffels, Stephan] Max Planck Inst Sci Human Hist, Dept Archaeogenet, Kahlaische Str 10, D-07745 Jena, Germany.
   [Albrechtsen, Anders; Moltke, Ida] Univ Copenhagen, Dept Biol, Bioinformat Ctr, Ole Maalees Vej 5, DK-2200 Copenhagen, Denmark.
   [Barbieri, Chiara] Max Planck Inst Sci Human Hist, Dept Linguist & Cultural Evolut, Kahlaische Str 10, D-07745 Jena, Germany.
   [Eriksson, Anders; Manica, Andrea; Willerslev, Eske] Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
   [Eriksson, Anders] King Abdullah Univ Sci & Technol, Div Biol & Environm Sci & Engn, Integrat Syst Biol Lab, Thuwal 239556900, Saudi Arabia.
   [Levkivskyi, Ivan P.] Swiss Fed Inst Technol, Inst Theoret Phys, Wolfgang Pauli Str 27, CH-8093 Zurich, Switzerland.
   [Aghakhanian, Farhang A.; Phipps, Maude E.] Monash Univ Malaysia, Jeffrey Cheah Sch Med Hlth Sci, Sunway City 46150, Selangor, Malaysia.
   [Brucato, Nicolas; Ricaut, Francois-Xavier] Univ Toulouse 3, CNRS, UMR 5288, Lab Anthropol Mol & Imagerie Synthese,Evolutionar, F-31073 Toulouse, France.
   [Brunak, Soren] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark.
   [Campos, Paula F.] Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, Rua Bragas 289, P-4050123 Oporto, Portugal.
   [Clark, Warren] Natl Parks & Wildlife, Sturt Highway, Buronga, NSW 2739, Australia.
   [Ellingvag, Sturla] Explico Fdn, Vagavegen 16, N-6900 Fiore, Norway.
   [Gerbault, Pascale; Thomas, Mark G.] UCL, Res Dept Genet Evolut & Environm, Gower St, London WC1E 6BT, England.
   [Gerbault, Pascale; Migliano, Andrea B.] UCL, Dept Anthropol, 14 Taviton St, London WC1H 0BW, England.
   [Injie, Darren] Yinhawangka Elder, Perth, WA 6062, Australia.
   [Koki, George; Pomat, William; Siba, Peter] Papua New Guinea Inst Med Res, POB 60, Goroka, Papua N Guinea.
   [Leavesley, Matthew] Univ Papua New Guinea, Archaeolo Sch Humanities & Social Sci, Univ POB 320, Port Moresby, Papua N Guinea.
   [Leavesley, Matthew] James Cook Univ, Coll Arts Soc & Educ, Cairns, Qld 4811, Australia.
   [Logan, Betty] Ngadju Elder, Coolgardie, WA 6429, Australia.
   [Lynch, Aubrey] Wongatha Elder, Kurrawang, WA 6430, Australia.
   [Matisoo-Smith, Elizabeth A.] Univ Otago, Dept Anat, Dunedin 9054, New Zealand.
   [McAllister, Peter J.] 2209 Springbrook Rd, Springbrook, Qld 4213, Australia.
   [Mentzer, Alexander J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Metspalu, Mait] Estonian Bioctr, Riia 23b, EE-51010 Tartu, Estonia.
   [Murgha, Les] 86 Workshop Rd, Yarrabah, Qld 4871, Australia.
   [Reynolds, Doc] Esperance Nyungar Elder, Esperance, WA 4871, Australia.
   [Wales, Thomas] Atakani St, Napranum, Qld 4874, Australia.
   [Wall, Colleen Ma'run] 2 Wynnum North Rd, Wynnum, Qld 4178, Australia.
   [Oppenheimer, Stephen J.] Univ Oxford, Sch Anthropol, Oxford OX2 6PE, England.
   [Dortch, Joe] Univ Western Australia, Ctr Rock Art Res & Management, M257, Perth, WA 6009, Australia.
   [Schierup, Mikkel H.; Foley, Robert A.; Lahr, Marta Mirazon] Univ Cambridge, Dept Archaeol & Anthropol, Leverhulme Ctr Human Evolutionary Studies, Fitzwilliam St, Cambridge CB2 1QH, England.
   [Bowern, Claire] Yale Univ, Dept Linguist, 370 Temple St, New Haven, CT 06520 USA.
   [Wall, Jeffrey D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
C3 University of Copenhagen; University of Bern; Swiss Institute of Bioinformatics; Griffith University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Instituto Gulbenkian de Ciencia; Wellcome Trust Sanger Institute; Aarhus University; University of California System; University of California Berkeley; Max Planck Society; University of Bern; University of Copenhagen; University of Cambridge; King Abdullah University of Science & Technology; Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University of Copenhagen; Universidade do Porto; University of London; University College London; University of London; University College London; PNG Institute Of Medical Research; University of Papua New Guinea; James Cook University; University of Otago; University of Oxford; Wellcome Centre for Human Genetics; Estonian Biocentre; University of Oxford; University of Western Australia; University of Cambridge; Yale University; University of California System; University of California San Francisco; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Willerslev, E (corresponding author), Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, Oster Voldgacle 5-7, DK-1350 Copenhagen, Denmark.; Excoffier, L; Lambert, DM (corresponding author), Univ Bern, Inst Ecol & Evolut, Baltzerstr 6, CH-3012 Bern, Switzerland.; Excoffier, L; Lambert, DM (corresponding author), Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.; Sandhu, MS; Lambert, DM; Willerslev, E (corresponding author), Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.; Willerslev, E (corresponding author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
EM ms23@sanger.ac.uk; laurent.excoffier@iee.unibe.ch; d.lambert@griffith.edu.au; ewillerslev@snm.ku.dk
FU Danish National Research Foundation; Lundbeck Foundation; Australian Research Council; Swiss National Science Foundation (SNSF) [PZ00P3_154717]; Australian Research Council (ARC) [DP110102635, DP140101405, LP140100387]; SNSF [31003A-143393, CRSII3_141940]; Ramon y Cajal grant from the Spanish Ministerio de Economia y Competitividad (MINECO) [RYC-2013-14797]; MINECO/FEDER [BFU2015-68759-P]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/73150/2010]; Wellcome Trust [WT098051, 106289/Z/14/Z, 100719/Z/12/Z, 090532/Z/09/Z]; ARC [DP110102635, DP140101405, LP140100387, LP120200144, LP150100583]; Griffith University; Danish Council for Independent Research [DFF-4090-00244]; Consejo Nacional de Ciencia y Tecnologia (Mexico); French Ministry of Foreign and European Affairs; French ANR [ANR14-CE31-0013-01]; Novo Nordisk Foundation [NNF14CC0001]; Leverhulme Programme grant at UCL Department of Anthropology [RP2011-R-045]; Leverhulme Programme grant at UCL Department of Genetics, Evolution and Environment; Estonian Institutional Research grant [IUT24-1]; ERC [647787, 295907]; Ministry of Science, Technology AMP; Innovation, Malaysia [100-RM1/BIOTEK 16/6/2B]; Danish Independence Research Council [FNU 12-125062, FNU 1323-00749]; Leverhulme Trust; USA National Science Foundation (NSF) [BCS-0844550, BCS-1423711]; Yale University; Swiss NSF [31003A-143393]; St John's College in Cambridge; cardio-metabolic research cluster at Jeffrey Cheah School of Medicine AMP; Health Sciences; Monash University Malaysia;  [KU2016]; Australian Research Council [LP150100583, LP120200144] Funding Source: Australian Research Council; European Research Council (ERC) [295907, 647787] Funding Source: European Research Council (ERC); Fundação para a Ciência e a Tecnologia [SFRH/BD/73150/2010] Funding Source: FCT; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1423711] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BB/H005854/1] Funding Source: researchfish; Lundbeck Foundation [R24-2008-2527, R70-2010-6286, R155-2013-16338, R215-2015-4174, R109-2012-9995, R38-2008-3048] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Søren Brunak] Funding Source: researchfish; Wellcome Trust [100719/Z/12/Z] Funding Source: researchfish; Swiss National Science Foundation (SNF) [PZ00P3_154717, CRSII3_141940] Funding Source: Swiss National Science Foundation (SNF); BBSRC [BB/H005854/1] Funding Source: UKRI; Wellcome Trust [106289/Z/14/Z] Funding Source: Wellcome Trust
NR 56
TC 366
Z9 406
U1 3
U2 188
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 207
EP +
DI 10.1038/nature18299
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000038
PM 27654914
DA 2026-03-09
ER

PT J
AU Mitrano, M
   Cantaluppi, A
   Nicoletti, D
   Kaiser, S
   Perucchi, A
   Lupi, S
   Di Pietro, P
   Pontiroli, D
   Riccò, M
   Clark, SR
   Jaksch, D
   Cavalleri, A
AF Mitrano, M.
   Cantaluppi, A.
   Nicoletti, D.
   Kaiser, S.
   Perucchi, A.
   Lupi, S.
   Di Pietro, P.
   Pontiroli, D.
   Ricco, M.
   Clark, S. R.
   Jaksch, D.
   Cavalleri, A.
TI Possible light-induced superconductivity in K3C60 at high temperature
SO NATURE
LA English
DT Article
ID optical-property; dynamics; transport; model
AB The non-equilibrium control of emergent phenomena in solids is an important research frontier, encompassing effects such as the optical enhancement of superconductivity(1). Nonlinear excitation(2,3) of certain phonons in bilayer copper oxides was recently shown to induce superconducting-like optical properties at temperatures far greater than the superconducting transition temperature, T-c (refs 4-6). This effect was accompanied by the disruption of competing charge-density-wave correlations(7,8), which explained some but not all of the experimental results. Here we report a similar phenomenon in a very different compound, K3C60. By exciting metallic K3C60 with mid-infrared optical pulses, we induce a large increase in carrier mobility, accompanied by the opening of a gap in the optical conductivity. These same signatures are observed at equilibrium when cooling metallic K3C60 below T-c (20 kelvin). Although optical techniques alone cannot unequivocally identify non-equilibrium high-temperature superconductivity, we propose this as a possible explanation of our results.
C1 [Mitrano, M.; Cantaluppi, A.; Nicoletti, D.; Kaiser, S.; Clark, S. R.; Cavalleri, A.] Max Planck Inst Struct & Dynam Matter, Luruper Chaussee 149, D-22761 Hamburg, Germany.
   [Cantaluppi, A.; Nicoletti, D.; Cavalleri, A.] Hamburg Ctr Ultrafast Imaging, Luruper Chaussee 149, D-22761 Hamburg, Germany.
   [Perucchi, A.; Di Pietro, P.] INSTM UdR Trieste ST, Area Sci Pk, I-34012 Trieste, Italy.
   [Perucchi, A.; Di Pietro, P.] Elettra Sincrotrone Trieste SCpA, Area Sci Pk, I-34012 Trieste, Italy.
   [Lupi, S.] Univ Roma La Sapienza, CNR IOM, Piazzale A Moro 2, I-00185 Rome, Italy.
   [Lupi, S.] Univ Roma La Sapienza, Dipartimento Fis, Piazzale A Moro 2, I-00185 Rome, Italy.
   [Pontiroli, D.; Ricco, M.] Univ Parma, Dipartimento Fis & Sci Terra, Parco Area Sci 7-A, I-43124 Parma, Italy.
   [Clark, S. R.] Univ Bath, Dept Phys, Bath BA2 7AY, Avon, England.
   [Clark, S. R.; Jaksch, D.; Cavalleri, A.] Univ Oxford, Dept Phys, Parks Rd, Oxford OX1 3PU, England.
   [Jaksch, D.] Natl Univ Singapore, Ctr Quantum Technol, 3 Sci Dr 2, Singapore 117543, Singapore.
C3 Max Planck Society; University of Hamburg; Elettra Sincrotrone Trieste; Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto Officina dei Materiali (IOM-CNR); Sapienza University Rome; University of Parma; University of Bath; University of Oxford; National University of Singapore
RP Cavalleri, A (corresponding author), Max Planck Inst Struct & Dynam Matter, Luruper Chaussee 149, D-22761 Hamburg, Germany.; Cavalleri, A (corresponding author), Hamburg Ctr Ultrafast Imaging, Luruper Chaussee 149, D-22761 Hamburg, Germany.
EM andrea.cavalleri@mpsd.mpg.de
FU European Research Council under the European Union [319286]; Deutsche Forschungsgemeinschaft via the excellence cluster 'The Hamburg Centre for Ultrafast Imaging - Structure, Dynamics and Control of Matter at the Atomic Scale' [SFB925]; Swiss National Supercomputing Center (CSCS) [s497]
NR 40
TC 674
Z9 742
U1 2
U2 322
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 461
EP +
DI 10.1038/nature16522
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800031
PM 26855424
DA 2026-03-09
ER

PT J
AU Vogt, S
   Zaid, NAM
   Ahmed, HE
   Fehr, E
   Efferson, C
AF Vogt, Sonja
   Zaid, Nadia Ahmed Mohmmed
   Ahmed, Hilal El Fadil
   Fehr, Ernst
   Efferson, Charles
TI Changing cultural attitudes towards female genital cutting
SO NATURE
LA English
DT Article
ID impact
AB As globalization brings people with incompatible attitudes into contact, cultural conflicts inevitably arise. Little is known about how to mitigate conflict and about how the conflicts that occur can shape the cultural evolution of the groups involved. Female genital cutting is a prominent example(1-3). Governments and international agencies have promoted the abandonment of cutting for decades, but the practice remains widespread with associated health risks for millions of girls and women(4,5). In their efforts to end cutting, international agents have often adopted the view that cutting is locally pervasive and entrenched(1). This implies the need to introduce values and expectations from outside the local culture. Members of the target society may view such interventions as unwelcome intrusions(1-3,6-9), and campaigns promoting abandonment have sometimes led to backlash(1,7,8,10,11) as they struggle to reconcile cultural tolerance with the conviction that cutting violates universal human rights(1,9). Cutting, however, is not necessarily locally pervasive and entrenched(1,3,12). We designed experiments on cultural change that exploited the existence of conflicting attitudes within cutting societies. We produced four entertaining movies that served as experimental treatments in two experiments in Sudan, and we developed an implicit association test to unobtrusively measure attitudes about cutting. The movies depart from the view that cutting is locally pervasive by dramatizing members of an extended family as they confront each other with divergent views about whether the family should continue cutting. The movies significantly improved attitudes towards girls who remain uncut, with one in particular having a relatively persistent effect. These results show that using entertainment to dramatize locally discordant views can provide a basis for applied cultural evolution without accentuating intercultural divisions.
C1 [Vogt, Sonja; Fehr, Ernst; Efferson, Charles] Univ Zurich, Dept Econ, CH-8006 Zurich, Switzerland.
C3 University of Zurich
RP Vogt, S; Fehr, E; Efferson, C (corresponding author), Univ Zurich, Dept Econ, CH-8006 Zurich, Switzerland.
EM sonja.vogt@econ.uzh.ch; ernst.fehr@econ.uzh.ch; charles.efferson@econ.uzh.ch
FU Gezira State government; Sudan Nation Council for Child Welfare; Gezira State Council for Child Welfare; local authority in Umalgoura; local authority in East Gezira; European Research Council grant on the Foundations of Economic Preferences
NR 29
TC 67
Z9 78
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 506
EP +
DI 10.1038/nature20100
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400057
PM 27732586
DA 2026-03-09
ER

PT J
AU Hedrick, NG
   Harward, SC
   Hall, CE
   Murakoshi, H
   McNamara, JO
   Yasuda, R
AF Hedrick, Nathan G.
   Harward, Stephen C.
   Hall, Charles E.
   Murakoshi, Hideji
   McNamara, James O.
   Yasuda, Ryohei
TI Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity
SO NATURE
LA English
DT Article
ID single dendritic spines; long-term potentiation; structural plasticity; fluorescent protein; neurotrophic factor; genetic approach; activation; rac1; trkb; dynamics
AB The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines(1), thereby exerting control over the structural and functional plasticity of spines(2-5) and, ultimately, learning and memory(6-8). Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis(9), the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.
C1 [Hedrick, Nathan G.; Harward, Stephen C.; Hall, Charles E.; McNamara, James O.; Yasuda, Ryohei] Duke Univ, Med Ctr, Dept Neurobiol, Res Dr, Durham, NC 27710 USA.
   [Murakoshi, Hideji] Natl Inst Physiol Sci, Okazaki, Aichi 4448585, Japan.
   [Yasuda, Ryohei] Max Planck Florida Inst Neurosci, 1 Max Planck Way, Jupiter, FL 33458 USA.
   [Hedrick, Nathan G.] Univ Calif San Diego, Ctr Neural Circuits & Behav, Neurobiol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Hedrick, Nathan G.] Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
C3 Duke University; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Physiological Sciences (NIPS); Max Planck Society; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Yasuda, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Res Dr, Durham, NC 27710 USA.; Yasuda, R (corresponding author), Max Planck Florida Inst Neurosci, 1 Max Planck Way, Jupiter, FL 33458 USA.
EM ryohei.yasuda@mpfi.org
FU NIMH [R01MH080047, R01NS068410]; NINDS [F31NS078847, R01NS05621, DP1NS096787]; JSPS KAKENHI; JST PRESTO; Wakeman Fellowship at Duke University; Max Planck Florida Institute; National Institute of Mental Health [R01MH080047] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS056217] Funding Source: NIH RePORTER
NR 36
TC 166
Z9 200
U1 1
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 104
EP +
DI 10.1038/nature19784
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900043
PM 27680697
DA 2026-03-09
ER

PT J
AU Wu, S
   Powers, S
   Zhu, W
   Hannun, YA
AF Wu, Song
   Powers, Scott
   Zhu, Wei
   Hannun, Yusuf A.
TI Substantial contribution of extrinsic risk factors to cancer development
SO NATURE
LA English
DT Article
AB Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than similar to 10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.
C1 [Wu, Song; Powers, Scott; Zhu, Wei] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
   [Wu, Song; Powers, Scott; Zhu, Wei; Hannun, Yusuf A.] SUNY Stony Brook, Stony Brook Cancer Ctr, Hlth Sci Ctr, Stony Brook, NY 11794 USA.
   [Powers, Scott; Hannun, Yusuf A.] SUNY Stony Brook, Dept Pathol, Hlth Sci Ctr, Stony Brook, NY 11794 USA.
   [Hannun, Yusuf A.] SUNY Stony Brook, Dept Med, Hlt Sci Ctr, Stony Brook, NY 11794 USA.
   [Hannun, Yusuf A.] SUNY Stony Brook, Dept Biochem, Hlt Sci Ctr, Stony Brook, NY 11794 USA.
C3 State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
RP Wu, S (corresponding author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
EM Song.Wu@stonybrook.edu; Yusuf.Hannun@sbumed.org
FU NCI [97132, 168409]; Stony Brook NYSTEM award [C026716]; National Cancer Institute [P30CA045508, P01CA097132] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R35GM118128] Funding Source: NIH RePORTER
NR 35
TC 493
Z9 586
U1 0
U2 131
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 43
EP 47
DI 10.1038/nature16166
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900041
PM 26675728
DA 2026-03-09
ER

PT J
AU Rodrik-Outmezguine, VS
   Okaniwa, M
   Yao, Z
   Novotny, CJ
   McWhirter, C
   Banaji, A
   Won, H
   Wong, W
   Berger, M
   de Stanchina, E
   Barratt, DG
   Cosulich, S
   Klinowska, T
   Rosen, N
   Shokat, KM
AF Rodrik-Outmezguine, Vanessa S.
   Okaniwa, Masanori
   Yao, Zhan
   Novotny, Chris J.
   McWhirter, Claire
   Banaji, Arpitha
   Won, Helen
   Wong, Wai
   Berger, Mike
   de Stanchina, Elisa
   Barratt, Derek G.
   Cosulich, Sabina
   Klinowska, Teresa
   Rosen, Neal
   Shokat, Kevan M.
TI Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor
SO NATURE
LA English
DT Article
ID protein; kinase; everolimus; phosphorylation; feedback; ligands
AB Precision medicines exert selective pressure on tumour cells that leads to the preferential growth of resistant subpopulations, necessitating the development of next-generation therapies to treat the evolving cancer. The PIK3CA-AKT-mTOR pathway is one of the most commonly activated pathways in human cancers(1), which has led to the development of small-molecule inhibitors that target various nodes in the pathway. Among these agents, first-generation mTOR inhibitors (rapalogs) have caused responses in 'N-of-1' cases, and second-generation mTOR kinase inhibitors (TORKi) are currently in clinical trials(2-4). Here we sought to delineate the likely resistance mechanisms to existing mTOR inhibitors in human cell lines, as a guide for next-generation therapies. The mechanism of resistance to the TORKi was unusual in that intrinsic kinase activity of mTOR was increased, rather than a direct active-site mutation interfering with drug binding. Indeed, identical drug-resistant mutations have been also identified in drug-naive patients, suggesting that tumours with activating MTOR mutations will be intrinsically resistant to second-generation mTOR inhibitors. We report the development of a new class of mTOR inhibitors that overcomes resistance to existing first-and second-generation inhibitors. The third-generation mTOR inhibitor exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction that allows inhibition of these resistant mutants.
C1 [Rodrik-Outmezguine, Vanessa S.; Yao, Zhan; Banaji, Arpitha; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol, New York, NY 10065 USA.
   [Okaniwa, Masanori; Novotny, Chris J.; Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Okaniwa, Masanori; Novotny, Chris J.; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [McWhirter, Claire; Barratt, Derek G.; Cosulich, Sabina; Klinowska, Teresa] AstraZeneca, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England.
   [Won, Helen; Berger, Mike] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Wong, Wai; de Stanchina, Elisa] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Core, New York, NY 10065 USA.
   [Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Shokat, Kevan M.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
C3 Memorial Sloan Kettering Cancer Center; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; AstraZeneca; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of California System; University of California Berkeley
RP Rosen, N (corresponding author), Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol, New York, NY 10065 USA.; Shokat, KM (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.; Shokat, KM (corresponding author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.; Rosen, N (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.; Shokat, KM (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM rosenn@mskcc.org; kevan.shokat@ucsf.edu
FU National Institutes of Health (NIH) [P01 CA094060]; Breast Cancer Research Foundation; National Cancer Institute Cancer Center [P30 CA008748]; Commonwealth Foundation for Cancer Research; Center for Experimental Therapeutics at Memorial Sloan Kettering Cancer Center; NIH [P50 AA017072]; Stand Up 2 Cancer Lung Cancer Dream Team; Samuel Waxman Cancer Research Foundation; Howard Hughes Medical Institute; National Cancer Institute [P01CA129243, P30CA008748] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM064337] Funding Source: NIH RePORTER
NR 29
TC 383
Z9 455
U1 1
U2 147
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 272
EP +
DI 10.1038/nature17963
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100046
PM 27279227
DA 2026-03-09
ER

PT J
AU Ballandras-Colas, A
   Browne, M
   Cook, NJ
   Dewdney, TG
   Domeler, B
   Cherepanov, P
   Lyumkis, D
   Engelman, AN
AF Ballandras-Colas, Allison
   Browne, Monica
   Cook, Nicola J.
   Dewdney, Tamaria G.
   Domeler, Barrios
   Cherepanov, Peter
   Lyumkis, Dmitry
   Engelman, Alan N.
TI Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function
SO NATURE
LA English
DT Article
ID sarcoma-virus integrase; viral-dna ends; photo-cross-linking; division-of-labor; hiv-1 integrase; in-vitro; macromolecular structures; retroviral integration; crystal-structure; strand transfer
AB Retroviral integrase catalyses the integration of viral DNA into host target DNA, which is an essential step in the life cycle of all retroviruses(1). Previous structural characterization of integrase-viral DNA complexes, or intasomes, from the spumavirus prototype foamy virus revealed a functional integrase tetramer(2-)5, and it is generally believed that intasomes derived from other retroviral genera use tetrameric integrase(6-9). However, the intasomes of orthoretroviruses, which include all known pathogenic species, have not been characterized structurally. Here, using single-particle cryo-electron microscopy and X-ray crystallography, we determine an unexpected octameric integrase architecture for the intasome of the betaretrovirus mouse mammary tumour virus. The structure is composed of two core integrase dimers, which interact with the viral DNA ends and structurally mimic the integrase tetramer of prototype foamy virus, and two flanking integrase dimers that engage the core structure via their integrase carboxy-terminal domains. Contrary to the belief that tetrameric integrase components are sufficient to catalyse integration, the flanking integrase dimers were necessary for mouse mammary tumour virus integrase activity. The integrase octamer solves a conundrum for betaretroviruses as well as alpharetroviruses by providing critical carboxy-terminal domains to the intasome core that cannot be provided in cis because of evolutionarily restrictive catalytic core domain-carboxy-terminal domain linker regions. The octameric architecture of the intasome of mouse mammary tumour virus provides new insight into the structural basis of retroviral DNA integration.
C1 [Ballandras-Colas, Allison; Dewdney, Tamaria G.; Engelman, Alan N.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & Virol, 450 Brookline Ave, Boston, MA 02215 USA.
   [Ballandras-Colas, Allison; Dewdney, Tamaria G.; Engelman, Alan N.] Harvard Univ, Dept Med, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA.
   [Browne, Monica; Lyumkis, Dmitry] Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Browne, Monica; Lyumkis, Dmitry] Salk Inst Biol Studies, Helmsley Ctr Genom Med, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Cook, Nicola J.; Cherepanov, Peter] Imperial Canc Res Fund, Clare Hall Labs, Francis Crick Inst, Potters Bar EN6 3LD, Herts, England.
   [Domeler, Barrios] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
   [Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, St Marys Campus,Norfolk Pl, London W2 1PG, England.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Salk Institute; Salk Institute; University of Texas System; University of Texas at San Antonio; Imperial College London
RP Engelman, AN (corresponding author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & Virol, 450 Brookline Ave, Boston, MA 02215 USA.; Engelman, AN (corresponding author), Harvard Univ, Dept Med, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA.; Lyumkis, D (corresponding author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.; Lyumkis, D (corresponding author), Salk Inst Biol Studies, Helmsley Ctr Genom Med, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM dlyumkis@salk.edu; alan.engelman@dfci.harvard.edu
FU US National Institutes of Health (NIH) [R01 AI070042]; NIH [P50 GM103368, P50 GM082251, P30 AI060354, P41 GM103331]; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; US National Science Foundation [NSF-ACI-1339649, TG-MCB070039]; San Antonio Cancer Institute [CA054174]; Cancer Research UK [15272] Funding Source: researchfish; The Francis Crick Institute [10061] Funding Source: researchfish; National Cancer Institute [P30CA054174, P30CA014195] Funding Source: NIH RePORTER; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Nursing Research; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Heart Lung and Blood Institute [P30AI060354] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103310] Funding Source: NIH RePORTER
NR 60
TC 71
Z9 76
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 358
EP +
DI 10.1038/nature16955
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100042
PM 26887496
DA 2026-03-09
ER

PT J
AU Bienfait, A
   Pla, JJ
   Kubo, Y
   Zhou, X
   Stern, M
   Lo, CC
   Weis, CD
   Schenkel, T
   Vion, D
   Esteve, D
   Morton, JJL
   Bertet, P
AF Bienfait, A.
   Pla, J. J.
   Kubo, Y.
   Zhou, X.
   Stern, M.
   Lo, C. C.
   Weis, C. D.
   Schenkel, T.
   Vion, D.
   Esteve, D.
   Morton, J. J. L.
   Bertet, P.
TI Controlling spin relaxation with a cavity
SO NATURE
LA English
DT Article
ID spontaneous emission; resonance experiments; silicon; polarization; microcavity; donors
AB Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized(1) that the rate of spontaneous emission can be greatly enhanced by placing the quantum system in a resonant cavity. This effect has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave(2) or optical(3,4) cavities, and is essential for the realization of high-efficiency single-photon sources(5). Here we report the application of this idea to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity with a high quality factor and a small mode volume, we reach the regime in which spontaneous emission constitutes the dominant mechanism of spin relaxation. The relaxation rate is increased by three orders of magnitude as the spins are tuned to the cavity resonance, demonstrating that energy relaxation can be controlled on demand. Our results provide a general way to initialize spin systems into their ground state and therefore have applications in magnetic resonance and quantum information processing(6). They also demonstrate that the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point at which quantum fluctuations have a marked effect on the spin dynamics; as such, they represent an important step towards the coherent magnetic coupling of individual spins to microwave photons.
C1 [Bienfait, A.; Kubo, Y.; Zhou, X.; Stern, M.; Vion, D.; Esteve, D.; Bertet, P.] Univ Paris Saclay, CEA Saclay, CNRS, Quantron Grp,SPEC,CEA, F-91191 Gif Sur Yvette, France.
   [Pla, J. J.; Lo, C. C.; Morton, J. J. L.] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Zhou, X.] CNRS, UMR 8520, ISEN Dept, Inst Elect Microelect & Nanotechnol, Ave Poincare,CS 60069, F-59652 Villeneuve Dascq, France.
   [Stern, M.] Bar Ilan Univ, BINA, Quantum Nanoelect Lab, Ramat Gan, Israel.
   [Weis, C. D.; Schenkel, T.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Accelerator Technol & Appl Phys Div, Berkeley, CA 94720 USA.
   [Pla, J. J.] Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW 2052, Australia.
   [Kubo, Y.] Okinawa Inst Sci & Technol, Grad Univ, Onna, Okinawa 9040495, Japan.
C3 CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; University of London; University College London; Centre National de la Recherche Scientifique (CNRS); Universite Polytechnique Hauts-de-France; Universite de Lille; CNRS - Institute for Engineering & Systems Sciences (INSIS); Bar Ilan University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of New South Wales Sydney; Okinawa Institute of Science & Technology Graduate University
RP Bertet, P (corresponding author), Univ Paris Saclay, CEA Saclay, CNRS, Quantron Grp,SPEC,CEA, F-91191 Gif Sur Yvette, France.
EM patrice.bertet@cea.fr
FU European Research Council under the European Community [615767, 279781, 630070]; C'Nano IdF project QUANTROCRYO; Royal Society; Royal Commission; US Department of Energy [DE-AC02-05CH11231]; European Research Council (ERC) [279781] Funding Source: European Research Council (ERC); Engineering and Physical Sciences Research Council [EP/K025945/1, EP/I035536/2, EP/H025952/2] Funding Source: researchfish; EPSRC [EP/H025952/2, EP/K025945/1, EP/I035536/2] Funding Source: UKRI
NR 40
TC 145
Z9 165
U1 2
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 74
EP +
DI 10.1038/nature16944
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900042
PM 26878235
DA 2026-03-09
ER

PT J
AU Lee, KS
   Huang, XY
   Fitzpatrick, D
AF Lee, Kuo-Sheng
   Huang, Xiaoying
   Fitzpatrick, David
TI Topology of ON and OFF inputs in visual cortex enables an invariant columnar architecture
SO NATURE
LA English
DT Article
ID simple receptive-fields; shrew striate cortex; tree shrew; simple cells; orientation selectivity; spatial structure; ocular dominance; organization; arrangement; connections
AB Circuits in the visual cortex integrate the information derived from separate ON (light-responsive) and OFF (dark-responsive) pathways to construct orderly columnar representations of stimulus orientation and visual space(1-7). How this transformation is achieved to meet the specific topographic constraints of each representation remains unclear. Here we report several novel features of ON-OFF convergence visualized by mapping the receptive fields of layer 2/3 neurons in the tree shrew (Tupaia belangeri) visual cortex using two-photon imaging of GCaMP6 calcium signals. We show that the spatially separate ON and OFF subfields of simple cells in layer 2/3 exhibit topologically distinct relationships with the maps of visual space and orientation preference. The centres of OFF subfields for neurons in a given region of cortex are confined to a compact region of visual space and display a smooth visuotopic progression. By contrast, the centres of the ON subfields are distributed over a wider region of visual space, display substantial visuotopic scatter, and have an orientation-specific displacement consistent with orientation preference map structure. As a result, cortical columns exhibit an invariant aggregate receptive field structure: an OFF-dominated central region flanked by ON-dominated subfields. This distinct arrangement of ON and OFF inputs enables continuity in the mapping of both orientation and visual space and the generation of a columnar map of absolute spatial phase.
C1 [Lee, Kuo-Sheng; Huang, Xiaoying; Fitzpatrick, David] Max Planck Florida Inst Neurosci, Dept Funct Architecture & Dev Cerebral Cortex, Jupiter, FL 33458 USA.
   [Lee, Kuo-Sheng] Florida Atlantic Univ, Integrat Biol & Neurosci Grad Program, Boca Raton, FL 33431 USA.
C3 Max Planck Society; State University System of Florida; Florida Atlantic University
RP Fitzpatrick, D (corresponding author), Max Planck Florida Inst Neurosci, Dept Funct Architecture & Dev Cerebral Cortex, Jupiter, FL 33458 USA.
EM david.fitzpatrick@mpfi.org
FU US National Institutes of Health; Max Planck Florida Institute for Neuroscience; Max Planck Society
NR 40
TC 101
Z9 114
U1 0
U2 31
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 90
EP +
DI 10.1038/nature17941
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900045
PM 27120162
DA 2026-03-09
ER

PT J
AU Chouchani, ET
   Kazak, L
   Jedrychowski, MP
   Lu, GNZ
   Erickson, BK
   Szpyt, J
   Pierce, KA
   Laznik-Bogoslavski, D
   Vetrivelan, R
   Clish, CB
   Robinson, AJ
   Gygi, SP
   Spiegelman, BM
AF Chouchani, Edward T.
   Kazak, Lawrence
   Jedrychowski, Mark P.
   Lu, Gina Z.
   Erickson, Brian K.
   Szpyt, John
   Pierce, Kerry A.
   Laznik-Bogoslavski, Dina
   Vetrivelan, Ramalingam
   Clish, Clary B.
   Robinson, Alan J.
   Gygi, Steve P.
   Spiegelman, Bruce M.
TI Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1
SO NATURE
LA English
DT Article
ID multiple sequence alignment; brown adipose-tissue; uncoupling protein-1; mass-spectrometry; chemical probes; redox state; adipocytes; expression; dimedone; fat
AB Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1)(1,2). Thermogenesis from these adipocytes can combat obesity and diabetes(3), encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders.
C1 [Chouchani, Edward T.; Kazak, Lawrence; Lu, Gina Z.; Laznik-Bogoslavski, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
   [Chouchani, Edward T.; Kazak, Lawrence; Jedrychowski, Mark P.; Lu, Gina Z.; Erickson, Brian K.; Szpyt, John; Gygi, Steve P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Pierce, Kerry A.; Clish, Clary B.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Vetrivelan, Ramalingam] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
   [Robinson, Alan J.] MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School
RP Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.; Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU JPB Foundation; National Institutes of Health [DK31405]; Human Frontiers Science Program; Canadian Institutes for Health Research; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER; MRC [MC_U105674181] Funding Source: UKRI; Medical Research Council [MC_U105674181] Funding Source: researchfish
NR 50
TC 378
Z9 434
U1 6
U2 220
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 112
EP +
DI 10.1038/nature17399
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500044
PM 27027295
DA 2026-03-09
ER

PT J
AU Takeuchi, T
   Duszkiewicz, AJ
   Sonneborn, A
   Spooner, PA
   Yamasaki, M
   Watanabe, M
   Smith, CC
   Fernández, G
   Deisseroth, K
   Greene, RW
   Morris, RGM
AF Takeuchi, Tomonori
   Duszkiewicz, Adrian J.
   Sonneborn, Alex
   Spooner, Patrick A.
   Yamasaki, Miwako
   Watanabe, Masahiko
   Smith, Caroline C.
   Fernandez, Guillen
   Deisseroth, Karl
   Greene, Robert W.
   Morris, Richard G. M.
TI Locus coeruleus and dopaminergic consolidation of everyday memory
SO NATURE
LA English
DT Article
ID long-term potentiation; protein-synthesis; ca1 region; neurons; receptors; expression; novelty; rat; information; acquisition
AB The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH+) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH+ neurons project more profusely than ventral tegmental area TH+ neurons to the hippocampus, optogenetic activation of locus coeruleus TH+ neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation. Surprisingly, two effects of locus coeruleus TH+ photoactivation are sensitive to hippocampal D-1/D-5 receptor blockade and resistant to adrenoceptor blockade: memory enhancement and long-lasting potentiation of synaptic transmission in CA1 ex vivo. Thus, locus coeruleus TH+ neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in the hippocampus.
C1 [Takeuchi, Tomonori; Duszkiewicz, Adrian J.; Spooner, Patrick A.; Morris, Richard G. M.] Univ Edinburgh, Edinburgh Neurosci, Ctr Cognit & Neural Syst, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Sonneborn, Alex; Smith, Caroline C.; Greene, Robert W.] Univ Texas Southwestern Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
   [Yamasaki, Miwako; Watanabe, Masahiko] Hokkaido Univ, Dept Anat, Grad Sch Med, Sapporo, Hokkaido 0608638, Japan.
   [Fernandez, Guillen] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Med Ctr, NL-6525 EZ Nijmegen, Netherlands.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Greene, Robert W.] Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki 3058575, Japan.
   [Morris, Richard G. M.] CSIC UMH, Inst Neurociencias, Alicante 03550, Spain.
C3 University of Edinburgh; University of Texas System; University of Texas Southwestern Medical Center; Hokkaido University; Radboud University Nijmegen; Stanford University; Stanford University; University of Tsukuba; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Miguel Hernandez de Elche; CSIC-UMH - Instituto de Neurociencias de Alicante (IN)
RP Morris, RGM (corresponding author), Univ Edinburgh, Edinburgh Neurosci, Ctr Cognit & Neural Syst, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.; Greene, RW (corresponding author), Univ Texas Southwestern Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.; Greene, RW (corresponding author), Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki 3058575, Japan.; Morris, RGM (corresponding author), CSIC UMH, Inst Neurociencias, Alicante 03550, Spain.
EM robertw.greene@utsouthwestern.edu; R.G.M.Morris@ed.ac.uk
FU European Research Council [ERC-2010-AdG-268800-NEUROSCHEMA]; UK Medical Research Council; European Commission [600725-GRIDMAP]; Department Veterans Affairs, National Institutes of Health [5R01MH080297];  [NIDA-T32-DA7290]; Medical Research Council [G0700447, MC_UU_12024/3, 1177572, MC_UU_12024/1, 1101577, MC_UU_12020/7] Funding Source: researchfish; MRC [G0700447] Funding Source: UKRI
NR 59
TC 549
Z9 645
U1 4
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 357
EP +
DI 10.1038/nature19325
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000045
PM 27602521
DA 2026-03-09
ER

PT J
AU Ataman, B
   Boulting, GL
   Harmin, DA
   Yang, MG
   Baker-Salisbury, M
   Yap, EL
   Malik, AN
   Mei, K
   Rubin, AA
   Spiegel, I
   Durresi, E
   Sharma, N
   Hu, LDS
   Pletikos, M
   Griffith, EC
   Partlow, JN
   Stevens, CR
   Adli, M
   Chahrour, M
   Sestan, N
   Walsh, CA
   Berezovskii, VK
   Livingstone, MS
   Greenberg, ME
AF Ataman, Bulent
   Boulting, Gabriella L.
   Harmin, David A.
   Yang, Marty G.
   Baker-Salisbury, Mollie
   Yap, Ee-Lynn
   Malik, Athar N.
   Mei, Kevin
   Rubin, Alex A.
   Spiegel, Ivo
   Durresi, Ershela
   Sharma, Nikhil
   Hu, Linda S.
   Pletikos, Mihovil
   Griffith, Eric C. .
   Partlow, Jennifer N.
   Stevens, Christine R.
   Adli, Mazhar
   Chahrour, Maria
   Sestan, Nenad
   Walsh, Christopher A.
   Berezovskii, Vladimir K.
   Livingstone, Margaret S.
   Greenberg, Michael E.
TI Evolution of Osteocrin as an activity-regulated factor in the primate brain
SO NATURE
LA English
DT Article
ID differential expression analysis; gene-expression; cortical inhibition; cerebral-cortex; striate cortex; visual-cortex; stem-cells; neurons; transcription; enhancers
AB Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species-or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates.
C1 [Ataman, Bulent; Boulting, Gabriella L.; Harmin, David A.; Yang, Marty G.; Baker-Salisbury, Mollie; Yap, Ee-Lynn; Malik, Athar N.; Mei, Kevin; Rubin, Alex A.; Spiegel, Ivo; Durresi, Ershela; Sharma, Nikhil; Hu, Linda S.; Griffith, Eric C. .; Berezovskii, Vladimir K.; Livingstone, Margaret S.; Greenberg, Michael E.] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.
   [Pletikos, Mihovil; Sestan, Nenad] Yale Sch Med, Dept Neurosci, New Haven, CT 06510 USA.
   [Pletikos, Mihovil; Sestan, Nenad] Yale Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
   [Partlow, Jennifer N.; Walsh, Christopher A.] Harvard Med Sch, Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA.
   [Stevens, Christine R.] Broad Inst & Harvard, Cambridge, MA 02142 USA.
   [Adli, Mazhar] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22903 USA.
   [Chahrour, Maria] Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, MvDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
C3 Harvard University; Harvard Medical School; Yale University; Yale University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Virginia; University of Texas System; University of Texas Southwestern Medical Center
RP Greenberg, ME (corresponding author), Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.
EM meg@hms.harvard.edu
FU NIH [P50MH106933, 1RC2MH089952, 5F32NS086270, EY16187, EY12196, T32GM007753]; Ellen R. and Melvin J. Gordon Center for the Cure and Treatment of Paralysis; National Eye Institute [R01EY016187, P30EY012196] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 45
TC 113
Z9 141
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 242
EP +
DI 10.1038/nature20111
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500035
PM 27830782
DA 2026-03-09
ER

PT J
AU Tremblay, GR
   Oonk, JBR
   Combes, F
   Salomé, P
   O'Dea, CP
   Baum, SA
   Voit, GM
   Donahue, M
   McNamara, BR
   Davis, TA
   McDonald, MA
   Edge, AC
   Clarke, TE
   Galván-Madrid, R
   Bremer, MN
   Edwards, LOV
   Fabian, AC
   Hamer, S
   Li, Y
   Maury, A
   Russell, HR
   Quillen, AC
   Urry, CM
   Sanders, JS
   Wise, MW
AF Tremblay, Grant R.
   Oonk, J. B. Raymond
   Combes, Franoise
   Salome, Philippe
   O'Dea, Christopher P.
   Baum, Stefi A.
   Voit, G. Mark
   Donahue, Megan
   McNamara, Brian R.
   Davis, Timothy A.
   McDonald, Michael A.
   Edge, Alastair C.
   Clarke, Tracy E.
   Galvan-Madrid, Roberto
   Bremer, Malcolm N.
   Edwards, Louise O. V.
   Fabian, Andrew C.
   Hamer, Stephen
   Li, Yuan
   Maury, Anaelle
   Russell, Helen R.
   Quillen, Alice C.
   Urry, C. Megan
   Sanders, Jeremy S.
   Wise, Michael W.
TI Cold, clumpy accretion onto an active supermassive black hole
SO NATURE
LA English
DT Article
ID galactic nucleus feedback; h i absorption; star-formation; molecular gas; core clusters; flow; precipitation; filaments; emission; a2597
AB Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales(1-3). The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas(4). Recent theory(5-7) and simulations(8-10) instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds-a departure from the 'hot mode' accretion model-although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z = 0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma(11-13). Under the right conditions, thermal instabilities produce a rain of cold clouds that fall towards the galaxy's centre(14), sustaining star formation amid a kiloparsec-scale molecular nebula that is found at its core(15). The observations show that these cold clouds also fuel black hole accretion, revealing 'shadows' cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole, which serves as a bright backlight. Corroborating evidence from prior observations(16) of warmer atomic gas at extremely high spatial resolution(17), along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it.
C1 [Tremblay, Grant R.; Edwards, Louise O. V.; Urry, C. Megan] Yale Univ, Yale Ctr Astron & Astrophys, 52 Hillhouse Ave, New Haven, CT 06511 USA.
   [Tremblay, Grant R.; Davis, Timothy A.; Galvan-Madrid, Roberto] European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
   [Oonk, J. B. Raymond; Wise, Michael W.] Netherlands Inst Radio Astron, ASTRON, POB 2, NL-7990 AA Dwingeloo, Netherlands.
   [Oonk, J. B. Raymond] Leiden Univ, Leiden Observ, Niels Borhweg 2, NL-2333 CA Leiden, Netherlands.
   [Combes, Franoise; Salome, Philippe; Hamer, Stephen] Univ Paris 04, CNRS, Lab Studies Radiat & Matter Astrophys & Atmospher, PSL Res Univ,Observ Paris,Coll France, Paris, France.
   [O'Dea, Christopher P.; Baum, Stefi A.] Univ Manitoba, Dept Phys & Astron, Winnipeg, MB R3T 2N2, Canada.
   [O'Dea, Christopher P.] Rochester Inst Technol, Sch Phys & Astron, 84 Lomb Mem Dr, Rochester, NY 14623 USA.
   [Baum, Stefi A.] Rochester Inst Technol, Chester F Carlson Ctr Imaging Sci, 84 Lomb Mem Dr, Rochester, NY 14623 USA.
   [Voit, G. Mark; Donahue, Megan] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [McNamara, Brian R.] Univ Waterloo, Dept Phys & Astron, 200 Univ Ave West, Waterloo, ON N2L 2GL, Canada.
   [Davis, Timothy A.] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, S Glam, Wales.
   [McDonald, Michael A.] MIT, Kavli Inst Astrophys & Space Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Edge, Alastair C.] Univ Durham, Dept Phys, Durham DHL 3LE, England.
   [Clarke, Tracy E.] Naval Res Lab, Remote Sensing Div, Code 7213,4555 Overlook Ave Southwest, Washington, DC 20375 USA.
   [Galvan-Madrid, Roberto] UNAM, Inst Radioastron & Astrofis, Apartado Postal 3-72 Xangari, Morelia 58089, Michoacan, Mexico.
   [Bremer, Malcolm N.] Univ Bristol, HW Wills Phys Lab, Tyndall Ave, Bristol BS8 1TL, Avon, England.
   [Fabian, Andrew C.; Russell, Helen R.] Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
   [Li, Yuan] Univ Michigan, Dept Astron, 1085 South Univ Ave, Ann Arbor, MI 48109 USA.
   [Maury, Anaelle] Univ Paris Diderot, CE Saclay, CNRS, CEA DSM Irfu,Lab AIM Paris Saclay, F-91191 Gif Sur Yvette, France.
   [Quillen, Alice C.] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA.
   [Sanders, Jeremy S.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
C3 Yale University; European Southern Observatory; Leiden University; Leiden University - Excl LUMC; Universite PSL; College de France; Sorbonne Universite; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); University of Manitoba; Rochester Institute of Technology; Rochester Institute of Technology; Michigan State University; University of Waterloo; Cardiff University; Massachusetts Institute of Technology (MIT); Durham University; United States Department of Defense; United States Navy; United States Naval Research Laboratory; Universidad Nacional Autonoma de Mexico; University of Bristol; University of Cambridge; University of Michigan System; University of Michigan; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of Rochester; Max Planck Society
RP Tremblay, GR (corresponding author), Yale Univ, Yale Ctr Astron & Astrophys, 52 Hillhouse Ave, New Haven, CT 06511 USA.; Tremblay, GR (corresponding author), European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
EM grant.tremblay@yale.edu
FU National Aeronautics and Space Administration (NASA) [PF-150128]; NASA [NAS8-03060]; European Research Council (ERC) [267399-Momentum]; Natural Sciences and Engineering Research Council of Canada; Science and Technology Facilities Council (STFC) Ernest Rutherford Fellowship; STFC [ST/L00075X/1]; ERC [340442-Feedback]; 6.1 Base funding; Science and Technology Facilities Council [ST/L004496/2, ST/N000927/1, ST/L004496/1, ST/L005042/1, ST/M000907/1, ST/L00075X/1] Funding Source: researchfish; STFC [ST/M000907/1, ST/L005042/1, ST/L004496/2, ST/L004496/1, ST/L00075X/1] Funding Source: UKRI
NR 34
TC 151
Z9 158
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 218
EP +
DI 10.1038/nature17969
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100034
PM 27279215
DA 2026-03-09
ER

PT J
AU Liu, M
   Pang, YJ
   Zhang, B
   De Luna, P
   Voznyy, O
   Xu, JX
   Zheng, XL
   Dinh, CT
   Fan, FJ
   Cao, CH
   de Arquer, FPG
   Safaei, TS
   Mepham, A
   Klinkova, A
   Kumacheva, E
   Filleter, T
   Sinton, D
   Kelley, SO
   Sargent, EH
AF Liu, Min
   Pang, Yuanjie
   Zhang, Bo
   De Luna, Phil
   Voznyy, Oleksandr
   Xu, Jixian
   Zheng, Xueli
   Dinh, Cao Thang
   Fan, Fengjia
   Cao, Changhong
   de Arquer, F. Pelayo Garcia
   Safaei, Tina Saberi
   Mepham, Adam
   Klinkova, Anna
   Kumacheva, Eugenia
   Filleter, Tobin
   Sinton, David
   Kelley, Shana O.
   Sargent, Edward H.
TI Enhanced electrocatalytic CO2 reduction via field-induced reagent concentration
SO NATURE
LA English
DT Article
ID carbon-dioxide; selective conversion; au nanoparticles; electroreduction; efficiency; catalysts; step
AB Electrochemical reduction of carbon dioxide (CO2) to carbon monoxide (CO) is the first step in the synthesis of more complex carbon-based fuels and feedstocks using renewable electricity(1-7). Unfortunately, the reaction suffers from slow kinetics(7,8) owing to the low local concentration of CO2 surrounding typical CO2 reduction reaction catalysts. Alkali metal cations are known to overcome this limitation through non-covalent interactions with adsorbed reagent species(9,10), but the effect is restricted by the solubility of relevant salts. Large applied electrode potentials can also enhance CO2 adsorption(11), but this comes at the cost of increased hydrogen (H-2) evolution. Here we report that nanostructured electrodes produce, at low applied overpotentials, local high electric fields that concentrate electrolyte cations, which in turn leads to a high local concentration of CO2 close to the active CO2 reduction reaction surface. Simulations reveal tenfold higher electric fields associated with metallic nanometre-sized tips compared to quasi-planar electrode regions, and measurements using gold nanoneedles confirm a field-induced reagent concentration that enables the CO2 reduction reaction to proceed with a geometric current density for CO of 22 milliamperes per square centimetre at -0.35 volts (overpotential of 0.24 volts). This performance surpasses by an order of magnitude the performance of the best gold nanorods, nanoparticles and oxide-derived noble metal catalysts. Similarly designed palladium nanoneedle electrocatalysts produce formate with a Faradaic efficiency of more than 90 per cent and an unprecedented geometric current density for formate of 10 milliamperes per square centimetre at -0.2 volts, demonstrating the wider applicability of the field-induced reagent concentration concept.
C1 [Liu, Min; Zhang, Bo; Voznyy, Oleksandr; Xu, Jixian; Zheng, Xueli; Dinh, Cao Thang; Fan, Fengjia; de Arquer, F. Pelayo Garcia; Safaei, Tina Saberi; Sargent, Edward H.] Univ Toronto, Dept Elect & Comp Engn, 35 St George St, Toronto, ON M5S 1A4, Canada.
   [Pang, Yuanjie; Cao, Changhong; Filleter, Tobin; Sinton, David] Univ Toronto, Dept Mech & Ind Engn, 5 Kings Coll Rd, Toronto, ON M5S 3G8, Canada.
   [Zhang, Bo] East China Univ Sci & Technol, Dept Phys, 130 Meilong Rd, Shanghai 200237, Peoples R China.
   [De Luna, Phil] Univ Toronto, Dept Mat Sci & Engn, 184 Coll St, Toronto, ON M5S 3E4, Canada.
   [Zheng, Xueli] Tianjin Univ, Sch Mat Sci & Engn, Tianjin Key Lab Composite & Funct Mat, Tianjin 300072, Peoples R China.
   [Mepham, Adam; Kelley, Shana O.] Univ Toronto, Inst Biomat & Biomed Engn, 164 Coll St, Toronto, ON M5S 3G9, Canada.
   [Klinkova, Anna; Kumacheva, Eugenia] Univ Toronto, Dept Chem, 80 St George St, Toronto, ON M5S 3H6, Canada.
   [Kelley, Shana O.] Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, 144 Coll St, Toronto, ON M5S 3M2, Canada.
   [Kelley, Shana O.] Univ Toronto, Dept Biochem, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University of Toronto; East China University of Science & Technology; University of Toronto; Tianjin University; University of Toronto; University of Toronto; University of Toronto; University of Toronto
RP Sargent, EH (corresponding author), Univ Toronto, Dept Elect & Comp Engn, 35 St George St, Toronto, ON M5S 1A4, Canada.
EM ted.sargent@utoronto.ca
FU Ontario Research Fund: Research Excellence programme; Natural Sciences and Engineering Research Council (NSERC) of Canada; CIFAR Bio-Inspired Solar Energy programme; University of Toronto Connaught grant; Shanghai Municipal Natural Science Foundation [14ZR1410200]; National Natural Science Foundation of China [21503079]; Southern Ontario Smart Computing Innovation Platform (SOSCIP)
NR 45
TC 1732
Z9 1880
U1 67
U2 2528
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 382
EP +
DI 10.1038/nature19060
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000050
PM 27487220
DA 2026-03-09
ER

PT J
AU Chen, YNP
   LaMarche, MJ
   Chan, HM
   Fekkes, P
   Garcia-Fortanet, J
   Acker, MG
   Antonakos, B
   Chen, CHT
   Chen, ZL
   Cooke, VG
   Dobson, JR
   Deng, Z
   Fei, F
   Firestone, B
   Fodor, M
   Fridrich, C
   Gao, H
   Grunenfelder, D
   Hao, HX
   Jacob, J
   Ho, S
   Hsiao, K
   Kang, ZB
   Karki, R
   Kato, M
   Larrow, J
   La Bonte, LR
   Lenoir, F
   Liu, G
   Liu, SM
   Majumdar, D
   Meyer, MJ
   Palermo, M
   Perez, L
   Pu, MY
   Price, E
   Quinn, C
   Shakya, S
   Shultz, MD
   Slisz, J
   Venkatesan, K
   Wang, P
   Warmuth, M
   Williams, S
   Yang, GZ
   Yuan, J
   Zhang, JH
   Zhu, P
   Ramsey, T
   Keen, NJ
   Sellers, WR
   Stams, T
   Fortin, PD
AF Chen, Ying-Nan P.
   LaMarche, Matthew J.
   Chan, Ho Man
   Fekkes, Peter
   Garcia-Fortanet, Jorge
   Acker, Michael G.
   Antonakos, Brandon
   Chen, Christine Hiu-Tung
   Chen, Zhouliang
   Cooke, Vesselina G.
   Dobson, Jason R.
   Deng, Zhan
   Fei, Feng
   Firestone, Brant
   Fodor, Michelle
   Fridrich, Cary
   Gao, Hui
   Grunenfelder, Denise
   Hao, Huai-Xiang
   Jacob, Jaison
   Ho, Samuel
   Hsiao, Kathy
   Kang, Zhao B.
   Karki, Rajesh
   Kato, Mitsunori
   Larrow, Jay
   La Bonte, Laura R.
   Lenoir, Francois
   Liu, Gang
   Liu, Shumei
   Majumdar, Dyuti
   Meyer, Matthew J.
   Palermo, Mark
   Perez, Lawrence
   Pu, Minying
   Price, Edmund
   Quinn, Christopher
   Shakya, Subarna
   Shultz, Michael D.
   Slisz, Joanna
   Venkatesan, Kavitha
   Wang, Ping
   Warmuth, Markus
   Williams, Sarah
   Yang, Guizhi
   Yuan, Jing
   Zhang, Ji-Hu
   Zhu, Ping
   Ramsey, Timothy
   Keen, Nicholas J.
   Sellers, William R.
   Stams, Travis
   Fortin, Pascal D.
TI Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases
SO NATURE
LA English
DT Article
ID ptpn11; protooncogene; target; potent
AB The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase(1). Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma(1-5). SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS-ERK signalling pathway(2,3). It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways(6,7). Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy(8,9). Here we report the discovery of a highly potent (IC50 = 0.071 mu M), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.
C1 [Chen, Ying-Nan P.; LaMarche, Matthew J.; Chan, Ho Man; Fekkes, Peter; Garcia-Fortanet, Jorge; Acker, Michael G.; Antonakos, Brandon; Chen, Christine Hiu-Tung; Chen, Zhouliang; Cooke, Vesselina G.; Dobson, Jason R.; Deng, Zhan; Fei, Feng; Firestone, Brant; Fodor, Michelle; Fridrich, Cary; Gao, Hui; Grunenfelder, Denise; Hao, Huai-Xiang; Jacob, Jaison; Ho, Samuel; Hsiao, Kathy; Kang, Zhao B.; Karki, Rajesh; Kato, Mitsunori; Larrow, Jay; La Bonte, Laura R.; Lenoir, Francois; Liu, Gang; Liu, Shumei; Majumdar, Dyuti; Meyer, Matthew J.; Palermo, Mark; Perez, Lawrence; Pu, Minying; Price, Edmund; Quinn, Christopher; Shakya, Subarna; Shultz, Michael D.; Slisz, Joanna; Venkatesan, Kavitha; Wang, Ping; Warmuth, Markus; Williams, Sarah; Yang, Guizhi; Yuan, Jing; Zhang, Ji-Hu; Zhu, Ping; Ramsey, Timothy; Keen, Nicholas J.; Sellers, William R.; Stams, Travis; Fortin, Pascal D.] Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
C3 Novartis; Novartis USA
RP Sellers, WR; Stams, T; Fortin, PD (corresponding author), Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
EM william.sellers@novartis.com; travis.stams@novartis.com; pafortin@gmail.com
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
NR 29
TC 735
Z9 861
U1 5
U2 329
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 148
EP +
DI 10.1038/nature18621
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600042
PM 27362227
DA 2026-03-09
ER

PT J
AU Huang, CD
   Rossi, P
   Saio, T
   Kalodimos, CG
AF Huang, Chengdong
   Rossi, Paolo
   Saio, Tomohide
   Kalodimos, Charalampos G.
TI Structural basis for the antifolding activity of a molecular chaperone
SO NATURE
LA English
DT Article
ID maltose-binding protein; escherichia-coli; crystal-structure; chemical-shifts; quality-control; secb chaperone; nmr; system; disaggregation; recognition
AB Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.
C1 [Huang, Chengdong; Rossi, Paolo; Saio, Tomohide; Kalodimos, Charalampos G.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Kalodimos, CG (corresponding author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
EM ckalodim@umn.edu
FU National Institutes of Health [GM073854]
NR 42
TC 132
Z9 144
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 202
EP +
DI 10.1038/nature18965
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100041
PM 27501151
DA 2026-03-09
ER

PT J
AU Badoux, S
   Tabis, W
   Laliberté, F
   Grissonnanche, G
   Vignolle, B
   Vignolles, D
   Béard, J
   Bonn, DA
   Hardy, WN
   Liang, R
   Doiron-Leyraud, N
   Taillefer, L
   Proust, C
AF Badoux, S.
   Tabis, W.
   Laliberte, F.
   Grissonnanche, G.
   Vignolle, B.
   Vignolles, D.
   Beard, J.
   Bonn, D. A.
   Hardy, W. N.
   Liang, R.
   Doiron-Leyraud, N.
   Taillefer, Louis
   Proust, Cyril
TI Change of carrier density at the pseudogap critical point of a cuprate superconductor
SO NATURE
LA English
DT Article
ID fermi-surface; quantum oscillations; single-crystals; state; dependence; scattering; order; tl2ba2cuo6+delta; transport; evolution
AB The pseudogap is a partial gap in the electronic density of states that opens in the normal (non-superconducting) state of cuprate superconductors and whose origin is a long-standing puzzle. Its connection to the Mott insulator phase at low doping (hole concentration, p) remains ambiguous(1) and its relation to the charge order(2-4) that reconstructs the Fermi surface(5,6) at intermediate doping is still unclear(7-10). Here we use measurements of the Hall coefficient in magnetic fields up to 88 tesla to show that Fermisurface reconstruction by charge order in the cuprate YBa2Cu3Oy ends sharply at a critical doping p = 0.16 that is distinctly lower than the pseudogap critical point p* = 0.19 (ref. 11). This shows that the pseudogap and charge order are separate phenomena. We find that the change in carrier density n from n = 1 + p in the conventional metal at high doping (ref. 12) to n = p at low doping (ref. 13) starts at the pseudogap critical point. This shows that the pseudogap and the antiferromagnetic Mott insulator are linked.
C1 [Badoux, S.; Grissonnanche, G.; Doiron-Leyraud, N.; Taillefer, Louis] Univ Sherbrooke, Dept Phys, Regrp Quebecois Mat Pointe, Sherbrooke, PQ J1K 2R1, Canada.
   [Tabis, W.; Laliberte, F.; Vignolle, B.; Vignolles, D.; Beard, J.; Proust, Cyril] UPS, Lab Natl Champs Magnet Intenses, CNRS, EMFL,INSA,UGA, F-31400 Toulouse, France.
   [Tabis, W.] AGH Univ Sci & Technol, Fac Phys & Appl Comp Sci, PL-30059 Krakow, Poland.
   [Bonn, D. A.; Hardy, W. N.; Liang, R.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Bonn, D. A.; Hardy, W. N.; Liang, R.; Taillefer, Louis; Proust, Cyril] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
C3 University of Sherbrooke; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite de Toulouse; Institut National des Sciences Appliquees de Toulouse; Universite Toulouse III - Paul Sabatier; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); AGH University of Krakow; University of British Columbia; Canadian Institute for Advanced Research (CIFAR)
RP Taillefer, L (corresponding author), Univ Sherbrooke, Dept Phys, Regrp Quebecois Mat Pointe, Sherbrooke, PQ J1K 2R1, Canada.; Proust, C (corresponding author), UPS, Lab Natl Champs Magnet Intenses, CNRS, EMFL,INSA,UGA, F-31400 Toulouse, France.; Taillefer, L; Proust, C (corresponding author), Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
EM louis.taillefer@usherbrooke.ca; cyril.proust@lncmi.cnrs.fr
FU LABEX NEXT; French ANR SUPERFIELD; EMFL; Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institute for Advanced Research (CIFAR); NSERC; Fonds de recherche du Quebec - Nature et Technologies (FRQNT); Canada Foundation for Innovation (CFI); Canada Research Chair
NR 39
TC 341
Z9 373
U1 3
U2 296
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 210
EP +
DI 10.1038/nature16983
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100036
PM 26901870
DA 2026-03-09
ER

PT J
AU de Wit, J
   Wakeford, HR
   Gillon, M
   Lewis, NK
   Valenti, JA
   Demory, BO
   Burgasser, AJ
   Burdanov, A
   Delrez, L
   Jehin, E
   Lederer, SM
   Queloz, D
   Triaud, AHMJ
   Van Grootel, V
AF de Wit, Julien
   Wakeford, Hannah R.
   Gillon, Michael
   Lewis, Nikole K.
   Valenti, Jeff A.
   Demory, Brice-Olivier
   Burgasser, Adam J.
   Burdanov, Artem
   Delrez, Laetitia
   Jehin, Emmanuel
   Lederer, Susan M.
   Queloz, Didier
   Triaud, Amaury H. M. J.
   Van Grootel, Valerie
TI A combined transmission spectrum of the Earth-sized exoplanets TRAPPIST-1 b and c
SO NATURE
LA English
DT Article
ID hubble-space-telescope; habitable-zone; light curves; super-earths; gj 1214b; spectroscopy; atmospheres; planets; kepler; evaporation
AB Three Earth-sized exoplanets were recently discovered close to the habitable zone(1,2) of the nearby ultracool dwarf star TRAPPIST-1 (ref. 3). The nature of these planets has yet to be determined, as their masses remain unmeasured and no observational constraint is available for the planetary population surrounding ultracool dwarfs, of which the TRAPPIST-1 planets are the first transiting example. Theoretical predictions span the entire atmospheric range, from depleted to extended hydrogen-dominated atmospheres(4-8). Here we report observations of the combined transmission spectrum of the two inner planets during their simultaneous transits on 4 May 2016. The lack of features in the combined spectrum rules out doud-free hydrogen-dominated atmospheres for each planet at >= 10 sigma levels; TRAPPIST-1 b and c are therefore unlikely to have an extended gas envelope as they occupy a region of parameter space in which high-altitude cloud/haze formation is not expected to be significant for hydrogen-dominated atmospheres(9). Many denser atmospheres remain consistent with the featureless transmission spectrum from a cloud-free water-vapour atmosphere to a Venus-like one.
C1 [de Wit, Julien] MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Wakeford, Hannah R.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Gillon, Michael; Burdanov, Artem; Delrez, Laetitia; Jehin, Emmanuel; Van Grootel, Valerie] Univ Liege, Inst Astrophys & Geophys, Allee 6 Aout 19C, B-4000 Liege, Belgium.
   [Lewis, Nikole K.; Valenti, Jeff A.] Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
   [Demory, Brice-Olivier; Queloz, Didier] Cavendish Lab, Astrophys Grp, 19 JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Burgasser, Adam J.] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
   [Lederer, Susan M.] NASA, Johnson Space Ctr, 2101 NASA Pkwy, Houston, TX 77058 USA.
   [Triaud, Amaury H. M. J.] Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
C3 Massachusetts Institute of Technology (MIT); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Liege; Space Telescope Science Institute; University of Cambridge; University of California System; University of California San Diego; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; University of Cambridge
RP de Wit, J (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jdewit@mit.edu
FU NASA through Space Telescope Science Institute [HST-GO-14500]; European Research Council (ERC) [336480]; Action de Recherche Concertee (ARC) by Wallonia-Brussels Federation; NASA; Fund for Research Training in Industry and Agriculture of the FRS-FNRS; European Research Council (ERC) [336480] Funding Source: European Research Council (ERC)
NR 26
TC 158
Z9 181
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 69
EP 72
DI 10.1038/nature18641
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900039
PM 27437572
DA 2026-03-09
ER

PT J
AU Pekel, JF
   Cottam, A
   Gorelick, N
   Belward, AS
AF Pekel, Jean-Francois
   Cottam, Andrew
   Gorelick, Noel
   Belward, Alan S.
TI High-resolution mapping of global surface water and its long-term changes
SO NATURE
LA English
DT Article
ID climate-change; time-series; lakes; resources; dynamics; imagery
AB The location and persistence of surface water (inland and coastal) is both affected by climate and human activity(1) and affects climate(2,3), biological diversity(4) and human wellbeing(5,6). Global data sets documenting surface water location and seasonality have been produced from inventories and national descriptions(7), statistical extrapolation of regional data(8) and satellite imagery(9-12), but measuring long-term changes at high resolution remains a challenge. Here, using three million Landsat satellite images(13), we quantify changes in global surface water over the past 32 years at 30-metre resolution. We record the months and years when water was present, where occurrence changed and what form changes took in terms of seasonality and persistence. Between 1984 and 2015 permanent surface water has disappeared from an area of almost 90,000 square kilometres, roughly equivalent to that of Lake Superior, though new permanent bodies of surface water covering 184,000 square kilometres have formed elsewhere. All continental regions show a net increase in permanent water, except Oceania, which has a fractional (one per cent) net loss. Much of the increase is from reservoir filling, although climate change(14) is also implicated. Loss is more geographically concentrated than gain. Over 70 per cent of global net permanent water loss occurred in the Middle East and Central Asia, linked to drought and human actions including river diversion or damming and unregulated withdrawal(15,16). Losses in Australia(17) and the USA(18) linked to long-term droughts are also evident. This globally consistent, validated data set shows that impacts of climate change and climate oscillations on surface water occurrence can be measured and that evidence can be gathered to show how surface water is altered by human activities. We anticipate that this freely available data will improve the modelling of surface forcing, provide evidence of state and change in wetland ecotones (the transition areas between biomes), and inform water-management decision-making.
C1 [Pekel, Jean-Francois; Cottam, Andrew; Belward, Alan S.] European Commiss, Joint Res Ctr, Directorate Sustainable Resources, I-20127 Ispra, Lombardy, Italy.
   [Gorelick, Noel] Google Switzerland GmbH, Brandschenkestr 110, CH-8002 Zurich, Switzerland.
C3 European Commission Joint Research Centre; EC JRC ISPRA Site; Alphabet Inc.; Google Incorporated
RP Pekel, JF (corresponding author), European Commiss, Joint Res Ctr, Directorate Sustainable Resources, I-20127 Ispra, Lombardy, Italy.
EM jean-francois.pekel@jrc.ec.europa.eu
NR 64
TC 3756
Z9 4377
U1 120
U2 2348
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 418
EP +
DI 10.1038/nature20584
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800039
PM 27926733
DA 2026-03-09
ER

PT J
AU Li, CY
   de Grijs, R
   Deng, LC
   Geller, AM
   Xin, Y
   Hu, Y
   Faucher-Giguère, CA
AF Li, Chengyuan
   de Grijs, Richard
   Deng, Licai
   Geller, Aaron M.
   Xin, Yu
   Hu, Yi
   Faucher-Giguere, Claude-Andre
TI Formation of new stellar populations from gas accreted by massive young star clusters
SO NATURE
LA English
DT Article
ID small-magellanic-cloud; main-sequence turnoffs; sub-giant branch; globular-clusters; multiple populations; milky-way; evolution; galaxy; enrichment; origin
AB Stars in clusters are thought to form in a single burst from a common progenitor cloud of molecular gas. However, massive, old 'globular' clusters-those with ages greater than ten billion years and masses several hundred thousand times that of the Sun-often harbour multiple stellar populations(1-4), indicating that more than one star-forming event occurred during their lifetimes. Colliding stellar winds from late-stage, asymptotic-giant-branch stars(5-7) are often suggested to be triggers of second-generation star formation. For this to occur(8), the initial cluster masses need to be greater than a few million solar masses. Here we report observations of three massive relatively young star clusters (1-2 billion years old) in the Magellanic Clouds that show clear evidence of burst-like star formation that occurred a few hundred million years after their initial formation era. We show that such clusters could have accreted sufficient gas to form new stars if they had orbited in their host galaxies' gaseous disks throughout the period between their initial formation and the more recent bursts of star formation. This process may eventually give rise to the ubiquitous multiple stellar populations in globular clusters.
C1 [Li, Chengyuan; de Grijs, Richard] Peking Univ, Kavli Inst Astron & Astrophys, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.
   [Li, Chengyuan; de Grijs, Richard] Peking Univ, Dept Astron, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.
   [Li, Chengyuan; Deng, Licai; Xin, Yu; Hu, Yi] Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, 20A Datun Rd, Beijing 100012, Peoples R China.
   [Li, Chengyuan] Chinese Acad Sci, Purple Mt Observ, 2 West Beijing Rd, Nanjing 210008, Jiangsu, Peoples R China.
   [de Grijs, Richard] Int Space Sci Inst Beijing, 1 Nanertiao, Beijing 100190, Peoples R China.
   [Geller, Aaron M.; Faucher-Giguere, Claude-Andre] Northwestern Univ, CIERA, 2145 Sheridan Rd, Evanston, IL 60208 USA.
   [Geller, Aaron M.; Faucher-Giguere, Claude-Andre] Northwestern Univ, Dept Phys & Astron, 2145 Sheridan Rd, Evanston, IL 60208 USA.
   [Geller, Aaron M.] Univ Chicago, Dept Astron & Astrophys, 5640 S Ellis Ave, Chicago, IL 60637 USA.
C3 Peking University; Peking University; Chinese Academy of Sciences; National Astronomical Observatory, CAS; Chinese Academy of Sciences; Nanjing Institute of Astronomical Optics & Technology, NAOC, CAS; Purple Mountain Observatory, CAS; Northwestern University; Northwestern University; University of Chicago
RP Li, CY (corresponding author), Peking Univ, Kavli Inst Astron & Astrophys, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.; Li, CY (corresponding author), Peking Univ, Dept Astron, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.; Li, CY (corresponding author), Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, 20A Datun Rd, Beijing 100012, Peoples R China.; Li, CY (corresponding author), Chinese Acad Sci, Purple Mt Observ, 2 West Beijing Rd, Nanjing 210008, Jiangsu, Peoples R China.
EM joshuali@pku.edu.cn
FU National Natural Science Foundation of China [11073001, 11373010, 11473037]; Chinese Academy of Sciences [XDB09000000]; 973 Program [2014CBB45700]; National Science Foundation Astronomy and Astrophysics Postdoctoral Fellowship [AST-1302765]; National Science Foundation [AST-1412836]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1302765] Funding Source: National Science Foundation
NR 44
TC 32
Z9 34
U1 0
U2 30
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 502
EP +
DI 10.1038/nature16493
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800031
PM 26819043
DA 2026-03-09
ER

PT J
AU Dong, L
   Yu, WM
   Zheng, H
   Loh, ML
   Bunting, ST
   Pauly, M
   Huang, G
   Zhou, MX
   Broxmeyer, HE
   Scadden, DT
   Qu, CK
AF Dong, Lei
   Yu, Wen-Mei
   Zheng, Hong
   Loh, Mignon L.
   Bunting, Silvia T.
   Pauly, Melinda
   Huang, Gang
   Zhou, Muxiang
   Broxmeyer, Hal E.
   Scadden, David T.
   Qu, Cheng-Kui
TI Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment
SO NATURE
LA English
DT Article
ID bone-marrow niche; chronic myelogenous leukemia; hematopoietic stem; noonan-syndrome; receptor gene; shp2 ptpn11; mouse model; maintenance; progenitors; regeneration
AB Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway(1), are found in 50% of patients with Noonan syndrome(2). These patients have an increased risk of developing leukaemia(3), especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity(4-7). However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1 alpha), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1 beta and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably, administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11-mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonansyndrome-associated leukaemias.
C1 [Dong, Lei; Yu, Wen-Mei; Zheng, Hong; Pauly, Melinda; Zhou, Muxiang; Qu, Cheng-Kui] Emory Univ, Sch Med, Div Hematol Oncol,Dept Pediat, Aflac Canc & Blood Disorders Ctr,Childrens Health, Atlanta, GA 30322 USA.
   [Loh, Mignon L.] Univ Calif San Francisco, Div Pediat Hematol Oncol, Dept Pediat, San Francisco, CA 94122 USA.
   [Bunting, Silvia T.] Emory Univ, Childrens Healthcare Atlanta, Dept Pathol, Atlanta, GA 30322 USA.
   [Huang, Gang] Univ Cincinnati, Cincinnati Childrens Hosp, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
   [Broxmeyer, Hal E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
   [Scadden, David T.] Harvard Univ, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Scadden, David T.] Harvard Univ, MGH Canc Ctr, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA.
   [Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA.
C3 Emory University; Children's Healthcare of Atlanta (CHOA); University of California System; University of California San Francisco; Emory University; Children's Healthcare of Atlanta (CHOA); University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Indiana University System; Indiana University Bloomington; Harvard University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University
RP Qu, CK (corresponding author), Emory Univ, Sch Med, Div Hematol Oncol,Dept Pediat, Aflac Canc & Blood Disorders Ctr,Childrens Health, Atlanta, GA 30322 USA.
EM cheng-kui.qu@emory.edu
FU National Institutes of Health [HL130995, DK092722]; National Heart Lung and Blood Institute [R01HL130995] Funding Source: NIH RePORTER
NR 39
TC 211
Z9 248
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 304
EP +
DI 10.1038/nature20131
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500048
PM 27783593
DA 2026-03-09
ER

PT J
AU Yttri, EA
   Dudman, JT
AF Yttri, Eric A.
   Dudman, Joshua T.
TI Opponent and bidirectional control of movement velocity in the basal ganglia
SO NATURE
LA English
DT Article
ID striatal neurons; cre-recombinase; dopamine; representation; organization; stimulation; activation; selection; circuit; light
AB For goal-directed behaviour it is critical that we can both select the appropriate action and learn to modify the underlying movements (for example, the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behaviour, such as the neocortex and thalamus, are integrated with reward signalling(1) to reinforce successful, purposive actions(2). The dorsal striatum, a major input structure of basal ganglia, is composed of two opponent pathways, direct and indirect, thought to select actions that elicit positive outcomes and suppress actions that do not, respectively(3,4). Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in the striatum(5,6). Although perturbations of basal ganglia function produce profound changes in movement(7), it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we use cell-type-specific stimulation in mice delivered in closed loop during movement to demonstrate that activity in either the direct or indirect pathway is sufficient to produce specific and sustained increases or decreases in velocity, without affecting action selection or motivation. These behavioural changes were a form of learning that accumulated over trials, persisted after the cessation of stimulation, and were abolished in the presence of dopamine antagonists. Our results reveal that the direct and indirect pathways can each bidirectionally control movement velocity, demonstrating unprecedented specificity and flexibility in the control of volition by the basal ganglia.
C1 [Yttri, Eric A.; Dudman, Joshua T.] Howard Hughes Med Inst, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Dudman, JT (corresponding author), Howard Hughes Med Inst, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM dudmanj@janelia.hhmi.org
FU Howard Hughes Medical Institute
NR 40
TC 199
Z9 226
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 402
EP +
DI 10.1038/nature17639
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300050
PM 27135927
DA 2026-03-09
ER

PT J
AU Herman, AM
   Ortiz-Guzman, J
   Kochukov, M
   Herman, I
   Quast, KB
   Patel, JM
   Tepe, B
   Carlson, JC
   Ung, K
   Selever, J
   Tong, QC
   Arenkiel, BR
AF Herman, Alexander M.
   Ortiz-Guzman, Joshua
   Kochukov, Mikhail
   Herman, Isabella
   Quast, Kathleen B.
   Patel, Jay M.
   Tepe, Burak
   Carlson, Jeffrey C.
   Ung, Kevin
   Selever, Jennifer
   Tong, Qingchun
   Arenkiel, Benjamin R.
TI A cholinergic basal forebrain feeding circuit modulates appetite suppression
SO NATURE
LA English
DT Article
ID central-nervous-system; food-intake; body-weight; neurons; acetylcholine; smoking; balance; leptin; mice; pomc
AB Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus(1-5), the major centre in the brain that regulates body weight homeostasis(6,7). However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding(8-10) owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant. Nicotine is an exogenous agonist for acetylcholine receptors, suggesting that endogenous cholinergic signalling may play a part in normal physiological regulation of feeding. However, it remains unclear how cholinergic neurons in the brain regulate food intake. Here we report that cholinergic neurons of the mouse basal forebrain potently influence food intake and body weight. Impairment of cholinergic signalling increases food intake and results in severe obesity, whereas enhanced cholinergic signalling decreases food consumption. We found that cholinergic circuits modulate appetite suppression on downstream targets in the hypothalamus. Together our data reveal the cholinergic basal forebrain as a major modulatory centre underlying feeding behaviour.
C1 [Herman, Alexander M.; Ortiz-Guzman, Joshua; Herman, Isabella; Tepe, Burak; Carlson, Jeffrey C.; Ung, Kevin; Arenkiel, Benjamin R.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
   [Kochukov, Mikhail; Quast, Kathleen B.; Selever, Jennifer; Arenkiel, Benjamin R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Herman, Isabella; Patel, Jay M.] Baylor Coll Med, Med Scientist Training Program, Houston, TX 77030 USA.
   [Patel, Jay M.; Arenkiel, Benjamin R.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
   [Selever, Jennifer; Arenkiel, Benjamin R.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
   [Tong, Qingchun] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; University of Texas System; University of Texas Health Science Center Houston
RP Arenkiel, BR (corresponding author), Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.; Arenkiel, BR (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.; Arenkiel, BR (corresponding author), Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
EM arenkiel@bcm.edu
FU NIH [5F31NS089411, R01NS078294, R01DK109934, P30DK079638, U54HD083092]; Klarman Family Foundation; Klingenstein-Simons Fellowship Award; Brain and Behavior Research Foundation; Charif Souki Fund; McNair Medical Institute; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK109934] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS078294] Funding Source: NIH RePORTER
NR 29
TC 98
Z9 114
U1 1
U2 35
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 253
EP +
DI 10.1038/nature19789
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000047
PM 27698417
DA 2026-03-09
ER

PT J
AU Topczewski, JJ
   Cabrera, PJ
   Saper, NI
   Sanford, MS
AF Topczewski, Joseph J.
   Cabrera, Pablo J.
   Saper, Noam I.
   Sanford, Melanie S.
TI Palladium-catalysed transannular C-H functionalization of alicyclic amines
SO NATURE
LA English
DT Article
ID c(sp(3))-h arylation; bond functionalization; aliphatic-amines; alpha-arylation; activation; molecules; acid
AB Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development(1-4). Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline)(5). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited(6,7). Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.
C1 [Topczewski, Joseph J.; Cabrera, Pablo J.; Saper, Noam I.; Sanford, Melanie S.] Univ Michigan, Dept Chem, 930 North Univ Ave, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Sanford, MS (corresponding author), Univ Michigan, Dept Chem, 930 North Univ Ave, Ann Arbor, MI 48109 USA.
EM mssanfor@umich.edu
FU NIH [F32 GM109479]; NIGMS grant [GM073836]; NSF [CHE-0840456]
NR 30
TC 277
Z9 312
U1 1
U2 282
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 220
EP 224
DI 10.1038/nature16957
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100038
PM 26886789
DA 2026-03-09
ER

PT J
AU Lin, Q
   Fan, SH
   Zhang, YH
   Xu, M
   Zhang, HX
   Yang, YL
   Lee, AP
   Woltering, JM
   Ravi, V
   Gunter, HM
   Luo, W
   Gao, ZX
   Lim, ZW
   Qin, G
   Schneider, RF
   Wang, X
   Xiong, PW
   Li, G
   Wang, K
   Min, JM
   Zhang, C
   Qiu, Y
   Bai, J
   He, WM
   Bian, C
   Zhang, XH
   Shan, D
   Qu, HY
   Sun, Y
   Gao, Q
   Huang, LM
   Shi, Q
   Meyer, A
   Venkatesh, B
AF Lin, Qiang
   Fan, Shaohua
   Zhang, Yanhong
   Xu, Meng
   Zhang, Huixian
   Yang, Yulan
   Lee, Alison P.
   Woltering, Joost M.
   Ravi, Vydianathan
   Gunter, Helen M.
   Luo, Wei
   Gao, Zexia
   Lim, Zhi Wei
   Qin, Geng
   Schneider, Ralf F.
   Wang, Xin
   Xiong, Peiwen
   Li, Gang
   Wang, Kai
   Min, Jiumeng
   Zhang, Chi
   Qiu, Ying
   Bai, Jie
   He, Weiming
   Bian, Chao
   Zhang, Xinhui
   Shan, Dai
   Qu, Hongyue
   Sun, Ying
   Gao, Qiang
   Huang, Liangmin
   Shi, Qiong
   Meyer, Axel
   Venkatesh, Byrappa
TI The seahorse genome and the evolution of its specialized morphology
SO NATURE
LA English
DT Article
ID male-pregnancy; phylogenetic analysis; adaptive evolution; genetic-basis; hippocampus; alignment; insights; tbx4; diversification; syngnathidae
AB Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.
C1 [Lin, Qiang; Zhang, Yanhong; Zhang, Huixian; Luo, Wei; Qin, Geng; Wang, Xin; Li, Gang; Qu, Hongyue; Huang, Liangmin; Shi, Qiong] Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Guangdong, Peoples R China.
   [Fan, Shaohua; Woltering, Joost M.; Gunter, Helen M.; Schneider, Ralf F.; Xiong, Peiwen; Meyer, Axel] Univ Konstanz, Dept Biol, Chair Zool & Evolutionary Biol, D-78457 Constance, Germany.
   [Xu, Meng; Min, Jiumeng; Zhang, Chi; He, Weiming; Shan, Dai; Gao, Qiang] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Zhang, Huixian; Lee, Alison P.; Ravi, Vydianathan; Lim, Zhi Wei; Venkatesh, Byrappa] ASTAR, Biopolis, Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Gao, Zexia] Huazhong Agr Univ, Coll Fisheries, Wuhan 430070, Peoples R China.
   [Qin, Geng; Wang, Xin; Qu, Hongyue; Huang, Liangmin] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Wang, Kai] Ludong Univ, Sch Agr, Yantai 264025, Peoples R China.
   [Qiu, Ying; Bai, Jie; Bian, Chao; Zhang, Xinhui; Sun, Ying; Shi, Qiong] BGI, Guangdong Prov Key Lab Mol Breeding Marine Econ A, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China.
   [Venkatesh, Byrappa] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 119228, Singapore.
   [Fan, Shaohua] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Lee, Alison P.] Bioproc Technol Inst, Biopolis, Singapore 138668, Singapore.
   [Gunter, Helen M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3FL, Midlothian, Scotland.
   [Lim, Zhi Wei] Nanyang Technol Univ, Sch Mat Sci & Engn, 50 Nanyang Ave, Singapore 639798, Singapore.
C3 Chinese Academy of Sciences; South China Sea Institute of Oceanology, CAS; University of Konstanz; Beijing Genomics Institute (BGI); Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Huazhong Agricultural University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Ludong University; Beijing Genomics Institute (BGI); National University of Singapore; University of Pennsylvania; Agency for Science Technology & Research (A*STAR); A*STAR - Bioprocessing Technology Institute (BTI); University of Edinburgh; Nanyang Technological University
RP Shi, Q (corresponding author), Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Guangdong, Peoples R China.; Meyer, A (corresponding author), Univ Konstanz, Dept Biol, Chair Zool & Evolutionary Biol, D-78457 Constance, Germany.; Venkatesh, B (corresponding author), ASTAR, Biopolis, Inst Mol & Cell Biol, Singapore 138673, Singapore.; Shi, Q (corresponding author), BGI, Guangdong Prov Key Lab Mol Breeding Marine Econ A, Shenzhen Key Lab Marine Genom, Shenzhen 518083, Peoples R China.; Venkatesh, B (corresponding author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 119228, Singapore.
EM shiqiong@genomics.cn; axel.meyer@uni-konstanz.de; mcbbv@imcb.a-star.edu.sg
FU National Science Fund for Excellent Young Scholars [41322038]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA13020103]; Youth Foundation of National High Technology Research and Development Program (863 Program) [2015AA020909]; Outstanding Youth Foundation in Guangdong Province [S2013050014802]; National Natural Science Foundation of China [41576145]; National Key Basic Research Program of China [2015CB452904]; Special Project on the Integration of Industry, Education and Research of Guangdong Province [2013B090800017]; Biomedical Research Council of A*STAR, Singapore
NR 61
TC 188
Z9 221
U1 8
U2 265
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 395
EP +
DI 10.1038/nature20595
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800034
PM 27974754
DA 2026-03-09
ER

PT J
AU Sevigny, J
   Chiao, P
   Bussiere, T
   Weinreb, PH
   Williams, L
   Maier, M
   Dunstan, R
   Salloway, S
   Chen, T
   Ling, Y
   O'Gorman, J
   Qian, F
   Arastu, M
   Li, MW
   Chollate, S
   Brennan, MS
   Quintero-Monzon, O
   Scannevin, RH
   Arnold, HM
   Engber, T
   Rhodes, K
   Ferrero, J
   Hang, YM
   Mikulskis, A
   Grimm, J
   Hock, C
   Nitsch, RM
   Sandrock, A
AF Sevigny, Jeff
   Chiao, Ping
   Bussiere, Thierry
   Weinreb, Paul H.
   Williams, Leslie
   Maier, Marcel
   Dunstan, Robert
   Salloway, Stephen
   Chen, Tianle
   Ling, Yan
   O'Gorman, John
   Qian, Fang
   Arastu, Mahin
   Li, Mingwei
   Chollate, Sowmya
   Brennan, Melanie S.
   Quintero-Monzon, Omar
   Scannevin, Robert H.
   Arnold, H. Moore
   Engber, Thomas
   Rhodes, Kenneth
   Ferrero, James
   Hang, Yaming
   Mikulskis, Alvydas
   Grimm, Jan
   Hock, Christoph
   Nitsch, Roger M.
   Sandrock, Alfred
TI The antibody aducanumab reduces Aβ plaques in Alzheimer's disease
SO NATURE
LA English
DT Article
ID amyloid-beta; imaging abnormality; mouse model; drug-development; prion protein; trials; neurodegeneration; therapeutics; bapineuzumab; gantenerumab
AB Alzheimer's disease (AD) is characterized by deposition of amyloid-beta (A beta) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against A beta to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated A beta. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal A beta, and reduce soluble and insoluble A beta in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain A beta in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.
C1 [Sevigny, Jeff; Chiao, Ping; Bussiere, Thierry; Weinreb, Paul H.; Williams, Leslie; Dunstan, Robert; Chen, Tianle; Ling, Yan; O'Gorman, John; Qian, Fang; Arastu, Mahin; Li, Mingwei; Chollate, Sowmya; Brennan, Melanie S.; Quintero-Monzon, Omar; Scannevin, Robert H.; Arnold, H. Moore; Engber, Thomas; Rhodes, Kenneth; Ferrero, James; Hang, Yaming; Mikulskis, Alvydas; Sandrock, Alfred] Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
   [Maier, Marcel; Grimm, Jan; Hock, Christoph; Nitsch, Roger M.] Neurimmune, CH-8952 Schlieren, Switzerland.
   [Salloway, Stephen] Butler Hosp, Providence, RI 02906 USA.
   [Hock, Christoph; Nitsch, Roger M.] Univ Zurich, Inst Regenerat Med, CH-8952 Zurich, Switzerland.
C3 Biogen; Butler Hospital Rhode Island; University of Zurich
RP Sandrock, A (corresponding author), Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
EM alfred.sandrock@biogen.com
FU Biogen
NR 33
TC 2400
Z9 2849
U1 22
U2 1167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 50
EP 56
DI 10.1038/nature19323
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900036
PM 27582220
DA 2026-03-09
ER

PT J
AU Perry, RJ
   Peng, L
   Barry, NA
   Cline, GW
   Zhang, DY
   Cardone, RL
   Petersen, KF
   Kibbey, RG
   Goodman, AL
   Shulman, GI
AF Perry, Rachel J.
   Peng, Liang
   Barry, Natasha A.
   Cline, Gary W.
   Zhang, Dongyan
   Cardone, Rebecca L.
   Petersen, Kitt Falk
   Kibbey, Richard G.
   Goodman, Andrew L.
   Shulman, Gerald I.
TI Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome
SO NATURE
LA English
DT Article
ID chain fatty-acids; hepatic vagus nerve; insulin-secretion; gut microbiota; electrical-stimulation; vagal-stimulation; overweight; glucose; activation; capacity
AB Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity.
C1 [Perry, Rachel J.; Peng, Liang; Cline, Gary W.; Cardone, Rebecca L.; Petersen, Kitt Falk; Kibbey, Richard G.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA.
   [Barry, Natasha A.; Goodman, Andrew L.] Yale Univ, Sch Med, Dept Microbial Pathogenesis, 333 Cedar St, New Haven, CT 06510 USA.
   [Barry, Natasha A.; Goodman, Andrew L.] Yale Univ, Sch Med, Microbial Sci Inst, New Haven, CT 06516 USA.
   [Zhang, Dongyan; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06519 USA.
   [Petersen, Kitt Falk; Shulman, Gerald I.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Kibbey, Richard G.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
C3 Yale University; Yale University; Yale University; Yale University; Howard Hughes Medical Institute; University of Copenhagen; Novo Nordisk Foundation; Yale University
RP Shulman, GI (corresponding author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA.; Shulman, GI (corresponding author), Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06519 USA.; Shulman, GI (corresponding author), Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.; Shulman, GI (corresponding author), Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
EM gerald.shulman@yale.edu
FU National Institutes of Health [R01 DK-40936, R01 AG-23686, P30 DK-45735, U24 DK-59635, T32 DK-101019, R01 DK-92606, R01 GM-103574, DP2 GM-105456]; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; National Center for Advancing Translational Sciences [UL1TR001863] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK045735, P30DK034989] Funding Source: NIH RePORTER; NNF Center for Basic Metabolic Research [Gillum Group] Funding Source: researchfish
NR 24
TC 1037
Z9 1278
U1 10
U2 475
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 213
EP +
DI 10.1038/nature18309
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100033
PM 27279214
DA 2026-03-09
ER

PT J
AU Kang, EJ
   Wu, J
   Gutierrez, NM
   Koski, A
   Tippner-Hedges, R
   Agaronyan, K
   Platero-Luengo, A
   Martinez-Redondo, P
   Ma, H
   Lee, Y
   Hayama, T
   Van Dyken, C
   Wang, XJ
   Luo, SY
   Ahmed, R
   Li, Y
   Ji, DM
   Kayali, R
   Cinnioglu, C
   Olson, S
   Jensen, J
   Battaglia, D
   Lee, D
   Wu, D
   Huang, TS
   Wolf, DP
   Temiakov, D
   Belmonte, JCI
   Amato, P
   Mitalipov, S
AF Kang, Eunju
   Wu, Jun
   Gutierrez, Nuria Marti
   Koski, Amy
   Tippner-Hedges, Rebecca
   Agaronyan, Karen
   Platero-Luengo, Aida
   Martinez-Redondo, Paloma
   Ma, Hong
   Lee, Yeonmi
   Hayama, Tomonari
   Van Dyken, Crystal
   Wang, Xinjian
   Luo, Shiyu
   Ahmed, Riffat
   Li, Ying
   Ji, Dongmei
   Kayali, Refik
   Cinnioglu, Cengiz
   Olson, Susan
   Jensen, Jeffrey
   Battaglia, David
   Lee, David
   Wu, Diana
   Huang, Taosheng
   Wolf, Don P.
   Temiakov, Dmitry
   Belmonte, Juan Carlos Izpisua
   Amato, Paula
   Mitalipov, Shoukhrat
TI Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations
SO NATURE
LA English
DT Article
ID embryonic stem-cells; pronuclear transfer; pluripotent cells; nuclear transfer; ovarian reserve; genetic drift; copy number; disease; transmission; replication
AB Maternally inherited mitochondrial (mt) DNA mutations can cause fatal or severely debilitating syndromes in children(1-3), with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue(4). Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States(5). Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA(6-8). Here we report MRT outcomes in several families with common mtDNA syndromes. The mother's oocytes were of normal quality and mutation levels correlated with those in existing children. Efficient replacement of oocyte mutant mtDNA was performed by spindle transfer(8), resulting in embryos containing > 99% donor mtDNA. Donor mtDNA was stably maintained in embryonic stem cells (ES cells) derived from most embryos. However, some ES cell lines demonstrated gradual loss of donor mtDNA and reversal to the maternal haplotype. In evaluating donor-to-maternal mtDNA interactions, it seems that compatibility relates to mtDNA replication efficiency rather than to mismatch or oxidative phosphorylation dysfunction. We identify a polymorphism within the conserved sequence box II region of the D-loop as a plausible cause of preferential replication of specific mtDNA haplotypes. In addition, some haplotypes confer proliferative and growth advantages to cells. Hence, we propose a matching paradigm for selecting compatible donor mtDNA for MRT.
C1 [Kang, Eunju; Gutierrez, Nuria Marti; Koski, Amy; Tippner-Hedges, Rebecca; Lee, Yeonmi; Hayama, Tomonari; Van Dyken, Crystal; Ahmed, Riffat; Li, Ying; Ji, Dongmei; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Ctr Embryon Cell & Gene Therapy, 3303 SW Bond Ave, Portland, OR 97239 USA.
   [Kang, Eunju; Gutierrez, Nuria Marti; Koski, Amy; Tippner-Hedges, Rebecca; Ma, Hong; Lee, Yeonmi; Hayama, Tomonari; Van Dyken, Crystal; Ahmed, Riffat; Li, Ying; Wolf, Don P.; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA.
   [Wu, Jun; Platero-Luengo, Aida; Martinez-Redondo, Paloma; Belmonte, Juan Carlos Izpisua] Salk Inst Biol Studies, Gene Express Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Agaronyan, Karen; Temiakov, Dmitry] Rowan Univ, Dept Cell Biol, Sch Osteopath Med, 2 Med Ctr Dr, Stratford, NJ 08084 USA.
   [Wang, Xinjian; Luo, Shiyu; Huang, Taosheng] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
   [Ji, Dongmei] Anhui Med Univ, Reprod Med Ctr, 218 Jixi Rd, Hefei 230022, Anhui, Peoples R China.
   [Kayali, Refik; Cinnioglu, Cengiz] IviGen Los Angeles, 406 Amapola Ave,Suite 215, Torrance, CA 90501 USA.
   [Olson, Susan] Oregon Hlth & Sci Univ, Res Cytogenet Lab, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
   [Jensen, Jeffrey; Battaglia, David; Lee, David; Wu, Diana; Amato, Paula; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Div Reprod Endocrinol, Dept Obstet & Gynecol, 3303 SW Bond Ave, Portland, OR 97239 USA.
   [Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
   [Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Dept Biomed Engn, 3303 SW Bond Ave, Portland, OR 97239 USA.
   [Kang, Eunju] ASAN Med Ctr, ASAN Inst Life Sci, Stem Cell Ctr, Olymp Ro 43 Gil, Seoul 138736, South Korea.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon National Primate Research Center; Salk Institute; Rowan University; Rowan University School of Osteopathic Medicine; Cincinnati Children's Hospital Medical Center; Anhui Medical University; Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University; University of Ulsan; Asan Medical Center
RP Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Ctr Embryon Cell & Gene Therapy, 3303 SW Bond Ave, Portland, OR 97239 USA.; Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA.; Amato, P; Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Div Reprod Endocrinol, Dept Obstet & Gynecol, 3303 SW Bond Ave, Portland, OR 97239 USA.; Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.; Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Dept Biomed Engn, 3303 SW Bond Ave, Portland, OR 97239 USA.
EM amatop@ohsu.edu; mitalipo@ohsu.edu
FU Leducq Foundation; OHSU institutional funds; Cincinnati Children's Hospital Research Foundation; G. Harold and Leila Y. Mathers Charitable Foundation; Leona M. and Harry B. Helmsley Charitable Trust; Moxie Foundation; Hewitt Foundation; Funciacion Alfonso Martin Escudero
NR 35
TC 232
Z9 274
U1 3
U2 152
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 270
EP +
DI 10.1038/nature20592
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700057
PM 27919073
DA 2026-03-09
ER

PT J
AU Chartron, JW
   Hunt, KCL
   Frydman, J
AF Chartron, Justin W.
   Hunt, Katherine C. L.
   Frydman, Judith
TI Cotranslational signal-independent SRP preloading during membrane targeting
SO NATURE
LA English
DT Article
ID protein biogenesis factors; endoplasmic-reticulum; recognition particle; global analysis; in-vivo; ribosome; translation; yeast; translocation; localization
AB Ribosome-associated factors must properly decode the limited information available in nascent polypeptides to direct them to their correct cellular fate(1). It is unclear how the low complexity information exposed by the nascent chain suffices for accurate recognition by the many factors competing for the limited surface near the ribosomal exit site(2,3). Questions remain even for the well-studied cotranslational targeting cycle to the endoplasmic reticulum, involving recognition of linear hydrophobic signal sequences or transmembrane domains by the signal recognition particle (SRP)(4,5). Notably, the SRP has low abundance relative to the large number of ribosome-nascent-chain complexes (RNCs), yet it accurately selects those destined for the endoplasmic reticulum(6). Despite their overlapping specificities, the SRP and the cotranslationally acting Hsp70 display precise mutually exclusive selectivity in vivo for their cognate RNCs7,8. To understand cotranslational nascent chain recognition in vivo, here we investigate the cotranslational membrane-targeting cycle using ribosome profiling(9) in yeast cells coupled with biochemical fractionation of ribosome populations. We show that the SRP preferentially binds secretory RNCs before their targeting signals are translated. Non-coding mRNA elements can promote this signal-independent pre-recruitment of SRP. Our study defines the complex kinetic interaction between elongation in the cytosol and determinants in the polypeptide and mRNA that modulate SRP-substrate selection and membrane targeting.
C1 [Chartron, Justin W.; Hunt, Katherine C. L.; Frydman, Judith] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Frydman, Judith] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Frydman, J (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.; Frydman, J (corresponding author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
EM jfrydman@stanford.edu
FU NIH NRSA award; NIH; HFSP; National Institute of General Medical Sciences [R37GM056433, R01GM056433] Funding Source: NIH RePORTER
NR 57
TC 142
Z9 179
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 224
EP +
DI 10.1038/nature19309
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100039
PM 27487213
DA 2026-03-09
ER

PT J
AU Govero, J
   Esakky, P
   Scheaffer, SM
   Fernandez, E
   Drury, A
   Platt, DJ
   Gorman, MJ
   Richner, JM
   Caine, EA
   Salazar, V
   Moley, KH
   Diamond, MS
AF Govero, Jennifer
   Esakky, Prabagaran
   Scheaffer, Suzanne M.
   Fernandez, Estefania
   Drury, Andrea
   Platt, Derek J.
   Gorman, Matthew J.
   Richner, Justin M.
   Caine, Elizabeth A.
   Salazar, Vanessa
   Moley, Kelle H.
   Diamond, Michael S.
TI Zika virus infection damages the testes in mice
SO NATURE
LA English
DT Article
ID sexual transmission; receptor; semen; spermatogenesis; model
AB Infection of pregnant women with Zika virus (ZIKV) can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen(1). In addition to transmission by mosquitoes, ZIKV can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually(2). Here, using a mouse-adapted African ZIKV strain (Dakar 41519), we evaluated the consequences of infection in the male reproductive tract of mice. We observed persistence of ZIKV, but not the closely related dengue virus (DENV), in the testis and epididymis of male mice, and this was associated with tissue injury that caused diminished testosterone and inhibin B levels and oligospermia. ZIKV preferentially infected spermatogonia, primary spermatocytes and Sertoli cells in the testis, resulting in cell death and destruction of the seminiferous tubules. Less damage was caused by a contemporary Asian ZIKV strain (H/PF/2013), in part because this virus replicates less efficiently in mice. The extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of sperm function and viability in ZIKV-infected humans seem warranted.
C1 [Govero, Jennifer; Richner, Justin M.; Caine, Elizabeth A.; Salazar, Vanessa; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Esakky, Prabagaran; Scheaffer, Suzanne M.; Drury, Andrea; Moley, Kelle H.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
   [Fernandez, Estefania; Gorman, Matthew J.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Platt, Derek J.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Moley, Kelle H.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.; Moley, KH (corresponding author), Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.; Moley, KH (corresponding author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
EM moleyk@wustl.edu; diamond@wusm.wustl.edu
FU NIH [R01 AI073755, R01 AI104972, R01 HD065435, R01HD083895, T32 AI007163]; Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences [UL1 TR000448]; Washington University Institute of Clinical and Translational Sciences from the National Institute of General Medical Sciences [P41 GM103422-35]; Veteran Affairs Office of Research and Development [IO1BX007080]; Eunice Kennedy Shriver NICHD/NIH (NCTRI) [P50-HD28934]; National Institute of Allergy and Infectious Diseases [R01AI101400, R01AI073755, T32AI007172, T32AI007163] Funding Source: NIH RePORTER
NR 35
TC 402
Z9 477
U1 1
U2 122
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 438
EP +
DI 10.1038/nature20556
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800043
PM 27798603
DA 2026-03-09
ER

PT J
AU O'Rourke, JG
   Stevenson, DJ
AF O'Rourke, Joseph G.
   Stevenson, David J.
TI Powering Earth's dynamo with magnesium precipitation from the core
SO NATURE
LA English
DT Article
ID transport-property; terrestrial planets; light-elements; high-pressure; solar-system; giant impact; outer core; accretion; iron; conductivity
AB Earth's global magnetic field arises from vigorous convection within the liquid outer core. Palaeomagnetic evidence reveals that the geodynamo has operated for at least 3.4 billion years(1), which places constraints on Earth's formation and evolution. Available power sources in standard models include compositional convection (driven by the solidifying inner core's expulsion of light elements), thermal convection (from slow cooling), and perhaps heat from the decay of radioactive isotopes. However, recent first-principles calculations(2,3) and diamond-anvil cell experiments(4,5) indicate that the thermal conductivity of iron is two or three times larger than typically assumed in these models. This presents a problem: a large increase in the conductive heat flux along the adiabat (due to the higher conductivity of iron) implies that the inner core is young (less than one billion years old(4)), but thermal convection and radiogenic heating alone may not have been able to sustain the geodynamo during earlier epochs. Here we show that the precipitation of magnesium-bearing minerals from the core could have served as an alternative power source. Equilibration at high temperatures in the aftermath of giant impacts allows a small amount of magnesium (one or two weight per cent) to partition into the core while still producing the observed abundances of siderophile elements in the mantle and avoiding an excess of silicon and oxygen in the core. The transport of magnesium as oxide or silicate from the cooling core to underneath the mantle is an order of magnitude more efficient per unit mass as a source of buoyancy than inner-core growth. We therefore conclude that Earth's dynamo would survive throughout geologic time (from at least 3.4 billion years ago to the present) even if core radiogenic heating were minimal and core cooling were slow.
C1 [O'Rourke, Joseph G.; Stevenson, David J.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP O'Rourke, JG (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM jorourke@caltech.edu
FU National Science Foundation Graduate Research Fellowship [DGE-1144469]
NR 34
TC 189
Z9 209
U1 1
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 387
EP +
DI 10.1038/nature16495
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800044
PM 26791727
DA 2026-03-09
ER

PT J
AU Galej, WP
   Wilkinson, ME
   Fica, SM
   Oubridge, C
   Newman, AJ
   Nagai, K
AF Galej, Wojciech P.
   Wilkinson, Max E.
   Fica, Sebastian M.
   Oubridge, Chris
   Newman, Andrew J.
   Nagai, Kiyoshi
TI Cryo-EM structure of the spliceosome immediately after branching
SO NATURE
LA English
DT Article
ID pre-messenger-rna; u4/u6.u5 tri-snrnp; crystal-structure; active-site; in-vitro; u6 snrna; conformational rearrangement; saccharomyces-cerevisiae; electron cryomicroscopy; catalytic activation
AB Precursor mRNA (pre-mRNA) splicing proceeds by two consecutive transesterification reactions via a lariat-intron intermediate. Here we present the 3.8 angstrom cryo-electron microscopy structure of the spliceosome immediately after lariat formation. The 5'-splice site is cleaved but remains close to the catalytic Mg2+ site in the U2/U6 small nuclear RNA (snRNA) triplex, and the 5'-phosphate of the intron nucleotide G(+1) is linked to the branch adenosine 2' OH. The 5'-exon is held between the Prp8 amino-terminal and linker domains, and base-pairs with U5 snRNA loop 1. Non-Watson-Crick interactions between the branch helix and 5'-splice site dock the branch adenosine into the active site, while intron nucleotides + 3 to + 6 base-pair with the U6 snRNA ACAGAGA sequence. Isy1 and the step-one factors Yju2 and Cwc25 stabilize docking of the branch helix. The intron downstream of the branch site emerges between the Prp8 reverse transcriptase and linker domains and extends towards the Prp16 helicase, suggesting a plausible mechanism of remodelling before exon ligation.
C1 [Galej, Wojciech P.; Wilkinson, Max E.; Fica, Sebastian M.; Oubridge, Chris; Newman, Andrew J.; Nagai, Kiyoshi] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Galej, WP; Nagai, K (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM wgalej@mrc-lmb.cam.ac.uk; kn@mrc-lmb.cam.ac.uk
FU Medical Research Council [MC_U105184330]; Rutherford Memorial Cambridge Scholarship; EMBO fellowship; Marie Sklodowska-Curie fellowship; MRC [MC_U105184330] Funding Source: UKRI; Medical Research Council [MC_U105184330] Funding Source: researchfish
NR 84
TC 185
Z9 232
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 197
EP +
DI 10.1038/nature19316
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100040
PM 27459055
DA 2026-03-09
ER

PT J
AU Shu, SK
   Lin, CY
   He, HH
   Witwicki, RM
   Tabassum, DP
   Roberts, JM
   Janiszewska, M
   Huh, SJ
   Liang, Y
   Ryan, J
   Doherty, E
   Mohammed, H
   Guo, H
   Stover, DG
   Ekram, MB
   Peluffo, G
   Brown, J
   D'Santos, C
   Krop, IE
   Dillon, D
   McKeown, M
   Ott, C
   Qi, J
   Ni, M
   Rao, PK
   Duarte, M
   Wu, SY
   Chiang, CM
   Anders, L
   Young, RA
   Winer, EP
   Letai, A
   Barry, WT
   Carroll, JS
   Long, HW
   Brown, M
   Liu, XS
   Meyer, CA
   Bradner, JE
   Polyak, K
AF Shu, Shaokun
   Lin, Charles Y.
   He, Housheng Hansen
   Witwicki, Robert M.
   Tabassum, Doris P.
   Roberts, Justin M.
   Janiszewska, Michalina
   Huh, Sung Jin
   Liang, Yi
   Ryan, Jeremy
   Doherty, Ernest
   Mohammed, Hisham
   Guo, Hao
   Stover, Daniel G.
   Ekram, Muhammad B.
   Peluffo, Guillermo
   Brown, Jonathan
   D'Santos, Clive
   Krop, Ian E.
   Dillon, Deborah
   McKeown, Michael
   Ott, Christopher
   Qi, Jun
   Ni, Min
   Rao, Prakash K.
   Duarte, Melissa
   Wu, Shwu-Yuan
   Chiang, Cheng-Ming
   Anders, Lars
   Young, Richard A.
   Winer, Eric P.
   Letai, Antony
   Barry, William T.
   Carroll, Jason S.
   Long, Henry W.
   Brown, Myles
   Liu, X. Shirley
   Meyer, Clifford A.
   Bradner, James E.
   Polyak, Kornelia
TI Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer
SO NATURE
LA English
DT Article
ID super-enhancers; selective-inhibition; cell identity; rna-seq; c-myc; inflammation; strategy; leukemia; subtypes; pp2a
AB Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy(1-3). BET bromodomain inhibitors, which have shown efficacy in several models of cancer(4-6), have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs(7-9). Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance.
C1 [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Tabassum, Doris P.; Roberts, Justin M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Doherty, Ernest; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; Dillon, Deborah; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Long, Henry W.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Barry, William T.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Shu, Shaokun; Lin, Charles Y.; He, Housheng Hansen; Witwicki, Robert M.; Janiszewska, Michalina; Huh, Sung Jin; Ryan, Jeremy; Stover, Daniel G.; Ekram, Muhammad B.; Peluffo, Guillermo; Brown, Jonathan; Krop, Ian E.; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Winer, Eric P.; Letai, Antony; Barry, William T.; Brown, Myles; Bradner, James E.; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [He, Housheng Hansen; Guo, Hao; Barry, William T.; Liu, X. Shirley; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [He, Housheng Hansen; Guo, Hao; Barry, William T.; Liu, X. Shirley; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [He, Housheng Hansen; Liang, Yi] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.
   [He, Housheng Hansen] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
   [Doherty, Ernest] Harvard Univ, Cambridge, MA 02138 USA.
   [Mohammed, Hisham; D'Santos, Clive; Carroll, Jason S.] Univ Cambridge, Cambridge Inst, Canc Res UK, Cambridge CB2 0RE, England.
   [Dillon, Deborah] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Dillon, Deborah] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Rao, Prakash K.; Duarte, Melissa; Long, Henry W.; Brown, Myles; Liu, X. Shirley; Polyak, Kornelia] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
   [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dept Biochem, Dallas, TX 75390 USA.
   [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dept Pharmacol, Dallas, TX 75390 USA.
   [Anders, Lars; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Liu, X. Shirley; Bradner, James E.; Polyak, Kornelia] Broad Inst, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; Harvard University; CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Polyak, K (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM james_bradner@dfci.harvard.edu; kornelia_polyak@dfci.harvard.edu
FU NIH DF/HCC SPORE in Breast Cancer [CA168504, CA080111, CA103867]; Susan G. Komen Foundation; CPRIT [RP110471, RP140367]; Welch Foundation; US Department of Defense CDMRP [BC122003, CA120184]; Princess Margaret Cancer Foundation; Canada Foundation for Innovation; Ontario Research Fund [CFI32372]; NSERC discovery grant [RGPIN-2015-04658]; Harvard Ludwig Center for Cancer Research; Cancer Research UK [22310, 20411] Funding Source: researchfish; National Cancer Institute [P30CA014051, P50CA168504] Funding Source: NIH RePORTER
NR 36
TC 525
Z9 607
U1 5
U2 276
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 413
EP +
DI 10.1038/nature16508
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800050
PM 26735014
DA 2026-03-09
ER

PT J
AU Shabahang, S
   Tao, GM
   Kaufman, JJ
   Qiao, YY
   Wei, L
   Bouchenot, T
   Gordon, AP
   Fink, Y
   Bai, YL
   Hoy, RS
   Abouraddy, AF
AF Shabahang, Soroush
   Tao, Guangming
   Kaufman, Joshua J.
   Qiao, Yangyang
   Wei, Lei
   Bouchenot, Thomas
   Gordon, Ali P.
   Fink, Yoel
   Bai, Yuanli
   Hoy, Robert S.
   Abouraddy, Ayman F.
TI Controlled fragmentation of multimaterial fibres and films via polymer cold-drawing
SO NATURE
LA English
DT Article
ID mechanical-property; elastic property; stress transfer; necking; composites; behavior; blends; matrix
AB Polymer cold-drawing(1-4) is a process in which tensile stress reduces the diameter of a drawn fibre (or thickness of a drawn film) and orients the polymeric chains. Cold-drawing has long been used in industrial applications(5-7), including the production of flexible fibres with high tensile strength such as polyester and nylon(8,9). However, cold-drawing of a composite structure has been less studied. Here we show that in a multimaterial fibre(10,11) composed of a brittle core embedded in a ductile polymer cladding, cold-drawing results in a surprising phenomenon: controllable and sequential fragmentation of the core to produce uniformly sized rods along metres of fibre, rather than the expected random or chaotic fragmentation. These embedded structures arise from mechanical-geometric instabilities associated with 'neck' propagation(2,3). Embedded, structured multimaterial threads with complex transverse geometry are thus fragmented into a periodic train of rods held stationary in the polymer cladding. These rods can then be easily extracted via selective dissolution of the cladding, or can self-heal by thermal restoration to re-form the brittle thread. Our method is also applicable to composites with flat rather than cylindrical geometries, in which case cold-drawing leads to the break-up of an embedded or coated brittle film into narrow parallel strips that are aligned normally to the drawing axis. A range of materials was explored to establish the universality of this effect, including silicon, germanium, gold, glasses, silk, polystyrene, biodegradable polymers and ice. We observe, and verify through nonlinear finite-element simulations, a linear relationship between the smallest transverse scale and the longitudinal break-up period. These results may lead to the development of dynamical and thermoreversible camouflaging via a nanoscale Venetian-blind effect, and the fabrication of large-area structured surfaces that facilitate high-sensitivity bio-detection.
C1 [Shabahang, Soroush; Tao, Guangming; Kaufman, Joshua J.; Abouraddy, Ayman F.] Univ Cent Florida, Coll Opt & Photon, CREOL, Orlando, FL 32816 USA.
   [Qiao, Yangyang; Bouchenot, Thomas; Gordon, Ali P.; Bai, Yuanli] Univ Cent Florida, Dept Mech & Aerosp Engn, Orlando, FL 32816 USA.
   [Wei, Lei] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore.
   [Fink, Yoel] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
   [Hoy, Robert S.] Univ S Florida, Dept Phys, Tampa, FL 33620 USA.
   [Abouraddy, Ayman F.] Univ Cent Florida, Dept Mat Sci & Engn, Orlando, FL 32816 USA.
C3 State University System of Florida; University of Central Florida; State University System of Florida; University of Central Florida; Nanyang Technological University; Massachusetts Institute of Technology (MIT); State University System of Florida; University of South Florida; State University System of Florida; University of Central Florida
RP Abouraddy, AF (corresponding author), Univ Cent Florida, Coll Opt & Photon, CREOL, Orlando, FL 32816 USA.; Abouraddy, AF (corresponding author), Univ Cent Florida, Dept Mat Sci & Engn, Orlando, FL 32816 USA.
EM raddy@creol.ucf.edu
FU US Air Force Office of Scientific Research (AFOSR) [FA-9550-12-1-0148]; AFOSR MURI [FA9550-14-1-0037]; US National Science Foundation [CMMI-1300773]; MIT MRSEC through the MRSEC Program of the National Science Foundation [DMR-1419807]
NR 56
TC 71
Z9 77
U1 10
U2 410
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 529
EP +
DI 10.1038/nature17980
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300049
PM 27281223
DA 2026-03-09
ER

PT J
AU Filacchione, G
   De Sanctis, MC
   Capaccioni, F
   Raponi, A
   Tosi, F
   Ciarniello, M
   Cerroni, P
   Piccioni, G
   Capria, MT
   Palomba, E
   Bellucci, G
   Erard, S
   Bockelee-Morvan, D
   Leyrat, C
   Arnold, G
   Barucci, MA
   Fulchignoni, M
   Schmitt, B
   Quirico, E
   Jaumann, R
   Stephan, K
   Longobardo, A
   Mennella, V
   Migliorini, A
   Ammannito, E
   Benkhoff, J
   Bibring, JP
   Blanco, A
   Blecka, MI
   Carlson, R
   Carsenty, U
   Colangeli, L
   Combes, M
   Combi, M
   Crovisier, J
   Drossart, P
   Encrenaz, T
   Federico, C
   Fink, U
   Fonti, S
   Ip, WH
   Irwin, P
   Kuehrt, E
   Langevin, Y
   Magni, G
   McCord, T
   Moroz, L
   Mottola, S
   Orofino, V
   Schade, U
   Taylor, F
   Tiphene, D
   Tozzi, GP
   Beck, P
   Biver, N
   Bonal, L
   Combe, JP
   Despan, D
   Flamini, E
   Formisano, M
   Fornasier, S
   Frigeri, A
   Grassi, D
   Gudipati, MS
   Kappel, D
   Mancarella, F
   Markus, K
   Merlin, F
   Orosei, R
   Rinaldi, G
   Cartacci, M
   Cicchetti, A
   Giuppi, S
   Hello, Y
   Henry, F
   Jacquinod, S
   Reess, JM
   Noschese, R
   Politi, R
   Peter, G
AF Filacchione, G.
   De Sanctis, M. C.
   Capaccioni, F.
   Raponi, A.
   Tosi, F.
   Ciarniello, M.
   Cerroni, P.
   Piccioni, G.
   Capria, M. T.
   Palomba, E.
   Bellucci, G.
   Erard, S.
   Bockelee-Morvan, D.
   Leyrat, C.
   Arnold, G.
   Barucci, M. A.
   Fulchignoni, M.
   Schmitt, B.
   Quirico, E.
   Jaumann, R.
   Stephan, K.
   Longobardo, A.
   Mennella, V.
   Migliorini, A.
   Ammannito, E.
   Benkhoff, J.
   Bibring, J. P.
   Blanco, A.
   Blecka, M. I.
   Carlson, R.
   Carsenty, U.
   Colangeli, L.
   Combes, M.
   Combi, M.
   Crovisier, J.
   Drossart, P.
   Encrenaz, T.
   Federico, C.
   Fink, U.
   Fonti, S.
   Ip, W. H.
   Irwin, P.
   Kuehrt, E.
   Langevin, Y.
   Magni, G.
   McCord, T.
   Moroz, L.
   Mottola, S.
   Orofino, V.
   Schade, U.
   Taylor, F.
   Tiphene, D.
   Tozzi, G. P.
   Beck, P.
   Biver, N.
   Bonal, L.
   Combe, J-Ph.
   Despan, D.
   Flamini, E.
   Formisano, M.
   Fornasier, S.
   Frigeri, A.
   Grassi, D.
   Gudipati, M. S.
   Kappel, D.
   Mancarella, F.
   Markus, K.
   Merlin, F.
   Orosei, R.
   Rinaldi, G.
   Cartacci, M.
   Cicchetti, A.
   Giuppi, S.
   Hello, Y.
   Henry, F.
   Jacquinod, S.
   Reess, J. M.
   Noschese, R.
   Politi, R.
   Peter, G.
TI Exposed water ice on the nucleus of comet 67P/Churyumov-Gerasimenko
SO NATURE
LA English
DT Article
ID optical-constants; crystalline h2o-ice; surface; virtis; rosetta
AB Although water vapour is the main species observed in the coma of comet 67P/Churyumov-Gerasimenko(1,2) and water is the major constituent of cometary nuclei(3,4), limited evidence for exposed water-ice regions on the surface of the nucleus has been found so far(5,6). The absence of large regions of exposed water ice seems a common finding on the surfaces of many of the comets observed so far(7-9). The nucleus of 67P/Churyumov-Gerasimenko appears to be fairly uniformly coated with dark, dehydrated, refractory and organic-rich material(10). Here we report the identification at infrared wavelengths of water ice on two debris falls in the Imhotep region of the nucleus. The ice has been exposed on the walls of elevated structures and at the base of the walls. A quantitative derivation of the abundance of ice in these regions indicates the presence of millimetre-sized pure water-ice grains, considerably larger than in all previous observations(6,7-9). Although micrometresized water-ice grains are the usual result of vapour recondensation in ice-free layers(6), the occurrence of millimetre-sized grains of pure ice as observed in the Imhotep debris falls is best explained by grain growth by vapour diffusion in ice-rich layers, or by sintering. As a consequence of these processes, the nucleus can develop an extended and complex coating in which the outer dehydrated crust(10) is superimposed on layers enriched in water ice. The stratigraphy observed on 67P/Churyumov-Gerasimenko(11,12) is therefore the result of evolutionary processes affecting the uppermost metres of the nucleus and does not necessarily require a global layering to have occurred at the time of the comet's formation.
C1 [Filacchione, G.; De Sanctis, M. C.; Capaccioni, F.; Raponi, A.; Tosi, F.; Ciarniello, M.; Cerroni, P.; Piccioni, G.; Capria, M. T.; Palomba, E.; Bellucci, G.; Longobardo, A.; Migliorini, A.; Magni, G.; Formisano, M.; Frigeri, A.; Grassi, D.; Rinaldi, G.; Cartacci, M.; Cicchetti, A.; Giuppi, S.; Noschese, R.; Politi, R.] IAPS, INAF, Rome, Italy.
   [Erard, S.; Bockelee-Morvan, D.; Leyrat, C.; Barucci, M. A.; Fulchignoni, M.; Combes, M.; Crovisier, J.; Drossart, P.; Encrenaz, T.; Tiphene, D.; Biver, N.; Despan, D.; Fornasier, S.; Merlin, F.; Hello, Y.; Henry, F.; Jacquinod, S.; Reess, J. M.] Univ Paris Diderot, UPMC, CNRS, LESIA,Observ Paris, Meudon, France.
   [Arnold, G.; Jaumann, R.; Stephan, K.; Carsenty, U.; Kuehrt, E.; Moroz, L.; Mottola, S.; Kappel, D.; Markus, K.] DLR, Inst Planetary Res, Berlin, Germany.
   [Schmitt, B.; Quirico, E.; Beck, P.; Bonal, L.] Univ Grenoble Alpes, CNRS, IPAG, Grenoble, France.
   [Mennella, V.] Osserv Astron Capodimonte, INAF, I-80131 Naples, Italy.
   [Ammannito, E.] Univ Calif Los Angeles, Los Angeles, CA USA.
   [Benkhoff, J.; Colangeli, L.] European Space Agcy ESTEC, Noordwijk, Netherlands.
   [Bibring, J. P.; Langevin, Y.] CNRS, Inst Astrophys Spatial, F-91405 Orsay, France.
   [Blanco, A.; Fonti, S.; Orofino, V.; Mancarella, F.] Univ Salento, Dipartimento Matemat & Fis Ennio De Giorgi, Lecce, Italy.
   [Blecka, M. I.] Polish Acad Sci, Space Res Ctr, PL-01237 Warsaw, Poland.
   [Carlson, R.; Gudipati, M. S.] NASA JPL, Pasadena, CA USA.
   [Combi, M.] Univ Michigan, Space Phys Res Lab, Ann Arbor, MI 48109 USA.
   [Federico, C.] Univ Perugia, I-06100 Perugia, Italy.
   [Fink, U.] Univ Arizona, Lunar Planetary Lab, Tucson, AZ USA.
   [Ip, W. H.] Natl Cent Univ, Taipei, Taiwan.
   [Irwin, P.; Taylor, F.] Univ Oxford, Dept Phys, Oxford, England.
   [McCord, T.; Combe, J-Ph.] Bear Fight Inst, Winthrop, WA USA.
   [Schade, U.] Helmholtz Zentrum Berlin Mat & Energie, Berlin, Germany.
   [Tozzi, G. P.] Osserv Astrofis Arcetri, INAF, I-50125 Florence, Italy.
   [Flamini, E.] Agenzia Spaziale Italiana, Rome, Italy.
   [Orosei, R.] INAF, Ist Radioastron, Bologna, Italy.
   [Peter, G.] DLR, Inst Opt Sensor Syst, Berlin, Germany.
C3 Istituto Nazionale Astrofisica (INAF); Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Helmholtz Association; German Aerospace Centre (DLR); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); Istituto Nazionale Astrofisica (INAF); University of California System; University of California Los Angeles; European Space Agency; European Space Research & Technology Centre; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); University of Salento; Polish Academy of Sciences; Space Research Centre of the Polish Academy of Sciences; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of Michigan System; University of Michigan; University of Perugia; University of Arizona; National Central University; University of Oxford; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); Istituto Nazionale Astrofisica (INAF); Agenzia Spaziale Italiana (ASI); Istituto Nazionale Astrofisica (INAF); Helmholtz Association; German Aerospace Centre (DLR)
RP Filacchione, G (corresponding author), IAPS, INAF, Rome, Italy.
EM gianrico.filacchione@iaps.inaf.it
FU Italian Space Agency (ASI, Italy); Centre National d'Etudes Spatiales (CNES, France); Deutsches Zentrum fur Luft - und Raumfahrt (DLR, Germany); National Aeronautic and Space Administration (NASA, USA); ASI; CNES; DLR; Science and Technology Facilities Council [ST/I001948/1, ST/K00106X/1, ST/N00082X/1] Funding Source: researchfish; UK Space Agency [ST/H004041/1, ST/I000658/1] Funding Source: researchfish; STFC [ST/N00082X/1, ST/K00106X/1, ST/I001948/1] Funding Source: UKRI
NR 35
TC 108
Z9 110
U1 0
U2 52
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 368
EP +
DI 10.1038/nature16190
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800040
PM 26760209
DA 2026-03-09
ER

PT J
AU Byrne, EFX
   Sircar, R
   Miller, PS
   Hedger, G
   Luchetti, G
   Nachtergaele, S
   Tully, MD
   Mydock-McGrane, L
   Covey, DF
   Rambo, RP
   Sansom, MSP
   Newstead, S
   Rohatgi, R
   Siebold, C
AF Byrne, Eamon F. X.
   Sircar, Ria
   Miller, Paul S.
   Hedger, George
   Luchetti, Giovanni
   Nachtergaele, Sigrid
   Tully, Mark D.
   Mydock-McGrane, Laurel
   Covey, Douglas F.
   Rambo, Robert P.
   Sansom, Mark S. P.
   Newstead, Simon
   Rohatgi, Rajat
   Siebold, Christian
TI Structural basis of Smoothened regulation by its extracellular domains
SO NATURE
LA English
DT Article
AB Developmental signals of the Hedgehog (Hh) and Wnt families are transduced across the membrane by Frizzled-class G-protein-coupled receptors (GPCRs) composed of both a heptahelical transmembrane domain (TMD) and an extracellular cysteine-rich domain (CRD). How the large extracellular domains of GPCRs regulate signalling by the TMD is unknown. We present crystal structures of the Hh signal transducer and oncoprotein Smoothened, a GPCR that contains two distinct ligand-binding sites: one in its TMD and one in the CRD. The CRD is stacked atop the TMD, separated by an intervening wedge-like linker domain. Structure-guided mutations show that the interface between the CRD, linker domain and TMD stabilizes the inactive state of Smoothened. Unexpectedly, we find a cholesterol molecule bound to Smoothened in the CRD binding site. Mutations predicted to prevent cholesterol binding impair the ability of Smoothened to transmit native Hh signals. Binding of a clinically used antagonist, vismodegib, to the TMD induces a conformational change that is propagated to the CRD, resulting in loss of cholesterol from the CRD-linker domain-TMD interface. Our results clarify the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains.
C1 [Byrne, Eamon F. X.; Miller, Paul S.; Siebold, Christian] Univ Oxford, Div Structural Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Sircar, Ria; Luchetti, Giovanni; Nachtergaele, Sigrid; Rohatgi, Rajat] Stanford Univ, Sch Med, Dept Biochem & Med, Stanford, CA 94305 USA.
   [Hedger, George; Sansom, Mark S. P.; Newstead, Simon] Univ Oxford, Dept Bioch, Oxford OX1 3QU, England.
   [Tully, Mark D.; Rambo, Robert P.] Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX1 0DE, Oxon, England.
   [Mydock-McGrane, Laurel; Covey, Douglas F.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
C3 University of Oxford; Wellcome Centre for Human Genetics; Stanford University; University of Oxford; Diamond Light Source; Washington University (WUSTL)
RP Rohatgi, R (corresponding author), Stanford Univ, Sch Med, Dept Biochem & Med, Stanford, CA 94305 USA.
EM rrohatgi@stanford.edu; christian@strubi.ox.ac.uk
FU Cancer Research UK [C20724/A14414]; US National Institutes of Health [GM106078, HL067773]; Wellcome Trust [102890/Z/13/Z, 092970/Z/10/Z, 090532/Z/09/Z]; Taylor Family Institute for Psychiatric Research; NDM Oxford; Medical Research Council UK; National Science Foundation; National Heart Lung and Blood Institute [R01HL067773] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007276, R35GM118082] Funding Source: NIH RePORTER; Cancer Research UK [14414] Funding Source: researchfish; Medical Research Council [1514534] Funding Source: researchfish; Wellcome Trust [102890/Z/13/Z] Funding Source: researchfish; Wellcome Trust [092970/Z/10/Z] Funding Source: Wellcome Trust
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NR 87
TC 289
Z9 333
U1 1
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 517
EP 522
DI 10.1038/nature18934
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600044
PM 27437577
DA 2026-03-09
ER

PT J
AU Rutz, C
   Klump, BC
   Komarczyk, L
   Leighton, R
   Kramer, J
   Wischnewski, S
   Sugasawa, S
   Morrissey, MB
   James, R
   St Clair, JJH
   Switzer, RA
   Masuda, BM
AF Rutz, Christian
   Klump, Barbara C.
   Komarczyk, Lisa
   Leighton, Rosanna
   Kramer, Joshua
   Wischnewski, Saskia
   Sugasawa, Shoko
   Morrissey, Michael B.
   James, Richard
   St Clair, James J. H.
   Switzer, Richard A.
   Masuda, Bryce M.
TI Discovery of species-wide tool use in the Hawaiian crow
SO NATURE
LA English
DT Article
ID alala corvus-hawaiiensis; caledonian crows; darwins finches; manufacture; evolution; incubation; behavior; ecology; origins; rooks
AB Only a handful of bird species are known to use foraging tools in the wild(1). Amongst them, the New Caledonian crow (Corvus moneduloides) stands out with its sophisticated tool-making skills(2,3). Despite considerable speculation, the evolutionary origins of this species' remarkable tool behaviour remain largely unknown, not least because no naturally tool-using congeners have yet been identified that would enable informative comparisons(4). Here we show that another tropical corvid, the 'Alala (C. hawaiiensis; Hawaiian crow), is a highly dexterous tool user. Although the 'Alala became extinct in the wild in the early 2000s, and currently survives only in captivity(5), at least two lines of evidence suggest that tool use is part of the species' natural behavioural repertoire: juveniles develop functional tool use without training, or social input from adults; and proficient tool use is a species-wide capacity. 'Alala and New Caledonian crows evolved in similar environments on remote tropical islands, yet are only distantly related(6), suggesting that their technical abilities arose convergently. This supports the idea that avian foraging tool use is facilitated by ecological conditions typical of islands, such as reduced competition for embedded prey and low predation risk(4,7). Our discovery creates exciting opportunities for comparative research on multiple tool-using and non-tool-using corvid species. Such work will in turn pave the way for replicated cross-taxonomic comparisons with the primate lineage, enabling valuable insights into the evolutionary origins of tool-using behaviour.
C1 [Rutz, Christian; Klump, Barbara C.; Wischnewski, Saskia; Sugasawa, Shoko; Morrissey, Michael B.; St Clair, James J. H.] Univ St Andrews, Sch Biol, Ctr Biol Divers, Sir Harold Mitchell Bldg, St Andrews KY16 9TH, Fife, Scotland.
   [Komarczyk, Lisa; Leighton, Rosanna; Masuda, Bryce M.] San Diego Zoo Global, Inst Conservat Res, POB 39, Volcano, HI 96785 USA.
   [Kramer, Joshua] San Diego Zoo Global, Inst Conservat Res, 2375 Olinda Rd, Makawao, HI 96768 USA.
   [James, Richard] Univ Bath, Dept Phys, Bath BA2 7AY, Avon, England.
   [James, Richard] Univ Bath, Ctr Networks & Collect Behav, Bath BA2 7AY, Avon, England.
   [Switzer, Richard A.] San Diego Zoo Global, Inst Conservat Res, 15600 San Pasqual Valley Rd, Escondido, CA 92027 USA.
C3 University of St Andrews; University of Bath; University of Bath
RP Rutz, C (corresponding author), Univ St Andrews, Sch Biol, Ctr Biol Divers, Sir Harold Mitchell Bldg, St Andrews KY16 9TH, Fife, Scotland.
EM christian.rutz@st-andrews.ac.uk
FU San Diego Zoo Global's IACUC animal welfare committee [12-017]; Biotechnology and Biological Sciences Research Council, UK (BBSRC) [BB/G023913/2]; University of St Andrews; JASSO; Royal Society of London; U.S. Fish and Wildlife Service; Hawai'i Division of Forestry and Wildlife; Moore Family Foundation; Marisla Foundation; Biotechnology and Biological Sciences Research Council [BB/G023913/2, 1466673] Funding Source: researchfish; BBSRC [BB/G023913/2] Funding Source: UKRI
NR 54
TC 80
Z9 94
U1 6
U2 188
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 403
EP +
DI 10.1038/nature19103
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000054
PM 27629645
DA 2026-03-09
ER

PT J
AU Li, L
   Park, E
   Ling, JJ
   Ingram, J
   Ploegh, H
   Rapoport, TA
AF Li, Long
   Park, Eunyong
   Ling, JingJing
   Ingram, Jessica
   Ploegh, Hidde
   Rapoport, Tom A.
TI Crystal structure of a substrate-engaged SecY protein-translocation channel
SO NATURE
LA English
DT Article
ID signal sequence recognition; endoplasmic-reticulum; membrane-protein; in-vivo; complex; mechanism; crystallization; visualization; peptides; system
AB Hydrophobic signal sequences target secretory polypeptides to a protein-conducting channel formed by a heterotrimeric membrane protein complex, the prokaryotic SecY or eukaryotic Sec61 complex. How signal sequences are recognized is poorly understood, particularly because they are diverse in sequence and length. Structures of the inactive channel show that the largest subunit, SecY or Sec61 alpha, consists of two halves that form an hourglass-shaped pore with a constriction in the middle of the membrane and a lateral gate that faces lipid(1-10). The cytoplasmic funnel is empty, while the extracellular funnel is filled with a plug domain. In bacteria, the SecY channel associates with the translating ribosome in co-translational translocation, and with the SecA ATPase in post-translational translocation(11). How a translocating polypeptide inserts into the channel is uncertain, as cryo-electron microscopy structures of the active channel have a relatively low resolution (similar to 10 angstrom) or are of insufficient quality(6-8). Here we report a crystal structure of the active channel, assembled from SecY complex, the SecA ATPase, and a segment of a secretory protein fused into SecA. The translocating protein segment inserts into the channel as a loop, displacing the plug domain. The hydrophobic core of the signal sequence forms a helix that sits in a groove outside the lateral gate, while the following polypeptide segment intercalates into the gate. The carboxy (C)-terminal section of the polypeptide loop is located in the channel, surrounded by residues of the pore ring. Thus, during translocation, the hydrophobic segments of signal sequences, and probably bilayer-spanning domains of nascent membrane proteins, exit the lateral gate and dock at a specific site that faces the lipid phase.
C1 [Li, Long; Park, Eunyong; Rapoport, Tom A.] Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA.
   [Li, Long; Park, Eunyong; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
   [Ling, JingJing; Ingram, Jessica; Ploegh, Hidde] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
   [Park, Eunyong] Rockefeller Univ, 1230 York Ave, New York, NY 10065 USA.
   [Park, Eunyong] Howard Hughes Med Inst, 1230 York Ave, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute; Rockefeller University; Howard Hughes Medical Institute
RP Li, L; Rapoport, TA (corresponding author), Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA.; Li, L; Rapoport, TA (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM long_li@hms.harvard.edu; tom_rapoport@hms.harvard.edu
FU National Institutes of Health [GM052586]; Pioneer Award; National Institute of General Medical Sciences [R01GM052586] Funding Source: NIH RePORTER
NR 51
TC 141
Z9 165
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 395
EP +
DI 10.1038/nature17163
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300058
PM 26950603
DA 2026-03-09
ER

PT J
AU Marcinkiewcz, CA
   Mazzone, CM
   D'Agostino, G
   Halladay, LR
   Hardaway, JA
   DiBerto, JF
   Navarro, M
   Burnham, N
   Cristiano, C
   Dorrier, CE
   Tipton, GJ
   Ramakrishnan, C
   Kozicz, T
   Deisseroth, K
   Thiele, TE
   McElligott, ZA
   Holmes, A
   Heisler, LK
   Kash, TL
AF Marcinkiewcz, Catherine A.
   Mazzone, Christopher M.
   D'Agostino, Giuseppe
   Halladay, Lindsay R.
   Hardaway, J. Andrew
   DiBerto, Jeffrey F.
   Navarro, Montserrat
   Burnham, Nathan
   Cristiano, Claudia
   Dorrier, Cayce E.
   Tipton, Gregory J.
   Ramakrishnan, Charu
   Kozicz, Tamas
   Deisseroth, Karl
   Thiele, Todd E.
   McElligott, Zoe A.
   Holmes, Andrew
   Heisler, Lora K.
   Kash, Thomas L.
TI Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala
SO NATURE
LA English
DT Article
ID stria terminalis; bed nucleus; citalopram; fluoxetine
AB Serotonin (also known as 5-hydroxytryptamine (5-HT)) is a neurotransmitter that has an essential role in the regulation of emotion. However, the precise circuits have not yet been defined through which aversive states are orchestrated by 5-HT. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminal's (CRFBNST,) in mice. Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT(2C)Rs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus. Furthermore, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behaviour following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin-releasing factor type 1 receptor (CRF1R, also known as CRHR1), given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN -> CRFBNST circuit governing fear and anxiety, and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders(1,2).
C1 [Marcinkiewcz, Catherine A.; Mazzone, Christopher M.; Hardaway, J. Andrew; DiBerto, Jeffrey F.; Dorrier, Cayce E.; Tipton, Gregory J.; Thiele, Todd E.; McElligott, Zoe A.; Kash, Thomas L.] Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
   [Mazzone, Christopher M.; Kash, Thomas L.] Univ North Carolina Chapel Hill, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA.
   [D'Agostino, Giuseppe; Cristiano, Claudia; Heisler, Lora K.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB25 2ZD, Scotland.
   [Halladay, Lindsay R.; Holmes, Andrew] NIAAA, NIH, Rockville, MD 20852 USA.
   [Navarro, Montserrat; Burnham, Nathan; Thiele, Todd E.; Kash, Thomas L.] Univ North Carolina Chapel Hill, Coll Arts & Sci, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA.
   [Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Kozicz, Tamas] Tulane Univ, Hayward Genet Ctr, New Orleans, LA 70112 USA.
   [Kozicz, Tamas] Radboud Univ Nijmegen, Med Ctr, Dept Anat, NL-6500 HB Nijmegen, Netherlands.
   [McElligott, Zoe A.] Univ North Carolina Chapel Hill, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [Kash, Thomas L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of Aberdeen; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Stanford University; Tulane University; Radboud University Nijmegen; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
RP Marcinkiewcz, CA (corresponding author), Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
FU NIH [AA019454, AA011605, K01AA023555]; Wellcome Trust [098012]; Biotechnology and Biological Sciences Research Council [BB/K001418/1]; Alcohol Beverage Medical Research Fund; NIAAA [AA021319-02, F31AA023440]; BBSRC [BB/K001418/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K001418/1] Funding Source: researchfish; National Institute on Alcohol Abuse and Alcoholism [ZIAAA000411, P60AA011605, R01AA019454] Funding Source: NIH RePORTER
NR 20
TC 350
Z9 425
U1 9
U2 164
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 97
EP 101
DI 10.1038/nature19318
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900046
PM 27556938
DA 2026-03-09
ER

PT J
AU Olsson, A
   Venkatasubramanian, M
   Chaudhri, VK
   Aronow, BJ
   Salomonis, N
   Singh, H
   Grimes, HL
AF Olsson, Andre
   Venkatasubramanian, Meenakshi
   Chaudhri, Viren K.
   Aronow, Bruce J.
   Salomonis, Nathan
   Singh, Harinder
   Grimes, H. Leighton
TI Single-cell analysis of mixed-lineage states leading to a binary cell fate choice
SO NATURE
LA English
DT Article
ID colony-stimulating factor; gene-expression-data; embryonic stem-cells; fluorescent protein; rna-seq; myeloid progenitor; human neutropenia; deficient mice; human genome; differentiation
AB Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators(1-5). Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level(6,7). Such mixed-lineage states may reflect the molecular priming of different developmental potentials by co-expressed alternative-lineage determinants, namely transcription factors. Although a bistable gene regulatory network has been proposed to regulate the specification of either neutrophils or macrophages(7,8), the nature of the transition states manifested in vivo, and the underlying dynamics of the cell-fate determinants, have remained elusive. Here we use single-cell RNA sequencing coupled with a new analytic tool, iterative clustering and guide-gene selection, and clonogenic assays to delineate hierarchical genomic and regulatory states that culminate in neutrophil or macrophage specification in mice. We show that this analysis captured prevalent mixed-lineage intermediates that manifested concurrent expression of haematopoietic stem cell/progenitor and myeloid progenitor cell genes. It also revealed rare metastable intermediates that had collapsed the haematopoietic stem cell/progenitor gene expression programme, instead expressing low levels of the myeloid determinants, Irf8 and Gfi1 (refs 9-13). Genetic perturbations and chromatin immunoprecipitation followed by sequencing revealed Irf8 and Gfi1 as key components of counteracting myeloid-gene-regulatory networks. Combined loss of these two determinants 'trapped' the metastable intermediate. We propose that mixed-lineage states are obligatory during cell-fate specification, manifest differing frequencies because of their dynamic instability and are dictated by counteracting gene-regulatory networks.
C1 [Olsson, Andre; Chaudhri, Viren K.; Singh, Harinder; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
   [Olsson, Andre; Chaudhri, Viren K.; Singh, Harinder; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Ctr Syst Immunol, Cincinnati, OH 45229 USA.
   [Venkatasubramanian, Meenakshi; Aronow, Bruce J.; Salomonis, Nathan] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
   [Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
C3 Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center
RP Singh, H; Grimes, HL (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.; Singh, H; Grimes, HL (corresponding author), Cincinnati Childrens Hosp Med Ctr, Ctr Syst Immunol, Cincinnati, OH 45229 USA.; Salomonis, N (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.; Grimes, HL (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
EM nathan.salomonis@cchmc.org; harinder.singh@cchmc.org; Lee.grimes@cchmc.org
FU NIH [AR-47363, DK78392, DK90971, RO1HL122661]; CCRF; CCHMC Divisions of Pathology and Oncology; National Center for Advancing Translational Sciences [UL1TR001425] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [R01HL122661] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK078392] Funding Source: NIH RePORTER
NR 50
TC 396
Z9 487
U1 0
U2 87
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 698
EP +
DI 10.1038/nature19348
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700054
PM 27580035
DA 2026-03-09
ER

PT J
AU Chung, JH
   Granja, I
   Taylor, MG
   Mpourmpakis, G
   Asplin, JR
   Rimer, JD
AF Chung, Jihae
   Granja, Ignacio
   Taylor, Michael G.
   Mpourmpakis, Giannis
   Asplin, John R.
   Rimer, Jeffrey D.
TI Molecular modifiers reveal a mechanism of pathological crystal growth inhibition
SO NATURE
LA English
DT Article
ID calcium-oxalate monohydrate; sodium-chlorate crystals; kidney-stones; crystallization; biomineralization; energy; shape; approximation; equilibrium; magnesium
AB Crystalline materials are crucial to the function of living organisms, in the shells of molluscs(1-3), the matrix of bone(4), the teeth of sea urchins5, and the exoskeletons of coccoliths(6). However, pathological biomineralization can be an undesirable crystallization process associated with human diseases(7-9). The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules(10,11) to large macromolecules(12). Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth(13,14). Complex inhibitor-crystal interactions in biomineralization are often not well elucidated(15). Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization-citrate and hydroxycitrate-exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones(16-19) and citrate is an often-used therapy(20), but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.
C1 [Chung, Jihae; Rimer, Jeffrey D.] Univ Houston, Dept Chem & Biomol Engn, Houston, TX 77204 USA.
   [Granja, Ignacio; Asplin, John R.] Litholink Corp, Lab Corp Amer Holdings, Chicago, IL 60612 USA.
   [Taylor, Michael G.; Mpourmpakis, Giannis] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15261 USA.
C3 University of Houston System; University of Houston; Litholink; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Rimer, JD (corresponding author), Univ Houston, Dept Chem & Biomol Engn, Houston, TX 77204 USA.; Asplin, JR (corresponding author), Litholink Corp, Lab Corp Amer Holdings, Chicago, IL 60612 USA.
EM asplinj@labcorp.com; jrimer@central.uh.edu
FU National Science Foundation [1207441, ACI-1053575]; Welch Foundation [E-1794]; University of Pittsburgh; Division Of Materials Research; Direct For Mathematical & Physical Scien [1207441] Funding Source: National Science Foundation
NR 65
TC 192
Z9 230
U1 5
U2 256
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 446
EP +
DI 10.1038/nature19062
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600039
PM 27501150
DA 2026-03-09
ER

PT J
AU Cocker, TL
   Peller, D
   Yu, P
   Repp, J
   Huber, R
AF Cocker, Tyler L.
   Peller, Dominik
   Yu, Ping
   Repp, Jascha
   Huber, Rupert
TI Tracking the ultrafast motion of a single molecule by femtosecond orbital imaging
SO NATURE
LA English
DT Article
ID attosecond control; dynamics; resolution; spectroscopy; electrons
AB Watching a single molecule move on its intrinsic timescale has been one of the central goals of modern nanoscience, and calls for measurements that combine ultrafast temporal resolution(1-8) with atomic spatial resolution(9-30). Steady-state experiments access the requisite spatial scales, as illustrated by direct imaging of individual molecular orbitals using scanning tunnelling microscopy(9-11) or the acquisition of tip-enhanced Raman and luminescence spectra with sub-molecular resolution(26-28). But tracking the intrinsic dynamics of a single molecule directly in the time domain faces the challenge that interactions with the molecule must be confined to a femtosecond time window. For individual nanoparticles, such ultrafast temporal confinement has been demonstrated(18) by combining scanning tunnelling microscopy with so-called lightwave electronics(1-8), which uses the oscillating carrier wave of tailored light pulses to directly manipulate electronic motion on timescales faster even than a single cycle of light. Here we build on ultrafast terahertz scanning tunnelling microscopy to access a state-selective tunnelling regime, where the peak of a terahertz electric-field waveform transiently opens an otherwise forbidden tunnelling channel through a single molecular state. It thereby removes a single electron from an individual pentacene molecule's highest occupied molecular orbital within a time window shorter than one oscillation cycle of the terahertz wave. We exploit this effect to record approximately 100-femtosecond snapshot images of the orbital structure with sub-angstrom spatial resolution, and to reveal, through pump/probe measurements, coherent molecular vibrations at terahertz frequencies directly in the time domain. We anticipate that the combination of lightwave electronics(1-8) and the atomic resolution of our approach will open the door to visualizing ultrafast photochemistry and the operation of molecular electronics on the single-orbital scale.
C1 [Cocker, Tyler L.; Peller, Dominik; Yu, Ping; Repp, Jascha; Huber, Rupert] Univ Regensburg, Dept Phys, D-93040 Regensburg, Germany.
C3 University of Regensburg
RP Repp, J; Huber, R (corresponding author), Univ Regensburg, Dept Phys, D-93040 Regensburg, Germany.
EM jascha.repp@physik.uni-regensburg.de; rupert.huber@physik.uni-regensburg.de
FU Volkswagen Foundation (Lichtenberg program); European Research Council [305003]; Deutsche Forschungsgemeinschaft (DFG) [GRK 1570];  [HU1598/3]; [CO1492/1]; European Research Council (ERC) [305003] Funding Source: European Research Council (ERC)
NR 36
TC 412
Z9 466
U1 9
U2 538
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 263
EP +
DI 10.1038/nature19816
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500039
PM 27830788
DA 2026-03-09
ER

PT J
AU Bulut-Karslioglu, A
   Biechele, S
   Jin, H
   Macrae, TA
   Hejna, M
   Gertsenstein, M
   Song, JS
   Ramalho-Santos, M
AF Bulut-Karslioglu, Aydan
   Biechele, Steffen
   Jin, Hu
   Macrae, Trisha A.
   Hejna, Miroslav
   Gertsenstein, Marina
   Song, Jun S.
   Ramalho-Santos, Miguel
TI Inhibition of mTOR induces a paused pluripotent state
SO NATURE
LA English
DT Article
ID mouse blastocyst; embryonic diapause; mice; differentiation; proliferation; implantation; derivation; autophagy; outgrowth; reveals
AB Cultured pluripotent stem cells are a cornerstone of regenerative medicine owing to their ability to give rise to all cell types of the body. Although pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a transient state in vivo, lasting 2-3 days around the time of blastocyst implantation(1). The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavourable conditions(2). Diapause is a physiological reproductive strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that the partial inhibition of mechanistic target of rapamycin (mTOR), a major nutrient sensor and promoter of growth(3), induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent-able to give rise to embryonic stem (ES) cells and live, fertile mice. We show that both naturally diapaused blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTOR activity, translation, histone modifications associated with gene activity and transcription. Pausing can be induced directly in cultured ES cells and sustained for weeks without appreciable cell death or deviations from cell cycle distributions. We show that paused ES cells display a remarkable global suppression of transcription, maintain a gene expression signature of diapaused blastocysts and remain pluripotent. These results uncover a new pluripotent stem cell state corresponding to the epiblast of the diapaused blastocyst and indicate that mTOR regulates developmental timing at the peri-implantation stage. Our findings have implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and ageing.
C1 [Bulut-Karslioglu, Aydan; Biechele, Steffen; Macrae, Trisha A.; Ramalho-Santos, Miguel] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Ctr Reprod Sci, San Francisco, CA 94143 USA.
   [Bulut-Karslioglu, Aydan; Biechele, Steffen; Macrae, Trisha A.; Ramalho-Santos, Miguel] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Ctr Diabet, San Francisco, CA 94143 USA.
   [Jin, Hu; Hejna, Miroslav; Song, Jun S.] Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61801 USA.
   [Jin, Hu; Hejna, Miroslav; Song, Jun S.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
   [Jin, Hu; Hejna, Miroslav; Song, Jun S.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Gertsenstein, Marina] Ctr Phenogen TCP, Toronto, ON M5T 3H7, Canada.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Ramalho-Santos, M (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Ctr Reprod Sci, San Francisco, CA 94143 USA.; Ramalho-Santos, M (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Ctr Diabet, San Francisco, CA 94143 USA.
EM mrsantos@ucsf.edu
FU [NIH 5P30CA082103];  [NIH P30DK063720];  [NSF 1442504];  [NIH R01CA163336];  [NIH R01OD012204];  [R01GM113014]; Div Of Biological Infrastructure; Direct For Biological Sciences [1442504] Funding Source: National Science Foundation; National Cancer Institute [P30CA082103, R01CA163336] Funding Source: NIH RePORTER
NR 37
TC 218
Z9 255
U1 1
U2 74
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 119
EP +
DI 10.1038/nature20578
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600060
PM 27880763
DA 2026-03-09
ER

PT J
AU Ma, XH
   Jing, Z
   Chang, P
   Liu, X
   Montuoro, R
   Small, RJ
   Bryan, FO
   Greatbatch, RJ
   Brandt, P
   Wu, DX
   Lin, XP
   Wu, LX
AF Ma, Xiaohui
   Jing, Zhao
   Chang, Ping
   Liu, Xue
   Montuoro, Raffaele
   Small, R. Justin
   Bryan, Frank O.
   Greatbatch, Richard J.
   Brandt, Peter
   Wu, Dexing
   Lin, Xiaopei
   Wu, Lixin
TI Western boundary currents regulated by interaction between ocean eddies and the atmosphere
SO NATURE
LA English
DT Article
ID kuroshio extension region; air-sea interaction; mesoscale eddy; climate model; north pacific; gulf-stream; eddy fluxes; variability; simulation; circulation
AB Current climate models systematically underestimate the strength of oceanic fronts associated with strong western boundary currents, such as the Kuroshio and Gulf Stream Extensions, and have difficulty simulating their positions at the mid-latitude ocean's western boundaries(1). Even with an enhanced grid resolution to resolve ocean mesoscale eddies-energetic circulations with horizontal scales of about a hundred kilometres that strongly interact with the fronts and currents-the bias problem can still persist(2); to improve climate models we need a better understanding of the dynamics governing these oceanic frontal regimes. Yet prevailing theories about the western boundary fronts are based on ocean internal dynamics without taking into consideration the intense air-sea feedbacks in these oceanic frontal regions. Here, by focusing on the Kuroshio Extension Jet east of Japan as the direct continuation of the Kuroshio, we show that feedback between ocean mesoscale eddies and the atmosphere (OME-A) is fundamental to the dynamics and control of these energetic currents. Suppressing OME-A feedback in eddy-resolving coupled climate model simulations results in a 20-40 per cent weakening in the Kuroshio Extension Jet. This is because OME-A feedback dominates eddy potential energy destruction, which dissipates more than 70 per cent of the eddy potential energy extracted from the Kuroshio Extension Jet. The absence of OME-A feedback inevitably leads to a reduction in eddy potential energy production in order to balance the energy budget, which results in a weakened mean current. The finding has important implications for improving climate models' representation of major oceanic fronts, which are essential components in the simulation and prediction of extratropical storms and other extreme events(3-6), as well as in the projection of the effect on these events of climate change.
C1 [Ma, Xiaohui; Jing, Zhao; Chang, Ping; Liu, Xue; Wu, Dexing; Lin, Xiaopei; Wu, Lixin] Ocean Univ China, Phys Oceanog Lab CIMST, Qingdao, Peoples R China.
   [Ma, Xiaohui; Jing, Zhao; Chang, Ping; Liu, Xue; Wu, Dexing; Lin, Xiaopei; Wu, Lixin] Qingdao Natl Lab Marine Sci & Technol, Qingdao, Peoples R China.
   [Ma, Xiaohui; Jing, Zhao; Chang, Ping; Liu, Xue] Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA.
   [Chang, Ping; Montuoro, Raffaele] Texas A&M Univ, Dept Atmospher Sci, College Stn, TX USA.
   [Small, R. Justin; Bryan, Frank O.] Natl Ctr Atmospher Res, Climate & Global Dynam Div, POB 3000, Boulder, CO 80307 USA.
   [Greatbatch, Richard J.; Brandt, Peter] GEOMAR Helmholtz Ctr Ocean Res Kiel, Kiel, Germany.
   [Greatbatch, Richard J.; Brandt, Peter] Univ Kiel, Fac Math & Nat Sci, Kiel, Germany.
C3 Ocean University of China; Laoshan Laboratory; Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; National Center Atmospheric Research (NCAR) - USA; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Kiel
RP Chang, P (corresponding author), Ocean Univ China, Phys Oceanog Lab CIMST, Qingdao, Peoples R China.; Chang, P (corresponding author), Qingdao Natl Lab Marine Sci & Technol, Qingdao, Peoples R China.; Chang, P (corresponding author), Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA.; Chang, P (corresponding author), Texas A&M Univ, Dept Atmospher Sci, College Stn, TX USA.
EM ping@tamu.edu
FU US National Science Foundation [AGS-1462127, AGS-1067937]; National Oceanic and Atmospheric Administration [NA11OAR4310154]; China's National Basic Research Priorities Programme [2013CB956204, 2014CB745000]; Natural Science Foundation of China [41490644, U1406401]; Excellence Cluster, Future Ocean, Kiel;  [SFB754]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1462127] Funding Source: National Science Foundation
NR 45
TC 286
Z9 313
U1 11
U2 254
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 533
EP +
DI 10.1038/nature18640
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600025
PM 27466126
DA 2026-03-09
ER

PT J
AU Zhang, SY
   Chang, LF
   Alfieri, C
   Zhang, ZG
   Yang, J
   Maslen, S
   Skehel, M
   Barford, D
AF Zhang, Suyang
   Chang, Leifu
   Alfieri, Claudio
   Zhang, Ziguo
   Yang, Jing
   Maslen, Sarah
   Skehel, Mark
   Barford, David
TI Molecular mechanism of APC/C activation by mitotic phosphorylation
SO NATURE
LA English
DT Article
ID anaphase-promoting complex; cyclin-ubiquitin ligase; cryo-em; mass-spectrometry; cell-cycle; protein; cyclosome; complex/cyclosome; recognition; binding
AB In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase(1,2). The catalytic activity of the APC/C and its ability to specify the destruction of particular proteins at different phases of the cell cycle are controlled by its interaction with two structurally related coactivator subunits, Cdc20 and Cdh1. Coactivators recognize substrate degrons(3), and enhance the affinity of the APC/C for its cognate E2 (refs 4-6). During mitosis, cyclin-dependent kinase (Cdk) and polo-like kinase (Plk) control Cdc20- and Cdh1-mediated activation of the APC/C. Hyperphosphorylation of APC/C subunits, notably Apc1 and Apc3, is required for Cdc20 to activate the APC/C7-12, whereas phosphorylation of Cdh1 prevents its association with the APC/C-9,C-13,C-14. Since both coactivators associate with the APC/C through their common C-box(15) and Ile-Arg tail motifs(16,17), the mechanism underlying this differential regulation is unclear, as is the role of specific APC/C phosphorylation sites. Here, using cryo-electron microscopy and biochemical analysis, we define the molecular basis of how phosphorylation of human APC/C allows for its control by Cdc20. An auto-inhibitory segment of Apc1 acts as a molecular switch that in apo unphosphorylated APC/C interacts with the C-box binding site and obstructs engagement of Cdc20. Phosphorylation of the auto-inhibitory segment displaces it from the C-box-binding site. Efficient phosphorylation of the auto-inhibitory segment, and thus relief of auto-inhibition, requires the recruitment of Cdk-cyclin in complex with a Cdk regulatory subunit (Cks) to a hyperphosphorylated loop of Apc3. We also find that the small-molecule inhibitor, tosyl-l-arginine methyl ester, preferentially suppresses APC/C-Cdc20 rather than APC/CCdh1, and interacts with the binding sites of both the C-box and Ile-Arg tail motifs. Our results reveal the mechanism for the regulation of mitotic APC/C by phosphorylation and provide a rationale for the development of selective inhibitors of this state.
C1 [Zhang, Suyang; Chang, Leifu; Alfieri, Claudio; Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Barford, D (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM dbarford@mrc-lmb.cam.ac.uk
FU MRC Laboratory of Molecular Biology; Cancer Research UK; Gates Cambridge Scholarship; Boehringer Ingelheim Fonds; MRC [MC_UP_1201/6] Funding Source: UKRI; Cancer Research UK [14109] Funding Source: researchfish; Medical Research Council [MC_UP_1201/6] Funding Source: researchfish
NR 45
TC 154
Z9 189
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 260
EP +
DI 10.1038/nature17973
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200053
PM 27120157
DA 2026-03-09
ER

PT J
AU Bloch, JI
   Woodruff, ED
   Wood, AR
   Rincon, AF
   Harrington, AR
   Morgan, GS
   Foster, DA
   Montes, C
   Jaramillo, CA
   Jud, NA
   Jones, DS
   MacFadden, BJ
AF Bloch, Jonathan I.
   Woodruff, Emily D.
   Wood, Aaron R.
   Rincon, Aldo F.
   Harrington, Arianna R.
   Morgan, Gary S.
   Foster, David A.
   Montes, Camilo
   Jaramillo, Carlos A.
   Jud, Nathan A.
   Jones, Douglas S.
   MacFadden, Bruce J.
TI First North American fossil monkey and early Miocene tropical biotic interchange
SO NATURE
LA English
DT Article
ID middle eocene; isthmus; platyrrhines; biogeography; calibration; chronology; emergence; mammalia; origins
AB New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma)(1). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions(2,3) of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants(4). Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.
C1 [Bloch, Jonathan I.; Woodruff, Emily D.; Wood, Aaron R.; Rincon, Aldo F.; Harrington, Arianna R.; Jud, Nathan A.; Jones, Douglas S.; MacFadden, Bruce J.] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [Woodruff, Emily D.; Harrington, Arianna R.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Wood, Aaron R.] Iowa State Univ, Dept Geol & Atmospher Sci, Ames, IA 50011 USA.
   [Rincon, Aldo F.; Foster, David A.] Univ Florida, Dept Geol Sci, Gainesville, FL 32611 USA.
   [Harrington, Arianna R.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA.
   [Morgan, Gary S.] New Mexico Museum Nat Hist & Sci, Albuquerque, NM 87104 USA.
   [Montes, Camilo] Univ Los Andes, Geociencias, Calle 1A 18A-10,Edificio IP, Bogota 111711, Colombia.
   [Jaramillo, Carlos A.] Smithsonian Trop Res Inst, Box 0843-03092, Balboa, Ancon, Panama.
C3 State University System of Florida; University of Florida; State University System of Florida; University of Florida; Iowa State University; State University System of Florida; University of Florida; Duke University; Universidad de los Andes (Colombia); Smithsonian Institution; Smithsonian Tropical Research Institute
RP Bloch, JI (corresponding author), Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
EM jbloch@flmnh.ufl.edu
FU National Science Foundation (NSF) [BCS 1304045, BCS 0851272]; Edward P. Bass Distinguished Visiting Environmental Scholar in the Yale Institute for Biospheric Studies (YIBS); NSF (PIRE project) [0966884]; Smithsonian Tropical Research Institute Paleobiology Fund; Florida Museum of Natural History; Direct For Biological Sciences; Div Of Biological Infrastructure [1203222] Funding Source: National Science Foundation; Office Of Internatl Science &Engineering; Office Of The Director [0966884] Funding Source: National Science Foundation
NR 30
TC 65
Z9 78
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 243
EP +
DI 10.1038/nature17415
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200049
PM 27096364
DA 2026-03-09
ER

PT J
AU Hacohen-Gourgy, S
   Martin, LS
   Flurin, E
   Ramasesh, VV
   Whaley, KB
   Siddiqi, I
AF Hacohen-Gourgy, Shay
   Martin, Leigh S.
   Flurin, Emmanuel
   Ramasesh, Vinay V.
   Whaley, K. Birgitta
   Siddiqi, Irfan
TI Quantum dynamics of simultaneously measured non-commuting observables
SO NATURE
LA English
DT Article
ID back-action
AB In quantum mechanics, measurements cause wavefunction collapse that yields precise outcomes, whereas for non-commuting observables such as position and momentum Heisenberg's uncertainty principle limits the intrinsic precision of a state. Although theoretical work(1) has demonstrated that it should be possible to perform simultaneous non-commuting measurements and has revealed the limits on measurement outcomes, only recently(2,3) has the dynamics of the quantum state been discussed. To realize this unexplored regime, we simultaneously apply two continuous quantum non-demolition probes of non-commuting observables to a superconducting qubit. We implement multiple readout channels by coupling the qubit to multiple modes of a cavity. To control the measurement observables, we implement a 'single quadrature' measurement by driving the qubit and applying cavity sidebands with a relative phase that sets the observable. Here, we use this approach to show that the uncertainty principle governs the dynamics of the wavefunction by enforcing a lower bound on the measurement-induced disturbance. Consequently, as we transition from measuring identical to measuring non-commuting observables, the dynamics make a smooth transition from standard wavefunction collapse to localized persistent diffusion and then to isotropic persistent diffusion. Although the evolution of the state differs markedly from that of a conventional measurement, information about both non-commuting observables is extracted by keeping track of the time ordering of the measurement record, enabling quantum state tomography without alternating measurements. Our work creates novel capabilities for quantum control, including rapid state purification(4), adaptive measurement(5,6), measurement-based state steering and continuous quantum error correction(7). As physical systems often interact continuously with their environment via non-commuting degrees of freedom, our work offers a way(8,9) to study how notions of contemporary quantum foundations(10-14) arise in such settings.
C1 [Hacohen-Gourgy, Shay; Martin, Leigh S.; Flurin, Emmanuel; Ramasesh, Vinay V.; Siddiqi, Irfan] Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
   [Hacohen-Gourgy, Shay; Martin, Leigh S.; Flurin, Emmanuel; Ramasesh, Vinay V.; Siddiqi, Irfan] Univ Calif Berkeley, Ctr Quantum Coherent Sci, Berkeley, CA 94720 USA.
   [Martin, Leigh S.; Whaley, K. Birgitta] Berkeley Ctr Quantum Informat & Computat, Berkeley, CA 94720 USA.
   [Whaley, K. Birgitta] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Hacohen-Gourgy, S (corresponding author), Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.; Hacohen-Gourgy, S (corresponding author), Univ Calif Berkeley, Ctr Quantum Coherent Sci, Berkeley, CA 94720 USA.
EM shayhh@berkeley.edu
FU National Science Foundation [1106400]; Berkeley Fellowship for Graduate Study; Air Force Office of Scientific Research [FA9550-12-1-0378]; Army Research Office [W911NF-15-1-0496]
CR Ahn C, 2002, PHYS REV A, V65, P0, DOI 10.1103/PhysRevA.65.042301
   ARTHURS E, 1965, AT&T TECH J, V44, P725, DOI 10.1002/j.1538-7305.1965.tb01684.x
   Castellanos-Beltran MA, 2008, NAT PHYS, V4, P929, DOI 10.1038/nphys1090
   CAVES CM, 1980, REV MOD PHYS, V52, P341, DOI 10.1103/RevModPhys.52.341
   Combes J, 2010, PHYS REV A, V81, P0, DOI 10.1103/PhysRevA.81.020301
   Didier N, 2015, PHYS REV LETT, V115, P0, DOI 10.1103/PhysRevLett.115.203601
   Dressel J, 2013, THESIS, V0, P0
   Dressel J, 2014, PHYS REV A, V89, P0, DOI 10.1103/PhysRevA.89.022106
   Erhart J, 2012, NAT PHYS, V8, P185, DOI 10.1038/NPHYS2194
   Gambetta J, 2008, PHYS REV A, V77, P0, DOI 10.1103/PhysRevA.77.012112
   Hatridge M, 2013, SCIENCE, V339, P178, DOI 10.1126/science.1226897
   Hertzberg JB, 2010, NAT PHYS, V6, P213, DOI 10.1038/NPHYS1479
   Jacobs K, 2003, PHYS REV A, V67, P0, DOI 10.1103/PhysRevA.67.030301
   Jordan AN, 2005, PHYS REV LETT, V95, P0, DOI 10.1103/PhysRevLett.95.220401
   Kirchmair G, 2009, NATURE, V460, P494, DOI 10.1038/nature08172
   Koch J, 2007, PHYS REV A, V76, P0, DOI 10.1103/PhysRevA.76.042319
   KOCHEN S, 1967, J MATH MECH, V17, P59
   Luis Pedro Garca-Pintos JD, 2016, PREPRINT, V0, P0
   Maccone L, 2014, PHYS REV LETT, V113, P0, DOI 10.1103/PhysRevLett.113.260401
   Murch KW, 2013, NATURE, V502, P211, DOI 10.1038/nature12539
   Murch KW, 2012, PHYS REV LETT, V109, P0, DOI 10.1103/PhysRevLett.109.183602
   Nielson MichaelA, 2010, QUANTUM COMPUTATION AND QUANTUM INFORMATION, V0, P0
   Nishizawa A, 2015, PREPRINT, V0, P0
   Ozawa M, 2003, PHYS REV A, V67, P0, DOI 10.1103/PhysRevA.67.042105
   Ruskov R, 2012, PHILOS T R SOC A, V370, P5291, DOI 10.1098/rsta.2011.0516
   Ruskov R, 2010, PHYS REV LETT, V105, P0, DOI 10.1103/PhysRevLett.105.100506
   Six P, 2016, PHYS REV A, V93, P0, DOI 10.1103/PhysRevA.93.012109
   Vool U, 2011, PREPRINT, V0, P0
   WISEMAN HM, 1995, PHYS REV LETT, V75, P4587, DOI 10.1103/PhysRevLett.75.4587
NR 29
TC 120
Z9 149
U1 2
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 491
EP +
DI 10.1038/nature19762
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400053
PM 27706145
DA 2026-03-09
ER

PT J
AU Schwörer, S
   Becker, F
   Feller, C
   Baig, AH
   Köber, U
   Henze, H
   Kraus, JM
   Xin, BB
   Lechel, A
   Lipka, DB
   Varghese, CS
   Schmidt, M
   Rohs, R
   Aebersold, R
   Medina, KL
   Kestler, HA
   Neri, F
   von Maltzahn, J
   Tumpel, S
   Rudolph, KL
AF Schwoerer, Simon
   Becker, Friedrich
   Feller, Christian
   Baig, Ali H.
   Koeber, Ute
   Henze, Henriette
   Kraus, Johann M.
   Xin, Beibei
   Lechel, Andre
   Lipka, Daniel B. .
   Varghese, Christy S.
   Schmidt, Manuel
   Rohs, Remo
   Aebersold, Ruedi
   Medina, Kay L.
   Kestler, Hans A.
   Neri, Francesco
   von Maltzahn, Julia
   Tumpel, Stefan
   Rudolph, K. Lenhard
TI Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals
SO NATURE
LA English
DT Article
ID skeletal-muscle; self-renewal; genes; mouse; bromodomain; inhibition; quiescence; defects; design; fate
AB The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function(1). Alterations in developmental pathways have been associated with declines in stem-cell function during ageing(2-6), but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing(7,8). Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGF beta, JAK/STAT and senescence signalling(2-4,6). Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.
C1 [Schwoerer, Simon; Becker, Friedrich; Baig, Ali H.; Koeber, Ute; Henze, Henriette; Varghese, Christy S.; Schmidt, Manuel; Kestler, Hans A.; Neri, Francesco; von Maltzahn, Julia; Tumpel, Stefan; Rudolph, K. Lenhard] FLI, Leibniz Inst Aging, Beutenbergstr 11, D-07745 Jena, Germany.
   [Feller, Christian; Aebersold, Ruedi] Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Auguste Piccard Hof 1, CH-8093 Zurich, Switzerland.
   [Kraus, Johann M.; Kestler, Hans A.] Univ Ulm, Inst Med Syst Biol, D-89081 Ulm, Germany.
   [Xin, Beibei; Rohs, Remo] Univ Southern Calif, Mol & Computat Biol Program, 1050 Childs Way, Los Angeles, CA 90089 USA.
   [Lechel, Andre] Univ Ulm, Dept Internal Med 1, Albert Einstein Allee 23, D-89081 Ulm, Germany.
   [Lipka, Daniel B. .] DKFZ, Div Epigen & Canc Risk Factors, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, Zurich, Switzerland.
   [Medina, Kay L.] Mayo Clin, Dept Immunol, 200 First St SW, Rochester, MN 55905 USA.
   [Rudolph, K. Lenhard] Friedrich Schiller Univ, Fac Med, Jena, Germany.
C3 Leibniz Association; Leibniz Institut fur Alternsforschung - Fritz-Lipmann-Institut (FLI); Friedrich Loeffler Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich; Ulm University; University of Southern California; Ulm University; Helmholtz Association; German Cancer Research Center (DKFZ); University of Zurich; Mayo Clinic; Friedrich Schiller University of Jena
RP von Maltzahn, J; Tumpel, S; Rudolph, KL (corresponding author), FLI, Leibniz Inst Aging, Beutenbergstr 11, D-07745 Jena, Germany.; Rudolph, KL (corresponding author), Friedrich Schiller Univ, Fac Med, Jena, Germany.
EM julia.vonmaltzahn@leibniz-fli.de; stefan.tuempel@leibniz-fli.de; lenhard.rudolph@leibniz-fli.de
FU DGF [RU-745/10, RU-745/12]; ERC [2012-AdG 323136, AdvGr 670821]; state of Thuringia; Leibniz association; DFG [MA-3975/2-1, FE-1544/1-1, SFB 1074]; EMBO [ALTF 55-2015]; NIH [HL096108, R01GM106056]; BMBF [0315894A]; European Community [602783]
NR 53
TC 104
Z9 121
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 428
EP +
DI 10.1038/nature20603
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800041
PM 27919074
DA 2026-03-09
ER

PT J
AU Davies, B
   Hatton, E
   Altemose, N
   Hussin, JG
   Pratto, F
   Zhang, G
   Hinch, AG
   Moralli, D
   Biggs, D
   Diaz, R
   Preece, C
   Li, R
   Bitoun, E
   Brick, K
   Green, CM
   Amerini-Otero, RDC
   Myers, SR
   Donnelly, P
AF Davies, Benjamin
   Hatton, Edouard
   Altemose, Nicolas
   Hussin, Julie G.
   Pratto, Florencia
   Zhang, Gang
   Hinch, Anjali Gupta
   Moralli, Daniela
   Biggs, Daniel
   Diaz, Rebeca
   Preece, Chris
   Li, Ran
   Bitoun, Emmanuelle
   Brick, Kevin
   Green, Catherine M.
   Amerini-Otero, R. Daniel C.
   Myers, Simon R.
   Donnelly, Peter
TI Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice
SO NATURE
LA English
DT Article
ID histone h3 methyltransferase; recombination hot-spot; meiotic recombination; homology search; alignment; complex; drive; gene
AB The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such ` symmetric' PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation.
C1 [Davies, Benjamin; Hatton, Edouard; Altemose, Nicolas; Hussin, Julie G.; Zhang, Gang; Hinch, Anjali Gupta; Moralli, Daniela; Biggs, Daniel; Diaz, Rebeca; Preece, Chris; Li, Ran; Bitoun, Emmanuelle; Green, Catherine M.; Myers, Simon R.; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Altemose, Nicolas; Li, Ran; Myers, Simon R.; Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3LB, England.
   [Pratto, Florencia; Brick, Kevin; Amerini-Otero, R. Daniel C.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
C3 University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Donnelly, P (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM myers@stats.ox.ac.uk; donnelly@well.ox.ac.uk
FU Wellcome Trust [090532/Z/09/Z, 095552/Z/11/Z, 098387/Z/12/Z]; NIDDK Intramural Research Program; Nuffield Department of Medicine Prize Studentship; Human Frontiers Postdoctoral Program [LT-001017/2013-L]; Wellcome Trust [095552/Z/11/Z] Funding Source: researchfish; National Institute of Diabetes and Digestive and Kidney Diseases [ZICDK071001, ZIADK052034] Funding Source: NIH RePORTER
NR 40
TC 151
Z9 188
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 171
EP +
DI 10.1038/nature16931
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700029
PM 26840484
DA 2026-03-09
ER

PT J
AU He, Y
   Yan, CL
   Fang, J
   Inouye, C
   Tjian, R
   Ivanov, I
   Nogales, E
AF He, Yuan
   Yan, Chunli
   Fang, Jie
   Inouye, Carla
   Tjian, Robert
   Ivanov, Ivaylo
   Nogales, Eva
TI Near-atomic resolution visualization of human transcription promoter opening
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; structural basis; general transcription; preinitiation complex; crystal-structure; conformational-changes; abortive initiation; elongation complex; swi2/snf2 atpase; binding domain
AB In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA-RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB.
C1 [He, Yuan; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrat Bioimaging Div, Berkeley, CA 94720 USA.
   [He, Yuan] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
   [Yan, Chunli; Ivanov, Ivaylo] Georgia State Univ, Ctr Diagnost & Therapeut, Dept Chem, Atlanta, GA 30302 USA.
   [Fang, Jie; Tjian, Robert; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Inouye, Carla; Tjian, Robert] Univ Calif Berkeley, Li Ka Shing Ctr Biomed & Hlth Sci, Berkeley, CA 94720 USA.
   [Tjian, Robert; Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Northwestern University; University System of Georgia; Georgia State University; Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Stanford University; Li Ka Shing Center; University of California System; University of California Berkeley
RP He, Y; Nogales, E (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrat Bioimaging Div, Berkeley, CA 94720 USA.; He, Y (corresponding author), Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.; Nogales, E (corresponding author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.; Nogales, E (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM yuanhe@northwestern.edu; ENogales@lbl.gov
FU NIGMS [GM63072, GM110387]; National Science Foundation [MCB-1149521]; National Cancer Institute [P30CA060553] Funding Source: NIH RePORTER; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1149521] Funding Source: National Science Foundation
NR 92
TC 238
Z9 287
U1 2
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 359
EP +
DI 10.1038/nature17970
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300041
PM 27193682
DA 2026-03-09
ER

PT J
AU Murphy, JJ
   Bastida, D
   Paria, S
   Fagnoni, M
   Melchiorre, P
AF Murphy, John J.
   Bastida, David
   Paria, Suva
   Fagnoni, Maurizio
   Melchiorre, Paolo
TI Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals
SO NATURE
LA English
DT Article
ID enantioselective synthesis; conjugate additions; centers; construction; photoredox; alkenes; advent
AB An important goal of modern organic chemistry is to develop new catalytic strategies for enantioselective carbon-carbon bond formation that can be used to generate quaternary stereogenic centres. Whereas considerable advances have been achieved by exploiting polar reactivity(1), radical transformations have been far less successful(2). This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors(3). Here we show how the combination of photoredox(4) and asymmetric organic catalysis(5) enables enantioselective radical conjugate additions to beta,beta-disubstituted cyclic enones to obtain quaternary carbon stereocentres with high fidelity. Critical to our success was the design of a chiral organic catalyst, containing a redox-active carbazole moiety, that drives the formation of iminium ions and the stereoselective trapping of photochemically generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts-this method represents the application of iminium ion activation(6) (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.
C1 [Murphy, John J.; Bastida, David; Paria, Suva; Melchiorre, Paolo] Barcelona Inst Sci & Technol, Inst Chem Res Catalonia ICIQ, Avda Paisos Catalans 16, Tarragona 43007, Spain.
   [Fagnoni, Maurizio] Univ Pavia, Dept Chem, Photogreen Lab, Viale Taramelli 12, I-27100 Pavia, Italy.
   [Melchiorre, Paolo] Catalan Inst Res & Adv Studies ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Universitat Rovira i Virgili; Institute of Chemical Research of Catalonia; University of Pavia; ICREA
RP Melchiorre, P (corresponding author), Barcelona Inst Sci & Technol, Inst Chem Res Catalonia ICIQ, Avda Paisos Catalans 16, Tarragona 43007, Spain.; Melchiorre, P (corresponding author), Catalan Inst Res & Adv Studies ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
EM pmelchiorre@iciq.es
FU ICIQ Foundation; MINECO [CTQ2013-45938-P]; MINECO (Severo Ochoa Excellence Accreditation) [SEV-2013-0319]; AGAUR [2014 SGR 1059]; European Research Council (ORGA-NAUT) [ERC 278541]; Marie Curie COFUND [291787-ICIQ-IPMP]; CELLEX Foundation; ICREA Funding Source: Custom
NR 30
TC 359
Z9 393
U1 14
U2 364
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 218
EP 222
DI 10.1038/nature17438
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100036
PM 27075098
DA 2026-03-09
ER

PT J
AU Ohta, K
   Kuwayama, Y
   Hirose, K
   Shimizu, K
   Ohishi, Y
AF Ohta, Kenji
   Kuwayama, Yasuhiro
   Hirose, Kei
   Shimizu, Katsuya
   Ohishi, Yasuo
TI Experimental determination of the electrical resistivity of iron at Earth's core conditions
SO NATURE
LA English
DT Article
ID thermal-conductivity; high-pressure; liquid fe; alloy; convection; evolution; state
AB Earth continuously generates a dipole magnetic field in its convecting liquid outer core by a self-sustained dynamo action. Metallic iron is a dominant component of the outer core, so its electrical and thermal conductivity controls the dynamics and thermal evolution of Earth's core(1). However, in spite of extensive research, the transport properties of iron under core conditions are still controversial(2-9). Since free electrons are a primary carrier of both electric current and heat, the electron scattering mechanism in iron under high pressure and temperature holds the key to understanding the transport properties of planetary cores. Here we measure the electrical resistivity (the reciprocal of electrical conductivity) of iron at the high temperatures (up to 4,500 kelvin) and pressures (megabars) of Earth's core in a laser-heated diamond-anvil cell. The value measured for the resistivity of iron is even lower than the value extrapolated from high-pressure, low-temperature data using the Bloch-Gruneisen law, which considers only the electron-phonon scattering. This shows that the iron resistivity is strongly suppressed by the resistivity saturation effect at high temperatures. The low electrical resistivity of iron indicates the high thermal conductivity of Earth's core, suggesting rapid core cooling and a young inner core less than 0.7 billion years old(10). Therefore, an abrupt increase in palaeomagnetic field intensity around 1.3 billion years ago(11) may not be related to the birth of the inner core.
C1 [Ohta, Kenji] Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, 2-12-1 Ookayama, Tokyo 1528551, Japan.
   [Kuwayama, Yasuhiro] Ehime Univ, Geodynam Res Ctr, 2-5 Bunkyo Cho, Matsuyama, Ehime 7908577, Japan.
   [Hirose, Kei] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, 2-12-1 Ookayama, Tokyo 1528550, Japan.
   [Hirose, Kei] Japan Agcy Marine Earth Sci & Technol, Lab Ocean Earth Life Evolut Res, 2-15 Natsushima Cho, Yokosuka, Kanagawa 2370061, Japan.
   [Shimizu, Katsuya] Osaka Univ, Ctr Sci & Technol Extreme Condit, 1-3 Machikaneyama, Toyonaka, Osaka 5608531, Japan.
   [Ohishi, Yasuo] Japan Synchrotron Radiat Res Inst, 1-1-1 Koto, Sayo, Hyogo 6795198, Japan.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; Ehime University; Institute of Science Tokyo; Tokyo Institute of Technology; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); University of Osaka; Japan Synchrotron Radiation Research Institute
RP Ohta, K (corresponding author), Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, 2-12-1 Ookayama, Tokyo 1528551, Japan.
EM k-ohta@geo.titech.ac.jp
FU Grants-in-Aid for Scientific Research [16H06285, 26800274, 26707029, 15H05827] Funding Source: KAKEN
NR 44
TC 232
Z9 265
U1 3
U2 150
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 95
EP +
DI 10.1038/nature17957
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300040
PM 27251282
DA 2026-03-09
ER

PT J
AU Oren-Suissa, M
   Bayer, EA
   Hobert, O
AF Oren-Suissa, Meital
   Bayer, Emily A.
   Hobert, Oliver
TI Sex-specific pruning of neuronal synapses in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID c. elegans; mating-behavior; nematode; genetics
AB Whether and how neurons that are present in both sexes of the same species can differentiate in a sexually dimorphic manner is not well understood. A comparison of the connectomes of the Caenorhabditis elegans hermaphrodite and male nervous systems reveals the existence of sexually dimorphic synaptic connections between neurons present in both sexes. Here we demonstrate sex-specific functions of these sex-shared neurons and show that many neurons initially form synapses in a hybrid manner in both the male and hermaphrodite pattern before sexual maturation. Sex-specific synapse pruning then results in the sex-specific maintenance of subsets of these connections. Reversal of the sexual identity of either the pre- or postsynaptic neuron alone transforms the patterns of synaptic connectivity to that of the opposite sex. A dimorphically expressed and phylogenetically conserved transcription factor is both necessary and sufficient to determine sex-specific connectivity patterns. Our studies reveal new insights into sex-specific circuit development.
C1 [Oren-Suissa, Meital; Bayer, Emily A.; Hobert, Oliver] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Oren-Suissa, Meital; Bayer, Emily A.; Hobert, Oliver] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
   [Oren-Suissa, Meital; Bayer, Emily A.; Hobert, Oliver] Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA.
C3 Columbia University; Columbia University; Columbia University; Howard Hughes Medical Institute
RP Oren-Suissa, M; Hobert, O (corresponding author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.; Oren-Suissa, M; Hobert, O (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.; Oren-Suissa, M; Hobert, O (corresponding author), Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA.
EM meitals@gmail.com; or38@columbia.edu
FU EMBO; HFSP; NIH [2R37NS039996]; HHMI; Weizmann Institute of Science, National Postdoctoral Award Program for Advancing Women in Science; National Institute of Neurological Disorders and Stroke [R37NS039996] Funding Source: NIH RePORTER
NR 38
TC 98
Z9 132
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 206
EP +
DI 10.1038/nature17977
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200041
PM 27144354
DA 2026-03-09
ER

PT J
AU Couvillion, MT
   Soto, IC
   Shipkovenska, G
   Churchman, LS
AF Couvillion, Mary T.
   Soto, Iliana C.
   Shipkovenska, Gergana
   Churchman, L. Stirling
TI Synchronized mitochondrial and cytosolic translation programs
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; in-vivo; protein-synthesis; gene-expression; yeast; rna; polymerase; initiation; adaptation; alignment
AB Oxidative phosphorylation (OXPHOS) is a vital process for energy generation, and is carried out by complexes within the mitochondria. OXPHOS complexes pose a unique challenge for cells because their subunits are encoded on both the nuclear and the mitochondrial genomes. Genomic approaches designed to study nuclear/cytosolic and bacterial gene expression have not been broadly applied to mitochondria, so the co-regulation of OXPHOS genes remains largely unexplored. Here we monitor mitochondrial and nuclear gene expression in Saccharomyces cerevisiae during mitochondrial biogenesis, when OXPHOS complexes are synthesized. We show that nuclear-and mitochondrial-encoded OXPHOS transcript levels do not increase concordantly. Instead, mitochondrial and cytosolic translation are rapidly, dynamically and synchronously regulated. Furthermore, cytosolic translation processes control mitochondrial translation unidirectionally. Thus, the nuclear genome coordinates mitochondrial and cytosolic translation to orchestrate the timely synthesis of OXPHOS complexes, representing an unappreciated regulatory layer shaping the mitochondrial proteome. Our whole-cell genomic profiling approach establishes a foundation for studies of global gene regulation in mitochondria.
C1 [Couvillion, Mary T.; Soto, Iliana C.; Shipkovenska, Gergana; Churchman, L. Stirling] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Churchman, LS (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM churchman@genetics.med.harvard.edu
FU Damon Runyon Cancer Research Foundation; Burroughs Wellcome Fund Career Award at the Scientific Interface; Ellison Medical Foundation; National Institutes of Health; Boehringer Ingelheim
NR 49
TC 267
Z9 301
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 499
EP +
DI 10.1038/nature18015
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100033
PM 27225121
DA 2026-03-09
ER

PT J
AU Wilhelm, K
   Happel, K
   Eelen, G
   Schoors, S
   Oellerich, MF
   Lim, R
   Zimmermann, B
   Aspalter, IM
   Franco, CA
   Boettger, T
   Braun, T
   Fruttiger, M
   Rajewsky, K
   Keller, C
   Brüning, JC
   Gerhardt, H
   Carmeliet, P
   Potente, M
AF Wilhelm, Kerstin
   Happel, Katharina
   Eelen, Guy
   Schoors, Sandra
   Oellerich, Mark F.
   Lim, Radiance
   Zimmermann, Barbara
   Aspalter, Irene M.
   Franco, Claudio A.
   Boettger, Thomas
   Braun, Thomas
   Fruttiger, Marcus
   Rajewsky, Klaus
   Keller, Charles
   Bruening, Jens C.
   Gerhardt, Holger
   Carmeliet, Peter
   Potente, Michael
TI FOXO1 couples metabolic activity and growth state in the vascular endothelium
SO NATURE
LA English
DT Article
ID transcription factor; gene-expression; myc; identification; angiogenesis; cells; mice; maintenance; homeostasis; insulin
AB Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements(1). Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation(2,3). Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function(1,4), yet it is poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by MYC (also known as c-MYC), a powerful driver of anabolic metabolism and growth(5,6). MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalizes metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1-MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation.
C1 [Wilhelm, Kerstin; Happel, Katharina; Oellerich, Mark F.; Lim, Radiance; Zimmermann, Barbara; Potente, Michael] Max Planck Inst Heart & Lung Res, Angiogenesis & Metab Lab, D-61231 Bad Nauheim, Germany.
   [Eelen, Guy; Schoors, Sandra; Carmeliet, Peter] Univ Leuven, Dept Oncol, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Leuven, Belgium.
   [Eelen, Guy; Schoors, Sandra; Carmeliet, Peter] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Leuven, Belgium.
   [Aspalter, Irene M.; Gerhardt, Holger] Canc Res UK, London Res Inst, Vasc Biol Lab, London WC2A 3LY, England.
   [Franco, Claudio A.] Univ Lisbon, Fac Med, Inst Med Mol, Vasc Morphogenesis Lab, P-1649028 Lisbon, Portugal.
   [Boettger, Thomas; Braun, Thomas] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, D-61231 Bad Nauheim, Germany.
   [Fruttiger, Marcus] UCL, UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Rajewsky, Klaus; Gerhardt, Holger] Max Delbruck Ctr Mol Med MDC, D-13125 Berlin, Germany.
   [Keller, Charles] Childrens Canc Therapy Dev Inst, Beaverton, OR 97005 USA.
   [Bruening, Jens C.] Univ Cologne, Max Planck Inst Metab Res, Excellence Cluster Cellular Stress Responses Agin, D-50931 Cologne, Germany.
   [Bruening, Jens C.] Univ Cologne, CMMC, Ctr Endocrinol Diabet & Prevent Med CEDP, D-50931 Cologne, Germany.
   [Gerhardt, Holger] VIB, Vesalius Res Ctr, Vasc Patterning Lab, B-3000 Leuven, Belgium.
   [Gerhardt, Holger] Univ Leuven, B-3000 Leuven, Belgium.
   [Gerhardt, Holger] DZHK German Ctr Cardiovasc Res, D-13347 Berlin, Germany.
   [Gerhardt, Holger] BIH, D-10117 Berlin, Germany.
   [Potente, Michael] Int Inst Mol & Cell Biol, PL-02109 Warsaw, Poland.
   [Potente, Michael] DZHK German Ctr Cardiovasc Res, D-13347 Berlin, Germany.
C3 Max Planck Society; KU Leuven; Flanders Institute for Biotechnology (VIB); Cancer Research UK; Universidade de Lisboa; Max Planck Society; University of London; University College London; Helmholtz Association; Max Delbruck Center for Molecular Medicine; University of Cologne; University of Cologne; Flanders Institute for Biotechnology (VIB); KU Leuven; German Centre for Cardiovascular Research; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; Miedzynarodowy Instytut Biologii Molekularnej i Komorkowej; German Centre for Cardiovascular Research
RP Potente, M (corresponding author), Max Planck Inst Heart & Lung Res, Angiogenesis & Metab Lab, D-61231 Bad Nauheim, Germany.
EM michael.potente@mpi-bn.mpg.de
FU Max Planck Society; European Research Council (ERC) [311546]; Deutsche Forschungsgemeinschaft [SFB 834]; Excellence Cluster Cardiopulmonary System [EXC 147/1]; Cluster of Excellence Macromolecular Complexes [EXC115]; Foundation Leducq Transatlantic Network (ARTEMIS); LOEWE grant Ub-Net; European Molecular Biology Organization Young Investigator Programme; Austrian Academy of Sciences; European Union FP7 Marie Curie Post-doctoral Fellowship; FCT [IF/00412/2012]; ERC [268921, 269073]; National Institutes of Health [K08CA090438]; Cancer Research UK; ERC consolidator grant (REshape); Lister Institute of Preventive Medicine; British Council under BIRAX Initiative; Flemish Government; Flanders Science Fund [FWO G.0834.13N]; MRC [G0501711] Funding Source: UKRI; European Research Council (ERC) [311546, 269073, 268921] Funding Source: European Research Council (ERC); Medical Research Council [G0501711] Funding Source: researchfish
NR 42
TC 459
Z9 523
U1 3
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 216
EP U226
DI 10.1038/nature16498
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700038
PM 26735015
DA 2026-03-09
ER

PT J
AU Hayes, RP
   Xiao, YB
   Ding, F
   van Erp, PBG
   Rajashankar, K
   Bailey, S
   Wiedenheft, B
   Ke, AL
AF Hayes, Robert P.
   Xiao, Yibei
   Ding, Fran
   van Erp, Paul B. G.
   Rajashankar, Kanagalaghatta
   Bailey, Scott
   Wiedenheft, Blake
   Ke, Ailong
TI Structural basis for promiscuous PAM recognition in type I-E Cascade from E. coli
SO NATURE
LA English
DT Article
ID guided surveillance complex; crystal-structure; dna recognition; foreign dna; vitro reconstitution; crispr immunity; degradation; mechanism; defense; targets
AB Clustered regularly interspaced short palindromic repeats (CRISPRs) and the cas (CRISPR-associated) operon form an RNA-based adaptive immune system against foreign genetic elements in prokaryotes(1). Type I accounts for 95% of CRISPR systems, and has been used to control gene expression and cell fate(2,3). During CRISPR RNA (crRNA)-guided interference, Cascade (CRISPR-associated complex for antiviral defence) facilitates the crRNA-guided invasion of double-stranded DNA for complementary base-pairing with the target DNA strand while displacing the nontarget strand, forming an R-loop(4,5). Cas3, which has nuclease and helicase activities, is subsequently recruited to degrade two DNA strands(4,6,7). A protospacer adjacent motif (PAM) sequence flanking target DNA is crucial for self versus foreign discrimination(4,8-16). Here we present the 2.45 angstrom crystal structure of Escherichia coli Cascade bound to a foreign double-stranded DNA target. The 5'-ATG PAM is recognized in duplex form, from the minor groove side, by three structural features in the Cascade Cse1 subunit. The promiscuity inherent to minor groove DNA recognition rationalizes the observation that a single Cascade complex can respond to several distinct PAM sequences. Optimal PAM recognition coincides with wedge insertion, initiating directional target DNA strand unwinding to allow segmented base-pairing with crRNA. The non-target strand is guided along a parallel path 25 angstrom apart, and the R-loop structure is further stabilized by locking this strand behind the Cse2 dimer. These observations provide the structural basis for understanding the PAM-dependent directional R-loop formation process(17,18).
C1 [Hayes, Robert P.; Xiao, Yibei; Ding, Fran; Ke, Ailong] Cornell Univ, Dept Mol Biol & Genet, 253 Biotechnol Bldg, Ithaca, NY 14853 USA.
   [Rajashankar, Kanagalaghatta] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, NE CAT,Adv Photon Source, Argonne, IL 60439 USA.
   [Bailey, Scott] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA.
   [van Erp, Paul B. G.; Wiedenheft, Blake] Montana State Univ, Dept Microbiol & Immunol, Bozeman, MT 59717 USA.
C3 Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Montana State University System; Montana State University Bozeman
RP Ke, AL (corresponding author), Cornell Univ, Dept Mol Biol & Genet, 253 Biotechnol Bldg, Ithaca, NY 14853 USA.
EM ak425@cornell.edu
FU National Institutes of Health (NIH) [GM102543, GM086766, GM097330, GM108888, P41 GM103403, S10 RR029205]; National Institute of General Medical Sciences [R01GM097330] Funding Source: NIH RePORTER
NR 33
TC 146
Z9 189
U1 4
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 499
EP +
DI 10.1038/nature16995
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800040
PM 26863189
DA 2026-03-09
ER

PT J
AU Sipilä, M
   Sarnela, N
   Jokinen, T
   Henschel, H
   Junninen, H
   Kontkanen, J
   Richters, S
   Kangasluoma, J
   Franchin, A
   Peräkylä, O
   Rissanen, MP
   Ehn, M
   Vehkamäki, H
   Kurten, T
   Berndt, T
   Petäjä, T
   Worsnop, D
   Ceburnis, D
   Kerminen, VM
   Kulmala, M
   O'Dowd, C
AF Sipila, Mikko
   Sarnela, Nina
   Jokinen, Tuija
   Henschel, Henning
   Junninen, Heikki
   Kontkanen, Jenni
   Richters, Stefanie
   Kangasluoma, Juha
   Franchin, Alessandro
   Perakyla, Otso
   Rissanen, Matti P.
   Ehn, Mikael
   Vehkamaki, Hanna
   Kurten, Theo
   Berndt, Torsten
   Petaja, Tuukka
   Worsnop, Douglas
   Ceburnis, Darius
   Kerminen, Veli-Matti
   Kulmala, Markku
   O'Dowd, Colin
TI Molecular-scale evidence of aerosol particle formation via sequential addition of HIO3
SO NATURE
LA English
DT Article
ID marine boundary-layer; iodine oxide; coastal antarctica; formation events; sulfuric-acid; nucleation; emissions; chemistry; macroalgae; precursor
AB Homogeneous nucleation and subsequent cluster growth leads to the formation of new aerosol particles in the atmosphere(1). The nucleation of sulfuric acid and organic vapours is thought to be responsible for the formation of new particles over continents(1,2), whereas iodine oxide vapours have been implicated in particle formation over coastal regions(3-7). The molecular clustering pathways that are involved in atmospheric particle formation have been elucidated in controlled laboratory studies of chemically simple systems(2,8-10), but direct molecular-level observations of nucleation in atmospheric field conditions that involve sulfuric acid, organic or iodine oxide vapours have yet to be reported(11). Here we present field data from Mace Head, Ireland, and supporting data from northern Greenland and Queen Maud Land, Antarctica, that enable us to identify the molecular steps involved in new particle formation in an iodine-rich, coastal atmospheric environment. We find that the formation and initial growth process is almost exclusively driven by iodine oxoacids and iodine oxide vapours, with average oxygen-to-iodine ratios of 2.4 found in the clusters. On the basis of this high ratio, together with the high concentrations of iodic acid (HIO3) observed, we suggest that cluster formation primarily proceeds by sequential addition of HIO3, followed by intracluster restructuring to I2O5 and recycling of water either in the atmosphere or on dehydration. Our study provides ambient atmospheric molecular-level observations of nucleation, supporting the previously suggested role of iodine-containing species in the formation of new aerosol particles(3-7,12-18), and identifies the key nucleating compound.
C1 [Sipila, Mikko; Sarnela, Nina; Jokinen, Tuija; Henschel, Henning; Junninen, Heikki; Kontkanen, Jenni; Kangasluoma, Juha; Franchin, Alessandro; Perakyla, Otso; Rissanen, Matti P.; Ehn, Mikael; Vehkamaki, Hanna; Petaja, Tuukka; Worsnop, Douglas; Kerminen, Veli-Matti; Kulmala, Markku] Univ Helsinki, Dept Phys, Helsinki, Finland.
   [Richters, Stefanie; Berndt, Torsten] Leibniz Inst Tropospher Res TROPOS, Leipzig, Germany.
   [Kurten, Theo] Univ Helsinki, Dept Chem, Helsinki, Finland.
   [Worsnop, Douglas] Univ Eastern Finland, Dept Appl Phys, Kuopio, Finland.
   [Worsnop, Douglas] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Worsnop, Douglas] Finnish Meteorol Inst, Helsinki, Finland.
   [Ceburnis, Darius; O'Dowd, Colin] Natl Univ Ireland Galway, Sch Phys, Univ Rd, Galway, Ireland.
   [Ceburnis, Darius; O'Dowd, Colin] Natl Univ Ireland Galway, Ryan Inst, Ctr Climate & Air Pollut Studies, Univ Rd, Galway, Ireland.
C3 University of Helsinki; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); University of Helsinki; University of Eastern Finland; Aerodyne Research; Finnish Meteorological Institute; Ollscoil na Gaillimhe-University of Galway; Ollscoil na Gaillimhe-University of Galway
RP Sipilä, M (corresponding author), Univ Helsinki, Dept Phys, Helsinki, Finland.
EM mikko.sipila@helsinki.fi
FU Academy of Finland (Centre of Excellence) [1118615, 251427, 266388]; PEGASOS project - European Commission [FP7-ENV-2010-265148]; ACTRIS; EPA-Ireland; Nordic Centre of Excellence (CRAICC); Finnish Antarctic Research Program; European Research Council [227463, 257360, 638703]; European Research Council (ERC) [257360, 638703] Funding Source: European Research Council (ERC); Villum Fonden [00007236] Funding Source: researchfish
NR 33
TC 265
Z9 299
U1 12
U2 350
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 532
EP 534
DI 10.1038/nature19314
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900052
PM 27580030
DA 2026-03-09
ER

PT J
AU Funato, H
   Miyoshi, C
   Fujiyama, T
   Kanda, T
   Kanda, T
   Sato, M
   Wang, ZQ
   Ma, J
   Nakane, S
   Tomita, J
   Ikkyu, A
   Kakizaki, M
   Hotta-Hirashima, N
   Kanno, S
   Komiya, H
   Asano, F
   Honda, T
   Kim, SJ
   Harano, K
   Muramoto, H
   Yonezawa, T
   Mizuno, S
   Miyazaki, S
   Connor, L
   Kumar, V
   Miura, I
   Suzuki, T
   Watanabe, A
   Abe, M
   Sugiyama, F
   Takahashi, S
   Sakimura, K
   Hayashi, Y
   Liu, QH
   Kume, K
   Wakana, S
   Takahashi, JS
   Yanagisawa, M
AF Funato, Hiromasa
   Miyoshi, Chika
   Fujiyama, Tomoyuki
   Kanda, Takeshi
   Kanda, Takeshi
   Sato, Makito
   Wang, Zhiqiang
   Ma, Jing
   Nakane, Shin
   Tomita, Jun
   Ikkyu, Aya
   Kakizaki, Miyo
   Hotta-Hirashima, Noriko
   Kanno, Satomi
   Komiya, Haruna
   Asano, Fuyuki
   Honda, Takato
   Kim, Staci J.
   Harano, Kanako
   Muramoto, Hiroki
   Yonezawa, Toshiya
   Mizuno, Seiya
   Miyazaki, Shinichi
   Connor, Linzi
   Kumar, Vivek
   Miura, Ikuo
   Suzuki, Tomohiro
   Watanabe, Atsushi
   Abe, Manabu
   Sugiyama, Fumihiro
   Takahashi, Satoru
   Sakimura, Kenji
   Hayashi, Yu
   Liu, Qinghua
   Kume, Kazuhiko
   Wakana, Shigeharu
   Takahashi, Joseph S.
   Yanagisawa, Masashi
TI Forward-genetics analysis of sleep in randomly mutagenized mice
SO NATURE
LA English
DT Article
ID salt-inducible kinase; rem-sleep; neuronal excitability; circadian pacemaker; gabaergic neurons; clock gene; arousal; mutants; circuit; rhythms
AB Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively.
C1 [Funato, Hiromasa; Miyoshi, Chika; Fujiyama, Tomoyuki; Kanda, Takeshi; Kanda, Takeshi; Sato, Makito; Wang, Zhiqiang; Ikkyu, Aya; Kakizaki, Miyo; Hotta-Hirashima, Noriko; Kanno, Satomi; Komiya, Haruna; Asano, Fuyuki; Honda, Takato; Kim, Staci J.; Harano, Kanako; Muramoto, Hiroki; Yonezawa, Toshiya; Miyazaki, Shinichi; Connor, Linzi; Hayashi, Yu; Liu, Qinghua; Takahashi, Joseph S.; Yanagisawa, Masashi] Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki 3058575, Japan.
   [Funato, Hiromasa] Toho Univ, Dept Anat, Fac Med, Ota Ku, Tokyo 1438540, Japan.
   [Sato, Makito; Yanagisawa, Masashi] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA.
   [Nakane, Shin; Tomita, Jun; Kume, Kazuhiko] Nagoya City Univ, Grad Sch Pharmaceut Sci, Dept Neuropharmacol, Nagoya, Aichi 4678603, Japan.
   [Mizuno, Seiya; Sugiyama, Fumihiro; Takahashi, Satoru] Univ Tsukuba, Lab Anim Resource Ctr, Tsukuba, Ibaraki 3058575, Japan.
   [Kumar, Vivek; Takahashi, Joseph S.] Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
   [Kumar, Vivek] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Miura, Ikuo; Suzuki, Tomohiro; Wakana, Shigeharu] RIKEN Bioresource Ctr, Technol & Dev Team Mouse Phenotype Anal, Tsukuba, Ibaraki 3050074, Japan.
   [Watanabe, Atsushi] Natl Ctr Geriatr & Gerontol, Lab Res Adv, Obu, Aichi 4748511, Japan.
   [Abe, Manabu; Sakimura, Kenji] Niigata Univ, Brain Res Inst, Dept Cellular Neurobiol, Niigata 9518585, Japan.
   [Hayashi, Yu] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Liu, Qinghua] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Takahashi, Joseph S.; Yanagisawa, Masashi] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Yanagisawa, Masashi] Univ Tsukuba, Tsukuba Adv Res Alliance, Life Sci Ctr, Tsukuba, Ibaraki 3058575, Japan.
C3 University of Tsukuba; University of Texas System; University of Texas Southwestern Medical Center; Nagoya City University; University of Tsukuba; University of Texas System; University of Texas Southwestern Medical Center; Jackson Laboratory; RIKEN; National Center for Geriatrics & Gerontology; Niigata University; Japan Science & Technology Agency (JST); University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Tsukuba
RP Funato, H; Takahashi, JS; Yanagisawa, M (corresponding author), Univ Tsukuba, Int Inst Integrat Sleep Med WPI IIIS, Tsukuba, Ibaraki 3058575, Japan.; Yanagisawa, M (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA.; Takahashi, JS (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.; Takahashi, JS; Yanagisawa, M (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.; Yanagisawa, M (corresponding author), Univ Tsukuba, Tsukuba Adv Res Alliance, Life Sci Ctr, Tsukuba, Ibaraki 3058575, Japan.
EM funato.hiromasa.km@u.tsukuba.ac.jp; joseph.takahashi@utsouthwestern.edu; yanagisawa.masa.fu@u.tsukuba.ac.jp
FU World Premier International Research Center Initiative from MEXT; JSPS KAKENHI [26220207, 16K15187, 26507003, 15K18966, 00635089, 16K18358, 15J06369, 16K18583]; MEXT KAKENHI [15H05935]; Welch Foundation [I-1608]; NIH [GM111367]; Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST program) from JSPS; Uehara Memorial Foundation; Takeda Science Foundation; NIH Office of Research Infrastructure Programs [P40 OD010440]; NIH Office of the Director; National Institute of General Medical Sciences [P40OD010440] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [26870077, 16H00590, 26507008, 16H00588, 16H04650, 15H05935, 26221004, 15K18966, 26250024, 16K15187, 26220207, 26507003, 16K18358, 15J06369, 16K18583] Funding Source: KAKEN
NR 34
TC 231
Z9 268
U1 1
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 378
EP 383
DI 10.1038/nature20142
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700044
PM 27806374
DA 2026-03-09
ER

PT J
AU Thomson, AR
   Walter, MJ
   Kohn, SC
   Brooker, RA
AF Thomson, Andrew R.
   Walter, Michael J.
   Kohn, Simon C.
   Brooker, Richard A.
TI Slab melting as a barrier to deep carbon subduction
SO NATURE
LA English
DT Article
ID experimental constraints; quartz solubility; diamond formation; oceanic-crust; mantle; eclogite; pressure; solidus; origin; gpa
AB Interactions between crustal and mantle reservoirs dominate the surface inventory of volatile elements over geological time, moderating atmospheric composition and maintaining a life-supporting planet(1). While volcanoes expel volatile components into surface reservoirs, subduction of oceanic crust is responsible for replenishment of mantle reservoirs(2,3). Many natural, 'superdeep' diamonds originating in the deep upper mantle and transition zone host mineral inclusions, indicating an affinity to subducted oceanic crust(4-7). Here we show that the majority of slab geotherms will intersect a deep depression along the melting curve of carbonated oceanic crust at depths of approximately 300 to 700 kilometres, creating a barrier to direct carbonate recycling into the deep mantle. Low-degree partial melts are alkaline carbonatites that are highly reactive with reduced ambient mantle, producing diamond. Many inclusions in superdeep diamonds are best explained by carbonate melt-peridotite reaction. A deep carbon barrier may dominate the recycling of carbon in the mantle and contribute to chemical and isotopic heterogeneity of the mantle reservoir.
C1 [Thomson, Andrew R.; Walter, Michael J.; Kohn, Simon C.; Brooker, Richard A.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Thomson, Andrew R.] UCL, Dept Earth Sci, Mortimer St, London WC1E 6BT, England.
C3 University of Bristol; University of London; University College London
RP Thomson, AR (corresponding author), Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.; Thomson, AR (corresponding author), UCL, Dept Earth Sci, Mortimer St, London WC1E 6BT, England.
EM a.r.thomson@ucl.ac.uk
FU NERC [NE/J500033/1, NE/J008583/1]; NERC [NE/J008583/1, NE/M000419/1] Funding Source: UKRI; Natural Environment Research Council [NE/J008583/1, NE/M000419/1, 1108948] Funding Source: researchfish
NR 59
TC 435
Z9 494
U1 20
U2 327
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 76
EP +
DI 10.1038/nature16174
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900029
PM 26738593
DA 2026-03-09
ER

PT J
AU Melde, K
   Mark, AG
   Qiu, T
   Fischer, P
AF Melde, Kai
   Mark, Andrew G.
   Qiu, Tian
   Fischer, Peer
TI Holograms for acoustics
SO NATURE
LA English
DT Article
ID radiation force; manipulation; objects; propagation; ultrasound; design; device; beam
AB Holographic techniques are fundamental to applications such as volumetric displays(1), high-density data storage and optical tweezers that require spatial control of intricate optical(2) or acoustic fields(3,4) within a three-dimensional volume. The basis of holography is spatial storage of the phase and/or amplitude profile of the desired wavefront(5,6) in a manner that allows that wavefront to be reconstructed by interference when the hologram is illuminated with a suitable coherent source. Modern computer-generated holography(7) skips the process of recording a hologram from a physical scene, and instead calculates the required phase profile before rendering it for reconstruction. In ultrasound applications, the phase profile is typically generated by discrete and independently driven ultrasound sources(3,4,8-12); however, these can only be used in small numbers, which limits the complexity or degrees of freedom that can be attained in the wavefront. Here we introduce monolithic acoustic holograms, which can reconstruct diffraction-limited acoustic pressure fields and thus arbitrary ultrasound beams. We use rapid fabrication to craft the holograms and achieve reconstruction degrees of freedom two orders of magnitude higher than commercial phased array sources. The technique is inexpensive, appropriate for both transmission and reflection elements, and scales well to higher information content, larger aperture size and higher power. The complex three-dimensional pressure and phase distributions produced by these acoustic holograms allow us to demonstrate new approaches to controlled ultrasonic manipulation of solids in water, and of liquids and solids in air. We expect that acoustic holograms will enable new capabilities in beam-steering and the contactless transfer of power, improve medical imaging, and drive new applications of ultrasound.
C1 [Melde, Kai; Mark, Andrew G.; Qiu, Tian; Fischer, Peer] Max Planck Inst Intelligent Syst, Heisenbergstr 3, D-70569 Stuttgart, Germany.
   [Fischer, Peer] Univ Stuttgart, Inst Phys Chem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
C3 Max Planck Society; University of Stuttgart
RP Fischer, P (corresponding author), Max Planck Inst Intelligent Syst, Heisenbergstr 3, D-70569 Stuttgart, Germany.; Fischer, P (corresponding author), Univ Stuttgart, Inst Phys Chem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
EM fischer@is.mpg.de
FU Max Planck Society; European Research Council (ERC) [278213]; European Research Council (ERC) [278213] Funding Source: European Research Council (ERC)
NR 33
TC 770
Z9 867
U1 40
U2 696
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 518
EP +
DI 10.1038/nature19755
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900049
PM 27652563
DA 2026-03-09
ER

PT J
AU Li, P
   Janczewski, WA
   Yackle, K
   Kam, K
   Pagliardini, S
   Krasnow, MA
   Feldman, JL
AF Li, Peng
   Janczewski, Wiktor A.
   Yackle, Kevin
   Kam, Kaiwen
   Pagliardini, Silvia
   Krasnow, Mark A.
   Feldman, Jack L.
TI The peptidergic control circuit for sighing
SO NATURE
LA English
DT Article
ID neuromedin-b-receptor; prebotzinger complex; respiratory rhythm; expressing neurons; ventral medulla; bombesin; generation; rats; mice; ventilation
AB Sighs are long, deep breaths expressing sadness, relief or exhaustion. Sighs also occur spontaneously every few minutes to reinflate alveoli, and sighing increases under hypoxia, stress, and certain psychiatric conditions. Here we use molecular, genetic, and pharmacologic approaches to identify a peptidergic sigh control circuit in murine brain. Small neural subpopulations in a key breathing control centre, the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), express bombesin-like neuropeptide genes neuromedin B (Nmb) or gastrin-releasing peptide (Grp). These project to the preBotzinger Complex (preBotC), the respiratory rhythm generator, which expresses NMB and GRP receptors in overlapping subsets of similar to 200 neurons. Introducing either neuropeptide into preBotC or onto preBtC slices, induced sighing or in vitro sigh activity, whereas elimination or inhibition of either receptor reduced basal sighing, and inhibition of both abolished it. Ablating receptor-expressing neurons eliminated basal and hypoxia-induced sighing, but left breathing otherwise intact initially. We propose that these overlapping peptidergic pathways comprise the core of a sigh control circuit that integrates physiological and perhaps emotional input to transform normal breaths into sighs.
C1 [Li, Peng; Yackle, Kevin; Krasnow, Mark A.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA.
   [Li, Peng; Yackle, Kevin; Krasnow, Mark A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Janczewski, Wiktor A.; Kam, Kaiwen; Pagliardini, Silvia; Feldman, Jack L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Syst Neurobiol Lab, Los Angeles, CA 90095 USA.
   [Kam, Kaiwen] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Cell Biol & Anat, N Chicago, IL 60064 USA.
   [Pagliardini, Silvia] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2E1, Canada.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Chicago Medical School; Rosalind Franklin University of Medicine & Science; University of Alberta
RP Krasnow, MA (corresponding author), Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA.; Krasnow, MA (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.; Feldman, JL (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Syst Neurobiol Lab, Los Angeles, CA 90095 USA.
EM krasnow@stanford.edu; feldman@g.ucla.edu
FU CIHR Funding Source: Medline; Howard Hughes Medical Institute Funding Source: Medline; NHLBI NIH HHS [U01 HL099995, R01 HL070029, HL40959, HL70029, R01 HL040959] Funding Source: Medline; NINDS NIH HHS [R01 NS072211, NS72211] Funding Source: Medline
NR 34
TC 156
Z9 187
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 293
EP +
DI 10.1038/nature16964
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100028
PM 26855425
DA 2026-03-09
ER

PT J
AU Eil, R
   Vodnala, SK
   Clever, D
   Klebanoff, CA
   Sukumar, M
   Pan, JH
   Palmer, DC
   Gros, A
   Yamamoto, TN
   Patel, SJ
   Guittard, GC
   Yu, ZY
   Carbonaro, V
   Okkenhaug, K
   Schrump, DS
   Linehan, WM
   Roychoudhuri, R
   Restifo, NP
AF Eil, Robert
   Vodnala, Suman K.
   Clever, David
   Klebanoff, Christopher A.
   Sukumar, Madhusudhanan
   Pan, Jenny H.
   Palmer, Douglas C.
   Gros, Alena
   Yamamoto, Tori N.
   Patel, Shashank J.
   Guittard, Geoffrey C.
   Yu, Zhiya
   Carbonaro, Valentina
   Okkenhaug, Klaus
   Schrump, David S.
   Linehan, W. Marston
   Roychoudhuri, Rahul
   Restifo, Nicholas P.
TI Ionic immune suppression within the tumour microenvironment limits T cell effector function
SO NATURE
LA English
DT Article
ID phosphatase 2a; cancer-immunotherapy; critical regulator; modulation; channels; quantification; lymphocytes; inhibition; activation; target
AB Tumours progress despite being infiltrated by tumour-specific effector T cells(1). Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers(2). Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K+](e)) impairs T cell receptor (TCR)driven Akt-mTOR phosphorylation and effector programmes. Potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A(3,4). Although the suppressive effect mediated by elevated [K+](e) is independent of changes in plasma membrane potential (V-m), it requires an increase in intracellular potassium ([K+](i)). Accordingly, augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv(1.3) lowers [K+](i) and improves effector functions in vitro and in vivo and enhances tumour clearance and survival in melanoma-bearing mice. These results uncover an ionic checkpoint that blocks T cell function in tumours and identify potential new strategies for cancer immunotherapy.
C1 [Eil, Robert; Vodnala, Suman K.; Clever, David; Klebanoff, Christopher A.; Sukumar, Madhusudhanan; Pan, Jenny H.; Palmer, Douglas C.; Gros, Alena; Yamamoto, Tori N.; Patel, Shashank J.; Guittard, Geoffrey C.; Yu, Zhiya; Schrump, David S.; Linehan, W. Marston; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
   [Klebanoff, Christopher A.] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA.
   [Klebanoff, Christopher A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Carbonaro, Valentina; Okkenhaug, Klaus; Roychoudhuri, Rahul] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England.
   [Eil, Robert] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA.
   [Gros, Alena] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, C Natzaret 115-117, Barcelona 08035, Spain.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; Oregon Health & Science University; Hospital Universitari Vall d'Hebron; Vall d'Hebron Institut d'Oncologia (VHIO)
RP Eil, R; Restifo, NP (corresponding author), NCI, NIH, Bethesda, MD 20892 USA.
EM eil@ohsu.edu; restifon@mail.nih.gov
FU NCI; Wellcome Trust/Royal Society [105663/Z/14/Z]; UK Biotechnology and Biological Sciences Research Council [BB/N007794/1]; BBSRC [BB/N007794/1, BBS/E/B/000C0407, 1642652] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/N007794/1, BBS/E/B/000C0407, 1642652] Funding Source: researchfish; Cancer Research UK [S_3402] Funding Source: researchfish; National Cancer Institute [ZIABC010763] Funding Source: NIH RePORTER; Wellcome Trust [105663/Z/14/Z] Funding Source: Wellcome Trust
NR 46
TC 560
Z9 633
U1 4
U2 230
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 539
EP +
DI 10.1038/nature19364
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900054
PM 27626381
DA 2026-03-09
ER

PT J
AU Sobolev, AV
   Asafov, EV
   Gurenko, AA
   Arndt, NT
   Batanova, VG
   Portnyagin, MV
   Garbe-Schönberg, D
   Krasheninnikov, SP
AF Sobolev, Alexander V.
   Asafov, Evgeny V.
   Gurenko, Andrey A.
   Arndt, Nicholas T.
   Batanova, Valentina G.
   Portnyagin, Maxim V.
   Garbe-Schoenberg, Dieter
   Krasheninnikov, Stepan P.
TI Komatiites reveal a hydrous Archaean deep-mantle reservoir
SO NATURE
LA English
DT Article
ID boron isotopic composition; abitibi greenstone-belt; melt inclusions; transition-zone; olivine crystallization; refractory mantle; ca boninites; origin; plume; h2o
AB Archaean komatiites (ultramafic lavas) result from melting under extreme conditions of the Earth's mantle. Their chemical compositions evoke very high eruption temperatures, up to 1,600 degrees Celsius, which suggests even higher temperatures in their mantle source(1,2). This message is clouded, however, by uncertainty about the water content in komatiite magmas. One school of thought holds that komatiites were essentially dry and originated in mantle plumes(3-6) while another argues that these magmas contained several per cent water, which drastically reduced their eruption temperature and links them to subduction processes(7-9). Here we report measurements of the content of water and other volatile components, and of major and trace elements in melt inclusions in exceptionally magnesian olivine (up to 94.5 mole per cent forsterite). This information provides direct estimates of the composition and crystallization temperature of the parental melts of Archaean komatiites. We show that the parental melt for 2.7-billion-year-old komatiites from the Abitibi greenstone belt in Canada contained 30 per cent magnesium oxide and 0.6 per cent water by weight, and was depleted in highly incompatible elements. This melt began to crystallize at around 1,530 degrees Celsius at shallow depth and under reducing conditions, and it evolved via fractional crystallization of olivine, accompanied by minor crustal assimilation. As its major-and trace-element composition and low oxygen fugacities are inconsistent with a subduction setting, we propose that its high H2O/Ce ratio (over 6,000) resulted from entrainment into the komatiite source of hydrous material from the mantle transition zone(10). These results confirm a plume origin for komatiites and high Archaean mantle temperatures, and evoke a hydrous reservoir in the deep mantle early in Earth's history.
C1 [Sobolev, Alexander V.; Arndt, Nicholas T.; Batanova, Valentina G.] Univ Grenoble Alpes, Inst Sci Terre ISTerre, CNRS, F-38041 Grenoble, France.
   [Sobolev, Alexander V.; Asafov, Evgeny V.; Batanova, Valentina G.; Portnyagin, Maxim V.; Krasheninnikov, Stepan P.] Russian Acad Sci, Vernadsky Inst Geochem & Analyt Chem, 19 Ul Kosygina, Moscow 119991, Russia.
   [Gurenko, Andrey A.] Univ Lorraine, CRPG, UMR 7358, F-54501 Vandoeuvre Les Nancy, France.
   [Portnyagin, Maxim V.] GEOMAR Helmholtz Ctr Ocean Res Kiel, Wischhofstr 1-3, D-24148 Kiel, Germany.
   [Garbe-Schoenberg, Dieter] Univ Kiel, Inst Geosci, Ludewig Meyn Str 10, D-24118 Kiel, Germany.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Gustave-Eiffel; Universite Savoie Mont Blanc; Russian Academy of Sciences; Vernadsky Institute of Geochemistry & Analytical Chemistry; Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Kiel
RP Sobolev, AV (corresponding author), Univ Grenoble Alpes, Inst Sci Terre ISTerre, CNRS, F-38041 Grenoble, France.; Sobolev, AV (corresponding author), Russian Acad Sci, Vernadsky Inst Geochem & Analyt Chem, 19 Ul Kosygina, Moscow 119991, Russia.
EM alexander.sobolev@ujf-grenoble.fr
FU Russian Science Foundation [14-17-00491]; Agence Nationale de la Recherche, France; Chair of Excellence grant [ANR-09-CEXC-003-01]; CNRS; Labex OSUG (Investissements d'avenir) [ANR10 LABX56]; Institut Universitaire de France; Deep Carbon Observatory; CRPG (A.A.G.'s internal funds); Russian Science Foundation [14-17-00491] Funding Source: Russian Science Foundation
NR 52
TC 160
Z9 180
U1 0
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 628
EP 632
DI 10.1038/nature17152
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400036
PM 27029278
DA 2026-03-09
ER

PT J
AU Kusumbe, AP
   Ramasamy, SK
   Itkin, T
   Mäe, MA
   Langen, UH
   Betsholtz, C
   Lapidot, T
   Adams, RH
AF Kusumbe, Anjali P.
   Ramasamy, Saravana K.
   Itkin, Tomer
   Mae, Maarja Andaloussi
   Langen, Urs H.
   Betsholtz, Christer
   Lapidot, Tsvee
   Adams, Ralf H.
TI Age-dependent modulation of vascular niches for haematopoietic stem cells
SO NATURE
LA English
DT Article
ID transcription factor; progenitor cells; angiogenesis; notch; protein; morphogenesis; osteogenesis; activation; receptors; pericytes
AB Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells(1-6). The properties of nicheforming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-beta (PDGFR beta)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFR beta-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.
C1 [Kusumbe, Anjali P.; Ramasamy, Saravana K.; Langen, Urs H.; Adams, Ralf H.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
   [Kusumbe, Anjali P.; Ramasamy, Saravana K.; Langen, Urs H.; Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
   [Itkin, Tomer; Lapidot, Tsvee] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Mae, Maarja Andaloussi; Betsholtz, Christer] Uppsala Univ, Dept Immunol Genet & Pathol, Vasc Biol Program, SE-75185 Uppsala, Sweden.
   [Betsholtz, Christer] Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, Scheeles Vag 2, SE-17177 Stockholm, Sweden.
C3 Max Planck Society; University of Munster; Weizmann Institute of Science; Uppsala University; Karolinska Institutet
RP Kusumbe, AP; Adams, RH (corresponding author), Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.; Kusumbe, AP (corresponding author), Univ Munster, Fac Med, D-48149 Munster, Germany.
EM anjali.kusumbe@mpi-muenster.mpg.de; ralf.adams@mpi-muenster.mpg.de
FU Max Planck Society; University of Munster; DFG cluster of excellence 'Cells in Motion'; European Research Council [AdG 339409]; Ministry of Science, Technology Space, Israel; DKFZ Germany; ERC [AdG 294556]; Knut and Alice Wallenberg Foundation; Swedish Cancer Foundation
NR 42
TC 392
Z9 464
U1 0
U2 100
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 380
EP +
DI 10.1038/nature17638
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700034
PM 27074508
DA 2026-03-09
ER

PT J
AU David, TJ
   Hillenbrand, LA
   Petigura, EA
   Carpenter, JM
   Crossfield, IJM
   Hinkley, S
   Ciardi, DR
   Howard, AW
   Isaacson, HT
   Cody, AM
   Schlieder, JE
   Beichman, CA
   Barenfeld, SA
AF David, Trevor J.
   Hillenbrand, Lynne A.
   Petigura, Erik A.
   Carpenter, John M.
   Crossfield, Ian J. M.
   Hinkley, Sasha
   Ciardi, David R.
   Howard, Andrew W.
   Isaacson, Howard T.
   Cody, Ann Marie
   Schlieder, Joshua E.
   Beichman, Charles A.
   Barenfeld, Scott A.
TI A Neptune-sized transiting planet closely orbiting a 5-10-million-year-old star
SO NATURE
LA English
DT Article
ID low-mass stars; pre-main-sequence; upper-scorpius; giant planets; m dwarfs; members; i.; kepler; model; multiplicity
AB Theories of the formation and early evolution of planetary systems postulate that planets are born in circumstellar disks, and undergo radial migration during and after dissipation of the dust and gas disk from which they formed(1,2). The precise ages of meteorites indicate that planetesimals-the building blocks of planets-are produced within the first million years of a star's life(3). Fully formed planets are frequently detected on short orbital periods around mature stars. Some theories suggest that the in situ formation of planets close to their host stars is unlikely and that the existence of such planets is therefore evidence of large-scale migration(4,5). Other theories posit that planet assembly at small orbital separations may be common(6-8). Here we report a newly born, transiting planet orbiting its star with a period of 5.4 days. The planet is 50 per cent larger than Neptune, and its mass is less than 3.6 times that of Jupiter (at 99.7 per cent confidence), with a true mass likely to be similar to that of Neptune. The star is 5-10 million years old and has a tenuous dust disk extending outward from about twice the Earth-Sun separation, in addition to the fully formed planet located at less than one-twentieth of the Earth-Sun separation.
C1 [David, Trevor J.; Hillenbrand, Lynne A.; Barenfeld, Scott A.] CALTECH, Cahill Ctr Astron & Astrophys, Pasadena, CA 91125 USA.
   [Petigura, Erik A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Carpenter, John M.] Joint ALMA Observ, Ave Alonso de Cordova 3107, Santiago, Chile.
   [Crossfield, Ian J. M.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Hinkley, Sasha] Univ Exeter, Dept Phys, Stocker Rd, Exeter EX4 4QL, Devon, England.
   [Ciardi, David R.; Beichman, Charles A.] CALTECH, NASA Exoplanet Sci Inst, Pasadena, CA 91125 USA.
   [Howard, Andrew W.] Univ Hawaii Manoa, Inst Astron, Honolulu, HI 96822 USA.
   [Isaacson, Howard T.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Cody, Ann Marie; Schlieder, Joshua E.] NASA Ames Res Ctr, Mountain View, CA 94035 USA.
C3 California Institute of Technology; California Institute of Technology; University of Arizona; University of Exeter; California Institute of Technology; National Aeronautics & Space Administration (NASA); University of Hawaii System; University of Hawaii Manoa; University of California System; University of California Berkeley; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP David, TJ (corresponding author), CALTECH, Cahill Ctr Astron & Astrophys, Pasadena, CA 91125 USA.
EM tjd@astro.caltech.edu
FU NSF [DGE1144469]; Hubble Fellowship; Sagan Fellowship; NASA [NNX16AE75G, 1541779]; NASA Science Mission directorate; American Heart Association (AHA) [906006] Funding Source: American Heart Association (AHA); NASA [906006, NNX16AE75G] Funding Source: Federal RePORTER; Science and Technology Facilities Council [ST/M00127X/1] Funding Source: researchfish; STFC [ST/M00127X/1] Funding Source: UKRI
NR 78
TC 155
Z9 179
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 658
EP +
DI 10.1038/nature18293
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000030
PM 27324846
DA 2026-03-09
ER

PT J
AU Riedinger, R
   Hong, S
   Norte, RA
   Slater, JA
   Shang, JY
   Krause, AG
   Anant, V
   Aspelmeyer, M
   Gröblacher, S
AF Riedinger, Ralf
   Hong, Sungkun
   Norte, Richard A.
   Slater, Joshua A.
   Shang, Juying
   Krause, Alexander G.
   Anant, Vikas
   Aspelmeyer, Markus
   Groblacher, Simon
TI Non-classical correlations between single photons and phonons from a mechanical oscillator
SO NATURE
LA English
DT Article
ID quantum ground-state; atomic ensembles; linear optics; resonator; microwave; motion; communication; generation; conversion; memory
AB Interfacing a single photon with another quantum system is a key capability in modern quantum information science. It allows quantum states of matter, such as spin states of atoms(1,2), atomic ensembles(3,4) or solids(5), to be prepared and manipulated by photon counting and, in particular, to be distributed over long distances. Such light-matter interfaces have become crucial to fundamental tests of quantum physics(6) and realizations of quantum networks(7). Here we report non-classical correlations between single photons and phonons-the quanta of mechanical motionfrom a nanomechanical resonator. We implement a full quantum protocol involving initialization of the resonator in its quantum ground state of motion and subsequent generation and read-out of correlated photon-phonon pairs. The observed violation of a Cauchy-Schwarz inequality is clear evidence for the non-classical nature of the mechanical state generated. Our results demonstrate the availability of on-chip solid-state mechanical resonators as light-matter quantum interfaces. The performance we achieved will enable studies of macroscopic quantum phenomena(8) as well as applications in quantum communication(9), as quantum memories(10) and as quantum transducers(11,12).
C1 [Riedinger, Ralf; Hong, Sungkun; Slater, Joshua A.; Aspelmeyer, Markus] Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol VCQ, Waehringer Guertel 18, A-1090 Vienna, Austria.
   [Norte, Richard A.; Krause, Alexander G.; Groblacher, Simon] Delft Univ Technol, Kavli Inst Nanosci, NL-2628 CJ Delft, Netherlands.
   [Shang, Juying; Anant, Vikas] Photon Spot Inc, Monrovia, CA 91016 USA.
C3 University of Vienna; Delft University of Technology
RP Aspelmeyer, M (corresponding author), Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol VCQ, Waehringer Guertel 18, A-1090 Vienna, Austria.; Gröblacher, S (corresponding author), Delft Univ Technol, Kavli Inst Nanosci, NL-2628 CJ Delft, Netherlands.
EM markus.aspelmeyer@univie.ac.at; s.groeblacher@tudelft.nl
FU Austrian Science Fund (FWF) [W1210, P28172] Funding Source: Austrian Science Fund (FWF); Austrian Science Fund (FWF) [P 28172] Funding Source: researchfish
NR 45
TC 400
Z9 454
U1 10
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 313
EP +
DI 10.1038/nature16536
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100032
PM 26779950
DA 2026-03-09
ER

PT J
AU Scialdone, A
   Tanaka, Y
   Jawaid, W
   Moignard, V
   Wilson, NK
   Macaulay, IC
   Marioni, JC
   Göttgens, B
AF Scialdone, Antonio
   Tanaka, Yosuke
   Jawaid, Wajid
   Moignard, Victoria
   Wilson, Nicola K.
   Macaulay, Iain C.
   Marioni, John C.
   Gottgens, Berthold
TI Resolving early mesoderm diversification through single-cell expression profiling
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; gene-expression; primitive streak; mouse embryos; rna-seq; hemogenic endothelium; clonal analysis; epiblast cells; germ layer; blood
AB In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the-pre-gastrula epiblast(1), but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays(2,3), that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.
C1 [Scialdone, Antonio; Marioni, John C.] EMBL European Bioinformat Inst EMBL EBI, Wellcome Genome Campus, Cambridge CB10 1SD, England.
   [Scialdone, Antonio; Macaulay, Iain C.; Marioni, John C.] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.
   [Tanaka, Yosuke; Jawaid, Wajid; Moignard, Victoria; Wilson, Nicola K.; Gottgens, Berthold] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
   [Tanaka, Yosuke; Jawaid, Wajid; Moignard, Victoria; Wilson, Nicola K.; Gottgens, Berthold] Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Cambridge, England.
   [Marioni, John C.] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
   [Tanaka, Yosuke] Univ Tokyo, Inst Med Sci, Div Cellular Therapy, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan.
C3 Wellcome Trust Sanger Institute; University of Cambridge; University of Cambridge; CRUK Cambridge Institute; University of Cambridge; Cancer Research UK; University of Tokyo
RP Marioni, JC (corresponding author), EMBL European Bioinformat Inst EMBL EBI, Wellcome Genome Campus, Cambridge CB10 1SD, England.; Marioni, JC (corresponding author), Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.; Göttgens, B (corresponding author), Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.; Göttgens, B (corresponding author), Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Cambridge, England.; Marioni, JC (corresponding author), Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
EM marioni@ebi.ac.uk; bg200@cam.ac.uk
FU Medical Research Council; Cancer Research UK; Biotechnology and Biological Sciences Research Council; Bloodwise; Leukemia and Lymphoma Society; Sanger-EBI Single Cell Centre; Wellcome Trust [105031/D/14/Z]; European Molecular Biology Laboratory; Japan Society for the Promotion of Science; BBSRC [BB/I00050X/1] Funding Source: UKRI; MRC [MR/M008975/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/I00050X/1] Funding Source: researchfish; Cancer Research UK [22231, 12765] Funding Source: researchfish; Medical Research Council [MR/M008975/1, MC_PC_12009] Funding Source: researchfish; Wellcome Trust [105031/Z/14/Z] Funding Source: researchfish
NR 106
TC 216
Z9 252
U1 0
U2 69
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 289
EP +
DI 10.1038/nature18633
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600058
PM 27383781
DA 2026-03-09
ER

PT J
AU DeVree, BT
   Mahoney, JP
   Vélez-Ruiz, GA
   Rasmussen, SGF
   Kuszak, AJ
   Edwald, E
   Fung, JJ
   Manglik, A
   Masureel, M
   Du, Y
   Matt, RA
   Pardon, E
   Steyaert, J
   Kobilka, BK
   Sunahara, RK
AF DeVree, Brian T.
   Mahoney, Jacob P.
   Velez-Ruiz, Gisselle A.
   Rasmussen, Soren G. F.
   Kuszak, Adam J.
   Edwald, Elin
   Fung, Juan-Jose
   Manglik, Aashish
   Masureel, Matthieu
   Du, Yang
   Matt, Rachel A.
   Pardon, Els
   Steyaert, Jan
   Kobilka, Brian K.
   Sunahara, Roger K.
TI Allosteric coupling from G protein to the agonist-binding pocket in GPCRs
SO NATURE
LA English
DT Article
ID beta-adrenergic-receptor; muscarinic acetylcholine-receptor; ternary complex model; neurotensin receptor; guanine-nucleotides; antagonist binding; adenylate-cyclase; crystal-structure; activation; affinity
AB G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other(1). Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades(1). Crystallographic evidence from a prototypic GPCR, the beta(2)-adrenergic receptor (beta(2)AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein a-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins(2). The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the beta(2)AR stabilizes a 'closed' receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR-G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity.
C1 [DeVree, Brian T.; Mahoney, Jacob P.; Velez-Ruiz, Gisselle A.; Kuszak, Adam J.; Edwald, Elin; Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Rasmussen, Soren G. F.; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A.; Kobilka, Brian K.] Stanford Univ, Dept Cellular & Mol Physiol, Palo Alto, CA 94305 USA.
   [Pardon, Els] VUB, Struct Biol Res Ctr, VIB, Pl Laan 2, B-1050 Brussels, Belgium.
   [Steyaert, Jan] VUB, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium.
   [Sunahara, Roger K.] Univ Calif San Diego, Dept Pharmacol, Sch Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
C3 University of Michigan System; University of Michigan; Stanford University; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; Vrije Universiteit Brussel; University of California System; University of California San Diego
RP Sunahara, RK (corresponding author), Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.; Sunahara, RK (corresponding author), Univ Calif San Diego, Dept Pharmacol, Sch Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM rsunahara@ucsd.edu
FU Lundbeck Foundation; Fund for Scientific Research of Flanders (FWO-Vlaanderen); Institute for the encouragement of Scientific Research and Innovation of Brussels (ISRIB); National Institute of Neural Disorders and Stroke [RO1-NS28471]; Mather Charitable Foundation; National Institute of General Medical Sciences [RO1-GM083118, U19-GM106990, RO1-GM068603]; National Institutes of Drug Abuse [R21-031418]; Michigan Diabetes Research and Training Center; National Institute of Diabetes and Digestive and Kidney Diseases [P60DK-20572]; University of Michigan Biological Sciences Scholars Program; Rackham School of Graduate Studies; Molecular Biophysics Training Grant [T32GM008270]; Cell and Molecular Biology Training Grant [T32GM007315]; Pharmacological Sciences Training Program [T32GM007767]; AHA Midwest Affiliate Predoctoral Fellowship [13PRE17110027]; Lundbeck Foundation [R37-2009-3457] Funding Source: researchfish; National Institute of General Medical Sciences [T32GM007315, R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER; American Heart Association (AHA) [13PRE17110027] Funding Source: American Heart Association (AHA)
NR 34
TC 237
Z9 273
U1 1
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 182
EP +
DI 10.1038/nature18324
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600049
PM 27362234
DA 2026-03-09
ER

PT J
AU Zink, KD
   Lieberman, DE
AF Zink, Katherine D.
   Lieberman, Daniel E.
TI Impact of meat and Lower Palaeolithic food processing techniques on chewing in humans
SO NATURE
LA English
DT Article
ID underground-storage organs; stone tools; practical guide; sensory quality; human-evolution; cooking; homo; hypothesis; force; energetics
AB The origins of the genus Homo are murky, but by H. erectus, bigger brains and bodies had evolved that, along with larger foraging ranges, would have increased the daily energetic requirements of hominins(1,2). Yet H. erectus differs from earlier hominins in having relatively smaller teeth, reduced chewing muscles, weaker maximum bite force capabilities, and a relatively smaller gut(3-5). This paradoxical combination of increased energy demands along with decreased masticatory and digestive capacities is hypothesized to have been made possible by adding meat to the diet(6-8), by mechanically processing food using stone tools(7,9,10), or by cooking(11,12). Cooking, however, was apparently uncommon until 500,000 years ago(13,14), and the effects of carnivory and Palaeolithic processing techniques on mastication are unknown. Here we report experiments that tested how Lower Palaeolithic processing technologies affect chewing force production and efficacy in humans consuming meat and underground storage organs (USOs). We find that if meat comprised one-third of the diet, the number of chewing cycles per year would have declined by nearly 2 million (a 13% reduction) and total masticatory force required would have declined by 15%. Furthermore, by simply slicing meat and pounding USOs, hominins would have improved their ability to chew meat into smaller particles by 41%, reduced the number of chews per year by another 5%, and decreased masticatory force requirements by an additional 12%. Although cooking has important benefits, it appears that selection for smaller masticatory features in Homo would have been initially made possible by the combination of using stone tools and eating meat.
C1 [Zink, Katherine D.; Lieberman, Daniel E.] Harvard Univ, Dept Human Evolutionary Biol, 11 Divin Ave, Cambridge, MA 02138 USA.
C3 Harvard University
RP Zink, KD; Lieberman, DE (corresponding author), Harvard Univ, Dept Human Evolutionary Biol, 11 Divin Ave, Cambridge, MA 02138 USA.
EM kzink@oeb.harvard.edu; danlieb@fas.harvard.edu
FU National Science Foundation [0925688]; American School of Prehistoric Research (Peabody Museum, Harvard University); Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [0925688] Funding Source: National Science Foundation
NR 37
TC 154
Z9 180
U1 4
U2 185
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 500
EP +
DI 10.1038/nature16990
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300040
PM 26958832
DA 2026-03-09
ER

PT J
AU Paquet, D
   Kwart, D
   Chen, A
   Sproul, A
   Jacob, S
   Teo, S
   Olsen, KM
   Gregg, A
   Noggle, S
   Tessier-Lavigne, M
AF Paquet, Dominik
   Kwart, Dylan
   Chen, Antonia
   Sproul, Andrew
   Jacob, Samson
   Teo, Shaun
   Olsen, Kimberly Moore
   Gregg, Andrew
   Noggle, Scott
   Tessier-Lavigne, Marc
TI Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9
SO NATURE
LA English
DT Article
ID familial alzheimers-disease; one-step generation; gene conversion; high-frequency; genome; crispr-cas9; nucleases; mice; models; repair
AB The bacterial CRISPR/Cas9 system allows sequence-specific gene editing in many organisms and holds promise as a tool to generate models of human diseases, for example, in human pluripotent stem cells(1,2). CRISPR/Cas9 introduces targeted double-stranded breaks (DSBs) with high efficiency, which are typically repaired by non-homologous end-joining (NHEJ) resulting in nonspecific insertions, deletions or other mutations (indels)(2). DSBs may also be repaired by homology-directed repair (HDR)(1,2) using a DNA repair template, such as an introduced single-stranded oligo DNA nucleotide (ssODN), allowing knock-in of specific mutations(3). Although CRISPR/Cas9 is used extensively to engineer gene knockouts through NHEJ, editing by HDR remains inefficient(3-8) and can be corrupted by additional indels(9), preventing its widespread use for modelling genetic disorders through introducing disease-associated mutations. Furthermore, targeted mutational knock-in at single alleles to model diseases caused by heterozygous mutations has not been reported. Here we describe a CRISPR/Cas9-based genome-editing framework that allows selective introduction of mono-and bi-allelic sequence changes with high efficiency and accuracy. We show that HDR accuracy is increased dramatically by incorporating silent CRISPR/Casblocking mutations along with pathogenic mutations, and establish a method termed 'CORRECT' for scarless genome editing. By characterizing and exploiting a stereotyped inverse relationship between a mutation's incorporation rate and its distance to the DSB, we achieve predictable control of zygosity. Homozygous introduction requires a guide RNA targeting close to the intended mutation, whereas heterozygous introduction can be accomplished by distance-dependent suboptimal mutation incorporation or by use of mixed repair templates. Using this approach, we generated human induced pluripotent stem cells with heterozygous and homozygous dominant early onset Alzheimer's disease-causing mutations in amyloid precursor protein (APP(Swe))(10) and presenilin 1 (PSEN1M146V)(11) and derived cortical neurons, which displayed genotype-dependent disease-associated phenotypes. Our findings enable efficient introduction of specific sequence changes with CRISPR/Cas9, facilitating study of human disease.
C1 [Paquet, Dominik; Kwart, Dylan; Chen, Antonia; Teo, Shaun; Olsen, Kimberly Moore; Gregg, Andrew; Tessier-Lavigne, Marc] Rockefeller Univ, Lab Brain Dev & Repair, 1230 York Ave, New York, NY 10065 USA.
   [Sproul, Andrew; Jacob, Samson; Noggle, Scott] New York Stem Cell Fdn Res Inst, New York, NY 10032 USA.
   [Gregg, Andrew] Rockefeller Univ, Weill Cornell Grad Sch Med Sci, 1300 York Ave, New York, NY 10065 USA.
   [Gregg, Andrew] Mem Sloan Kettering Canc Ctr, Triinst MD PhD Program, 1300 York Ave, New York, NY 10065 USA.
   [Sproul, Andrew] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, 630 West 168th St, New York, NY 10032 USA.
   [Sproul, Andrew] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Med Ctr, 630 West 168th St, New York, NY 10032 USA.
C3 Rockefeller University; Rockefeller University; Cornell University; Memorial Sloan Kettering Cancer Center; Columbia University; Columbia University
RP Tessier-Lavigne, M (corresponding author), Rockefeller Univ, Lab Brain Dev & Repair, 1230 York Ave, New York, NY 10065 USA.
EM marctl@rockefeller.edu
FU Rockefeller University; New York Stem Cell Foundation; Ellison Foundation; Cure Alzheimer's Fund; Empire State Stem Cell fund through New York State Department of Health [C023046]; CTSA, RUCCTS grant from the National Center for Advancing Translational Sciences (NCATS, NIH) [8 UL1 TR000043]; German Academy of Sciences Leopoldina; National Sciences and Engineering Research Council of Canada; Agency for Science, Technology and Research of Singapore; Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the National Institutes of Health [T32GM007739]; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
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NR 49
TC 674
Z9 902
U1 5
U2 367
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 125
EP +
DI 10.1038/nature17664
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900052
PM 27120160
DA 2026-03-09
ER

PT J
AU Tian, HQ
   Lu, CQ
   Ciais, P
   Michalak, AM
   Canadell, JG
   Saikawa, E
   Huntzinger, DN
   Gurney, KR
   Sitch, S
   Zhang, BW
   Yang, J
   Bousquet, P
   Bruhwiler, L
   Chen, GS
   Dlugokencky, E
   Friedlingstein, P
   Melillo, J
   Pan, SF
   Poulter, B
   Prinn, R
   Saunois, M
   Schwalm, CR
   Wofsy, SC
AF Tian, Hanqin
   Lu, Chaoqun
   Ciais, Philippe
   Michalak, Anna M.
   Canadell, Josep G.
   Saikawa, Eri
   Huntzinger, Deborah N.
   Gurney, Kevin R.
   Sitch, Stephen
   Zhang, Bowen
   Yang, Jia
   Bousquet, Philippe
   Bruhwiler, Lori
   Chen, Guangsheng
   Dlugokencky, Edward
   Friedlingstein, Pierre
   Melillo, Jerry
   Pan, Shufen
   Poulter, Benjamin
   Prinn, Ronald
   Saunois, Marielle
   Schwalm, Christopher R.
   Wofsy, Steven C.
TI The terrestrial biosphere as a net source of greenhouse gases to the atmosphere
SO NATURE
LA English
DT Article
ID carbon-nitrogen interactions; land-use; climate extremes; oxide emissions; global methane; budget; co2; feedbacks; fluxes; deforestation
AB The terrestrial biosphere can release or absorb the greenhouse gases, carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O), and therefore has an important role in regulating atmospheric composition and climate1. Anthropogenic activities such as land-use change, agriculture and waste management have altered terrestrial biogenic greenhouse gas fluxes, and the resulting increases in methane and nitrous oxide emissions in particular can contribute to climate change(2,3). The terrestrial biogenic fluxes of individual greenhouse gases have been studied extensively(4-6), but the net biogenic greenhouse gas balance resulting from anthropogenic activities and its effect on the climate system remains uncertain. Here we use bottom-up (inventory, statistical extrapolation of local flux measurements, and process-based modelling) and top-down (atmospheric inversions) approaches to quantify the global net biogenic greenhouse gas balance between 1981 and 2010 resulting from anthropogenic activities and its effect on the climate system. We find that the cumulative warming capacity of concurrent biogenic methane and nitrous oxide emissions is a factor of about two larger than the cooling effect resulting from the global land carbon dioxide uptake from 2001 to 2010. This results in a net positive cumulative impact of the three greenhouse gases on the planetary energy budget, with a best estimate (in petagrams of CO2 equivalent per year) of 3.9 +/- 3.8 (top down) and 5.4 +/- 4.8 (bottom up) based on the GWP100 metric (global warming potential on a 100-year time horizon). Our findings suggest that a reduction in agricultural methane and nitrous oxide emissions, particularly in Southern Asia, may help mitigate climate change.
C1 [Tian, Hanqin; Lu, Chaoqun; Zhang, Bowen; Yang, Jia; Pan, Shufen] Auburn Univ, Sch Forestry & Wildlife Sci, Int Ctr Climate & Global Change Res, Auburn, AL 36849 USA.
   [Lu, Chaoqun] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
   [Ciais, Philippe; Bousquet, Philippe; Saunois, Marielle] Lab Sci Climat & Environm, F-91191 Gif Sur Yvette, France.
   [Michalak, Anna M.] Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
   [Canadell, Josep G.] CSIRO Oceans & Atmosphere Res, Global Carbon Project, GPO Box 3023, Canberra, ACT 2601, Australia.
   [Saikawa, Eri] Emory Univ, Dept Environm Sci, Atlanta, GA 30322 USA.
   [Huntzinger, Deborah N.; Schwalm, Christopher R.] No Arizona Univ, Sch Earth Sci & Environm Sustainabil, Flagstaff, AZ 86011 USA.
   [Gurney, Kevin R.] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
   [Sitch, Stephen] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4RJ, Devon, England.
   [Bruhwiler, Lori; Dlugokencky, Edward] NOAA, Earth Syst Res Lab, Global Monitoring Div, Boulder, CO 80305 USA.
   [Chen, Guangsheng] Oak Ridge Natl Lab, Div Environm Sci, POB 2008, Oak Ridge, TN 37831 USA.
   [Friedlingstein, Pierre] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
   [Melillo, Jerry] Marine Biol Lab, Ctr Ecosyst, Woods Hole, MA 02543 USA.
   [Poulter, Benjamin] Montana State Univ, Inst Ecosyst, Bozeman, MT 59717 USA.
   [Poulter, Benjamin] Montana State Univ, Dept Ecol, Bozeman, MT 59717 USA.
   [Prinn, Ronald] MIT, Ctr Global Change Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Schwalm, Christopher R.] Woods Hole Res Ctr, Falmouth, MA 02540 USA.
   [Wofsy, Steven C.] Harvard Univ, Dept Earth & Planetary Sci, 29 Oxford St, Cambridge, MA 02138 USA.
C3 Auburn University System; Auburn University; Iowa State University; Universite Paris Saclay; Carnegie Institution for Science; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Emory University; Northern Arizona University; Arizona State University; Arizona State University-Tempe; University of Exeter; National Oceanic Atmospheric Admin (NOAA) - USA; United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Exeter; Marine Biological Laboratory - Woods Hole; Montana State University System; Montana State University Bozeman; Montana State University System; Montana State University Bozeman; Massachusetts Institute of Technology (MIT); Woodwell Climate Research Center; Harvard University
RP Tian, HQ (corresponding author), Auburn Univ, Sch Forestry & Wildlife Sci, Int Ctr Climate & Global Change Res, Auburn, AL 36849 USA.
EM tianhan@auburn.edu
FU NASA [NNX08AL73G, NNX14AO73G, NNX10AU06G, NNX11AD47G, NNG04GM39C, NNX12AP74G, NNX10AG01A, NNX11AO08A]; NSF [AGS 1243232, AGS-1243220, CNH1210360]; Australian Climate Change Science Program; NOAA Climate Program Office [NA13OAR4310059]; NSF CAREER [AGS-0846358]; NASA Upper Atmosphere Research Program AGAGE grant [NNX11AF17G]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1243220] Funding Source: National Science Foundation; Directorate For Geosciences; ICER [1450657] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1243232] Funding Source: National Science Foundation; NASA [NNX11AO08A, 137432, NNX12AP74G, NNX11AD47G, 148661, 14147] Funding Source: Federal RePORTER
NR 77
TC 475
Z9 564
U1 37
U2 1330
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 225
EP +
DI 10.1038/nature16946
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100039
PM 26961656
DA 2026-03-09
ER

PT J
AU Zhou, ZN
   Tang, AT
   Wong, WY
   Bamezai, S
   Goddard, LM
   Shenkar, R
   Zhou, S
   Yang, JS
   Wright, AC
   Foley, M
   Arthur, JSC
   Whitehead, KJ
   Awad, IA
   Li, DY
   Zheng, XJ
   Kahn, ML
AF Zhou, Zinan
   Tang, Alan T.
   Wong, Weng-Yew
   Bamezai, Sharika
   Goddard, Lauren M.
   Shenkar, Robert
   Zhou, Su
   Yang, Jisheng
   Wright, Alexander C.
   Foley, Matthew
   Arthur, J. Simon C.
   Whitehead, Kevin J.
   Awad, Issam A.
   Li, Dean Y.
   Zheng, Xiangjian
   Kahn, Mark L.
TI Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling
SO NATURE
LA English
DT Article
ID 2-hit mechanism; rho kinase; ccm1; angiogenesis; proteins; model
AB Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause strokes and seizures in younger individuals(1). CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous proteins that form an adaptor complex(2). How disruption of the CCM complex results in disease remains controversial, with numerous signalling pathways (including Rho(3,4), SMAD(5) and Wnt/beta-catenin(6)) and processes such as endothelial-mesenchymal transition (EndMT)(5) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7-11), and we have recently shown that CCM complex regulation of MEKK3 is essential during vertebrate heart development(12). Here we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we show that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates the MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.
C1 [Zhou, Zinan; Tang, Alan T.; Bamezai, Sharika; Goddard, Lauren M.; Zhou, Su; Yang, Jisheng; Kahn, Mark L.] Univ Penn, Dept Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
   [Zhou, Zinan; Tang, Alan T.; Bamezai, Sharika; Goddard, Lauren M.; Zhou, Su; Yang, Jisheng; Kahn, Mark L.] Univ Penn, Cardiovasc Inst, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
   [Wong, Weng-Yew; Zheng, Xiangjian] Centenary Inst, Lab Cardiovasc Signaling, Sydney, NSW 2050, Australia.
   [Shenkar, Robert; Awad, Issam A.] Univ Chicago, Dept Surg, Neurovasc Surg Program, Sect Neurosurg,Med & Biol Sci, Chicago, IL 60637 USA.
   [Wright, Alexander C.] Univ Penn, Med Ctr, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA.
   [Foley, Matthew] Univ Sydney, Sydney Microscopy & Microanal, Sydney, NSW 2050, Australia.
   [Arthur, J. Simon C.] Univ Dundee, Div Cell Signaling & Immunol, Dundee DD1 5EH, Scotland.
   [Whitehead, Kevin J.; Li, Dean Y.] Univ Utah, Div Cardiovasc Med, Salt Lake City, UT 84112 USA.
   [Whitehead, Kevin J.; Li, Dean Y.] Univ Utah, Program Mol Med, Salt Lake City, UT 84112 USA.
   [Li, Dean Y.] Sichuan Acad Med Sci, Key Lab Human Dis Gene Study Sichuan Prov, Inst Lab Med, Chengdu 610072, Sichuan, Peoples R China.
   [Li, Dean Y.] Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China.
   [Zheng, Xiangjian] Univ Sydney, Sydney Med Sch, Fac Med, Sydney, NSW 2050, Australia.
C3 University of Pennsylvania; University of Pennsylvania; University of Sydney; Centenary Institute; University of Chicago; University of Pennsylvania; University of Sydney; University of Dundee; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Sichuan Provincial People's Hospital; Sichuan Provincial People's Hospital; University of Sydney
RP Kahn, ML (corresponding author), Univ Penn, Dept Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.; Kahn, ML (corresponding author), Univ Penn, Cardiovasc Inst, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM markkahn@mail.med.upenn.edu
FU National Institutes of Health (NIH) [R01HL094326, P01NS092521, VAMC 1IO1BX002976, RO1HL-084516, R01NS075168, T32HL07439]; Australian NHMRC project [161558]; National Heart Lung and Blood Institute [T32HL007439] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS100949, P01NS092521] Funding Source: NIH RePORTER
NR 34
TC 244
Z9 286
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 122
EP +
DI 10.1038/nature17178
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500046
PM 27027284
DA 2026-03-09
ER

PT J
AU Harper, KL
   Sosa, MS
   Entenberg, D
   Hosseini, H
   Cheung, JF
   Nobre, R
   Avivar-Valderas, A
   Nagi, C
   Girnius, N
   Davis, RJ
   Farias, EF
   Condeelis, J
   Klein, CA
   Aguirre-Ghiso, JA
AF Harper, Kathryn L.
   Sosa, Maria Soledad
   Entenberg, David
   Hosseini, Hedayatollah
   Cheung, Julie F.
   Nobre, Rita
   Avivar-Valderas, Alvaro
   Nagi, Chandandaneep
   Girnius, Nomeda
   Davis, Roger J.
   Farias, Eduardo F.
   Condeelis, John
   Klein, Christoph A.
   Aguirre-Ghiso, Julio A.
TI Mechanism of early dissemination and metastasis in Her2+ mammary cancer
SO NATURE
LA English
DT Article
ID breast-cancer; mesenchymal transition; tumor-cells; bone-marrow; expression; diagnosis; emt
AB Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant(1). Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours(2). However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases(3-5). These findings, and those in pancreatic cancer(6) and melanoma(7) models, indicate that dissemination might occur during the early stages of tumour evolution(3,8,9). However, the mechanisms that might allow early disseminated cancer cells (eDCCs) to complete all steps of metastasis are unknown(8). Here we show that, in early lesions in mice and before any apparent primary tumour masses are detected, there is a sub-population of Her2(+) p-p38lop-Atf2loTwist1hiE-cadlo early cancer cells that is invasive and can spread to target organs. Intra-vital imaging and organoid studies of early lesions showed that Her2(+) eDCC precursors invaded locally, intravasated and lodged in target organs. Her2(+) eDCCs activated a Wnt-dependent epithelial-mesenchymal transition (EMT)-like dissemination program but without complete loss of the epithelial phenotype, which was reversed by Her2 or Wnt inhibition. Notably, although the majority of eDCCs were Twist1(hi)E-cadlo and dormant, they eventually initiated metastasis. Our work identifies a mechanism for early dissemination in which Her2 aberrantly activates a program similar to mammary ductal branching that generates eDCCs that are capable of forming metastasis after a dormancy phase.
C1 [Harper, Kathryn L.; Sosa, Maria Soledad; Cheung, Julie F.; Nobre, Rita; Avivar-Valderas, Alvaro; Nagi, Chandandaneep; Farias, Eduardo F.; Aguirre-Ghiso, Julio A.] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Dept Oncol Sci,Tisch Canc Inst, Div Hematol & Oncol,Dept Med,Dept Otolaryngol, 1 Gustave L Levy Pl, New York, NY 10029 USA.
   [Entenberg, David; Condeelis, John] Albert Einstein Coll Med, Dept Anat & Struct Biol, Integrated Imaging Program, Gruss Lipper Biophoton Ctr, 1300 Morris Pk Ave, New York, NY 10461 USA.
   [Hosseini, Hedayatollah; Klein, Christoph A.] Univ Regensburg, Expt Med & Therapy Res, D-93053 Regensburg, Germany.
   [Girnius, Nomeda; Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
   [Klein, Christoph A.] Fraunhofer Inst Toxicol & Expt Med, Project Grp Personalized Tumour Therapy, D-93053 Regensburg, Germany.
   [Sosa, Maria Soledad] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Pharmacol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Yeshiva University; University of Regensburg; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester; Fraunhofer Gesellschaft; Fraunhofer Germany; Fraunhofer Toxicology & Experimental Medicine; Icahn School of Medicine at Mount Sinai
RP Sosa, MS; Aguirre-Ghiso, JA (corresponding author), Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Dept Oncol Sci,Tisch Canc Inst, Div Hematol & Oncol,Dept Med,Dept Otolaryngol, 1 Gustave L Levy Pl, New York, NY 10029 USA.; Sosa, MS (corresponding author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Pharmacol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM maria.sosa@mssm.edu; julio.aguirre-ghiso@mssm.edu
FU HHMI; SWCRF [CA109182, CA196521, CA163131, CA100324, F31CA183185, BC132674, BC112380]; NIH [1S10RR024745]; Microscopy CoRE at ISMMS; DFG [KL 1233/10-1]; ERC [322602]; European Research Council (ERC) [322602] Funding Source: European Research Council (ERC); National Cancer Institute [R01CA109182, P30CA196521] Funding Source: NIH RePORTER
NR 35
TC 415
Z9 473
U1 2
U2 125
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 588
EP +
DI 10.1038/nature20609
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500053
PM 27974798
DA 2026-03-09
ER

PT J
AU Hirabayashi, M
   Scheeres, DJ
   Chesley, SR
   Marchi, S
   McMahon, JW
   Steckloff, J
   Mottola, S
   Naidu, SP
   Bowling, T
AF Hirabayashi, Masatoshi
   Scheeres, Daniel J.
   Chesley, Steven R.
   Marchi, Simone
   McMahon, Jay W.
   Steckloff, Jordan
   Mottola, Stefano
   Naidu, Shantanu P.
   Bowling, Timothy
TI Fission and reconfiguration of bilobate comets as revealed by 67P/Churyumov-Gerasimenko
SO NATURE
LA English
DT Article
ID asteroids; pressure; nucleus; origin; period; shape
AB The solid, central part of a comet-its nucleus-is subject to destructive processes(1,2), which cause nuclei to split at a rate of about 0.01 per year per comet(3). These destructive events are due to a range of possible thermophysical effects(4); however, the geophysical expressions of these effects are unknown. Separately, over two-thirds of comet nuclei that have been imaged at high resolution show bilobate shapes(5), including the nucleus of comet 67P/Churyumov-Gerasimenko (67P), visited by the Rosetta spacecraft. Analysis of the Rosetta observations suggests that 67P's components were brought together at low speed after their separate formation(6). Here, we study the structure and dynamics of 67P's nucleus. We find that sublimation torques have caused the nucleus to spin up in the past to form the large cracks observed on its neck. However, the chaotic evolution of its spin state has so far forestalled its splitting, although it should eventually reach a rapid enough spin rate to do so. Once this occurs, the separated components will be unable to escape each other; they will orbit each other for a time, ultimately undergoing a low-speed merger that will result in a new bilobate configuration. The components of four other imaged bilobate nuclei have volume ratios that are consistent with a similar reconfiguration cycle, pointing to such cycles as a fundamental process in the evolution of short-period comet nuclei. It has been shown(7,8) that comets were not strong contributors to the so-called late heavy bombardment about 4 billion years ago. The reconfiguration process suggested here would preferentially decimate comet nuclei during migration to the inner solar system, perhaps explaining this lack of a substantial cometary flux.
C1 [Hirabayashi, Masatoshi; Scheeres, Daniel J.; McMahon, Jay W.] Univ Colorado, Dept Aerosp Engn Sci, 429 UCB, Boulder, CO 80309 USA.
   [Chesley, Steven R.; Naidu, Shantanu P.] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
   [Marchi, Simone] Southwest Res Inst, 1050 Walnut St,Suite 300, Boulder, CO 80302 USA.
   [Hirabayashi, Masatoshi; Steckloff, Jordan] Purdue Univ, Dept Earth Atmospher & Planetary Sci, 550 Stadium Mall Dr, W Lafayette, IN 47907 USA.
   [Mottola, Stefano] German Aerosp Ctr DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany.
   [Bowling, Timothy] Univ Chicago, Dept Geophys Sci, 5734 S Ellis Ave, Chicago, IL 60637 USA.
C3 University of Colorado System; University of Colorado Boulder; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Southwest Research Institute; Purdue University System; Purdue University; Helmholtz Association; German Aerospace Centre (DLR); University of Chicago
RP Hirabayashi, M; Scheeres, DJ (corresponding author), Univ Colorado, Dept Aerosp Engn Sci, 429 UCB, Boulder, CO 80309 USA.; Hirabayashi, M (corresponding author), Purdue Univ, Dept Earth Atmospher & Planetary Sci, 550 Stadium Mall Dr, W Lafayette, IN 47907 USA.
EM thirabayashi@purdue.edu; scheeres@colorado.edu
FU NASA [NNX14AL16G, NNX14AB08G, NNA14AB03A]; Jet Propulsion Laboratory; NASA [686831, NNX14AB08G] Funding Source: Federal RePORTER
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NR 51
TC 71
Z9 81
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 352
EP +
DI 10.1038/nature17670
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800028
PM 27281196
DA 2026-03-09
ER

PT J
AU van Saders, JL
   Ceillier, T
   Metcalfe, TS
   Aguirre, VS
   Pinsonneault, MH
   García, RA
   Mathur, S
   Davies, GR
AF van Saders, Jennifer L.
   Ceillier, Tugdual
   Metcalfe, Travis S.
   Aguirre, Victor Silva
   Pinsonneault, Marc H.
   Garcia, Rafael A.
   Mathur, Savita
   Davies, Guy R.
TI Weakened magnetic braking as the origin of anomalously rapid rotation in old field stars
SO NATURE
LA English
DT Article
ID angular-momentum loss; stellar rotation; ngc 6811; kepler; cluster; gyrochronology; targets; binary; clock; model
AB A knowledge of stellar ages is crucial for our understanding of many astrophysical phenomena, and yet ages can be difficult to determine. As they become older, stars lose mass and angular momentum, resulting in an observed slowdown in surface rotation(1). The technique of 'gyrochronology' uses the rotation period of a star to calculate its age(2,3). However, stars of known age must be used for calibration, and, until recently, the approach was untested for old stars (older than 1 gigayear, Gyr). Rotation periods are now known for stars in an open cluster of intermediate age(4) (NGC 6819; 2.5 Gyr old), and for old field stars whose ages have been determined with asteroseismology(5,6). The data for the cluster agree with previous period-age relations(4), but these relations fail to describe the asteroseismic sample(7). Here we report stellar evolutionary modelling(5,6,8-10), and confirm the presence of unexpectedly rapid rotation in stars that are more evolved than the Sun. We demonstrate that models that incorporate dramatically weakened magnetic braking for old stars can-unlike existing models-reproduce both the asteroseismic and the cluster data. Our findings might suggest a fundamental change in the nature of ageing stellar dynamos, with the Sun being close to the critical transition to much weaker magnetized winds. This weakened braking limits the diagnostic power of gyrochronology for those stars that are more than halfway through their main-sequence lifetimes.
C1 [van Saders, Jennifer L.] Carnegie Observ, Pasadena, CA 91101 USA.
   [van Saders, Jennifer L.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [van Saders, Jennifer L.; Pinsonneault, Marc H.; Garcia, Rafael A.; Mathur, Savita] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Ceillier, Tugdual; Garcia, Rafael A.] Univ Paris Diderot, Inst Res Fundamental Laws Universe IRFU,Ctr Sacla, Alternat Energies & Atom Energy Commiss CEA,Lab A, Phys Sci Div DSM,Ctr Natl Etud Spatiales CNRS,Ser, F-91191 Gif Sur Yvette, France.
   [Metcalfe, Travis S.; Mathur, Savita] Space Sci Inst, Boulder, CO 80301 USA.
   [Aguirre, Victor Silva; Davies, Guy R.] Aarhus Univ, Dept Phys & Astron, Stellar Astrophys Ctr, DK-8000 Aarhus, Denmark.
   [Pinsonneault, Marc H.] Ohio State Univ, Dept Astron, Columbus, OH 43210 USA.
   [Davies, Guy R.] Univ Birmingham, Sch Phys & Astron, Birmingham B15 2TT, W Midlands, England.
C3 Carnegie Institution for Science; Princeton University; University of California System; University of California Santa Barbara; Universite Paris Cite; CEA; Aarhus University; University System of Ohio; Ohio State University; University of Birmingham
RP van Saders, JL (corresponding author), Carnegie Observ, 813 Santa Barbara St, Pasadena, CA 91101 USA.
EM jvansaders@obs.carnegiescience.edu; rafael.garcia@cea.fr
FU UK Science and Technology Facilities Council (STFC); NASA [NNX15AF13G]; National Science Foundation (NSF) [AST-1411685]; Centre National d'Etudes Spatiales (CNES) at the French Alternative Energies and Atomic Energy Commission (CEA); European Community [312844, 269194]; NSF [NSF PHY11-25915]; Danish National Research Foundation [DNRF106]; ASTERISK project - European Research Council [267864]; VILLUM FONDEN [10118]; STFC [ST/M00077X/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/M00077X/1] Funding Source: researchfish; Villum Fonden [00010118] Funding Source: researchfish
NR 31
TC 339
Z9 366
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 181
EP U117
DI 10.1038/nature16168
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700030
PM 26727162
DA 2026-03-09
ER

PT J
AU Siegert, T
   Diehl, R
   Greiner, J
   Krause, MGH
   Beloborodov, AM
   Bel, MC
   Guglielmetti, F
   Rodriguez, J
   Strong, AW
   Zhang, XL
AF Siegert, Thomas
   Diehl, Roland
   Greiner, Jochen
   Krause, Martin G. H.
   Beloborodov, Andrei M.
   Bel, Marion Cadolle
   Guglielmetti, Fabrizia
   Rodriguez, Jerome
   Strong, Andrew W.
   Zhang, Xiaoling
TI Positron annihilation signatures associated with the outburst of the microquasar V404 Cygni
SO NATURE
LA English
DT Article
ID x-ray binary; black-hole binary; pair production; emission; accretion; galaxy; nova; line; spi; spectroscopy
AB Microquasars(1-4) are stellar-mass black holes accreting matter from a companion star(5) and ejecting plasma jets at almost the speed of light. They are analogues of quasars that contain supermassive black holes of 10(6) to 10(10) solar masses. Accretion in microquasars varies on much shorter timescales than in quasars and occasionally produces exceptionally bright X-ray flares(6). How the flares are produced is unclear, as is the mechanism for launching the relativistic jets and their composition. An emission line near 511 kiloelectronvolts has long been sought in the emission spectrum of microquasars as evidence for the expected electron-positron plasma. Transient high-energy spectral features have been reported in two objects(7,8), but their positron interpretation(9) remains contentious. Here we report observations of gamma-ray emission from the microquasar V404 Cygni during a recent period of strong flaring activity(10). The emission spectrum around 511 kiloelectronvolts shows clear signatures of variable positron annihilation, which implies a high rate of positron production. This supports the earlier conjecture that microquasars may be the main sources of the electron-positron plasma responsible for the bright diffuse emission of annihilation gamma-rays in the bulge region of our Galaxy(11). Additionally, microquasars could be the origin of the observed megaelectronvolt continuum excess in the inner Galaxy.
C1 [Siegert, Thomas; Diehl, Roland; Greiner, Jochen; Krause, Martin G. H.; Guglielmetti, Fabrizia; Strong, Andrew W.; Zhang, Xiaoling] Max Planck Inst Extraterr Phys, Giessenbachstr 1, D-85748 Garching, Germany.
   [Krause, Martin G. H.] Univ Munich, Univ Sternwarte Munchen, Scheinerstr 1, D-81679 Munich, Germany.
   [Beloborodov, Andrei M.] Columbia Univ, Dept Phys, 550 West 120th St, New York, NY 10027 USA.
   [Beloborodov, Andrei M.] Columbia Univ, Columbia Astrophys Lab, 550 West 120th St, New York, NY 10027 USA.
   [Bel, Marion Cadolle] Max Planck Comp & Data Facil, Giessenbachstr 2, D-85748 Garching, Germany.
   [Rodriguez, Jerome] Univ Paris Diderot, CNRS, CEA,IRFU,SAp, Lab Astrophys Instrumentat Modelisat,UMR 7158,DSM, F-91191 Gif Sur Yvette, France.
C3 Max Planck Society; University of Munich; Columbia University; Columbia University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Saclay; CEA; Universite Paris Cite
RP Siegert, T (corresponding author), Max Planck Inst Extraterr Phys, Giessenbachstr 1, D-85748 Garching, Germany.
EM tsiegert@mpe.mpg.de
FU Munich excellence cluster 'Origin and evolution of the Universe'; Deutsche Forschungsgemeinschaft [PR 569/10-1, 1573]; French Research National Agency; CHAOS project [ANR-12-BS05-0009]; UnivEarthS Labex program of Sorbonne Paris Cite
NR 38
TC 81
Z9 85
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 341
EP +
DI 10.1038/nature16978
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300046
PM 26934231
DA 2026-03-09
ER

PT J
AU Li, JH
   Lu, E
   Yi, TS
   Cyster, JG
AF Li, Jianhua
   Lu, Erick
   Yi, Tangsheng
   Cyster, Jason G.
TI EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells
SO NATURE
LA English
DT Article
ID follicular helper-cells; germinal center; immune-responses; t-cells; listeria-monocytogenes; antibody-responses; differentiation; interleukin-2; expression; generation
AB T follicular helper (Tfh) cells are a subset of T cells carrying the CD4 antigen; they are important in supporting plasma cell and germinal centre responses(1,2). The initial induction of Tfh cell properties occurs within the first few days after activation by antigen recognition on dendritic cells, although how dendritic cells promote this cell-fate decision is not fully understood(1,2). Moreover, although Tfh cells are uniquely defined by expression of the follicle-homing receptor CXCR5 (refs 1, 2), the guidance receptor promoting the earlier localization of activated T cells at the interface of the B-cell follicle and T zone has been unclear(3-5). Here we show that the G-protein-coupled receptor EBI2 (GPR183) and its ligand 7 alpha,25-dihydroxycholesterol mediate positioning of activated CD4 T cells at the interface of the follicle and T zone. In this location they interact with activated dendritic cells and are exposed to Tfh-cell-promoting inducible co-stimulator (ICOS) ligand. Interleukin-2 (IL-2) is a cytokine that has multiple influences on T-cell fate, including negative regulation of Tfh cell differentiation(6-10). We demonstrate that activated dendritic cells in the outer T zone further augment Tfh cell differentiation by producing membrane and soluble forms of CD25, the IL-2 receptor alpha-chain, and quenching T-cell-derived IL-2. Mice lacking EBI2 in T cells or CD25 in dendritic cells have reduced Tfh cells and mount defective T-cell-dependent plasma cell and germinal centre responses. These findings demonstrate that distinct niches within the lymphoid organ T zone support distinct cell fate decisions, and they establish a function for dendritic-cell-derived CD25 in controlling IL-2 availability and T-cell differentiation.
C1 [Li, Jianhua; Lu, Erick; Yi, Tangsheng; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Li, Jianhua; Lu, Erick; Yi, Tangsheng; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Li, Jianhua] Fudan Univ, Dept Med Microbiol, Sch Basic Med Sci, Key Lab Med Mol Virol,Shanghai Med Coll, Shanghai 200433, Peoples R China.
   [Yi, Tangsheng] Genentech Inc, Dept Discovery Immunol, San Francisco, CA 94080 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Fudan University; Roche Holding; Roche Holding USA; Genentech
RP Cyster, JG (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.; Cyster, JG (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM jason.cyster@ucsf.edu
FU University of California, San Francisco, Biomedical Sciences (BMS) Graduate program; National Science Foundation [1144247]; National Institutes of Health [AI40098]; National Institute of Allergy and Infectious Diseases [T32AI007334, R01AI040098] Funding Source: NIH RePORTER; Direct For Education and Human Resources; Division Of Graduate Education [1144247] Funding Source: National Science Foundation
NR 36
TC 243
Z9 298
U1 0
U2 38
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 110
EP +
DI 10.1038/nature17947
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900049
PM 27147029
DA 2026-03-09
ER

PT J
AU Kranz, LM
   Diken, M
   Haas, H
   Kreiter, S
   Loquai, C
   Reuter, KC
   Meng, M
   Fritz, D
   Vascotto, F
   Hefesha, H
   Grunwitz, C
   Vormehr, M
   Hüsemann, Y
   Selmi, A
   Kuhn, AN
   Buck, J
   Derhovanessian, E
   Rae, R
   Attig, S
   Diekmann, J
   Jabulowsky, RA
   Heesch, S
   Hassel, J
   Langguth, P
   Grabbe, S
   Huber, C
   Türeci, Ö
   Sahin, U
AF Kranz, Lena M.
   Diken, Mustafa
   Haas, Heinrich
   Kreiter, Sebastian
   Loquai, Carmen
   Reuter, Kerstin C.
   Meng, Martin
   Fritz, Daniel
   Vascotto, Fulvia
   Hefesha, Hossam
   Grunwitz, Christian
   Vormehr, Mathias
   Huesemann, Yves
   Selmi, Abderraouf
   Kuhn, Andreas N.
   Buck, Janina
   Derhovanessian, Evelyna
   Rae, Richard
   Attig, Sebastian
   Diekmann, Jan
   Jabulowsky, Robert A.
   Heesch, Sandra
   Hassel, Jessica
   Langguth, Peter
   Grabbe, Stephan
   Huber, Christoph
   Tuereci, Oezlem
   Sahin, Ugur
TI Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
SO NATURE
LA English
DT Article
ID cytolytic t-lymphocytes; in-vivo; immune-responses; antitumor immunity; antigen; interferons; macropinocytosis; vaccination; efficiency; induction
AB Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses(1). However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-alpha (IFN alpha) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated(2). We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFN alpha-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFN alpha and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA3,4, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.
C1 [Kranz, Lena M.; Diken, Mustafa; Kreiter, Sebastian; Vascotto, Fulvia; Rae, Richard; Attig, Sebastian; Huber, Christoph; Sahin, Ugur] Johannes Gutenberg Univ gGmbH, TRON Translat Oncol, Univ Med Ctr, Freiligrathstr 12, D-55131 Mainz, Germany.
   [Kranz, Lena M.; Grunwitz, Christian; Vormehr, Mathias; Selmi, Abderraouf; Attig, Sebastian; Sahin, Ugur] Johannes Gutenberg Univ Mainz, Res Ctr Immunotherapy FZI, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany.
   [Diken, Mustafa; Haas, Heinrich; Kreiter, Sebastian; Reuter, Kerstin C.; Meng, Martin; Fritz, Daniel; Hefesha, Hossam; Grunwitz, Christian; Vormehr, Mathias; Huesemann, Yves; Kuhn, Andreas N.; Buck, Janina; Derhovanessian, Evelyna; Diekmann, Jan; Jabulowsky, Robert A.; Heesch, Sandra; Huber, Christoph; Sahin, Ugur] Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany.
   [Loquai, Carmen; Grabbe, Stephan] Johannes Gutenberg Univ Mainz, Dept Dermatol, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany.
   [Hassel, Jessica] Univ Heidelberg Hosp, Dept Dermatol, Neuenheimer Feld 440, D-69120 Heidelberg, Germany.
   [Langguth, Peter] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Langenbeckstr 1, D-55131 Mainz, Germany.
   [Tuereci, Oezlem] Cluster Individualized Immune Intervent, Kupferbergterasse 19, D-55116 Mainz, Germany.
C3 Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; BioNTech SE; Johannes Gutenberg University of Mainz; Ruprecht Karls University Heidelberg; Johannes Gutenberg University of Mainz
RP Sahin, U (corresponding author), Johannes Gutenberg Univ gGmbH, TRON Translat Oncol, Univ Med Ctr, Freiligrathstr 12, D-55131 Mainz, Germany.; Sahin, U (corresponding author), Johannes Gutenberg Univ Mainz, Res Ctr Immunotherapy FZI, Univ Med Ctr, Langenbeckstr 1, D-55131 Mainz, Germany.; Sahin, U (corresponding author), Biopharmaceut New Technol BioNTech Corp, Goldgrube 12, D-55131 Mainz, Germany.
EM sahin@uni-mainz.de
FU Rhineland Palatinate government; InnoTop program; CI3 Cutting Edge Cluster Funding of the German Ministry of Technology (BMBF); Collaborative Research Group 1066 of Deutsche Forschungsgemeinschaft (DFG); Graduate School of Immunotherapy 1043 of DFG
NR 52
TC 1415
Z9 1670
U1 9
U2 817
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 396
EP +
DI 10.1038/nature18300
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800038
PM 27281205
DA 2026-03-09
ER

PT J
AU Küffer, A
   Lakkaraju, AKK
   Mogha, A
   Petersen, SC
   Airich, K
   Doucerain, C
   Marpakwar, R
   Bakirci, P
   Senatore, A
   Monnard, A
   Schiavi, C
   Nuvolone, M
   Grosshans, B
   Hornemann, S
   Bassilana, F
   Monk, KR
   Aguzzi, A
AF Kuffer, Alexander
   Lakkaraju, Asvin K. K.
   Mogha, Amit
   Petersen, Sarah C.
   Airich, Kristina
   Doucerain, Cedric
   Marpakwar, Rajlakshmi
   Bakirci, Pamela
   Senatore, Assunta
   Monnard, Arnaud
   Schiavi, Carmen
   Nuvolone, Mario
   Grosshans, Bianka
   Hornemann, Simone
   Bassilana, Frederic
   Monk, Kelly R.
   Aguzzi, Adriano
TI The prion protein is an agonistic ligand of the G protein-coupled receptor Adgrg6
SO NATURE
LA English
DT Article
ID peripheral myelin maintenance; schwann-cell development; gpr126; zebrafish; apoptosis; neurons; domain; mice; rna
AB Ablation of the cellular prion protein PrPC leads to a chronic demyelinating polyneuropathy affecting Schwann cells. Neuron-restricted expression of PrPC prevents the disease(1), suggesting that PrPC acts in trans through an unidentified Schwann cell receptor. Here we show that the cAMP concentration in sciatic nerves from PrPC-deficient mice is reduced, suggesting that PrPC acts via a G protein-coupled receptor (GPCR). The amino-terminal flexible tail (residues 23-120) of PrPC triggered a concentration-dependent increase in cAMP in primary Schwann cells, in the Schwann cell line SW10, and in HEK293T cells overexpressing the GPCR Adgrg6 (also known as Gpr126). By contrast, naive HEK293T cells and HEK293T cells expressing several other GPCRs did not react to the flexible tail, and ablation of Gpr126 from SW10 cells abolished the flexible tail-induced cAMP response. The flexible tail contains a polycationic cluster (KKRPKPG) similar to the GPRGKPG motif of the Gpr126 agonist type-IV collagen(2). A KKRPKPG-containing PrPC-derived peptide (FT23-50) sufficed to induce a Gpr126-dependent cAMP response in cells and mice, and improved myelination in hypomorphic gpr126 mutant zebrafish (Danio rerio). Substitution of the cationic residues with alanines abolished the biological activity of both FT23-50 and the equivalent type-IV collagen peptide. We conclude that PrPC promotes myelin homeostasis through flexible tail-mediated Gpr126 agonism. As well as clarifying the physiological role of PrPC, these observations are relevant to the pathogenesis of demyelinating polyneuropathies-common debilitating diseases for which there are limited therapeutic options.
C1 [Kuffer, Alexander; Lakkaraju, Asvin K. K.; Airich, Kristina; Doucerain, Cedric; Marpakwar, Rajlakshmi; Bakirci, Pamela; Senatore, Assunta; Monnard, Arnaud; Schiavi, Carmen; Nuvolone, Mario; Hornemann, Simone; Aguzzi, Adriano] Univ Zurich, Inst Neuropathol, CH-8091 Zurich, Switzerland.
   [Mogha, Amit; Petersen, Sarah C.; Monk, Kelly R.] Washington Univ, Sch Med, Dept Dev Biol, 660 South Euclid Ave,Campus Box 8103, St Louis, MO 63110 USA.
   [Mogha, Amit; Petersen, Sarah C.; Monk, Kelly R.] Hope Ctr Neurol Disorders, 660 South Euclid Ave,Campus Box 8103, St Louis, MO 63110 USA.
   [Grosshans, Bianka; Bassilana, Frederic] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland.
C3 University of Zurich; Washington University (WUSTL); Novartis
RP Aguzzi, A (corresponding author), Univ Zurich, Inst Neuropathol, CH-8091 Zurich, Switzerland.
EM adriano.aguzzi@usz.ch
FU European Research Council; European Union; Swiss National Research Foundation; Sinergia grant [147660]; Clinical Research Priority Program 'Small RNAs'; Clinical Research Priority Program 'Human Hemato-Lymphatic Diseases'; SystemsX.ch; EU Joint Programme on Neurodegenerative Disease Research (JPND) CureALS and REfrAME; Novartis Research Foundation; MD/PhD fellowship from the Swiss National Science Foundation; Synapsis Foundation; NIH [F32 NS087786, NS079445]
NR 29
TC 179
Z9 210
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 464
EP +
DI 10.1038/nature19312
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600043
PM 27501152
DA 2026-03-09
ER

PT J
AU Feeney, KA
   Hansen, LL
   Putker, M
   Olivares-Yañez, C
   Day, J
   Eades, LJ
   Larrondo, LF
   Hoyle, NP
   O'Neill, JS
   van Ooijen, G
AF Feeney, Kevin A.
   Hansen, Louise L.
   Putker, Marrit
   Olivares-Yanez, Consuelo
   Day, Jason
   Eades, Lorna J.
   Larrondo, Luis F.
   Hoyle, Nathaniel P.
   O'Neill, John S.
   van Ooijen, Gerben
TI Daily magnesium fluxes regulate cellular timekeeping and energy balance
SO NATURE
LA English
DT Article
ID circadian-rhythms; picoeukaryote ostreococcus; clocks; model; transcription; exchanger; reveals; phosphorylation; translation; annotation
AB Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes(1-3). A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology(4,5). Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg2+]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago(6). Given the essential role of Mg2+ as a cofactor for ATP, a functional consequence of [Mg2+] i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg2+ availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes(7) and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR(8) is regulated through [Mg2+] i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease.
C1 [Feeney, Kevin A.; Putker, Marrit; Hoyle, Nathaniel P.; O'Neill, John S.] MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England.
   [Hansen, Louise L.; van Ooijen, Gerben] Univ Edinburgh, Sch Biol Sci, Max Born Crescent, Edinburgh EH9 3BF, Midlothian, Scotland.
   [Olivares-Yanez, Consuelo; Larrondo, Luis F.] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Genet Mol & Microbiol, Millennium Nucleus Fungal Integrat & Synthet Biol, Casilla 114-D, Santiago, Chile.
   [Day, Jason] Univ Cambridge, Dept Earth Sci, Downing St, Cambridge CB2 3EQ, England.
   [Eades, Lorna J.] Univ Edinburgh, Sch Chem, David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland.
C3 MRC Laboratory Molecular Biology; University of Edinburgh; Pontificia Universidad Catolica de Chile; University of Cambridge; University of Edinburgh
RP O'Neill, JS (corresponding author), MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England.; van Ooijen, G (corresponding author), Univ Edinburgh, Sch Biol Sci, Max Born Crescent, Edinburgh EH9 3BF, Midlothian, Scotland.
EM oneillj@mrc-lmb.cam.ac.uk; Gerben.vanOoijen@ed.ac.uk
FU Royal Society University Research Fellowship [UF110173]; Medical Research Council [MC_UP_1201/4]; Wellcome Trust [093734/Z/10/Z]; KWF BUIT [2014-6637]; Millennium Nucleus for Fungal Integrative and Synthetic Biology [NC120043]; Fondo Nacional de Desarrollo Cientifico y Tecnologico [FONDECYT 1131030];  [RS120372];  [RS140275]; Wellcome Trust [093734/Z/10/Z] Funding Source: Wellcome Trust; Medical Research Council [MC_UP_1201/4] Funding Source: researchfish; MRC [MC_UP_1201/4] Funding Source: UKRI
NR 47
TC 218
Z9 248
U1 3
U2 128
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 375
EP +
DI 10.1038/nature17407
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700033
PM 27074515
DA 2026-03-09
ER

PT J
AU Wang, X
   Feng, J
   Xue, Y
   Guan, ZY
   Zhang, DL
   Liu, Z
   Gong, Z
   Wang, Q
   Huang, JB
   Tang, C
   Zou, TT
   Yin, P
AF Wang, Xiang
   Feng, Jing
   Xue, Yuan
   Guan, Zeyuan
   Zhang, Delin
   Liu, Zhu
   Gong, Zhou
   Wang, Qiang
   Huang, Jinbo
   Tang, Chun
   Zou, Tingting
   Yin, Ping
TI Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex
SO NATURE
LA English
DT Article
ID messenger-rna methylation; nuclear-rna; m(6)a; n-6-methyladenosine; reveals; dna; n6-methyladenosine; widespread; micrornas
AB Chemical modifications of RNA have essential roles in a vast range of cellular processes(1-3). N-6-methyladenosine (m(6)A) is an abundant internal modification in messenger RNA and long non-coding RNA that can be dynamically added and removed by RNA methyltransferases (MTases) and demethylases, respectively(2-5). An MTase complex comprising methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) efficiently catalyses methyl group transfer(6,7). In contrast to the well-studied DNA MTase(8), the exact roles of these two RNA MTases in the complex remain to be elucidated. Here we report the crystal structures of the METTL3-METTL14 heterodimer with MTase domains in the ligand-free, S-adenosyl methionine (AdoMet)-bound and S-adenosyl homocysteine (AdoHcy)-bound states, with resolutions of 1.9, 1.71 and 1.61 angstrom, respectively. Both METTL3 and METTL14 adopt a class I MTase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove. Notably, AdoMet was observed in only the METTL3 pocket and not in METTL14. Combined with biochemical analysis, these results suggest that in the m(6)A MTase complex, METTL3 primarily functions as the catalytic core, while METTL14 serves as an RNA-binding platform, reminiscent of the target recognition domain of DNA N-6-adenine MTase(9,10). This structural information provides an important framework for the functional investigation of m(6)A.
C1 [Wang, Xiang; Feng, Jing; Xue, Yuan; Guan, Zeyuan; Zhang, Delin; Wang, Qiang; Huang, Jinbo; Zou, Tingting; Yin, Ping] Huazhong Agr Univ, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China.
   [Wang, Xiang; Feng, Jing; Xue, Yuan; Guan, Zeyuan; Zhang, Delin; Wang, Qiang; Huang, Jinbo; Zou, Tingting; Yin, Ping] Huazhong Agr Univ, Natl Ctr Plant Gene Res, Wuhan 430070, Peoples R China.
   [Liu, Zhu; Tang, Chun] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310028, Zhejiang, Peoples R China.
   [Gong, Zhou; Tang, Chun] Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan 430071, Peoples R China.
   [Zou, Tingting] Huazhong Agr Univ, Coll Life Sci & Technol, Wuhan 430070, Peoples R China.
C3 Huazhong Agricultural University; Huazhong Agricultural University; Zhejiang University; Chinese Academy of Sciences; Huazhong Agricultural University
RP Yin, P (corresponding author), Huazhong Agr Univ, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China.; Yin, P (corresponding author), Huazhong Agr Univ, Natl Ctr Plant Gene Res, Wuhan 430070, Peoples R China.
EM yinping@mail.hzau.edu.cn
FU Ministry of Science and Technology [2015CB910900, 2013CB900200]; Fok Ying-Tong Education Foundation [151021]; Fundamental Research Funds for the Central Universities [2014PY026, 2015PY219, 2014JQ001]; Huazhong Agricultural University Scientific & Technological Self-innovation Foundation [2013RC013]
NR 37
TC 989
Z9 1163
U1 7
U2 354
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 575
EP +
DI 10.1038/nature18298
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300059
PM 27281194
DA 2026-03-09
ER

PT J
AU He, Y
   Zeng, MY
   Yang, DH
   Metro, B
   Núñez, G
AF He, Yuan
   Zeng, Melody Y.
   Yang, Dahai
   Metro, Benny
   Nunez, Gabriel
TI NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux
SO NATURE
LA English
DT Article
ID noncanonical inflammasome activation; protein-kinases; caspase-11; cytokinesis; mutations; immunity; innate; family; toxins; cells
AB Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases(1). So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1 beta and IL-18 proteins(2,3). The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases(4,5) as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations(6,7). Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli(8,9). Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins)(10), as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of NEK7, caspase-1 activation and IL-1 beta release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasomes. NLRP3-activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high-molecular-mass NLRP3-NEK7 complex, which, along with ASC oligomerization and ASC speck formation, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed that NEK7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that NEK7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome assembly and activation.
C1 [He, Yuan; Zeng, Melody Y.; Yang, Dahai; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [He, Yuan; Zeng, Melody Y.; Yang, Dahai; Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
   [Yang, Dahai] E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China.
   [Metro, Benny] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; East China University of Science & Technology; Bar Ilan University
RP Núñez, G (corresponding author), Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.; Núñez, G (corresponding author), Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
EM gabriel.nunez@umich.edu
FU NIH [T32HL007517, T32DK094775, R01AI063331, R01DK091191]; China Scholarship Council [201306740018]; Israel Science Foundation [768/11]; University of Michigan's Cancer Center Support Grant; National Heart Lung and Blood Institute [T32HL007517] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R37AI063331] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK094775, P30DK034933] Funding Source: NIH RePORTER
NR 35
TC 1042
Z9 1189
U1 7
U2 249
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 354
EP +
DI 10.1038/nature16959
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100041
PM 26814970
DA 2026-03-09
ER

PT J
AU Evers, CHJ
   Luiken, JA
   Bolhuis, PG
   Kegel, WK
AF Evers, Chris H. J.
   Luiken, Jurriaan A.
   Bolhuis, Peter G.
   Kegel, Willem K.
TI Self-assembly of microcapsules via colloidal bond hybridization and anisotropy
SO NATURE
LA English
DT Article
ID seeded emulsion polymerization; patchy particles; grafted nanoparticles; protein
AB Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures(1-3). Mutually attractive nanoparticles that are deformable owing to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles(4-6). Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and the colloidal equivalents of molecules and micelles(7-9). However, model systems that combine mutual attraction, anisotropy and deformability have not yet been realized. Here we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogously to the simplest chemical bond-in which two isotropic orbitals hybridize into the molecular orbital of H-2-these flexible groups redistribute on binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, whereas anisotropic snowman-shaped particles self-assemble into hollow monolayer microcapsules. A modest change in the building blocks thus results in much greater complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into markedly more complex structures than do similar particles that are isotropic or non-deformable.
C1 [Evers, Chris H. J.; Kegel, Willem K.] Univ Utrecht, Vant Hoff Lab Phys & Colloid Chem, Debye Inst Nanomat Sci, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
   [Luiken, Jurriaan A.; Bolhuis, Peter G.] Univ Amsterdam, Vant Hoff Inst Mol Sci, POB 94157, NL-1090 GD Amsterdam, Netherlands.
C3 Utrecht University; University of Amsterdam
RP Evers, CHJ; Kegel, WK (corresponding author), Univ Utrecht, Vant Hoff Lab Phys & Colloid Chem, Debye Inst Nanomat Sci, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
EM c.h.j.evers@uu.nl; w.k.kegel@uu.nl
FU Netherlands Organization for Scientific Research [VICI 700.58.442, TOP-GO 700.10.355]
CR Akcora P, 2009, NAT MATER, V8, P354, DOI 10.1038/nmat2404
   Asai M, 2015, SOFT MATTER, V11, P793, DOI 10.1039/c4sm02295e
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   BATES FS, 1991, SCIENCE, V251, P898, DOI 10.1126/science.251.4996.898
   Bhattacharyay A, 2008, CHEM PHYS LETT, V458, P210, DOI 10.1016/j.cplett.2008.04.052
   Chen Q, 2011, NATURE, V469, P381, DOI 10.1038/nature09713
   Chen T, 2007, LANGMUIR, V23, P6598, DOI 10.1021/la063755d
   Crassous JJ, 2014, NAT COMMUN, V5, P0, DOI 10.1038/ncomms6516
   Deegan RD, 1997, NATURE, V389, P827, DOI 10.1038/39827
   Dinsmore AD, 2002, SCIENCE, V298, P1006, DOI 10.1126/science.1074868
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   Geerts N, 2010, SOFT MATTER, V6, P664, DOI 10.1039/b917846e
   Glotzer SC, 2007, NAT MATER, V6, P557, DOI 10.1038/nmat1949
   Gröschel AH, 2013, NATURE, V503, P247, DOI 10.1038/nature12610
   Hu X, 2009, CHEM LETT, V38, P854
   Kraft DJ, 2012, P NATL ACAD SCI USA, V109, P10787, DOI 10.1073/pnas.1116820109
   Kraft DJ, 2009, SOFT MATTER, V5, P3823, DOI 10.1039/b910593j
   Larson-Smith K, 2011, SOFT MATTER, V7, P5339, DOI 10.1039/c0sm01497d
   Luiken JA, 2013, PHYS REV E, V88, P0, DOI 10.1103/PhysRevE.88.012303
   MARCHANDBRYNAERT J, 1995, J COLLOID INTERF SCI, V173, P236, DOI 10.1006/jcis.1995.1319
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   Tompa P, 2008, TRENDS BIOCHEM SCI, V33, P2, DOI 10.1016/j.tibs.2007.10.003
   van Ravensteijn BGP, 2013, CHEM MATER, V25, P4348, DOI 10.1021/cm4025606
   Wang PH, 2002, COLLOID POLYM SCI, V280, P152, DOI 10.1007/s003960100588
   Wang YF, 2012, NATURE, V491, P51, DOI 10.1038/nature11564
   Yi GR, 2013, J PHYS-CONDENS MAT, V25, P0, DOI 10.1088/0953-8984/25/19/193101
   Zhang ZL, 2004, NANO LETT, V4, P1407, DOI 10.1021/nl0493500
NR 30
TC 75
Z9 85
U1 7
U2 325
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 364
EP +
DI 10.1038/nature17956
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800031
PM 27281213
DA 2026-03-09
ER

PT J
AU Jacques, DA
   McEwan, WA
   Hilditch, L
   Price, AJ
   Towers, GJ
   James, LC
AF Jacques, David A.
   McEwan, William A.
   Hilditch, Laura
   Price, Amanda J.
   Towers, Greg J.
   James, Leo C.
TI HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis
SO NATURE
LA English
DT Article
ID amino-terminal domain; crystal-structures; protein; recognition
AB During the early stages of infection, the HIV-1 capsid protects viral components from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while allowing access to nucleotides for efficient reverse transcription1. Here we show that each capsid hexamer has a size-selective pore bound by a ring of six arginine residues and a 'molecular iris' formed by the amino-terminal beta-hairpin. The arginine ring creates a strongly positively charged channel that recruits the four nucleotides with on-rates that approach diffusion limits. Progressive removal of pore arginines results in a dose-dependent and concomitant decrease in nucleotide affinity, reverse transcription and infectivity. This positively charged channel is universally conserved in lentiviral capsids despite the fact that it is strongly destabilizing without nucleotides to counteract charge repulsion. We also describe a channel inhibitor, hexacarboxybenzene, which competes for nucleotide binding and efficiently blocks encapsidated reverse transcription, demonstrating the tractability of the pore as a novel drug target.
C1 [Jacques, David A.; McEwan, William A.; Price, Amanda J.; James, Leo C.] MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
   [Hilditch, Laura; Towers, Greg J.] UCL, Infect & Immun, Cruciform Bldg 3-3,90 Gower St, London WC1E 6BT, England.
   [Price, Amanda J.] Astex Pharmaceut, 436 Cambridge Sci Pk,Milton Rd, Cambridge CB4 0QA, England.
C3 MRC Laboratory Molecular Biology; University of London; University College London; Astex Pharmaceuticals
RP James, LC (corresponding author), MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.; Towers, GJ (corresponding author), UCL, Infect & Immun, Cruciform Bldg 3-3,90 Gower St, London WC1E 6BT, England.
EM g.towers@ucl.ac.uk; lcj@mrc-lmb.cam.ac.uk
FU Medical Research Council (UK) [U105181010]; European Research Council [281627 -IAI]; European Research Council under the European Union; ERC [339223]; National Institute for Health Research University College London Hospitals Biomedical Research Centre; Wellcome Trust; NHMRC [GNT1036521]; Emmanuel College, Cambridge; MRC [G9721629, MC_U105181010, MC_PC_12024, G0801172] Funding Source: UKRI; Medical Research Council [1368839, MC_U105181010, MC_PC_12024, G0801172, 1195793, G9721629] Funding Source: researchfish; Wellcome Trust [108183/Z/15/Z] Funding Source: researchfish; European Research Council (ERC) [339223] Funding Source: European Research Council (ERC)
NR 40
TC 188
Z9 222
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 349
EP +
DI 10.1038/nature19098
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900039
PM 27509857
DA 2026-03-09
ER

PT J
AU Hikabe, O
   Hamazaki, N
   Nagamatsu, G
   Obata, Y
   Hirao, Y
   Hamada, N
   Shimamoto, S
   Imamura, T
   Nakashima, K
   Saitou, M
   Hayashi, K
AF Hikabe, Orie
   Hamazaki, Nobuhiko
   Nagamatsu, Go
   Obata, Yayoi
   Hirao, Yuji
   Hamada, Norio
   Shimamoto, So
   Imamura, Takuya
   Nakashima, Kinichi
   Saitou, Mitinori
   Hayashi, Katsuhiko
TI Reconstitution in vitro of the entire cycle of the mouse female germ line
SO NATURE
LA English
DT Article
ID embryonic stem-cells; oocytes; gene; mice; quantification; generation; induction; memory; ovary; fate
AB The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg(1,2). The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.
C1 [Hikabe, Orie; Hamazaki, Nobuhiko; Nagamatsu, Go; Hamada, Norio; Shimamoto, So; Imamura, Takuya; Nakashima, Kinichi; Hayashi, Katsuhiko] Kyushu Univ, Grad Sch Med Sci, Dept Stem Cell Biol & Med, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.
   [Obata, Yayoi] Tokyo Univ Agr, Dept Biosci, Setagaya Ku, 1-1-1 Sakuragaoka, Tokyo 1568502, Japan.
   [Hirao, Yuji] NARO Inst Livestock & Grassland Sci, Ikenodai 2, Tsukuba, Ibaraki 3050901, Japan.
   [Hamada, Norio] Kyushu Univ, Grad Sch Med Sci, Dept Obstet & Gynecol, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.
   [Saitou, Mitinori] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
   [Saitou, Mitinori] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.
   [Saitou, Mitinori] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan.
   [Saitou, Mitinori] JST, ERATO, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
   [Hayashi, Katsuhiko] JST, PRESTO, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.
C3 Kyushu University; Tokyo University of Agriculture; National Agriculture & Food Research Organization - Japan; Kyushu University; Kyoto University; Kyoto University; Kyoto University; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST)
RP Hayashi, K (corresponding author), Kyushu Univ, Grad Sch Med Sci, Dept Stem Cell Biol & Med, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.; Hayashi, K (corresponding author), JST, PRESTO, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.
EM hayashik@hgs.med.kyushu-u.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKENHI) [25114006]; JST-PRESTO; Uehara Memorial Foundation; Takeda Science Foundation; Grants-in-Aid for Scientific Research [16K14740, 15H04603, 25114006, 16K15054, 16K18816] Funding Source: KAKEN
NR 32
TC 445
Z9 503
U1 2
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 299
EP +
DI 10.1038/nature20104
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500047
PM 27750280
DA 2026-03-09
ER

PT J
AU Hamidian, MH
   Edkins, SD
   Joo, SH
   Kostin, A
   Eisaki, H
   Uchida, S
   Lawler, MJ
   Kim, EA
   Mackenzie, AP
   Fujita, K
   Lee, J
   Davis, JCS
AF Hamidian, M. H.
   Edkins, S. D.
   Joo, Sang Hyun
   Kostin, A.
   Eisaki, H.
   Uchida, S.
   Lawler, M. J.
   Kim, E. -A.
   Mackenzie, A. P. .
   Fujita, K.
   Lee, Jinho
   Davis, J. C. Seamus
TI Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x
SO NATURE
LA English
DT Article
ID high-temperature superconductors; electromagnetic environment; cuprate superconductors; josephson-junctions; charge order; symmetry
AB The quantum condensate of Cooper pairs forming a superconductor was originally conceived as being translationally invariant. In theory, however, pairs can exist with finite momentum Q, thus generating a state with a spatially modulated Cooper-pair density(1,2). Such a state has been created in ultracold Li-6 gas(3) but never observed directly in any superconductor. It is now widely hypothesized that the pseudogap phase(4) of the copper oxide superconductors contains such a 'pair density wave' state(5-21). Here we report the use of nanometre-resolution scanned Josephson tunnelling microscopy(22-24) to image Cooper pair tunnelling from a d-wave superconducting microscope tip to the condensate of the superconductor Bi2Sr2CaCu2O8+x. We demonstrate condensate visualization capabilities directly by using the Cooper-pair density variations surrounding zinc impurity atoms(25) and at the Bi2Sr2CaCu2O8+x crystal supermodulation(26). Then, by using Fourier analysis of scanned Josephson tunnelling images, we discover the direct signature of a Cooper-pair density modulation at wavevectors Q(P) approximate to (0.25, 0)2 pi/a(0) and (0, 0.25)2 pi/a(0) in Bi2Sr2CaCu2O8+x. The amplitude of these modulations is about five per cent of the background condensate density and their form factor exhibits primarily s or s' symmetry. This phenomenology is consistent with Ginzburg-Landau theory(5,13,14) when a charge density wave(5,27) with d-symmetry form factor(28-30) and wavevector Q(C) = Q(P) coexists with a d-symmetry superconductor; it is also predicted by several contemporary microscopic theories for the pseudogap phase(18-21).
C1 [Hamidian, M. H.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Edkins, S. D.; Kostin, A.; Lawler, M. J.; Kim, E. -A.; Davis, J. C. Seamus] Cornell Univ, Dept Phys, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
   [Edkins, S. D.; Mackenzie, A. P. .; Davis, J. C. Seamus] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Joo, Sang Hyun; Lee, Jinho] Seoul Natl Univ, Inst Appl Phys, Dept Phys & Astron, Seoul 151747, South Korea.
   [Joo, Sang Hyun; Lee, Jinho] Inst for Basic Sci Korea, Ctr Correlated Electron Syst, Seoul 151742, South Korea.
   [Eisaki, H.; Uchida, S.] Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058568, Japan.
   [Uchida, S.] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130011, Japan.
   [Lawler, M. J.] SUNY Binghamton, Dept Phys, Binghamton, NY 13902 USA.
   [Mackenzie, A. P. .] Max Planck Inst Chem Phys Solids, D-01187 Dresden, Germany.
   [Fujita, K.; Davis, J. C. Seamus] Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.
   [Davis, J. C. Seamus] Cornell Univ, Cornell Nanoscale Sci, Kavli Inst, Ithaca, NY 14853 USA.
C3 Harvard University; Cornell University; University of St Andrews; Seoul National University (SNU); Institute for Basic Science - Korea (IBS); National Institute of Advanced Industrial Science & Technology (AIST); University of Tokyo; State University of New York (SUNY) System; Binghamton University, SUNY; Max Planck Society; United States Department of Energy (DOE); Brookhaven National Laboratory; Cornell University
RP Davis, JCS (corresponding author), Cornell Univ, Dept Phys, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.; Davis, JCS (corresponding author), Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.; Lee, J (corresponding author), Seoul Natl Univ, Inst Appl Phys, Dept Phys & Astron, Seoul 151747, South Korea.; Lee, J (corresponding author), Inst for Basic Sci Korea, Ctr Correlated Electron Syst, Seoul 151742, South Korea.; Davis, JCS (corresponding author), Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.; Davis, JCS (corresponding author), Cornell Univ, Cornell Nanoscale Sci, Kavli Inst, Ithaca, NY 14853 USA.
EM jinholee@snu.ac.kr; jcseamusdavis@gmail.com
FU Engineering and Physical Sciences Research Council [1265368, EP/I031014/1] Funding Source: researchfish; EPSRC [EP/I031014/1] Funding Source: UKRI
NR 44
TC 264
Z9 298
U1 6
U2 244
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 343
EP +
DI 10.1038/nature17411
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DZ9WR
UT WOS:000386232400001
PM 27074504
DA 2026-03-09
ER

PT J
AU Mashaghi, A
   Bezrukavnikov, S
   Minde, DP
   Wentink, AS
   Kityk, R
   Zachmann-Brand, B
   Mayer, MP
   Kramer, G
   Bukau, B
   Tans, SJ
AF Mashaghi, Alireza
   Bezrukavnikov, Sergey
   Minde, David P.
   Wentink, Anne S.
   Kityk, Roman
   Zachmann-Brand, Beate
   Mayer, Matthias P.
   Kramer, Guenter
   Bukau, Bernd
   Tans, Sander J.
TI Alternative modes of client binding enable functional plasticity of Hsp70
SO NATURE
LA English
DT Article
ID transcription factor sigma(32); molecular chaperones; substrate-binding; dnak; protein; grpe; atp; system; cycle; mechanism
AB The Hsp70 system is a central hub of chaperone activity in all domains of life. Hsp70 performs a plethora of tasks, including folding assistance, protection against aggregation, protein trafficking, and enzyme activity regulation(1-5), and interacts with non-folded chains, as well as near-native, misfolded, and aggregated proteins(6-10). Hsp70 is thought to achieve its many physiological roles by binding peptide segments that extend from these different protein conformers within a groove that can be covered by an ATP-driven helical lid(11-15). However, it has been difficult to test directly how Hsp70 interacts with protein substrates in different stages of folding and how it affects their structure. Moreover, recent indications of diverse lid conformations in Hsp70-substrate complexes raise the possibility of additional interaction mechanisms(15-18). Addressing these issues is technically challenging, given the conformational dynamics of both chaperone and client, the transient nature of their interaction, and the involvement of co-chaperones and the ATP hydrolysis cycle(19). Here, using optical tweezers, we show that the bacterial Hsp70 homologue (DnaK) binds and stabilizes not only extended peptide segments, but also partially folded and near-native protein structures. The Hsp70 lid and groove act synergistically when stabilizing folded structures: stabilization is abolished when the lid is truncated and less efficient when the groove is mutated. The diversity of binding modes has important consequences: Hsp70 can both stabilize and destabilize folded structures, in a nucleotide regulated manner; like Hsp90 and GroEL, Hsp70 can affect the late stages of protein folding; and Hsp70 can suppress aggregation by protecting partially folded structures as well as unfolded protein chains. Overall, these findings in the DnaK system indicate an extension of the Hsp70 canonical model that potentially affects a wide range of physiological roles of the Hsp70 system.
C1 [Mashaghi, Alireza; Bezrukavnikov, Sergey; Minde, David P.; Tans, Sander J.] FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
   [Wentink, Anne S.; Kityk, Roman; Zachmann-Brand, Beate; Mayer, Matthias P.; Kramer, Guenter; Bukau, Bernd] Heidelberg Univ ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
   [Wentink, Anne S.; Zachmann-Brand, Beate; Kramer, Guenter; Bukau, Bernd] German Canc Res Ctr, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
C3 AMOLF; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Tans, SJ (corresponding author), FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
EM tans@amolf.nl
FU Foundation for Fundamental Research on Matter (FOM); Netherlands Organization for Scientific Research (NWO); Deutsche Forschungsgemeinschaft [SFB638, FOR1805, MA 1278/4-1]
NR 31
TC 154
Z9 173
U1 0
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 448
EP 451
DI 10.1038/nature20137
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700058
PM 27783598
DA 2026-03-09
ER

PT J
AU Vasek, MJ
   Garber, C
   Dorsey, D
   Durrant, DM
   Bollman, B
   Soung, A
   Yu, JS
   Perez-Torres, C
   Frouin, A
   Wilton, DK
   Funk, K
   DeMasters, BK
   Jiang, XP
   Bowen, JR
   Mennerick, S
   Robinson, JK
   Garbow, JR
   Tyler, KL
   Suthar, MS
   Schmidt, RE
   Stevens, B
   Klein, RS
AF Vasek, Michael J.
   Garber, Charise
   Dorsey, Denise
   Durrant, Douglas M.
   Bollman, Bryan
   Soung, Allison
   Yu, Jinsheng
   Perez-Torres, Carlos
   Frouin, Arnaud
   Wilton, Daniel K.
   Funk, Kristen
   DeMasters, Bette K.
   Jiang, Xiaoping
   Bowen, James R.
   Mennerick, Steven
   Robinson, John K.
   Garbow, Joel R.
   Tyler, Kenneth L.
   Suthar, Mehul S.
   Schmidt, Robert E.
   Stevens, Beth
   Klein, Robyn S.
TI A complement-microglial axis drives synapse loss during virus-induced memory impairment
SO NATURE
LA English
DT Article
ID west-nile-virus; infection; activation; cns; trafficking; protects; death
AB Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae(1,2). Although thousands of cases of WNV-mediated memory dysfunction accrue annually(3), the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development(4,5). Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein(6,7) leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.
C1 [Vasek, Michael J.; Garber, Charise; Dorsey, Denise; Durrant, Douglas M.; Bollman, Bryan; Soung, Allison; Funk, Kristen; Klein, Robyn S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Durrant, Douglas M.] Calif State Polytech Univ Pomona, Dept Biol Sci, 3801 West Temple Ave, Pomona, CA 91768 USA.
   [Yu, Jinsheng] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Perez-Torres, Carlos; Garbow, Joel R.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
   [Frouin, Arnaud; Wilton, Daniel K.; Stevens, Beth] Harvard Univ, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Sch Med,Dept Neurol, Boston, MA 02115 USA.
   [DeMasters, Bette K.; Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA.
   [Jiang, Xiaoping; Mennerick, Steven] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Bowen, James R.; Suthar, Mehul S.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30329 USA.
   [Bowen, James R.; Suthar, Mehul S.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Emory Vaccine Ctr,Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Robinson, John K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
   [Schmidt, Robert E.; Klein, Robyn S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Klein, Robyn S.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); California State University System; California State Polytechnic University Pomona; Washington University (WUSTL); Washington University (WUSTL); Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; University of Colorado System; University of Colorado Anschutz Medical Campus; Washington University (WUSTL); Emory University; Emory University; Children's Healthcare of Atlanta (CHOA); State University of New York (SUNY) System; Stony Brook University; Washington University (WUSTL); Washington University (WUSTL)
RP Klein, RS (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.; Klein, RS (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.; Klein, RS (corresponding author), Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
EM rklein@dom.wustl.edu
FU NIH [F31 NS077640, R01 NS052632, U19 AI083019]; National Cancer Institute [P30CA091842] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI101400, T32AI052066] Funding Source: NIH RePORTER
NR 33
TC 504
Z9 583
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 538
EP +
DI 10.1038/nature18283
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300051
PM 27337340
DA 2026-03-09
ER

PT J
AU Manglik, A
   Lin, H
   Aryal, DK
   McCorvy, JD
   Dengler, D
   Corder, G
   Levit, A
   Kling, RC
   Bernat, V
   Hübner, H
   Huang, XP
   Sassano, MF
   Giguère, PM
   Löber, S
   Duan, D
   Scherrer, G
   Kobilka, BK
   Gmeiner, P
   Roth, BL
   Shoichet, BK
AF Manglik, Aashish
   Lin, Henry
   Aryal, Dipendra K.
   McCorvy, John D.
   Dengler, Daniela
   Corder, Gregory
   Levit, Anat
   Kling, Ralf C.
   Bernat, Viachaslau
   Huebner, Harald
   Huang, Xi-Ping
   Sassano, Maria F.
   Giguere, Patrick M.
   Loeber, Stefan
   Duan, Da
   Scherrer, Gregory
   Kobilka, Brian K.
   Gmeiner, Peter
   Roth, Bryan L.
   Shoichet, Brian K.
TI Structure-based discovery of opioid analgesics with reduced side effects
SO NATURE
LA English
DT Article
ID a(2a) receptor antagonists; protein-coupled receptor; crystal-structure; morphine analgesia; ligand discovery; biased agonism; mice; pain; identification; model
AB Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by mu-opioid-receptor (mu OR) signalling through the beta-arrestin pathway or by actions at other receptors. Conversely, G-protein mu OR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the mu OR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent G(i) activator with exceptional selectivity for mu OR and minimal beta-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle mu OR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.
C1 [Manglik, Aashish; Scherrer, Gregory; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Lin, Henry; Levit, Anat; Duan, Da; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Aryal, Dipendra K.; McCorvy, John D.; Huang, Xi-Ping; Sassano, Maria F.; Giguere, Patrick M.; Roth, Bryan L.] UNC Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC 27514 USA.
   [Dengler, Daniela; Kling, Ralf C.; Bernat, Viachaslau; Huebner, Harald; Loeber, Stefan; Gmeiner, Peter] Univ Erlangen Nurnberg, Dept Chem & Pharm, Schuhstr 19, D-91052 Erlangen, Germany.
   [Corder, Gregory; Scherrer, Gregory] Stanford Univ, Sch Med, Stanford Neurosci Inst, Dept Anesthesiol Perioperat & Pain Med,Neurosurg, Stanford, CA 94305 USA.
   [Kling, Ralf C.] Paracelsus Med Univ, Inst Physiol & Pathophysiol, D-90419 Nurnberg, Germany.
C3 Stanford University; University of California System; University of California San Francisco; University of Erlangen Nuremberg; Stanford University
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.; Shoichet, BK (corresponding author), Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.; Roth, BL (corresponding author), UNC Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC 27514 USA.; Gmeiner, P (corresponding author), Univ Erlangen Nurnberg, Dept Chem & Pharm, Schuhstr 19, D-91052 Erlangen, Germany.
EM kobilka@stanford.edu; peter.gmeiner@fau.de; bryan_roth@med.unc.edu; shoichet@cgl.ucsf.edu
FU US National Institutes of Health [GM106990, DA036246, GM59957]; National Institutes of Mental Health Psychoactive Drug Screening Program; Michael Hooker Distinguished Professorship; German Research Foundation [Gm 13/10, GRK 1910]; Stanford University Medical Scientist Training Program [T32GM007365]; American Heart Association [12PRE8120001];  [DA017204];  [DA035764]; American Heart Association (AHA) [12PRE8120001] Funding Source: American Heart Association (AHA); National Institute of General Medical Sciences [T32GM067547, T32GM007365] Funding Source: NIH RePORTER
NR 75
TC 769
Z9 916
U1 10
U2 439
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 185
EP +
DI 10.1038/nature19112
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100038
PM 27533032
DA 2026-03-09
ER

PT J
AU Treutlein, B
   Lee, QY
   Camp, JG
   Mall, M
   Koh, W
   Shariati, SAM
   Sim, S
   Neff, NF
   Skotheim, JM
   Wernig, M
   Quake, SR
AF Treutlein, Barbara
   Lee, Qian Yi
   Camp, J. Gray
   Mall, Moritz
   Koh, Winston
   Shariati, Seyed Ali Mohammad
   Sim, Sopheak
   Neff, Norma F.
   Skotheim, Jan M.
   Wernig, Marius
   Quake, Stephen R.
TI Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq
SO NATURE
LA English
DT Article
ID functional-neurons; direct conversion; heterogeneity; expression; mechanisms; generation; regulators; mouse
AB Direct lineage reprogramming represents a remarkable conversion of cellular and transcriptome states(1-3). However, the intermediate stages through which individual cells progress during reprogramming are largely undefined. Here we use single-cell RNA sequencing(4-7) at multiple time points to dissect direct reprogramming from mouse embryonic fibroblasts to induced neuronal cells. By deconstructing heterogeneity at each time point and ordering cells by transcriptome similarity, we find that the molecular reprogramming path is remarkably continuous. Overexpression of the proneural pioneer factor Ascl1 results in a well-defined initialization, causing cells to exit the cell cycle and re-focus gene expression through distinct neural transcription factors. The initial transcriptional response is relatively homogeneous among fibroblasts, suggesting that the early steps are not limiting for productive reprogramming. Instead, the later emergence of a competing myogenic program and variable transgene dynamics over time appear to be the major efficiency limits of direct reprogramming. Moreover, a transcriptional state, distinct from donor and target cell programs, is transiently induced in cells undergoing productive reprogramming. Our data provide a high-resolution approach for understanding transcriptome states during lineage differentiation.
C1 [Treutlein, Barbara; Lee, Qian Yi; Koh, Winston; Neff, Norma F.; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Treutlein, Barbara] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Lee, Qian Yi; Mall, Moritz; Sim, Sopheak; Wernig, Marius] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA.
   [Lee, Qian Yi; Mall, Moritz; Wernig, Marius] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
   [Camp, J. Gray] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA.
   [Shariati, Seyed Ali Mohammad; Skotheim, Jan M.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Quake, Stephen R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Quake, Stephen R.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
C3 Stanford University; Max Planck Society; Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Quake, SR (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.; Wernig, M (corresponding author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA.; Wernig, M (corresponding author), Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.; Quake, SR (corresponding author), Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.; Quake, SR (corresponding author), Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
EM wernig@stanford.edu; quake@stanford.edu
FU NIH [RC4NS073015-01, GM092925]; Stinehart-Reed Foundation; Ellison Medical Foundation; New York Stem Cell Foundation; CIRM [RB5-07466]; National Science Scholarship from the Agency for Science, Technology and Research; German Research Foundation; PhRMA foundation Informatics fellowship
NR 45
TC 347
Z9 426
U1 1
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 391
EP +
DI 10.1038/nature18323
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800037
PM 27281220
DA 2026-03-09
ER

PT J
AU Reischauer, S
   Stone, OA
   Villasenor, A
   Chi, N
   Jin, SW
   Martin, M
   Lee, MT
   Fukuda, N
   Marass, M
   Witty, A
   Fiddes, I
   Kuo, T
   Chung, WS
   Salek, S
   Lerrigo, R
   Alsiö, J
   Luo, SJ
   Tworus, D
   Augustine, SM
   Mucenieks, S
   Nystedt, B
   Giraldez, AJ
   Schroth, GP
   Andersson, O
   Stainier, DYR
AF Reischauer, Sven
   Stone, Oliver A.
   Villasenor, Alethia
   Chi, Neil
   Jin, Suk-Won
   Martin, Marcel
   Lee, Miler T.
   Fukuda, Nana
   Marass, Michele
   Witty, Alec
   Fiddes, Ian
   Kuo, Taiyi
   Chung, Won-Suk
   Salek, Sherveen
   Lerrigo, Robert
   Alsio, Jessica
   Luo, Shujun
   Tworus, Dominika
   Augustine, Sruthy M.
   Mucenieks, Sophie
   Nystedt, Bjorn
   Giraldez, Antonio J.
   Schroth, Gary P.
   Andersson, Olov
   Stainier, Didier Y. R.
TI Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification
SO NATURE
LA English
DT Article
ID zebrafish gene cloche; rna-seq; hemogenic endothelium; ribosomal-rna; differentiation; blood; scl; identification; progenitor; acts
AB Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells(1-4) and a significant increase in cardiomyocyte numbers(5). Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation(1-7) and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location. Here we used a deletion allele of cloche to identify several new cloche candidate genes within this genomic region, and systematically genome-edited each candidate. Through this comprehensive interrogation, we succeeded in isolating the cloche gene and discovered that it encodes a PAS-domain-containing bHLH transcription factor, and that it is expressed in a highly specific spatiotemporal pattern starting during late gastrulation. Gain-of-function experiments show that it can potently induce endothelial gene expression. Epistasis experiments reveal that it functions upstream of etv2 and tal1, the earliest expressed endothelial and haematopoietic transcription factor genes identified to date. A mammalian cloche orthologue can also rescue blood vessel formation in zebrafish cloche mutants, indicating a highly conserved role in vertebrate vasculogenesis and haematopoiesis. The identification of this master regulator of endothelial and haematopoietic fate enhances our understanding of early mesoderm diversification and may lead to improved protocols for the generation of endothelial and haematopoietic cells in vivo and in vitro.
C1 [Reischauer, Sven; Stone, Oliver A.; Villasenor, Alethia; Chi, Neil; Jin, Suk-Won; Fiddes, Ian; Kuo, Taiyi; Chung, Won-Suk; Salek, Sherveen; Lerrigo, Robert; Alsio, Jessica; Stainier, Didier Y. R.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
   [Reischauer, Sven; Stone, Oliver A.; Villasenor, Alethia; Fukuda, Nana; Marass, Michele; Augustine, Sruthy M.; Mucenieks, Sophie; Stainier, Didier Y. R.] Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany.
   [Chi, Neil; Witty, Alec] Univ Calif San Diego, Inst Genom Med, Div Cardiol, Dept Med, La Jolla, CA 92037 USA.
   [Martin, Marcel] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden.
   [Lee, Miler T.; Giraldez, Antonio J.] Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA.
   [Luo, Shujun; Schroth, Gary P.] Illumina, San Diego, CA 92122 USA.
   [Tworus, Dominika; Andersson, Olov] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Nystedt, Bjorn] Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, S-75124 Uppsala, Sweden.
   [Jin, Suk-Won] Gwangju Inst Sci & Technol, Sch Life Sci, Gwangju 61005, South Korea.
   [Jin, Suk-Won] Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT 06511 USA.
   [Lee, Miler T.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
   [Fiddes, Ian] Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA.
   [Fiddes, Ian] Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Kuo, Taiyi] Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA.
   [Kuo, Taiyi] Columbia Univ Coll Phys & Surg, Berrie Diabet Ctr, 630 W 168th St, New York, NY 10032 USA.
   [Chung, Won-Suk] Korea Adv Inst Sci & Technol, Dept Biol Sci, Daejeon 34141, South Korea.
   [Salek, Sherveen] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21224 USA.
   [Lerrigo, Robert] Univ Washington, Div Gen Internal Med, Seattle, WA 98104 USA.
   [Alsio, Jessica] Novartis, CH-4056 Basel, Switzerland.
   [Luo, Shujun] Personalis, Menlo Pk, CA 94025 USA.
C3 University of California System; University of California San Francisco; Max Planck Society; University of California System; University of California San Diego; Stockholm University; Yale University; Illumina; Karolinska Institutet; Uppsala University; Gwangju Institute of Science & Technology (GIST); Yale University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; Columbia University; Columbia University; Korea Advanced Institute of Science & Technology (KAIST); Johns Hopkins University; Johns Hopkins Medicine; University of Washington; University of Washington Seattle
RP Stainier, DYR (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.; Stainier, DYR (corresponding author), Max Planck Inst Heart & Lung Res, Dept Dev Genet, D-61231 Bad Nauheim, Germany.
EM didier.stainier@mpi-bn.mpg.de
FU DFG; AHA; NIH; Ragnar Soderberg Foundation; Swedish Research Council; Packard Foundation; Max Planck Society
NR 53
TC 125
Z9 145
U1 0
U2 29
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 294
EP +
DI 10.1038/nature18614
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600059
PM 27411634
DA 2026-03-09
ER

PT J
AU Suzuki, Y
   Cardone, G
   Restrepo, D
   Zavattieri, PD
   Baker, TS
   Tezcan, FA
AF Suzuki, Yuta
   Cardone, Giovanni
   Restrepo, David
   Zavattieri, Pablo D.
   Baker, Timothy S.
   Tezcan, F. Akif
TI Self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals
SO NATURE
LA English
DT Article
ID image; membrane; platform; polymer; design; oxide
AB Two-dimensional (2D) crystalline materials possess unique structural, mechanical and electronic properties(1,2) that make them highly attractive in many applications(3-5). Although there have been advances in preparing 2D materials that consist of one or a few atomic or molecular layers(6,7), bottom-up assembly of 2D crystalline materials remains a challenge and an active area of development(8-10). More challenging is the design of dynamic 2D lattices that can undergo large-scale motions without loss of crystallinity. Dynamic behaviour in porous three-dimensional (3D) crystalline solids has been exploited for stimuli-responsive functions and adaptive behaviour(11-13). As in such 3D materials, integrating flexibility and adaptiveness into crystalline 2D lattices would greatly broaden the functional scope of 2D materials. Here we report the self-assembly of unsupported, 2D protein lattices with precise spatial arrangements and patterns using a readily accessible design strategy. Three single-or double-point mutants of the C4-symmetric protein RhuA were designed to assemble via different modes of intermolecular interactions (single-disulfide, double-disulfide and metal-coordination) into crystalline 2D arrays. Owing to the flexibility of the single-disulfide interactions, the lattices of one of the variants ((C98)RhuA) are essentially defect-free and undergo substantial, but fully correlated, changes in molecular arrangement, yielding coherently dynamic 2D molecular lattices. (C98)RhuA lattices display a Poisson's ratio of -1-the lowest thermodynamically possible value for an isotropic material-making them auxetic.
C1 [Suzuki, Yuta; Cardone, Giovanni; Baker, Timothy S.; Tezcan, F. Akif] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Restrepo, David; Zavattieri, Pablo D.] Purdue Univ, Sch Civil Engn, W Lafayette, IN 47907 USA.
   [Baker, Timothy S.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Purdue University System; Purdue University; University of California System; University of California San Diego
RP Tezcan, FA (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM tezcan@ucsd.edu
FU US Department of Energy (DOE) (Division of Materials Sciences, Office of Basic Energy Sciences) [DE-FG02-10ER46677]; Air Force Office of Scientific Research (AFOSR) [BRI FA9550-12-1-0414]; NIH [1S10 RR-020016, GM-033050]; Agouron Foundation; UCSD
NR 42
TC 261
Z9 313
U1 5
U2 342
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 369
EP +
DI 10.1038/nature17633
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300043
PM 27135928
DA 2026-03-09
ER

PT J
AU Tobin, JJ
   Kratter, KM
   Persson, MV
   Looney, LW
   Dunham, MM
   Segura-Cox, D
   Li, ZY
   Chandler, CJ
   Sadavoy, SI
   Harris, RJ
   Melis, C
   Pérez, LM
AF Tobin, John J.
   Kratter, Kaitlin M.
   Persson, Magnus V.
   Looney, Leslie W.
   Dunham, Michael M.
   Segura-Cox, Dominique
   Li, Zhi-Yun
   Chandler, Claire J.
   Sadavoy, Sarah I.
   Harris, Robert J.
   Melis, Carl
   Perez, Laura M.
TI A triple protostar system formed via fragmentation of a gravitationally unstable disk
SO NATURE
LA English
DT Article
ID perseus molecular cloud; star-forming regions; class-i sources; circumstellar disks; brown dwarf; protoplanetary disk; youngest protostars; stellar-systems; keplerian disk; giant planets
AB Binary and multiple star systems are a frequent outcome of the star formation process(1,2) and as a result almost half of all stars with masses similar to that of the Sun have at least one companion star(3). Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large-scale fragmentation of turbulent gas cores and filaments(4,5) or smaller-scale fragmentation of a massive protostellar disk due to gravitational instability(6,7). Observational evidence for turbulent fragmentation on scales of more than 1,000 astronomical units has recently emerged(8,9). Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems(10-13). The triple protostar system L1448 IRS3B is an ideal system with which to search for evidence of disk fragmentation as it is in an early phase of the star formation process, it is likely to be less than 150,000 years old(14) and all of the protostars in the system are separated by less than 200 astronomical units. Here we report observations of dust and molecular gas emission that reveal a disk with a spiral structure surrounding the three protostars. Two protostars near the centre of the disk are separated by 61 astronomical units and a tertiary protostar is coincident with a spiral arm in the outer disk at a separation of 183 astronomical units(13). The inferred mass of the central pair of protostellar objects is approximately one solar mass, while the disk surrounding the three protostars has a total mass of around 0.30 solar masses. The tertiary protostar itself has a minimum mass of about 0.085 solar masses. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150 and 320 astronomical units, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.
C1 [Tobin, John J.] Univ Oklahoma, Homer L Dodge Dept Phys & Astron, 440 W Brooks St, Norman, OK 73019 USA.
   [Tobin, John J.; Persson, Magnus V.] Leiden Univ, Leiden Observ, POB 9513, NL-2300 RA Leiden, Netherlands.
   [Kratter, Kaitlin M.] Univ Arizona, Dept Astron, 933 N Cherry Ave, Tucson, AZ 85721 USA.
   [Kratter, Kaitlin M.] Univ Arizona, Steward Observ, 933 N Cherry Ave, Tucson, AZ 85721 USA.
   [Persson, Magnus V.] Chalmers Univ Technol, Dept Earth & Space Sci, Onsala Space Observ, S-43992 Onsala, Sweden.
   [Looney, Leslie W.; Segura-Cox, Dominique; Harris, Robert J.] Univ Illinois, Dept Astron, Urbana, IL 61801 USA.
   [Dunham, Michael M.] SUNY Coll Fredonia, Dept Phys, Fredonia, NY 14063 USA.
   [Li, Zhi-Yun] Univ Virginia, Dept Astron, Charlottesville, VA 22903 USA.
   [Chandler, Claire J.] Natl Radio Astron Observ, POB O, Socorro, NM 87801 USA.
   [Sadavoy, Sarah I.] Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
   [Melis, Carl] Univ Calif San Diego, Ctr Astrophys & Space Sci, San Diego, CA 92093 USA.
   [Perez, Laura M.] Max Planck Inst Radio Astron, Hugel 69, D-53121 Bonn, Germany.
C3 University of Oklahoma System; University of Oklahoma - Norman; Leiden University - Excl LUMC; Leiden University; University of Arizona; University of Arizona; Chalmers University of Technology; University of Illinois System; University of Illinois Urbana-Champaign; State University of New York (SUNY) System; SUNY Fredonia; University of Virginia; National Radio Astronomy Observatory (NRAO); Max Planck Society; University of California System; University of California San Diego; Max Planck Society
RP Tobin, JJ (corresponding author), Univ Oklahoma, Homer L Dodge Dept Phys & Astron, 440 W Brooks St, Norman, OK 73019 USA.; Tobin, JJ (corresponding author), Leiden Univ, Leiden Observ, POB 9513, NL-2300 RA Leiden, Netherlands.
EM jjtobin@ou.edu
FU University of Oklahoma; Homer L. Dodge endowed chair; Netherlands Organisation for Scientific Research (NWO) [639.041.439]; National Science Foundation [AST-1410174]; ERC [614264]; A-ERC grant [291141]; CHEMPLAN; NSF [AST-1139950, 313083]; NSF/NRAO [AST-0836064]; NSF from the NRAO [SOSPA2-021]; NASA [NNX14AB38G]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1410174] Funding Source: National Science Foundation
NR 73
TC 197
Z9 211
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 483
EP +
DI 10.1038/nature20094
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400051
PM 27786204
DA 2026-03-09
ER

PT J
AU Ruffieux, P
   Wang, SY
   Yang, B
   Sánchez-Sánchez, C
   Liu, J
   Dienel, T
   Talirz, L
   Shinde, P
   Pignedoli, CA
   Passerone, D
   Dumslaff, T
   Feng, XL
   Müllen, K
   Fasel, R
AF Ruffieux, Pascal
   Wang, Shiyong
   Yang, Bo
   Sanchez-Sanchez, Carlos
   Liu, Jia
   Dienel, Thomas
   Talirz, Leopold
   Shinde, Prashant
   Pignedoli, Carlo A.
   Passerone, Daniele
   Dumslaff, Tim
   Feng, Xinliang
   Muellen, Klaus
   Fasel, Roman
TI On-surface synthesis of graphene nanoribbons with zigzag edge topology
SO NATURE
LA English
DT Article
ID band-gap; state
AB Graphene-based nanostructures exhibit electronic properties that are not present in extended graphene. For example, quantum confinement in carbon nanotubes and armchair graphene nanoribbons leads to the opening of substantial electronic bandgaps that are directly linked to their structural boundary conditions(1,2). Nanostructures with zigzag edges are expected to host spin-polarized electronic edge states and can thus serve as key elements for graphene-based spintronics(3). The edge states of zigzag graphene nanoribbons (ZGNRs) are predicted to couple ferromagnetically along the edge and antiferromagnetically between the edges(4), but direct observation of spin-polarized edge states for zigzag edge topologies-including ZGNRs-has not yet been achieved owing to the limited precision of current top-down approaches(5-10). Here we describe the bottom-up synthesis of ZGNRs through surface-assisted polymerization and cyclodehydrogenation of specifically designed precursor monomers to yield atomically precise zigzag edges. Using scanning tunnelling spectroscopy we show the existence of edge-localized states with large energy splittings. We expect that the availability of ZGNRs will enable the characterization of their predicted spin-related properties, such as spin confinement(11) and filtering(12,13), and will ultimately add the spin degree of freedom to graphene-based circuitry.
C1 [Ruffieux, Pascal; Wang, Shiyong; Sanchez-Sanchez, Carlos; Liu, Jia; Dienel, Thomas; Talirz, Leopold; Shinde, Prashant; Pignedoli, Carlo A.; Passerone, Daniele; Fasel, Roman] Empa, Swiss Fed Labs Mat Sci & Technol, CH-8600 Dubendorf, Switzerland.
   [Yang, Bo; Dumslaff, Tim; Muellen, Klaus] Max Planck Inst Polymer Res, D-55128 Mainz, Germany.
   [Pignedoli, Carlo A.] Empa, Swiss Fed Labs Mat Sci & Technol, NCCR MARVEL, CH-8600 Dubendorf, Switzerland.
   [Feng, Xinliang] Tech Univ Dresden, Ctr Adv Elect Dresden, D-01062 Dresden, Germany.
   [Feng, Xinliang] Tech Univ Dresden, Dept Chem & Food Chem, D-01062 Dresden, Germany.
   [Fasel, Roman] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); Max Planck Society; Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); Technische Universitat Dresden; Technische Universitat Dresden; University of Bern
RP Fasel, R (corresponding author), Empa, Swiss Fed Labs Mat Sci & Technol, CH-8600 Dubendorf, Switzerland.; Müllen, K (corresponding author), Max Planck Inst Polymer Res, D-55128 Mainz, Germany.; Fasel, R (corresponding author), Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland.
EM roman.fasel@empa.ch
FU Swiss National Science Foundation; Office of Naval Research BRC Program; European Research Council; DFG Priority Program SPP 1459; Graphene Flagship [CNECT-ICT-604391]; European Union; Swiss Supercomputing Center (CSCS) [s507]
NR 40
TC 711
Z9 815
U1 15
U2 1176
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 489
EP +
DI 10.1038/nature17151
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300037
PM 27008967
DA 2026-03-09
ER

PT J
AU Turner, J
   Lu, H
   White, I
   King, JC
   Phillips, T
   Hosking, JS
   Bracegirdle, TJ
   Marshall, GJ
   Mulvaney, R
   Deb, P
AF Turner, John
   Lu, Hua
   White, Ian
   King, John C.
   Phillips, Tony
   Hosking, J. Scott
   Bracegirdle, Thomas J.
   Marshall, Gareth J.
   Mulvaney, Robert
   Deb, Pranab
TI Absence of 21st century warming on Antarctic Peninsula consistent with natural variability
SO NATURE
LA English
DT Article
ID annular mode; split jet; ice-shelf; sea-ice; climate; trends; impact; ocean
AB Since the 1950s, research stations on the Antarctic Peninsula have recorded some of the largest increases in near-surface air temperature in the Southern Hemisphere(1). This warming has contributed to the regional retreat of glaciers(2), disintegration of floating ice shelves(3) and a 'greening' through the expansion in range of various flora(4). Several interlinked processes have been suggested as contributing to the warming, including stratospheric ozone depletion(5), local sea-ice loss(6), an increase in westerly winds(5,7), and changes in the strength and location of low-high-latitude atmospheric teleconnections(8,9). Here we use a stacked temperature record to show an absence of regional warming since the late 1990s. The annual mean temperature has decreased at a statistically significant rate, with the most rapid cooling during the Austral summer. Temperatures have decreased as a consequence of a greater frequency of cold, east-to-southeasterly winds, resulting from more cyclonic conditions in the northern Weddell Sea associated with a strengthening mid-latitude jet. These circulation changes have also increased the advection of sea ice towards the east coast of the peninsula, amplifying their effects. Our findings cover only 1% of the Antarctic continent and emphasize that decadal temperature changes in this region are not primarily associated with the drivers of global temperature change but, rather, reflect the extreme natural internal variability of the regional atmospheric circulation.
C1 [Turner, John; Lu, Hua; White, Ian; King, John C.; Phillips, Tony; Hosking, J. Scott; Bracegirdle, Thomas J.; Marshall, Gareth J.; Mulvaney, Robert; Deb, Pranab] British Antarctic Survey, NERC, Madingley Rd, Cambridge CB3 0ET, England.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey
RP Turner, J (corresponding author), British Antarctic Survey, NERC, Madingley Rd, Cambridge CB3 0ET, England.
EM jtu@bas.ac.uk
FU UK Natural Environment Research Council [NE/K00445X/1]; NERC [bas0100032, bas0100034, NE/K00445X/1] Funding Source: UKRI; Natural Environment Research Council [bas0100032, bas0100034, NE/K00445X/1] Funding Source: researchfish
NR 40
TC 606
Z9 669
U1 4
U2 252
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 411
EP +
DI 10.1038/nature18645
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200038
PM 27443743
DA 2026-03-09
ER

PT J
AU Tan, CH
   McNaughton, PA
AF Tan, Chun-Hsiang
   McNaughton, Peter A.
TI The TRPM2 ion channel is required for sensitivity to warmth
SO NATURE
LA English
DT Article
ID 2-aminoethoxydiphenyl borate; capsaicin-receptor; mice lacking; ca2+ influx; adp-ribose; heat; trpv2; thermosensation; neurons; sensor
AB Thermally activated ion channels are known to detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3 and ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1)(1-7). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice(6-12), with the exception of TRPM8, the deletion of which has marked effects on the perception of moderate coolness in the range 10-25 degrees C-13. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved. Here we used calcium imaging to identify a population of thermally sensitive somatosensory neurons which do not express any of the known thermally activated TRP channels. We then used a combination of calcium imaging, electrophysiology and RNA sequencing to show that the ion channel generating heat sensitivity in these neurons is TRPM2. Autonomic neurons, usually thought of as exclusively motor, also express TRPM2 and respond directly to heat. Mice in which TRPM2 had been genetically deleted showed a striking deficit in their sensation of non-noxious warm temperatures, consistent with the idea that TRPM2 initiates a 'warm' signal which drives cool-seeking behaviour.
C1 [Tan, Chun-Hsiang; McNaughton, Peter A.] Kings Coll London, Wolfson Ctr Age Related Dis, Guys Campus, London SE1 1UL, England.
   [Tan, Chun-Hsiang] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Neurol, Kaohsiung, Taiwan.
C3 University of London; King's College London; Kaohsiung Medical University; Kaohsiung Medical University Hospital
RP McNaughton, PA (corresponding author), Kings Coll London, Wolfson Ctr Age Related Dis, Guys Campus, London SE1 1UL, England.
EM peter.mcnaughton@kcl.ac.uk
FU BBSRC (UK); Raymond & Beverley Sackler studentship; Biotechnology and Biological Sciences Research Council [BB/L002787/1] Funding Source: researchfish; BBSRC [BB/L002787/1] Funding Source: UKRI
NR 31
TC 220
Z9 256
U1 2
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 460
EP +
DI 10.1038/nature19074
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600042
PM 27533035
DA 2026-03-09
ER

PT J
AU Xu, H
   Mason, D
   Jiang, LY
   Harris, JGE
AF Xu, H.
   Mason, D.
   Jiang, Luyao
   Harris, J. G. E.
TI Topological energy transfer in an optomechanical system with exceptional points
SO NATURE
LA English
DT Article
ID quantum computation; phase; cavity; degeneracy; holonomy; anyons
AB Topological operations can achieve certain goals without requiring accurate control over local operational details; for example, they have been used to control geometric phases and have been proposed as a way of controlling the state of certain systems within their degenerate subspaces(1-8). More recently, it was predicted that topological operations can be used to transfer energy between normal modes, provided that the system possesses a specific type of degeneracy known as an exceptional point(9-11). Here we demonstrate the transfer of energy between two vibrational modes of a cryogenic optomechanical device using topological operations. We show that this transfer arises from the presence of an exceptional point in the spectrum of the device. We also show that this transfer is non-reciprocal(12-14). These results open up new directions in system control; they also open up the possibility of exploring other dynamical effects related to exceptional points(15,16), including the behaviour of thermal and quantum fluctuations in their vicinity.
C1 [Xu, H.; Mason, D.; Jiang, Luyao; Harris, J. G. E.] Yale Univ, Dept Phys, New Haven, CT 06511 USA.
   [Harris, J. G. E.] Yale Univ, Dept Appl Phys, New Haven, CT 06511 USA.
C3 Yale University; Yale University
RP Harris, JGE (corresponding author), Yale Univ, Dept Phys, New Haven, CT 06511 USA.
EM jack.harris@yale.edu
FU AFOSR [FA9550-15-1-0270]
CR Ando T, 1998, J PHYS SOC JPN, V67, P2857, DOI 10.1143/JPSJ.67.2857
   ARNOLD VI, 1989, MATH METHODS CLASSIC, V0, PCH10
   AROVAS D, 1984, PHYS REV LETT, V53, P722, DOI 10.1103/PhysRevLett.53.722
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   Gao T, 2015, NATURE, V526, P554, DOI 10.1038/nature15522
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NR 31
TC 843
Z9 940
U1 6
U2 222
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 80
EP 83
DI 10.1038/nature18604
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900042
PM 27454555
DA 2026-03-09
ER

PT J
AU Dhawan, NS
   Scopton, AP
   Dar, AC
AF Dhawan, Neil S.
   Scopton, Alex P.
   Dar, Arvin C.
TI Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling
SO NATURE
LA English
DT Article
ID kinase suppressor; mek inhibition; complex reveals; gene encodes; c-elegans; activation; protein; mechanism; braf; scaffold
AB Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies'. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes'. Kinase suppressor of Ras (KSR) is a MAPK scaffold(3-5) that is subject to allosteric regulation through dimerization with RAF(6,7). Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function. Guided by KSR mutations that selectively suppress oncogenic, but not wild-type, Ras signalling, we developed a class of compounds that stabilize a previously unrecognized inactive state of KSR. These compounds, exemplified by APS-2-79, modulate KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). Furthermore, APS-2-79 increased the potency of several MEK inhibitors specifically within Ras mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. These results reveal conformational switching in KSR as a druggable regulator of oncogenic Ras, and further suggest co-targeting of enzymatic and scaffolding activities within Ras-MAPK signalling complexes as a therapeutic strategy for overcoming Ras-driven cancers.
C1 [Dhawan, Neil S.; Scopton, Alex P.; Dar, Arvin C.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA.
   [Dhawan, Neil S.; Scopton, Alex P.; Dar, Arvin C.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Struct & Chem Biol, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Dhawan, NS (corresponding author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA.; Dhawan, NS (corresponding author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Struct & Chem Biol, New York, NY 10029 USA.
FU NIH [1DP2CA186570-01]; Damon Runyon-Rachleff Foundation; National Cancer Institute [P30CA196521] Funding Source: NIH RePORTER
NR 27
TC 82
Z9 100
U1 3
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 112
EP 116
DI 10.1038/nature19327
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900049
PM 27556948
DA 2026-03-09
ER

PT J
AU Dominissini, D
   Nachtergaele, S
   Moshitch-Moshkovitz, S
   Peer, E
   Kol, N
   Ben-Haim, MS
   Dai, Q
   Di Segni, A
   Salmon-Divon, M
   Clark, WC
   Zheng, GQ
   Pan, T
   Solomon, O
   Eyal, E
   Hershkovitz, V
   Han, D
   Doré, LC
   Amariglio, N
   Rechavi, G
   He, C
AF Dominissini, Dan
   Nachtergaele, Sigrid
   Moshitch-Moshkovitz, Sharon
   Peer, Eyal
   Kol, Nitzan
   Ben-Haim, Moshe Shay
   Dai, Qing
   Di Segni, Ayelet
   Salmon-Divon, Mali
   Clark, Wesley C.
   Zheng, Guanqun
   Pan, Tao
   Solomon, Oz
   Eyal, Eran
   Hershkovitz, Vera
   Han, Dali
   Dore, Louis C.
   Amariglio, Ninette
   Rechavi, Gideon
   He, Chuan
TI The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA
SO NATURE
LA English
DT Article
ID translation initiation sites; single-nucleotide-resolution; embryonic stem-cells; 25s ribosomal-rna; saccharomyces-cerevisiae; base modification; m(1)a58 methyltransferase; ribonucleic-acid; mapping reveals; methylation
AB Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N-6-methyladenosine (m6A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N-1-methyladenosine (m(1)A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m(1)A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA.
C1 [Dominissini, Dan; Nachtergaele, Sigrid; Dai, Qing; Han, Dali; Dore, Louis C.; He, Chuan] Univ Chicago, Dept Chem, 929 East 57th St,Chicago, Chicago, IL 60637 USA.
   [Dominissini, Dan; Nachtergaele, Sigrid; Dai, Qing; Han, Dali; Dore, Louis C.; He, Chuan] Univ Chicago, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA.
   [Dominissini, Dan; Nachtergaele, Sigrid; Dai, Qing; Han, Dali; Dore, Louis C.; He, Chuan] Univ Chicago, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA.
   [Moshitch-Moshkovitz, Sharon; Peer, Eyal; Kol, Nitzan; Ben-Haim, Moshe Shay; Di Segni, Ayelet; Salmon-Divon, Mali; Solomon, Oz; Eyal, Eran; Hershkovitz, Vera; Amariglio, Ninette; Rechavi, Gideon] Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel.
   [Peer, Eyal; Ben-Haim, Moshe Shay; Rechavi, Gideon] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Solomon, Oz; Amariglio, Ninette] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
   [Clark, Wesley C.; Zheng, Guanqun; Pan, Tao; He, Chuan] Univ Chicago, Dept Biochem & Mol Biol, 929 East 57th St, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; Howard Hughes Medical Institute; University of Chicago; Chaim Sheba Medical Center; Tel Aviv University; Tel Aviv University; Sackler Faculty of Medicine; Bar Ilan University; University of Chicago
RP Dominissini, D; He, C (corresponding author), Univ Chicago, Dept Chem, 929 East 57th St,Chicago, Chicago, IL 60637 USA.; Dominissini, D; He, C (corresponding author), Univ Chicago, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA.; Dominissini, D; He, C (corresponding author), Univ Chicago, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA.; Rechavi, G (corresponding author), Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel.; Rechavi, G (corresponding author), Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.; He, C (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 929 East 57th St, Chicago, IL 60637 USA.
EM dandominissini@gmail.com; gidi.rechavi@sheba.health.gov.il; chuanhe@uchicago.edu
FU National Institutes of Health [HG008688, GM71440, GM113194, HG006699]; Flight Attendant Medical Research Institute (FAMRI); Israel Science Foundation (ISF) [1667/12]; Israeli Centers of Excellence (I-CORE) Program (ISF grants) [41/11, 1796/12]; Ernest and Bonnie Beutler Research Program; Kahn Family Foundation; Chicago Biomedical Consortium; Searle Funds at The Chicago Community Trust; Human Frontier Science Program (HFSP) long-term fellowship; Yen post-doctoral fellowship in interdisciplinary research; National Institute of General Medical Sciences [R01GM113194] Funding Source: NIH RePORTER
NR 77
TC 797
Z9 950
U1 5
U2 282
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 441
EP +
DI 10.1038/nature16998
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800027
PM 26863196
DA 2026-03-09
ER

PT J
AU Iwasaki, S
   Floor, SN
   Ingolia, NT
AF Iwasaki, Shintaro
   Floor, Stephen N.
   Ingolia, Nicholas T.
TI Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor
SO NATURE
LA English
DT Article
ID rna helicase; initiation-factors; in-vivo; binding; roles; codon
AB Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumour cells and repress translation of specific messenger RNAs1-4. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its messenger RNA selectivity is proposed to reflect highly structured 5' untranslated regions that depend strongly on eIF4A-mediated unwinding(5). However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA(1,2,6). Here we show that secondary structure in 5' untranslated regions is only a minor determinant for RocA selectivity and that RocA does not repress translation by reducing eIF4A availability. Rather, in vitro and in cells, RocA specifically clamps eIF4A onto polypurine sequences in an ATP-independent manner. This artificially clamped eIF4A blocks 43S scanning, leading to premature, upstream translation initiation and reducing protein expression from transcripts bearing the RocA-eIF4A target sequence. In elucidating the mechanism of selective translation repression by this lead anti-cancer compound, we provide an example of a drug stabilizing sequence-selective RNA-protein interactions.
C1 [Iwasaki, Shintaro; Floor, Stephen N.; Ingolia, Nicholas T.] Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr RNA Syst Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Ingolia, NT (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr RNA Syst Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM ingolia@berkeley.edu
FU Damon Runyon Cancer Research Foundation [DRR-37-15]; Searle Scholars Program [11-SSP-229]; National Institute of General Medical Sciences of the National Institutes of Health [P50GM102706]; National Institutes of Health S10 Instrumentation Grants [S10RR029668, S10RR027303, OD018174]; Human Frontier Science Program long-term fellowship
NR 37
TC 230
Z9 277
U1 0
U2 58
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 558
EP +
DI 10.1038/nature17978
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300055
PM 27309803
DA 2026-03-09
ER

PT J
AU Moll, PJW
   Nair, NL
   Helm, T
   Potter, AC
   Kimchi, I
   Vishwanath, A
   Analytis, JG
AF Moll, Philip J. W.
   Nair, Nityan L.
   Helm, Toni
   Potter, Andrew C.
   Kimchi, Itamar
   Vishwanath, Ashvin
   Analytis, James G.
TI Transport evidence for Fermi-arc-mediated chirality transfer in the Dirac semimetal Cd3As2
SO NATURE
LA English
DT Article
ID surface-state; weyl; oscillations
AB The dispersion of charge carriers in a metal is distinctly different from that of free electrons owing to their interactions with the crystal lattice. These interactions may lead to quasiparticles mimicking the massless relativistic dynamics of high-energy particle physics(1-3), and they can twist the quantum phase of electrons into topologically non-trivial knots-producing protected surface states with anomalous electromagnetic properties(4-9). These effects intertwine in materials known as Weyl semimetals, and in their crystal-symmetry-protected analogues, Dirac semimetals(10). The latter show a linear electronic dispersion in three dimensions described by two copies of the Weyl equation (a theoretical description of massless relativistic fermions). At the surface of a crystal, the broken translational symmetry creates topological surface states, so-called Fermi arcs(11), which have no counterparts in high-energy physics or conventional condensed matter systems. Here we present Shubnikov-de Haas oscillations in focused-ion-beam-prepared microstructures of Cd3As2 that are consistent with the theoretically predicted 'Weyl orbits', a kind of cyclotron motion that weaves together Fermi-arc and chiral bulk states(12). In contrast to conventional cyclotron orbits, this motion is driven by the transfer of chirality from one Weyl node to another, rather than momentum transfer of the Lorentz force. Our observations provide evidence for direct access to the topological properties of charge in a transport experiment, a first step towards their potential application.
C1 [Moll, Philip J. W.; Nair, Nityan L.; Helm, Toni; Potter, Andrew C.; Kimchi, Itamar; Vishwanath, Ashvin; Analytis, James G.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Moll, Philip J. W.; Nair, Nityan L.] Max Planck Inst Chem Phys Solids, Noethnitzer Str 40, D-01187 Dresden, Germany.
   [Analytis, James G.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; Max Planck Society; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Moll, PJW; Analytis, JG (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.; Moll, PJW (corresponding author), Max Planck Inst Chem Phys Solids, Noethnitzer Str 40, D-01187 Dresden, Germany.
EM philip.moll@cpfs.mpg.de; analytis@berkeley.edu
FU SCOPE-M centre for electron microscopy at ETH Zurich; Gordon and Betty Moore Foundation's EPiQS Initiative [GBMF4307, GBMF4374]; Office of Science, Office of Basic Energy Sciences, Materials Sciences Division, of the US Department of Energy [DE-AC02-05CH11231]; University of California, Berkeley; Quantum Materials FWP, US Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division [DE-AC02- 05CH11231]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Gordon and Betty Moore Foundation (GBMF) [GBMF4374, GBMF4307] Funding Source: Gordon and Betty Moore Foundation (GBMF)
NR 43
TC 327
Z9 373
U1 4
U2 340
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 266
EP +
DI 10.1038/nature18276
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600053
PM 27376477
DA 2026-03-09
ER

PT J
AU Speyerer, EJ
   Povilaitis, RZ
   Robinson, MS
   Thomas, PC
   Wagner, RV
AF Speyerer, Emerson J.
   Povilaitis, Reinhold Z.
   Robinson, Mark S.
   Thomas, Peter C.
   Wagner, Robert V.
TI Quantifying crater production and regolith overturn on the Moon with temporal imaging
SO NATURE
LA English
DT Article
C1 [Speyerer, Emerson J.; Povilaitis, Reinhold Z.; Robinson, Mark S.; Wagner, Robert V.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Thomas, Peter C.] Cornell Univ, Cornell Ctr Astrophys & Planetary Sci, Ithaca, NY 14853 USA.
C3 Arizona State University; Arizona State University-Tempe; Cornell University
RP Speyerer, EJ (corresponding author), Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
EM Emerson.Speyerer@asu.edu
FU Lunar Reconnaissance Orbiter (LRO) Project; Arizona State University LROC contract
NR 40
TC 161
Z9 186
U1 1
U2 27
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 215
EP 218
DI 10.1038/nature19829
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000056
PM 27734864
DA 2026-03-09
ER

PT J
AU Komor, AC
   Kim, YB
   Packer, MS
   Zuris, JA
   Liu, DR
AF Komor, Alexis C.
   Kim, Yongjoo B.
   Packer, Michael S.
   Zuris, John A.
   Liu, David R.
TI Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
SO NATURE
LA English
DT Article
ID crispr-cas9 nucleases; enzyme apobec1; endonuclease; proteins
AB Current genome-editing technologies introduce double-stranded (ds) DNA breaks at a target locus as the first step to gene correction1,2. Although most genetic diseases arise from point mutations, current approaches to point mutation correction are inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus resulting from the cellular response to dsDNA breaks(1,2). Here we report the development of 'base editing', a new approach to genome editing that enables the direct, irreversible conversion of one target DNA base into another in a programmable manner, without requiring dsDNA backbone cleavage or a donor template. We engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C -> T (or G -> A) substitution. The resulting 'base editors' convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease. In four transformed human and murine cell lines, second-and third-generation base editors that fuse uracil glycosylase inhibitor, and that use a Cas9 nickase targeting the non-edited strand, manipulate the cellular DNA repair response to favour desired base-editing outcomes, resulting in permanent correction of similar to 15-75% of total cellular DNA with minimal (typically <= 1%) indel formation. Base editing expands the scope and efficiency of genome editing of point mutations.
C1 [Komor, Alexis C.; Kim, Yongjoo B.; Packer, Michael S.; Zuris, John A.; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Komor, Alexis C.; Kim, Yongjoo B.; Packer, Michael S.; Zuris, John A.; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Howard Hughes Medical Institute; Harvard University
RP Liu, DR (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.; Liu, DR (corresponding author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM drliu@fas.harvard.edu
FU US National Institutes of Health (NIH) [R01 EB022376]; F-Prime Biomedical Research Initiative [A28161]; Howard Hughes Medical Institute; Ruth L. Kirchstein National Research Service [F32 GM 112366-2]; Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship (NSERC PGS-D); Harvard Biophysics NIH training grant [T32 GM008313]; Ruth L. Kirschstein National Research Service Award Postdoctoral Fellow [F32 GM 106601-2]
NR 33
TC 3944
Z9 5228
U1 96
U2 1816
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 420
EP +
DI 10.1038/nature17946
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300054
PM 27096365
DA 2026-03-09
ER

PT J
AU Purzycki, BG
   Apicella, C
   Atkinson, QD
   Cohen, E
   McNamara, RA
   Willard, AK
   Xygalatas, D
   Norenzayan, A
   Henrich, J
AF Purzycki, Benjamin Grant
   Apicella, Caren
   Atkinson, Quentin D.
   Cohen, Emma
   McNamara, Rita Anne
   Willard, Aiyana K.
   Xygalatas, Dimitris
   Norenzayan, Ara
   Henrich, Joseph
TI Moralistic gods, supernatural punishment and the expansion of human sociality
SO NATURE
LA English
DT Article
ID cooperation; evolution; religion; belief
AB Since the origins of agriculture, the scale of human cooperation and societal complexity has dramatically expanded(1,2). This fact challenges standard evolutionary explanations of prosociality because well-studied mechanisms of cooperation based on genetic relatedness, reciprocity and partner choice falter as people increasingly engage in fleeting transactions with genetically unrelated strangers in large anonymous groups. To explain this rapid expansion of prosociality, researchers have proposed several mechanisms(3,4). Here we focus on one key hypothesis: cognitive representations of gods as increasingly knowledgeable and punitive, and who sanction violators of interpersonal social norms, foster and sustain the expansion of cooperation, trust and fairness towards co-religionist strangers(5-8). We tested this hypothesis using extensive ethnographic interviews and two behavioural games designed to measure impartial rule-following among people (n = 591, observations = 35,400) from eight diverse communities from around the world: (1) inland Tanna, Vanuatu; (2) coastal Tanna, Vanuatu; (3) Yasawa, Fiji; (4) Lovu, Fiji; (5) Pesqueiro, Brazil; (6) Pointe aux Piments, Mauritius; (7) the Tyva Republic (Siberia), Russia; and (8) Hadzaland, Tanzania. Participants reported adherence to a wide array of world religious traditions including Christianity, Hinduism and Buddhism, as well as notably diverse local traditions, including animism and ancestor worship. Holding a range of relevant variables constant, the higher participants rated their moralistic gods as punitive and knowledgeable about human thoughts and actions, the more coins they allocated to geographically distant co-religionist strangers relative to both themselves and local co-religionists. Our results support the hypothesis that beliefs in moralistic, punitive and knowing gods increase impartial behaviour towards distant co-religionists, and therefore can contribute to the expansion of prosociality.
C1 [Purzycki, Benjamin Grant] Univ British Columbia, Ctr Human Evolut Cognit & Culture, 1871 West Mall, Vancouver, BC V6T 1Z2, Canada.
   [Apicella, Caren] Univ Penn, Dept Psychol, Solomon Labs, 3720 Walnut St, Philadelphia, PA 19104 USA.
   [Atkinson, Quentin D.] Univ Auckland, Dept Psychol, Human Sci Bldg,10 Symonds St, Auckland 1010, New Zealand.
   [Atkinson, Quentin D.] Max Planck Inst Sci Human Hist, Kahla Str 10, D-07745 Jena, Germany.
   [Cohen, Emma] Univ Oxford, Inst Cognit & Evolutionary Anthropol, 64 Banbury Rd, Oxford OX2 6PN, England.
   [Cohen, Emma] Univ Oxford Wadham Coll, Oxford OX1 3PN, England.
   [McNamara, Rita Anne; Norenzayan, Ara; Henrich, Joseph] Univ British Columbia, Dept Psychol, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada.
   [Willard, Aiyana K.] Univ Texas Austin, Dept Psychol, Culture & Dev Lab, 1 Univ Stn A8000, Austin, TX 78712 USA.
   [Xygalatas, Dimitris] Univ Connecticut, Dept Anthropol, 354 Mansfield Rd,Unit 1176, Storrs, CT 06029 USA.
   [Xygalatas, Dimitris] Aarhus Univ, Interacting Minds Ctr, Jens Chr Skous Vej 4,Bldg 1483, DK-8000 Aarhus, Denmark.
   [Xygalatas, Dimitris] Masaryk Univ, LEVYNA, Brno 60200, Czech Republic.
   [Henrich, Joseph] Univ British Columbia, Dept Econ, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada.
   [Henrich, Joseph] Harvard Univ, Dept Human Evolutionary Biol, 11 Divin Ave, Cambridge, MA 02138 USA.
C3 University of British Columbia; University of Pennsylvania; University of Auckland; University of Oxford; University of Oxford; University of British Columbia; University of Texas System; University of Texas Austin; University of Connecticut; Aarhus University; Masaryk University; University of British Columbia; Harvard University
RP Purzycki, BG (corresponding author), Univ British Columbia, Ctr Human Evolut Cognit & Culture, 1871 West Mall, Vancouver, BC V6T 1Z2, Canada.; Henrich, J (corresponding author), Univ British Columbia, Dept Psychol, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada.; Henrich, J (corresponding author), Univ British Columbia, Dept Econ, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada.; Henrich, J (corresponding author), Harvard Univ, Dept Human Evolutionary Biol, 11 Divin Ave, Cambridge, MA 02138 USA.
EM bgpurzycki@alumni.ubc.ca; henrich@psych.ubc.ca
NR 31
TC 300
Z9 346
U1 8
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 327
EP +
DI 10.1038/nature16980
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100035
PM 26863190
DA 2026-03-09
ER

PT J
AU Golden, SA
   Heshmati, M
   Flanigan, M
   Christoffel, DJ
   Guise, K
   Pfau, ML
   Aleyasin, H
   Menard, C
   Zhang, HX
   Hodes, GE
   Bregman, D
   Khibnik, L
   Tai, J
   Rebusi, N
   Krawitz, B
   Chaudhury, D
   Walsh, JJ
   Han, MH
   Shapiro, ML
   Russo, SJ
AF Golden, Sam A.
   Heshmati, Mitra
   Flanigan, Meghan
   Christoffel, Daniel J.
   Guise, Kevin
   Pfau, Madeline L.
   Aleyasin, Hossein
   Menard, Caroline
   Zhang, Hongxing
   Hodes, Georgia E.
   Bregman, Dana
   Khibnik, Lena
   Tai, Jonathan
   Rebusi, Nicole
   Krawitz, Brian
   Chaudhury, Dipesh
   Walsh, Jessica J.
   Han, Ming-Hu
   Shapiro, Matt L.
   Russo, Scott J.
TI Basal forebrain projections to the lateral habenula modulate aggression reward
SO NATURE
LA English
DT Article
ID deep brain-stimulation; optogenetic inhibition; social defeat; neurons; depression; nucleus; stress; behavior; activation; experience
AB Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders(1) and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli(2). Nuclei within the ventromedial hypothalamus(3-5), extended amygdala(6) and limbic(7) circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour(8). Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.
C1 [Golden, Sam A.; Heshmati, Mitra; Flanigan, Meghan; Guise, Kevin; Pfau, Madeline L.; Aleyasin, Hossein; Menard, Caroline; Hodes, Georgia E.; Bregman, Dana; Khibnik, Lena; Tai, Jonathan; Rebusi, Nicole; Krawitz, Brian; Han, Ming-Hu; Shapiro, Matt L.; Russo, Scott J.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA.
   [Golden, Sam A.; Heshmati, Mitra; Flanigan, Meghan; Guise, Kevin; Pfau, Madeline L.; Aleyasin, Hossein; Menard, Caroline; Hodes, Georgia E.; Bregman, Dana; Khibnik, Lena; Tai, Jonathan; Rebusi, Nicole; Krawitz, Brian; Han, Ming-Hu; Shapiro, Matt L.; Russo, Scott J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
   [Golden, Sam A.; Heshmati, Mitra; Flanigan, Meghan; Guise, Kevin; Pfau, Madeline L.; Krawitz, Brian] Icahn Sch Med Mt Sinai, Grad Program Neurosci, New York, NY 10029 USA.
   [Christoffel, Daniel J.; Walsh, Jessica J.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Palo Alto, CA 94305 USA.
   [Zhang, Hongxing; Chaudhury, Dipesh; Han, Ming-Hu] Icahn Sch Med Mt Sinai, Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [Zhang, Hongxing; Chaudhury, Dipesh; Han, Ming-Hu] Icahn Sch Med Mt Sinai, Inst Syst Biomed, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Stanford University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Russo, SJ (corresponding author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA.; Russo, SJ (corresponding author), Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
EM scott.russo@mssm.edu
FU US National Institutes of Health [R01 MH090264, P50 MH096890, P50 AT008661-01, R01 MH092306, T32 MH087004, T32 MH096678, F30 MH100835, F31 MH105217]; National Institute of General Medical Sciences [1FI2GM117583-01]; Natural National Science Foundation of China [81200862]; National Institute of Mental Health [T32MH087004, P50MH096890, R01MH104559, R01MH073689] Funding Source: NIH RePORTER
NR 44
TC 177
Z9 203
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 688
EP +
DI 10.1038/nature18601
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000037
PM 27357796
DA 2026-03-09
ER

PT J
AU Kaiser, TS
   Poehn, B
   Szkiba, D
   Preussner, M
   Sedlazeck, FJ
   Zrim, A
   Neumann, T
   Nguyen, LT
   Betancourt, AJ
   Hummel, T
   Vogel, H
   Dorner, S
   Heyd, F
   von Haeseler, A
   Tessmar-Raible, K
AF Kaiser, Tobias S.
   Poehn, Birgit
   Szkiba, David
   Preussner, Marco
   Sedlazeck, Fritz J.
   Zrim, Alexander
   Neumann, Tobias
   Lam-Tung Nguyen
   Betancourt, Andrea J.
   Hummel, Thomas
   Vogel, Heiko
   Dorner, Silke
   Heyd, Florian
   von Haeseler, Arndt
   Tessmar-Raible, Kristin
TI The genomic basis of circadian and circalunar timing adaptations in a midge
SO NATURE
LA English
DT Article
ID binding protein; drosophila; clock; gene; camkii; clunio; populations; insights; diptera; creb
AB Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes. The region most strongly associated with circadian chronotypes generates strain-specific differences in the abundance of calcium/calmodulin-dependent kinase II.1 (CaMKII. 1) splice variants. As equivalent variants were shown to alter CaMKII activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma-CYCLE, we suggest that modulation of alternative splicing is a mechanism for natural adaptation in circadian timing.
C1 [Kaiser, Tobias S.; Poehn, Birgit; Neumann, Tobias; Dorner, Silke; Tessmar-Raible, Kristin] Univ Vienna, Max F Perutz Labs, Campus Vienna Bioctr,Dr Bohr Gasse 9-4, A-1030 Vienna, Austria.
   [Kaiser, Tobias S.; Szkiba, David; Sedlazeck, Fritz J.; Zrim, Alexander; Neumann, Tobias; Lam-Tung Nguyen; von Haeseler, Arndt] Univ Vienna, Max F Perutz Labs, Ctr Integrat Bioinformat Vienna, Dr Bohr Gasse 9, A-1030 Vienna, Austria.
   [Kaiser, Tobias S.; Szkiba, David; Sedlazeck, Fritz J.; Zrim, Alexander; Neumann, Tobias; Lam-Tung Nguyen; von Haeseler, Arndt] Med Univ Vienna, Dr Bohr Gasse 9, A-1030 Vienna, Austria.
   [Kaiser, Tobias S.; Poehn, Birgit; Hummel, Thomas; von Haeseler, Arndt; Tessmar-Raible, Kristin] Univ Vienna, Res Platform Rhythms Life, A-1030 Vienna, Austria.
   [Preussner, Marco; Heyd, Florian] FU Berlin, Inst Chem & Biochem, Dept Biol Chem Pharm, D-14195 Berlin, Germany.
   [Lam-Tung Nguyen; von Haeseler, Arndt] Univ Vienna, Fac Comp Sci, Bioinformat & Computat Biol, A-1030 Vienna, Austria.
   [Betancourt, Andrea J.] Univ Vet Med Vienna, Dept Biomed Sci, Inst Populat Genet, Josef Baumann Gasse 1, A-1210 Vienna, Austria.
   [Hummel, Thomas] Univ Vienna, Fac Life Sci, Dept Neurobiol, A-1090 Vienna, Austria.
   [Vogel, Heiko] Max Planck Inst Chem Ecol, Dept Entomol, Hans Knoll Str 8, D-07745 Jena, Germany.
   [Kaiser, Tobias S.] Max Planck Inst Evolutionary Biol, August Thienemann Str 2, D-24306 Plon, Germany.
   [Sedlazeck, Fritz J.] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21211 USA.
C3 Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); University of Vienna; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); University of Vienna; Medical University of Vienna; University of Vienna; Free University of Berlin; University of Vienna; University of Veterinary Medicine Vienna; University of Vienna; Max Planck Society; Max Planck Society; Johns Hopkins University
RP Kaiser, TS (corresponding author), Univ Vienna, Max F Perutz Labs, Campus Vienna Bioctr,Dr Bohr Gasse 9-4, A-1030 Vienna, Austria.; Kaiser, TS (corresponding author), Univ Vienna, Max F Perutz Labs, Ctr Integrat Bioinformat Vienna, Dr Bohr Gasse 9, A-1030 Vienna, Austria.; Kaiser, TS (corresponding author), Med Univ Vienna, Dr Bohr Gasse 9, A-1030 Vienna, Austria.
EM kaiser@evolbio.mpg.de; kristin.tessmar@mfpl.ac.at
FU University of Vienna; FWF [AY0041321]; HFSP [RGY0082/2010]; ERC [337011]; DFG [HE5398/4-1]; Vienna International PostDoctoral Program for Molecular Life Sciences (VIPS); University of Vienna Initiativkolleg [I059-N]; Austrian Science Fund (FWF) [Y 413] Funding Source: researchfish; European Research Council (ERC) [337011] Funding Source: European Research Council (ERC)
NR 77
TC 87
Z9 101
U1 0
U2 44
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 69
EP +
DI 10.1038/nature20151
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600049
PM 27871090
DA 2026-03-09
ER

PT J
AU Li, YJ
   Han, JM
   Zhang, YB
   Cao, F
   Liu, ZJ
   Li, S
   Wu, J
   Hu, CY
   Wang, Y
   Shuai, J
   Chen, J
   Cao, LR
   Li, DS
   Shi, P
   Tian, CL
   Zhang, J
   Dou, YL
   Li, GH
   Chen, Y
   Lei, M
AF Li, Yanjing
   Han, Jianming
   Zhang, Yuebin
   Cao, Fang
   Liu, Zhijun
   Li, Shuai
   Wu, Jian
   Hu, Chunyi
   Wang, Yan
   Shuai, Jin
   Chen, Juan
   Cao, Liaoran
   Li, Dangsheng
   Shi, Pan
   Tian, Changlin
   Zhang, Jian
   Dou, Yali
   Li, Guohui
   Chen, Yong
   Lei, Ming
TI Structural basis for activity regulation of MLL family methyltransferases
SO NATURE
LA English
DT Article
ID lineage leukemia protein-1; histone-modifying genes; h3k4 methylation; set1 family; expression; complex; domain; rbbp5; activation; chromatin
AB The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.
C1 [Li, Yanjing; Han, Jianming; Liu, Zhijun; Wu, Jian; Hu, Chunyi; Wang, Yan; Shuai, Jin; Chen, Juan; Chen, Yong; Lei, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, 333 Haike Rd, Shanghai 201210, Peoples R China.
   [Li, Yanjing; Han, Jianming; Liu, Zhijun; Wu, Jian; Hu, Chunyi; Wang, Yan; Shuai, Jin; Chen, Juan; Chen, Yong; Lei, Ming] Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China.
   [Zhang, Yuebin; Cao, Liaoran; Li, Guohui] Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Liaoning, Peoples R China.
   [Cao, Fang; Dou, Yali] Univ Michigan, Dept Pathol, Sch Med, 1301 Catherine, Ann Arbor, MI 48109 USA.
   [Li, Shuai; Zhang, Jian] Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai 200025, Peoples R China.
   [Li, Dangsheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China.
   [Shi, Pan; Tian, Changlin] Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Peoples R China.
   [Tian, Changlin] Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China.
   [Tian, Changlin] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Dalian Institute of Chemical Physics, CAS; University of Michigan System; University of Michigan; Shanghai Jiao Tong University; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Chen, Y; Lei, M (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, 333 Haike Rd, Shanghai 201210, Peoples R China.; Chen, Y; Lei, M (corresponding author), Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China.; Li, GH (corresponding author), Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Liaoning, Peoples R China.
EM ghli@dicp.ac.cn; yongchen@sibcb.ac.cn; leim@sibcb.ac.cn
FU Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08010201, XDB08030302]; Ministry of Science and Technology of China [2013CB910402, 2013CB910401, 2012AA01A305, 2012CB721002, 2011CB910400]; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China [2014ZX09507002-005]; National Natural Science Foundation of China [31330040, 31470737, 91430110]; Basic Research Project of Shanghai Science and Technology Commission [14JC1407200]; National Institutes of Health [R01 GM082856]; Fundamental Research for the Central University [WK2340000064]; National Institute of General Medical Sciences [R01GM082856] Funding Source: NIH RePORTER
NR 41
TC 188
Z9 260
U1 2
U2 168
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 447
EP +
DI 10.1038/nature16952
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800028
PM 26886794
DA 2026-03-09
ER

PT J
AU Ketel, K
   Krauss, M
   Nicot, AS
   Puchkov, D
   Wieffer, M
   Müller, R
   Subramanian, D
   Schultz, C
   Laporte, J
   Haucke, V
AF Ketel, Katharina
   Krauss, Michael
   Nicot, Anne-Sophie
   Puchkov, Dmytro
   Wieffer, Marnix
   Mueller, Rainer
   Subramanian, Devaraj
   Schultz, Carsten
   Laporte, Jocelyn
   Haucke, Volker
TI A phosphoinositide conversion mechanism for exit from endosomes
SO NATURE
LA English
DT Article
ID linked myotubular myopathy; phosphatidylinositol 4-kinase; cell regulation; ii-alpha; trafficking; complex; phosphatases; multiple; receptor; 3-kinase
AB Phosphoinositides are a minor class of short-lived membrane phospholipids that serve crucial functions in cell physiology ranging from cell signalling and motility to their role as signposts of compartmental membrane identity(1,2). Phosphoinositide 4-phosphates such as phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) are concentrated at the plasma membrane, on secretory organelles(3), and on lysosomes(4), whereas phosphoinositide 3-phosphates, most notably phosphatidylinositol 3-phosphate (PI(3)P)(5), are a hallmark of the endosomal system(1,2). Directional membrane traffic between endosomal and secretory compartments, although inherently complex, therefore requires regulated phosphoinositide conversion. The molecular mechanism underlying this conversion of phosphoinositide identity during cargo exit from endosomes by exocytosis is unknown. Here we report that surface delivery of endosomal cargo requires hydrolysis of PI(3) P by the phosphatidylinositol 3-phosphatase MTM1, an enzyme whose loss of function leads to X-linked centronuclear myopathy (also called myotubular myopathy) in humans(6). Removal of endosomal PI(3) P by MTM1 is accompanied by phosphatidylinositol 4-kinase-2 alpha (PI4K2 alpha)-dependent generation of PI(4) P and recruitment of the exocyst tethering complex to enable membrane fusion. Our data establish a mechanism for phosphoinositide conversion from PI(3) P to PI(4) P at endosomes en route to the plasma membrane and suggest that defective phosphoinositide conversion at endosomes underlies X-linked centronuclear myopathy caused by mutation of MTM1 in humans.
C1 [Ketel, Katharina; Krauss, Michael; Puchkov, Dmytro; Haucke, Volker] Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany.
   [Nicot, Anne-Sophie; Laporte, Jocelyn] Strasbourg Univ, INSERM, U964, CNRS,UMR7104,Dept Translat Med & Neurogenet,IGBMC, F-67404 Illkirch Graffenstaden, France.
   [Wieffer, Marnix; Haucke, Volker] Free Univ Berlin, Fac Biol Chem & Pharm, D-14195 Berlin, Germany.
   [Mueller, Rainer; Subramanian, Devaraj; Schultz, Carsten] European Mol Biol Lab, Cell Biol & Biophys Unit, D-69117 Heidelberg, Germany.
   [Haucke, Volker] Charite, NeuroCure Cluster Excellence, D-10117 Berlin, Germany.
C3 Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Free University of Berlin; European Molecular Biology Laboratory (EMBL); Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Haucke, V (corresponding author), Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany.
EM haucke@fmp-berlin.de
FU German Research Foundation [SFB740/C8, SFB958/A11]; Agence Nationale de la Recherche [ANR-14-CE12-0009/13-BSV2-0004]
NR 32
TC 153
Z9 184
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 408
EP +
DI 10.1038/nature16516
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800049
PM 26760201
DA 2026-03-09
ER

PT J
AU Wehr, R
   Munger, JW
   McManus, JB
   Nelson, DD
   Zahniser, MS
   Davidson, EA
   Wofsy, SC
   Saleska, SR
AF Wehr, R.
   Munger, J. W.
   McManus, J. B.
   Nelson, D. D.
   Zahniser, M. S.
   Davidson, E. A.
   Wofsy, S. C.
   Saleska, S. R.
TI Seasonality of temperate forest photosynthesis and daytime respiration
SO NATURE
LA English
DT Article
ID gross primary production; ecosystem carbon exchange; term eddy covariance; water-use efficiency; terrestrial ecosystems; co2; fluorescence; assimilation; vegetation; fluxes
AB Terrestrial ecosystems currently offset one-quarter of anthropogenic carbon dioxide (CO2) emissions because of a slight imbalance between global terrestrial photosynthesis and respiration(1). Understanding what controls these two biological fluxes is therefore crucial to predicting climate change(2). Yet there is no way of directly measuring the photosynthesis or daytime respiration of a whole ecosystem of interacting organisms; instead, these fluxes are generally inferred from measurements of net ecosystem-atmosphere CO2 exchange (NEE), in a way that is based on assumed ecosystem-scale responses to the environment. The consequent view of temperate deciduous forests (an important CO2 sink) is that, first, ecosystem respiration is greater during the day than at night; and second, ecosystem photosynthetic light-use efficiency peaks after leaf expansion in spring and then declines(3), presumably because of leaf ageing or water stress. This view has underlain the development of terrestrial biosphere models used in climate prediction(4,5) and of remote sensing indices of global biosphere productivity(5,6). Here, we use new isotopic instrumentation(7) to determine ecosystem photosynthesis and daytime respiration(8) in a temperate deciduous forest over a three-year period. We find that ecosystem respiration is lower during the day than at night-the first robust evidence of the inhibition of leaf respiration by light(9-11) at the ecosystem scale. Because they do not capture this effect, standard approaches(12,13) overestimate ecosystem photosynthesis and daytime respiration in the first half of the growing season at our site, and inaccurately portray ecosystem photosynthetic light-use efficiency. These findings revise our understanding of forest-atmosphere carbon exchange, and provide a basis for investigating how leaf-level physiological dynamics manifest at the canopy scale in other ecosystems.
C1 [Wehr, R.; Saleska, S. R.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [Munger, J. W.; Wofsy, S. C.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Munger, J. W.; Wofsy, S. C.] Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
   [McManus, J. B.; Nelson, D. D.; Zahniser, M. S.] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Davidson, E. A.] Univ Maryland, Ctr Environm Sci, Appalachian Lab, Frostburg, MD 21532 USA.
C3 University of Arizona; Harvard University; Harvard University; Aerodyne Research; University System of Maryland; University of Maryland Center for Environmental Science
RP Wehr, R; Saleska, SR (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
EM rawehr@email.arizona.edu; saleska@email.arizona.edu
FU US Department Of Energy (DOE), Office of Science, Terrestrial Ecosystem Science (TES) program [DE-SC0006741]; Agnese Nelms Haury Program in Environment and Social Justice at the University of Arizona; National Science Foundation (NSF); DOE TES program; NSF LTER program; Division Of Environmental Biology; Direct For Biological Sciences [1237491] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0006741] Funding Source: U.S. Department of Energy (DOE)
NR 43
TC 203
Z9 236
U1 8
U2 493
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 680
EP +
DI 10.1038/nature17966
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000035
PM 27357794
DA 2026-03-09
ER

PT J
AU Wetzel, WC
   Kharouba, HM
   Robinson, M
   Holyoak, M
   Karban, R
AF Wetzel, William C.
   Kharouba, Heather M.
   Robinson, Moria
   Holyoak, Marcel
   Karban, Richard
TI Variability in plant nutrients reduces insect herbivore performance
SO NATURE
LA English
DT Article
ID genetic diversity; defenses
AB The performance and population dynamics of insect herbivores depend on the nutritive and defensive traits of their host plants(1). The literature on plant-herbivore interactions focuses on plant trait mean values(2-4), but recent studies showing the importance of plant genetic diversity for herbivores suggest that plant trait variance may be equally important(5,6). The consequences of plant trait variance for herbivore performance, however, have been largely overlooked. Here we report an extensive assessment of the effects of within population plant trait variance on herbivore performance using 457 performance datasets from 53 species of insect herbivores. We show that variance in plant nutritive traits substantially reduces mean herbivore performance via non-linear averaging of performance relationships that were overwhelmingly concave down. By contrast, relationships between herbivore performance and plant defence levels were typically linear, with variance in plant defence not affecting herbivore performance via non-linear averaging. Our results demonstrate that plants contribute to the suppression of herbivore populations through variable nutrient levels, not just by having low average quality as is typically thought. We propose that this phenomenon could play a key role in the suppression of herbivore populations in natural systems, and that increased nutrient heterogeneity within agricultural crops could contribute to the sustainable control of insect pests in agroecosystems.
C1 [Wetzel, William C.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA.
   [Wetzel, William C.] Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
   [Wetzel, William C.; Kharouba, Heather M.; Robinson, Moria] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA.
   [Kharouba, Heather M.] Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada.
   [Holyoak, Marcel] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA.
   [Karban, Richard] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
C3 Cornell University; Cornell University; University of California System; University of California Davis; University of Ottawa; University of California System; University of California Davis; University of California System; University of California Davis
RP Wetzel, WC (corresponding author), Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA.; Wetzel, WC (corresponding author), Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.; Wetzel, WC (corresponding author), Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA.
EM wcwetzel@cornell.edu
FU Center for Population at the University of California, Davis; Direct For Biological Sciences [1456225] Funding Source: National Science Foundation; Division Of Environmental Biology [1456225] Funding Source: National Science Foundation
NR 21
TC 200
Z9 235
U1 11
U2 200
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 425
EP 427
DI 10.1038/nature20140
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700053
PM 27749815
DA 2026-03-09
ER

PT J
AU Zander, G
   Hackmann, A
   Bender, L
   Becker, D
   Lingner, T
   Salinas, G
   Krebber, H
AF Zander, Gesa
   Hackmann, Alexandra
   Bender, Lysann
   Becker, Daniel
   Lingner, Thomas
   Salinas, Gabriela
   Krebber, Heike
TI mRNA quality control is bypassed for immediate export of stress-responsive transcripts
SO NATURE
LA English
DT Article
ID heterogeneous nuclear ribonucleoprotein; saccharomyces-cerevisiae; arginine methylation; binding-proteins; shuttle vectors; poly(a)(+) rna; yeast; complex; npl3p; identification
AB Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated1. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown. In Saccharomyces cerevisiae, the shuttling RNA adaptor proteins Npl3, Gbp2, Hrb1 and Nab2 are loaded co-transcriptionally onto growing pre-mRNAs. For nuclear export, they recruit the export-receptor heterodimer Mex67-Mtr2 (TAP-p15 in humans)(2). Here we show that cellular stress induces the dissociation of Mex67 and its adaptor proteins from regular mRNAs to prevent general mRNA export. At the same time, heat-shock mRNAs are rapidly exported in association with Mex67, without the need for adapters. The immediate co-transcriptional loading of Mex67 onto heat-shock mRNAs involves Hsf1, a heat-shock transcription factor that binds to heat-shock-promoter elements in stress-responsive genes. An important difference between the export modes is that adaptor-protein-bound mRNAs undergo quality control, whereas stress-specific transcripts do not. In fact, regular mRNAs are converted into uncontrolled stress-responsive transcripts if expressed under the control of a heat-shock promoter, suggesting that whether an mRNA undergoes quality control is encrypted therein. Under normal conditions, Mex67 adaptor proteins are recruited for RNA surveillance, with only quality-controlled mRNAs allowed to associate with Mex67 and leave the nucleus. Thus, at the cost of error-free mRNA formation, heat-shock mRNAs are exported and translated without delay, allowing cells to survive extreme situations.
C1 [Zander, Gesa; Hackmann, Alexandra; Bender, Lysann; Becker, Daniel; Krebber, Heike] Georg August Univ Gottingen, Gottinger Zentrum Mol Biowissensch, Inst Mikrobiol & Genet, Abt Mol Genet, Gottingen, Germany.
   [Lingner, Thomas; Salinas, Gabriela] Georg August Univ Gottingen, Transkriptomanalyselab, Inst Entwicklungsbiochem, Gottingen, Germany.
C3 University of Gottingen; University of Gottingen
RP Krebber, H (corresponding author), Georg August Univ Gottingen, Gottinger Zentrum Mol Biowissensch, Inst Mikrobiol & Genet, Abt Mol Genet, Gottingen, Germany.
EM heike.krebber@biologie.uni-goettingen.de
FU Deutsche Forschungsgemeinschaft;  [SFB860]
NR 48
TC 79
Z9 93
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 593
EP +
DI 10.1038/nature20572
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500054
PM 27951587
DA 2026-03-09
ER

PT J
AU Baude, M
   Kunin, WE
   Boatman, ND
   Conyers, S
   Davies, N
   Gillespie, MAK
   Morton, RD
   Smart, SM
   Memmott, J
AF Baude, Mathilde
   Kunin, William E.
   Boatman, Nigel D.
   Conyers, Simon
   Davies, Nancy
   Gillespie, Mark A. K.
   Morton, R. Daniel
   Smart, Simon M.
   Memmott, Jane
TI Historical nectar assessment reveals the fall and rise of floral resources in Britain
SO NATURE
LA English
DT Article
ID great-britain; plants; pollinators; declines; england; conservation; wales; community; netherlands; diversity
AB There is considerable concern over declines in insect pollinator communities and potential impacts on the pollination of crops and wildflowers(1-4). Among the multiple pressures facing pollinators(2-4), decreasing floral resources due to habitat loss and degradation has been suggested as a key contributing factor(2-8). However, a lack of quantitative data has hampered testing for historical changes in floral resources. Here we show that overall floral rewards can be estimated at a national scale by combining vegetation surveys and direct nectar measurements. We find evidence for substantial losses in nectar resources in England and Wales between the 1930s and 1970s; however, total nectar provision in Great Britain as a whole had stabilized by 1978, and increased from 1998 to 2007. These findings concur with trends in pollinator diversity, which declined in the mid-twentieth century(9) but stabilized more recently(10). The diversity of nectar sources declined from 1978 to 1990 and thereafter in some habitats, with four plant species accounting for over 50% of national nectar provision in 2007. Calcareous grassland, broadleaved woodland and neutral grassland are the habitats that produce the greatest amount of nectar per unit area from the most diverse sources, whereas arable land is the poorest with respect to amount of nectar per unit area and diversity of nectar sources. Although agri-environment schemes add resources to arable landscapes, their national contribution is low. Owing to their large area, improved grasslands could add substantially to national nectar provision if they were managed to increase floral resource provision. This national-scale assessment of floral resource provision affords new insights into the links between plant and pollinator declines, and offers considerable opportunities for conservation.
C1 [Baude, Mathilde; Davies, Nancy; Memmott, Jane] Univ Bristol, Sch Biol Sci, Life Sci Bldg, Bristol BS8 1TQ, Avon, England.
   [Baude, Mathilde; Davies, Nancy; Memmott, Jane] Univ Bristol, Cabot Inst, Bristol BS8 1UJ, Avon, England.
   [Kunin, William E.; Gillespie, Mark A. K.] Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England.
   [Boatman, Nigel D.; Conyers, Simon] Fera Sci Ltd, York Y041 1LZ, N Yorkshire, England.
   [Morton, R. Daniel; Smart, Simon M.] NERC Ctr Ecol & Hydrol, Lancaster LA1 4AP, England.
   [Baude, Mathilde] Univ Orleans, Coll Sci & Tech EA LBLGC 1207, F-45067 Orleans, France.
   [Gillespie, Mark A. K.] Sogn Fjordane Univ Coll, Dept Sci & Engn, N-6851 Sogndal, Norway.
C3 University of Bristol; University of Bristol; University of Leeds; Food & Environment Research Agency; UK Centre for Ecology & Hydrology (UKCEH); Universite de Orleans; Western Norway University of Applied Sciences
RP Baude, M (corresponding author), Univ Bristol, Sch Biol Sci, Life Sci Bldg, Bristol BS8 1TQ, Avon, England.
EM mathilde.baude@univ-orleans.fr
FU UK Insect Pollinators Initiative (IPI) - Biotechnology and Biological Sciences Research Council (BBSRC); Wellcome Trust; Scottish Government; Department of Environment, Food and Rural Affairs (DEFRA); Natural Environment Research Council (NERC) under Living with Environmental Change partnership [BB/H014934/1]; Biotechnology and Biological Sciences Research Council [BB/I000119/1, BB/I000577/1, BB/I000437/1, BB/I000364/1] Funding Source: researchfish; Natural Environment Research Council [ceh020002] Funding Source: researchfish; BBSRC [BB/I000437/1, BB/I000577/1, BB/I000119/1, BB/I000364/1] Funding Source: UKRI; NERC [ceh020002] Funding Source: UKRI
NR 38
TC 348
Z9 386
U1 13
U2 326
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 85
EP +
DI 10.1038/nature16532
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500037
PM 26842058
DA 2026-03-09
ER

PT J
AU Schlindwein, V
   Schmid, F
AF Schlindwein, Vera
   Schmid, Florian
TI Mid-ocean-ridge seismicity reveals extreme types of ocean lithosphere
SO NATURE
LA English
DT Article
ID southwest indian ridge; spreading gakkel ridge; sea-floor generation; crustal thickness; midocean ridges; atlantic ridge; 69-degrees-e; peridotites; exhumation; tectonics
AB Along ultraslow-spreading ridges, where oceanic tectonic plates drift very slowly apart, conductive cooling is thought to limit mantle melting(1) and melt production has been inferred to be highly discontinuous(2-4). Along such spreading centres, long ridge sections without any igneous crust alternate with magmatic sections that host massive volcanoes capable of strong earthquakes(5). Hence melt supply, lithospheric composition and tectonic structure seem to vary considerably along the axis of the slowest-spreading ridges(6). However, owing to the lack of seismic data, the lithospheric structure of ultraslow ridges is poorly constrained. Here we describe the structure and accretion modes of two end-member types of oceanic lithosphere using a detailed seismicity survey along 390 kilometres of ultraslow-spreading ridge axis. We observe that a magmatic sections lack shallow seismicity in the upper 15 kilometres of the lithosphere, but unusually contain earthquakes down to depths of 35 kilometres. This observation implies a cold, thick lithosphere, with an upper aseismic zone that probably reflects substantial serpentinization. We find that regions of magmatic lithosphere thin dramatically under volcanic centres, and infer that the resulting topography of the lithosphere-asthenosphere boundary could allow along-axis melt flow, explaining the uneven crustal production at ultraslow-spreading ridges. The seismicity data indicate that alteration in ocean lithosphere may reach far deeper than previously thought, with important implications towards seafloor deformation and fluid circulation.
C1 [Schlindwein, Vera; Schmid, Florian] Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, Alten Hafen 26, D-27568 Bremerhaven, Germany.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Schlindwein, V (corresponding author), Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, Alten Hafen 26, D-27568 Bremerhaven, Germany.
EM Vera.Schlindwein@awi.de
FU German Science Foundation [SCHL853/1-1, SCHL853/3-1]
NR 39
TC 113
Z9 131
U1 3
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 276
EP U185
DI 10.1038/nature18277
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600055
PM 27362231
DA 2026-03-09
ER

PT J
AU Suzuki, K
   Tsunekawa, Y
   Hernandez-Benitez, R
   Wu, J
   Zhu, J
   Kim, EJ
   Hatanaka, F
   Yamamoto, M
   Araoka, T
   Li, Z
   Kurita, M
   Hishida, T
   Li, M
   Aizawa, E
   Guo, SC
   Chen, S
   Goebl, A
   Soligalla, RD
   Qu, J
   Jiang, TS
   Fu, X
   Jafari, M
   Esteban, CR
   Berggern, WT
   Lajara, J
   Nuñez-Delicado, E
   Guillen, P
   Campistol, JM
   Matsuzaki, F
   Liu, GH
   Magistretti, P
   Zhang, K
   Callaway, EM
   Zhang, K
   Belmonte, JCI
AF Suzuki, Keiichiro
   Tsunekawa, Yuji
   Hernandez-Benitez, Reyna
   Wu, Jun
   Zhu, Jie
   Kim, Euiseok J.
   Hatanaka, Fumiyuki
   Yamamoto, Mako
   Araoka, Toshikazu
   Li, Zhe
   Kurita, Masakazu
   Hishida, Tomoaki
   Li, Mo
   Aizawa, Emi
   Guo, Shicheng
   Chen, Song
   Goebl, April
   Soligalla, Rupa Devi
   Qu, Jing
   Jiang, Tingshuai
   Fu, Xin
   Jafari, Maryam
   Esteban, Concepcion Rodriguez
   Berggern, W. Travis
   Lajara, Jeronimo
   Nunez-Delicado, Estrella
   Guillen, Pedro
   Campistol, Josep M.
   Matsuzaki, Fumio
   Liu, Guang-Hui
   Magistretti, Pierre
   Zhang, Kun
   Callaway, Edward M.
   Zhang, Kang
   Belmonte, Juan Carlos Izpisua
TI In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration
SO NATURE
LA English
DT Article
ID lebers congenital amaurosis; minicircle dna vectors; gene-therapy; transgene expression; stem-cells; ipscs; electroporation; recombination; progenitors; mechanism
AB Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient(1), especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders(2). Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)(3,4) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.
C1 [Suzuki, Keiichiro; Hernandez-Benitez, Reyna; Wu, Jun; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua] Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Tsunekawa, Yuji; Matsuzaki, Fumio] RIKEN, Ctr Dev Biol, Lab Cell Asymmetry, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.
   [Hernandez-Benitez, Reyna; Magistretti, Pierre] 4700 King Abdullah Univ Sci & Technol KAUST, Thuwal 239556900, Saudi Arabia.
   [Wu, Jun; Araoka, Toshikazu; Lajara, Jeronimo; Nunez-Delicado, Estrella; Guillen, Pedro] Univ Catolica San Antonio Murcia UCAM, Campus Jeronimos 135, Murcia 30107, Spain.
   [Zhu, Jie; Fu, Xin; Zhang, Kang] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou 510623, Guangdong, Peoples R China.
   [Zhu, Jie; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Zhang, Kang] Univ Calif San Diego, Shiley Eye Inst, Inst Genom Med, Inst Engn Med, 9500 Gilman Dr 0946, La Jolla, CA 92023 USA.
   [Kim, Euiseok J.; Callaway, Edward M.] Salk Inst Biol Studies, Syst Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Li, Zhe; Guo, Shicheng; Chen, Song; Zhang, Kun] Univ Calif San Diego, Bioengn, 9500 Gilman Dr,MC0412, La Jolla, CA 92093 USA.
   [Qu, Jing] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.
   [Qu, Jing] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Jiang, Tingshuai] Guangzhou EliteHlth Biol Pharmaceut Technol Co Lt, Guangzhou 510005, Guangdong, Peoples R China.
   [Berggern, W. Travis] Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Guillen, Pedro] Fdn Dr Pedro Guillen, Invest Biomed Clin CEMTRO, Ave Ventisquero de la Condesa 42, Madrid 28035, Spain.
   [Campistol, Josep M.] Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain.
   [Liu, Guang-Hui] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Liu, Guang-Hui] Jinan Univ, Inst Aging & Regenerat Med, Key Lab Regenerat Med, Minist Educ, Guangzhou 510632, Guangdong, Peoples R China.
   [Liu, Guang-Hui] Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.
   [Zhang, Kang] Sichuan Univ, West China Hosp, Mol Med Res Ctr, Chengdu 610041, Peoples R China.
   [Zhang, Kang] Vet Adm Healthcare Syst, San Diego, CA 92093 USA.
C3 Salk Institute; RIKEN; King Abdullah University of Science & Technology; Universidad Catolica de Murcia; Guangzhou Medical University; University of California System; University of California San Diego; Salk Institute; University of California System; University of California San Diego; Chinese Academy of Sciences; Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Salk Institute; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Chinese Academy of Sciences; Institute of Biophysics, CAS; Jinan University; Sichuan University
RP Belmonte, JCI (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM belmonte@salk.edu
FU UCSD [P30 NS047101]; CONACYT of Mexico; 973 Program [2013CB967504, 2015CB964600]; 863 Program [2014AA021604]; Nomis Foundation; Salk Women & Science Special Award; NSFC [81601872]; National Basic Research Program of China (973 Program) [2013CB967504, 2015CB964800, 2014CB910503]; National Natural Science Foundation of China [81625009, 81371342, 81271266]; National High Technology Research and Development Program of China [2014AA021604, 2015AA020307]; Beijing Municipal Science and Technology Commission [Z151100003915072]; RIKEN; NIH [R01HL123755]; King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) [OSR-2015-CRG4-2631]; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; G. Harold and Leila Y. Mathers Charitable Foundation; McKnight Foundation; Moxie Foundation; Fundacion Dr. Pedro Guillen; Universidad Catolica San Antonio de Murcia (UCAM); National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Eye Institute [P30EY022589] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 45
TC 903
Z9 1184
U1 11
U2 570
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 144
EP +
DI 10.1038/nature20565
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600065
PM 27851729
DA 2026-03-09
ER

PT J
AU Liggio, J
   Li, SM
   Hayden, K
   Taha, YM
   Stroud, C
   Darlington, A
   Drollette, BD
   Gordon, M
   Lee, P
   Liu, P
   Leithead, A
   Moussa, SG
   Wang, D
   O'Brien, J
   Mittermeier, RL
   Brook, JR
   Lu, G
   Staebler, RM
   Han, YM
   Tokarek, TW
   Osthoff, HD
   Makar, PA
   Zhang, JH
   Plata, DL
   Gentner, DR
AF Liggio, John
   Li, Shao-Meng
   Hayden, Katherine
   Taha, Youssef M.
   Stroud, Craig
   Darlington, Andrea
   Drollette, Brian D.
   Gordon, Mark
   Lee, Patrick
   Liu, Peter
   Leithead, Amy
   Moussa, Samar G.
   Wang, Danny
   O'Brien, Jason
   Mittermeier, Richard L.
   Brook, Jeffrey R.
   Lu, Gang
   Staebler, Ralf M.
   Han, Yuemei
   Tokarek, Travis W.
   Osthoff, Hans D.
   Makar, Paul A.
   Zhang, Junhua
   Plata, Desiree L.
   Gentner, Drew R.
TI Oil sands operations as a large source of secondary organic aerosols
SO NATURE
LA English
DT Article
ID emission rates; particulate matter; black carbon; isoprene; alberta; simulation; deposition; impact
AB Worldwide heavy oil and bitumen deposits amount to 9 trillion barrels of oil distributed in over 280 basins around the world(1), with Canada home to oil sands deposits of 1.7 trillion barrels(2). The global development of this resource and the increase in oil production from oil sands has caused environmental concerns over the presence of toxic compounds in nearby ecosystems(3,4) and acid deposition(5,6). The contribution of oil sands exploration to secondary organic aerosol formation, an important component of atmospheric particulate matter that affects air quality and climate(7), remains poorly understood. Here we use data from airborne measurements over the Canadian oil sands, laboratory experiments and a box-model study to provide a quantitative assessment of the magnitude of secondary organic aerosol production from oil sands emissions. We find that the evaporation and atmospheric oxidation of low-volatility organic vapours from the mined oil sands material is directly responsible for the majority of the observed secondary organic aerosol mass. The resultant production rates of 45-84 tonnes per day make the oil sands one of the largest sources of anthropogenic secondary organic aerosols in North America. Heavy oil and bitumen account for over ten per cent of global oil production today(8), and this figure continues to grow(9). Our findings suggest that the production of the more viscous crude oils could be a large source of secondary organic aerosols in many production and refining regions worldwide, and that such production should be considered when assessing the environmental impacts of current and planned bitumen and heavy oil extraction projects globally.
C1 [Liggio, John; Li, Shao-Meng; Hayden, Katherine; Stroud, Craig; Darlington, Andrea; Gordon, Mark; Lee, Patrick; Liu, Peter; Leithead, Amy; Moussa, Samar G.; Wang, Danny; O'Brien, Jason; Mittermeier, Richard L.; Brook, Jeffrey R.; Lu, Gang; Staebler, Ralf M.; Han, Yuemei; Makar, Paul A.; Zhang, Junhua] Environm & Climate Change Canada, Air Qual Res Div, Toronto, ON M3H 5T4, Canada.
   [Taha, Youssef M.; Tokarek, Travis W.; Osthoff, Hans D.] Univ Calgary, Dept Chem, Calgary, AB T2N 1N4, Canada.
   [Drollette, Brian D.; Plata, Desiree L.; Gentner, Drew R.] Yale Univ, Dept Chem & Environm Engn, New Haven, CT 06520 USA.
C3 Environment & Climate Change Canada; University of Calgary; Yale University
RP Liggio, J; Li, SM (corresponding author), Environm & Climate Change Canada, Air Qual Res Div, Toronto, ON M3H 5T4, Canada.
EM John.Liggio@canada.ca; Shao-Meng.Li@canada.ca
FU Clean Air Regulatory Agenda; Joint Oil Sands Monitoring program
NR 49
TC 137
Z9 167
U1 2
U2 261
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 91
EP +
DI 10.1038/nature17646
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300039
PM 27251281
DA 2026-03-09
ER

PT J
AU Clarke, JA
   Chatterjee, S
   Li, ZH
   Riede, T
   Agnolin, F
   Goller, F
   Isasi, MP
   Martinioni, DR
   Mussel, FJ
   Novas, FE
AF Clarke, Julia A.
   Chatterjee, Sankar
   Li, Zhiheng
   Riede, Tobias
   Agnolin, Federico
   Goller, Franz
   Isasi, Marcelo P.
   Martinioni, Daniel R.
   Mussel, Francisco J.
   Novas, Fernando E.
TI Fossil evidence of the avian vocal organ from the Mesozoic
SO NATURE
LA English
DT Article
ID lambeosaurine dinosaurs; syrinx; brain
AB From complex songs to simple honks, birds produce sounds using a unique vocal organ called the syrinx(1,2). Located close to the heart at the tracheobronchial junction, vocal folds or membranes attached to modified mineralized rings vibrate to produce sound(1-7). Syringeal components were not thought to commonly enter the fossil record(6), and the few reported fossilized parts of the syrinx are geologically young(8-11) (from the Pleistocene and Holocene (approximately 2.5 million years ago to the present)). The only known older syrinx is an Eocene specimen that was not described or illustrated(12). Data on the relationship between soft tissue structures and syringeal three-dimensional geometry are also exceptionally limited(5). Here we describe the first remains, to our knowledge, of a fossil syrinx from the Mesozoic Era, which are preserved in three dimensions in a specimen from the Late Cretaceous (approximately 66 to 69 million years ago) of Antarctica. With both cranial and postcranial remains, the new Vegavis iaai specimen is the most complete to be recovered from a part of the radiation of living birds (Aves). Enhanced-contrast X-ray computed tomography (CT) of syrinx structure in twelve extant non-passerine birds, as well as CT imaging of the Vegavis and Eocene syrinxes, informs both the reconstruction of ancestral states in birds and properties of the vocal organ in the extinct species. Fused rings in Vegavis form a well-mineralized pessulus, a derived neognath bird feature, proposed to anchor enlarged vocal folds or labia(5). Left-right bronchial asymmetry, as seen in Vegavis, is only known in extant birds with two sets of vocal fold sound sources. The new data show the fossilization potential of the avian vocal organ and beg the question why these remains have not been found in other dinosaurs. The lack of other Mesozoic tracheobronchial remains, and the poorly mineralized condition in archosaurian taxa without a syrinx, may indicate that a complex syrinx was a late arising feature in the evolution of birds, well after the origin of flight and respiratory innovations.
C1 [Clarke, Julia A.; Li, Zhiheng] Univ Texas Austin, Dept Geol Sci, Austin, TX 78756 USA.
   [Chatterjee, Sankar] Texas Tech Univ Museum, Box 43191, Lubbock, TX 79409 USA.
   [Li, Zhiheng] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Riede, Tobias] Midwestern Univ, Dept Physiol, 19555 N 59th Ave, Glendale, AZ 85308 USA.
   [Agnolin, Federico; Isasi, Marcelo P.; Novas, Fernando E.] Museo Argentino Ciencias Nat Bernardino Rivadavia, CONICET, Lab Anat Comparada & Evoluc Vertebrados, Av Angel Gallardo 470,C1405DJR, Buenos Aires, DF, Argentina.
   [Agnolin, Federico] Univ Maimonides, Fdn Hist Nat Felix Azara, Hidalgo 775,C1405BDB, Buenos Aires, DF, Argentina.
   [Goller, Franz] Univ Utah, Dept Biol, 257 South 1400 East, Salt Lake City, UT 84112 USA.
   [Martinioni, Daniel R.] CADIC Conicet, Lab Geol Andina, B Houssay 200,CP V9410CAB, Tierra Del Fuego, Argentina.
   [Mussel, Francisco J.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Ciencias Geol, CP C1405DJR, Buenos Aires, DF, Argentina.
C3 University of Texas System; University of Texas Austin; Texas Tech University System; Texas Tech University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Midwestern University; Midwestern University - Glendale; Museo Argentino de Ciencias Naturales Bernardino Rivadavia (MACN); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Utah System of Higher Education; University of Utah; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires
RP Clarke, JA (corresponding author), Univ Texas Austin, Dept Geol Sci, Austin, TX 78756 USA.
EM Julia_Clarke@jsg.utexas.edu
FU Gordon and Betty Moore Foundation [GBMF4498]; National Science Foundation [OPP ANT-1141820, OPP 0927341, EAR 1355292]; Agencia Nacional de Promocion Cientifica y Tecnica [PICT 2010-066]; Instituto Antartico Argentino (IAA); Directorate For Geosciences; Division Of Earth Sciences [1355292] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [1142129] Funding Source: National Science Foundation; Gordon and Betty Moore Foundation (GBMF) [GBMF4498] Funding Source: Gordon and Betty Moore Foundation (GBMF)
NR 30
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U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 502
EP U211
DI 10.1038/nature19852
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400056
PM 27732575
DA 2026-03-09
ER

PT J
AU Wallner, A
   Feige, J
   Kinoshita, N
   Paul, M
   Fifield, LK
   Golser, R
   Honda, M
   Linnemann, U
   Matsuzaki, H
   Merchel, S
   Rugel, G
   Tims, SG
   Steier, P
   Yamagata, T
   Winkler, SR
AF Wallner, A.
   Feige, J.
   Kinoshita, N.
   Paul, M.
   Fifield, L. K.
   Golser, R.
   Honda, M.
   Linnemann, U.
   Matsuzaki, H.
   Merchel, S.
   Rugel, G.
   Tims, S. G.
   Steier, P.
   Yamagata, T.
   Winkler, S. R.
TI Recent near-Earth supernovae probed by global deposition of interstellar radioactive 60Fe
SO NATURE
LA English
DT Article
ID massive stars; nucleosynthesis; explosion; al-26; dust
AB The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2-4 million years, based on the total rate in the Milky Way (2.0 +/- 0.7 per century(1,2)). Recent massive-star and supernova activity in Earth's vicinity may be traced by radionuclides with half-lives of up to 100 million years(3-6), if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is Fe-60 (with a half-life of 2.6 million years)(7,8), which is ejected in supernova explosions and winds from massive stars(1,2,9). Here we report that the Fe-60 signal observed previously in deep-sea crusts(10,11) is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for Fe-60 deposition via the accretion of interstellar dust particles. Our results reveal Fe-60 interstellar influxes onto Earth at 1.5-3.2 million years ago and at 6.5-8.7 million years ago. The signal measured implies that a few per cent of fresh Fe-60 was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.
C1 [Wallner, A.; Fifield, L. K.; Tims, S. G.] Australian Natl Univ, Res Sch Phys & Engn, Dept Nucl Phys, GPO Box 4, Canberra, ACT 2601, Australia.
   [Feige, J.; Golser, R.; Steier, P.; Winkler, S. R.] Univ Vienna, Fac Phys Isotope Res, VERA Lab, Wahringer Str 17, A-1090 Vienna, Austria.
   [Kinoshita, N.] Shimizu Corp, Inst Technol, Tokyo 1358530, Japan.
   [Paul, M.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Honda, M.] Univ Tsukuba, Grad Sch Pure & Appl Sci, Tsukuba, Ibaraki 3058577, Japan.
   [Linnemann, U.] Senckenberg Collect Nat Hist Dresden, GeoPlasmaLab, Konigsbrucker Landstr 159, D-01109 Dresden, Germany.
   [Matsuzaki, H.] Univ Tokyo, Univ Museum, MALT Micro Anal Lab, Tandem Accelerator, Tokyo 1130032, Japan.
   [Merchel, S.; Rugel, G.] Helmholtz Inst Resource Technol, HZDR, D-01328 Dresden, Germany.
   [Yamagata, T.] Nihon Univ, Grad Sch Integrated Basic Sci, Tokyo 1568550, Japan.
   [Feige, J.] Berlin Inst Technol, Dept Astron & Astrophys, Hardenbergstr 36, D-10623 Berlin, Germany.
C3 Australian National University; University of Vienna; Shimizu Corporation; Hebrew University of Jerusalem; University of Tsukuba; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); University of Tokyo; Helmholtz Association; Helmholtz-Zentrum Dresden-Rossendorf (HZDR); Nihon University; Technical University of Berlin
RP Wallner, A (corresponding author), Australian Natl Univ, Res Sch Phys & Engn, Dept Nucl Phys, GPO Box 4, Canberra, ACT 2601, Australia.
EM anton.wallner@anu.edu.au
FU Austrian Science Fund (FWF) [I428-N16]; ESF Eurogenesis programme; Australian Research Council (ARC) [DP14100136]; Japan Society for the Promotion of Science (JSPS) KAKENHI [26800161]; University of Vienna; Grants-in-Aid for Scientific Research [26800161] Funding Source: KAKEN
NR 31
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 69
EP 72
DI 10.1038/nature17196
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500034
PM 27078565
DA 2026-03-09
ER

PT J
AU Bernecky, C
   Herzog, F
   Baumeister, W
   Plitzko, JM
   Cramer, P
AF Bernecky, Carrie
   Herzog, Franz
   Baumeister, Wolfgang
   Plitzko, Juergen M.
   Cramer, Patrick
TI Structure of transcribing mammalian RNA polymerase II
SO NATURE
LA English
DT Article
ID transcription elongation; crystal-structure; atomic-structure; complex; architecture; resolution; protein; dna; initiation; system
AB RNA polymerase (Pol) II produces messenger RNA during transcription of protein-coding genes in all eukaryotic cells. The Pol II structure is known at high resolution from X-ray crystallography for two yeast species(1-3). Structural studies of mammalian Pol II, however, remain limited to low-resolution electron microscopy analysis of human Pol II and its complexes with various proteins(4-10). Here we report the 3.4 angstrom resolution cryo-electron microscopy structure of mammalian Pol II in the form of a transcribing complex comprising DNA template and RNA transcript. We use bovine Pol II, which is identical to the human enzyme except for seven amino-acid residues. The obtained atomic model closely resembles its yeast counterpart, but also reveals unknown features. Binding of nucleic acids to the polymerase involves 'induced fit' of the mobile Pol II clamp and active centre region. DNA downstream of the transcription bubble contacts a conserved 'TPSA motif' in the jaw domain of the Pol II subunit RPB5, an interaction that is apparently already established during transcription initiation(7). Upstream DNA emanates from the active centre cleft at an angle of approximately 105 degrees with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II. Our results define the structure of mammalian Pol II in its functional state, indicate that previous crystallographic analysis of yeast Pol II is relevant for understanding gene transcription in all eukaryotes, and provide a starting point for a mechanistic analysis of human transcription.
C1 [Bernecky, Carrie; Cramer, Patrick] Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.
   [Herzog, Franz] Univ Munich, Gene Ctr Munich, Feodor Lynen Str 25, D-81377 Munich, Germany.
   [Baumeister, Wolfgang; Plitzko, Juergen M.] Max Planck Inst Biochem, Dept Mol Struct Biol, Klopferspitz 18, D-82152 Martinsried, Germany.
C3 Max Planck Society; University of Munich; Max Planck Society
RP Cramer, P (corresponding author), Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.
EM pcramer@mpibpc.mpg.de
FU Alexander von Humboldt Foundation; Deutsche Forschungsgemeinschaft [SFB860]; European Research Council; Volkswagen Foundation
NR 59
TC 163
Z9 210
U1 3
U2 59
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 551
EP +
DI 10.1038/nature16482
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800042
PM 26789250
DA 2026-03-09
ER

PT J
AU Chung, BC
   Mashalidis, EH
   Tanino, T
   Kim, M
   Matsuda, A
   Hong, J
   Ichikawa, S
   Lee, SY
AF Chung, Ben C.
   Mashalidis, Ellene H.
   Tanino, Tetsuya
   Kim, Mijung
   Matsuda, Akira
   Hong, Jiyong
   Ichikawa, Satoshi
   Lee, Seok-Yong
TI Structural insights into inhibition of lipid I production in bacterial cell wall synthesis
SO NATURE
LA English
DT Article
ID pentapeptide translocase; muraymycin analogs; escherichia-coli; high-throughput; mray; biosynthesis; tools; model; step; site
AB Antibiotic-resistant bacterial infection is a serious threat to public health. Peptidoglycan biosynthesis is a well-established target for antibiotic development. MraY (phospho-MurNAc-pentapeptide translocase) catalyses the first and an essential membrane step of peptidoglycan biosynthesis. It is considered a very promising target for the development of new antibiotics, as many naturally occurring nucleoside inhibitors with antibacterial activity target this enzyme(1-4). However, antibiotics targeting MraY have not been developed for clinical use, mainly owing to a lack of structural insight into inhibition of this enzyme. Here we present the crystal structure of MraY from Aquifex aeolicus (MraY(AA)) in complex with its naturally occurring inhibitor, muraymycin D2 (MD2). We show that after binding MD2, MraY(AA) undergoes remarkably large conformational rearrangements near the active site, which lead to the formation of a nucleoside-binding pocket and a peptide-binding site. MD2 binds the nucleoside-binding pocket like a two-pronged plug inserting into a socket. Further interactions it makes in the adjacent peptide-binding site anchor MD2 to and enhance its affinity for MraY(AA). Surprisingly, MD2 does not interact with three acidic residues or the Mg2+ cofactor required for catalysis, suggesting that MD2 binds to MraY(AA) in a manner that overlaps with, but is distinct from, its natural substrate, UDP-MurNAc-pentapeptide. We have determined the principles of MD2 binding to MraY(AA), including how it avoids the need for pyrophosphate and sugar moieties, which are essential features for substrate binding. The conformational plasticity of MraY could be the reason that it is the target of many structurally distinct inhibitors. These findings can inform the design of new inhibitors targeting MraY as well as its paralogues, WecA and TarO.
C1 [Chung, Ben C.; Mashalidis, Ellene H.; Lee, Seok-Yong] Duke Univ, Dept Biochem, Med Ctr, 303 Res Dr, Durham, NC 27710 USA.
   [Tanino, Tetsuya; Matsuda, Akira; Ichikawa, Satoshi] Hokkaido Univ, Fac Pharmaceut Sci, Kita Ku, Kita 12,Nihi 6, Sapporo, Hokkaido 0600812, Japan.
   [Kim, Mijung; Hong, Jiyong] Duke Univ, Dept Chem, Durham, NC 27708 USA.
C3 Duke University; Hokkaido University; Duke University
RP Lee, SY (corresponding author), Duke Univ, Dept Biochem, Med Ctr, 303 Res Dr, Durham, NC 27710 USA.
EM seok-yong.lee@duke.edu
FU NIH [R01 GM100984]; Duke startup funds; JSPS [24102502, 25293026]; Grants-in-Aid for Scientific Research [16H05097, 24102502] Funding Source: KAKEN
NR 36
TC 102
Z9 114
U1 0
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 557
EP +
DI 10.1038/nature17636
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100046
PM 27088606
DA 2026-03-09
ER

PT J
AU Sankar, TS
   Wastuwidyaningtyas, BD
   Dong, YX
   Lewis, SA
   Wang, JD
AF Sankar, T. Sabari
   Wastuwidyaningtyas, Brigitta D.
   Dong, Yuexin
   Lewis, Sarah A.
   Wang, Jue D.
TI The nature of mutations induced by replication-transcription collisions
SO NATURE
LA English
DT Article
ID escherichia-coli plasmids; bacillus-subtilis; dna-replication; rna-polymerase; maximum-likelihood; genome instability; structural basis; fork movement; e. coli; gene
AB The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on(1,2). Replication-transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity(1-10). Collisions may also trigger mutations, which are major contributors to genetic disease and evolution(5,7,11). However, the nature and mechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication-transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encounters a transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major sigma factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication-transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements.
C1 [Sankar, T. Sabari; Dong, Yuexin; Wang, Jue D.] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA.
   [Sankar, T. Sabari; Wastuwidyaningtyas, Brigitta D.; Lewis, Sarah A.; Wang, Jue D.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Baylor College of Medicine
RP Wang, JD (corresponding author), Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA.; Wang, JD (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM wang@bact.wisc.edu
FU National Institutes of Health Director's New Innovator Award [DP2OD004433]
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NR 48
TC 112
Z9 135
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 178
EP +
DI 10.1038/nature18316
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600048
PM 27362223
DA 2026-03-09
ER

PT J
AU Luo, C
   Lim, JH
   Lee, Y
   Granter, SR
   Thomas, A
   Vazquez, F
   Widlund, HR
   Puigserver, P
AF Luo, Chi
   Lim, Ji-Hong
   Lee, Yoonjin
   Granter, Scott R.
   Thomas, Ajith
   Vazquez, Francisca
   Widlund, Hans R.
   Puigserver, Pere
TI A PGC1α-mediated transcriptional axis suppresses melanoma metastasis
SO NATURE
LA English
DT Article
ID oxidative-metabolism; malignant-melanoma; id proteins; differentiation; inhibitor; receptors; adhesion; cells; beta
AB Melanoma is the deadliest form of commonly encountered skin cancer because of its rapid progression towards metastasis(1,2). Although metabolic reprogramming is tightly associated with tumour progression, the effect of metabolic regulatory circuits on metastatic processes is poorly understood. PGC1 alpha is a transcriptional coactivator that promotes mitochondrial biogenesis, protects against oxidative stress(3) and reprograms melanoma metabolism to influence drug sensitivity and survival(4,5). Here, we provide data indicating that PGC1 alpha suppresses melanoma metastasis, acting through a pathway distinct from that of its bioenergetic functions. Elevated PGC1 alpha expression inversely correlates with vertical growth in human melanoma specimens. PGC1 alpha silencing makes poorly metastatic melanoma cells highly invasive and, conversely, PGC1 alpha reconstitution suppresses metastasis. Within populations of melanoma cells, there is a marked heterogeneity in PGC1 alpha levels, which predicts their inherent high or low metastatic capacity. Mechanistically, PGC1 alpha directly increases transcription of ID2, which in turn binds to and inactivates the transcription factor TCF4. Inactive TCF4 causes downregulation of metastasis-related genes, including integrins that are known to influence invasion and metastasis(6-8). Inhibition of BRAF(V600E) using vemurafenib(9), independently of its cytostatic effects, suppresses metastasis by acting on the PGC1 alpha-ID2-TCF4-integrin axis. Together, our findings reveal that PGC1 alpha maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. Consequently, components of these circuits define new therapeutic opportunities that may help to curb melanoma metastasis.
C1 [Luo, Chi; Lim, Ji-Hong; Lee, Yoonjin; Thomas, Ajith; Vazquez, Francisca; Puigserver, Pere] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Luo, Chi; Lim, Ji-Hong; Lee, Yoonjin; Thomas, Ajith; Vazquez, Francisca; Puigserver, Pere] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
   [Lee, Yoonjin] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Granter, Scott R.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Vazquez, Francisca] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Vazquez, Francisca] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Widlund, Hans R.] Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Lim, Ji-Hong] Konkuk Univ, Dept Biomed Chem, Coll Biomed & Hlth Sci, Chungju 380701, Chung, South Korea.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Konkuk University
RP Puigserver, P (corresponding author), Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Puigserver, P (corresponding author), Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
FU American Heart Association [13POST14750008]; National Research Foundation from South-Korean government [2015R1A2A2A01002483]; Claudia Adams Barr Program in Cancer Research; Dana-Farber Cancer Institute; NIH [R01CA181217]; Friends of Dana-Farber Award; National Cancer Institute [R01CA181217] Funding Source: NIH RePORTER; American Heart Association (AHA) [13POST14750008] Funding Source: American Heart Association (AHA)
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NR 36
TC 182
Z9 194
U1 1
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 422
EP +
DI 10.1038/nature19347
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000058
PM 27580028
DA 2026-03-09
ER

PT J
AU Lazaridis, I
   Nadel, D
   Rollefson, G
   Merrett, DC
   Rohland, N
   Mallick, S
   Fernandes, D
   Novak, M
   Gamarra, B
   Sirak, K
   Connell, S
   Stewardson, K
   Harney, E
   Fu, QM
   González Fortes, G
   Jones, ER
   Roodenberg, SA
   Lengyel, G
   Bocquentin, F
   Gasparian, B
   Monge, JM
   Gregg, M
   Eshed, V
   Mizrahi, AS
   Meiklejohn, C
   Gerritsen, F
   Bejenaru, L
   Blüher, M
   Campbell, A
   Cavalleri, G
   Comas, D
   Froguel, P
   Gilbert, E
   Kerr, SM
   Kovacs, P
   Krause, J
   McGettigan, D
   Merrigan, M
   Merriwether, DA
   O'Reilly, S
   Richards, MB
   Semino, O
   Shamoon-Pour, M
   Stefanescu, G
   Stumvoll, M
   Tönjes, A
   Torroni, A
   Wilson, JF
   Yengo, L
   Hovhannisyan, NA
   Patterson, N
   Pinhasi, R
   Reich, D
AF Lazaridis, Iosif
   Nadel, Dani
   Rollefson, Gary
   Merrett, Deborah C.
   Rohland, Nadin
   Mallick, Swapan
   Fernandes, Daniel
   Novak, Mario
   Gamarra, Beatriz
   Sirak, Kendra
   Connell, Sarah
   Stewardson, Kristin
   Harney, Eadaoin
   Fu, Qiaomei
   Gonzalez Fortes, Gloria
   Jones, Eppie R.
   Roodenberg, Songul Alpaslan
   Lengyel, Gyorgy
   Bocquentin, Fanny
   Gasparian, Boris
   Monge, Janet M.
   Gregg, Michael
   Eshed, Vered
   Mizrahi, Ahuva-Sivan
   Meiklejohn, Christopher
   Gerritsen, Fokke
   Bejenaru, Luminita
   Blueher, Matthias
   Campbell, Archie
   Cavalleri, Gianpiero
   Comas, David
   Froguel, Philippe
   Gilbert, Edmund
   Kerr, Shona M.
   Kovacs, Peter
   Krause, Johannes
   McGettigan, Darren
   Merrigan, Michael
   Merriwether, D. Andrew
   O'Reilly, Seamus
   Richards, Martin B.
   Semino, Ornella
   Shamoon-Pour, Michel
   Stefanescu, Gheorghe
   Stumvoll, Michael
   Toenjes, Anke
   Torroni, Antonio
   Wilson, James F.
   Yengo, Loic
   Hovhannisyan, Nelli A.
   Patterson, Nick
   Pinhasi, Ron
   Reich, David
TI Genomic insights into the origin of farming in the ancient Near East
SO NATURE
LA English
DT Article
ID bronze-age; sequence; neanderthal; ancestry; admixture; plink; cave
AB We report genome-wide ancient DNA from 44 ancient Near Easterners ranging in time between similar to 12,000 and 1,400 BC, from Natufian hunter-gatherers to Bronze Age farmers. We show that the earliest populations of the Near East derived around half their ancestry from a 'Basal Eurasian' lineage that had little if any Neanderthal admixture and that separated from other non-African lineages before their separation from each other. The first farmers of the southern Levant (Israel and Jordan) and Zagros Mountains (Iran) were strongly genetically differentiated, and each descended from local huntergatherers. By the time of the Bronze Age, these two populations and Anatolian-related farmers had mixed with each other and with the hunter-gatherers of Europe to greatly reduce genetic differentiation. The impact of the Near Eastern farmers extended beyond the Near East: farmers related to those of Anatolia spread westward into Europe; farmers related to those of the Levant spread southward into East Africa; farmers related to those of Iran spread northward into the Eurasian steppe; and people related to both the early farmers of Iran and to the pastoralists of the Eurasian steppe spread eastward into South Asia.
C1 [Lazaridis, Iosif; Rohland, Nadin; Mallick, Swapan; Stewardson, Kristin; Harney, Eadaoin; Fu, Qiaomei; Reich, David] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
   [Lazaridis, Iosif; Mallick, Swapan; Patterson, Nick; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Nadel, Dani] Univ Haifa, Zinman Inst Archaeol, IL-3498838 Haifa, Israel.
   [Rollefson, Gary] Whitman Coll, Dept Anthropol, Walla Walla, WA 99362 USA.
   [Merrett, Deborah C.] Simon Fraser Univ, Dept Archaeol, Burnaby, BC V5A 1S6, Canada.
   [Mallick, Swapan; Stewardson, Kristin; Harney, Eadaoin; Reich, David] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Fernandes, Daniel; Novak, Mario; Gamarra, Beatriz; Sirak, Kendra; Connell, Sarah; Pinhasi, Ron] Univ Coll Dublin, Sch Archaeol & Earth Inst, Dublin 4, Ireland.
   [Fernandes, Daniel] Univ Coimbra, Dept Life Sci, CIAS, P-3000456 Coimbra, Portugal.
   [Novak, Mario] Inst Anthropol Res, Zagreb 10000, Croatia.
   [Sirak, Kendra] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA.
   [Harney, Eadaoin] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Fu, Qiaomei] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Fu, Qiaomei] Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Gonzalez Fortes, Gloria] Univ Ferrara, Dept Biol & Evolut, I-44121 Ferrara, Italy.
   [Jones, Eppie R.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Roodenberg, Songul Alpaslan] JM van Nassaulaan 9, NL-2071 VA Santpoort Noord, Netherlands.
   Univ Miskolc, Dept Prehistory & Archaeol, H-3515 Miskolc, Hungary.
   [Bocquentin, Fanny] French Natl Ctr Sci Res, UMR 7041, F-92023 Nanterre, France.
   [Gasparian, Boris] Natl Acad Sci Republ Armenia, Inst Archaeol & Ethnol, Yerevan 0025, Armenia.
   [Monge, Janet M.; Gregg, Michael] Univ Penn, Museum Archaeol & Anthropol, Philadelphia, PA 19104 USA.
   [Eshed, Vered; Mizrahi, Ahuva-Sivan] Israel Antiqu Author, IL-91004 Jerusalem, Israel.
   [Meiklejohn, Christopher] Univ Winnipeg, Dept Anthropol, Winnipeg, MB R3B 2E9, Canada.
   [Gerritsen, Fokke] Netherlands Inst Turkey, TR-34433 Istanbul, Turkey.
   [Bejenaru, Luminita] Alexandru Ioan Cuza Univ, Fac Biol, Iasi 700505, Romania.
   [Blueher, Matthias; Stumvoll, Michael; Toenjes, Anke] Clin Endocrinol & Nephrol, Dept Internal Med & Dermatol, D-04103 Leipzig, Germany.
   [Campbell, Archie; Kerr, Shona M.] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Generat Scotland,Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Cavalleri, Gianpiero; Gilbert, Edmund] Royal Coll Surgeons Ireland, RCSI Mol & Cellular Therapeut, Dublin 2, Ireland.
   [Comas, David] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Inst Biol Evolut CSIC UPF, Barcelona 08003, Spain.
   [Froguel, Philippe; Yengo, Loic] Univ Lille, CNRS, Inst Pasteur Lille, UMR EGID 8199, F-59000 Lille, France.
   [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, London Hammersmith Hosp, Dept Genom Common Dis, London W12 0HS, England.
   [Kovacs, Peter] Univ Leipzig, Med Ctr, IFB Adipos Dis, D-04103 Leipzig, Germany.
   [Krause, Johannes] Max Planck Inst Sci Human Hist, D-07745 Jena, Germany.
   [McGettigan, Darren] Univ Coll Dublin, Sch Hist, Newman Bldg, Dublin 4, Ireland.
   [Merrigan, Michael; O'Reilly, Seamus] Geneal Soc Ireland, Dun Laoghaire, Dublin, Ireland.
   [Merriwether, D. Andrew; Shamoon-Pour, Michel] SUNY Binghamton, Dept Anthropol, Binghamton, NY 13902 USA.
   [Richards, Martin B.] Univ Huddersfield, Sch Appl Sci, Dept Biol Sci, Huddersfield HD1 3DH, W Yorkshire, England.
   [Semino, Ornella; Torroni, Antonio] Univ Pavia, Dipartimento Biol & Biotecnol L Spallanzani, I-27100 Pavia, Italy.
   [Stefanescu, Gheorghe] Inst Cercetari Biol, Iasi 700505, Romania.
   [Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Wilson, James F.] Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Hovhannisyan, Nelli A.] Yerevan State Univ, Ctr Excellence Appl Biosci, Yerevan 0025, Armenia.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Haifa; Whitman College; Simon Fraser University; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; University College Dublin; Universidade de Coimbra; Institute for Anthropological Research Zagreb; Emory University; Harvard University; Max Planck Society; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University of Ferrara; University of Cambridge; University of Miskolc; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social Sciences (INSHS); National Academy of Sciences of Armenia; Institute of Archaeology & Ethnography - NAS RA; University of Pennsylvania; University of Winnipeg; Netherlands Institute in Turkey; Alexandru Ioan Cuza University; University of Edinburgh; Royal College of Surgeons in Ireland - RCSI; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Lille; Pasteur Network; Institut Pasteur Lille; Imperial College London; Leipzig University; University College Dublin; State University of New York (SUNY) System; Binghamton University, SUNY; University of Huddersfield; University of Pavia; University of Edinburgh; University of Edinburgh; Yerevan State University
RP Lazaridis, I; Reich, D (corresponding author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Lazaridis, I; Reich, D (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Reich, D (corresponding author), Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.; Pinhasi, R (corresponding author), Univ Coll Dublin, Sch Archaeol & Earth Inst, Dublin 4, Ireland.
EM lazaridis@genetics.med.harvard.edu; ron.pinhasi@ucd.ie; reich@genetics.med.harvard.edu
FU Irish Research Council [GOIPG/2013/36, GOIPD/2013/1]; Irish Research Council for Humanities and Social Sciences (IRCHSS) ERC Support Programme; Bureau of International Cooperation of the Chinese Academy of Sciences; National Natural Science Foundation of China [L1524016]; Chinese Academy of Sciences [2015-DX-C-03]; Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]; Scottish Funding Council [HR03006]; Scottish Executive Health Department, Chief Scientist Office [CZB/4/285]; German Research Foundation [CRC 1052, B01, B03, C01]; Wenner-Gren Foundation Dissertation Fieldwork grant [9005]; National Science Foundation DDRIG [BCS-1455744]; Federal Ministry of Education and Research, Germany [FKZ: 01EO1501]; MRC 'QTL in Health and Disease' programme grant; EC Commission, Directorate General XII (Supplementary Agreement ERBCIPDCT [940038, 920032]; Leverhulme Trust's Doctoral Scholarship programme; University of Pavia (MIGRAT-IN-G); Italian Ministry of Education, University and Research: Progetti Ricerca Interesse Nazionale; National Geographic Society [8915-11]; WennerGren Foundation [7481]; Irene Levi-Sala CARE Foundation; Israel Science Foundation [475/10]; ERC [263441]; NIH [GM100233]; NSF HOMINID [BCS-1032255]; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1455744, 1032255] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [7481] Funding Source: National Health and Medical Research Council (NHMRC); Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish; Medical Research Council [MC_PC_U127561128] Funding Source: researchfish; MRC [MC_PC_U127561128] Funding Source: UKRI
NR 49
TC 650
Z9 713
U1 6
U2 204
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 419
EP +
DI 10.1038/nature19310
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600034
PM 27459054
DA 2026-03-09
ER

PT J
AU Bzdusek, T
   Wu, QS
   Rüegg, A
   Sigrist, M
   Soluyanov, AA
AF Bzdusek, Tomas
   Wu, QuanSheng
   Ruegg, Andreas
   Sigrist, Manfred
   Soluyanov, Alexey A.
TI Nodal-chain metals
SO NATURE
LA English
DT Article
ID weyl fermion semimetal; flat bands; transition; discovery
AB The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model(1-10), but others do not have a counterpart in relativistic high-energy theories(11-18). A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain-a chain of connected loops in momentum space-along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF4), as well as in other compounds of this class of materials. Using IrF4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.
C1 [Bzdusek, Tomas; Wu, QuanSheng; Ruegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A.] ETH, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
   [Wu, QuanSheng; Soluyanov, Alexey A.] ETH, Stn Zurich Q, CH-8093 Zurich, Switzerland.
   [Soluyanov, Alexey A.] St Petersburg State Univ, Dept Phys, St Petersburg 199034, Russia.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Saint Petersburg State University
RP Bzdusek, T (corresponding author), ETH, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
EM bzdusek@itp.phys.ethz.ch
FU ETH research grant; Swiss National Science Foundation; Microsoft Research; Swiss National Science Foundation through the National Competence Centre in Research MARVEL; Swiss National Science Foundation through the National Competence Centre in Research QSIT
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NR 30
TC 502
Z9 538
U1 1
U2 170
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 75
EP 78
DI 10.1038/nature19099
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900036
PM 27556949
DA 2026-03-09
ER

PT J
AU Ji, AP
   Frebel, A
   Chiti, A
   Simon, JD
AF Ji, Alexander P.
   Frebel, Anna
   Chiti, Anirudh
   Simon, Joshua D.
TI R-process enrichment from a single event in an ancient dwarf galaxy
SO NATURE
LA English
DT Article
ID neutron-star mergers; metal-poor stars; chemical signatures; capture elements; process-rich; reticulum 2; milky; abundance; spectroscopy; evolution
AB Elements heavier than zinc are synthesized through the rapid (r) and slow (s) neutron-capture processes(1,2). The main site of production of the r-process elements (such as europium) has been debated for nearly 60 years(2). Initial studies of trends in chemical abundances in old Milky Way halo stars suggested that these elements are produced continually, in sites such as core-collapse supernovae(3,4). But evidence from the local Universe favours the idea that r-process production occurs mainly during rare events, such as neutron star mergers(5,6). The appearance of a plateau of europium abundance in some dwarf spheroidal galaxies has been suggested as evidence for rare r-process enrichment in the early Universe(7), but only under the assumption that no gas accretes into those dwarf galaxies; gas accretion(8) favours continual r-process enrichment in these systems. Furthermore, the universal r-process pattern(1,9) has not been cleanly identified in dwarf spheroidals. The smaller, chemically simpler, and more ancient ultrafaint dwarf galaxies assembled shortly after the first stars formed, and are ideal systems with which to study nucleosynthesis events such as the r-process(10,11). Reticulum II is one such galaxy(12-14). The abundances of non-neutron-capture elements in this galaxy (and others like it) are similar to those in other old stars(15). Here, we report that seven of the nine brightest stars in Reticulum II, observed with high-resolution spectroscopy, show strong enhancements in heavy neutron-capture elements, with abundances that follow the universal r-process pattern beyond barium. The enhancement seen in this 'r-process galaxy' is two to three orders of magnitude higher than that detected in any other ultrafaint dwarf galaxy(11,16,17). This implies that a single, rare event produced the r-process material in Reticulum II. The r-process yield and event rate are incompatible with the source being ordinary core-collapse supernovae(18), but consistent with other possible sources, such as neutron star mergers(19).
C1 [Ji, Alexander P.; Frebel, Anna; Chiti, Anirudh] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Ji, Alexander P.; Frebel, Anna; Chiti, Anirudh] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Ji, Alexander P.; Frebel, Anna] Ctr Evolut Elements, Joint Inst Nucl Astrophys, E Lansing, MI 48824 USA.
   [Simon, Joshua D.] Observ Carnegie Inst Washington, Pasadena, CA 91101 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Carnegie Institution for Science
RP Ji, AP (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.; Ji, AP (corresponding author), MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
EM alexji@mit.edu
FU National Science Foundation (NSF)-CAREER grant [AST-1255160]; Silverman Family Career Development Professorship; NSF [AST-1108811]; DOE; NSF (USA); MISE (Spain); STFC (UK); HEFCE (UK); NCSA (UIUC); KICP (Univ. Chicago); CCAPP (Ohio State); MIFPA (Texas AM); CNPQ; FAPERJ; FINEP (Brazil); MINECO (Spain); DFG (Germany); Dark Energy Survey; Argonne Lab; UC Santa Cruz; University of Cambridge; CIEMAT-Madrid; University of Chicago; University College London; DES-Brazil Consortium; University of Edinburgh; ETH Zurich; Fermilab; University of Illinois; ICE (IEEC-CSIC); IFAE Barcelona; Lawrence Berkeley Lab; LMU Munchen; associated Excellence Cluster Universe; University of Michigan; NOAO; University of Nottingham; Ohio State University; University of Pennsylvania; University of Portsmouth; SLAC National Lab; Stanford University; University of Sussex; Texas AM University; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1255160] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1108811] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1430152] Funding Source: National Science Foundation
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NR 51
TC 322
Z9 358
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 610
EP +
DI 10.1038/nature17425
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400032
PM 27001693
DA 2026-03-09
ER

PT J
AU Lee, BH
   Lu, Y
   Prado, MA
   Shi, Y
   Tian, G
   Sun, SW
   Elsasser, S
   Gygi, SP
   King, RW
   Finley, D
AF Lee, Byung-Hoon
   Lu, Ying
   Prado, Miguel A.
   Shi, Yuan
   Tian, Geng
   Sun, Shuangwu
   Elsasser, Suzanne
   Gygi, Steven P.
   King, Randall W.
   Finley, Daniel
TI USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites
SO NATURE
LA English
DT Article
ID 26s proteasome; cyclin b1; degradation; ubp6; protein; phosphorylation; sufficient; mechanisms; expression; provides
AB USP14 is a major regulator of the proteasome and one of three proteasome-associated deubiquitinating enzymes(1-9). Its effects on protein turnover are substrate-specific, for unknown reasons. We report that USP14 shows a marked preference for ubiquitin-cyclin B conjugates that carry more than one ubiquitin modification or chain. This specificity is conserved from yeast to humans and is independent of chain linkage type. USP14 has been thought to cleave single ubiquitin groups from the distal tip of a chain, but we find that it removes chains from cyclin B en bloc, proceeding until a single chain remains. The suppression of degradation by USP14's catalytic activity reflects its capacity to act on a millisecond time scale, before the proteasome can initiate degradation of the substrate. In addition, single-molecule studies showed that the dwell time of ubiquitin conjugates at the proteasome was reduced by USP14-dependent deubiquitination. In summary, the specificity of the proteasome can be regulated by rapid ubiquitin chain removal, which resolves substrates based on a novel aspect of ubiquitin conjugate architecture.
C1 [Lee, Byung-Hoon; Prado, Miguel A.; Shi, Yuan; Tian, Geng; Sun, Shuangwu; Elsasser, Suzanne; Gygi, Steven P.; King, Randall W.; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
   [Lu, Ying] Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
   [Sun, Shuangwu] Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China.
   [Shi, Yuan] Univ Calif Los Angeles, Dept Mol & Clin Pharmacol, Factor 10-638,650 Charles E Young Dr South, Los Angeles, CA 90095 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Zhejiang University; University of California System; University of California Los Angeles
RP Lee, BH; King, RW; Finley, D (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM byung-hoon_lee@hms.harvard.edu; randy_king@hms.harvard.edu; daniel_finley@hms.harvard.edu
FU NIH [R01GM5660052, R37-GM043601, R01GM66492-9, 5R01GM039023-26]; Rainwater Foundation
NR 29
TC 165
Z9 201
U1 0
U2 52
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 398
EP +
DI 10.1038/nature17433
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700037
PM 27074503
DA 2026-03-09
ER

PT J
AU Maître, JL
   Turlier, H
   Illukkumbura, R
   Eismann, B
   Niwayama, R
   Nédélec, F
   Hiiragi, T
AF Maitre, Jean-Leon
   Turlier, Herve
   Illukkumbura, Rukshala
   Eismann, Bjoern
   Niwayama, Ritsuya
   Nedelec, Francois
   Hiiragi, Takashi
TI Asymmetric division of contractile domains couples cell positioning and fate specification
SO NATURE
LA English
DT Article
ID polarity; forces; 16-cell; yap/taz
AB During pre-implantation development, the mammalian embryo self-organizes into the blastocyst, which consists of an epithelial layer encapsulating the inner-cell mass (ICM) giving rise to all embryonic tissues(1). In mice, oriented cell division, apicobasal polarity and actomyosin contractility are thought to contribute to the formation of the ICM2-5. However, how these processes work together remains unclear. Here we show that asymmetric segregation of the apical domain generates blastomeres with different contractilities, which triggers their sorting into inner and outer positions. Three-dimensional physical modelling of embryo morphogenesis reveals that cells internalize only when differences in surface contractility exceed a predictable threshold. We validate this prediction using biophysical measurements, and successfully redirect cell sorting within the developing blastocyst using maternal myosin (Myh9)-knockout chimaeric embryos. Finally, we find that loss of contractility causes blastomeres to show ICM-like markers, regardless of their position. In particular, contractility controls Yap subcellular localization(6), raising the possibility that mechanosensing occurs during blastocyst lineage specification. We conclude that contractility couples the positioning and fate specification of blastomeres. We propose that this ensures the robust self-organization of blastomeres into the blastocyst, which confers remarkable regulative capacities to mammalian embryos.
C1 [Maitre, Jean-Leon; Turlier, Herve; Illukkumbura, Rukshala; Eismann, Bjoern; Niwayama, Ritsuya; Nedelec, Francois; Hiiragi, Takashi] European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
   [Maitre, Jean-Leon] Inst Curie, CNRS, INSERM, U934,UMR 3215,Mech Mammalian Dev Grp, 26 Rue Ulm, Paris 05, France.
   [Eismann, Bjoern] Bioquant, Neuenheimer Feld 267, D-69120 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL); Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Ruprecht Karls University Heidelberg
RP Maître, JL; Hiiragi, T (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.; Maître, JL (corresponding author), Inst Curie, CNRS, INSERM, U934,UMR 3215,Mech Mammalian Dev Grp, 26 Rue Ulm, Paris 05, France.
EM jean-leon.maitre@curie.fr; hiiragi@embl.de
FU Marie Curie individual fellowships; Research Executive Agency [329044, 656306, 326701]; Bettencourt-Schueller foundation; EMBL; European Research Council; VolkswagenStifftung; Joachim Herz foundation; Marie Curie Actions (MSCA) [656306] Funding Source: Marie Curie Actions (MSCA)
NR 28
TC 292
Z9 335
U1 5
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 344
EP +
DI 10.1038/nature18958
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900038
PM 27487217
DA 2026-03-09
ER

PT J
AU Gao, Y
   Cao, EH
   Julius, D
   Cheng, YF
AF Gao, Yuan
   Cao, Erhu
   Julius, David
   Cheng, Yifan
TI TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action
SO NATURE
LA English
DT Article
ID cryo-em structure; capsaicin receptor; k+ channel; membrane; activation; resiniferatoxin; crystallization; visualization; determinants; capsazepine
AB When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which lipids have both structural and regulatory roles. Here we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of the rat TRPV1 ion channel in a native bilayer environment. Using this approach, we determined the locations of annular and regulatory lipids and showed that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting the release of bioactive lipids from a critical allosteric regulatory site.
C1 [Gao, Yuan; Cao, Erhu; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   [Gao, Yuan; Cheng, Yifan] Univ Calif San Francisco, Keck Adv Microscopy Lab, San Francisco, CA 94143 USA.
   [Gao, Yuan; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
   [Cheng, Yifan] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Cao, Erhu] Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84112 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Utah System of Higher Education; University of Utah
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.; Cheng, YF (corresponding author), Univ Calif San Francisco, Keck Adv Microscopy Lab, San Francisco, CA 94143 USA.; Cheng, YF (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.; Cheng, YF (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM david.julius@ucsf.edu; ycheng@ucsf.edu
FU National Institutes of Health [R01NS047723, R37NS065071, R01NS055299, S10OD020054, R01GM098672, P01GM111126, P50GM082250]; National Institute of General Medical Sciences [T32GM008284] Funding Source: NIH RePORTER
NR 61
TC 672
Z9 769
U1 9
U2 387
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 347
EP +
DI 10.1038/nature17964
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800027
PM 27281200
DA 2026-03-09
ER

PT J
AU Din, MO
   Danino, T
   Prindle, A
   Skalak, M
   Selimkhanov, J
   Allen, K
   Julio, E
   Atolia, E
   Tsimring, LS
   Bhatia, SN
   Hasty, J
AF Din, M. Omar
   Danino, Tal
   Prindle, Arthur
   Skalak, Matt
   Selimkhanov, Jangir
   Allen, Kaitlin
   Julio, Ellixis
   Atolia, Eta
   Tsimring, Lev S.
   Bhatia, Sangeeta N.
   Hasty, Jeff
TI Synchronized cycles of bacterial lysis for in vivo delivery
SO NATURE
LA English
DT Article
ID cancer; salmonella
AB The widespread view of bacteria as strictly pathogenic has given way to an appreciation of the prevalence of some beneficial microbes within the human body(1-3). It is perhaps inevitable that some bacteria would evolve to preferentially grow in environments that harbour disease and thus provide a natural platform for the development of engineered therapies(4-6). Such therapies could benefit from bacteria that are programmed to limit bacterial growth while continually producing and releasing cytotoxic agents in situ(7-10). Here we engineer a clinically relevant bacterium to lyse synchronously at a threshold population density and to release genetically encoded cargo. Following quorum lysis, a small number of surviving bacteria reseed the growing population, thus leading to pulsatile delivery cycles. We used microfluidic devices to characterize the engineered lysis strain and we demonstrate its potential as a drug delivery platform via co-culture with human cancer cells in vitro. As a proof of principle, we tracked the bacterial population dynamics in ectopic syngeneic colorectal tumours in mice via a luminescent reporter. The lysis strain exhibits pulsatile population dynamics in vivo, with mean bacterial luminescence that remained two orders of magnitude lower than an unmodified strain. Finally, guided by previous findings that certain bacteria can enhance the efficacy of standard therapies(11), we orally administered the lysis strain alone or in combination with a clinical chemotherapeutic to a syngeneic mouse transplantation model of hepatic colorectal metastases. We found that the combination of both circuit-engineered bacteria and chemotherapy leads to a notable reduction of tumour activity along with a marked survival benefit over either therapy alone. Our approach establishes a methodology for leveraging the tools of synthetic biology to exploit the natural propensity for certain bacteria to colonize disease sites.
C1 [Din, M. Omar; Prindle, Arthur; Selimkhanov, Jangir; Julio, Ellixis; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Danino, Tal; Skalak, Matt; Allen, Kaitlin; Atolia, Eta; Bhatia, Sangeeta N.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Tsimring, Lev S.; Hasty, Jeff] Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA.
   [Bhatia, Sangeeta N.] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] Brigham & Womens Hosp, Dept Med, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] MIT, Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] MIT, Marble Ctr Canc Nanomed, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] MIT, Ludwig Ctr Mol Oncol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Bhatia, Sangeeta N.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Hasty, Jeff] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
   [Danino, Tal] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
C3 University of California System; University of California San Diego; Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; University of California System; University of California San Diego; Columbia University
RP Hasty, J (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.; Hasty, J (corresponding author), Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA.; Hasty, J (corresponding author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
EM jhasty@eng.ucsd.edu
FU National Institute of General Medical Sciences of the National Institutes of Health [R01GM069811]; San Diego Center for Systems Biology [P50 GM085764]; Koch Institute Support Grant from the National Cancer Institute (Swanson Biotechnology Center) [P30-CA14051]; Core Center Grant from the National Institute of Environmental Health Sciences [P30-ES002109]; Ludwig Center for Molecular Oncology at MIT; Amar G. Bose Research Grant; Misrock Postdoctoral fellowship; NIH Pathway to Independence Award NIH [K99 CA197649-01]; Department of Defense National Defense Science and Engineering Graduate Fellowship; Helen Hay Whitney Foundation; Burroughs Wellcome Fund; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM069811] Funding Source: NIH RePORTER
NR 29
TC 587
Z9 737
U1 18
U2 632
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 81
EP +
DI 10.1038/nature18930
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200034
PM 27437587
DA 2026-03-09
ER

PT J
AU Notta, F
   Chan-Seng-Yue, M
   Lemire, M
   Li, YL
   Wilson, GW
   Connor, AA
   Denroche, RE
   Liang, SB
   Brown, AMK
   Kim, JC
   Wang, T
   Simpson, JT
   Beck, T
   Borgida, A
   Buchner, N
   Chadwick, D
   Hafezi-Bakhtiari, S
   Dick, JE
   Heisler, L
   Hollingsworth, MA
   Ibrahimov, E
   Jang, GH
   Johns, J
   Jorgensen, LGT
   Law, C
   Ludkovski, O
   Lungu, I
   Ng, K
   Pasternack, D
   Petersen, GM
   Shlush, LI
   Timms, L
   Tsao, MS
   Wilson, JM
   Yung, CK
   Zogopoulos, G
   Bartlett, JMS
   Alexandrov, LB
   Real, FX
   Cleary, SP
   Roehrl, MH
   McPherson, JD
   Stein, LD
   Hudson, TJ
   Campbell, PJ
   Gallinger, S
AF Notta, Faiyaz
   Chan-Seng-Yue, Michelle
   Lemire, Mathieu
   Li, Yilong
   Wilson, Gavin W.
   Connor, Ashton A.
   Denroche, Robert E.
   Liang, Sheng-Ben
   Brown, Andrew M. K.
   Kim, Jaeseung C.
   Wang, Tao
   Simpson, Jared T.
   Beck, Timothy
   Borgida, Ayelet
   Buchner, Nicholas
   Chadwick, Dianne
   Hafezi-Bakhtiari, Sara
   Dick, John E.
   Heisler, Lawrence
   Hollingsworth, Michael A.
   Ibrahimov, Emin
   Jang, Gun Ho
   Johns, Jeremy
   Jorgensen, Lars G. T.
   Law, Calvin
   Ludkovski, Olga
   Lungu, Ilinca
   Ng, Karen
   Pasternack, Danielle
   Petersen, Gloria M.
   Shlush, Liran I.
   Timms, Lee
   Tsao, Ming-Sound
   Wilson, Julie M.
   Yung, Christina K.
   Zogopoulos, George
   Bartlett, John M. S.
   Alexandrov, Ludmil B.
   Real, Francisco X.
   Cleary, Sean P.
   Roehrl, Michael H.
   McPherson, John D.
   Stein, Lincoln D.
   Hudson, Thomas J.
   Campbell, Peter J.
   Gallinger, Steven
TI A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns
SO NATURE
LA English
DT Article
ID intraepithelial neoplasia; ductal adenocarcinoma; barretts-esophagus; occurs late; progression; tumor; chromothripsis; inactivation; mutations; instability
AB Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development(1). The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations(2-5) (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage(2,5-9), indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage(10). However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection(11), suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory(12). In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.
C1 [Notta, Faiyaz; Chan-Seng-Yue, Michelle; Lemire, Mathieu; Wilson, Gavin W.; Connor, Ashton A.; Denroche, Robert E.; Brown, Andrew M. K.; Kim, Jaeseung C.; Simpson, Jared T.; Beck, Timothy; Buchner, Nicholas; Hafezi-Bakhtiari, Sara; Dick, John E.; Heisler, Lawrence; Ibrahimov, Emin; Jang, Gun Ho; Johns, Jeremy; Jorgensen, Lars G. T.; Lungu, Ilinca; Ng, Karen; Pasternack, Danielle; Timms, Lee; Wilson, Julie M.; Yung, Christina K.; Bartlett, John M. S.; McPherson, John D.; Stein, Lincoln D.; Hudson, Thomas J.; Gallinger, Steven] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Li, Yilong; Campbell, Peter J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Liang, Sheng-Ben; Chadwick, Dianne; Hafezi-Bakhtiari, Sara; Roehrl, Michael H.] Univ Hlth Network, Dept Pathol, UHN Program BioSpecimen Sci, Toronto, ON M5G 2C4, Canada.
   [Kim, Jaeseung C.; Wang, Tao; Tsao, Ming-Sound; McPherson, John D.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Wang, Tao] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S IA8, Canada.
   [Dick, John E.; Stein, Lincoln D.; Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Simpson, Jared T.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada.
   [Borgida, Ayelet; Hollingsworth, Michael A.] Nebraska Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA.
   [Dick, John E.; Ludkovski, Olga; Shlush, Liran I.; Tsao, Ming-Sound; Roehrl, Michael H.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [Law, Calvin] Sunnybrook Hlth Sci Ctr, Odette Canc Ctr, Div Surg Oncol, Toronto, ON M4N 3M5, Canada.
   [Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
   [Zogopoulos, George] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3H 2L9, Canada.
   [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Theoret Biol & Biophys T6, Los Alamos, NM 87545 USA.
   [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA.
   [Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain.
   [Cleary, Sean P.; Gallinger, Steven] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
   [Cleary, Sean P.] Univ Hlth Network, Dept Surg, Toronto, ON M5G 2C4, Canada.
   [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England.
C3 Ontario Institute for Cancer Research; University of Toronto; Wellcome Trust Sanger Institute; University of Toronto; University Health Network Toronto; University of Toronto; University of Toronto; University of Toronto; University of Toronto; University of Nebraska System; University of Nebraska Medical Center; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; Sunnybrook Research Institute; Sunnybrook Health Science Center; Mayo Clinic; McGill University; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory; Centro Nacional de Investigaciones Oncologicas (CNIO); University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University Health Network Toronto; University of Cambridge
RP Notta, F; Hudson, TJ (corresponding author), Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.; Hudson, TJ (corresponding author), Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
EM faiyaz.notta@oicr.on.ca; tom.hudson@oicr.on.ca
FU Ontario Institute for Cancer Research (OICR) through the Ontario Ministry of Research and Innovation; Canada Foundation for Innovation; OICR; Canadian Institutes for Health Research (CIHR); Canadian Friends of the Hebrew University; SMGS Family Foundation; NCI [P50 CA102701, R01 CA97075]; CIHR; Ontario Institute of Cancer Research (OICR) through the Ontario Ministry of Research and Innovation; Ontario Institute for Cancer Research; National Cancer Institute [P30CA015083] Funding Source: NIH RePORTER
NR 30
TC 419
Z9 505
U1 1
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 378
EP +
DI 10.1038/nature19823
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100038
PM 27732578
DA 2026-03-09
ER

PT J
AU Gopinath, A
   Miyazono, E
   Faraon, A
   Rothemund, PWK
AF Gopinath, Ashwin
   Miyazono, Evan
   Faraon, Andrei
   Rothemund, Paul W. K.
TI Engineering and mapping nanocavity emission via precision placement of DNA origami
SO NATURE
LA English
DT Article
ID photonic crystal cavity; single quantum-dot; nanoscale; shapes; light; arrays; pure
AB Many hybrid devices integrate functional molecular or nanoparticle components with microstructures, as exemplified by the nanophotonic devices that couple emitters to optical resonators(1) for potential use in single-molecule detection(2,)3, precision magnetometry(4), low threshold lasing(5,6) and quantum information processing(7-12). These systems also illustrate a common difficulty for hybrid devices: although many proof-of-principle devices exist, practical applications face the challenge of how to incorporate large numbers of chemically diverse functional components into microfabricated resonators at precise locations. Here we show that the directed self-assembly(13,14) of DNA origami(15) onto lithographically patterned binding sites allows reliable and controllable coupling of molecular emitters to photonic crystal cavities (PCCs). The precision of this method is sufficient to enable us to visualize the local density of states within PCCs by simple wide-field microscopy and to resolve the antinodes of the cavity mode at a resolution of about one-tenth of a wavelength. By simply changing the number of binding sites, we program the delivery of up to seven DNA origami onto distinct antinodes within a single cavity and thereby digitally vary the intensity of the cavity emission. To demonstrate the scalability of our technique, we fabricate 65,536 independently programmed PCCs on a single chip. These features, in combination with the widely used modularity of DNA origami(16-20), suggest that our method is well suited for the rapid prototyping of a broad array of hybrid nanophotonic devices.
C1 [Gopinath, Ashwin; Rothemund, Paul W. K.] CALTECH, Dept Bioengn, Pasadena, CA 91125 USA.
   [Miyazono, Evan; Faraon, Andrei] CALTECH, Dept Appl Phys & Mat Sci, Pasadena, CA 91125 USA.
   [Rothemund, Paul W. K.] CALTECH, Comp & Math Sci, Pasadena, CA 91125 USA.
   [Rothemund, Paul W. K.] CALTECH, Computat & Neural Syst, Pasadena, CA 91125 USA.
C3 California Institute of Technology; California Institute of Technology; California Institute of Technology; California Institute of Technology
RP Gopinath, A; Rothemund, PWK (corresponding author), CALTECH, Dept Bioengn, Pasadena, CA 91125 USA.; Rothemund, PWK (corresponding author), CALTECH, Comp & Math Sci, Pasadena, CA 91125 USA.; Rothemund, PWK (corresponding author), CALTECH, Computat & Neural Syst, Pasadena, CA 91125 USA.
EM ashwing@caltech.edu; pwkr@dna.caltech.edu
FU Army Research Office [W911NF-11-1-0117]; Office of Naval Research [N000141410702]; Air Force Office of Scientific Research [FA9550-15-1-0252]; US National Science Foundation [0832824, 1317694]; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [1317694] Funding Source: National Science Foundation
NR 35
TC 220
Z9 255
U1 3
U2 386
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 401
EP +
DI 10.1038/nature18287
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200036
PM 27398616
DA 2026-03-09
ER

PT J
AU Chen, HW
   Zhang, PF
   Zhang, LW
   Iu, HLL
   Jiang, Y
   Zhang, DY
   Han, ZW
   Jiang, L
AF Chen, Huawei
   Zhang, Pengfei
   Zhang, Liwen
   Iu, Hongliang L.
   Jiang, Ying
   Zhang, Deyuan
   Han, Zhiwu
   Jiang, Lei
TI Continuous directional water transport on the peristome surface of Nepenthes alata
SO NATURE
LA English
DT Article
ID collection; capillary; capture; corners; drops; rise
AB Numerous natural systems contain surfaces or threads that enable directional water transport(1-7). This behaviour is usually ascribed to hierarchical structural features at the microscale and nanoscale, with gradients in surface energy(8),9 and gradients in Laplace pressure(10) thought to be the main driving forces. Here we study the prey-trapping pitcher organs of the carnivorous plant Nepenthes alata. We find that continuous, directional water transport occurs on the surface of the 'peristome'-the rim of the pitcher-because of its multiscale structure, which optimizes and enhances capillary rise(11,12) in the transport direction, and prevents backflow by pinning in place any water front that is moving in the reverse direction. This results not only in unidirectional flow despite the absence of any surface-energy gradient, but also in a transport speed that is much higher than previously thought. We anticipate that the basic 'design' principles underlying this behaviour could be used to develop artificial fluid-transport systems with practical applications.
C1 [Chen, Huawei; Zhang, Pengfei; Zhang, Liwen; Zhang, Deyuan] Beihang Univ, Sch Mech Engn & Automat, Beijing 100191, Peoples R China.
   [Iu, Hongliang L.; Jiang, Lei] Chinese Acad Sci, Tech Inst Phys & Chem, Lab Bioinspired Smart Interface Sci, Beijing 100190, Peoples R China.
   [Jiang, Ying; Jiang, Lei] Beihang Univ, Sch Chem & Environm, Beijing 100191, Peoples R China.
   [Han, Zhiwu] Jilin Univ, Minist Educ, Key Lab Bion Engn, Changchun 130022, Peoples R China.
C3 Beihang University; Chinese Academy of Sciences; Technical Institute of Physics & Chemistry, CAS; Beihang University; Jilin University
RP Chen, HW; Zhang, DY (corresponding author), Beihang Univ, Sch Mech Engn & Automat, Beijing 100191, Peoples R China.; Jiang, L (corresponding author), Chinese Acad Sci, Tech Inst Phys & Chem, Lab Bioinspired Smart Interface Sci, Beijing 100190, Peoples R China.; Jiang, L (corresponding author), Beihang Univ, Sch Chem & Environm, Beijing 100191, Peoples R China.
EM chenhw75@buaa.edu.cn; zhangdy@buaa.edu.cn; jianglei@iccas.ac.cn
FU National Natural Science Foundation of China [51290292, 51175020, 51475029, 21431009]; Beihang University
NR 30
TC 1112
Z9 1234
U1 106
U2 2700
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 85
EP +
DI 10.1038/nature17189
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500038
PM 27078568
DA 2026-03-09
ER

PT J
AU Herbst, DA
   Jakob, RP
   Zähringer, F
   Maier, T
AF Herbst, Dominik A.
   Jakob, Roman P.
   Zaehringer, Franziska
   Maier, Timm
TI Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases
SO NATURE
LA English
DT Article
ID crystal-structure; protein interactions; swiss-model; biosynthesis; module; software; domain; organization; flexibility; iteration
AB Polyketide synthases (PKSs) are biosynthetic factories that produce natural products with important biological and pharmacological activities(1-3). Their exceptional product diversity is encoded in a modular architecture. Modular PKSs (modPKSs) catalyse reactions colinear to the order of modules in an assembly line(3), whereas iterative PKSs (iPKSs) use a single module iteratively as exemplified by fungal iPKSs (fiPKSs)(3). However, in some cases non-colinear iterative action is also observed for modPKSs modules and is controlled by the assembly line environment(4,5). PKSs feature a structural and functional separation into a condensing and a modifying region as observed for fatty acid synthases(6). Despite the outstanding relevance of PKSs, the detailed organization of PKSs with complete fully reducing modifying regions remains elusive. Here we report a hybrid crystal structure of Mycobacterium smegmatis mycocerosic acid synthase based on structures of its condensing and modifying regions. Mycocerosic acid synthase is a fully reducing iPKS, closely related to modPKSs, and the prototype of mycobacterial mycocerosic acid synthase-like(7,8) PKSs. It is involved in the biosynthesis of C20-C28 branched-chain fatty acids, which are important virulence factors of mycobacteria(9). Our structural data reveal a dimeric linker-based organization of the modifying region and visualize dynamics and conformational coupling in PKSs. On the basis of comparative small-angle X-ray scattering, the observed modifying region architecture may be common also in modPKSs. The linker-based organization provides a rationale for the characteristic variability of PKS modules as a main contributor to product diversity. The comprehensive architectural model enables functional dissection and re-engineering of PKSs.
C1 [Herbst, Dominik A.; Jakob, Roman P.; Zaehringer, Franziska; Maier, Timm] Univ Basel, Dept Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland.
   [Zaehringer, Franziska] F Hoffmann La Roche & Cie AG, Grenzacherstr 124, CH-4070 Basel, Switzerland.
C3 University of Basel; Roche Holding
RP Maier, T (corresponding author), Univ Basel, Dept Biozentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland.
EM timm.maier@unibas.ch
FU Swiss National Science Foundation [125357, 138262, 159696, 145023]; Werner-Siemens Foundation
NR 67
TC 65
Z9 92
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 533
EP +
DI 10.1038/nature16993
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300047
PM 26976449
DA 2026-03-09
ER

PT J
AU Spitler, LG
   Scholz, P
   Hessels, JWT
   Bogdanov, S
   Brazier, A
   Camilo, F
   Chatterjee, S
   Cordes, JM
   Crawford, F
   Deneva, J
   Ferdman, RD
   Freire, PCC
   Kaspi, VM
   Lazarus, P
   Lynch, R
   Madsen, EC
   McLaughlin, MA
   Patel, C
   Ransom, SM
   Seymour, A
   Stairs, IH
   Stappers, BW
   van Leeuwen, J
   Zhu, WW
AF Spitler, L. G.
   Scholz, P.
   Hessels, J. W. T.
   Bogdanov, S.
   Brazier, A.
   Camilo, F.
   Chatterjee, S.
   Cordes, J. M.
   Crawford, F.
   Deneva, J.
   Ferdman, R. D.
   Freire, P. C. C.
   Kaspi, V. M.
   Lazarus, P.
   Lynch, R.
   Madsen, E. C.
   McLaughlin, M. A.
   Patel, C.
   Ransom, S. M.
   Seymour, A.
   Stairs, I. H.
   Stappers, B. W.
   van Leeuwen, J.
   Zhu, W. W.
TI A repeating fast radio burst
SO NATURE
LA English
DT Article
ID pulsar; discovery; signatures; emission; origin; alpha
AB Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances(1-8). Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections(9). The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events(10). Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst(4). This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star(11,12).
C1 [Spitler, L. G.; Freire, P. C. C.; Lazarus, P.; Zhu, W. W.] Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
   [Scholz, P.; Ferdman, R. D.; Kaspi, V. M.; Madsen, E. C.; Patel, C.; Stairs, I. H.] McGill Univ, Dept Phys, 3600 Univ St, Montreal, PQ H3A 2T8, Canada.
   [Scholz, P.; Ferdman, R. D.; Kaspi, V. M.; Madsen, E. C.; Patel, C.; Stairs, I. H.] McGill Univ, McGill Space Inst, 3600 Univ St, Montreal, PQ H3A 2T8, Canada.
   [Hessels, J. W. T.; van Leeuwen, J.] Netherlands Inst Radio Astron, ASTRON, Postbus 2, NL-7990 AA Dwingeloo, Netherlands.
   [Hessels, J. W. T.; van Leeuwen, J.] Univ Amsterdam, Astron Inst Anton Pannekoek, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
   [Bogdanov, S.; Camilo, F.] Columbia Univ, Columbia Astrophys Lab, 538 W 120th St, New York, NY 10027 USA.
   [Brazier, A.; Chatterjee, S.; Cordes, J. M.] Cornell Univ, Dept Astron & Space Sci, Ithaca, NY 14853 USA.
   [Brazier, A.] Cornell Univ, Cornell Ctr Adv Comp, Ithaca, NY 14853 USA.
   [Camilo, F.] Square Kilometre Array South Africa, ZA-7405 Pinelands, South Africa.
   [Crawford, F.] Franklin & Marshall Coll, Dept Phys & Astron, Lancaster, PA 17604 USA.
   [Deneva, J.] Naval Res Lab, Natl Res Council, 4555 Overlook Ave SW, Washington, DC 20375 USA.
   [Lynch, R.] Natl Radio Astron Observ, POB 2, Green Bank, WV 24944 USA.
   [Lynch, R.; McLaughlin, M. A.] W Virginia Univ, Dept Phys & Astron, Morgantown, WV 26506 USA.
   [Ransom, S. M.] Natl Radio Astron Observ, Edgemont Rd, Charlottesville, VA 22903 USA.
   [Seymour, A.] Arecibo Observ, HC3 Box 53995, Arecibo, PR 00612 USA.
   [Stairs, I. H.] Univ British Columbia, Dept Phys & Astron, 6224 Agr Rd, Vancouver, BC V6T 1Z1, Canada.
   [Stappers, B. W.] Univ Manchester, Sch Phys & Astron, Jodrell Bank, Ctr Astrophys, Manchester M13 9PL, Lancs, England.
C3 Max Planck Society; McGill University; McGill University; University of Amsterdam; Columbia University; Cornell University; Cornell University; Franklin & Marshall College; United States Department of Defense; United States Navy; United States Naval Research Laboratory; National Academies of Sciences, Engineering & Medicine; National Radio Astronomy Observatory (NRAO); West Virginia University; National Radio Astronomy Observatory (NRAO); National Aeronautics & Space Administration (NASA); University of British Columbia; University of Manchester; Jodrell Bank Centre for Astrophysics
RP Hessels, JWT (corresponding author), Netherlands Inst Radio Astron, ASTRON, Postbus 2, NL-7990 AA Dwingeloo, Netherlands.; Hessels, JWT (corresponding author), Univ Amsterdam, Astron Inst Anton Pannekoek, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
EM j.w.t.hessels@uva.nl
FU National Science Foundation [AST-1100968]; European Research Council (ERC) under the European Union; ERC Starting Grant BEACON [279702]; ERC Starting Grant DRAGNET [337062]; NSF [AST-1104617, AST-1008213]; NSERC; FQRNT via the Centre de Recherche Astrophysique de Quebec; Canadian Institute for Advanced Research; ERC Consolidator Grant [617199]; NSERC Discovery Grant; European Research Council (ERC) [279702] Funding Source: European Research Council (ERC); STFC [ST/L000768/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/L000768/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Physics [1430284] Funding Source: National Science Foundation; Office of Integrative Activities; Office Of The Director [1458952] Funding Source: National Science Foundation
NR 34
TC 752
Z9 844
U1 2
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 202
EP +
DI 10.1038/nature17168
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100034
PM 26934226
DA 2026-03-09
ER

PT J
AU van den Bergh, GD
   Kaifu, Y
   Kurniawan, I
   Kono, RT
   Brumm, A
   Setiyabudi, E
   Aziz, F
   Morwood, MJ
AF van den Bergh, Gerrit D.
   Kaifu, Yousuke
   Kurniawan, Iwan
   Kono, Reiko T.
   Brumm, Adam
   Setiyabudi, Erick
   Aziz, Fachroel
   Morwood, Michael J.
TI Homo floresiensis-like fossils from the early Middle Pleistocene of Flores
SO NATURE
LA English
DT Article
ID taxonomic affinity; liang-bua; dental remains; hominin; shape; morphology; sangiran; dmanisi; diversity; georgia
AB The evolutionary origin of Homo floresiensis, a diminutive hominin species previously known only by skeletal remains from Liang Bua in western Flores, Indonesia, has been intensively debated. It is a matter of controversy whether this primitive form, dated to the Late Pleistocene, evolved from early Asian Homo erectus and represents a unique and striking case of evolutionary reversal in hominin body and brain size within an insular environment(1-4). The alternative hypothesis is that H. floresiensis derived from an older, smaller-brained member of our genus, such as Homo habilis, or perhaps even late Australopithecus, signalling a hitherto undocumented dispersal of hominins from Africa into eastern Asia by two million years ago (2 Ma)(5,6). Here we describe hominin fossils excavated in 2014 from an early Middle Pleistocene site (Mata Menge) in the So'a Basin of central Flores. These specimens comprise a mandible fragment and six isolated teeth belonging to at least three small-jawed and small-toothed individuals. Dating to similar to 0.7 Ma, these fossils now constitute the oldest hominin remains from Flores(7). The Mata Menge mandible and teeth are similar in dimensions and morphological characteristics to those of H. floresiensis from Liang Bua. The exception is the mandibular first molar, which retains a more primitive condition. Notably, the Mata Menge mandible and molar are even smaller in size than those of the two existing H. floresiensis individuals from Liang Bua. The Mata Menge fossils are derived compared with Australopithecus and H. habilis, and so tend to support the view that H. floresiensis is a dwarfed descendent of early Asian H. erectus. Our findings suggest that hominins on Flores had acquired extremely small body size and other morphological traits specific to H. floresiensis at an unexpectedly early time.
C1 [van den Bergh, Gerrit D.; Morwood, Michael J.] Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [Kaifu, Yousuke; Kono, Reiko T.] Natl Museum Nat & Sci, Dept Anthropol, 4-1-1 Amakubo, Tsukuba, Ibaraki 3050005, Japan.
   [Kurniawan, Iwan; Setiyabudi, Erick; Aziz, Fachroel] Geol Museum Bandung, Geol Agcy, Jalan Diponegoro 57, Bandung 40122, Indonesia.
   [Brumm, Adam] Griffith Univ, Environm Futures Res Inst, Res Ctr Human Evolut, Nathan, Qld 4111, Australia.
   [Brumm, Adam] Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.
C3 University of Wollongong; National Museum of Nature and Science; Griffith University; University of Wollongong
RP Kaifu, Y (corresponding author), Natl Museum Nat & Sci, Dept Anthropol, 4-1-1 Amakubo, Tsukuba, Ibaraki 3050005, Japan.
EM kaifu@kahaku.go.jp
FU Australian Research Council (ARC) [DP1093342]; Japan Society for the Promotion of Science [24247044]; Geological Survey Centre of Indonesia; Australian Research Council [DP1093342] Funding Source: Australian Research Council
NR 53
TC 102
Z9 121
U1 0
U2 141
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 245
EP +
DI 10.1038/nature17999
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100040
PM 27279221
DA 2026-03-09
ER

PT J
AU Tsementzi, D
   Wu, JY
   Deutsch, S
   Nath, S
   Rodriguez, LM
   Burns, AS
   Ranjan, P
   Sarode, N
   Malmstrom, RR
   Padilla, CC
   Stone, BK
   Bristow, LA
   Larsen, M
   Glass, JB
   Thamdrup, B
   Woyke, T
   Konstantinidis, KT
   Stewart, FJ
AF Tsementzi, Despina
   Wu, Jieying
   Deutsch, Samuel
   Nath, Sangeeta
   Rodriguez-R, Luis M.
   Burns, Andrew S.
   Ranjan, Piyush
   Sarode, Neha
   Malmstrom, Rex R.
   Padilla, Cory C.
   Stone, Benjamin K.
   Bristow, Laura A.
   Larsen, Morten
   Glass, Jennifer B.
   Thamdrup, Bo
   Woyke, Tanja
   Konstantinidis, Konstantinos T.
   Stewart, Frank J.
TI SAR11 bacteria linked to ocean anoxia and nitrogen loss
SO NATURE
LA English
DT Article
ID nitrite-oxidizing bacterium; 2nd nitrate reductase; metagenomic analysis; seasonal dynamics; single-cell; sequence; genome; identification; genes; classification
AB Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N-2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted similar to 40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.
C1 [Tsementzi, Despina; Konstantinidis, Konstantinos T.] Georgia Inst Technol, Sch Civil & Environm Engn, Ford Environm Sci & Technol Bldg,311 Ferst Dr, Atlanta, GA 30332 USA.
   [Wu, Jieying; Rodriguez-R, Luis M.; Burns, Andrew S.; Ranjan, Piyush; Sarode, Neha; Padilla, Cory C.; Konstantinidis, Konstantinos T.; Stewart, Frank J.] Georgia Inst Technol, Sch Biol Sci, Ford Environm Sci & Technol Bldg,311 Ferst Dr, Atlanta, GA 30332 USA.
   [Deutsch, Samuel; Nath, Sangeeta; Malmstrom, Rex R.; Woyke, Tanja] Dept Energy Joint Genome Inst, 2800 Mitchell Dr, Walnut Creek, CA 94598 USA.
   [Stone, Benjamin K.] Bowdoin Coll, Dept Biol, 255 Maine St, Brunswick, ME 04011 USA.
   [Bristow, Laura A.] Max Planck Inst Marine Microbiol, Biochem Grp, D-28359 Bremen, Germany.
   [Larsen, Morten; Thamdrup, Bo] Univ Southern Denmark, Dept Biol, Campusvej 55, DK-5230 Odense M, Denmark.
   [Larsen, Morten; Thamdrup, Bo] Univ Southern Denmark, Nord Ctr Earth Evolut NordCEE, Campusvej 55, DK-5230 Odense M, Denmark.
   [Glass, Jennifer B.] Georgia Inst Technol, Sch Earth & Atmospher Sci, Ford Environm Sci & Technol Bldg,311 Ferst Dr, Atlanta, GA 30332 USA.
C3 University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Bowdoin College; Max Planck Society; University of Southern Denmark; University of Southern Denmark; University System of Georgia; Georgia Institute of Technology
RP Stewart, FJ (corresponding author), Georgia Inst Technol, Sch Biol Sci, Ford Environm Sci & Technol Bldg,311 Ferst Dr, Atlanta, GA 30332 USA.
EM frank.stewart@biology.gatech.edu
FU National Science Foundation [1151698, 1416673]; NASA Exobiology Program [NNX14AJ87G]; Sloan Foundation [RC944]; Community Science Program grant from the Department of Energy (DOE); European Research Council [267233]; Danish National Research Foundation [DNRF53]; Onassis Foundation Fellowship;  [DE-AC02-05CH11231]; NASA [680757, NNX14AJ87G] Funding Source: Federal RePORTER; Directorate For Geosciences; Division Of Ocean Sciences [1151698] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1416673] Funding Source: National Science Foundation
NR 76
TC 139
Z9 165
U1 2
U2 163
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 179
EP +
DI 10.1038/nature19068
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100029
PM 27487207
DA 2026-03-09
ER

PT J
AU Chen, Q
   Boire, A
   Jin, X
   Valiente, M
   Er, EE
   Lopez-Soto, A
   Jacob, LS
   Patwa, R
   Shah, H
   Xu, K
   Cross, JR
   Massagué, J
AF Chen, Qing
   Boire, Adrienne
   Jin, Xin
   Valiente, Manuel
   Er, Ekrem Emrah
   Lopez-Soto, Alejandro
   Jacob, Leni S.
   Patwa, Ruzeen
   Shah, Hardik
   Xu, Ke
   Cross, Justin R.
   Massague, Joan
TI Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer
SO NATURE
LA English
DT Article
ID breast-cancer metastasis; cadherin superfamily; expression analysis; tumor-cells; genes; connexin; classification; recognition; survival; pathway
AB Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer cells express protocadherin 7 (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-alpha (IFN alpha) and tumour necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-kappa B pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis.
C1 [Chen, Qing; Boire, Adrienne; Jin, Xin; Valiente, Manuel; Er, Ekrem Emrah; Lopez-Soto, Alejandro; Jacob, Leni S.; Patwa, Ruzeen; Massague, Joan] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
   [Boire, Adrienne] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
   [Shah, Hardik; Cross, Justin R.] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, New York, NY 10065 USA.
   [Xu, Ke] Mem Sloan Kettering Canc Ctr, Mol Cytol Core Facil, New York, NY 10065 USA.
   [Chen, Qing] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
   [Jin, Xin] Eli & Edythe L Broad Inst, Canc Program, Cambridge, MA 02142 USA.
   [Valiente, Manuel] Spanish Natl Canc Res Ctr CNIO, Brain Metastasis Grp, E-28029 Madrid, Spain.
   [Lopez-Soto, Alejandro] Univ Oviedo, Fac Med, Dept Funct Biol IUOPA, Oriedo 33006, Spain.
   [Jacob, Leni S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Genet, 3 Blackfan Circle,CLS 417, Boston, MA 02115 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; The Wistar Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Centro Nacional de Investigaciones Oncologicas (CNIO); University of Oviedo; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School
RP Massagué, J (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
EM j-massague@ski.mskcc.org
FU NIH [P01-CA129243, U54-163167, P30 CA008748]; DOD [W81XWH-12-0074]; Alan and Sandra Gerry Metastasis Research Initiative; MSKCC Clinical Scholars Training Program; Solomon R. and Rebecca D. Baker Foundation; Susan G. Komen Organization; National Cancer Institute [P01CA129243, P30CA008748] Funding Source: NIH RePORTER
NR 51
TC 789
Z9 907
U1 10
U2 220
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 493
EP +
DI 10.1038/nature18268
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100032
PM 27225120
DA 2026-03-09
ER

PT J
AU Karki, R
   Man, SM
   Malireddi, RKS
   Kesavardhana, S
   Zhu, QF
   Burton, AR
   Sharma, BR
   Qi, XP
   Pelletier, S
   Vogel, P
   Rosenstiel, P
   Kanneganti, TD
AF Karki, Rajendra
   Man, Si Ming
   Malireddi, R. K. Subbarao
   Kesavardhana, Sannula
   Zhu, Qifan
   Burton, Amanda R.
   Sharma, Bhesh Raj
   Qi, Xiaopeng
   Pelletier, Stephane
   Vogel, Peter
   Rosenstiel, Philip
   Kanneganti, Thirumala-Devi
TI NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer
SO NATURE
LA English
DT Article
ID protein-kinase b; nod-like receptor; nf-kappa-b; colon inflammation; cutting edge; amino-acids; cell-death; activation; aim2; tumorigenesis
AB NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases, but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases(1). Cytoplasmic innate immune sensors, including NLRs, are central regulators of intestinal homeostasis(2-9). NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains(10,1)1. Expression of NLRC3 is drastically reduced in the tumour tissue of patients with colorectal cancer compared to healthy tissues(12), highlighting an undefined potential function for this sensor in the development of cancer. Here we show that mice lacking NLRC3 are hyper-susceptible to colitis and colorectal tumorigenesis. The effect of NLRC3 is most dominant in enterocytes, in which it suppresses activation of the mTOR signalling pathways and inhibits cellular proliferation and stem-cell-derived organoid formation. NLRC3 associates with PI3Ks and blocks activation of the PI3K-dependent kinase AKT following binding of growth factor receptors or Toll-like receptor 4. These findings reveal a key role for NLRC3 as an inhibitor of the mTOR pathways, mediating protection against colorectal cancer.
C1 [Karki, Rajendra; Man, Si Ming; Malireddi, R. K. Subbarao; Kesavardhana, Sannula; Zhu, Qifan; Burton, Amanda R.; Sharma, Bhesh Raj; Qi, Xiaopeng; Pelletier, Stephane; Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Zhu, Qifan] Univ Tennessee, Integrated Biomed Sci Program, Hlth Sci Ctr, Memphis, TN 38163 USA.
   [Pelletier, Stephane] St Jude Childrens Res Hosp, Embryon Stem Cell Lab, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Anim Resources Ctr, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Vet Pathol Core, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Rosenstiel, Philip] Christian Albrechts Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
C3 St Jude Children's Research Hospital; University of Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Kiel
RP Kanneganti, TD (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM thirumala-devi.kanneganti@stjude.org
FU SJCRH; NCI [P30 CA021765-35]; US National Institutes of Health [AI101935, AI124346, AR056296, CA163507]; ALSAC; ExC306 Inflammation at Interfaces; DFG [SFB 877 B9, SFB1182 C2]; R. G. Menzies Early Career Fellowship from the National Health and Medical Research Council of Australia; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R37AI101935, R01AI124346] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR056296] Funding Source: NIH RePORTER
NR 32
TC 164
Z9 192
U1 1
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 583
EP +
DI 10.1038/nature20597
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500052
PM 27951586
DA 2026-03-09
ER

PT J
AU Mazhab-Jafari, MT
   Rohou, A
   Schmidt, C
   Bueler, SA
   Benlekbir, S
   Robinson, CV
   Rubinstein, JL
AF Mazhab-Jafari, Mohammad T.
   Rohou, Alexis
   Schmidt, Carla
   Bueler, Stephanie A.
   Benlekbir, Samir
   Robinson, Carol V.
   Rubinstein, John L.
TI Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase
SO NATURE
LA English
DT Article
ID cryo-em; anisotropic magnification; saccharomyces-cerevisiae; subunit; resolution; synthase; mechanism; frealign; defocus; ring
AB Vacuolar-type ATPases (V-ATPases) are ATP-powered proton pumps involved in processes such as endocytosis, lysosomal degradation, secondary transport, TOR signalling, and osteoclast and kidney function. ATP hydrolysis in the soluble catalytic V-1 region drives proton translocation through the membrane-embedded V-O region via rotation of a rotor subcomplex. Variability in the structure of the intact enzyme has prevented construction of an atomic model for the membrane-embedded motor of any rotary ATPase(1-5). We induced dissociation and auto-inhibition of the V1 and VO regions of the V-ATPase by starving the yeast Saccharomyces cerevisiae(6,7), allowing us to obtain a resolution electron cryomicroscopy map of the VO complex and build atomic models for the majority of its subunits. The analysis reveals the structures of subunits ac(8)c'c '' de and a protein that we identify and propose to be a new subunit (subunit f). A large cavity between subunit a and the c-ring creates a cytoplasmic half-channel for protons. The c-ring has an asymmetric distribution of proton-carrying Glu residues, with the Glu residue of subunit c '' interacting with Arg735 of subunit a. The structure suggests sequential protonation and deprotonation of the c-ring, with ATP-hydrolysis-driven rotation causing protonation of a Glu residue at the cytoplasmic half-channel and subsequent deprotonation of a Glu residue at a luminal half-channel.
C1 [Mazhab-Jafari, Mohammad T.; Bueler, Stephanie A.; Benlekbir, Samir; Rubinstein, John L.] Hosp Sick Children, Mol Struct & Funct Program, Toronto, ON M5G 0A4, Canada.
   [Rohou, Alexis] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
   [Schmidt, Carla; Robinson, Carol V.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
   [Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Rubinstein, John L.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Schmidt, Carla] Univ Halle Wittenberg, Interdisciplinary Res Ctr HALOmem, D-06120 Halle, Saale, Germany.
C3 University of Toronto; Hospital for Sick Children (SickKids); Howard Hughes Medical Institute; University of Oxford; University of Toronto; University of Toronto; Martin Luther University Halle Wittenberg
RP Rubinstein, JL (corresponding author), Hosp Sick Children, Mol Struct & Funct Program, Toronto, ON M5G 0A4, Canada.; Rubinstein, JL (corresponding author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.; Rubinstein, JL (corresponding author), Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
EM john.rubinstein@utoronto.ca
FU Canadian Institutes of Health Research (CIHR); Canadian Institutes of Health Research [MOP81294]; Wellcome Trust [WT008150, WT099141]; European Research Council IMPRESS [ERC268851]
NR 51
TC 132
Z9 151
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 118
EP +
DI 10.1038/nature19828
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100041
PM 27776355
DA 2026-03-09
ER

PT J
AU Mills, SM
   Fabrycky, DC
   Migaszewski, C
   Ford, EB
   Petigura, E
   Isaacson, H
AF Mills, Sean M.
   Fabrycky, Daniel C.
   Migaszewski, Cezary
   Ford, Eric B.
   Petigura, Erik
   Isaacson, Howard
TI A resonant chain of four transiting, sub-Neptune planets
SO NATURE
LA English
DT Article
ID mean motion resonances; hot super-earths; low-mass; system; kepler; candidates; migration; dynamics; ii.; planetesimals
AB Surveys have revealed many multi-planet systems containing super-Earths and Neptunes in orbits of a few days to a few months(1). There is debate whether in situ assembly(2) or inward migration is the dominant mechanism of the formation of such planetary systems. Simulations suggest that migration creates tightly packed systems with planets whose orbital periods may be expressed as ratios of small integers (resonances)(3-5), often in a many-planet series (chain)(6). In the hundreds of multi-planet systems of sub-Neptunes, more planet pairs are observed near resonances than would generally be expected(7), but no individual system has hitherto been identified that must have been formed by migration. Proximity to resonance enables the detection of planets perturbing each other(8). Here we report transit timing variations of the four planets in the Kepler-223 system, model these variations as resonant-angle librations, and compute the long-term stability of the resonant chain. The architecture of Kepler-223 is too finely tuned to have been formed by scattering, and our numerical simulations demonstrate that its properties are natural outcomes of the migration hypothesis. Similar systems could be destabilized by any of several mechanisms(5,9-11), contributing to the observed orbital-period distribution, where many planets are not in resonances. Planetesimal interactions in particular are thought to be responsible for establishing the current orbits of the four giant planets in the Solar System by disrupting a theoretical initial resonant chain(12) similar to that observed in Kepler-223.
C1 [Mills, Sean M.; Fabrycky, Daniel C.] Univ Chicago, Dept Astron & Astrophys, 5640 S Ellis Ave, Chicago, IL 60637 USA.
   [Migaszewski, Cezary] Univ Szczecin, Inst Phys, Wielkopolska 15, PL-70451 Szczecin, Poland.
   [Migaszewski, Cezary] Univ Szczecin, CASA, Wielkopolska 15, PL-70451 Szczecin, Poland.
   [Migaszewski, Cezary] Nicolaus Copernicus Univ, Torun Ctr Astron, Gagarina 11, PL-87100 Torun, Poland.
   [Ford, Eric B.] Penn State Univ, Ctr Exoplanets & Habitable Worlds, University Pk, PA 16802 USA.
   [Ford, Eric B.] Penn State Univ, Dept Astron & Astrophys, 525 Davey Lab, University Pk, PA 16802 USA.
   [Ford, Eric B.] Penn State Univ, Ctr Astrostat, University Pk, PA 16802 USA.
   [Petigura, Erik; Isaacson, Howard] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Petigura, Erik] CALTECH, Pasadena, CA 91125 USA.
C3 University of Chicago; University of Szczecin; University of Szczecin; Nicolaus Copernicus University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California Berkeley; California Institute of Technology
RP Mills, SM (corresponding author), Univ Chicago, Dept Astron & Astrophys, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM sean.martin.mills@gmail.com
FU NASA issued through the Kepler Participating Scientist Program [NNX14AB87G, NNX12AF73G, NNX14AN76G]; NASA [NNX15AE21G]; Alfred P. Sloan Foundation; Polish National Science Centre [DEC-2012/06/A/ST9/00276]; NASA [804841, NNX15AE21G] Funding Source: Federal RePORTER
NR 51
TC 164
Z9 192
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 509
EP +
DI 10.1038/nature17445
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100035
PM 27225123
DA 2026-03-09
ER

PT J
AU Lu, J
   Lee, YJ
   Luo, XY
   Lau, KC
   Asadi, M
   Wang, HH
   Brombosz, S
   Wen, JG
   Zhai, DY
   Chen, ZH
   Miller, DJ
   Jeong, YS
   Park, JB
   Fang, ZZ
   Kumar, B
   Salehi-Khojin, A
   Sun, YK
   Curtiss, LA
   Amine, K
AF Lu, Jun
   Lee, Yun Jung
   Luo, Xiangyi
   Lau, Kah Chun
   Asadi, Mohammad
   Wang, Hsien-Hau
   Brombosz, Scott
   Wen, Jianguo
   Zhai, Dengyun
   Chen, Zonghai
   Miller, Dean J.
   Jeong, Yo Sub
   Park, Jin-Bum
   Fang, Zhigang Zak
   Kumar, Bijandra
   Salehi-Khojin, Amin
   Sun, Yang-Kook
   Curtiss, Larry A.
   Amine, Khalil
TI A lithium-oxygen battery based on lithium superoxide
SO NATURE
LA English
DT Article
ID reduced graphene oxide; li-o-2; stability; catalyst; disproportionation; architecture; reduction; electrode; clusters; spectra
AB Batteries based on sodium superoxide and on potassium superoxide have recently been reported(1-3). However, there have been no reports of a battery based on lithium superoxide (LiO2), despite much research(4-8) into the lithium-oxygen (Li-O-2) battery because of its potential high energy density. Several studies(9-16) of Li-O-2 batteries have found evidence of LiO2 being formed as one component of the discharge product along with lithium peroxide (Li2O2). In addition, theoretical calculations have indicated that some forms of LiO2 may have a long lifetime(17). These studies also suggest that it might be possible to form LiO2 alone for use in a battery. However, solid LiO2 has been difficult to synthesize in pure form(18) because it is thermodynamically unstable with respect to disproportionation, giving Li2O2 (refs 19, 20). Here we show that crystalline LiO2 can be stabilized in a Li-O-2 battery by using a suitable graphene-based cathode. Various characterization techniques reveal no evidence for the presence of Li2O2. A novel templating growth mechanism involving the use of iridium nanoparticles on the cathode surface may be responsible for the growth of crystalline LiO2. Our results demonstrate that the LiO2 formed in the Li-O-2 battery is stable enough for the battery to be repeatedly charged and discharged with a very low charge potential (about 3.2 volts). We anticipate that this discovery will lead to methods of synthesizing and stabilizing LiO2, which could open the way to high-energy-density batteries based on LiO2 as well as to other possible uses of this compound, such as oxygen storage.
C1 [Lu, Jun; Zhai, Dengyun; Chen, Zonghai; Amine, Khalil] Argonne Natl Lab, Chem Sci & Engn Div, Argonne, IL 60439 USA.
   [Lee, Yun Jung; Jeong, Yo Sub; Park, Jin-Bum; Sun, Yang-Kook] Hanyang Univ, Dept Energy Engn, Seoul 133791, South Korea.
   [Luo, Xiangyi; Lau, Kah Chun; Wang, Hsien-Hau; Brombosz, Scott; Curtiss, Larry A.] Argonne Natl Lab, Div Mat Sci, Argonne, IL 60439 USA.
   [Luo, Xiangyi; Fang, Zhigang Zak] Univ Utah, Dept Met Engn, Salt Lake City, UT 84112 USA.
   [Asadi, Mohammad; Salehi-Khojin, Amin] Univ Illinois, Dept Mech & Ind Engn, Chicago, IL 60607 USA.
   [Wen, Jianguo; Miller, Dean J.] Argonne Natl Lab, Ctr Nanoscale Mat, Argonne, IL 60439 USA.
   [Kumar, Bijandra] Univ Louisville, Conn Ctr Renewable Energy Res, Louisville, KY 40292 USA.
C3 United States Department of Energy (DOE); Argonne National Laboratory; Hanyang University; United States Department of Energy (DOE); Argonne National Laboratory; Utah System of Higher Education; University of Utah; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; United States Department of Energy (DOE); Argonne National Laboratory; University of Louisville
RP Curtiss, LA (corresponding author), Argonne Natl Lab, Div Mat Sci, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM yksun@hanyang.ac.kr; curtiss@anl.gov; amine@anl.gov
FU US Department of Energy from the Vehicle Technologies Office, Department of Energy, Office of Energy Efficiency and Renewable Energy [DE-AC02-06CH11357]; Center for Electrochemical Energy Science (CEES), an Energy Frontier Research Center (EFRC) - US Department of Energy, Office of Science, Office of Basic Energy Sciences; University of Illinois-Chicago Chancellor Proof of Concept Fund; INCITE; US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Human Resources Development of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) - Korea government Ministry of Knowledge Economy [20124010203310]; Basic Science Research Program [NRF-2014R1A2A1A11049801]
NR 44
TC 653
Z9 721
U1 21
U2 1419
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 377
EP +
DI 10.1038/nature16484
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800042
PM 26751057
DA 2026-03-09
ER

PT J
AU Griffiths, CA
   Sagar, R
   Geng, Y
   Primavesi, LF
   Patel, MK
   Passarelli, MK
   Gilmore, IS
   Steven, RT
   Bunch, J
   Paul, MJ
   Davis, BG
AF Griffiths, Cara A.
   Sagar, Ram
   Geng, Yiqun
   Primavesi, Lucia F.
   Patel, Mitul K.
   Passarelli, Melissa K.
   Gilmore, Ian S.
   Steven, Rory T.
   Bunch, Josephine
   Paul, Matthew J.
   Davis, Benjamin G.
TI Chemical intervention in plant sugar signalling increases yield and resilience
SO NATURE
LA English
DT Article
ID adp-glucose pyrophosphorylase; trehalose 6-phosphate; mass-spectrometry; scale synthesis; caged compounds; starch; trehalose-6-phosphate; inhibition; tissue; metabolites
AB The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience(1,2). Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat(3). Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development(4,5). Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a 'signalling-precursor' concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function.
C1 [Griffiths, Cara A.; Primavesi, Lucia F.; Paul, Matthew J.] Rothamsted Res, Plant Biol & Crop Sci, Harpenden AL5 2JQ, Herts, England.
   [Sagar, Ram; Geng, Yiqun; Patel, Mitul K.; Davis, Benjamin G.] Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England.
   [Passarelli, Melissa K.; Gilmore, Ian S.; Steven, Rory T.; Bunch, Josephine] Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England.
   [Bunch, Josephine] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England.
   [Sagar, Ram] Shiv Nadar Univ, Sch Nat Sci, Dept Chem, Greater Noida 201314, India.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; University of Oxford; National Physical Laboratory - UK; University of Nottingham; Shiv Nadar University
RP Paul, MJ (corresponding author), Rothamsted Res, Plant Biol & Crop Sci, Harpenden AL5 2JQ, Herts, England.; Davis, BG (corresponding author), Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England.
EM matthew.paul@rothamsted.ac.uk; Ben.Davis@chem.ox.ac.uk
FU BBSRC Selective Chemical Intervention in Biological Systems initiative [BB/D006112/1]; BBSRC Sparking Impact initiative; ICL Innovations; 3D NanoSIMS and AIMS-HIGHER projects of the Chemical and Biological programme of the National Measurement System of the UK Department of Business, Innovation and Skills; Royal Society Wolfson Research Merit Award; BBSRC; Biotechnology and Biological Sciences Research Council [BB/N004205/1, BBS/E/C/00005202, BB/D006112/1] Funding Source: researchfish; BBSRC [BB/N004205/1, BB/D006112/1, BBS/E/C/00005202] Funding Source: UKRI
NR 39
TC 178
Z9 195
U1 19
U2 326
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 574
EP +
DI 10.1038/nature20591
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500050
PM 27974806
DA 2026-03-09
ER

PT J
AU Avgousti, DC
   Herrmann, C
   Kulej, K
   Pancholi, NJ
   Sekulic, N
   Petrescu, J
   Molden, RC
   Blumenthal, D
   Paris, AJ
   Reyes, ED
   Ostapchuk, P
   Hearing, P
   Seeholzer, SH
   Worthen, GS
   Black, BE
   Garcia, BA
   Weitzman, MD
AF Avgousti, Daphne C.
   Herrmann, Christin
   Kulej, Katarzyna
   Pancholi, Neha J.
   Sekulic, Nikolina
   Petrescu, Joana
   Molden, Rosalynn C.
   Blumenthal, Daniel
   Paris, Andrew J.
   Reyes, Emigdio D.
   Ostapchuk, Philomena
   Hearing, Patrick
   Seeholzer, Steven H.
   Worthen, G. Scott
   Black, Ben E.
   Garcia, Benjamin A.
   Weitzman, Matthew D.
TI A core viral protein binds host nucleosomes to sequester immune danger signals
SO NATURE
LA English
DT Article
ID template-activating factor; cenp-a nucleosm; acute lung injury; adenovirus chromatin; mass-spectrometry; virus-infection; dna; mobility; cells; hmgb1
AB Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses(1). Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important part in innate immune responses(2). Viralen-coded core basic proteins compact viral genomes, but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones(3). Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles(4,5), it is unknown whether protein VII affects cellular chromatin. Here we show that protein VII alters cellular chromatin, leading us to hypothesize that this has an impact on antiviral responses during adenovirus infection in human cells. We find that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter the protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in the chromatin of members of the high-mobility-group protein B family (HMGB1, HMGB2 and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses(6,7). We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation-induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together, our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signalling.
C1 [Avgousti, Daphne C.; Kulej, Katarzyna; Reyes, Emigdio D.; Weitzman, Matthew D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Avgousti, Daphne C.; Herrmann, Christin; Kulej, Katarzyna; Pancholi, Neha J.; Petrescu, Joana; Reyes, Emigdio D.; Weitzman, Matthew D.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Canc Pathobiol, Philadelphia, PA 19104 USA.
   [Herrmann, Christin; Pancholi, Neha J.] Univ Penn, Perelman Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
   [Sekulic, Nikolina; Black, Ben E.; Garcia, Benjamin A.] Univ Penn, Dept Biochem Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Sekulic, Nikolina; Molden, Rosalynn C.; Black, Ben E.; Garcia, Benjamin A.] Univ Penn, Epigenet Program, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Petrescu, Joana] Villanova Univ, Villanova, PA 19085 USA.
   [Blumenthal, Daniel] Childrens Hosp Philadelphia, Div Cell Pathol, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Paris, Andrew J.] Hosp Univ Penn, Div Pulm Allergy & Crit Care Med, 3400 Spruce St, Philadelphia, PA 19104 USA.
   [Paris, Andrew J.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Ostapchuk, Philomena; Hearing, Patrick] SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
   [Seeholzer, Steven H.] Childrens Hosp Philadelphia, Prot & Prote Core, Philadelphia, PA 19104 USA.
   [Worthen, G. Scott] Childrens Hosp Philadelphia, Div Neonatol, Philadelphia, PA 19104 USA.
   [Worthen, G. Scott] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Sekulic, Nikolina] Univ Oslo, Biotechnol Ctr Oslo, N-0316 Oslo, Norway.
   [Sekulic, Nikolina] Univ Oslo, Dept Chem, N-0316 Oslo, Norway.
C3 University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Villanova University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; State University of New York (SUNY) System; Stony Brook University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Oslo; University of Oslo
RP Weitzman, MD (corresponding author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.; Weitzman, MD (corresponding author), Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Canc Pathobiol, Philadelphia, PA 19104 USA.
EM weitzmanm@email.chop.edu
FU American Cancer Society; National Institutes of Health [CA097093, AI102577, CA122677, AI118891, GM110174, GM082989]; Institute for Immunology of the University of Pennsylvania; Children's Hospital of Philadelphia;  [T32 CA115299];  [F32 GM112414];  [T32 NS007180]; National Cancer Institute [R01CA122677, T32CA115299] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI118891] Funding Source: NIH RePORTER
NR 51
TC 124
Z9 144
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 173
EP +
DI 10.1038/nature18317
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600047
PM 27362237
DA 2026-03-09
ER

PT J
AU Yu, Y
   Tsang, JCH
   Wang, C
   Clare, S
   Wang, JX
   Chen, X
   Brandt, C
   Kane, L
   Campos, LS
   Lu, LM
   Belz, GT
   McKenzie, ANJ
   Teichmann, SA
   Dougan, G
   Liu, PT
AF Yu, Yong
   Tsang, Jason C. H.
   Wang, Cui
   Clare, Simon
   Wang, Juexuan
   Chen, Xi
   Brandt, Cordelia
   Kane, Leanne
   Campos, Lia S.
   Lu, Liming
   Belz, Gabrielle T.
   McKenzie, Andrew N. J.
   Teichmann, Sarah A.
   Dougan, Gordon
   Liu, Pentao
TI Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway
SO NATURE
LA English
DT Article
ID innate lymphoid-cells; transcription factor gata3; expression; lineage; checkpoints; bcl11b; tcf-1; nfil3
AB Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis(1,2). ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the alpha-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments(3-8). ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3)(9). Despite recent advances(1,2,10), the cellular heterogeneity, developmental trajectory and signalling dependence of ILC progenitors are not fully understood. Here, using single-cell RNA-sequencing (scRNA-seq) of mouse bone marrow progenitors, we reveal ILC precursor subsets, delineate distinct ILC development stages and pathways, and report that high expression of programmed death 1 (PD-1(hi)) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1(hi)IL-25R(hi) as an early checkpoint in ILC2 development, which was abolished by deficiency in the zinc-finger protein Bcl11b but restored by IL-25R overexpression. Similar to T lymphocytes, PD-1 was upregulated on activated ILCs. Administration of a PD-1 antibody depleted PD-1(hi) ILCs and reduced cytokine levels in an influenza infection model in mice, and blocked papain-induced acute lung inflammation. These results provide a perspective for exploring PD-1 and its ligand (PD-L1) in immunotherapy, and allow effective manipulation of the immune system for disease prevention and therapy.
C1 [Yu, Yong; Tsang, Jason C. H.; Wang, Cui; Clare, Simon; Wang, Juexuan; Chen, Xi; Brandt, Cordelia; Kane, Leanne; Campos, Lia S.; Teichmann, Sarah A.; Dougan, Gordon; Liu, Pentao] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Tsang, Jason C. H.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China.
   [Tsang, Jason C. H.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China.
   [Wang, Cui] Shanghai Acad Agr Sci, Inst Anim Husb & Vet Sci, Shanghai 201106, Peoples R China.
   [Lu, Liming] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai 200025, Peoples R China.
   [Belz, Gabrielle T.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia.
   [Belz, Gabrielle T.] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia.
   [McKenzie, Andrew N. J.] MRC, Mol Biol Lab, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
   [Teichmann, Sarah A.] EMBL EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
   [Dougan, Gordon] Univ Cambridge, Addenbrookes Hosp, Dept Med, Hills Rd, Cambridge CB2 0SP, England.
C3 Wellcome Trust Sanger Institute; Prince of Wales Hospital Hong Kong; Chinese University of Hong Kong; Chinese University of Hong Kong; Shanghai Academy of Agricultural Sciences; Shanghai Jiao Tong University; Chinese Academy of Sciences; Walter & Eliza Hall Institute; University of Melbourne; MRC Laboratory Molecular Biology; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Wellcome Trust Sanger Institute; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital
RP Liu, PT (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
EM pl2@sanger.ac.uk
FU Plan of Youth Growth from Shanghai Municipal Agricultural Committee [A-35]; National Natural Science Foundation of China [31370904, 81671579]; Australian Research Council [FT110100283]; National Health and Medical Research Council [10402092]; Medical Research Council [U105178805]; Wellcome Trust [100963/Z/13/Z, 098051]; Medical Research Council [MC_U105178805] Funding Source: researchfish; Wellcome Trust [100963/Z/13/Z] Funding Source: researchfish; MRC [MC_U105178805] Funding Source: UKRI; Australian Research Council [FT110100283] Funding Source: Australian Research Council
NR 39
TC 252
Z9 276
U1 1
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 102
EP +
DI 10.1038/nature20105
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100038
PM 27749818
DA 2026-03-09
ER

PT J
AU Shiddiq, M
   Komijani, D
   Duan, Y
   Gaita-Ariño, A
   Coronado, E
   Hill, S
AF Shiddiq, Muhandis
   Komijani, Dorsa
   Duan, Yan
   Gaita-Arino, Alejandro
   Coronado, Eugenio
   Hill, Stephen
TI Enhancing coherence in molecular spin qubits via atomic clock transitions
SO NATURE
LA English
DT Article
ID quantum information; decoherence; tm; tb; ho; dy; er
AB Quantum computing is an emerging area within the information sciences revolving around the concept of quantum bits (qubits). A major obstacle is the extreme fragility of these qubits due to interactions with their environment that destroy their quantumness. This phenomenon, known as decoherence, is of fundamental interest(1,2). There are many competing candidates for qubits, including superconducting circuits(3), quantum optical cavities(4), ultracold atoms(5) and spin qubits(6-8), and each has its strengths and weaknesses. When dealing with spin qubits, the strongest source of decoherence is the magnetic dipolar interaction(9). To minimize it, spins are typically diluted in a diamagnetic matrix. For example, this dilution can be taken to the extreme of a single phosphorus atom in silicon(6), whereas in molecular matrices a typical ratio is one magnetic molecule per 10,000 matrix molecules(10). However, there is a fundamental contradiction between reducing decoherence by dilution and allowing quantum operations via the interaction between spin qubits. To resolve this contradiction, the design and engineering of quantum hardware can benefit from a 'bottom-up' approach whereby the electronic structure of magnetic molecules is chemically tailored to give the desired physical behaviour. Here we present a way of enhancing coherence in solid-state molecular spin qubits without resorting to extreme dilution. It is based on the design of molecular structures with crystal field ground states possessing large tunnelling gaps that give rise to optimal operating points, or atomic clock transitions, at which the quantum spin dynamics become protected against dipolar decoherence. This approach is illustrated with a holmium molecular nanomagnet in which long coherence times (up to 8.4 microseconds at 5 kelvin) are obtained at unusually high concentrations. This finding opens new avenues for quantum computing based on molecular spin qubits.
C1 [Shiddiq, Muhandis; Komijani, Dorsa; Hill, Stephen] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Shiddiq, Muhandis; Komijani, Dorsa; Hill, Stephen] Florida State Univ, Dept Phys, Tallahassee, FL 32310 USA.
   [Duan, Yan; Gaita-Arino, Alejandro; Coronado, Eugenio] Univ Valencia, Inst Ciencia Mol, C Catedrat Jose Beltran 2, Paterna 46980, Spain.
C3 State University System of Florida; Florida State University; State University System of Florida; Florida State University; University of Valencia
RP Hill, S (corresponding author), Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.; Hill, S (corresponding author), Florida State Univ, Dept Phys, Tallahassee, FL 32310 USA.; Coronado, E (corresponding author), Univ Valencia, Inst Ciencia Mol, C Catedrat Jose Beltran 2, Paterna 46980, Spain.
EM eugenio.coronado@uv.es; shill@magnet.fsu.edu
FU NSF [DMR-1309463, DMR-1157490]; US AFOSR (AOARD) [134031 FA2386-13-1-4029]; State of Florida; European Research Council; Spanish MINECO [MAT-2014-56143-R, CTQ2014-52758-P]; Spanish MINECO (Excellence Unit Maria de Maeztu) [MDM-2015-0538]; Generalidad Valenciana (Prometeo); Generalidad Valenciana (ISIC-Nano Programs of Excellence); Spanish MINECO; Direct For Mathematical & Physical Scien; Division Of Materials Research [1309463] Funding Source: National Science Foundation
NR 32
TC 520
Z9 567
U1 3
U2 301
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 348
EP +
DI 10.1038/nature16984
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300048
PM 26983539
DA 2026-03-09
ER

PT J
AU Seneviratne, SI
   Donat, MG
   Pitman, AJ
   Knutti, R
   Wilby, RL
AF Seneviratne, Sonia I.
   Donat, Markus G.
   Pitman, Andy J.
   Knutti, Reto
   Wilby, Robert L.
TI Allowable CO2 emissions based on regional and impact-related climate targets
SO NATURE
LA English
DT Article
ID extremes index; cmip5; precipitation; temperature; ensemble; pattern; bias
AB Global temperature targets, such as the widely accepted limit of an increase above pre-industrial temperatures of two degrees Celsius, may fail to communicate the urgency of reducing carbon dioxide (CO2) emissions. The translation of CO2 emissions into regional-and impact-related climate targets could be more powerful because such targets are more directly aligned with individual national interests. We illustrate this approach using regional changes in extreme temperatures and precipitation. These scale robustly with global temperature across scenarios, and thus with cumulative CO2 emissions. This is particularly relevant for changes in regional extreme temperatures on land, which are much greater than changes in the associated global mean.
C1 [Seneviratne, Sonia I.; Knutti, Reto] Swiss Fed Inst Technol, Dept Environm Syst Sci, Inst Atmospher & Climate Sci, Zurich, Switzerland.
   [Donat, Markus G.; Pitman, Andy J.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW, Australia.
   [Donat, Markus G.; Pitman, Andy J.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW, Australia.
   [Wilby, Robert L.] Univ Loughborough, Dept Geog, Loughborough, Leics, England.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; ARC Centre of Excellence for Climate System Science; University of New South Wales Sydney; University of New South Wales Sydney; Loughborough University
RP Seneviratne, SI (corresponding author), Swiss Fed Inst Technol, Dept Environm Syst Sci, Inst Atmospher & Climate Sci, Zurich, Switzerland.
EM sonia.seneviratne@ethz.ch
FU European Community's Seventh Framework Programme [FP7-IDEAS-ERC-617518]; Australian Research Council (ARC) Centre of Excellence for Climate System Science [CE110001028]; ARC [DE150100456]
NR 59
TC 594
Z9 664
U1 6
U2 377
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 477
EP 483
DI 10.1038/nature16542
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800027
PM 26789252
DA 2026-03-09
ER

PT J
AU Chick, JM
   Munger, SC
   Simecek, P
   Huttlin, EL
   Choi, K
   Gatti, DM
   Raghupathy, N
   Svenson, KL
   Churchill, GA
   Gygi, SP
AF Chick, Joel M.
   Munger, Steven C.
   Simecek, Petr
   Huttlin, Edward L.
   Choi, Kwangbom
   Gatti, Daniel M.
   Raghupathy, Narayanan
   Svenson, Karen L.
   Churchill, Gary A.
   Gygi, Steven P.
TI Defining the consequences of genetic variation on a proteome-wide scale
SO NATURE
LA English
DT Article
ID nicotinamide nucleotide transhydrogenase; collaborative cross; abundance; mouse; expression; diversity; resource; quantification; dissection
AB Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, here we combine a multiplexed, mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in livers from 192 Diversity outbred mice, we identify 2,866 protein quantitative trait loci (pQTL) with twice as many local as distant genetic variants. These data support distinct transcriptional and post-transcriptional models underlying the observed pQTL effects. Using a sensitive approach to mediation analysis, we often identified a second protein or transcript as the causal mediator of distant pQTL. Our analysis reveals an extensive network of direct protein-protein interactions. Finally, we show that local genotype can provide accurate predictions of protein abundance in an independent cohort of collaborative cross mice.
C1 [Chick, Joel M.; Huttlin, Edward L.; Gygi, Steven P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Munger, Steven C.; Simecek, Petr; Choi, Kwangbom; Gatti, Daniel M.; Raghupathy, Narayanan; Svenson, Karen L.; Churchill, Gary A.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
C3 Harvard University; Harvard Medical School; Jackson Laboratory
RP Gygi, SP (corresponding author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Churchill, GA (corresponding author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM gary.churchill@jax.org; steven_gygi@hms.harvard.edu
FU Harvard Medical School; Jackson Laboratory; National Institutes of Health (NIH) [P50GM076468, F32HD074299, GM67945, U41HG006673]; National Cancer Institute [P30CA034196] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM067945, R01GM070683] Funding Source: NIH RePORTER
NR 58
TC 273
Z9 328
U1 0
U2 58
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 500
EP +
DI 10.1038/nature18270
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300043
PM 27309819
DA 2026-03-09
ER

PT J
AU Donati, JF
   Moutou, C
   Malo, L
   Baruteau, C
   Yu, L
   Hébrard, E
   Hussain, G
   Alencar, S
   Ménard, F
   Bouvier, J
   Petit, P
   Takami, M
   Doyon, R
   Cameron, AC
AF Donati, J. F.
   Moutou, C.
   Malo, L.
   Baruteau, C.
   Yu, L.
   Hebrard, E.
   Hussain, G.
   Alencar, S.
   Menard, F.
   Bouvier, J.
   Petit, P.
   Takami, M.
   Doyon, R.
   Cameron, A. Collier
TI A hot Jupiter orbiting a 2-million-year-old solar-mass T Tauri star
SO NATURE
LA English
DT Article
ID spectropolarimetric observations; differential rotation; magnetic-field; active stars; young suns; planet; system; disk; variability; evolution
AB Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star(1). It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks(2), or later, once multiple planets are formed and interact(3). Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars(4-6), whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planet-disk interactions(2).
C1 [Donati, J. F.; Baruteau, C.; Yu, L.; Petit, P.] Univ Toulouse, UPS OMP, IRAP, 14 Ave Belin, F-31400 Toulouse, France.
   [Donati, J. F.; Baruteau, C.; Yu, L.; Petit, P.] CNRS, IRAP, UMR 5277, 14 Ave Belin, F-31400 Toulouse, France.
   [Moutou, C.; Malo, L.] Canada France Hawaii Telescope CFHT Corp, 65-1238 Mamalahoa Highway, Kamuela, HI 96743 USA.
   [Hebrard, E.] York Univ, Dept Phys & Astron, Toronto, ON L3T 3R1, Canada.
   [Hussain, G.] ESO, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
   [Alencar, S.] Univ Fed Minas Gerais, Dept Fis, ICEx, Ave Antonio Carlos 6627, BR-30270901 Belo Horizonte, MG, Brazil.
   [Menard, F.; Bouvier, J.] Univ Grenoble Alpes, IPAG, BP 53, F-38041 Grenoble 09, France.
   [Menard, F.; Bouvier, J.] CNRS, IPAG, UMR 5274, BP 53, F-38041 Grenoble 09, France.
   [Takami, M.] Acad Sinica, Inst Astron & Astrophys, POB 23-141, Taipei 106, Taiwan.
   [Doyon, R.] Univ Montreal, Dept Phys, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
   [Cameron, A. Collier] Univ St Andrews, Sch Phys & Astron, SUPA, St Andrews KY16 9SS, Fife, Scotland.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Canada France Hawaii Telescope; York University - Canada; Universidade Federal de Minas Gerais; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Academia Sinica - Taiwan; Universite de Montreal; University of St Andrews
RP Donati, JF (corresponding author), Univ Toulouse, UPS OMP, IRAP, 14 Ave Belin, F-31400 Toulouse, France.; Donati, JF (corresponding author), CNRS, IRAP, UMR 5277, 14 Ave Belin, F-31400 Toulouse, France.
EM jean-francois.donati@irap.omp.eu
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (Fapemig); STFC [ST/M001296/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/M001296/1] Funding Source: researchfish
NR 36
TC 106
Z9 121
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 662
EP +
DI 10.1038/nature18305
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000031
PM 27324847
DA 2026-03-09
ER

PT J
AU Morales-Perez, CL
   Noviello, CM
   Hibbs, RE
AF Morales-Perez, Claudio L.
   Noviello, Colleen M.
   Hibbs, Ryan E.
TI X-ray structure of the human α4β2 nicotinic receptor
SO NATURE
LA English
DT Article
ID gated ion channels; acetylcholine-receptors; protein structures; crystal-structure; ligand; desensitization; permeation; mechanism; alignment; binding
AB Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century(1,2). In addition to the receptors' prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery(2-4). The overall architecture of the receptor was described in landmark studies of the nicotinic receptor isolated from the electric organ of Torpedo marmorata(5). Structures of a soluble ligand-binding domain have provided atomic-scale insights into receptor-ligand interactions(6), while high-resolution structures of other members of the pentameric receptor superfamily provide touchstones for an emerging allosteric gating mechanism(7). All available high-resolution structures are of homopentameric receptors. However, the vast majority of pentameric receptors (called Cys-loop receptors in eukaryotes) present physiologically are heteromeric. Here we present the X-ray crystallographic structure of the human alpha 4 beta 2 nicotinic receptor, the most abundant nicotinic subtype in the brain. This structure provides insights into the architectural principles governing ligand recognition, heteromer assembly, ion permeation and desensitization in this prototypical receptor class.
C1 [Morales-Perez, Claudio L.; Noviello, Colleen M.; Hibbs, Ryan E.] Univ Texas Southwestern Med Ctr, Dept Neurosci, Dallas, TX 75390 USA.
   [Morales-Perez, Claudio L.; Noviello, Colleen M.; Hibbs, Ryan E.] Univ Texas Southwestern Med Ctr, Dept Biophys, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Hibbs, RE (corresponding author), Univ Texas Southwestern Med Ctr, Dept Neurosci, Dallas, TX 75390 USA.; Hibbs, RE (corresponding author), Univ Texas Southwestern Med Ctr, Dept Biophys, Dallas, TX 75390 USA.
EM ryan.hibbs@utsouthwestern.edu
FU NIH [T32 NS069562, DA037492, DA042072, NS077983]; Howard Hughes Medical Institute; McKnight Scholar Award; Klingenstein-Simons Fellowship Award in the Neurosciences; Welch Foundation [I-1812]; Friends of the Alzheimer's Disease Center
NR 62
TC 337
Z9 375
U1 4
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 411
EP +
DI 10.1038/nature19785
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100045
PM 27698419
DA 2026-03-09
ER

PT J
AU Liu, XY
   Wang, CF
   Liu, WQ
   Li, JY
   Li, C
   Kou, XC
   Chen, JY
   Zhao, YH
   Gao, HB
   Wang, H
   Zhang, Y
   Gao, YW
   Gao, SR
AF Liu, Xiaoyu
   Wang, Chenfei
   Liu, Wenqiang
   Li, Jingyi
   Li, Chong
   Kou, Xiaochen
   Chen, Jiayu
   Zhao, Yanhong
   Gao, Haibo
   Wang, Hong
   Zhang, Yong
   Gao, Yawei
   Gao, Shaorong
TI Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos
SO NATURE
LA English
DT Article
ID dna methylation; mouse; pluripotent; polycomb; reveals; genes; marks; enhancer; state
AB Histone modifications have critical roles in regulating the expression of developmental genes during embryo development in mammals(1,2). However, genome-wide analyses of histone modifications in pre-implantation embryos have been impeded by the scarcity of the required materials. Here, by using a small-scale chromatin immunoprecipitation followed by sequencing (ChIP-seq) method(3), we map the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), which are associated with gene activation and repression4,5, respectively, in mouse pre-implantation embryos. We find that the re-establishment of H3K4me3, especially on promoter regions, occurs much more rapidly than that of H3K27me3 following fertilization, which is consistent with the major wave of zygotic genome activation at the two-cell stage. Furthermore, H3K4me3 and H3K27me3 possess distinct features of sequence preference and dynamics in preimplantation embryos. Although H3K4me3 modifications occur consistently at transcription start sites, the breadth of the H3K4me3 domain is a highly dynamic feature. Notably, the broad H3K4me3 domain (wider than 5 kb) is associated with higher transcription activity and cell identity not only in pre-implantation development but also in the process of deriving embryonic stem cells from the inner cell mass and trophoblast stem cells from the trophectoderm. Compared to embryonic stem cells, we found that the bivalency (that is, co-occurrence of H3K4me3 and H3K27me3) in early embryos is relatively infrequent and unstable. Taken together, our results provide a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, facilitating further exploration of the mechanism for epigenetic regulation in early embryos.
C1 [Liu, Xiaoyu; Wang, Chenfei; Liu, Wenqiang; Li, Jingyi; Li, Chong; Kou, Xiaochen; Chen, Jiayu; Zhao, Yanhong; Gao, Haibo; Wang, Hong; Zhang, Yong; Gao, Yawei; Gao, Shaorong] Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China.
   [Liu, Xiaoyu; Gao, Shaorong] Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China.
   [Liu, Xiaoyu; Gao, Haibo; Gao, Shaorong] NIBS, Beijing 102206, Peoples R China.
C3 Tongji University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; National Institute of Biological Sciences, Beijing
RP Zhang, Y; Gao, YW; Gao, SR (corresponding author), Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Life Sci & Technol, Clin & Translat Res Ctr,Shanghai Key Lab Signalin, Shanghai 200092, Peoples R China.; Gao, SR (corresponding author), Peking Union Med Coll, Grad Sch, Beijing 100730, Peoples R China.; Gao, SR (corresponding author), NIBS, Beijing 102206, Peoples R China.
EM yzhang@tongji.edu.cn; gaoyawei@tongji.edu.cn; gaoshaorong@tongji.edu.cn
FU National Natural Science Foundation of China [31325019, 31430056, 91319306, 31401266, 31501196, 31401247, 31501197, 31322031, 31371288, 31571365]; Ministry of Science and Technology of China [2015CB964503, 2016YFA0100400, 2015CB964800]; Science and Technology Commission of Shanghai Municipality [14CG16, 15XD1503500]; Major Program of Development Fund for Zhangjiang National Innovation Demonstration Zone [ZJ2014-ZD-002]
NR 44
TC 572
Z9 673
U1 7
U2 311
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 558
EP +
DI 10.1038/nature19362
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900058
PM 27626379
DA 2026-03-09
ER

PT J
AU Norris, JR
   Allen, RJ
   Evan, AT
   Zelinka, MD
   O'Dell, CW
   Klein, SA
AF Norris, Joel R.
   Allen, Robert J.
   Evan, Amato T.
   Zelinka, Mark D.
   O'Dell, Christopher W.
   Klein, Stephen A.
TI Evidence for climate change in the satellite cloud record
SO NATURE
LA English
DT Article
ID trends; isccp
AB Clouds substantially affect Earth's energy budget by reflecting solar radiation back to space and by restricting emission of thermal radiation to space(1). They are perhaps the largest uncertainty in our understanding of climate change, owing to disagreement among climate models and observational datasets over what cloud changes have occurred during recent decades and will occur in response to global warming(2,3). This is because observational systems originally designed for monitoring weather have lacked sufficient stability to detect cloud changes reliably over decades unless they have been corrected to remove artefacts(4,5). Here we show that several independent, empirically corrected satellite records exhibit large-scale patterns of cloud change between the 1980s and the 2000s that are similar to those produced by model simulations of climate with recent historical external radiative forcing. Observed and simulated cloud change patterns are consistent with poleward retreat of mid-latitude storm tracks, expansion of subtropical dry zones, and increasing height of the highest cloud tops at all latitudes. The primary drivers of these cloud changes appear to be increasing greenhouse gas concentrations and a recovery from volcanic radiative cooling. These results indicate that the cloud changes most consistently predicted by global climate models are currently occurring in nature.
C1 [Norris, Joel R.; Evan, Amato T.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Allen, Robert J.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Zelinka, Mark D.; Klein, Stephen A.] Lawrence Livermore Natl Lab, Program Climate Model Diag & Intercomparison, Livermore, CA USA.
   [O'Dell, Christopher W.] Colorado State Univ, Cooperat Inst Res Atmosphere, Ft Collins, CO 80523 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; University of California System; University of California Riverside; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Colorado State University System; Colorado State University Fort Collins
RP Norris, JR (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
EM jnorris@ucsd.edu
FU National Oceanic and Atmospheric Administration (NOAA) [NA10OAR4310140, NA10OAR4310141]; US Department of Energy (DOE), Office of Science, Office of Biological and Environmental Research through its Regional and Global Climate Modeling Program; DOE by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; National Aeronautics and Space Administration (NASA) New Investigator Program [NNH14AX83I]; NASA MEaSUREs Program [NNH12ZDA001N]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1455682] Funding Source: National Science Foundation
NR 35
TC 300
Z9 342
U1 9
U2 244
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 72
EP +
DI 10.1038/nature18273
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200032
PM 27398619
DA 2026-03-09
ER

PT J
AU Cheng, H
   Edwards, RL
   Sinha, A
   Spotl, C
   Yi, L
   Chen, ST
   Kelly, M
   Kathayat, G
   Wang, XF
   Li, XL
   Kong, XG
   Wang, YJ
   Ning, YF
   Zhang, HW
AF Cheng, Hai
   Edwards, R. Lawrence
   Sinha, Ashish
   Spotl, Christoph
   Yi, Liang
   Chen, Shitao
   Kelly, Megan
   Kathayat, Gayatri
   Wang, Xianfeng
   Li, Xianglei
   Kong, Xinggong
   Wang, Yongjin
   Ning, Youfeng
   Zhang, Haiwei
TI The Asian monsoon over the past 640,000 years and ice age terminations
SO NATURE
LA English
DT Article
ID millennial-scale; climate variability; high-resolution; ocean circulation; north-atlantic; glacial cycles; dongge cave; record; holocene; transitions
AB Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record's length and temporal precision allow us to test the idea that insolation changes caused by the Earth's precession drove the terminations of each of the last seven ice ages as well as the millennia-long intervals of reduced monsoon rainfall associated with each of the terminations. On the basis of our record's timing, the terminations are separated by four or five precession cycles, supporting the idea that the '100,000-year' ice age cycle is an average of discrete numbers of precession cycles. Furthermore, the suborbital component of monsoon rainfall variability exhibits power in both the precession and obliquity bands, and is nearly in anti-phase with summer boreal insolation. These observations indicate that insolation, in part, sets the pace of the occurrence of millennial-scale events, including those associated with terminations and 'unfinished terminations'.
C1 [Cheng, Hai; Kathayat, Gayatri; Li, Xianglei; Ning, Youfeng; Zhang, Haiwei] Xi An Jiao Tong Univ, Inst Global Environm Change, Xian 710049, Peoples R China.
   [Cheng, Hai; Edwards, R. Lawrence; Kelly, Megan] Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
   [Sinha, Ashish] Calif State Univ Dominguez Hills, Dept Earth Sci, Carson, CA 90747 USA.
   [Spotl, Christoph] Univ Innsbruck, Inst Geol, A-6020 Innsbruck, Austria.
   [Yi, Liang] Tongji Univ, State Key Lab Marine Geol, Shanghai 200092, Peoples R China.
   [Chen, Shitao; Kong, Xinggong; Wang, Yongjin] Nanjing Normal Univ, Coll Geog Sci, Nanjing 210023, Peoples R China.
   [Wang, Xianfeng] Nanyang Technol Univ, Earth Observ Singapore, Singapore 639798, Singapore.
C3 Xi'an Jiaotong University; University of Minnesota System; University of Minnesota Twin Cities; California State University System; California State University Dominguez Hills; University of Innsbruck; Tongji University; Nanjing Normal University; Nanyang Technological University
RP Cheng, H (corresponding author), Xi An Jiao Tong Univ, Inst Global Environm Change, Xian 710049, Peoples R China.; Cheng, H; Edwards, RL (corresponding author), Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
EM cheng021@mail.xjtu.edu.cn; edwar001@umn.edu
FU China grant NBRP [2013CB955902]; China grant NSFC [41230524, 4157020432, 41561144003]; US NSF [0502535, 1103404, 0823554, 1003690, 1137693, 1317693]; Singapore grant [NRF-NRFF2011-08]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0823554, 1003690] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1103403] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1337693] Funding Source: National Science Foundation
NR 61
TC 1337
Z9 1592
U1 41
U2 691
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 640
EP +
DI 10.1038/nature18591
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000027
PM 27357793
DA 2026-03-09
ER

PT J
AU Wu, S
   Tutuncuoglu, B
   Yan, KG
   Brown, H
   Zhang, YX
   Tan, D
   Gamalinda, M
   Yuan, Y
   Li, ZF
   Jakovljevic, J
   Ma, CY
   Lei, JL
   Dong, MQ
   Woolford, JL
   Gao, N
AF Wu, Shan
   Tutuncuoglu, Beril
   Yan, Kaige
   Brown, Hailey
   Zhang, Yixiao
   Tan, Dan
   Gamalinda, Michael
   Yuan, Yi
   Li, Zhifei
   Jakovljevic, Jelena
   Ma, Chengying
   Lei, Jianlin
   Dong, Meng-Qiu
   Woolford, John L., Jr.
   Gao, Ning
TI Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes
SO NATURE
LA English
DT Article
ID rna; biogenesis; maturation; association; subunit; complex; identification; initiation; resolution; refinement
AB Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm(1,2). Hundreds of assembly factors, organized into sequential functional groups(3,4), facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly.
C1 [Wu, Shan; Yan, Kaige; Zhang, Yixiao; Yuan, Yi; Li, Zhifei; Ma, Chengying; Lei, Jianlin; Gao, Ning] Tsinghua Univ, Sch Life Sci, Beijing Adv Innovat Ctr Struct Biol, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Tutuncuoglu, Beril; Brown, Hailey; Gamalinda, Michael; Jakovljevic, Jelena; Woolford, John L., Jr.] Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA.
   [Tan, Dan; Dong, Meng-Qiu] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China.
   [Tan, Dan; Dong, Meng-Qiu] Peking Union Med Coll, Beijing 100730, Peoples R China.
   [Tan, Dan; Dong, Meng-Qiu] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
C3 Tsinghua University; Carnegie Mellon University; Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; National Institute of Biological Sciences, Beijing
RP Gao, N (corresponding author), Tsinghua Univ, Sch Life Sci, Beijing Adv Innovat Ctr Struct Biol, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China.; Woolford, JL (corresponding author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA.
EM jw17@andrew.cmu.edu; ninggao@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2013CB910404, 2014CB849800]; National Natural Science Foundation of China [31422016, 31470722, 21375010]; National Institutes of Health [R01GM028301]; National Institute of General Medical Sciences [R01GM028301] Funding Source: NIH RePORTER
NR 60
TC 174
Z9 193
U1 1
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 133
EP +
DI 10.1038/nature17942
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300049
PM 27251291
DA 2026-03-09
ER

PT J
AU Zhu, YJ
   Wienecke, CFR
   Nachtrab, G
   Chen, XK
AF Zhu, Yingjie
   Wienecke, Carl F. R.
   Nachtrab, Gregory
   Chen, Xiaoke
TI A thalamic input to the nucleus accumbens mediates opiate dependence
SO NATURE
LA English
DT Article
ID synaptic adaptations; reward; transmission; motivation; withdrawal; receptors; behavior; morphine; amygdala; activation
AB Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use(1-3), and the nucleus accumbens is important for orchestrating both processes(4,5). While multiple inputs to the nucleus accumbens regulate reward(6-9), little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway-and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.
C1 [Zhu, Yingjie; Wienecke, Carl F. R.; Nachtrab, Gregory; Chen, Xiaoke] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
C3 Stanford University
RP Chen, XK (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM xkchen@stanford.edu
FU Whitehall Foundation; Ajinomoto innovation alliance program; Terman Scholarship; Stanford University; National Institute on Drug Abuse [5T32DA035165-02]; National Institute on Drug Abuse [T32DA035165] Funding Source: NIH RePORTER
NR 35
TC 323
Z9 391
U1 4
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 219
EP +
DI 10.1038/nature16954
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700039
PM 26840481
DA 2026-03-09
ER

PT J
AU Darby, SE
   Hackney, CR
   Leyland, J
   Kummu, M
   Lauri, H
   Parsons, DR
   Best, JL
   Nicholas, AP
   Aalto, R
AF Darby, Stephen E.
   Hackney, Christopher R.
   Leyland, Julian
   Kummu, Matti
   Lauri, Hannu
   Parsons, Daniel R.
   Best, James L.
   Nicholas, Andrew P.
   Aalto, Rolf
TI Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity
SO NATURE
LA English
DT Article
ID mekong river delta; climate-change; transport; erosion; impact; rainfall; variability; accretion; discharge; resource
AB The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually(1), with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping(2,3), and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being ` drowned' by rising relative sea levels(2-4). Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P < 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 +/- 10.2 megatonnes over recent years (1981-2005), of which 33.0 +/- 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past(5-7), and anticipating future(8,9), declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems.
C1 [Darby, Stephen E.; Hackney, Christopher R.; Leyland, Julian] Univ Southampton, Geog & Environm, Southampton SO17 1BJ, Hants, England.
   [Kummu, Matti] Aalto Univ, Water & Dev Res Grp, Espoo 02150, Finland.
   [Lauri, Hannu] EIA Finland Ltd, Sinimaentie 10B, Espoo 02630, Finland.
   [Parsons, Daniel R.] Univ Hull, Dept Geog Environm & Earth Sci, Kingston Upon Hull HU6 7RX, N Humberside, England.
   [Best, James L.] Univ Illinois, Dept Geol Geog & GIS, Mech Sci & Engn & Ven Te Chow Hydrosyst Lab, Champaign, IL 61820 USA.
   [Nicholas, Andrew P.; Aalto, Rolf] Univ Exeter, Dept Geog, Exeter EX4 4RJ, Devon, England.
C3 University of Southampton; Aalto University; University of Hull; University of Illinois System; University of Illinois Urbana-Champaign; University of Exeter
RP Darby, SE (corresponding author), Univ Southampton, Geog & Environm, Southampton SO17 1BJ, Hants, England.
EM S.E.Darby@soton.ac.uk
FU UK Natural Environmental Research Council (NERC) [NE/JO21970/1, NE/JO21571/1, NE/JO21881/1]; Academy of Finland [267463]; University of Southampton Diamond Jubilee Fellowship; National Great Rivers Research and Education Centre Fellowship; NERC [NE/J021571/1, NE/J021970/1, NE/J021881/1] Funding Source: UKRI; Natural Environment Research Council [NE/J021970/1, NE/J021571/1, NE/J021881/1] Funding Source: researchfish
NR 60
TC 211
Z9 244
U1 4
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 276
EP +
DI 10.1038/nature19809
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500042
PM 27760114
DA 2026-03-09
ER

PT J
AU Gizowski, C
   Zaelzer, C
   Bourque, CW
AF Gizowski, C.
   Zaelzer, C.
   Bourque, C. W.
TI Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep
SO NATURE
LA English
DT Article
ID vasculosum laminae terminalis; suprachiasmatic nucleus; circadian-rhythms; body-temperature; rat-brain; organization; drinking; water; stress
AB Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle(1). Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown(2-4). Here we show that the sleep period in mice (Zeitgeber time, ZT0-12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5-23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5-21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons.
C1 [Gizowski, C.; Zaelzer, C.; Bourque, C. W.] McGill Univ, Ctr Hlth, Ctr Res Neurosci, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada.
   [Gizowski, C.; Zaelzer, C.; Bourque, C. W.] McGill Univ, Ctr Hlth, Brain Repair & Integrat Neurosci Program, Res Inst, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada.
C3 McGill University; McGill University
RP Bourque, CW (corresponding author), McGill Univ, Ctr Hlth, Ctr Res Neurosci, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada.; Bourque, CW (corresponding author), McGill Univ, Ctr Hlth, Brain Repair & Integrat Neurosci Program, Res Inst, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada.
EM charles.bourque@mcgill.ca
FU Canadian Institutes of Health Research [FDN 143337]; James McGill Chair; Research Institute of the McGill University Health Centre (RIMUHC); Fonds de Recherche Quebec Sante
NR 34
TC 146
Z9 167
U1 2
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 685
EP +
DI 10.1038/nature19756
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700051
PM 27680940
DA 2026-03-09
ER

PT J
AU Rousseau, A
   Bertolotti, A
AF Rousseau, Adrien
   Bertolotti, Anne
TI An evolutionarily conserved pathway controls proteasome homeostasis
SO NATURE
LA English
DT Article
ID yeast saccharomyces-cerevisiae; activated protein-kinase; endoplasmic-reticulum; regulatory particle; assembly pathway; degradation; stress; chaperone; torc1; mtor
AB The proteasome is essential for the selective degradation of most cellular proteins, but how cells maintain adequate amounts of proteasome is unclear. Here we show that there is an evolutionarily conserved signalling pathway controlling proteasome homeostasis. Central to this pathway is TORC1, the inhibition of which induced all known yeast 19S regulatory particle assembly-chaperones (RACs), as well as proteasome subunits. Downstream of TORC1 inhibition, the yeast mitogen-activated protein kinase, Mpk1, acts to increase the supply of RACs and proteasome subunits under challenging conditions in order to maintain proteasomal degradation and cell viability. This adaptive pathway was evolutionarily conserved, with mTOR and ERK5 controlling the levels of the four mammalian RACs and proteasome abundance. Thus, the central growth and stress controllers, TORC1 and Mpk1/ERK5, endow cells with a rapid and vital adaptive response to adjust proteasome abundance in response to the rising needs of cells. Enhancing this pathway may be a useful therapeutic approach for diseases resulting from impaired proteasomal degradation.
C1 [Rousseau, Adrien; Bertolotti, Anne] MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Bertolotti, A (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
EM aberto@mrc-lmb.cam.ac.uk
FU Medical Research Council (UK) [MC_U105185860]; EMBO long-term fellowship; MRC [MC_U105185860] Funding Source: UKRI; Medical Research Council [MC_U105185860] Funding Source: researchfish
NR 41
TC 147
Z9 170
U1 1
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 184
EP +
DI 10.1038/nature18943
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100030
PM 27462806
DA 2026-03-09
ER

PT J
AU Lek, M
   Karczewski, KJ
   Minikel, EV
   Samocha, KE
   Banks, E
   Fennell, T
   O'Donnell-Luria, AH
   Ware, JS
   Hill, AJ
   Cummings, BB
   Tukiainen, T
   Birnbaum, DP
   Kosmicki, JA
   Duncan, LE
   Estrada, K
   Zhao, FM
   Zou, J
   Pierce-Hollman, E
   Berghout, J
   Cooper, DN
   Deflaux, N
   DePristo, M
   Do, R
   Flannick, J
   Fromer, M
   Gauthier, L
   Goldstein, J
   Gupta, N
   Howrigan, D
   Kiezun, A
   Kurki, MI
   Moonshine, AL
   Natarajan, P
   Orozeo, L
   Peloso, GM
   Poplin, R
   Rivas, MA
   Ruano-Rubio, V
   Rose, SA
   Ruderfer, DM
   Shakir, K
   Stenson, PD
   Stevens, C
   Thomas, BP
   Tiao, G
   Tusie-Luna, MT
   Weisburd, B
   Won, HH
   Yu, DM
   Altshuler, DM
   Ardissino, D
   Boehnke, M
   Danesh, J
   Donnelly, S
   Elosua, R
   Florez, JC
   Gabriel, SB
   Getz, G
   Glatt, SJ
   Hultman, CM
   Kathiresan, S
   Laakso, M
   NcCarroll, S
   McCarthy, MI
   McGovern, D
   McPherson, R
   Neale, BM
   Palotie, A
   Purcell, SM
   Saleheen, D
   Scharf, JM
   Sklar, P
   Sullivan, PF
   Tuomilehto, J
   Tsuang, MT
   Watkins, HC
   Wilson, JG
   Daly, MJ
   MacArthur, DG
AF Lek, Monkol
   Karczewski, Konrad J.
   Minikel, Eric V.
   Samocha, Kaitlin E.
   Banks, Eric
   Fennell, Timothy
   O'Donnell-Luria, Anne H.
   Ware, James S.
   Hill, Andrew J.
   Cummings, Beryl B.
   Tukiainen, Taru
   Birnbaum, Daniel P.
   Kosmicki, Jack A.
   Duncan, Laramie E.
   Estrada, Karol
   Zhao, Fengmei
   Zou, James
   Pierce-Hollman, Emma
   Berghout, Joanne
   Cooper, David N.
   Deflaux, Nicole
   DePristo, Mark
   Do, Ron
   Flannick, Jason
   Fromer, Menachem
   Gauthier, Laura
   Goldstein, Jackie
   Gupta, Namrata
   Howrigan, Daniel
   Kiezun, Adam
   Kurki, Mitja I.
   Moonshine, Ami Levy
   Natarajan, Pradeep
   Orozeo, Lorena
   Peloso, Gina M.
   Poplin, Ryan
   Rivas, Manuel A.
   Ruano-Rubio, Valentin
   Rose, Samuel A.
   Ruderfer, Douglas M.
   Shakir, Khalid
   Stenson, Peter D.
   Stevens, Christine
   Thomas, Brett P.
   Tiao, Grace
   Tusie-Luna, Maria T.
   Weisburd, Ben
   Won, Hong-Hee
   Yu, Dongmei
   Altshuler, David M.
   Ardissino, Diego
   Boehnke, Michael
   Danesh, John
   Donnelly, Stacey
   Elosua, Roberto
   Florez, Jose C.
   Gabriel, Stacey B.
   Getz, Gad
   Glatt, Stephen J.
   Hultman, Christina M.
   Kathiresan, Sekar
   Laakso, Markku
   NcCarroll, Steven
   McCarthy, Mark I.
   McGovern, Dermot
   McPherson, Ruth
   Neale, Benjamin M.
   Palotie, Aarno
   Purcell, Shaun M.
   Saleheen, Danish
   Scharf, Jeremiah M.
   Sklar, Pamela
   Sullivan, Patrick F.
   Tuomilehto, Jaakko
   Tsuang, Ming T.
   Watkins, Hugh C.
   Wilson, James G.
   Daly, Mark J.
   MacArthur, Daniel G.
TI Analysis of protein-coding genetic variation in 60,706 humans
SO NATURE
LA English
DT Article
ID human-population history; sequence variants; mutation; guidelines; evolution; framework
AB Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
C1 [Lek, Monkol; Karczewski, Konrad J.; Minikel, Eric V.; Samocha, Kaitlin E.; O'Donnell-Luria, Anne H.; Hill, Andrew J.; Cummings, Beryl B.; Tukiainen, Taru; Kosmicki, Jack A.; Duncan, Laramie E.; Estrada, Karol; Pierce-Hollman, Emma; Fromer, Menachem; Goldstein, Jackie; Howrigan, Daniel; Thomas, Brett P.; Neale, Benjamin M.; Palotie, Aarno; Daly, Mark J.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Lek, Monkol; Karczewski, Konrad J.; Minikel, Eric V.; Samocha, Kaitlin E.; Banks, Eric; O'Donnell-Luria, Anne H.; Ware, James S.; Hill, Andrew J.; Cummings, Beryl B.; Tukiainen, Taru; Birnbaum, Daniel P.; Kosmicki, Jack A.; Duncan, Laramie E.; Estrada, Karol; Zou, James; Pierce-Hollman, Emma; Flannick, Jason; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kurki, Mitja I.; Natarajan, Pradeep; Peloso, Gina M.; Rivas, Manuel A.; Stevens, Christine; Thomas, Brett P.; Weisburd, Ben; Altshuler, David M.; Donnelly, Stacey; Florez, Jose C.; Gabriel, Stacey B.; Kathiresan, Sekar; Neale, Benjamin M.; Palotie, Aarno; Scharf, Jeremiah M.; Daly, Mark J.; MacArthur, Daniel G.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Lek, Monkol] Univ Sydney, Sch Paediat & Child Hlth, Sydney, NSW 2145, Australia.
   [Lek, Monkol] Childrens Hosp VVestmead, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.
   [Minikel, Eric V.; Samocha, Kaitlin E.; Cummings, Beryl B.; Palotie, Aarno] Harvard Med Sch, Program Biol & Biomed Sci, Boston, MA 02115 USA.
   [Samocha, Kaitlin E.; Kosmicki, Jack A.; Duncan, Laramie E.; Fromer, Menachem; Goldstein, Jackie; Howrigan, Daniel; Rose, Samuel A.; Yu, Dongmei; NcCarroll, Steven; Neale, Benjamin M.; Scharf, Jeremiah M.; Daly, Mark J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [O'Donnell-Luria, Anne H.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA.
   [Ware, James S.; NcCarroll, Steven] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
   [Ware, James S.] Imperial Coll London, Natl Heart & Lung Inst, London SW7 2AZ, England.
   [Ware, James S.] Royal Brompton Hosp, NIHR Royal Brompton Cardiovasc Biomed Res Unit, London SW3 6NP, England.
   [Ware, James S.] Imperial Coll London, MRC Clin Sci Ctr, London SW7 2AZ, England.
   [Hill, Andrew J.; Zhao, Fengmei] Univ Washington, Genome Sci, Seattle, WA 98195 USA.
   [Kosmicki, Jack A.] Harvard Med Sch, Program Bioinformat & Integrat Genom, Boston, MA 02115 USA.
   [Berghout, Joanne] Jackson Lab, Mouse Genome Informat, 600 Main St, Bar Harbor, ME 04609 USA.
   [Berghout, Joanne] Univ Arizona, Ctr Biomed Informat & Biostat, Tucson, AZ 85721 USA.
   [Cooper, David N.; Stenson, Peter D.] Cardiff Univ, Inst Med Genet, Cardiff CF10 3XQ, S Glam, Wales.
   [Deflaux, Nicole] Google, Mountain View, CA 94043 USA.
   [DePristo, Mark; Gauthier, Laura; Kiezun, Adam; Moonshine, Ami Levy; Poplin, Ryan; Ruano-Rubio, Valentin; Shakir, Khalid; Tiao, Grace; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Do, Ron; Fromer, Menachem; Ruderfer, Douglas M.; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Fennell, Timothy; Do, Ron; Fromer, Menachem; Ruderfer, Douglas M.; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
   [Do, Ron] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
   [Do, Ron] Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY 10029 USA.
   [Flannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Fromer, Menachem; Ruderfer, Douglas M.; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
   [Kurki, Mitja I.; Yu, Dongmei; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
   [Natarajan, Pradeep; Florez, Jose C.; Getz, Gad; Kathiresan, Sekar] Harvard Med Sch, Boston, MA 02115 USA.
   [Natarajan, Pradeep; Peloso, Gina M.; Yu, Dongmei; Florez, Jose C.; Kathiresan, Sekar; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Natarajan, Pradeep; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Orozeo, Lorena] Inst Nacl Med Genom, Immunogen & Metab Dis Lab, Mexico City 14610, DF, Mexico.
   [Tusie-Luna, Maria T.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mol Biol & Genom Med Unit, Mexico City 14080, DF, Mexico.
   [Won, Hong-Hee] Sungkyunkwan Univ, Samsung Med Ctr, Samsung Adv Inst Hlth Sci & Technol SAIHST, Seoul, South Korea.
   [Yu, Dongmei; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   [Altshuler, David M.] Vertex Pharmaceut, Boston, MA 02210 USA.
   [Ardissino, Diego] Univ Hosp, Dept Cardiol, I-43100 Parma, Italy.
   [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Danesh, John] Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
   [Elosua, Roberto] Hosp Mar Med Res Inst, Cardiovasc Epidemiol & Genet, Barcelona 08003, Spain.
   [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Glatt, Stephen J.] SUNY Upstate Med Univ, Psychiat Genet Epidemiol & Neurobiol Lab, Syracuse, NY 13210 USA.
   [Glatt, Stephen J.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA.
   [Glatt, Stephen J.] SUNY Upstate Med Univ, Dept Neurobiol & Physiol, Syracuse, NY 13210 USA.
   [Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70211, Finland.
   [Laakso, Markku] Kuopio Univ Hosp, Kuopio 70211, Finland.
   [McCarthy, Mark I.; Watkins, Hugh C.] Univ Oxford, Wellcome Trust Ctr Human Genet, S Parks Rd, Oxford OX1 2JD, England.
   [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, S Parks Rd, Oxford OX1 2JD, England.
   [McCarthy, Mark I.] Oxford Univ Hosp Fdn Trust, Oxford NIHR Biomed Res Ctr, Oxford OX1 2JD, England.
   [McGovern, Dermot] Cedars Sinai Med Ctr, Inflammatory Bowel Dis & Immunobiol Res Inst, Los Angeles, CA 90048 USA.
   [McPherson, Ruth] Univ Ottawa, Atherogen Lab, Inst Heart, Ottawa, ON K1Y 4W7, Canada.
   [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, SF-00100 Helsinki, Finland.
   [Saleheen, Danish] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Saleheen, Danish] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
   [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
   [Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
   [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, SF-00100 Helsinki, Finland.
   [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   [Watkins, Hugh C.] Univ Oxford, Racicliffe Dept Med, S Parks Rd, Oxford OX1 2JD, England.
   [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Sydney; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Imperial College London; Royal Brompton Hospital; Imperial College London; University of Washington; University of Washington Seattle; Harvard University; Harvard Medical School; Jackson Laboratory; University of Arizona; Cardiff University; Alphabet Inc.; Google Incorporated; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Instituto Nacional de Medicina Genomica; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran - Mexico; Samsung; Sungkyunkwan University (SKKU); Samsung Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Vertex Pharmaceuticals; University of Parma; University Hospital of Parma; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Hospital del Mar Research Institute; Hospital del Mar; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; State University of New York (SUNY) System; SUNY Upstate Medical University; State University of New York (SUNY) System; SUNY Upstate Medical University; State University of New York (SUNY) System; SUNY Upstate Medical University; Karolinska Institutet; University of Eastern Finland; University of Eastern Finland; University of Eastern Finland Hospital; Kuopio University Hospital; University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; Oxford University Hospitals NHS Foundation Trust; University of Oxford; Cedars Sinai Medical Center; University of Ottawa; University of Ottawa Heart Institute; University of Helsinki; University of Pennsylvania; University of Pennsylvania; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of North Carolina; University of North Carolina Chapel Hill; Karolinska Institutet; University of Helsinki; University of California System; University of California San Diego; University of Oxford; University of Mississippi; University of Mississippi Medical Center
RP MacArthur, DG (corresponding author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM danmac@broadinstitute.org
FU MRC [G0601261, G0800509, MC_UP_1102/20, G0801418, MR/L003120/1] Funding Source: UKRI; British Heart Foundation [FS/14/55/30806, RG/13/13/30194] Funding Source: researchfish; Medical Research Council [G0800509, MR/L003120/1, G0801418, G0601261, MC_UP_1102/20, MR/L010305/1] Funding Source: researchfish; National Institute for Health Research [NF-SI-0514-10027, NF-SI-0611-10219, NF-SI-0507-10228, NF-SI-0611-10099, NF-SI-0513-10087] Funding Source: researchfish; Wellcome Trust [107469/Z/15/Z] Funding Source: researchfish; National Heart Lung and Blood Institute [T32HL007208] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020572, P30DK043351, U01DK062370, R01DK062370] Funding Source: NIH RePORTER; National Institute on Aging [P30AG038072] Funding Source: NIH RePORTER; British Heart Foundation [RG/13/13/30194, FS/14/55/30806] Funding Source: Medline; CIHR [MOP77682, MOP136936, MOP82810] Funding Source: Medline; Medical Research Council [G0800509, G0801418, MC_UP_1102/20, G0601261, MR/L003120/1] Funding Source: Medline; NHGRI NIH HHS [U41 HG000330, 5U54HG003067-11, U54HG003067, 5 U54 HG003067-13] Funding Source: Medline; NHLBI NIH HHS [HHSN268201300046C, T32 HL007208, HHSN268201300048C, R01HL107816, R01HL24799, HHSN268201300049C, K01HL125751, K01 HL125751, HHSN268201300047C, HHSN268201300050C] Funding Source: Medline; NIA NIH HHS [P30 AG038072] Funding Source: Medline; NIDDK NIH HHS [U01DK085526, P30 DK043351, RC2F DK088389, DK088389, U01 DK085501, R01 DK098032, DK085545, U01 DK062370, U01-DK085545, R01DK098032, 1RC2DK088389, U01 DK085545, P30 DK020572, RC2-DK088389, R01DK062370, U01 DK085526, DK098032, U01 DK085584, U01 DK085524, RC2DK088389, U54 DK105566] Funding Source: Medline; NIGMS NIH HHS [F32GM115208, R01 GM104371] Funding Source: Medline; NIMH NIH HHS [MH089905, R01MH085521, MH095034, MH077139, MH094421, 2P50MH066392-05A1, R01 MH077139, R01MH085560, U01 MH094432] Funding Source: Medline; NINDS NIH HHS [NS40024-09S1, U01 NS40024-09S1, NS085048, U01 NS040024, K02 NS085048] Funding Source: Medline; PHS HHS [NIMHRC2MH089905] Funding Source: Medline; Wellcome Trust [098381, 090532, 090367] Funding Source: Medline
NR 40
TC 7708
Z9 8572
U1 6
U2 486
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 285
EP +
DI 10.1038/nature19057
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900026
PM 27535533
DA 2026-03-09
ER

PT J
AU Kriek, M
   Conroy, C
   van Dokkum, PG
   Shapley, AE
   Choi, J
   Reddy, NA
   Siana, B
   van de Voort, F
   Coil, AL
   Mobasher, B
AF Kriek, Mariska
   Conroy, Charlie
   van Dokkum, Pieter G.
   Shapley, Alice E.
   Choi, Jieun
   Reddy, Naveen A.
   Siana, Brian
   van de Voort, Freeke
   Coil, Alison L.
   Mobasher, Bahram
TI A massive, quiescent, population II galaxy at a redshift of 2.1
SO NATURE
LA English
DT Article
ID absorption-line spectroscopy; element abundance ratios; stellar populations; ia supernovae; evolution; models; growth; uncertainty; metallicity; propagation
AB Unlike spiral galaxies such as the Milky Way, the majority of the stars in massive elliptical galaxies were formed in a short period early in the history of the Universe. The duration of this formation period can be measured using the ratio of magnesium to iron abundance ([Mg/Fe]) in spectra(1-4), which reflects the relative enrichment by core-collapse and type Ia supernovae. For local galaxies, [Mg/Fe] probes the combined formation history of all stars currently in the galaxy, including younger and metal-poor stars that were added during late-time mergers. Therefore, to directly constrain the initial star-formation period, we must study galaxies at earlier epochs. The most distant galaxy for which [Mg/Fe] had previously been measured(6) is at a redshift of z approximate to 1.4, with [Mg/Fe] = 0.45(-0.19)(+0.05) A slightly earlier epoch (z approximate to 1.6) was probed by combining the spectra of 24 massive quiescent galaxies, yielding an average [Mg/Fe] = 0.31 +/- 0.12 (ref. 7). However, the relatively low signal-tonoise ratio of the data and the use of index analysis techniques for both of these studies resulted in measurement errors that are too large to allow us to form strong conclusions. Deeper spectra at even earlier epochs in combination with analysis techniques based on full spectral fitting are required to precisely measure the abundance pattern shortly after the major star-forming phase (z > 2). Here we report a measurement of [Mg/Fe] for a massive quiescent galaxy at a redshift of z= 2.1, when the Universe was three billion years old. With [Mg/Fe] = 0.59 +/- 0.11, this galaxy is the most Mg-enhanced massive galaxy found so far, having twice the Mg enhancement of similar -mass galaxies today. The abundance pattern of the galaxy is consistent with enrichment exclusively by core-collapse supernovae and with a star -formation timescale of 0.1 to 0.5 billion years-characteristics that are similar to population II stars in the Milky Way. With an average past star -formation rate of 600 to 3,000 solar masses per year, this galaxy was among the most vigorous star forming galaxies in the Universe.
C1 [Kriek, Mariska; van de Voort, Freeke] Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
   [Conroy, Charlie; Choi, Jieun] Harvard Univ, Dept Astron, Cambridge, MA 02138 USA.
   [van Dokkum, Pieter G.] Yale Univ, Dept Astron, New Haven, CT 06511 USA.
   [Shapley, Alice E.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Reddy, Naveen A.; Siana, Brian; Mobasher, Bahram] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA.
   [Coil, Alison L.] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California Berkeley; Harvard University; Yale University; University of California System; University of California Los Angeles; University of California System; University of California Riverside; University of California System; University of California San Diego
RP Kriek, M (corresponding author), Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
EM mkriek@berkeley.edu
FU W. M. Keck Foundation; NSF MG collaborative grants [AST-1312780, 1312547, 1312764, 1313171]; NASA through Space Telescope Science Institute [AR-13907]; NASA [NNX13AI46G]; NSF [AST-1313280]; Packard Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1524161, 1313171] Funding Source: National Science Foundation
NR 40
TC 96
Z9 107
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 248
EP +
DI 10.1038/nature20570
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700052
PM 27929014
DA 2026-03-09
ER

PT J
AU Bozovic, I
   He, X
   Wu, J
   Bollinger, AT
AF Bozovic, I.
   He, X.
   Wu, J.
   Bollinger, A. T.
TI Dependence of the critical temperature in overdoped copper oxides on superfluid density
SO NATURE
LA English
DT Article
ID magnetic penetration depth; muon-spin-rotation; mutual inductance; interface superconductivity; field penetration; 2-coil apparatus; la2-xsrxcuo4; transition; insulator; films
AB The physics of underdoped copper oxide superconductors, including the pseudogap, spin and charge ordering and their relation to superconductivity(1-3), is intensely debated. The overdoped copper oxides are perceived as simpler, with strongly correlated fermion physics evolving smoothly into the conventional Bardeen-Cooper-Schrieffer behaviour. Pioneering studies on a few overdoped samples(4-11) indicated that the superfluid density was much lower than expected, but this was attributed to pair-breaking, disorder and phase separation. Here we report the way in which the magnetic penetration depth and the phase stiffness depend on temperature and doping by investigating the entire overdoped side of the La2-xSrxCuO4 phase diagram. We measured the absolute values of the magnetic penetration depth and the phase stiffness to an accuracy of one per cent in thousands of samples; the large statistics reveal clear trends and intrinsic properties. The films are homogeneous; variations in the critical superconducting temperature within a film are very small (less than one kelvin). At every level of doping the phase stiffness decreases linearly with temperature. The dependence of the zero-temperature phase stiffness on the critical superconducting temperature is generally linear, but with an offset; however, close to the origin this dependence becomes parabolic. This scaling law is incompatible with the standard Bardeen-Cooper-Schrieffer description.
C1 [Bozovic, I.; He, X.; Wu, J.; Bollinger, A. T.] Brookhaven Natl Lab, Upton, NY 11973 USA.
   [Bozovic, I.; He, X.] Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory; Yale University
RP Bozovic, I (corresponding author), Brookhaven Natl Lab, Upton, NY 11973 USA.; Bozovic, I (corresponding author), Yale Univ, Dept Appl Phys, New Haven, CT 06520 USA.
EM bozovic@bnl.gov
FU US Department of Energy, Basic Energy Sciences, Materials Sciences and Engineering Division; Gordon and Betty Moore Foundation's EPiQS Initiative [GBMF4410]
NR 60
TC 300
Z9 339
U1 12
U2 296
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 309
EP +
DI 10.1038/nature19061
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900030
PM 27535534
DA 2026-03-09
ER

PT J
AU Backus, KM
   Correia, BE
   Lum, KM
   Forli, S
   Horning, BD
   González-Páez, GE
   Chatterjee, S
   Lanning, BR
   Teijaro, JR
   Olson, AJ
   Wolan, DW
   Cravatt, BF
AF Backus, Keriann M.
   Correia, Bruno E.
   Lum, Kenneth M.
   Forli, Stefano
   Horning, Benjamin D.
   Gonzalez-Paez, Gonzalo E.
   Chatterjee, Sandip
   Lanning, Bryan R.
   Teijaro, John R.
   Olson, Arthur J.
   Wolan, Dennis W.
   Cravatt, Benjamin F.
TI Proteome-wide covalent ligand discovery in native biological systems
SO NATURE
LA English
DT Article
ID inhibitors; site; selectivity; design; death
AB Small molecules are powerful tools for investigating protein function and can serve as leads for new therapeutics. Most human proteins, however, lack small-molecule ligands, and entire protein classes are considered 'undruggable'(1,2). Fragment-based ligand discovery can identify small-molecule probes for proteins that have proven difficult to target using high-throughput screening of complex compound libraries(1,3). Although reversibly binding ligands are commonly pursued, covalent fragments provide an alternative route to small-molecule probes(4-10), including those that can access regions of proteins that are difficult to target through binding affinity alone(5,10,11). Here we report a quantitative analysis of cysteine-reactive small-molecule fragments screened against thousands of proteins in human proteomes and cells. Covalent ligands were identified for >700 cysteines found in both druggable proteins and proteins deficient in chemical probes, including transcription factors, adaptor/scaffolding proteins, and uncharacterized proteins. Among the atypical ligand-protein interactions discovered were compounds that react preferentially with pro-(inactive) caspases. We used these ligands to distinguish extrinsic apoptosis pathways in human cell lines versus primary human T cells, showing that the former is largely mediated by caspase-8 while the latter depends on both caspase-8 and -10. Fragment-based covalent ligand discovery provides a greatly expanded portrait of the ligandable proteome and furnishes compounds that can illuminate protein functions in native biological systems.
C1 [Backus, Keriann M.; Correia, Bruno E.; Lum, Kenneth M.; Horning, Benjamin D.; Lanning, Bryan R.; Cravatt, Benjamin F.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92307 USA.
   [Forli, Stefano; Olson, Arthur J.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92307 USA.
   [Gonzalez-Paez, Gonzalo E.; Chatterjee, Sandip; Wolan, Dennis W.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92307 USA.
   [Teijaro, John R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92307 USA.
C3 Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute
RP Backus, KM; Cravatt, BF (corresponding author), Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92307 USA.
EM kbackus@scripps.edu; cravatt@scripps.edu
FU National Institutes of Health [CA087660, GM090294, GM108208, GM069832]; National Institute of General Medical Sciences [R01GM069832] Funding Source: NIH RePORTER
NR 43
TC 717
Z9 874
U1 8
U2 339
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 570
EP +
DI 10.1038/nature18002
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300058
PM 27309814
DA 2026-03-09
ER

PT J
AU Dong, X
   Milholland, B
   Vijg, J
AF Dong, Xiao
   Milholland, Brandon
   Vijg, Jan
TI Evidence for a limit to human lifespan
SO NATURE
LA English
DT Article
ID longevity
AB Driven by technological progress, human life expectancy has increased greatly since the nineteenth century. Demographic evidence has revealed an ongoing reduction in old-age mortality and a rise of the maximum age at death, which may gradually extend human longevity(1,2). Together with observations that lifespan in various animal species is flexible and can be increased by genetic or pharmaceutical intervention, these results have led to suggestions that longevity may not be subject to strict, species-specific genetic constraints. Here, by analysing global demographic data, we show that improvements in survival with age tend to decline after age 100, and that the age at death of the world's oldest person has not increased since the 1990s. Our results strongly suggest that the maximum lifespan of humans is fixed and subject to natural constraints.
C1 [Dong, Xiao; Milholland, Brandon; Vijg, Jan] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.
   [Vijg, Jan] Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10461 USA.
C3 Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Vijg, J (corresponding author), Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.; Vijg, J (corresponding author), Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10461 USA.
EM jan.vijg@einstein.yu.edu
FU NIH [AG017242, AG047200]; Albert Einstein College of Medicine Institute for Aging Research/Nathan Shock Center; Paul F. Glenn Center for the Biology of Human Aging at the Albert Einstein College of Medicine; National Institute on Aging [P01AG017242] Funding Source: NIH RePORTER
NR 15
TC 280
Z9 346
U1 2
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 257
EP +
DI 10.1038/nature19793
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EY9BX
UT WOS:000404295200001
PM 27706136
DA 2026-03-09
ER

PT J
AU Li, J
   Song, J
   Zaytseva, YY
   Liu, YJ
   Rychahou, P
   Jiang, K
   Starr, ME
   Kim, JT
   Harris, JW
   Yiannikouris, FB
   Katz, WS
   Nilsson, PM
   Orho-Melander, M
   Chen, J
   Zhu, HN
   Fahrenholz, T
   Higashi, RM
   Gao, TY
   Morris, AJ
   Cassis, LA
   Fan, TWM
   Weiss, HL
   Dobner, PR
   Melander, O
   Jia, JH
   Evers, BM
AF Li, Jing
   Song, Jun
   Zaytseva, Yekaterina Y.
   Liu, Yajuan
   Rychahou, Piotr
   Jiang, Kai
   Starr, Marlene E.
   Kim, Ji Tae
   Harris, Jennifer W.
   Yiannikouris, Frederique B.
   Katz, Wendy S.
   Nilsson, Peter M.
   Orho-Melander, Marju
   Chen, Jing
   Zhu, Haining
   Fahrenholz, Timothy
   Higashi, Richard M.
   Gao, Tianyan
   Morris, Andrew J.
   Cassis, Lisa A.
   Fan, Teresa W. -M.
   Weiss, Heidi L.
   Dobner, Paul R.
   Melander, Olle
   Jia, Jianhang
   Evers, B. Mark
TI An obligatory role for neurotensin in high-fat-diet-induced obesity
SO NATURE
LA English
DT Article
ID striatal fos expression; food-intake; enteroendocrine cells; gene-expression; drosophila; secretion; pathway; homeostasis; midgut; cancer
AB Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually(1) and are among the most prevalent and challenging conditions confronting the medical profession(2,3). Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine(4) and released by fat ingestion(5), facilitates fatty acid translocation in rat intestine(6), and stimulates the growth of various cancers(7). The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively)(8). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality(9); however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.
C1 [Li, Jing; Song, Jun; Rychahou, Piotr; Starr, Marlene E.; Kim, Ji Tae; Harris, Jennifer W.; Evers, B. Mark] Univ Kentucky, Dept Surg, Lexington, KY 40536 USA.
   [Li, Jing; Song, Jun; Zaytseva, Yekaterina Y.; Liu, Yajuan; Rychahou, Piotr; Jiang, Kai; Kim, Ji Tae; Harris, Jennifer W.; Fahrenholz, Timothy; Higashi, Richard M.; Gao, Tianyan; Fan, Teresa W. -M.; Weiss, Heidi L.; Jia, Jianhang; Evers, B. Mark] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA.
   [Zaytseva, Yekaterina Y.; Fahrenholz, Timothy; Higashi, Richard M.; Fan, Teresa W. -M.] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY 40536 USA.
   [Yiannikouris, Frederique B.; Katz, Wendy S.; Cassis, Lisa A.] Univ Kentucky, Dept Pharmacol & Nutr Sci, Lexington, KY 40536 USA.
   [Nilsson, Peter M.; Orho-Melander, Marju; Melander, Olle] Lund Univ, Dept Clin Sci, S-22100 Lund, Sweden.
   [Nilsson, Peter M.; Melander, Olle] Skane Univ Hosp, Dept Internal Med, S-20502 Malmo, Sweden.
   [Chen, Jing; Zhu, Haining; Gao, Tianyan; Jia, Jianhang] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
   [Chen, Jing; Zhu, Haining] Univ Kentucky, Struct Biol Ctr, Lexington, KY 40536 USA.
   [Fahrenholz, Timothy; Higashi, Richard M.; Fan, Teresa W. -M.] Univ Kentucky, Ctr Environm & Syst Biochem, Lexington, KY 40536 USA.
   [Morris, Andrew J.] Univ Kentucky, Gill Heart Inst, Div Cardiovasc Med, Lexington, KY 40536 USA.
   [Morris, Andrew J.] Lexington Vet Affairs Med Ctr, Lexington, KY 40536 USA.
   [Weiss, Heidi L.] Univ Kentucky, Dept Biostat, Lexington, KY 40536 USA.
   [Dobner, Paul R.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA.
C3 University of Kentucky; University of Kentucky; University of Kentucky; University of Kentucky; Lund University; Lund University; Skane University Hospital; University of Kentucky; University of Kentucky; University of Kentucky; University of Kentucky; US Department of Veterans Affairs; Veterans Health Administration (VHA); Lexington VA Medical Center; University of Kentucky; University of Massachusetts System; University of Massachusetts Worcester
RP Evers, BM (corresponding author), Univ Kentucky, Dept Surg, Lexington, KY 40536 USA.; Evers, BM (corresponding author), Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA.
EM mark.evers@uky.edu
FU National Cancer Institute [P30 CA177558]; National Institutes of Health (NIH) [R37 AG10885, R01 DK048498, R01 GM079684, U24 DK097215, R01 ES022191, P01 CA163223, P20 GM103527, R01 HL120507, RO1 NS077284, R01 HL073085]; Swedish National Research Council; Swedish Heart-Lung Foundation; Novo Nordisk Foundation; Swedish Diabetes Association; Region Skane, ALF; European Research Council [StG-2011-282255]; Markey Cancer Foundation; NIH [T32 CA165990, T32 CA160003]; National Center for Research Resources [S10 RR029127]; National Cancer Institute [P30CA177558, T32CA165990, T32CA160003] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK048498] Funding Source: NIH RePORTER; Novo Nordisk Fonden [NNF16OC0021370, NNF15OC0016320, NNF14OC0011049] Funding Source: researchfish
NR 64
TC 212
Z9 251
U1 4
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 411
EP +
DI 10.1038/nature17662
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300052
PM 27193687
DA 2026-03-09
ER

PT J
AU Jeschek, M
   Reuter, R
   Heinisch, T
   Trindler, C
   Klehr, J
   Panke, S
   Ward, TR
AF Jeschek, Markus
   Reuter, Raphael
   Heinisch, Tillmann
   Trindler, Christian
   Klehr, Juliane
   Panke, Sven
   Ward, Thomas R.
TI Directed evolution of artificial metalloenzymes for in vivo metathesis
SO NATURE
LA English
DT Article
ID olefin-metathesis; protein; streptavidin; catalysts; enzymes; avidin
AB The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions(1). Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions(2,3). For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist(3): repurposing natural metalloenzymes for abiotic transformations(2,4); in silico metalloenzyme (re-)design(5-7); and incorporation of abiotic cofactors into proteins(8-11). The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein(12-15). This limits the throughput of genetic optimization schemes applied to artificial metalloenzymes and their applicability in vivo to expand natural metabolism. Here we report the compartmentalization and in vivo evolution of an artificial metalloenzyme for olefin metathesis, which represents an archetypal organometallic reaction(16-22) without equivalent in nature. Building on previous work(6) on an artificial metallohydrolase, we exploit the periplasm of Escherichia coli as a reaction compartment for the 'metathase' because it offers an auspicious environment for artificial metalloenzymes, mainly owing to low concentrations of inhibitors such as glutathione, which has recently been identified as a major inhibitor(15). This strategy facilitated the assembly of a functional metathase in vivo and its directed evolution with substantially increased throughput compared to conventional approaches that rely on purified protein variants. The evolved metathase compares favourably with commercial catalysts, shows activity for different metathesis substrates and can be further evolved in different directions by adjusting the workflow. Our results represent the systematic implementation and evolution of an artificial metalloenzyme that catalyses an abiotic reaction in vivo, with potential applications in, for example, non-natural metabolism.
C1 [Jeschek, Markus; Panke, Sven] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
   [Reuter, Raphael; Heinisch, Tillmann; Trindler, Christian; Klehr, Juliane; Ward, Thomas R.] Univ Basel, Dept Chem, CH-4056 Basel, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Basel
RP Panke, S (corresponding author), Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.; Ward, TR (corresponding author), Univ Basel, Dept Chem, CH-4056 Basel, Switzerland.
EM sven.panke@bsse.ethz.ch; thomas.ward@unibas.ch
FU European Commission [289572-METACODE]; Swiss National Science Foundation as part of the NCCR Molecular Systems Engineering
NR 41
TC 374
Z9 417
U1 15
U2 432
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 661
EP +
DI 10.1038/nature19114
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700046
PM 27571282
DA 2026-03-09
ER

PT J
AU DeConto, RM
   Pollard, D
AF DeConto, Robert M.
   Pollard, David
TI Contribution of Antarctica to past and future sea-level rise
SO NATURE
LA English
DT Article
ID greenland ice-sheet; west antarctica; outlet glaciers; atmospheric co2; pine island; model; collapse; ocean; driven; pleistocene
AB Polar temperatures over the last several million years have, at times, been slightly warmer than today, yet global mean sea level has been 6-9 metres higher as recently as the Last Interglacial (130,000 to 115,000 years ago) and possibly higher during the Pliocene epoch (about three million years ago). In both cases the Antarctic ice sheet has been implicated as the primary contributor, hinting at its future vulnerability. Here we use a model coupling ice sheet and climate dynamics-including previously underappreciated processes linking atmospheric warming with hydrofracturing of buttressing ice shelves and structural collapse of marine-terminating ice cliffs-that is calibrated against Pliocene and Last Interglacial sea-level estimates and applied to future greenhouse gas emission scenarios. Antarctica has the potential to contribute more than a metre of sea-level rise by 2100 and more than 15 metres by 2500, if emissions continue unabated. In this case atmospheric warming will soon become the dominant driver of ice loss, but prolonged ocean warming will delay its recovery for thousands of years.
C1 [DeConto, Robert M.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
   [Pollard, David] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
C3 University of Massachusetts System; University of Massachusetts Amherst; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP DeConto, RM (corresponding author), Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
EM deconto@geo.umass.edu
FU NSF [OCE 1202632 PLIOMAX, AGS 1203910/1203792]; Directorate For Geosciences; Office of Polar Programs (OPP) [1443190, 1443394, 1417886] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1203910] Funding Source: National Science Foundation
NR 80
TC 1380
Z9 1650
U1 22
U2 794
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 591
EP 597
DI 10.1038/nature17145
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400029
PM 27029274
DA 2026-03-09
ER

PT J
AU Imada, H
   Miwa, K
   Imai-Imada, M
   Kawahara, S
   Kimura, K
   Kim, Y
AF Imada, Hiroshi
   Miwa, Kuniyuki
   Imai-Imada, Miyabi
   Kawahara, Shota
   Kimura, Kensuke
   Kim, Yousoo
TI Real-space investigation of energy transfer in heterogeneous molecular dimers
SO NATURE
LA English
DT Article
ID scanning tunneling microscope; wave basis-set; photon-emission; fluorescence; efficiency; resolution; surfaces; crystal; systems; cell
AB Given its central role in photosynthesis(1-4) and artificial energy-harvesting devices(5-7), energy transfer has been widely studied using optical spectroscopy to monitor excitation dynamics and probe the molecular-level control of energy transfer between coupled molecules(2-4). However, the spatial resolution of conventional optical spectroscopy is limited to a few hundred nanometres and thus cannot reveal the nanoscale spatial features associated with such processes. In contrast, scanning tunnelling luminescence spectroscopy(8-19) has revealed the energy dynamics associated with phenomena ranging from single-molecule electroluminescence(11,12,14,17,19), absorption of localized plasmons(19) and quantum interference effects(19-21) to energy delocalization(17) and intervalley electron scattering(15) with submolecular spatial resolution in real space. Here we apply this technique to individual molecular dimers that comprise a magnesium phthalocyanine and a free-base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the tunnelling current of the scanning tunnelling microscope generates a luminescence signal from a nearby H2Pc molecule as a result of resonance energy transfer from the former to the latter. A reciprocating resonance energy transfer is observed when exciting the second singlet state (S-2) of H2Pc, which results in energy transfer to the first singlet state (S-1) of MgPc and final funnelling to the S-1 state of H2Pc. We also show that tautomerization(22) of H2Pc changes the energy transfer characteristics within the dimer system, which essentially makes H2Pc a single-molecule energy transfer valve device that manifests itself by blinking resonance energy transfer behaviour.
C1 [Imada, Hiroshi; Miwa, Kuniyuki; Imai-Imada, Miyabi; Kawahara, Shota; Kimura, Kensuke; Kim, Yousoo] RIKEN, Surface & Interface Sci Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
   [Imai-Imada, Miyabi; Kawahara, Shota; Kimura, Kensuke] Univ Tokyo, Grad Sch Frontier Sci, Dept Adv Mat Sci, 5-1-5 Kashiwanoha, Kashiwa, Chiba 2778651, Japan.
C3 RIKEN; University of Tokyo
RP Kim, Y (corresponding author), RIKEN, Surface & Interface Sci Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM ykim@riken.jp
FU MEXT/JSPS KAKENHI [15H02025, 26886013, 16K21623]; MEXT/JSPS [15J03915]; Grants-in-Aid for Scientific Research [15J03915, 15H02025, 16K21623, 26886013] Funding Source: KAKEN
NR 35
TC 181
Z9 204
U1 2
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 364
EP +
DI 10.1038/nature19765
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100035
PM 27698415
DA 2026-03-09
ER

PT J
AU Skoglund, P
   Posth, C
   Sirak, K
   Spriggs, M
   Valentin, F
   Bedford, S
   Clark, GR
   Reepmeyer, C
   Petchey, F
   Fernandes, D
   Fu, QM
   Harney, E
   Lipson, M
   Mallick, S
   Novak, M
   Rohland, N
   Stewardson, K
   Abdullah, S
   Cox, MP
   Friedlaender, FR
   Friedlaender, JS
   Kivisild, T
   Koki, G
   Kusuma, P
   Merriwether, DA
   Ricaut, FX
   Wee, JTS
   Patterson, N
   Krause, J
   Pinhasi, R
   Reich, D
AF Skoglund, Pontus
   Posth, Cosimo
   Sirak, Kendra
   Spriggs, Matthew
   Valentin, Frederique
   Bedford, Stuart
   Clark, Geoffrey R.
   Reepmeyer, Christian
   Petchey, Fiona
   Fernandes, Daniel
   Fu, Qiaomei
   Harney, Eadaoin
   Lipson, Mark
   Mallick, Swapan
   Novak, Mario
   Rohland, Nadin
   Stewardson, Kristin
   Abdullah, Syafiq
   Cox, Murray P.
   Friedlaender, Francoise R.
   Friedlaender, Jonathan S.
   Kivisild, Toomas
   Koki, George
   Kusuma, Pradiptajati
   Merriwether, D. Andrew
   Ricaut, Francois-X.
   Wee, Joseph T. S.
   Patterson, Nick
   Krause, Johannes
   Pinhasi, Ron
   Reich, David
TI Genomic insights into the peopling of the Southwest Pacific
SO NATURE
LA English
DT Article
ID island southeast-asia; population history; austronesian expansion; ancient dna; genetic history; admixture; neanderthal; ancestry; sequence; oceania
AB The appearance of people associated with the Lapita culture in the South Pacific around 3,000 years ago(1) marked the beginning of the last major human dispersal to unpopulated lands. However, the relationship of these pioneers to the long-established Papuan people of the New Guinea region is unclear. Here we present genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100-2,700 years before present) and one from Tonga (about 2,700-2,300 years before present), and analyse them with data from 778 present-day East Asians and Oceanians. Today, indigenous people of the South Pacific harbour a mixture of ancestry from Papuans and a population of East Asian origin that no longer exists in unmixed form, but is a match to the ancient individuals. Most analyses have interpreted the minimum of twenty-five per cent Papuan ancestry in the region today as evidence that the first humans to reach Remote Oceania, including Polynesia, were derived from population mixtures near New Guinea, before their further expansion into Remote Oceania(2-5). However, our finding that the ancient individuals had little to no Papuan ancestry implies that later human population movements spread Papuan ancestry through the South Pacific after the first peopling of the islands.
C1 [Skoglund, Pontus; Harney, Eadaoin; Lipson, Mark; Mallick, Swapan; Rohland, Nadin; Stewardson, Kristin; Reich, David] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
   [Skoglund, Pontus; Harney, Eadaoin; Mallick, Swapan; Patterson, Nick; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Skoglund, Pontus] Stockholm Univ, Dept Archaeol & Class Studies, Archaeol Res Lab, S-10691 Stockholm, Sweden.
   [Posth, Cosimo] Univ Tubingen, Inst Archaeol Sci Archaeo & Palaeogenet, D-72070 Tubingen, Germany.
   [Posth, Cosimo; Krause, Johannes] Max Planck Inst Sci Human Hist, D-07745 Jena, Germany.
   [Sirak, Kendra; Fernandes, Daniel; Novak, Mario] Univ Coll Dublin, Sch Archaeol & Earth Inst, Dublin 4, Ireland.
   [Sirak, Kendra] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA.
   [Spriggs, Matthew] Australian Natl Univ, Coll Arts & Social Sci, Sch Archaeol & Anthropol, Canberra, ACT 2601, Australia.
   [Spriggs, Matthew; Bedford, Stuart] Vanuatu Natl Museum, Vanuatu Cultural Ctr, Port Vila, Vanuatu.
   [Valentin, Frederique] CNRS, Maison Archeol & Ethnol, UMR 7041, F-92023 Nanterre, France.
   [Clark, Geoffrey R.] Australian Natl Univ, Coll Asia & Pacific, Dept Archaeol & Nat Hist, Canberra, ACT 2601, Australia.
   [Reepmeyer, Christian] James Cook Univ, Coll Arts Soc & Educ, Townsville, Qld 4870, Australia.
   [Petchey, Fiona] Univ Waikato, Radiocarbon Dating Lab, Hamilton 3240, New Zealand.
   [Fernandes, Daniel] Univ Coimbra, CIAS, Dept Life Sci, P-3000456 Coimbra, Portugal.
   [Fu, Qiaomei] Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Fu, Qiaomei] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Novak, Mario] Inst Anthropol Res, Zagreb 10000, Croatia.
   [Stewardson, Kristin; Reich, David] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Abdullah, Syafiq] RIPAS Hosp, Bandar Seri Begawan, Brunei.
   [Cox, Murray P.] Massey Univ, Inst Fundamental Sci, Palmerston North 4442, New Zealand.
   [Friedlaender, Jonathan S.] Temple Univ, Dept Anthropol, Gladfelter Hall, Philadelphia, PA 19122 USA.
   [Kivisild, Toomas] Estonian Bioctr, Evolutionary Biol Grp, EE-51010 Tartu, Estonia.
   [Kivisild, Toomas] Univ Cambridge, Archaeol Div, Fitzwilliam St, Cambridge CB2 1QH, England.
   [Koki, George] Papua New Guinea Inst Med Res, Goroka 441, Eastern Highlan, Papua N Guinea.
   [Kusuma, Pradiptajati] Eijkman Inst Mol Biol, Jakarta 10430, Indonesia.
   [Merriwether, D. Andrew] Binghamton Univ, Dept Anthropol, Binghamton, NY 13902 USA.
   [Ricaut, Francois-X.] Univ Toulouse, CNRS, Evolutionary Med Grp, Lab Anthropol Mol & Imagerie Synth,UMr 5288, F-31073 Toulouse, France.
   [Wee, Joseph T. S.] Natl Canc Ctr Singapore, Singapore 169610, Singapore.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Stockholm University; Eberhard Karls University of Tubingen; University College Dublin; Emory University; Australian National University; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social Sciences (INSHS); Australian National University; James Cook University; University of Waikato; Universidade de Coimbra; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Max Planck Society; Institute for Anthropological Research Zagreb; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Massey University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; Estonian Biocentre; University of Cambridge; PNG Institute Of Medical Research; Eijkman Institute; State University of New York (SUNY) System; Binghamton University, SUNY; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); National Cancer Centre Singapore (NCCS)
RP Skoglund, P; Reich, D (corresponding author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Skoglund, P; Reich, D (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Skoglund, P (corresponding author), Stockholm Univ, Dept Archaeol & Class Studies, Archaeol Res Lab, S-10691 Stockholm, Sweden.; Posth, C (corresponding author), Univ Tubingen, Inst Archaeol Sci Archaeo & Palaeogenet, D-72070 Tubingen, Germany.
EM skoglund@genetics.med.harvard.edu; ron.pinhasi@ucd.ie; reich@genetics.med.harvard.edu
FU Wenner-Gren foundation; SciLifeLab; Swedish Research Council (VR) [2014453]; Australian Research Council [DP0880789, DP110101415]; National Geographic Society; Australia-Pacific Science Foundation; CNRS-UMR [7041]; Irish Research Council [GOIPD/2013/1, GOIPG/2013/36]; Key Research Program of Frontier Sciences of CAS [QYZDB-SS W-D00003]; National Natural Science Foundation of China [L1524016]; Chinese Academy of Sciences Discipline Development Strategy Project [2015-DX-C-03]; ERC [FP7-261213, 263441]; Baden Wuerttemberg Foundation; DFG [KR 4015/1-1]; Max Planck Society; NIH [GM100233]; NSF HOMINID [BCS-1032255]; Wenner-Gren foundation; SciLifeLab; Swedish Research Council (VR) [2014453]; Australian Research Council [DP0880789, DP110101415]; National Geographic Society; Australia-Pacific Science Foundation; CNRS-UMR [7041]; Irish Research Council [GOIPD/2013/1, GOIPG/2013/36]; Key Research Program of Frontier Sciences of CAS [QYZDB-SS W-D00003]; National Natural Science Foundation of China [L1524016]; Chinese Academy of Sciences Discipline Development Strategy Project [2015-DX-C-03]; ERC [FP7-261213, 263441]; Baden Wuerttemberg Foundation; DFG [KR 4015/1-1]; Max Planck Society; NIH [GM100233]; NSF HOMINID [BCS-1032255]; European Research Council (ERC) [263441] Funding Source: European Research Council (ERC); Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1032255] Funding Source: National Science Foundation
NR 62
TC 217
Z9 242
U1 3
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 510
EP +
DI 10.1038/nature19844
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400058
PM 27698418
DA 2026-03-09
ER

PT J
AU Narvaez, J
   Vasquez-Sancho, F
   Catalan, G
AF Narvaez, Jackeline
   Vasquez-Sancho, Fabian
   Catalan, Gustau
TI Enhanced flexoelectric-like response in oxide semiconductors
SO NATURE
LA English
DT Article
ID ferroelectric thin-films; barium-titanate; polarization; batio3; solids; srtio3
AB Flexoelectricity is a property of all dielectric materials whereby they polarize in response to deformation gradients such as those produced by bending(1-5). Although it is generally thought of as a property of dielectric insulators, insulation is not a formal requirement: in principle, semiconductors can also redistribute their free charge in response to strain gradients. Here we show that bending a semiconductor not only generates a flexoelectric-like response, but that this response can in fact be much larger than in insulators. By doping single crystals of wide-bandgap oxides to increase their conductivity, their effective flexoelectric coefficient was increased by orders of magnitude. This large response can be explained by a barrier-layer mechanism that remains important even at the macroscale, where conventional (insulator) flexoelectricity otherwise tends to be small. Our results open up the possibility of using semiconductors as active ingredients in electromechanical transducer applications.
C1 [Narvaez, Jackeline; Vasquez-Sancho, Fabian; Catalan, Gustau] CSIC, Inst Catala Nanociencia & Nanotecnol ICN2, Campus UAB, Barcelona 08193, Spain.
   [Narvaez, Jackeline; Vasquez-Sancho, Fabian; Catalan, Gustau] Barcelona Inst Nanosci & Technol BIST, Campus UAB, Barcelona 08193, Spain.
   [Vasquez-Sancho, Fabian] Univ Costa Rica, Ctr Invest Ciencia & Ingn Mat, San Jose 11501, Costa Rica.
   [Catalan, Gustau] ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
C3 Autonomous University of Barcelona; Barcelona Institute of Science & Technology; Catalan Institute of Nanoscience & Nanotechnology (ICN2); Consejo Superior de Investigaciones Cientificas (CSIC); Autonomous University of Barcelona; Universidad Costa Rica; ICREA
RP Catalan, G (corresponding author), CSIC, Inst Catala Nanociencia & Nanotecnol ICN2, Campus UAB, Barcelona 08193, Spain.; Catalan, G (corresponding author), Barcelona Inst Nanosci & Technol BIST, Campus UAB, Barcelona 08193, Spain.; Catalan, G (corresponding author), ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
EM gustau.catalan@icn2.cat
FU ERC Starting grant from the EU [ERC 308023]; Spanish MINECO [FIS2013-48668-C2-1-P]; Severo Ochoa Excellence Programme [SEV-2013-0295]; MICITT; CONICIT; ICREA Funding Source: Custom
NR 37
TC 282
Z9 297
U1 14
U2 427
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 219
EP +
DI 10.1038/nature19761
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000039
PM 27669023
DA 2026-03-09
ER

PT J
AU Fan, J
   Leroux-Coyau, M
   Avery, NJS
   Strick, TR
AF Fan, Jun
   Leroux-Coyau, Mathieu
   Avery, Nigel J. S.
   Strick, Terence R.
TI Reconstruction of bacterial transcription-coupled repair at single-molecule resolution
SO NATURE
LA English
DT Article
ID rna-polymerase; dna-repair; escherichia-coli; structural basis; nanomanipulation; initiation; complexes; excinuclease; mechanism; damage
AB Escherichia coli Mfd translocase enables transcription-coupled repair by displacing RNA polymerase (RNAP) stalled on a DNA lesion and then coordinating assembly of the UvrAB(C) components at the damage site(1-4.) Recent studies have shown that after binding to and dislodging stalled RNAP, Mfd remains on the DNA in the form of a stable, slowly translocating complex with evicted RNAP attached(5,6). Here we find, using a series of single-molecule assays, that recruitment of UvrA and UvrAB to Mfd-RNAP arrests the translocating complex and causes its dissolution. Correlative single-molecule nanomanipulation and fluorescence measurements show that dissolution of the complex leads to loss of both RNAP and Mfd. Subsequent DNA incision by UvrC is faster than when only UvrAB(C) are available, in part because UvrAB binds 20-200 times more strongly to Mfd-RNAP than to DNA damage. These observations provide a quantitative framework for comparing complementary DNA repair pathways in vivo.
C1 [Fan, Jun; Leroux-Coyau, Mathieu; Strick, Terence R.] Univ Paris Diderot, CNRS, Inst Jacques Monod, Sorbonne Paris Cite,UMR7592, F-75205 Paris, France.
   [Avery, Nigel J. S.] Univ Bristol, Sch Biochem, DNA Prot Interact Unit, Bristol BS8 1TD, Avon, England.
   [Strick, Terence R.] PSL Res Univ, Ecole Normale Super, INSERM, CNRS,IBENS, F-75005 Paris, France.
   [Strick, Terence R.] Programme Equipe Labellisees Ligue Contre Canc, F-75013 Paris, France.
C3 Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); University of Bristol; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS)
RP Strick, TR (corresponding author), Univ Paris Diderot, CNRS, Inst Jacques Monod, Sorbonne Paris Cite,UMR7592, F-75205 Paris, France.; Strick, TR (corresponding author), PSL Res Univ, Ecole Normale Super, INSERM, CNRS,IBENS, F-75005 Paris, France.; Strick, TR (corresponding author), Programme Equipe Labellisees Ligue Contre Canc, F-75013 Paris, France.
EM strick@biologie.ens.fr
FU China Scholarship Council; French Agence Nationale pour la Recherche (RepOne); European Science Foundation (EURYI); CNRS; University of Paris Diderot
NR 28
TC 77
Z9 84
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 234
EP +
DI 10.1038/nature19080
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100041
PM 27487215
DA 2026-03-09
ER

PT J
AU Choe, YJ
   Park, SH
   Hassemer, T
   Körner, R
   Vincenz-Donnelly, L
   Hayer-Hartl, M
   Hartl, FU
AF Choe, Young-Jun
   Park, Sae-Hun
   Hassemer, Timm
   Koerner, Roman
   Vincenz-Donnelly, Lisa
   Hayer-Hartl, Manajit
   Hartl, F. Ulrich
TI Failure of RQC machinery causes protein aggregation and proteotoxic stress
SO NATURE
LA English
DT Article
ID quality-control complex; ubiquitin-proteasome-system; messenger-rna surveillance; saccharomyces-cerevisiae; subunit dissociation; budding yeast; ribosome; degradation; translation; chaperone
AB Translation of messenger RNAs lacking a stop codon results in the addition of a carboxy-terminal poly-lysine tract to the nascent polypeptide, causing ribosome stalling. Non-stop proteins and other stalled nascent chains are recognized by the ribosome quality control (RQC) machinery and targeted for proteasomal degradation. Failure of this process leads to neurodegeneration by unknown mechanisms. Here we show that deletion of the E3 ubiquitin ligase Ltn1p in yeast, a key RQC component, causes stalled proteins to form detergent-resistant aggregates and inclusions. Aggregation is dependent on a C-terminal alanine/threonine tail that is added to stalled polypeptides by the RQC component, Rqc2p. Formation of inclusions additionally requires the poly-lysine tract present in non-stop proteins. The aggregates sequester multiple cytosolic chaperones and thereby interfere with general protein quality control pathways. These findings can explain the proteotoxicity of ribosome-stalled polypeptides and demonstrate the essential role of the RQC in maintaining proteostasis.
C1 [Choe, Young-Jun; Park, Sae-Hun; Hassemer, Timm; Koerner, Roman; Vincenz-Donnelly, Lisa; Hayer-Hartl, Manajit; Hartl, F. Ulrich] Max Planck Inst Biochem, Dept Cellular Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
C3 Max Planck Society
RP Hartl, FU (corresponding author), Max Planck Inst Biochem, Dept Cellular Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM uhartl@biochem.mpg.de
FU European Commission [ERC-2012-SyG_318987-ToPAG]; Munich Cluster for Systems Neurology (SyNergy); Center for integrated Protein Science Munich (CiPSM)
NR 55
TC 185
Z9 227
U1 0
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 191
EP +
DI 10.1038/nature16973
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100032
PM 26934223
DA 2026-03-09
ER

PT J
AU Kashiwagi, K
   Takahashi, M
   Nishimoto, M
   Hiyama, TB
   Higo, T
   Umehara, T
   Sakamoto, K
   Ito, T
   Yokoyama, S
AF Kashiwagi, Kazuhiro
   Takahashi, Mari
   Nishimoto, Madoka
   Hiyama, Takuya B.
   Higo, Toshiaki
   Umehara, Takashi
   Sakamoto, Kensaku
   Ito, Takuhiro
   Yokoyama, Shigeyuki
TI Crystal structure of eukaryotic translation initiation factor 2B
SO NATURE
LA English
DT Article
ID guanine-nucleotide exchange; factor eif 2b; alpha-subunit; regulatory subcomplex; protein-synthesis; genetic-code; reveals; identification; mutations; eif2-alpha
AB Eukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B)(1,2). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of alpha-, beta- and gamma-subunits. eIF2B exchanges GDP for GTP on the.-subunit of eIF2 (eIF2.), and is inhibited by stress-induced phosphorylation of eIF2 alpha. eIF2B is a heterodecameric complex of two copies each of the alpha-, beta- and gamma-and e-subunits(3); its alpha-, beta- and delta-subunits constitute the regulatory subcomplex(4), while the gamma-and epsilon-subunits form the catalytic subcomplex(5). The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the alpha(2)beta(2)delta(2) hexameric regulatory subcomplex binds two.e dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross-linking method identified the eIF2a-binding and eIF2 gamma-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2 gamma-binding interface is located close to the conserved ` NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2 alpha, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2 alpha phosphorylation generates the ` nonproductive' eIF2-eIF2B complex(5), which prevents nucleotide exchange on eIF2 gamma, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control.
C1 [Kashiwagi, Kazuhiro; Hiyama, Takuya B.; Ito, Takuhiro; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Kashiwagi, Kazuhiro; Hiyama, Takuya B.; Higo, Toshiaki; Umehara, Takashi; Sakamoto, Kensaku; Ito, Takuhiro; Yokoyama, Shigeyuki] RIKEN Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Kashiwagi, Kazuhiro; Takahashi, Mari; Nishimoto, Madoka; Higo, Toshiaki; Umehara, Takashi; Sakamoto, Kensaku; Ito, Takuhiro] RIKEN Ctr Life Sci Technol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Yokoyama, Shigeyuki] RIKEN Struct Biol Lab, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
C3 University of Tokyo; RIKEN; RIKEN; RIKEN
RP Ito, T; Yokoyama, S (corresponding author), Univ Tokyo, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.; Ito, T; Yokoyama, S (corresponding author), RIKEN Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.; Ito, T; Yokoyama, S (corresponding author), RIKEN Ctr Life Sci Technol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.; Yokoyama, S (corresponding author), RIKEN Struct Biol Lab, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
EM takuhiro.ito@riken.jp; yokoyama@riken.jp
FU JSPS KAKENHI [23687013, 25121737]; Targeted Proteins Research Program (TPRP); Platform for Drug Discovery, Informatics and Structural Life Science, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; UT-RIKEN Cooperation Laboratory of Structural Biology; Grants-in-Aid for Scientific Research [23687013, 15H01548, 26291035] Funding Source: KAKEN
NR 47
TC 88
Z9 110
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 122
EP +
DI 10.1038/nature16991
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900053
PM 26901872
DA 2026-03-09
ER

PT J
AU Parmigiani, A
   Faroughi, S
   Huber, C
   Bachmann, O
   Su, Y
AF Parmigiani, A.
   Faroughi, S.
   Huber, C.
   Bachmann, O.
   Su, Y.
TI Bubble accumulation and its role in the evolution of magma reservoirs in the upper crust
SO NATURE
LA English
DT Article
ID lattice-boltzmann model; taupo volcanic zone; gas; eruption; perspectives; petrogenesis; suspensions; timescales; emulsions; volatiles
AB Volcanic eruptions transfer huge amounts of gas to the atmosphere1,2. In particular, the sulfur released during large silicic explosive eruptions can induce global cooling3. A fundamental goal in volcanology, therefore, is to assess the potential for eruption of the large volumes of crystal-poor, silicic magma that are stored at shallow depths in the crust, and to obtain theoretical bounds for the amount of volatiles that can be released during these eruptions. It is puzzling that highly evolved, crystal-poor silicic magmas are more likely to generate volcanic rocks than plutonic rocks(4,5). This observation suggests that such magmas are more prone to erupting than are their crystal-rich counterparts. Moreover, well studied examples of largely crystal-poor eruptions (for example, Katmai(6), Taupo(7) and Minoan(8)) often exhibit a release of sulfur that is 10 to 20 times higher than the amount of sulfur estimated to be stored in the melt. Here we argue that these two observations rest on how the magmatic volatile phase (MVP) behaves as it rises buoyantly in zoned magma reservoirs. By investigating the fluid dynamics that controls the transport of the MVP in crystal-rich and crystal-poor magmas, we show how the interplay between capillary stresses and the viscosity contrast between the MVP and the host melt results in a counterintuitive dynamics, whereby the MVP tends to migrate efficiently in crystal-rich parts of a magma reservoir and accumulate in crystal-poor regions. The accumulation of low-density bubbles of MVP in crystal-poor magmas has implications for the eruptive potential of such magmas(9,10), and is the likely source of the excess sulfur released during explosive eruptions.
C1 [Parmigiani, A.; Bachmann, O.] ETH, Inst Geochem & Petr, CH-8092 Zurich, Switzerland.
   [Parmigiani, A.; Faroughi, S.; Huber, C.; Su, Y.] Georgia Inst Technol, Sch Earth & Atmospher Sci, Atlanta, GA 30332 USA.
   [Faroughi, S.; Huber, C.] Georgia Inst Technol, Sch Civil & Environm Engn, Atlanta, GA 30332 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology
RP Parmigiani, A (corresponding author), ETH, Inst Geochem & Petr, CH-8092 Zurich, Switzerland.; Parmigiani, A (corresponding author), Georgia Inst Technol, Sch Earth & Atmospher Sci, Atlanta, GA 30332 USA.
EM andrea.parmigiani@erdw.ethz.ch
FU Swiss National Science Foundation [154854, 200021-103441]; National Science Foundation [1454821]; Swiss National Supercomputing Centre (CSCS) [s479, s597]; Euler Supercomputer from ETHZ; Division Of Earth Sciences; Directorate For Geosciences [1719480] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1454821] Funding Source: National Science Foundation
NR 59
TC 187
Z9 213
U1 3
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 492
EP +
DI 10.1038/nature17401
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900045
PM 27074507
DA 2026-03-09
ER

PT J
AU Feng, JD
   Graf, M
   Liu, K
   Ovchinnikov, D
   Dumcenco, D
   Heiranian, M
   Nandigana, V
   Aluru, NR
   Kis, A
   Radenovic, A
AF Feng, Jiandong
   Graf, Michael
   Liu, Ke
   Ovchinnikov, Dmitry
   Dumcenco, Dumitru
   Heiranian, Mohammad
   Nandigana, Vishal
   Aluru, Narayana R.
   Kis, Andras
   Radenovic, Aleksandra
TI Single-layer MoS2 nanopores as nanopower generators
SO NATURE
LA English
DT Article
ID reverse electrodialysis; water desalination; molecular-dynamics; energy-conversion; power-generation; dialytic battery; nanochannels; difference; membranes; salinity
AB Making use of the osmotic pressure difference between fresh water and seawater is an attractive, renewable and clean way to generate power and is known as 'blue energy'(1-3). Another electrokinetic phenomenon, called the streaming potential, occurs when an electrolyte is driven through narrow pores either by a pressure gradient(4) or by an osmotic potential resulting from a salt concentration gradient(5). For this task, membranes made of two-dimensional materials are expected to be the most efficient, because water transport through a membrane scales inversely with membrane thickness(5-7). Here we demonstrate the use of single-layer molybdenum disulfide (MoS2) nanopores as osmotic nanopower generators. We observe a large, osmotically induced current produced from a salt gradient with an estimated power density of up to 10(6) watts per square metre-a current that can be attributed mainly to the atomically thin membrane of MoS2. Low power requirements for nanoelectronic and optoelectric devices can be provided by a neighbouring nanogenerator that harvests energy from the local environment(8-11)-for example, a piezoelectric zinc oxide nanowire array(8) or single-layer MoS2 (ref. 12). We use our MoS2 nanopore generator to power a MoS2 transistor, thus demonstrating a self-powered nanosystem.
C1 [Feng, Jiandong; Graf, Michael; Liu, Ke; Radenovic, Aleksandra] Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lab Nanoscale Biol, CH-1015 Lausanne, Switzerland.
   [Ovchinnikov, Dmitry; Dumcenco, Dumitru; Kis, Andras] Ecole Polytech Fed Lausanne, Sch Engn, Inst Elect Engn, Lab Nanoscale Elect & Struct, CH-1015 Lausanne, Switzerland.
   [Ovchinnikov, Dmitry; Dumcenco, Dumitru; Kis, Andras] Ecole Polytech Fed Lausanne, Sch Engn, Inst Mat Sci & Engn, CH-1015 Lausanne, Switzerland.
   [Heiranian, Mohammad; Nandigana, Vishal; Aluru, Narayana R.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Mech Sci & Engn, Urbana, IL 61801 USA.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Illinois System; University of Illinois Urbana-Champaign
RP Feng, JD; Radenovic, A (corresponding author), Ecole Polytech Fed Lausanne, Sch Engn, Inst Bioengn, Lab Nanoscale Biol, CH-1015 Lausanne, Switzerland.
EM jiandong.feng@epfl.ch; aleksandra.radenovic@epfl.ch
FU European Research Council [259398]; Swiss National Science Foundation (SNSF) [BIONIC BSCGI0_157802]; SNSF Sinergia grant [147607]; European Union [318804]; Air Force Office of Scientific Research [FA9550-12-1-0464]; National Science Foundation [1264282, 1420882, 1506619, 1545907]; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [1264282] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Electrical, Commun & Cyber Sys [1506619] Funding Source: National Science Foundation; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [1420882] Funding Source: National Science Foundation; European Research Council (ERC) [259398] Funding Source: European Research Council (ERC)
NR 45
TC 1067
Z9 1160
U1 42
U2 2010
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 197
EP +
DI 10.1038/nature18593
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100033
PM 27409806
DA 2026-03-09
ER

PT J
AU Fourgeaud, L
   Través, PG
   Tufail, Y
   Leal-Bailey, H
   Lew, ED
   Burrola, PG
   Callaway, P
   Zagórska, A
   Rothlin, CV
   Nimmerjahn, A
   Lemke, G
AF Fourgeaud, Lawrence
   Traves, Paqui G.
   Tufail, Yusuf
   Leal-Bailey, Humberto
   Lew, Erin D.
   Burrola, Patrick G.
   Callaway, Perri
   Zagorska, Anna
   Rothlin, Carla V.
   Nimmerjahn, Axel
   Lemke, Greg
TI TAM receptors regulate multiple features of microglial physiology
SO NATURE
LA English
DT Article
ID central-nervous-system; apoptotic cells; fractalkine receptor; tyrosine kinases; gene-expression; tyro-3 family; phagocytosis; protein; neurogenesis; macrophages
AB Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells(1). Here we show that the TAM receptor tyrosine kinases Mer and Axl(2) regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis(3,4) is normally driven by both TAM receptor ligands Gas6 and protein S-5. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease(6). Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.
C1 [Fourgeaud, Lawrence; Traves, Paqui G.; Leal-Bailey, Humberto; Lew, Erin D.; Burrola, Patrick G.; Callaway, Perri; Zagorska, Anna; Lemke, Greg] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
   [Traves, Paqui G.] Inst Invest Biomed Alberto Sols CSIC UAM, Madrid 28029, Spain.
   [Tufail, Yusuf; Nimmerjahn, Axel] Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Leal-Bailey, Humberto] Univ Strasbourg, Joint Master Neurosci Program, F-67081 Strasbourg, France.
   [Rothlin, Carla V.] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
   [Lemke, Greg] Salk Inst Biol Studies, Immunobiol & Microbial Pathogenesis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
C3 Salk Institute; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Investigaciones Biomedicas Alberto Sols (IIBM); Salk Institute; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Yale University; Salk Institute
RP Lemke, G (corresponding author), Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.; Rothlin, CV (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.; Lemke, G (corresponding author), Salk Inst Biol Studies, Immunobiol & Microbial Pathogenesis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM carla.rothlin@yale.edu; lemke@salk.edu
FU US National Institutes of Health [R01 NS085296, R01 AI101400, DP2 NS083038, R01 NS085938, R01 AI089824, P30CA014195]; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; Nomis Foundation; H.N. and Frances C. Berger Foundation; Fritz B. Burns Foundation; HKT Foundation; Waitt Foundation; Rita Allen and Hearst Foundation; Marie Curie International Outgoing Fellowship Program; Howard Hughes Medical Institute Life Sciences Research Foundation; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI101400] Funding Source: NIH RePORTER
NR 39
TC 461
Z9 562
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 240
EP +
DI 10.1038/nature17630
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100041
PM 27049947
DA 2026-03-09
ER

PT J
AU Storm, EE
   Durinck, S
   Melo, FDE
   Tremayne, J
   Kljavin, N
   Tan, C
   Ye, XF
   Chiu, C
   Pham, T
   Hongo, JA
   Bainbridge, T
   Firestein, R
   Blackwood, E
   Metcalfe, C
   Stawiski, EW
   Yauch, RL
   Wu, Y
   de Sauvage, FJ
AF Storm, Elaine E.
   Durinck, Steffen
   de Sousa e Melo, Felipe
   Tremayne, Jarrod
   Kljavin, Noelyn
   Tan, Christine
   Ye, Xiaofen
   Chiu, Cecilia
   Thinh Pham
   Hongo, Jo-Anne
   Bainbridge, Travis
   Firestein, Ron
   Blackwood, Elizabeth
   Metcalfe, Ciara
   Stawiski, Eric W.
   Yauch, Robert L.
   Wu, Yan
   de Sauvage, Frederic J.
TI Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function
SO NATURE
LA English
DT Article
ID colorectal-cancer; wnt/beta-catenin; small-intestine; read alignment; in-vitro; crypt; identification; maintenance; homeostasis
AB Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed(1-3). We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours(4). Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
C1 [Storm, Elaine E.; de Sousa e Melo, Felipe; Kljavin, Noelyn; de Sauvage, Frederic J.] Genentech Inc, Mol Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Durinck, Steffen; Stawiski, Eric W.] Genentech Inc, Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Tremayne, Jarrod; Blackwood, Elizabeth; Metcalfe, Ciara] Genentech Inc, Translat Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Tan, Christine; Chiu, Cecilia; Hongo, Jo-Anne; Wu, Yan] Genentech Inc, Antibody Engn, 1 DNA Way, San Francisco, CA 94080 USA.
   [Ye, Xiaofen; Yauch, Robert L.] Genentech Inc, Discovery Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Thinh Pham; Firestein, Ron] Genentech Inc, Res Pathol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Bainbridge, Travis] Genentech Inc, Prot Chem, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech
RP de Sauvage, FJ (corresponding author), Genentech Inc, Mol Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
EM desauvage.fred@gene.com
NR 36
TC 202
Z9 237
U1 0
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 97
EP +
DI 10.1038/nature16466
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900034
PM 26700806
DA 2026-03-09
ER

PT J
AU Zhang, R
   Miner, JJ
   Gorman, MJ
   Rausch, K
   Ramage, H
   White, JP
   Zuiani, A
   Zhang, P
   Fernandez, E
   Zhang, Q
   Dowd, KA
   Pierson, TC
   Cherry, S
   Diamond, MS
AF Zhang, Rong
   Miner, Jonathan J.
   Gorman, Matthew J.
   Rausch, Keiko
   Ramage, Holly
   White, James P.
   Zuiani, Adam
   Zhang, Ping
   Fernandez, Estefania
   Zhang, Qiang
   Dowd, Kimberly A.
   Pierson, Theodore C.
   Cherry, Sara
   Diamond, Michael S.
TI A CRISPR screen defines a signal peptide processing pathway required by flaviviruses
SO NATURE
LA English
DT Article
ID west-nile-virus; borne encephalitis-virus; hepatitis-c virus; monoclonal-antibody; envelope protein; human-cells; infection; genes; neutralization; identification
AB Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available(1,2). We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern.
C1 [Zhang, Rong; Miner, Jonathan J.; Gorman, Matthew J.; White, James P.; Zuiani, Adam; Zhang, Ping; Fernandez, Estefania; Zhang, Qiang; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Rausch, Keiko; Ramage, Holly; Cherry, Sara] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Zhang, Ping] Sun Yat Sen Univ, Inst Human Virol, Zhongshan Sch Med, Dept Immunol, Guangzhou 510080, Guangdong, Peoples R China.
   [Dowd, Kimberly A.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); University of Pennsylvania; Sun Yat Sen University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
EM diamond@borcim.wustl.edu
FU NIH [U19 AI083019, U19 AI106772, R01 AI104972, T32 AI007163]; Washington University Institute of Clinical and Translational Sciences from the National Center for Advancing Translational Sciences [UL1 TR000448]; Washington University Institute of Clinical and Translational Sciences from the National Institute of General Medical Sciences [P41 GM103422-35]; NIAID; National Institute of Allergy and Infectious Diseases [ZIAAI001209, T32AI007163] Funding Source: NIH RePORTER
NR 49
TC 304
Z9 386
U1 3
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 164
EP +
DI 10.1038/nature18625
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600045
PM 27383988
DA 2026-03-09
ER

PT J
AU Labuhn, H
   Barredo, D
   Ravets, S
   de Léséleuc, S
   Macrì, T
   Lahaye, T
   Browaeys, A
AF Labuhn, Henning
   Barredo, Daniel
   Ravets, Sylvain
   de Leseleuc, Sylvain
   Macri, Tommaso
   Lahaye, Thierry
   Browaeys, Antoine
TI Tunable two-dimensional arrays of single Rydberg atoms for realizing quantum Ising models
SO NATURE
LA English
DT Article
ID simulations
AB Spin models are the prime example of simplified many-body Hamiltonians used to model complex, strongly correlated real-world materials(1). However, despite the simplified character of such models, their dynamics often cannot be simulated exactly on classical computers when the number of particles exceeds a few tens. For this reason, quantum simulation(2) of spin Hamiltonians using the tools of atomic and molecular physics has become a very active field over the past years, using ultracold atoms(3) or molecules(4) in optical lattices, or trapped ions(5). All of these approaches have their own strengths and limitations. Here we report an alternative platform for the study of spin systems, using individual atoms trapped in tunable two-dimensional arrays of optical microtraps with arbitrary geometries, where filling fractions range from 60 to 100 per cent. When excited to high-energy Rydberg D states, the atoms undergo strong interactions whose anisotropic character opens the way to simulating exotic matter(6). We illustrate the versatility of our system by studying the dynamics of a quantum Ising-like spin-1/2 system in a transverse field with up to 30 spins, for a variety of geometries in one and two dimensions, and for a wide range of interaction strengths. For geometries where the anisotropy is expected to have small effects on the dynamics, we find excellent agreement with ab initio simulations of the spin-1/2 system, while for strongly anisotropic situations the multilevel structure of the D states has a measurable influence(7,8). Our findings establish arrays of single Rydberg atoms as a versatile platform for the study of quantum magnetism.
C1 [Labuhn, Henning; Barredo, Daniel; Ravets, Sylvain; de Leseleuc, Sylvain; Lahaye, Thierry; Browaeys, Antoine] Univ Paris Sud, Univ Paris 11, Lab Charles Fabry, Inst Opt, 2 Ave Augustin Fresnel, F-91127 Palaiseau, France.
   [Macri, Tommaso] Univ Fed Rio Grande do Norte, Dept Fis Teor & Expt, Natal, RN, Brazil.
   [Macri, Tommaso] Int Inst Phys, Natal, RN, Brazil.
C3 Universite Paris Saclay; Universidade Federal do Rio Grande do Norte
RP Lahaye, T (corresponding author), Univ Paris Sud, Univ Paris 11, Lab Charles Fabry, Inst Opt, 2 Ave Augustin Fresnel, F-91127 Palaiseau, France.
EM thierry.lahaye@institutoptique.fr
FU EU (FET-Open Xtrack Project HAIRS); EU (FET-PROACT Project RySQ); EU (EU Marie-Curie Program ITN COHERENCE) [FP7-PEOPLE-2010-ITN-265031]; 'PALM' Labex (project QUANTICA); Region Ile-de-France
NR 34
TC 654
Z9 742
U1 7
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 667
EP +
DI 10.1038/nature18274
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000032
PM 27281203
DA 2026-03-09
ER

PT J
AU Lechtenberg, BC
   Rajput, A
   Sanishvili, R
   Dobaczewska, MK
   Ware, CF
   Mace, PD
   Riedl, SJ
AF Lechtenberg, Bernhard C.
   Rajput, Akhil
   Sanishvili, Ruslan
   Dobaczewska, Malgorzata K.
   Ware, Carl F.
   Mace, Peter D.
   Riedl, Stefan J.
TI Structure of a HOIP/E2∼ubiquitin complex reveals RBR E3 ligase mechanism and regulation
SO NATURE
LA English
DT Article
ID nf-kappa-b; linear ubiquitin chains; ring domain; conjugating enzyme; parkin; insights; refinement; activation; sharpin; system
AB Ubiquitination is a central process affecting all facets of cellular signalling and function(1). A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate(2,3). The RING-between-RING (RBR) family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases(4-6). The RBR family includes Parkin(4) and HOIP, the central catalytic factor of the LUBAC (linear ubiquitin chain assembly complex)(7). While structural insights into the RBR E3 ligases Parkin and HHARI in their overall auto-inhibited forms are available(8-13), no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely unknown. Here we present the first structure, to our knowledge, of the fully active human HOIP RBR in its transfer complex with an E2 similar to ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP RBR adopts a conformation markedly different from that of auto-inhibited RBRs. HOIP RBR binds the E2 similar to ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centres ideally aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. In addition, three distinct helix-IBR-fold motifs inherent to RBRs form ubiquitin-binding regions that engage the activated ubiquitin of the E2 similar to ubiquitin conjugate and, surprisingly, an additional regulatory ubiquitin molecule. The features uncovered reveal critical states of the HOIP RBR E3 ligase cycle, and comparison with Parkin and HHARI suggests a general mechanism for RBR E3 ligases.
C1 [Lechtenberg, Bernhard C.; Dobaczewska, Malgorzata K.; Riedl, Stefan J.] Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Rajput, Akhil; Ware, Carl F.] Sanford Burnham Prebys Med Discovery Inst, Infect & Inflammatory Dis Ctr, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Sanishvili, Ruslan] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, 9700 S Cass Ave, Argonne, IL 60439 USA.
   [Mace, Peter D.] Univ Otago, Dept Biochem, Dunedin 9054, New Zealand.
C3 Sanford Burnham Prebys Medical Discovery Institute; Sanford Burnham Prebys Medical Discovery Institute; United States Department of Energy (DOE); Argonne National Laboratory; University of Otago
RP Riedl, SJ (corresponding author), Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM sriedl@SBPdiscovery.org
FU NIH [R01AA017238]; EMBO Long-term Postdoctoral Fellowship; Rutherford Discovery Fellowship from the New Zealand government; NCI Cancer Center Support Grant [P30CA030199]; DOE Office of Science [DE-AC02-06CH11357]; National Cancer Institute [ACB-12002]; National Institute of General Medical Sciences [AGM-12006]; National Cancer Institute [P30CA030199] Funding Source: NIH RePORTER
NR 59
TC 149
Z9 178
U1 1
U2 49
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 546
EP +
DI 10.1038/nature16511
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800041
PM 26789245
DA 2026-03-09
ER

PT J
AU Santisteban, JVH
   Knigge, C
   Littlefair, SP
   Breton, RP
   Dhillon, VS
   Gänsicke, BT
   Marsh, TR
   Pretorius, ML
   Southworth, J
   Hauschildt, PH
AF Santisteban, Juan V. Hernandez
   Knigge, Christian
   Littlefair, Stuart P.
   Breton, Rene P.
   Dhillon, Vikram S.
   Gansicke, Boris T.
   Marsh, Thomas R.
   Pretorius, Magaretha L.
   Southworth, John
   Hauschildt, Peter H.
TI An irradiated brown-dwarf companion to an accreting white dwarf
SO NATURE
LA English
DT Article
ID cataclysmic variables; model atmospheres; thermal structure; mass donor; stars; evolution
AB Interacting compact binary systems provide a natural laboratory in which to study irradiated substellar objects. As the mass-losing secondary (donor) in these systems makes a transition from the stellar to the substellar regime, it is also irradiated by the primary (compact accretor)(1,2). The internal and external energy fluxes are both expected to be comparable in these objects, providing access to an unexplored irradiation regime. The atmospheric properties of donors are largely unknown(3), but could be modified by the irradiation. To constrain models of donor atmospheres, it is necessary to obtain accurate observational estimates of their physical properties (masses, radii, temperatures and albedos). Here we report the spectroscopic detection and characterization of an irradiated substellar donor in an accreting white-dwarf binary system. Our near-infrared observations allow us to determine a model-independent mass estimate for the donor of 0.055 +/- 0.008 solar masses and an average spectral type of L1 +/- 1, supporting both theoretical predictions and model-dependent observational constraints that suggest that the donor is a brown dwarf. Our time-resolved data also allow us to estimate the average irradiation-induced temperature difference between the dayside and nightside of the substellar donor (57 kelvin) and the maximum difference between the hottest and coolest parts of its surface (200 kelvin). The observations are well described by a simple geometric reprocessing model with a bolometric (Bond) albedo of less than 0.54 at the 2 sigma confidence level, consistent with high reprocessing efficiency, but poor lateral heat redistribution in the atmosphere of the brown-dwarf donor(4,5). These results add to our knowledge of binary evolution, in that the donor has survived the transition from the stellar to the substellar regime, and of substellar atmospheres, in that we have been able to test a regime in which the irradiation and the internal energy of a brown dwarf are comparable.
C1 [Santisteban, Juan V. Hernandez; Knigge, Christian; Breton, Rene P.] Univ Southampton, Dept Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Littlefair, Stuart P.; Dhillon, Vikram S.] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
   [Breton, Rene P.] Univ Manchester, Sch Phys & Astron, Jodrell Bank, Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Dhillon, Vikram S.] Inst Astrofis Canarias, E-38205 San Cristobal la Laguna, Santa Cruz De T, Spain.
   [Gansicke, Boris T.; Marsh, Thomas R.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Pretorius, Magaretha L.] Univ Oxford, Dept Phys, Denys Wilkinson Bldg,Keble Rd, Oxford OX1 3RH, England.
   [Southworth, John] Keele Univ, Astrophys Grp, Newcastle Upon Tyne ST5 5BG, Tyne & Wear, England.
   [Hauschildt, Peter H.] Hamburger Sternwarte, Gojenbergsweg 112, D-21029 Hamburg, Germany.
C3 University of Southampton; University of Sheffield; University of Manchester; Jodrell Bank Centre for Astrophysics; Instituto de Astrofisica de Canarias; University of Warwick; University of Oxford; Keele University; University of Hamburg
RP Santisteban, JVH (corresponding author), Univ Southampton, Dept Phys & Astron, Southampton SO17 1BJ, Hants, England.
EM j.v.hernandez@soton.ac.uk
FU CONACyT (Mexico); University of Southampton; Royal Astronomical Society; European Union [PIIF-GA-2012-332393]; ERC [320964]; Office of Science of the US Department of Energy [DE-AC03-76SF00098]; European Research Council (ERC) [320964] Funding Source: European Research Council (ERC); STFC [ST/L000733/1, ST/M002012/1, ST/H005307/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/L000733/1, ST/H005307/1, ST/M002012/1] Funding Source: researchfish
NR 28
TC 37
Z9 39
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 366
EP +
DI 10.1038/nature17952
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300042
PM 27193683
DA 2026-03-09
ER

PT J
AU Mróz, P
   Udalski, A
   Pietrukowicz, P
   Szymanski, MK
   Soszynski, I
   Wyrzykowski, L
   Poleski, R
   Kozlowski, S
   Skowron, J
   Ulaczyk, K
   Skowron, D
   Pawlak, M
AF Mroz, Przemek
   Udalski, Andrzej
   Pietrukowicz, Pawel
   Szymanski, Michal K.
   Soszynski, Igor
   Wyrzykowski, Lukasz
   Poleski, Radoslaw
   Kozlowski, Szymon
   Skowron, Jan
   Ulaczyk, Krzysztof
   Skowron, Dorota
   Pawlak, Michal
TI The awakening of a classical nova from hibernation
SO NATURE
LA English
DT Article
ID gravitational lensing experiment; galactic disk; light curves; dwarf novae; old nova; ogle; outbursts; evolution; atlas
AB Cataclysmic variable stars-novae, dwarf novae, and nova-likes-are close binary systems consisting of a white dwarf star (the primary) that is accreting matter from a low-mass companion star (the secondary)(1). From time to time such systems undergo large-amplitude brightenings. The most spectacular eruptions, with a ten-thousandfold increase in brightness, occur in classical novae and are caused by a thermonuclear runaway on the surface of the white dwarf(2). Such eruptions are thought to recur on timescales of ten thousand to a million years(3). In between, the system's properties depend primarily on the mass-transfer rate: if it is lower than a billionth of a solar mass per year, the accretion becomes unstable and the matter is dumped onto the white dwarf during quasi-periodic dwarf nova outbursts(4). The hibernation hypothesis(5) predicts that nova eruptions strongly affect the mass-transfer rate in the binary, keeping it high for centuries after the event(6). Subsequently, the mass-transfer rate should significantly decrease for a thousand to a million years, starting the hibernation phase. After that the nova awakes again-with accretion returning to the pre-eruption level and leading to a new nova explosion. The hibernation model predicts cyclical evolution of cataclysmic variables through phases of high and low mass-transfer. The theory gained some support from the discovery of ancient nova shells around the dwarf novae Z Camelopardalis(7) and AT Cancri(8), but direct evidence for considerable mass-transfer changes prior, during and after nova eruptions has not hitherto been found. Here we report long-term observations of the classical nova V1213 Cen (Nova Centauri 2009) covering its pre- and post-eruption phases and precisely documenting its evolution. Within the six years before the explosion, the system revealed dwarf nova outbursts indicative of a low mass-transfer rate. The post-nova is two orders of magnitude brighter than the pre-nova at minimum light with no trace of dwarf nova behaviour, implying that the mass-transfer rate increased considerably as a result of the nova explosion.
C1 [Mroz, Przemek; Udalski, Andrzej; Pietrukowicz, Pawel; Szymanski, Michal K.; Soszynski, Igor; Wyrzykowski, Lukasz; Poleski, Radoslaw; Kozlowski, Szymon; Skowron, Jan; Ulaczyk, Krzysztof; Skowron, Dorota; Pawlak, Michal] Univ Warsaw Observ, Aleje Ujazdowskie 4, PL-00478 Warsaw, Poland.
   [Poleski, Radoslaw] Ohio State Univ, Dept Astron, 140 West 18th Ave, Columbus, OH 43210 USA.
   [Ulaczyk, Krzysztof] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
C3 University of Warsaw; Warsaw University Observatory; University System of Ohio; Ohio State University; University of Warwick
RP Mróz, P (corresponding author), Univ Warsaw Observ, Aleje Ujazdowskie 4, PL-00478 Warsaw, Poland.
EM pmroz@astrouw.edu.pl
FU Polish Ministry of Science and Higher Education [DI2013/014743]; National Science Center, Poland [MAESTRO 2014/14/A/ST9/00121]; STFC [ST/L000733/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/L000733/1] Funding Source: researchfish
NR 42
TC 29
Z9 31
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 649
EP +
DI 10.1038/nature19066
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700043
PM 27533036
DA 2026-03-09
ER

PT J
AU Coulais, C
   Teomy, E
   de Reus, K
   Shokef, Y
   van Hecke, M
AF Coulais, Corentin
   Teomy, Eial
   de Reus, Koen
   Shokef, Yair
   van Hecke, Martin
TI Combinatorial design of textured mechanical metamaterials
SO NATURE
LA English
DT Article
ID negative poissons ratio; artificial spin ice; frustration
AB The structural complexity of metamaterials is limitless, but, in practice, most designs comprise periodic architectures that lead to materials with spatially homogeneous features(1-11). More advanced applications in soft robotics, prosthetics and wearable technology involve spatially textured mechanical functionality, which requires aperiodic architectures. However, a naive implementation of such structural complexity invariably leads to geometrical frustration (whereby local constraints cannot be satisfied everywhere), which prevents coherent operation and impedes functionality. Here we introduce a combinatorial strategy for the design of aperiodic, yet frustration-free, mechanical metamaterials that exhibit spatially textured functionalities. We implement this strategy using cubic building blocks-voxels-that deform anisotropically, a local stacking rule that allows cooperative shape changes by guaranteeing that deformed building blocks fit together as in a three-dimensional jigsaw puzzle, and three-dimensional printing. These aperiodic metamaterials exhibit long-range holographic order, whereby the two-dimensional pixelated surface texture dictates the three-dimensional interior voxel arrangement. They also act as programmable shape-shifters, morphing into spatially complex, but predictable and designable, shapes when uniaxially compressed. Finally, their mechanical response to compression by a textured surface reveals their ability to perform sensing and pattern analysis. Combinatorial design thus opens up a new avenue towards mechanical metamaterials with unusual order and machine-like functionalities.
C1 [Coulais, Corentin; de Reus, Koen; van Hecke, Martin] Leiden Univ, Huygens Kamerlingh Onnes Lab, POB 9504, NL-2300 RA Leiden, Netherlands.
   [Coulais, Corentin; van Hecke, Martin] FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
   [Teomy, Eial; Shokef, Yair] Tel Aviv Univ, Sch Mech Engn, IL-69978 Tel Aviv, Israel.
   [Teomy, Eial; Shokef, Yair] Tel Aviv Univ, Sackler Ctr Computat Mol & Mat Sci, IL-69978 Tel Aviv, Israel.
C3 Leiden University; Leiden University - Excl LUMC; AMOLF; Tel Aviv University; Tel Aviv University
RP Coulais, C (corresponding author), Leiden Univ, Huygens Kamerlingh Onnes Lab, POB 9504, NL-2300 RA Leiden, Netherlands.; Coulais, C (corresponding author), FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
EM coulais@amolf.nl
FU Netherlands Organisation for Scientific Research through VICI [NWO-680-47-609]; Netherlands Organisation for Scientific Research through VENI [NWO-680-47-445]; Israel Science Foundation [617/12, 1730/12]
NR 30
TC 365
Z9 427
U1 27
U2 580
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 529
EP +
DI 10.1038/nature18960
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600024
PM 27466125
DA 2026-03-09
ER

PT J
AU Tajima, N
   Karakas, E
   Grant, T
   Simorowski, N
   Diaz-Avalos, R
   Grigorieff, N
   Furukawa, H
AF Tajima, Nami
   Karakas, Erkan
   Grant, Timothy
   Simorowski, Noriko
   Diaz-Avalos, Ruben
   Grigorieff, Nikolaus
   Furukawa, Hiro
TI Activation of NMDA receptors and the mechanism of inhibition by ifenprodil
SO NATURE
LA English
DT Article
ID amino-terminal domain; spinal-cord neurons; subunit arrangement; structural mechanism; glutamate receptors; binding; kainate; software; kinetics; channels
AB The physiology of N-methyl-D-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel.
C1 [Tajima, Nami; Karakas, Erkan; Simorowski, Noriko; Furukawa, Hiro] Cold Spring Harbor Lab, WM Keck Struct Biol Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
   [Grant, Timothy; Diaz-Avalos, Ruben; Grigorieff, Nikolaus] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
C3 Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
RP Furukawa, H (corresponding author), Cold Spring Harbor Lab, WM Keck Struct Biol Lab, POB 100, Cold Spring Harbor, NY 11724 USA.; Grigorieff, N (corresponding author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
EM grigorieffn@janelia.hhmi.org; furukawa@cshl.edu
FU National Institutes of Health [MH085926, GM105730]; Stanley Institute of Cognitive Genomics; Burroughs Wellcome Fund Collaborative Research Travel Grant; Robertson Research Fund of Cold Spring Harbor Laboratory; Japan Society for the Promotion of Science; Visiting Scientist program of the Janelia Research Center; National Institute of Mental Health [R01MH085926] Funding Source: NIH RePORTER
NR 45
TC 188
Z9 215
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 63
EP +
DI 10.1038/nature17679
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300033
PM 27135925
DA 2026-03-09
ER

PT J
AU Mueller, AA
   van Velthoven, CT
   Fukumoto, KD
   Cheung, TH
   Rando, TA
AF Mueller, Alisa A.
   van Velthoven, Cindy T.
   Fukumoto, Kathryn D.
   Cheung, Tom H.
   Rando, Thomas A.
TI Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis
SO NATURE
LA English
DT Article
ID alternative polyadenylation; growth-factor; expression; receptor; dystrophy; fibrogenesis; progenitors; repair
AB Platelet-derived growth factor receptor a (PDGFR alpha) exhibits divergent effects in skeletal muscle. At physiological levels, signalling through this receptor promotes muscle development in growing embryos and angiogenesis in regenerating adult muscle(1,2). However, both increased PDGF ligand abundance and enhanced PDGFRa pathway activity cause pathological fibrosis(3,4). This excessive collagen deposition, which is seen in aged and diseased muscle(5-7), interferes with muscle function and limits the effectiveness of gene-and cell-based therapies for muscle disorders(8,9). Although compelling evidence exists for the role of PDGFRa in fibrosis, little is known about the cells through which this pathway acts. Here we show in mice that PDGFRa signalling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated 10(-13). We found that FAPs produce multiple transcriptional variants of Pdgfra with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signalling and to prevent FAP over-activation. Moreover, increasing the expression of this isoform limits fibrosis in vivo in mice, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem-cell populations.
C1 [Mueller, Alisa A.; van Velthoven, Cindy T.; Fukumoto, Kathryn D.; Cheung, Tom H.; Rando, Thomas A.] Stanford Univ, Paul F Glenn Ctr Biol Aging, Sch Med, Stanford, CA 94305 USA.
   [Mueller, Alisa A.; van Velthoven, Cindy T.; Fukumoto, Kathryn D.; Cheung, Tom H.; Rando, Thomas A.] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA.
   [Mueller, Alisa A.] Stanford Univ, Program Canc Biol, Sch Med, Stanford, CA 94305 USA.
   [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 USA.
   [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Rehabil Res & Dev REAP, Palo Alto, CA 94304 USA.
   [Mueller, Alisa A.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
   [Cheung, Tom H.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Stanford University; Stanford University; Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Hong Kong University of Science & Technology
RP Rando, TA (corresponding author), Stanford Univ, Paul F Glenn Ctr Biol Aging, Sch Med, Stanford, CA 94305 USA.; Rando, TA (corresponding author), Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA.; Rando, TA (corresponding author), Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 USA.; Rando, TA (corresponding author), Vet Affairs Palo Alto Hlth Care Syst, Rehabil Res & Dev REAP, Palo Alto, CA 94304 USA.
EM rando@stanford.edu
FU Glenn Foundation for Medical Research; National Institutes of Health [F30 AG043235]; California Institute for Regenerative Medicine [TG2-01159]; Department of Veterans Affairs; NIH [P01 AG036695, R01 AG23806, R01 AR062185, TR01 AG47820]; National Institute on Aging [P01AG036695] Funding Source: NIH RePORTER
NR 33
TC 112
Z9 132
U1 2
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 276
EP 279
DI 10.1038/nature20160
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700058
PM 27894125
DA 2026-03-09
ER

PT J
AU Hassan, R
   Müller, RD
   Gurnis, M
   Williams, SE
   Flament, N
AF Hassan, Rakib
   Mueller, R. Dietmar
   Gurnis, Michael
   Williams, Simon E.
   Flament, Nicolas
TI A rapid burst in hotspot motion through the interaction of tectonics and deep mantle flow
SO NATURE
LA English
DT Article
ID boundary-layer; plate motions; earth models; plumes; dynamics; temperature; convection; tomography; evolution; pacific
AB Volcanic hotspot tracks featuring linear progressions in the age of volcanism are typical surface expressions of plate tectonic movement on top of narrow plumes of hot material within Earth's mantle(1). Seismic imaging reveals that these plumes can be of deep origin(2)-probably rooted on thermochemical structures in the lower mantle(3-6). Although palaeomagnetic and radiometric age data suggest that mantle flow can advect plume conduits laterally(7,8), the flow dynamics underlying the formation of the sharp bend occurring only in the Hawaiian-Emperor hotspot track in the Pacific Ocean remains enigmatic. Here we present palaeogeographically constrained numerical models of thermochemical convection and demonstrate that flow in the deep lower mantle under the north Pacific was anomalously vigorous between 100 million years ago and 50 million years ago as a consequence of long-lasting subduction systems, unlike those in the south Pacific. These models show a sharp bend in the Hawaiian-Emperor hotspot track arising from the interplay of plume tilt and the lateral advection of plume sources. The different trajectories of the Hawaiian and Louisville hotspot tracks arise from asymmetric deformation of thermochemical structures under the Pacific between 100 million years ago and 50 million years ago. This asymmetric deformation waned just before the Hawaiian-Emperor bend developed, owing to flow in the deepest lower mantle associated with slab descent in the north and south Pacific.
C1 [Hassan, Rakib; Mueller, R. Dietmar; Williams, Simon E.; Flament, Nicolas] Univ Sydney, Sch Geosci, EarthByte Grp, Sydney, NSW 2006, Australia.
   [Gurnis, Michael] CALTECH, Seismol Lab, Pasadena, CA 91125 USA.
C3 University of Sydney; California Institute of Technology
RP Hassan, R (corresponding author), Univ Sydney, Sch Geosci, EarthByte Grp, Sydney, NSW 2006, Australia.
EM rakib.hassan@sydney.edu.au
FU NSF [EAR-1161046, EAR-1247022]; ARC [IH130200012]; Australian Government; Directorate For Geosciences; Division Of Earth Sciences [1600956] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1247022] Funding Source: National Science Foundation
NR 42
TC 74
Z9 88
U1 4
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 239
EP +
DI 10.1038/nature17422
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200048
PM 27172048
DA 2026-03-09
ER

PT J
AU Li, LJ
   O'Farrell, ECT
   Loh, KP
   Eda, G
   Özyilmaz, B
   Neto, AHC
AF Li, L. J.
   O'Farrell, E. C. T.
   Loh, K. P.
   Eda, G.
   Ozyilmaz, B.
   Neto, A. H. Castro
TI Controlling many-body states by the electric-field effect in a two-dimensional material
SO NATURE
LA English
DT Article
ID superlattice formation; transition; superconductivity; transport; graphene
AB To understand the complex physics of a system with strong electron-electron interactions, the ideal is to control and monitor its properties while tuning an external electric field applied to the system (the electric-field effect). Indeed, complete electric-field control of many-body states in strongly correlated electron systems is fundamental to the next generation of condensed matter research and devices(1-3). However, the material must be thin enough to avoid shielding of the electric field in the bulk material. Two-dimensional materials do not experience electrical screening, and their charge-carrier density can be controlled by gating. Octahedral titanium diselenide (1T-TiSe2) is a prototypical two-dimensional material that reveals a charge-density wave (CDW) and superconductivity in its phase diagram(4), presenting several similarities with other layered systems such as copper oxides(5), iron pnictides(6), and crystals of rare-earth elements and actinide atoms(7). By studying 1T-TiSe2 single crystals with thicknesses of 10 nanometres or less, encapsulated in two-dimensional layers of hexagonal boron nitride, we achieve unprecedented control over the CDW transition temperature (tuned from 170 kelvin to 40 kelvin), and over the superconductivity transition temperature (tuned from a quantum critical point at 0 kelvin up to 3 kelvin). Electrically driving TiSe2 over different ordered electronic phases allows us to study the details of the phase transitions between many-body states. Observations of periodic oscillations of magnetoresistance induced by the Little-Parks effect show that the appearance of superconductivity is directly correlated with the spatial texturing of the amplitude and phase of the superconductivity order parameter, corresponding to a two-dimensional matrix of superconductivity. We infer that this superconductivity matrix is supported by a matrix of incommensurate CDW states embedded in the commensurate CDW states. Our results show that spatially modulated electronic states are fundamental to the appearance of two-dimensional superconductivity.
C1 [Li, L. J.; O'Farrell, E. C. T.; Loh, K. P.; Eda, G.; Ozyilmaz, B.; Neto, A. H. Castro] Natl Univ Singapore, Ctr Adv Mat 2D, Singapore 117546, Singapore.
   [Li, L. J.; O'Farrell, E. C. T.; Loh, K. P.; Eda, G.; Ozyilmaz, B.; Neto, A. H. Castro] Natl Univ Singapore, Graphene Res Ctr, Singapore 117546, Singapore.
   [Li, L. J.; O'Farrell, E. C. T.; Eda, G.; Ozyilmaz, B.; Neto, A. H. Castro] Natl Univ Singapore, Dept Phys, Singapore 117542, Singapore.
   [Li, L. J.; Loh, K. P.; Eda, G.] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore.
C3 National University of Singapore; National University of Singapore; National University of Singapore; National University of Singapore
RP Neto, AHC (corresponding author), Natl Univ Singapore, Ctr Adv Mat 2D, Singapore 117546, Singapore.
EM phycastr@nus.edu.sg
FU MOE [R-143-000-556-112]; National Research Foundation (NRF) [NRF-NRFF2011-02]; NRF, Prime Minister's Office, Singapore under Competitive Research Programme (CRP award) [NRF-CRP9-2011-3]; SMF-NUS Research Horizons Award; CRP award [NRF-CRP6-2010-05]
NR 39
TC 446
Z9 494
U1 14
U2 849
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 185
EP U129
DI 10.1038/nature16175
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700031
PM 26700810
DA 2026-03-09
ER

PT J
AU Glasser, MF
   Coalson, TS
   Robinson, EC
   Hacker, CD
   Harwell, J
   Yacoub, E
   Ugurbil, K
   Andersson, J
   Beckmann, CF
   Jenkinson, M
   Smith, SM
   Van Essen, DC
AF Glasser, Matthew F.
   Coalson, Timothy S.
   Robinson, Emma C.
   Hacker, Carl D.
   Harwell, John
   Yacoub, Essa
   Ugurbil, Kamil
   Andersson, Jesper
   Beckmann, Christian F.
   Jenkinson, Mark
   Smith, Stephen M.
   Van Essen, David C.
TI A multi-modal parcellation of human cerebral cortex
SO NATURE
LA English
DT Article
ID human connectome project; resting-state fmri; hemispheric asymmetry; functional connectivity; individual-differences; brain activity; myelin content; mri; areas; organization
AB Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multimodal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal 'fingerprint' of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.
C1 [Glasser, Matthew F.; Coalson, Timothy S.; Harwell, John; Van Essen, David C.] Washington Univ, Sch Med, Dept Neurosci, St Louis, MO 63110 USA.
   [Robinson, Emma C.; Andersson, Jesper; Jenkinson, Mark; Smith, Stephen M.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, FMRIB Ctr, Oxford OX3 9DU, England.
   [Robinson, Emma C.] Imperial Coll, Dept Comp, London SW7 2AZ, England.
   [Hacker, Carl D.] Washington Univ, Dept Biomed Engn, St Louis, MO 63110 USA.
   [Yacoub, Essa; Ugurbil, Kamil] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA.
   [Beckmann, Christian F.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 EN Nijmegen, Netherlands.
   [Beckmann, Christian F.] Radboud Univ Nijmegen, Med Ctr Nijmegen, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands.
C3 Washington University (WUSTL); University of Oxford; Imperial College London; Washington University (WUSTL); University of Minnesota System; University of Minnesota Twin Cities; Radboud University Nijmegen; Radboud University Nijmegen
RP Glasser, MF; Van Essen, DC (corresponding author), Washington Univ, Sch Med, Dept Neurosci, St Louis, MO 63110 USA.
EM glasserm@wustl.edu; vanessen@wustl.edu
FU NIH [F30 MH097312, ROIMH-60974, F30 MH099877]; Human Connectome Project grant from the 16 NIH Institutes and Centers [1U54MH091657]; Wellcome Trust [098369/Z/12/Z]; National Institute of Mental Health [R01MH060974] Funding Source: NIH RePORTER
NR 42
TC 3389
Z9 3872
U1 32
U2 701
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 171
EP +
DI 10.1038/nature18933
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100028
PM 27437579
DA 2026-03-09
ER

PT J
AU Kara, E
   Miller, JM
   Reynolds, C
   Dai, LX
AF Kara, Erin
   Miller, Jon M.
   Reynolds, Chris
   Dai, Lixin
TI Relativistic reverberation in the accretion flow of a tidal disruption event
SO NATURE
LA English
DT Article
ID x-ray reverberation; active galactic nuclei; broad-line region; black-hole mass; radius-luminosity relationship; k-alpha reverberation; narrow-line; xmm-newton; iron k; time lags
AB Our current understanding of the curved space-time around supermassive black holes is based on actively accreting black holes, which make up only ten per cent or less of the overall population. X-ray observations of that small fraction reveal strong gravitational redshifts that indicate that many of these black holes are rapidly rotating(1); however, selection biases suggest that these results are not necessarily reflective of the majority of black holes in the Universe(2). Tidal disruption events, where a star orbiting an otherwise dormant black hole gets tidally shredded and accreted onto the black hole(3), can provide a short, unbiased glimpse at the space-time around the other ninety per cent of black holes. Observations of tidal disruptions have hitherto revealed the formation of an accretion disk and the onset of an accretion-powered jet(4-8), but have failed to reveal emission from the inner accretion flow, which enables the measurement of black hole spin. Here we report observations of reverberation(9-12) arising from gravitationally redshifted iron Ka photons reflected off the inner accretion flow in the tidal disruption event Swift J1644+57. From the reverberation timescale, we estimate the mass of the black hole to be a few million solar masses, suggesting an accretion rate of 100 times the Eddington limit or more(13). The detection of reverberation from the relativistic depths of this rare super-Eddington event demonstrates that the X-rays do not arise from the relativistically moving regions of a jet, as previously thought(5,14).
C1 [Kara, Erin; Reynolds, Chris] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Kara, Erin] NASA, Xray Astrophys Lab, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Kara, Erin; Reynolds, Chris; Dai, Lixin] Univ Maryland, Joint Space Sci Inst, College Pk, MD 20742 USA.
   [Miller, Jon M.] Univ Michigan, Dept Astron, Ann Arbor, MI 48103 USA.
   [Dai, Lixin] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
C3 University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; University of Michigan System; University of Michigan; University System of Maryland; University of Maryland College Park
RP Kara, E (corresponding author), Univ Maryland, Dept Astron, College Pk, MD 20742 USA.; Kara, E (corresponding author), NASA, Xray Astrophys Lab, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.; Kara, E (corresponding author), Univ Maryland, Joint Space Sci Inst, College Pk, MD 20742 USA.
EM ekara@astro.umd.edu
FU Hubble Fellowship Program from Space Telescope Science Institute [HST-HF2-51360.001-A]; NASA [NAS5-26555, NNX14AF86G]; NASA/NSF/TCAN [NNX14AB46G]; NSF/XSEDE/TACC [TG-PHY120005]; NASA/Pleiades [SMD-14-5451]; ESA member states; US (NASA); Suzaku satellite; NASA [NNX14AF86G, 684363] Funding Source: Federal RePORTER; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1333514] Funding Source: National Science Foundation
NR 61
TC 72
Z9 77
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 388
EP +
DI 10.1038/nature18007
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200033
PM 27338795
DA 2026-03-09
ER

PT J
AU Kotzin, JJ
   Spencer, SP
   McCright, SJ
   Kumar, DBU
   Collet, MA
   Mowel, WK
   Elliott, EN
   Uyar, A
   Makiya, MA
   Dunagin, MC
   Harman, CCD
   Virtue, AT
   Zhu, S
   Bailis, W
   Stein, J
   Hughes, C
   Raj, A
   Wherry, EJ
   Goff, LA
   Klion, AD
   Rinn, JL
   Williams, A
   Flavell, RA
   Henao-Mejia, J
AF Kotzin, Jonathan J.
   Spencer, Sean P.
   McCright, Sam J.
   Kumar, Dinesh B. Uthaya
   Collet, Magalie A.
   Mowel, Walter K.
   Elliott, Ellen N.
   Uyar, Asli
   Makiya, Michelle A.
   Dunagin, Margaret C.
   Harman, Christian C. D.
   Virtue, Anthony T.
   Zhu, Stella
   Bailis, Will
   Stein, Judith
   Hughes, Cynthia
   Raj, Arjun
   Wherry, E. John
   Goff, Loyal A.
   Klion, Amy D.
   Rinn, John L.
   Williams, Adam
   Flavell, Richard A.
   Henao-Mejia, Jorge
TI The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan
SO NATURE
LA English
DT Article
ID chromatin; macrophages; homeostasis; monocytes; bcl-2; differentiation; vernalization; expression; survival; prc2
AB Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body(1,2). Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation(1,2). However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long non-coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long non-coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
C1 [Kotzin, Jonathan J.; Spencer, Sean P.; McCright, Sam J.; Mowel, Walter K.; Virtue, Anthony T.; Henao-Mejia, Jorge] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Kotzin, Jonathan J.; Spencer, Sean P.; McCright, Sam J.; Mowel, Walter K.; Virtue, Anthony T.; Wherry, E. John; Henao-Mejia, Jorge] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
   [Kumar, Dinesh B. Uthaya; Collet, Magalie A.; Elliott, Ellen N.; Uyar, Asli; Zhu, Stella; Williams, Adam] Jackson Lab Genom Med, Farmington, CT 06032 USA.
   [Kumar, Dinesh B. Uthaya; Williams, Adam] Univ Connecticut, Ctr Hlth, Dept Genet & Genom Sci, Farmington, CT 06032 USA.
   [Makiya, Michelle A.; Klion, Amy D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Dunagin, Margaret C.; Raj, Arjun] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
   [Harman, Christian C. D.; Bailis, Will; Stein, Judith; Hughes, Cynthia; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
   [Harman, Christian C. D.; Stein, Judith; Hughes, Cynthia; Flavell, Richard A.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06510 USA.
   [Wherry, E. John] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Goff, Loyal A.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Goff, Loyal A.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA.
   [Rinn, John L.] Harvard Med Sch, Biol & Biomed Sci, Boston, MA 02115 USA.
   [Rinn, John L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Henao-Mejia, Jorge] Childrens Hosp Philadelphia, Div Transplant Immunol, Philadelphia, PA 19104 USA.
   [Spencer, Sean P.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
C3 University of Pennsylvania; University of Pennsylvania; Jackson Laboratory; University of Connecticut; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Pennsylvania; Yale University; Yale University; Howard Hughes Medical Institute; University of Pennsylvania; Johns Hopkins University; Johns Hopkins University; Harvard University; Harvard Medical School; Harvard University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Henao-Mejia, J (corresponding author), Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.; Henao-Mejia, J (corresponding author), Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.; Williams, A (corresponding author), Jackson Lab Genom Med, Farmington, CT 06032 USA.; Williams, A (corresponding author), Univ Connecticut, Ctr Hlth, Dept Genet & Genom Sci, Farmington, CT 06032 USA.; Flavell, RA (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.; Flavell, RA (corresponding author), Yale Univ, Howard Hughes Med Inst, New Haven, CT 06510 USA.; Henao-Mejia, J (corresponding author), Childrens Hosp Philadelphia, Div Transplant Immunol, Philadelphia, PA 19104 USA.
EM adam.williams@jax.org; richard.flavell@yale.edu; jhena@mail.med.upenn.edu
FU Children's Hospital of Philadelphia; IFI; IDOM; COE at the University of Pennsylvania; NIH NIAID [1R21AI110776-01]; Howard Hughes Medical Institute; NIH NIDDK [T32-DK00778017]; NIH NRSA [F30-DK094708]; NSF [1350601]; Division of Intramural Research, NIAID, NIH;  [T32-AI05542803];  [1DP2OD008514];  [1R33EB019767]; National Cancer Institute [P30CA016359] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001863] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI001130, T32AI055428] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007780] Funding Source: NIH RePORTER
NR 26
TC 241
Z9 290
U1 2
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 239
EP +
DI 10.1038/nature19346
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100049
PM 27525555
DA 2026-03-09
ER

PT J
AU Crowther, TW
   Todd-Brown, KEO
   Rowe, CW
   Wieder, WR
   Carey, JC
   Machmuller, MB
   Snoek, BL
   Fang, S
   Zhou, G
   Allison, SD
   Blair, JM
   Bridgham, SD
   Burton, AJ
   Carrillo, Y
   Reich, PB
   Clark, JS
   Classen, AT
   Dijkstra, FA
   Elberling, B
   Emmett, BA
   Estiarte, M
   Frey, SD
   Guo, J
   Harte, J
   Jiang, L
   Johnson, BR
   Kröel-Dulay, G
   Larsen, KS
   Laudon, H
   Lavallee, JM
   Luo, Y
   Lupascu, M
   Ma, LN
   Marhan, S
   Michelsen, A
   Mohan, J
   Niu, S
   Pendall, E
   Peñuelas, J
   Pfeifer-Meister, L
   Poll, C
   Reinsch, S
   Reynolds, LL
   Schmidt, IK
   Sistla, S
   Sokol, NW
   Templer, PH
   Treseder, KK
   Welker, JM
   Bradford, MA
AF Crowther, T. W.
   Todd-Brown, K. E. O.
   Rowe, C. W.
   Wieder, W. R.
   Carey, J. C.
   Machmuller, M. B.
   Snoek, B. L.
   Fang, S.
   Zhou, G.
   Allison, S. D.
   Blair, J. M.
   Bridgham, S. D.
   Burton, A. J.
   Carrillo, Y.
   Reich, P. B.
   Clark, J. S.
   Classen, A. T.
   Dijkstra, F. A.
   Elberling, B.
   Emmett, B. A.
   Estiarte, M.
   Frey, S. D.
   Guo, J.
   Harte, J.
   Jiang, L.
   Johnson, B. R.
   Kroel-Dulay, G.
   Larsen, K. S.
   Laudon, H.
   Lavallee, J. M.
   Luo, Y.
   Lupascu, M.
   Ma, L. N.
   Marhan, S.
   Michelsen, A.
   Mohan, J.
   Niu, S.
   Pendall, E.
   Penuelas, J.
   Pfeifer-Meister, L.
   Poll, C.
   Reinsch, S.
   Reynolds, L. L.
   Schmidt, I. K.
   Sistla, S.
   Sokol, N. W.
   Templer, P. H.
   Treseder, K. K.
   Welker, J. M.
   Bradford, M. A.
TI Quantifying global soil carbon losses in response to warming
SO NATURE
LA English
DT Article
ID earth system models; climate-change; temperature sensitivity; organic-carbon; feedbacks; tundra; decomposition; uncertainty; projections; ecosystems
AB The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming(1-4). Despite evidence that warming enhances carbon fluxes to and from the soil(5,6), the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 +/- 30 petagrams of carbon to 203 +/- 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 +/- 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period(7,8). Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.
C1 [Crowther, T. W.; Snoek, B. L.; Bradford, M. A.] Netherlands Inst Ecol, Droevendaalsesteeg 10, NL-6708 PB Wageningen, Netherlands.
   [Crowther, T. W.; Rowe, C. W.; Bradford, M. A.] Yale Univ, Yale Sch Forestry & Environm Studies, 370 Prospect St, New Haven, CT 06511 USA.
   [Todd-Brown, K. E. O.; Sokol, N. W.] Pacific Northwest Natl Lab, Richland, WA 99354 USA.
   [Wieder, W. R.] Natl Ctr Atmospher Res, Climate & Global Dynam Lab, Boulder, CO 80307 USA.
   [Wieder, W. R.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80303 USA.
   [Carey, J. C.] Marine Biol Lab, 7 MBL St, Woods Hole, MA 02543 USA.
   [Machmuller, M. B.; Lavallee, J. M.] Colorado State Univ, Nat Resource Ecol Lab, 1499 Campus Delivery, Ft Collins, CO 80523 USA.
   [Snoek, B. L.] Wageningen Univ, Lab Nematol, Droevendaalsesteeg 1, NL-6708 PB Wageningen, Netherlands.
   [Fang, S.; Zhou, G.] Chinese Acad Meteorol Sci, 46 Zhongguancun South St, Beijing 100081, Peoples R China.
   [Fang, S.] Nanjing Univ Informat Sci & Technol, Collaborat Innovat Ctr Forecast Meteorol Disast, Nanjing 210044, Jiangsu, Peoples R China.
   [Allison, S. D.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Allison, S. D.; Treseder, K. K.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA.
   [Blair, J. M.] Kansas State Univ, Div Biol, Ackert Hall, Manhattan, KS 66506 USA.
   [Bridgham, S. D.; Pfeifer-Meister, L.; Reynolds, L. L.] Univ Oregon, Inst Ecol & Evolut, Eugene, OR 97403 USA.
   [Burton, A. J.] Michigan Technol Univ, Sch Forest Resources & Environm Sci, Houghton, MI 49931 USA.
   [Carrillo, Y.; Reich, P. B.; Pendall, E.] Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2570, Australia.
   [Reich, P. B.] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Clark, J. S.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
   [Classen, A. T.] Univ Copenhagen, Nat Hist Museum Denmark, Ctr Macroecol Evolut & Climate, Univ Pk 15, DK-2100 Copenhagen O, Denmark.
   [Classen, A. T.] Univ Tennessee, Dept Ecol & Evolutionary Biol, 569 Dabney Hall,1416 Circle Dr, Knoxville, TN 37996 USA.
   [Dijkstra, F. A.] Univ Sydney, Ctr Carbon Water & Food, Camden, NSW 2570, Australia.
   [Elberling, B.; Michelsen, A.] Univ Copenhagen, Dept Geosci & Nat Resource Management, Ctr Permafrost CENPERM, Oster Voldgade 10, DK-1350 Copenhagen K, Denmark.
   [Emmett, B. A.; Reinsch, S.] Environm Ctr Wales, Ctr Ecol & Hydrol, Bangor LL57 2UW, Gwynedd, Wales.
   [Estiarte, M.; Penuelas, J.] CSIC, Global Ecol Unit CREAF CSIC, Cerdanyola Del Valles 08193, Catalonia, Spain.
   [Estiarte, M.; Penuelas, J.] CREAF, Cerdanyola Del Valles 08193, Catalonia, Spain.
   [Frey, S. D.] Univ New Hampshire, Dept Nat Resources & Environm, Durham, NH 03824 USA.
   [Guo, J.] Northeast Normal Univ, Minist Educ, Key Lab Vegetat Ecol, Changchun 130024, Jilin, Peoples R China.
   [Harte, J.] Univ Calif Berkeley, Energy & Resources Grp, Berkeley, CA 94720 USA.
   [Jiang, L.; Luo, Y.] Univ Oklahoma, Dept Microbiol & Plant Biol, Norman, OK 73019 USA.
   [Johnson, B. R.] Univ Oregon, Dept Landscape Architecture, Eugene, OR 97403 USA.
   [Kroel-Dulay, G.] Magyar Tud Akad Ctr Ecol Res, Inst Ecol & Bot, 2-4 Alkotmany Utcakereso, H-2163 Vacratot, Hungary.
   [Larsen, K. S.; Schmidt, I. K.] Univ Copenhagen, Dept Geosci & Nat Resource Management, Rolighedsvej 23, DK-1958 Frederiksberg C, Denmark.
   [Laudon, H.] Swedish Univ Agr Sci, Dept Forest Ecol & Management, S-90183 Umea, Sweden.
   [Lavallee, J. M.] Univ Manchester, Fac Life Sci, Dover St, Manchester M13 9PT, Lancs, England.
   [Luo, Y.] Tsinghua Univ, Ctr Earth Syst Sci, Beijing 100084, Peoples R China.
   [Lupascu, M.] Natl Univ Singapore, Dept Geog, 1 Arts Link, Singapore 117570, Singapore.
   [Ma, L. N.] Chinese Acad Sci, Inst Bot, State Key Lab Vegetat & Environm Change, Beijing 100093, Peoples R China.
   [Marhan, S.; Poll, C.] Univ Hohenheim, Inst Soil Sci & Land Evaluat, D-70593 Stuttgart, Germany.
   [Michelsen, A.] Univ Copenhagen, Dept Biol, Univ Pk 15, DK-2100 Copenhagen, Denmark.
   [Mohan, J.] Univ Georgia, Odum Sch Ecol, Athens, GA 30601 USA.
   [Niu, S.] Chinese Acad Sci, Inst Geog Sci & Nat Resources Res, Key Lab Ecosyst Network Observat & Modeling, Beijing 100101, Peoples R China.
   [Sistla, S.] Hampshire Coll, Sch Nat Sci, 893 West St, Amherst, MA 01002 USA.
   [Templer, P. H.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
   [Welker, J. M.] Univ Alaska Anchorage, Dept Biol Sci, Anchorage, AK 99508 USA.
C3 Royal Netherlands Academy of Arts & Sciences; Netherlands Institute of Ecology (NIOO-KNAW); Yale University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; National Center Atmospheric Research (NCAR) - USA; University of Colorado System; University of Colorado Boulder; Marine Biological Laboratory - Woods Hole; Colorado State University System; Colorado State University Fort Collins; Wageningen University & Research; China Meteorological Administration; Chinese Academy of Meteorological Sciences (CAMS); Nanjing University of Information Science & Technology; University of California System; University of California Irvine; University of California System; University of California Irvine; Kansas State University; University of Oregon; Michigan Technological University; Western Sydney University; University of Minnesota System; University of Minnesota Twin Cities; Duke University; University of Copenhagen; University of Tennessee System; University of Tennessee Knoxville; University of Sydney; University of Copenhagen; UK Centre for Ecology & Hydrology (UKCEH); Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Consejo Superior de Investigaciones Cientificas (CSIC); Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); University System Of New Hampshire; University of New Hampshire; Northeast Normal University - China; University of California System; University of California Berkeley; University of Oklahoma System; University of Oklahoma - Norman; University of Oregon; HUN-REN; HUN-REN Centre for Ecological Research; University of Copenhagen; Swedish University of Agricultural Sciences; University of Manchester; Tsinghua University; National University of Singapore; Chinese Academy of Sciences; Institute of Botany, CAS; University Hohenheim; University of Copenhagen; University System of Georgia; University of Georgia; Chinese Academy of Sciences; Institute of Geographic Sciences & Natural Resources Research, CAS; Boston University; University of Alaska System; University of Alaska Anchorage
RP Crowther, TW (corresponding author), Netherlands Inst Ecol, Droevendaalsesteeg 10, NL-6708 PB Wageningen, Netherlands.; Crowther, TW (corresponding author), Yale Univ, Yale Sch Forestry & Environm Studies, 370 Prospect St, New Haven, CT 06511 USA.
EM thomas.crowther11@gmail.com
FU Global Soil Biodiversity Initiative (GSBI); Marie Sklodowska-Curie actions; British Ecological Society; Yale Climate and Energy Institute; US National Science Foundation; US Department of Energy; Linus Pauling Distinguished Postdoctoral Fellowship programme; NERC [ceh020008] Funding Source: UKRI; Natural Environment Research Council [ceh020008] Funding Source: researchfish; Direct For Biological Sciences; Emerging Frontiers [1318164, 1137364] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1340847, 1457614, 1026843, 1237491] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1242531, 1234162, 1456610, 1120064, 1257183] Funding Source: National Science Foundation
NR 30
TC 1002
Z9 1191
U1 81
U2 1910
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 104
EP +
DI 10.1038/nature20150
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600057
PM 27905442
DA 2026-03-09
ER

PT J
AU Fischer, N
   Neumann, P
   Bock, LV
   Maracci, C
   Wang, Z
   Paleskava, A
   Konevega, AL
   Schröder, GF
   Grubmüller, H
   Ficner, R
   Rodnina, MV
   Stark, H
AF Fischer, Niels
   Neumann, Piotr
   Bock, Lars V.
   Maracci, Cristina
   Wang, Zhe
   Paleskava, Alena
   Konevega, Andrey L.
   Schroeder, Gunnar F.
   Grubmueller, Helmut
   Ficner, Ralf
   Rodnina, Marina V.
   Stark, Holger
TI The pathway to GTPase activation of elongation factor SelB on the ribosome
SO NATURE
LA English
DT Article
ID aminoacyl-transfer-rna; factor-tu; messenger-rna; crystal-structure; ef-tu; selenocysteine incorporation; active-role; recognition; hydrolysis; binding
AB In all domains of life, selenocysteine (Sec) is delivered to the ribosome by selenocysteine-specific tRNA (tRNA(Sec)) with the help of a specialized translation factor, SelB in bacteria. Sec-tRNA(Sec) recodes a UGA stop codon next to a downstream mRNA stem-loop. Here we present the structures of six intermediates on the pathway of UGA recoding in Escherichia coli by single-particle cryo-electron microscopy. The structures explain the specificity of Sec-tRNA(Sec) binding by SelB and show large-scale rearrangements of Sec-tRNA(Sec). Upon initial binding of SelB-Sec-tRNA(Sec) to the ribosome and codon reading, the 30S subunit adopts an open conformation with Sec-tRNA(Sec) covering the sarcin-ricin loop (SRL) on the 50S subunit. Subsequent codon recognition results in a local closure of the decoding site, which moves Sec-tRNA(Sec) away from the SRL and triggers a global closure of the 30S subunit shoulder domain. As a consequence, SelB docks on the SRL, activating the GTPase of SelB. These results reveal how codon recognition triggers GTPase activation in translational GTPases.
C1 [Fischer, Niels; Stark, Holger] Max Planck Inst Biophys Chem, Dept Struct Dynam, Fassberg 11, D-37077 Gottingen, Germany.
   [Neumann, Piotr; Ficner, Ralf] Georg August Univ Gottingen, Inst Microbiol & Genet, Dept Mol Struct Biol, GZMB, Justus von Liebig Weg 11, D-37077 Gottingen, Germany.
   [Bock, Lars V.; Grubmueller, Helmut] Max Planck Inst Biophys Chem, Dept Theoret & Computat Biophys, Fassberg 11, D-37077 Gottingen, Germany.
   [Maracci, Cristina; Paleskava, Alena; Konevega, Andrey L.; Rodnina, Marina V.] Max Planck Inst Biophys Chem, Dept Phys Biochem, Fassberg 11, D-37077 Gottingen, Germany.
   [Wang, Zhe; Schroeder, Gunnar F.] Forschungszentrum, Inst Complex Syst ICS 6, D-52425 Julich, Germany.
   [Schroeder, Gunnar F.] Heinrich Heine Univ Dusseldorf, Dept Phys, D-40225 Dusseldorf, Germany.
   [Paleskava, Alena; Konevega, Andrey L.] Kurchatov Inst, Mol & Radiat Biophys Dept, BP Konstantinov Petersburg Nucl Phys Inst, Natl Res Ctr, Gatchina 188300, Russia.
   [Paleskava, Alena; Konevega, Andrey L.] St Petersburg Polytech Univ, Polytech Skaya 29, St Petersburg 195251, Russia.
C3 Max Planck Society; University of Gottingen; Max Planck Society; Max Planck Society; Helmholtz Association; Heinrich Heine University Dusseldorf; National Research Centre - Kurchatov Institute; Petersburg Nuclear Physics Institute; Peter the Great St. Petersburg Polytechnic University
RP Fischer, N; Stark, H (corresponding author), Max Planck Inst Biophys Chem, Dept Struct Dynam, Fassberg 11, D-37077 Gottingen, Germany.
EM niels.fischer@mpibpc.mpg.de; hstark1@gwdg.de
FU Deutsche Forschungsgemeinschaft [FOR 1805];  [Sonderforschungsbereich 860]
NR 95
TC 95
Z9 111
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 80
EP +
DI 10.1038/nature20560
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600051
PM 27842381
DA 2026-03-09
ER

PT J
AU Aviram, N
   Ast, T
   Costa, EA
   Arakel, EC
   Chuartzman, SG
   Jan, CH
   Hassenteufel, S
   Dudek, J
   Jung, M
   Schorr, S
   Zimmermann, R
   Schwappach, B
   Weissman, JS
   Schuldiner, M
AF Aviram, Naama
   Ast, Tslil
   Costa, Elizabeth A.
   Arakel, Eric C.
   Chuartzman, Silvia G.
   Jan, Calvin H.
   Hassenteufel, Sarah
   Dudek, Johanna
   Jung, Martin
   Schorr, Stefan
   Zimmermann, Richard
   Schwappach, Blanche
   Weissman, Jonathan S.
   Schuldiner, Maya
TI The SND proteins constitute an alternative targeting route to the endoplasmic reticulum
SO NATURE
LA English
DT Article
ID signal recognition particle; saccharomyces-cerevisiae; membrane-protein; gene disruption; yeast; translocation; insertion; identification; transformation; deletion
AB In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments(1). Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway(2) or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40)(3,4) and homologous yeast guided entry of tail-anchored proteins (GET)(5,6) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay(7,8). We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae(9,10), and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.
C1 [Aviram, Naama; Ast, Tslil; Chuartzman, Silvia G.; Schuldiner, Maya] Weizmann Inst Sci, Dept Mol Genet, IL-7610001 Rehovot, Israel.
   [Costa, Elizabeth A.; Jan, Calvin H.; Weissman, Jonathan S.] UCSF, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Costa, Elizabeth A.; Jan, Calvin H.; Weissman, Jonathan S.] Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Arakel, Eric C.; Schwappach, Blanche] Univ Med Ctr Gottingen, Dept Mol Biol, D-37073 Gottingen, Germany.
   [Hassenteufel, Sarah; Dudek, Johanna; Jung, Martin; Schorr, Stefan; Zimmermann, Richard] Univ Saarland, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany.
   [Schwappach, Blanche] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany.
   [Ast, Tslil] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02114 USA.
C3 Weizmann Institute of Science; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of Gottingen; University of Gottingen Hospital; Saarland University; Max Planck Society; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Ast, T; Schuldiner, M (corresponding author), Weizmann Inst Sci, Dept Mol Genet, IL-7610001 Rehovot, Israel.; Ast, T (corresponding author), Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02114 USA.
EM tast@broadinstitute.org; maya.schuldiner@weizmann.ac.il
FU Israel Academy of Sciences and Humanities; DFG [IRTG 1830, ZI 234/13-1]; HOMFOR; Deutsche Forschungsgemeinschaft [SFB 1190 P04]; NIH/NGMS (Center for RNA Systems Biology) [P50 GM102706]; National Science Foundation [1144247]; Minerva foundation; Israel Science Foundation [791/14]
NR 40
TC 169
Z9 208
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 134
EP +
DI 10.1038/nature20169
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600063
PM 27905431
DA 2026-03-09
ER

PT J
AU Mallick, S
   Li, H
   Lipson, M
   Mathieson, I
   Gymrek, M
   Racimo, F
   Zhao, MY
   Chennagiri, N
   Nordenfelt, S
   Tandon, A
   Skoglund, P
   Lazaridis, I
   Sankararaman, S
   Fu, QM
   Rohland, N
   Renaud, G
   Erlich, Y
   Willems, T
   Gallo, C
   Spence, JP
   Song, YS
   Poletti, G
   Balloux, F
   van Driem, G
   de Knijff, P
   Romero, IG
   Jha, AR
   Behar, DM
   Bravi, CM
   Capelli, C
   Hervig, T
   Moreno-Estrada, A
   Posukh, OL
   Balanovska, E
   Balanovsky, O
   Karachanak-Yankova, S
   Sahakyan, H
   Toncheva, D
   Yepiskoposyan, L
   Tyler-Smith, C
   Xue, Y
   Abdullah, MS
   Ruiz-Linares, A
   Beall, CM
   Di Rienzo, A
   Jeong, C
   Starikovskaya, EB
   Metspalu, E
   Parik, J
   Villems, R
   Henn, BM
   Hodoglugil, U
   Mahley, R
   Sajantila, A
   Stamatoyannopoulos, G
   Wee, JTS
   Khusainova, R
   Khusnutdinova, E
   Litvinov, S
   Ayodo, G
   Comas, D
   Hammer, MF
   Kivisild, T
   Klitz, W
   Winkler, CA
   Labuda, D
   Bamshad, M
   Jorde, LB
   Tishkoff, SA
   Watkins, WS
   Metspalu, M
   Dryomov, S
   Sukernik, R
   Singh, L
   Thangaraj, K
   Pääbo, S
   Kelso, J
   Patterson, N
   Reich, D
AF Mallick, Swapan
   Li, Heng
   Lipson, Mark
   Mathieson, Iain
   Gymrek, Melissa
   Racimo, Fernando
   Zhao, Mengyao
   Chennagiri, Niru
   Nordenfelt, Susanne
   Tandon, Arti
   Skoglund, Pontus
   Lazaridis, Iosif
   Sankararaman, Sriram
   Fu, Qiaomei
   Rohland, Nadin
   Renaud, Gabriel
   Erlich, Yaniv
   Willems, Thomas
   Gallo, Carla
   Spence, Jeffrey P.
   Song, Yun S.
   Poletti, Giovanni
   Balloux, Francois
   van Driem, George
   de Knijff, Peter
   Romero, Irene Gallego
   Jha, Aashish R.
   Behar, Doron M.
   Bravi, Claudio M.
   Capelli, Cristian
   Hervig, Tor
   Moreno-Estrada, Andres
   Posukh, Olga L.
   Balanovska, Elena
   Balanovsky, Oleg
   Karachanak-Yankova, Sena
   Sahakyan, Hovhannes
   Toncheva, Draga
   Yepiskoposyan, Levon
   Tyler-Smith, Chris
   Xue, Yali
   Abdullah, M. Syafiq
   Ruiz-Linares, Andres
   Beall, Cynthia M.
   Di Rienzo, Anna
   Jeong, Choongwon
   Starikovskaya, Elena B.
   Metspalu, Ene
   Parik, Juri
   Villems, Richard
   Henn, Brenna M.
   Hodoglugil, Ugur
   Mahley, Robert
   Sajantila, Antti
   Stamatoyannopoulos, George
   Wee, Joseph T. S.
   Khusainova, Rita
   Khusnutdinova, Elza
   Litvinov, Sergey
   Ayodo, George
   Comas, David
   Hammer, Michael F.
   Kivisild, Toomas
   Klitz, William
   Winkler, Cheryl A.
   Labuda, Damian
   Bamshad, Michael
   Jorde, Lynn B.
   Tishkoff, Sarah A.
   Watkins, W. Scott
   Metspalu, Mait
   Dryomov, Stanislav
   Sukernik, Rem
   Singh, Lalji
   Thangaraj, Kumarasamy
   Paeaebo, Svante
   Kelso, Janet
   Patterson, Nick
   Reich, David
TI The Simons Genome Diversity Project: 300 genomes from 142 diverse populations
SO NATURE
LA English
DT Article
ID modern humans; neanderthal; ancestry; sequence; history; admixture; dispersal; inference; selection; plink
AB Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
C1 [Mallick, Swapan; Lipson, Mark; Mathieson, Iain; Zhao, Mengyao; Chennagiri, Niru; Nordenfelt, Susanne; Tandon, Arti; Skoglund, Pontus; Lazaridis, Iosif; Sankararaman, Sriram; Fu, Qiaomei; Rohland, Nadin; Reich, David] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
   [Mallick, Swapan; Li, Heng; Gymrek, Melissa; Zhao, Mengyao; Chennagiri, Niru; Nordenfelt, Susanne; Tandon, Arti; Skoglund, Pontus; Lazaridis, Iosif; Sankararaman, Sriram; Fu, Qiaomei; Rohland, Nadin; Patterson, Nick; Reich, David] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Mallick, Swapan; Zhao, Mengyao; Chennagiri, Niru; Nordenfelt, Susanne; Reich, David] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Gymrek, Melissa] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Gymrek, Melissa] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
   [Gymrek, Melissa; Erlich, Yaniv; Willems, Thomas; Klitz, William] New York Genome Ctr, New York, NY 10013 USA.
   [Racimo, Fernando] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Fu, Qiaomei] Chinese Acad Sci, Key Lab Vertebrate Evolut & Human Origins Chinese, IVPP, Beijing 100044, Peoples R China.
   [Renaud, Gabriel; Paeaebo, Svante; Kelso, Janet] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Erlich, Yaniv] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
   [Erlich, Yaniv] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Willems, Thomas] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA.
   [Gallo, Carla; Poletti, Giovanni] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Labs Invest & Desarrollo, Lima 15102, Peru.
   [Spence, Jeffrey P.] Univ Calif Berkeley, Computat Biol Grad Grp, Berkeley, CA 94720 USA.
   [Song, Yun S.] Univ Calif Berkeley, Div Comp Sci, Berkeley, CA 94720 USA.
   [Song, Yun S.] Univ Penn, Dept Stat, Philadelphia, PA 19104 USA.
   [Song, Yun S.] Univ Penn, Dept Math, Philadelphia, PA 19104 USA.
   [Song, Yun S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Balloux, Francois] UCL, Genet Inst, Gower St, London WC1E 6BT, England.
   Univ Bern, Inst Linguist, CH-3012 Bern, Switzerland.
   [de Knijff, Peter] Leiden Univ, Med Ctr, Dept Human & Clin Genet, Postzone S5-P, NL-2333 ZA Leiden, Netherlands.
   [Romero, Irene Gallego] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore.
   [Romero, Irene Gallego] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 636921, Singapore.
   [Jha, Aashish R.; Di Rienzo, Anna; Jeong, Choongwon] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Behar, Doron M.; Sahakyan, Hovhannes; Metspalu, Ene; Parik, Juri; Villems, Richard; Litvinov, Sergey; Kivisild, Toomas; Metspalu, Mait] Estonian Bioctr, Evolutionary Biol Grp, EE-51010 Tartu, Estonia.
   [Bravi, Claudio M.] Univ Nacl La Plata, Inst Multidisciplinario Biol Celular IMBICE, Lab Genet Mol Poblac, CCT CONICET La Plata,CIC Buenos Aires, B1906APO, La Plata, Buenos Aires, Argentina.
   [Capelli, Cristian] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Hervig, Tor] Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.
   [Moreno-Estrada, Andres] CINVESTAV, Natl Lab Genom Biodivers LANGEBIO, Guanajuato 36821, Mexico.
   [Posukh, Olga L.] Siberian Branch Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Posukh, Olga L.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
   [Balanovska, Elena; Balanovsky, Oleg] Med Genet Res Ctr, Moscow 115478, Russia.
   [Balanovsky, Oleg] Vavilov Inst Gen Genet, Moscow 119991, Russia.
   [Balanovsky, Oleg] Moscow Inst Phys & Technol, Dolgopruclniy 141700, Russia.
   [Karachanak-Yankova, Sena; Toncheva, Draga] Med Univ Sofia, Dept Med Genet, Natl Human Genome Ctr, Sofia 1431, Bulgaria.
   [Sahakyan, Hovhannes; Yepiskoposyan, Levon] Natl Acad Sci Armenia, Inst Mol Biol, Lab Ethnogen, Yerevan 0014, Armenia.
   [Tyler-Smith, Chris; Xue, Yali] Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton CB1O 1SA, Cambs, England.
   [Abdullah, M. Syafiq] RIPAS Hosp, Bandar Seri Begawan, Brunei.
   [Ruiz-Linares, Andres] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Beall, Cynthia M.] Case Western Reserve Univ, Dept Anthropol, Cleveland, OH 44106 USA.
   [Starikovskaya, Elena B.; Dryomov, Stanislav; Sukernik, Rem] Russian Acad Sci, Siberian Branch, Inst Mol & Cellular Biol, Lab Human Mol Genet, Novosibirsk 630090, Russia.
   [Metspalu, Ene; Villems, Richard] Univ Tartu, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Villems, Richard] Estonian Acad Sci, EE-10130 Tallinn, Estonia.
   [Henn, Brenna M.] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA.
   [Hodoglugil, Ugur] NextBio, Santa Clara, CA 95050 USA.
   [Mahley, Robert] Gladstone Inst, San Francisco, CA 94158 USA.
   [Sajantila, Antti] Univ Helsinki, Dept Forens Med, FIN-00014 Helsinki, Finland.
   [Stamatoyannopoulos, George] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA.
   [Wee, Joseph T. S.] Natl Canc Ctr Singapore, Singapore 169610, Singapore.
   [Khusainova, Rita; Khusnutdinova, Elza; Litvinov, Sergey] Russian Acad Sci, Inst Biochem & Genet, Ufa Res Ctr, Ufa 450054, Russia.
   [Khusainova, Rita; Khusnutdinova, Elza; Litvinov, Sergey] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450074, Russia.
   [Ayodo, George] Jaramogi Oginga Odinga Univ Sci & Technol, Banda 40601, Kenya.
   [Comas, David] Univ Pompeu Fabra, Dept Ciencies Expt St, Inst Biol Evolut CSIC UPF, Barcelona 08003, Spain.
   [Hammer, Michael F.] Univ Arizona, ARL Div Biotechnol, Tucson, AZ 85721 USA.
   [Kivisild, Toomas] Univ Cambridge, Div Biol Anthropol, Fitzwilliam St, Cambridge CB2 1QH, England.
   [Winkler, Cheryl A.] Leiclos Biomed Res Inc, NCI, Ctr Canc Res, Frederick Natl Lab,Basie Res Lab, Frederick, MD 21702 USA.
   [Labuda, Damian] Univ Montreal, CHU St Justine, Dept Pediat, Montreal, PQ H3T 1C5, Canada.
   [Bamshad, Michael] Univ Washington, Dept Pediat, Seattle, WA 98119 USA.
   [Jorde, Lynn B.] Univ Utah, Dept Human Genet, Sch Med, Salt Lake City, UT 34112 USA.
   [Tishkoff, Sarah A.] Univ Penn, Dept Genet & Biol, Philadelphia, PA 19104 USA.
   [Watkins, W. Scott] Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT 84112 USA.
   [Dryomov, Stanislav] Russian Acad Sci, Siberian Branch, Inst Archaeol & Ethnog, Dept Paleolith Archaeol, Novosibirsk 630090, Russia.
   [Sukernik, Rem] Altai State Univ, Barnaul 656000, Russia.
   [Singh, Lalji; Thangaraj, Kumarasamy] CSIR Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
   [Sankararaman, Sriram] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA.
   [Sankararaman, Sriram] Univ Calif Los Angeles, Dept Human Genet Sci, Los Angeles, CA 90095 USA.
   [Singh, Lalji] Genome Fdn, Hyderabad 500076, Andhra Pradesh, India.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Harvard University; University of California System; University of California Berkeley; Chinese Academy of Sciences; Max Planck Society; Columbia University; Columbia University; Massachusetts Institute of Technology (MIT); Universidad Peruana Cayetano Heredia; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of London; University College London; University of Bern; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Nanyang Technological University; Nanyang Technological University; University of Chicago; Estonian Biocentre; National University of La Plata; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Oxford; University of Bergen; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; Novosibirsk State University; Research Centre for Medical Genetics; Russian Academy of Sciences; Vavilov Institute of General Genetics; Moscow Institute of Physics & Technology; Medical University Sofia; National Academy of Sciences of Armenia; Institute of Molecular Biology - NAS RA; Wellcome Trust Sanger Institute; University of London; University College London; University System of Ohio; Case Western Reserve University; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; University of Tartu; Estonian Academy of Sciences; State University of New York (SUNY) System; Stony Brook University; University of California System; University of California San Francisco; The J David Gladstone Institutes; University of Helsinki; University of Washington; University of Washington Seattle; National Cancer Centre Singapore (NCCS); Russian Academy of Sciences; Institute of Biochemistry & Genetics of Ufa Science Centre of the RAS; Ufa University of Science & Technology; Jaramogi Oginga Odinga University of Science & Technology; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); University of Arizona; University of Cambridge; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Universite de Montreal; Centre Hospitalier Universitaire Sainte-Justine; University of Washington; University of Washington Seattle; Utah System of Higher Education; University of Utah; University of Pennsylvania; Utah System of Higher Education; University of Utah; Russian Academy of Sciences; Institute of Archaeology & Ethnography, Siberian Branch of Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Altai State University; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Mallick, S (corresponding author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Mallick, S (corresponding author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.; Mallick, S (corresponding author), Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM shop@genetics.med.harvard.edu; reich@genetics.med.harvard.edu
FU Simons Foundation [SFARI 280376]; US National Science Foundation [BCS-1032255]; Human Frontier Science program [LT001095/2014]; Wenner-Gren foundation; Swedish Research Council (VR) [2014-453]; NIJ [2014-DN-BX-K089]; Career Award at the Scientific Interface from the Burroughs Wellcome Fund; Natural Sciences and Engineering Research Council of Canada; ERC [FP7- 261213]; Russian Foundation for Basic Research [15-04-02543, 16-34-00599, 11-04-00725-a, 16-06-00303, 16-04-00890]; Russian Scientific Fund [14-04-00827]; Estonian Research Council; European Regional Development Fund (European Union) through the Centre of Excellence in Genomics to Estonian Biocentre; University of Tartu; Spanish MINECO [CGL-44351-P]; NIH [GM59290, 5DPIES022577 05, 1R01DK104339-01, 1R01GM113657-01, R01-GM094402, GM100233]; Wellcome Trust [093051]; NSF [0924726, 1153911]; CSIR Network Project grant [GENESIS: BSC0121]; Packard Fellowship for Science and Engineering; Max Planck Society; BBSRC [BB/H008802/1, BB/H008802/2] Funding Source: UKRI; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [0924726, 1153911, 1032255] Funding Source: National Science Foundation; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/H008802/2, BB/H008802/1] Funding Source: researchfish; Russian Science Foundation [14-14-00827] Funding Source: Russian Science Foundation
NR 45
TC 1004
Z9 1148
U1 9
U2 226
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 201
EP +
DI 10.1038/nature18964
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000037
PM 27654912
DA 2026-03-09
ER

PT J
AU Erdemir, A
   Ramirez, G
   Eryilmaz, OL
   Narayanan, B
   Liao, YF
   Kamath, G
   Sankaranarayanan, SKRS
AF Erdemir, Ali
   Ramirez, Giovanni
   Eryilmaz, Osman L.
   Narayanan, Badri
   Liao, Yifeng
   Kamath, Ganesh
   Sankaranarayanan, Subramanian K. R. S.
TI Carbon-based tribofilms from lubricating oils
SO NATURE
LA English
DT Article
ID future; challenges; mechanisms; additives; tribology; fullerene; metals; zddp; wear
AB Moving mechanical interfaces are commonly lubricated and separated by a combination of fluid films and solid 'tribofilms', which together ensure easy slippage and long wear life(1). The efficacy of the fluid film is governed by the viscosity of the base oil in the lubricant; the efficacy of the solid tribofilm, which is produced as a result of sliding contact between moving parts, relies upon the effectiveness of the lubricant's anti-wear additive (typically zinc dialkyldithiophosphate)(2). Minimizing friction and wear continues to be a challenge, and recent efforts have focused on enhancing the anti-friction and anti-wear properties of lubricants by incorporating inorganic nanoparticles and ionic liquids(3,4). Here, we describe the in operando formation of carbon-based tribofilms via dissociative extraction from base-oil molecules on catalytically active, sliding nanometre-scale crystalline surfaces, enabling base oils to provide not only the fluid but also the solid tribofilm. We study nanocrystalline catalytic coatings composed of nitrides of either molybdenum or vanadium, containing either copper or nickel catalysts, respectively. Structurally, the resulting tribofilms are similar to diamond-like carbon(5). Ball-on-disk tests at contact pressures of 1.3 gigapascals reveal that these tribofilms nearly eliminate wear, and provide lower friction than tribofilms formed with zinc dialkyldithiophosphate. Reactive and ab initio molecular-dynamics simulations show that the catalytic action of the coatings facilitates dehydrogenation of linear olefins in the lubricating oil and random scission of their carbon-carbon backbones; the products recombine to nucleate and grow a compact, amorphous lubricating tribofilm.
C1 [Erdemir, Ali; Ramirez, Giovanni; Eryilmaz, Osman L.; Liao, Yifeng] Argonne Natl Lab, Div Energy Syst, 9700 S Cass Ave, Argonne, IL 60439 USA.
   [Narayanan, Badri; Kamath, Ganesh; Sankaranarayanan, Subramanian K. R. S.] Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA.
   [Liao, Yifeng] Dow Corning Corp, 2200 West Salzburg Rd, Midland, MI 48642 USA.
C3 United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Corning Inc; Dow Chemical Company; Dow Corning
RP Erdemir, A (corresponding author), Argonne Natl Lab, Div Energy Syst, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM erdemir@anl.gov
FU US Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy, Vehicle Technologies and Advanced Manufacturing Offices [DE-AC02-06CH11357]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Office of Science of the US Department of Energy [DE-AC02-06CH11357, DE-AC02-05CH11231]
NR 29
TC 475
Z9 517
U1 53
U2 648
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 67
EP +
DI 10.1038/nature18948
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200031
PM 27488799
DA 2026-03-09
ER

PT J
AU Takeuchi, H
   Higashiyama, T
AF Takeuchi, Hidenori
   Higashiyama, Tetsuya
TI Tip-localized receptors control pollen tube growth and LURE sensing in Arabidopsis
SO NATURE
LA English
DT Article
ID kinases leprk1; in-vitro; cell; protein; family; attraction; dynamics; fertilization; interacts; mechanism
AB Directional control of tip-growing cells is essential for proper tissue organization and cell-to-cell communication in animals and plants(1,2). In the sexual reproduction of flowering plants, the tip growth of the male gametophyte, the pollen tube, is precisely guided by female cues to achieve fertilization(3). Several female-secreted peptides have recently been identified as species-specific attractants that directly control the direction of pollen tube growth(4-6). However, the method by which pollen tubes precisely and promptly respond to the guidance signal from their own species is unknown. Here we show that tip-localized pollen-specific receptor-like kinase 6 (PRK6) with an extracellular leucine-rich repeat domain is an essential receptor for sensing of the LURE1 attractant peptide in Arabidopsis thaliana under semi-in-vivo conditions, and is important for ovule targeting in the pistil. PRK6 interacted with pollen-expressed ROPGEFs (Rho of plant guanine nucleotide-exchange factors), which are important for pollen tube growth through activation of the signalling switch Rho GTPase ROP1 (refs 7, 8). PRK6 conferred responsiveness to AtLURE1 in pollen tubes of the related species Capsella rubella. Furthermore, our genetic and physiological data suggest that PRK6 signalling through ROPGEFs and sensing of AtLURE1 are achieved in cooperation with the other PRK family receptors, PRK1, PRK3 and PRK8. Notably, the tip-focused PRK6 accumulated asymmetrically towards an external AtLURE1 source before reorientation of pollen tube tip growth. These results demonstrate that PRK6 acts as a key membrane receptor for external AtLURE1 attractants, and recruits the core tip-growth machinery, including ROP signalling proteins. This work provides insights into the orchestration of efficient pollen tube growth and species-specific pollen tube attraction by multiple receptors during male-female communication.
C1 [Takeuchi, Hidenori; Higashiyama, Tetsuya] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.
   [Takeuchi, Hidenori; Higashiyama, Tetsuya] Nagoya Univ, JST ERATO Higashiyama Live Holon Project, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.
   [Higashiyama, Tetsuya] Nagoya Univ, Inst Transformat Biomol ITbM, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.
C3 Nagoya University; Nagoya University; Nagoya University
RP Takeuchi, H; Higashiyama, T (corresponding author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.; Takeuchi, H; Higashiyama, T (corresponding author), Nagoya Univ, JST ERATO Higashiyama Live Holon Project, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.; Higashiyama, T (corresponding author), Nagoya Univ, Inst Transformat Biomol ITbM, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648602, Japan.
EM hidenori.takeuchi@gmi.oeaw.ac.at; higashi@bio.nagoya-u.ac.jp
FU Japan Science and Technology Agency (ERATO project); Japan Society for the Promotion of Science [5834]
NR 40
TC 241
Z9 290
U1 6
U2 204
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 245
EP +
DI 10.1038/nature17413
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100044
PM 26961657
DA 2026-03-09
ER

PT J
AU Kondoh, K
   Lu, ZH
   Ye, XL
   Olson, DP
   Lowell, BB
   Buck, LB
AF Kondoh, Kunio
   Lu, Zhonghua
   Ye, Xiaolan
   Olson, David P.
   Lowell, Bradford B.
   Buck, Linda B.
TI A specific area of olfactory cortex involved in stress hormone responses to predator odours
SO NATURE
LA English
DT Article
ID gabaergic neurons; organization; expression; epithelium; receptors; protein; bulb; information; innate; family
AB Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger(1,2). How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising < 5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.
C1 [Kondoh, Kunio; Lu, Zhonghua; Ye, Xiaolan; Buck, Linda B.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Howard Hughes Med Inst, 1100 Fairview Ave North, Seattle, WA 98109 USA.
   [Olson, David P.; Lowell, Bradford B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
   [Olson, David P.; Lowell, Bradford B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Olson, David P.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
C3 Fred Hutchinson Cancer Center; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; University of Michigan System; University of Michigan
RP Buck, LB (corresponding author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, Howard Hughes Med Inst, 1100 Fairview Ave North, Seattle, WA 98109 USA.
EM lbuck@fhcrc.org
FU Howard Hughes Medical Institute (HHMI); National Institutes of Health (National Institute on Deafness and Other Communication Disorders); Japan Society for the Promotion of Science; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK075632] Funding Source: NIH RePORTER
NR 35
TC 120
Z9 141
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 103
EP +
DI 10.1038/nature17156
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500042
PM 27001694
DA 2026-03-09
ER

PT J
AU McNeil, BI
   Sasse, TP
AF McNeil, Ben I.
   Sasse, Tristan P.
TI Future ocean hypercapnia driven by anthropogenic amplification of the natural CO2 cycle
SO NATURE
LA English
DT Article
ID homing ability; acidification; predator; fluxes; cmip5; fish
AB High carbon dioxide (CO2) concentrations in sea-water (ocean hypercapnia) can induce neurological, physiological and behavioural deficiencies in marine animals(1-10). Prediction of the onset and evolution of hypercapnia in the ocean requires a good understanding of annual variations in oceanic CO2 concentration, but there is a lack of relevant global observational data. Here we identify global ocean patterns of monthly variability in carbon concentration using observations that allow us to examine the evolution of surface-ocean CO2 levels over the entire annual cycle under increasing atmospheric CO2 concentrations. We predict that the present-day amplitude of the natural oscillations in oceanic CO2 concentration will be amplified by up to tenfold in some regions by 2100, if atmospheric CO2 concentrations continue to rise throughout this century (according to the RCP8.5 scenario of the Intergovernmental Panel on Climate Change)(11). The findings from our data are broadly consistent with projections from Earth system climate models(12-15). Our predicted amplification of the annual CO2 cycle displays distinct global patterns that may expose major fisheries in the Southern, Pacific and North Atlantic oceans to hypercapnia many decades earlier than is expected from average atmospheric CO2 concentrations. We suggest that these ocean 'CO2 hotspots' evolve as a combination of the strong seasonal dynamics of CO2 concentration and the long-term effective storage of anthropogenic CO2 in the oceans that lowers the buffer capacity in these regions, causing a nonlinear amplification of CO2 concentration over the annual cycle. The onset of ocean hypercapnia (when the partial pressure of CO2 in sea-water exceeds 1,000 micro-atmospheres) is forecast for atmospheric CO2 concentrations that exceed 650 parts per million, with hypercapnia expected in up to half the surface ocean by 2100, assuming a high-emissions scenario (RCP8.5)(11). Such extensive ocean hypercapnia has detrimental implications for fisheries during the twenty-first century.
C1 [McNeil, Ben I.; Sasse, Tristan P.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW, Australia.
   [McNeil, Ben I.] Thinkable Org, Sydney, NSW, Australia.
   [Sasse, Tristan P.] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia.
C3 University of New South Wales Sydney; University of New South Wales Sydney
RP McNeil, BI (corresponding author), Univ New S Wales, Climate Change Res Ctr, Sydney, NSW, Australia.
EM b.mcneil@unsw.edu.au
FU Australian Research Council [DP110104955]
NR 33
TC 157
Z9 178
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 383
EP +
DI 10.1038/nature16156
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800043
PM 26791726
DA 2026-03-09
ER

PT J
AU Sabarinathan, R
   Mularoni, L
   Deu-Pons, J
   Gonzalez-Perez, A
   López-Bigas, N
AF Sabarinathan, Radhakrishnan
   Mularoni, Loris
   Deu-Pons, Jordi
   Gonzalez-Perez, Abel
   Lopez-Bigas, Nuria
TI Nucleotide excision repair is impaired by binding of transcription factors to DNA
SO NATURE
LA English
DT Article
ID chromatin organization; mutational landscape; somatic mutations; nucleosome core; uv damage; cancer; mechanisms; discovery; shapes; rates
AB Somatic mutations are the driving force of cancer genome evolution(1). The rate of somatic mutations appears to be greatly variable across the genome due to variations in chromatin organization, DNA accessibility and replication timing(2-5). However, other variables that may influence the mutation rate locally are unknown, such as a role for DNA-binding proteins, for example. Here we demonstrate that the rate of somatic mutations in melanomas is highly increased at active transcription factor binding sites and nucleosome embedded DNA, compared to their flanking regions. Using recently available excision-repair sequencing (XR-seq) data(6), we show that the higher mutation rate at these sites is caused by a decrease of the levels of nucleotide excision repair (NER) activity. Our work demonstrates that DNA-bound proteins interfere with the NER machinery, which results in an increased rate of DNA mutations at the protein binding sites. This finding has important implications for our understanding of mutational and DNA repair processes and in the identification of cancer driver mutations.
C1 [Sabarinathan, Radhakrishnan; Mularoni, Loris; Deu-Pons, Jordi; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria] IMIM Hosp del Mar Med Res Inst, Res Program Biomed Informat, Doctor Aiguader 88, Barcelona 08003, Spain.
   [Sabarinathan, Radhakrishnan; Mularoni, Loris; Deu-Pons, Jordi; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria] Univ Pompeu Fabra, Doctor Aiguader 88, Barcelona 08003, Spain.
   [Lopez-Bigas, Nuria] ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
C3 Hospital del Mar Research Institute; Hospital del Mar; Pompeu Fabra University; ICREA
RP López-Bigas, N (corresponding author), IMIM Hosp del Mar Med Res Inst, Res Program Biomed Informat, Doctor Aiguader 88, Barcelona 08003, Spain.; López-Bigas, N (corresponding author), Univ Pompeu Fabra, Doctor Aiguader 88, Barcelona 08003, Spain.; López-Bigas, N (corresponding author), ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
FU Spanish Ministry of Economy and Competitiveness [SAF2012-36199]; Marato de TV3 Foundation; Spanish National Institute of Bioinformatics (INB); EMBO - European Commission (EMBOCOFUND) from Marie Curie Actions [ALTF 568-2014, GA-2012-600394]; Ramon y Cajal contract [RYC-2013-14554]; ICREA Funding Source: Custom
NR 35
TC 227
Z9 283
U1 0
U2 125
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 264
EP +
DI 10.1038/nature17661
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100046
PM 27075101
DA 2026-03-09
ER

PT J
AU Boël, G
   Letso, R
   Neely, H
   Price, WN
   Wong, KH
   Su, M
   Luff, JD
   Valecha, M
   Everett, JK
   Acton, TB
   Xiao, R
   Montelione, GT
   Aalberts, DP
   Hunt, JF
AF Boel, Gregory
   Letso, Reka
   Neely, Helen
   Price, W. Nicholson
   Wong, Kam-Ho
   Su, Min
   Luff, Jon D.
   Valecha, Mayank
   Everett, John K.
   Acton, Thomas B.
   Xiao, Rong
   Montelione, Gaetano T.
   Aalberts, Daniel P.
   Hunt, John F.
TI Codon influence on protein expression in E. coli correlates with mRNA levels
SO NATURE
LA English
DT Article
ID structural genomics consortium; escherichia-coli; gene-expression; translation efficiency; production platform; stalled ribosm; elongation rates; usage bias; in-vivo; abundance
AB Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial similar to 16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli.
C1 [Boel, Gregory; Letso, Reka; Neely, Helen; Price, W. Nicholson; Wong, Kam-Ho; Su, Min; Luff, Jon D.; Valecha, Mayank; Hunt, John F.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Boel, Gregory; Letso, Reka; Neely, Helen; Price, W. Nicholson; Wong, Kam-Ho; Su, Min; Luff, Jon D.; Valecha, Mayank; Hunt, John F.] Columbia Univ, Northeast Struct Genom Consortium, New York, NY 10027 USA.
   [Boel, Gregory] CNRS, UMR8261, Inst Biol Phys Chim, F-75005 Paris, France.
   [Everett, John K.; Acton, Thomas B.; Xiao, Rong; Montelione, Gaetano T.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
   [Everett, John K.; Acton, Thomas B.; Xiao, Rong; Montelione, Gaetano T.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Northeast Struct Genom Consortium, Piscataway, NJ 08854 USA.
   [Montelione, Gaetano T.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
   [Aalberts, Daniel P.] Williams Coll, Dept Phys, Williamstown, MA 01267 USA.
C3 Columbia University; Columbia University; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Williams College
RP Hunt, JF (corresponding author), Columbia Univ, Dept Biol Sci, 702 Fairchild Ctr,MC2434, New York, NY 10027 USA.
EM aalberts@williams.edu; jfh21@columbia.edu
FU NIGMS Protein Structure Initiative [U54-GM094597]; NIH [GM106372]
NR 62
TC 306
Z9 376
U1 2
U2 195
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 358
EP +
DI 10.1038/nature16509
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800038
PM 26760206
DA 2026-03-09
ER

PT J
AU Anglada-Escudé, G
   Amado, PJ
   Barnes, J
   Berdiñas, ZM
   Butler, RP
   Coleman, GAL
   de la Cueva, I
   Dreizler, S
   Endl, M
   Giesers, B
   Jeffers, SV
   Jenkins, JS
   Jones, HRA
   Kiraga, M
   Kürster, M
   López-González, MJ
   Marvin, CJ
   Morales, N
   Morin, J
   Nelson, RP
   Ortiz, JL
   Ofir, A
   Paardekooper, SJ
   Reiners, A
   Rodríguez, E
   Rodríguez-López, C
   Sarmiento, LF
   Strachan, JP
   Tsapras, Y
   Tuomi, M
   Zechmeister, M
AF Anglada-Escude, Guillem
   Amado, Pedro J.
   Barnes, John
   Berdinas, Zaira M.
   Butler, R. Paul
   Coleman, Gavin A. L.
   de la Cueva, Ignacio
   Dreizler, Stefan
   Endl, Michael
   Giesers, Benjamin
   Jeffers, Sandra V.
   Jenkins, James S.
   Jones, Hugh R. A.
   Kiraga, Marcin
   Kuerster, Martin
   Lopez-Gonzalez, Maria J.
   Marvin, Christopher J.
   Morales, Nicolas
   Morin, Julien
   Nelson, Richard P.
   Ortiz, Jose L.
   Ofir, Aviv
   Paardekooper, Sijme-Jan
   Reiners, Ansgar
   Rodriguez, Eloy
   Rodriguez-Lopez, Cristina
   Sarmiento, Luis F.
   Strachan, John P.
   Tsapras, Yiannis
   Tuomi, Mikko
   Zechmeister, Mathias
TI A terrestrial planet candidate in a temperate orbit around Proxima Centauri
SO NATURE
LA English
DT Article
ID time-series analysis; main-sequence stars; radial-velocity; habitable zone; southern stars; super-earth; spaced data; no planet; gj 221; search
AB At a distance of 1.295 parsecs(1), the red dwarf Proxima Centauri (a Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun2 and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X-ray luminosity(4) are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface(5).
C1 [Anglada-Escude, Guillem; Coleman, Gavin A. L.; Nelson, Richard P.; Paardekooper, Sijme-Jan; Strachan, John P.] Queen Mary Univ London, Sch Phys & Astron, 327 Mile End Rd, London E1 4NS, England.
   [Amado, Pedro J.; Berdinas, Zaira M.; Lopez-Gonzalez, Maria J.; Morales, Nicolas; Ortiz, Jose L.; Rodriguez, Eloy; Rodriguez-Lopez, Cristina] CSIC, Inst Astrofis Andalucia, Glorieta Astron S-N, E-18008 Granada, Spain.
   [Barnes, John] Open Univ, Dept Phys Sci, Walton Hall, Milton Keynes MK7 6AA, Bucks, England.
   [Butler, R. Paul] Carnegie Inst Sci, Dept Terr Magnetism, 5241 Broad Branch Rd NW, Washington, DC 20015 USA.
   [de la Cueva, Ignacio] Astroimagen, C Abad & Lasierra 58 Bis,6-2, Ibiza 07800, Spain.
   [Dreizler, Stefan; Giesers, Benjamin; Jeffers, Sandra V.; Marvin, Christopher J.; Reiners, Ansgar; Sarmiento, Luis F.; Zechmeister, Mathias] Univ Gottingen, Inst Astrophys, Friedrich Hund Pl 1, D-37077 Gottingen, Germany.
   [Endl, Michael] Univ Texas Austin, McDonald Observ, 2515 Speedway,C1400, Austin, TX 78712 USA.
   [Jenkins, James S.] Univ Chile, Dept Astron, Camino El Observ 1515, Santiago, Chile.
   [Jones, Hugh R. A.; Tuomi, Mikko] Univ Hertfordshire, Sci & Technol Res Inst, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Kiraga, Marcin] Univ Warsaw Observ, Aleje Ujazdowskie 4, Warsaw, Poland.
   [Kuerster, Martin] Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
   [Morin, Julien] Univ Montpellier, Lab Univers & Particules Montpellier, Pl E Bataillon CC 72, F-34095 Montpellier 05, France.
   [Ofir, Aviv] Weizmann Inst Sci, Dept Earth & Planetary Sci, 234 Herzl St, IL-76100 Rehovot, Israel.
   [Tsapras, Yiannis] Astron Rech Inst, Monchhofstr 12-14, D-69120 Heidelberg, Germany.
C3 University of London; Queen Mary University London; University College London; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Open University - UK; Carnegie Institution for Science; University of Gottingen; University of Texas System; University of Texas Austin; Universidad de Chile; University of Hertfordshire; University of Warsaw; Warsaw University Observatory; Max Planck Society; Universite de Montpellier; Weizmann Institute of Science; Ruprecht Karls University Heidelberg
RP Anglada-Escudé, G (corresponding author), Queen Mary Univ London, Sch Phys & Astron, 327 Mile End Rd, London E1 4NS, England.
EM g.anglada@qmul.ac.uk
FU Leverhulme Trust/UK [RPG-2014-281]; MINECO/Spain [ESP2014-54362-P, AYA-2014-54348-C3-1-R, AYA-2014-56637-C2-1-P]; J. A./Spain [2012-FQM1776]; CATA-Basal/Chile PB06 Conicyt; Fondecyt/Chile [1161218]; STFC/UK [ST/M001008/1, ST/L000776/1]; ERC/EU [279347]; DFG/Germany Research [RE 1664/9-2, RE 1664/12-1]; DFG/Germany Colloborative Research Center 963; DFG/Germany Research Training Group 1351; NSF/USA [AST-1313075]; ESO Telescopes at the La Silla Paranal Observatory [096.C-0082, 191.C-0505]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1313075] Funding Source: National Science Foundation; STFC [ST/G002622/1, ST/F007280/1, ST/M001008/1, ST/L000776/1, ST/M001202/1, ST/L001403/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F007280/1, ST/M001202/1, ST/L001403/1, ST/M001008/1, ST/G002622/1, ST/L000776/1] Funding Source: researchfish
NR 64
TC 771
Z9 879
U1 53
U2 367
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 437
EP +
DI 10.1038/nature19106
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600037
PM 27558064
DA 2026-03-09
ER

PT J
AU Haverty, PM
   Lin, E
   Tan, J
   Yu, YH
   Lam, B
   Lianoglou, S
   Neve, RM
   Artin, SM
   Ettleman, JS
   Yauch, RL
   Bourgon, R
AF Haverty, Peter M.
   Lin, Eva
   Tan, Jenille
   Yu, Yihong
   Lam, Billy
   Lianoglou, Steve
   Neve, Richard M.
   Artin, Scott M.
   Ettleman, Jeff S.
   Yauch, Robert L.
   Bourgon, Richard
TI Reproducible pharmacogenomic profiling of cancer cell line panels
SO NATURE
LA English
DT Article
ID breast-cancer; identification; sensitivity; annotation; variants; quality; genes
AB The use of large-scale genomic and drug response screening of cancer cell lines depends crucially on the reproducibility of results. Here we consider two previously published screens, plus a later critique of these studies. Using independent data, we show that consistency is achievable, and provide a systematic description of the best laboratory and analysis practices for future studies.
C1 [Haverty, Peter M.; Lianoglou, Steve; Bourgon, Richard] Genentech Inc, Dept Bioinformat & Computat Biol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Lin, Eva; Tan, Jenille; Yu, Yihong; Lam, Billy; Neve, Richard M.; Artin, Scott M.; Ettleman, Jeff S.; Yauch, Robert L.] Genentech Inc, Dept Discovery Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
RP Bourgon, R (corresponding author), Genentech Inc, Dept Bioinformat & Computat Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM bourgon.richard@gene.com
NR 26
TC 210
Z9 245
U1 0
U2 42
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 333
EP +
DI 10.1038/nature17987
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300037
PM 27193678
DA 2026-03-09
ER

PT J
AU van't Hof, AE
   Campagne, P
   Rigden, DJ
   Yung, CJ
   Lingley, J
   Quail, MA
   Hall, N
   Darby, AC
   Saccheri, IJ
AF van't Hof, Arjen E.
   Campagne, Pascal
   Rigden, Daniel J.
   Yung, Carl J.
   Lingley, Jessica
   Quail, Michael A.
   Hall, Neil
   Darby, Alistair C.
   Saccheri, Ilik J.
TI The industrial melanism mutation in British peppered moths is a transposable element
SO NATURE
LA English
DT Article
ID evolution; genetics; adaptation; selection; sequence; apc/c
AB Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution(1). The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria-typica polymorphism, and the gene it influences, are unknown(2). Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of 'jumping genes' as a source of major phenotypic novelty(3).
C1 [van't Hof, Arjen E.; Campagne, Pascal; Rigden, Daniel J.; Yung, Carl J.; Lingley, Jessica; Hall, Neil; Darby, Alistair C.; Saccheri, Ilik J.] Univ Liverpool, Inst Integrat Biol, Biosci Bldg,Crown St, Liverpool L69 7ZB, Merseyside, England.
   [Quail, Michael A.] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.
C3 University of Liverpool; Wellcome Trust Sanger Institute
RP Saccheri, IJ (corresponding author), Univ Liverpool, Inst Integrat Biol, Biosci Bldg,Crown St, Liverpool L69 7ZB, Merseyside, England.
EM saccheri@liverpool.ac.uk
FU Natural Environment Research Council [NE/H024352/1, NE/J022993/1]; BBSRC [BBS/E/T/000PR5885, BBS/E/T/000PR6193] Funding Source: UKRI; NERC [NBAF010002, NE/J022993/1, NE/H024352/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR5885, BBS/E/T/000PR6193] Funding Source: researchfish; Natural Environment Research Council [NBAF010002, NE/H024352/1, NE/J022993/1] Funding Source: researchfish
NR 39
TC 337
Z9 406
U1 20
U2 468
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 102
EP +
DI 10.1038/nature17951
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300042
PM 27251284
DA 2026-03-09
ER

PT J
AU Capogrosso, M
   Milekovic, T
   Borton, D
   Wagner, F
   Moraud, EM
   Mignardot, JB
   Buse, N
   Gandar, J
   Barraud, Q
   Xing, D
   Rey, E
   Duis, S
   Yang, JZ
   Ko, WKD
   Li, Q
   Detemple, P
   Denison, T
   Micera, S
   Bezard, E
   Bloch, J
   Courtine, G
AF Capogrosso, Marco
   Milekovic, Tomislav
   Borton, David
   Wagner, Fabien
   Moraud, Eduardo Martin
   Mignardot, Jean-Baptiste
   Buse, Nicolas
   Gandar, Jerome
   Barraud, Quentin
   Xing, David
   Rey, Elodie
   Duis, Simone
   Yang Jianzhong
   Ko, Wai Kin D.
   Li, Qin
   Detemple, Peter
   Denison, Tim
   Micera, Silvestro
   Bezard, Erwan
   Bloch, Jocelyne
   Courtine, Gregoire
TI A brain-spine interface alleviating gait deficits after spinal cord injury in primates
SO NATURE
LA English
DT Article
ID functional electrical-stimulation; motor control; free behavior; locomotion; paralysis; neuromodulation; translation; prosthesis; mechanisms; movement
AB Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces(1-3) have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis(1,4). Theoretically, this strategy could also restore control over leg muscle activity for walking(5). However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges(6,7). Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion(8-10). Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with realtime triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.
C1 [Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Mignardot, Jean-Baptiste; Gandar, Jerome; Barraud, Quentin; Rey, Elodie; Duis, Simone; Courtine, Gregoire] Swiss Fed Inst Technol EPFL, Ctr Neuroprosthet, Lausanne, Switzerland.
   [Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Mignardot, Jean-Baptiste; Gandar, Jerome; Barraud, Quentin; Rey, Elodie; Duis, Simone; Courtine, Gregoire] Swiss Fed Inst Technol EPFL, Brain Mind Inst, Sch Life Sci, Lausanne, Switzerland.
   [Capogrosso, Marco; Moraud, Eduardo Martin; Micera, Silvestro] Ecole Polytech Fed Lausanne, Sch Bioengn, Ctr Neuroprosthet, Lausanne, Switzerland.
   [Capogrosso, Marco; Moraud, Eduardo Martin; Micera, Silvestro] Ecole Polytech Fed Lausanne, Sch Bioengn, Inst Bioengn, Lausanne, Switzerland.
   [Borton, David; Xing, David] Brown Univ, Sch Engn, Providence, RI 02912 USA.
   [Buse, Nicolas; Denison, Tim] Medtronic, Minneapolis, MN USA.
   [Yang Jianzhong; Ko, Wai Kin D.; Li, Qin; Bezard, Erwan] Motac Neurosci Ltd, Manchester, Lancs, England.
   [Li, Qin; Bezard, Erwan] China Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China.
   [Detemple, Peter] Fraunhofer Inst Chem Technol ICT IMM, Mainz Inst Microtechnol, Mainz, Germany.
   [Micera, Silvestro] Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy.
   [Bezard, Erwan] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France.
   [Bezard, Erwan] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France.
   [Bloch, Jocelyne; Courtine, Gregoire] CHU Vaudois, Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Brown University; Medtronic; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Laboratory Animal Science - CAMS; Fraunhofer Gesellschaft; Scuola Superiore Sant'Anna; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; CNRS - National Institute for Biology (INSB); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV)
RP Courtine, G (corresponding author), Swiss Fed Inst Technol EPFL, Ctr Neuroprosthet, Lausanne, Switzerland.; Courtine, G (corresponding author), Swiss Fed Inst Technol EPFL, Brain Mind Inst, Sch Life Sci, Lausanne, Switzerland.; Courtine, G (corresponding author), CHU Vaudois, Lausanne, Switzerland.
EM gregoire.courtine@epfl.ch
FU Medtronic; European Community [CP-IP 258654]; International Paraplegic foundation; European Research Council [ERC 261247]; Wyss centre in Geneva; Marie Curie Fellowship [331602]; Marie Curie COFUND EPFL fellowships; Morton Cure Paralysis Fund fellowship; Swiss National Science Foundation including the National Centre of Competence in Research in Robotics; Sinergia program [CRSII3_160696]; Sino-Swiss Science and Technology Cooperation [IZLCZ3_156331]; NanoTera.ch programme (SpineRepair); Swiss National Science Foundation (SNF) [IZLCZ3_156331] Funding Source: Swiss National Science Foundation (SNF)
NR 37
TC 485
Z9 611
U1 17
U2 434
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 284
EP +
DI 10.1038/nature20118
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500044
PM 27830790
DA 2026-03-09
ER

PT J
AU Fischer, MG
   Hackl, T
AF Fischer, Matthias G.
   Hackl, Thomas
TI Host genome integration and giant virus-induced reactivation of the virophage mavirus
SO NATURE
LA English
DT Article
ID dna virus; provirophages; transposons; particles
AB Endogenous viral elements are increasingly found in eukaryotic genomes(1), yet little is known about their origins, dynamics, or function. Here we provide a compelling example of a DNA virus that readily integrates into a eukaryotic genome where it acts as an inducible antiviral defence system. We found that the virophage mavirus(2), a parasite of the giant Cafeteria roenbergensis virus (CroV)(3), integrates at multiple sites within the nuclear genome of the marine protozoan Cafeteria roenbergensis(4). The endogenous mavirus is structurally and genetically similar to eukaryotic DNA transposons and endogenous viruses of the Maverick/Polinton family(5-7). Provirophage genes are not constitutively expressed, but are specifically activated by superinfection with CroV, which induces the production of infectious mavirus particles. Virophages can inhibit the replication of mimivirus-like giant viruses and an anti-viral protective effect of provirophages on their hosts has been hypothesized(2,8). We find that provirophage-carrying cells are not directly protected from CroV; however, lysis of these cells releases infectious mavirus particles that are then able to suppress CroV replication and enhance host survival during subsequent rounds of infection. The microbial host-parasite interaction described here involves an altruistic aspect and suggests that giant-virus-induced activation of provirophages might be ecologically relevant in natural protist populations.
C1 [Fischer, Matthias G.; Hackl, Thomas] Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany.
   [Hackl, Thomas] MIT, 15 Vassar St, Cambridge, MA 02139 USA.
C3 Max Planck Society; Massachusetts Institute of Technology (MIT)
RP Fischer, MG (corresponding author), Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany.
EM mfischer@mpimf-heidelberg.mpg.de
FU Max Planck Society
NR 35
TC 109
Z9 117
U1 0
U2 47
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 288
EP +
DI 10.1038/nature20593
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700061
PM 27929021
DA 2026-03-09
ER

PT J
AU Pedersen, MW
   Ruter, A
   Schweger, C
   Friebe, H
   Staff, RA
   Kjeldsen, KK
   Mendoza, MLZ
   Beaudoin, AB
   Zutter, C
   Larsen, NK
   Potter, BA
   Nielsenlo, R
   Rainville, RA
   Orlando, L
   Meltzer, DJ
   Kjær, KH
   Willerslev, E
AF Pedersen, Mikkel W.
   Ruter, Anthony
   Schweger, Charles
   Friebe, Harvey
   Staff, Richard A.
   Kjeldsen, Kristian K.
   Mendoza, Marie L. Z.
   Beaudoin, Alwynne B.
   Zutter, Cynthia
   Larsen, Nicolaj K.
   Potter, Ben A.
   Nielsenlo, Rasmus
   Rainville, Rebecca A.
   Orlando, Ludovic
   Meltzer, David J.
   Kjaer, Kurt H.
   Willerslev, Eske
TI Postglacial viability and colonization in North America's ice-free corridor
SO NATURE
LA English
DT Article
ID lake-sediments; dna; survival; history; alberta; pollen; canada; sheet; horse; site
AB During the Last Glacial Maximum, continental ice sheets isolated Beringia (northeast Siberia and northwest North America) from unglaciated North America. By around 15 to 14 thousand calibrated radiocarbon years before present (cal. kyr BP), glacial retreat opened an approximately 1,500-km-long corridor between the ice sheets. It remains unclear when plants and animals colonized this corridor and it became biologically viable for human migration. We obtained radiocarbon dates, pollen, macrofossils and metagenomic DNA from lake sediment cores in a bottleneck portion of the corridor. We find evidence of steppe vegetation, bison and mammoth by approximately 12.6 cal. kyr BP, followed by open forest, with evidence of moose and elk at about 11.5 cal. kyr BP, and boreal forest approximately 10 cal. kyr BP Our findings reveal that the first Americans, whether Clovis or earlier groups in unglaciated North America before 12.6 cal. kyr BP, are unlikely to have travelled by this route into the Americas. However, later groups may have used this north south passageway.
C1 [Pedersen, Mikkel W.; Ruter, Anthony; Kjeldsen, Kristian K.; Mendoza, Marie L. Z.; Larsen, Nicolaj K.; Nielsenlo, Rasmus; Orlando, Ludovic; Meltzer, David J.; Kjaer, Kurt H.; Willerslev, Eske] Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum, DK-1350 Copenhagen, Denmark.
   [Schweger, Charles; Friebe, Harvey] Univ Alberta, Dept Anthropol, Edmonton, AB T6G 2H4, Canada.
   [Staff, Richard A.] Univ Oxford, Sch Archaeol, Oxford OX1 3QY, England.
   [Kjeldsen, Kristian K.] Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
   [Beaudoin, Alwynne B.] Royal Alberta Museum, Edmonton, AB T5N 0M6, Canada.
   [Zutter, Cynthia] MacEwan Univ, Dept Anthropol, Edmonton, AB T5J 4S2, Canada.
   [Larsen, Nicolaj K.] Aarhus Univ, Dept Geosci, DK-8000 Aarhus, Denmark.
   [Potter, Ben A.] Univ Alaska Fairbanks, Dept Anthropol, Fairbanks, AK 99775 USA.
   [Nielsenlo, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Nielsenlo, Rasmus] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Rainville, Rebecca A.] Univ Calgary, Dept Archaeol, Calgary, AB T2N 1N4, Canada.
   [Meltzer, David J.] Southern Methodist Univ, Dept Anthropol, Dallas, TX 75275 USA.
   [Willerslev, Eske] Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
   [Willerslev, Eske] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 University of Copenhagen; University of Alberta; University of Oxford; University of Ottawa; MacEwan University; Aarhus University; University of Alaska System; University of Alaska Fairbanks; University of California System; University of California Berkeley; University of Copenhagen; University of Calgary; Southern Methodist University; University of Cambridge; Wellcome Trust Sanger Institute
RP Willerslev, E (corresponding author), Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum, DK-1350 Copenhagen, Denmark.; Willerslev, E (corresponding author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.; Willerslev, E (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM ewillerslev@snm.ku.dk
FU Danish National Research Foundation [DNRF94]; Lundbeck Foundation; KU; Lundbeck Foundation [R70-2010-6286, R155-2013-16338, R109-2012-9995, R24-2008-2527, R38-2008-3048] Funding Source: researchfish
NR 50
TC 294
Z9 361
U1 9
U2 259
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 45
EP 49
DI 10.1038/nature19085
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900035
PM 27509852
DA 2026-03-09
ER

PT J
AU Bulla, M
   Valcu, M
   Dokter, AM
   Dondua, AG
   Kosztolányi, A
   Rutten, AL
   Helm, B
   Sandercock, BK
   Casler, B
   Ens, BJ
   Spiegel, CS
   Hassell, CJ
   Küpper, C
   Minton, C
   Burgas, D
   Lank, DB
   Payer, DC
   Loktionov, EY
   Nol, E
   Kwon, E
   Smith, F
   Gates, HR
   Vitnerová, H
   Prüter, H
   Johnson, JA
   St Clair, JJH
   Lamarre, JF
   Rausch, J
   Reneerkens, J
   Conklin, JR
   Burger, J
   Liebezeit, J
   Bêty, J
   Coleman, JT
   Figuerola, J
   Hooijmeijer, JCEW
   Alves, JA
   Smith, JAM
   Weidinger, K
   Koivula, K
   Gosbell, K
   Exo, KM
   Niles, L
   Koloski, L
   McKinnon, L
   Praus, L
   Klaassen, M
   Giroux, MA
   Sládecek, M
   Boldenow, ML
   Goldstein, MI
   Sálek, M
   Senner, N
   Rönkä, N
   Lecomte, N
   Gilg, O
   Vincze, O
   Johnson, OW
   Smith, PA
   Woodard, PF
   Tomkovich, PS
   Battley, PF
   Bentzen, R
   Lanctot, RB
   Porter, R
   Saalfeld, ST
   Freeman, S
   Brown, SC
   Yezerinac, S
   Székely, T
   Montalvo, T
   Piersma, T
   Loverti, V
   Pakanen, VM
   Tijsen, W
   Kempenaers, B
AF Bulla, Martin
   Valcu, Mihai
   Dokter, Adriaan M. .
   Dondua, Alexei G.
   Kosztolanyi, Andras
   Rutten, Anne L.
   Helm, Barbara
   Sandercock, Brett K.
   Casler, Bruce
   Ens, Bruno J.
   Spiegel, Caleb S.
   Hassell, Chris J.
   Kuepper, Clemens
   Minton, Clive
   Burgas, Daniel
   Lank, David B.
   Payer, David C.
   Loktionov, Egor Y.
   Nol, Erica
   Kwon, Eunbi
   Smith, Fletcher
   Gates, H. River
   Vitnerova, Hana
   Prueter, Hanna
   Johnson, James A.
   St Clair, James J. H.
   Lamarre, Jean-Francois
   Rausch, Jennie
   Reneerkens, Jeroen
   Conklin, Jesse R. .
   Burger, Joanna
   Liebezeit, Joe
   Bety, Joel
   Coleman, Jonathan T.
   Figuerola, Jordi
   Hooijmeijer, Jos C. . E. . W.
   Alves, Jose A.
   Smith, Joseph A. M. .
   Weidinger, Karel
   Koivula, Kari
   Gosbell, Ken
   Exo, Klaus-Michael
   Niles, Larry
   Koloski, Laura
   McKinnon, Laura
   Praus, Libor
   Klaassen, Marcel
   Giroux, Marie-Andree
   Sladecek, Martin
   Boldenow, Megan L.
   Goldstein, Michael I.
   Salek, Miroslav
   Senner, Nathan
   Ronka, Nelli
   Lecomte, Nicolas
   Gilg, Olivier
   Vincze, Orsolya
   Johnson, Oscar W.
   Smith, Paul A.
   Woodard, Paul F.
   Tomkovich, Pavel S.
   Battley, Phil F.
   Bentzen, Rebecca
   Lanctot, Richard B. .
   Porter, Ron
   Saalfeld, Sarah T.
   Freeman, Scott
   Brown, Stephen C. .
   Yezerinac, Stephen
   Szekely, Tamas
   Montalvo, Tomas
   Piersma, Theunis
   Loverti, Vanessa
   Pakanen, Veli-Matti
   Tijsen, Wim
   Kempenaers, Bart
TI Unexpected diversity in socially synchronized rhythms of shorebirds
SO NATURE
LA English
DT Article
ID incubation patterns; sexual selection; geolocator data; birds; phylogeny; evolution; roles; risk; care
AB The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment(1-4). Such behavioural rhythms are well studied in isolated individuals under laboratory conditions(1,5), but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators(6-10). Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring)(6-9,11). The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood(5-7,9). Here we investigate these rhythms in the context of biparental care, a particularly sensitive phase of social synchronization(12) where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within-and between-species diversity in incubation rhythms. Between species, the median length of one parent's incubation bout varied from 1-19 h, whereas period length-the time in which a parent's probability to incubate cycles once between its highest and lowest value-varied from 6-43 h. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or who actively protect their nest against predators. Rhythms entrainable to the 24-h light-dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity(5-7,9). The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.
C1 [Bulla, Martin; Valcu, Mihai; Rutten, Anne L.; Kempenaers, Bart] Max Planck Inst Ornithol, Dept Behav Ecol & Evolutionary Genet, Eberhard Gwinner Str, D-82319 Seewiesen, Germany.
   [Dokter, Adriaan M. .] Univ Amsterdam, Inst Biodivers & Ecosystem Dynam, Computat Geo Ecol, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
   [Dondua, Alexei G.] Gatchinskaya,Apartment 27, St Petersburg 197198, Russia.
   [Kosztolanyi, Andras] Univ Vet Med Budapest, Dept Ecol, Rottenbiller U 50, H-1077 Budapest, Hungary.
   [Kosztolanyi, Andras; Vincze, Orsolya] Univ Debrecen, Dept Evolutionary Zool, MTA DE Lendulet Behav Ecol Res Grp, H-4032 Debrecen, Hungary.
   [Rutten, Anne L.] Apiloa GmbH, D-82319 Starnberg, Germany.
   [Helm, Barbara] Univ Glasgow, Inst Biodivers Anim Hlth & Comparat Med, Graham Kerr Bldg, Glasgow G12 8QQ, Lanark, Scotland.
   [Sandercock, Brett K.] Kansas State Univ, Div Biol, 116 Ackert Hall, Manhattan, KS 66506 USA.
   [Casler, Bruce] POB 1094, Fallon, NV 89407 USA.
   [Ens, Bruno J.] Sovon Dutch Ctr Field Ornithol, Coastal Ecol Team, POB 59, NL-1790 AB Den Burg, Texel, Netherlands.
   [Spiegel, Caleb S.] US Fish & Wildlife Serv, Div Migratory Birds, 300 Westgate Ctr Dr, Hadley, MA 01035 USA.
   [Hassell, Chris J.] Global Flyway Network, POB 3089, Broome, Western Austral 6725, Australia.
   [Kuepper, Clemens] Graz Univ, Inst Zool, Univ Pl 2, A-8010 Graz, Austria.
   [Minton, Clive] Victorian Wader Study Grp, 165 Dalgetty Rd, Melbourne, Vic, Australia.
   [Burgas, Daniel] Univ Helsinki, Dept Forest Sci, POB 27, FI-00014 Helsinki, Finland.
   [Burgas, Daniel] Univ Jyvaskyla, Dept Biol & Environm Sci, POB 35, FI-40014 Jyvaskyla, Finland.
   [Lank, David B.] Simon Fraser Univ, Dept Biol Sci, 8888 Univ Dr, Burnaby V5A 1S6, BC V5A 1S6, Canada.
   [Payer, David C.] Natl Pk Serv, Alaska Reg, 240 W 5th Ave, Anchorage, AK 99501 USA.
   [Loktionov, Egor Y.] Bauman Moscow State Tech Univ, State Lab Photon Energet, 2nd Baumanskaya St,5-1, Moscow 105005, Russia.
   [Nol, Erica] Trent Univ, Biol Dept, 2140 East Bank Dr, Peterborough K9L 0G2, ON, Canada.
   [Kwon, Eunbi] Virginia Polytech Inst & State Univ, Dept Fish & Wildlife Conservat, 310 West Campus Dr, Blacksburg, VA 24061 USA.
   [Smith, Fletcher] Virginia Commonwealth Univ, POB 8795, Williamsburg, VA USA.
   [Smith, Fletcher] Coll William & Mary, Ctr Conservat Biol, POB 8795, Williamsburg, VA USA.
   [Gates, H. River] Pacific Ecol Serv, 17520 Snow Crest Lane, Anchorage, AK 99516 USA.
   [Gates, H. River; Johnson, James A.; Lanctot, Richard B. .; Saalfeld, Sarah T.] US Fish & Wildlife Serv, Migratory Bird Management, 1011 East Tudor Rd, Anchorage, AK 99503 USA.
   [Gates, H. River; Brown, Stephen C. .] Shorebird Recovery Program, POB 545, Saxtons River, VT 05154 USA.
   [Vitnerova, Hana] Charles Univ Prague, Fac Sci, Albertov 6, Prague 12843, Czech Republic.
   [Prueter, Hanna] Leibniz Inst Zoo & Wildlife Res, Dept Wildlife Dis, Alfred Kowalke Str 17, D-10315 Berlin, Germany.
   [St Clair, James J. H.] Univ Bath, Dept Biol & Biochem, Biodivers Lab, Bath BA1 7AY, Avon, England.
   [St Clair, James J. H.] Univ Western Australia, Ctr Evolutionary Biol, Sch Biol, Stirling Highway, Crawley, Western Austral 6009, Australia.
   [Lamarre, Jean-Francois; Bety, Joel] Univ Quebe Rimouski, Dept Biol Chim & Geographie, 300 Alle Ursulines, Rimouski G5L 3A1, PQ G5L 3A1, Canada.
   [Lamarre, Jean-Francois; Bety, Joel] Univ Quebe Rimouski, CEN, 300 Alle Ursulines, Rimouski, PQ G5L 3A1, Canada.
   [Rausch, Jennie; Woodard, Paul F.] Environm & Climate Change Canada, Canadian Wildlife Serv, POB 2310,5019-52nd St,4th Floor, Yellowknife X1A 2P7, NT, Canada.
   [Reneerkens, Jeroen; Conklin, Jesse R. .; Hooijmeijer, Jos C. . E. . W.; Senner, Nathan; Piersma, Theunis] Univ Groningen, Groningen Inst Evolutionary Life Sci, Conservat Ecol Grp, Nijenborgh 7, NL-9747 AG Groningen, Netherlands.
   [Burger, Joanna] Rutgers State Univ, Div Life Sci, 604-Allison Rd, Piscataway, NJ 08854 USA.
   [Liebezeit, Joe] Audubon Soc Portland, 5151 NW Cornell Rd, Portland, OR 97210 USA.
   [Coleman, Jonathan T.] Queensland Wader Study Grp, 22 Parker St, Brisbane, Qld 4128, Australia.
   [Figuerola, Jordi] CSIC, Donana Biol Stn, Dept Wetland Ecol, Ave Amer Vespucio,S-N, Seville 41092, Spain.
   [Alves, Jose A.] Univ Aveiro, Dept Biol, Ctr Environm & Marine Studies CESAM, Campus Santiago, P-3810193 Aveiro, Portugal.
   [Alves, Jose A.] Univ Iceland, South Iceland Res Ctr, IS-800 Fjolheimar, Selfoss, Iceland.
   [Smith, Joseph A. M. .] LJ Niles Associates, POB 784, Cape May, NJ 08204 USA.
   [Weidinger, Karel; Praus, Libor] Palacky Univ, Dept Zool & Lab Ornithol, 17 Listopadu 50, Olomouc 77146, Czech Republic.
   [Koivula, Kari; Ronka, Nelli; Pakanen, Veli-Matti] Univ Oulu, Dept Ecol, POB 3000, Oulu 90014, Finland.
   [Gosbell, Ken] Australasian Wader Studies Grp, 1-19 Baldwin Rd, Melbourne, Vic, Australia.
   [Exo, Klaus-Michael] Inst Avian Res, Vogelwarte Helgoland, Vogelwarte 21, D-26386 Wilhelmshaven, Germany.
   [Niles, Larry] LJ Niles Associates, 109 Market Lane, Greenwich, CT 08323 USA.
   [Koloski, Laura] Trent Univ, Environm & Life Sci, 1600 West Bank Dr, Peterborough, ON K0L 0G2, Canada.
   [McKinnon, Laura] York Univ Glendon Campus, Bilingual Biol Program, 2275 Bayview Ave, Toronto, ON M4N 3M6, Canada.
   [Klaassen, Marcel] Deakin Univ, Ctr Integrat Ecol, 75 Pigdons Rd, Geelong, Vic 3216, Australia.
   [Giroux, Marie-Andree] Univ Quebec Rimouski, Canada Res Northern Biodivers, 300,Allee Ursulines, Rimouski, PQ G5L 3A8, Canada.
   [Giroux, Marie-Andree] Univ Quebec Rimouski, Ctr Etudes Nord, 300,Allee Ursulines, Rimouski, PQ G5L 3A8, Canada.
   [Giroux, Marie-Andree; Lecomte, Nicolas] Univ Moncton, Canada Res Polar & Boreal Ecol, 18 Ave Antonine Maillet, Moncton, NB E4K 1A6, Canada.
   [Giroux, Marie-Andree; Lecomte, Nicolas] Univ Moncton, Ctr Etudes Nord, 18 Ave Antonine Maillet, Moncton, NB E4K 1A6, Canada.
   [Sladecek, Martin; Salek, Miroslav] Czech Univ Life Sci Prague, Fac Environm Sci, Kamyck 1176, Prague 16521, Czech Republic.
   [Boldenow, Megan L.] Univ Alaska Fairbanks, Dept Biol & Wildlife, POB 756100, Fairbanks, AK 99775 USA.
   [Goldstein, Michael I.] Univ Alaska Southeast, Alaska Coastal Rainforest Ctr, 11120 Glacier Hwy, Juneau, AK 99801 USA.
   [Senner, Nathan] Cornell Lab Ornithol, 159 Sapsucker Woods Rd, Ithaca, NY 14850 USA.
   [Gilg, Olivier] Univ Bourgogne Franche Comte, Equipe Ecol Evolut, UMR Biogeosci 6282, 6 Bd Gabriel, F-21000 Dijon, France.
   [Gilg, Olivier] Grp Rech Ecol Arct, 16 Rue Vernot, F-21440 Francheville, France.
   [Vincze, Orsolya] Babes Bolyai Univ, Hungarian Dept Biol & Ecol, Evolutionary Ecol Grp, Clinicilor 5-7, RO-400006 Cluj Napoca, Romania.
   [Johnson, Oscar W.] Montana State Univ, Dept Ecol, Bozeman, MT 59717 USA.
   [Smith, Paul A.] Environm & Climate Change Canada, Wildlife Res Div, 1125 Colonel Dr, Ottawa, ON K1A 0H3, Canada.
   [Tomkovich, Pavel S.] Lomonosov Moscow State Univ, Zool Museum, Bolshaya Nikitskaya St 6, Moscow 125009, Russia.
   [Battley, Phil F.] Massey Univ, Inst Agr Environm, Private Bag 11 222, Palmerston North 4442, New Zealand.
   [Bentzen, Rebecca] Arctic Beringia Program, Wildlife Conservat Soc, 925 Schloesser Dr, Fairbanks, AK 99709 USA.
   [Porter, Ron] Delaware Bay Shorebird Project, Ambler, PA 19002 USA.
   [Freeman, Scott] US Fish & Wildlife Serv, Arctic Natl Wildlife Refuge, 101 12th Ave, Fairbanks, AK 99701 USA.
   [Yezerinac, Stephen] Fieldday Consulting, Surrey, BC V4N 6M5, Canada.
   [Szekely, Tamas] Univ Bath, Dept Biol & Biochem, Milner Ctr Evolut, Claverton, Bath BA2 7AY, Avon, England.
   [Montalvo, Tomas] Agencia Salut Publ Barcelona, Serv Vigilancia & Control Plagues Urbanes, Ave Princep Asturies 63, Barcelona 8012, Spain.
   [Piersma, Theunis] NIOZ Royal Netherlands, Inst Sea Res, Dept Coastal Syst, POB 59, NL-1790 AB Den Burg, Texel, Netherlands.
   [Piersma, Theunis] Univ Utrecht, POB 59, NL-1790 AB Den Burg, Texel, Netherlands.
   [Loverti, Vanessa] US Fish & Wildlife Serv, Migratory Bird & Habitat Program, 911 NE 11th Ave, Portland, OR 97232 USA.
   [Tijsen, Wim] Poelweg 12, NL-1778 KB Westerland, Netherlands.
C3 Max Planck Society; University of Amsterdam; University of Veterinary Medicine Budapest; University of Debrecen; University of Glasgow; Kansas State University; United States Department of the Interior; US Fish & Wildlife Service; University of Graz; University of Helsinki; University of Jyvaskyla; Simon Fraser University; United States Department of the Interior; US National Park Service; Bauman Moscow State Technical University; Trent University; Virginia Polytechnic Institute & State University; Virginia Commonwealth University; William & Mary; United States Department of the Interior; US Fish & Wildlife Service; Charles University Prague; Leibniz Institut fur Zoo und Wildtierforschung; University of Bath; University of Western Australia; University of Quebec; Universite du Quebec a Rimouski; University of Quebec; Universite du Quebec a Rimouski; Environment & Climate Change Canada; Canadian Wildlife Service; University of Groningen; Rutgers University System; Rutgers University New Brunswick; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); Universidade de Aveiro; University of Iceland; Palacky University Olomouc; University of Oulu; Trent University; York University - Canada; Deakin University; University of Quebec; Universite du Quebec a Rimouski; University of Quebec; Universite du Quebec a Rimouski; University of Moncton; University of Moncton; Czech University of Life Sciences Prague; University of Alaska System; University of Alaska Fairbanks; University of Alaska System; University of Alaska Southeastern; Cornell University; Universite Bourgogne Europe; Babes Bolyai University from Cluj; Montana State University System; Montana State University Bozeman; Environment & Climate Change Canada; Canadian Wildlife Service; Wildlife Research Division - Environment Canada; Lomonosov Moscow State University; Massey University; Wildlife Conservation Society; United States Department of the Interior; US Fish & Wildlife Service; University of Bath; Public Health Agency of Barcelona; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Utrecht University; United States Department of the Interior; US Fish & Wildlife Service
RP Bulla, M; Kempenaers, B (corresponding author), Max Planck Inst Ornithol, Dept Behav Ecol & Evolutionary Genet, Eberhard Gwinner Str, D-82319 Seewiesen, Germany.
EM bulla.mar@gmail.com; b.kempenaers@orn.mpg.de
FU Max Planck Society
NR 72
TC 104
Z9 115
U1 3
U2 211
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 109
EP +
DI 10.1038/nature20563
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600058
PM 27880762
DA 2026-03-09
ER

PT J
AU Lüpold, S
   Manier, MK
   Puniamoorthy, N
   Schoff, C
   Starmer, WT
   Luepold, SHB
   Belote, JM
   Pitnick, S
AF Lupold, Stefan
   Manier, Mollie K.
   Puniamoorthy, Nalini
   Schoff, Christopher
   Starmer, William T.
   Luepold, Shannon H. Buckley
   Belote, John M.
   Pitnick, Scott
TI How sexual selection can drive the evolution of costly sperm ornamentation
SO NATURE
LA English
DT Article
ID competitive fertilization success; drosophila-melanogaster; phylogenetic analysis; trade-off; allometry; ejaculate; size; dimorphism; mechanisms; intensity
AB Post-copulatory sexual selection (PSS), fuelled by female promiscuity, is credited with the rapid evolution of sperm quality traits across diverse taxa(1). Yet, our understanding of the adaptive significance of sperm ornaments and the cryptic female preferences driving their evolution is extremely limited(1,2). Here we review the evolutionary allometry of exaggerated sexual traits (for example, antlers, horns, tail feathers, mandibles and dewlaps), show that the giant sperm of some Drosophila species are possibly the most extreme ornaments(3,4) in all of nature and demonstrate how their existence challenges theories explaining the intensity of sexual selection, mating-system evolution and the fundamental nature of sex differences(5-9). We also combine quantitative genetic analyses of interacting sex-specific traits in D. melanogaster with comparative analyses of the condition dependence of male and female reproductive potential across species with varying ornament size to reveal complex dynamics that may underlie sperm-length evolution. Our results suggest that producing few gigantic sperm evolved by (1) Fisherian runaway selection mediated by genetic correlations between sperm length, the female preference for long sperm and female mating frequency, and (2) longer sperm increasing the indirect benefits to females. Our results also suggest that the developmental integration of sperm quality and quantity renders post-copulatory sexual selection on ejaculates unlikely to treat male-male competition and female choice as discrete processes.
C1 [Lupold, Stefan; Manier, Mollie K.; Puniamoorthy, Nalini; Schoff, Christopher; Starmer, William T.; Luepold, Shannon H. Buckley; Belote, John M.; Pitnick, Scott] Syracuse Univ, Dept Biol, Ctr Reprod Evolut, 107 Coll Pl, Syracuse, NY 13244 USA.
   [Lupold, Stefan] Univ Zurich, Dept Evolutionary Biol & Environm Studies, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
   [Manier, Mollie K.] George Washington Univ, Dept Biol Sci, 800 22nd St NW,Suite 6000, Washington, DC 20052 USA.
   [Puniamoorthy, Nalini] Natl Univ Singapore, Dept Biol Sci, 14 Sci Dr, SG-117543 Singapore, Singapore.
C3 Syracuse University; University of Zurich; George Washington University; National University of Singapore
RP Pitnick, S (corresponding author), Syracuse Univ, Dept Biol, Ctr Reprod Evolut, 107 Coll Pl, Syracuse, NY 13244 USA.
EM sspitnic@syr.edu
FU National Science Foundation [DEB-9806649, DEB-1145965]; Swiss National Science Foundation [PA00P3_134191, PZ00P3_154767]; National University of Singapore; Swiss National Science Foundation (SNF) [PA00P3_134191, PZ00P3_154767] Funding Source: Swiss National Science Foundation (SNF)
NR 71
TC 131
Z9 146
U1 2
U2 160
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 535
EP +
DI 10.1038/nature18005
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100041
PM 27225128
DA 2026-03-09
ER

PT J
AU Luo, CT
   Liao, W
   Dadi, S
   Toure, A
   Li, MO
AF Luo, Chong T.
   Liao, Will
   Dadi, Saida
   Toure, Ahmed
   Li, Ming O.
TI Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity
SO NATURE
LA English
DT Article
ID transcription factors; l-selectin; migration; tolerance; ultrafast; survival; cancer; ccr7
AB Regulatory T (T-reg) cells expressing the transcription factor Foxp3 have a pivotal role in maintaining immunological self-tolerance(1-5); yet, excessive T-reg cell activities suppress anti-tumour immune responses(6-8). Compared to the resting T-reg (rT(reg)) cell phenotype in secondary lymphoid organs, T-reg cells in non-lymphoid tissues exhibit an activated T-reg (aT(reg)) cell phenotype(9-11). However, the function of aT(reg) cells and whether their generation can be manipulated are largely unexplored. Here we show that the transcription factor Foxo1, previously demonstrated to promote T-reg cell suppression of lymphoproliferative diseases(12,13), has an unexpected function in inhibiting aT(reg)-cell-mediated immune tolerance in mice. We find that aT(reg) cells turned over at a slower rate than rT(reg) cells, but were not locally maintained in tissues. aT(reg) cell differentiation was associated with repression of Foxo1-dependent gene transcription, concomitant with reduced Foxo1 expression, cytoplasmic localization and enhanced phosphorylation at the Akt sites. T-reg-cell-specific expression of an Akt-insensitive Foxo1 mutant prevented downregulation of lymphoid organ homing molecules, and impeded T-reg cell homing to non-lymphoid organs, causing CD8(+) T-cell-mediated autoimmune diseases. Compared to T-reg cells from healthy tissues, tumour-infiltrating T-reg cells downregulated Foxo1 target genes more substantially. Expression of the Foxo1 mutant at a lower dose was sufficient to deplete tumour-associated T-reg cells, activate effector CD8(+) T cells, and inhibit tumour growth without inflicting autoimmunity. Thus, Foxo1 inactivation is essential for the migration of aT(reg) cells that have a crucial function in suppressing CD8(+) T-cell responses; and the Foxo signalling pathway in T-reg cells can be titrated to break tumour immune tolerance preferentially.
C1 [Luo, Chong T.; Dadi, Saida; Toure, Ahmed; Li, Ming O.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
   [Luo, Chong T.] Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA.
   [Liao, Will] New York Genome Ctr, New York, NY 10013 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Li, MO (corresponding author), Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
EM lim@mskcc.org
FU National Institutes of Health [RO1 AI102888-01A1]; Ludwig Center for Cancer Immunology; Memorial Sloan Kettering Cancer Center Support Grant/Core Grant [P30 CA008748]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI102888] Funding Source: NIH RePORTER
NR 40
TC 164
Z9 188
U1 1
U2 48
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 532
EP +
DI 10.1038/nature16486
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800038
PM 26789248
DA 2026-03-09
ER

PT J
AU Johnston, CP
   Smith, RT
   Allmendinger, S
   MacMillan, DWC
AF Johnston, Craig P.
   Smith, Russell T.
   Allmendinger, Simon
   MacMillan, David W. C.
TI Metallaphotoredox-catalysed sp3-sp3 cross-coupling of carboxylic acids with alkyl halides
SO NATURE
LA English
DT Article
ID photoredox catalysis; visible-light; room-temperature; nickel catalysis; aryl halides; reagents; bromides; iodides; complex; design
AB In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research(1). However, the construction of a bond between two sp(3)-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions(2). In comparison to related procedures with sp(2)-hybridized species, the development of methods for sp(3)-sp(3) bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as beta-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition(3,4.) To address this issue, nickel-catalysed cross-coupling processes can be used to form sp(3)-sp(3) bonds that utilize organometallic nucleophiles and alkyl electrophiles(5-7). In particular, the coupling of alkyl halides with pre-generated organozinc(8,9), Grignard(10) and organoborane(11) species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step-and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp(3)-sp(3) coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp(3)-sp(3) bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for many primary and secondary carboxylic acids. The merit of this coupling strategy is illustrated by the synthesis of the pharmaceutical tirofiban in four steps from commercially available starting materials.
C1 [Johnston, Craig P.; Smith, Russell T.; Allmendinger, Simon; MacMillan, David W. C.] Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA.
C3 Princeton University
RP MacMillan, DWC (corresponding author), Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA.
EM dmacmill@princeton.edu
FU NIHGMS [R01 GM093213-01]; Marie Curie Actions [PIOF-GA-2013-627695]; Deutsche Forschungsgemeinschaft (DFG) [AL 1860/2-1]
NR 30
TC 395
Z9 454
U1 13
U2 451
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 322
EP 325
DI 10.1038/nature19056
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900033
PM 27535536
DA 2026-03-09
ER

PT J
AU Lin, YF
   Schulz, AM
   Pellegrino, MW
   Lu, Y
   Shaham, S
   Haynes, CM
AF Lin, Yi-Fan
   Schulz, Anna M.
   Pellegrino, Mark W.
   Lu, Yun
   Shaham, Shai
   Haynes, Cole M.
TI Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response
SO NATURE
LA English
DT Article
ID c-elegans; dna deletions; skeletal-muscle; cells; mtdna; heteroplasmy; activation; mitophagy; parkin; accumulation
AB Mitochondrial genomes (mitochondrial DNA, mtDNA) encode essential oxidative phosphorylation (OXPHOS) components. Because hundreds of mtDNAs exist per cell, a deletion in a single mtDNA has little impact. However, if the deletion genome is enriched, OXPHOS declines, resulting in cellular dysfunction. For example, Kearns-Sayre syndrome is caused by a single heteroplasmic mtDNA deletion. More broadly, mtDNA deletion accumulation has been observed in individual muscle cells(1) and dopaminergic neurons(2) during ageing. It is unclear how mtDNA deletions are tolerated or how they are propagated in somatic cells. One mechanism by which cells respond to OXPHOS dysfunction is by activating the mitochondrial unfolded protein response (UPRmt), a transcriptional response mediated by the transcription factor ATFS-1 that promotes the recovery and regeneration of defective mitochondria(3,4). Here we investigate the role of ATFS-1 in the maintenance and propagation of a deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain that stably expresses wild-type mtDNA and mtDNA with a 3.1-kilobase deletion (Delta mtDNA) lacking four essential genes(5). The heteroplasmic strain, which has 60% Delta mtDNA, displays modest mitochondrial dysfunction and constitutive UPRmt activation. ATFS-1 impairment reduced the Delta mtDNA nearly tenfold, decreasing the total percentage to 7%. We propose that in the context of mtDNA heteroplasmy, UPRmt activation caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics.
C1 [Lin, Yi-Fan; Schulz, Anna M.; Pellegrino, Mark W.; Haynes, Cole M.] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA.
   [Lu, Yun; Shaham, Shai] Rockefeller Univ, Lab Dev Genet, New York, NY 10065 USA.
   [Haynes, Cole M.] Weill Cornell Med Coll, BCMB Allied Program, 1300 York Ave, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Rockefeller University; Cornell University; Weill Cornell Medicine
RP Haynes, CM (corresponding author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA.; Haynes, CM (corresponding author), Weill Cornell Med Coll, BCMB Allied Program, 1300 York Ave, New York, NY 10065 USA.
EM haynesc@mskcc.org
FU NIH Office of Research 362 Infrastructure Programs [P40 OD010440]; Genomics and Bioinformatics Facilities at Memorial Sloan Kettering Cancer Center; National Institutes of Health [R01AG040061, R01AG047182, R01HD078703, R01NS081490]; Parkinson's Disease Foundation [PDF-FBS-1314]; Deutsche Forschungsgemeinschaft (DFG) [SCHU 3023/1-1]
NR 28
TC 251
Z9 296
U1 1
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 416
EP +
DI 10.1038/nature17989
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300053
PM 27135930
DA 2026-03-09
ER

PT J
AU Song, JR
   Ampatzis, K
   Björnfors, ER
   El Manira, A
AF Song, Jianren
   Ampatzis, Konstantinos
   Bjoernfors, E. Rebecka
   El Manira, Abdeljabbar
TI Motor neurons control locomotor circuit function retrogradely via gap junctions
SO NATURE
LA English
DT Article
ID mammalian spinal-cord; excitatory interneurons; adult zebrafish; electrical synapses; reflex inhibition; renshaw cells; transmission; motoneurons; recruitment; brain
AB Motor neurons are the final stage of neural processing for the execution of motor behaviours. Traditionally, motor neurons have been viewed as the 'final common pathway', serving as passive recipients merely conveying to the muscles the final motor program generated by upstream interneuron circuits(1,2). Here we reveal an unforeseen role of motor neurons in controlling the locomotor circuit function via gap junctions in zebrafish. These gap junctions mediate a retrograde analogue propagation of voltage fluctuations from motor neurons to control the synaptic release and recruitment of the upstream V2a interneurons that drive locomotion. Selective inhibition of motor neurons during ongoing locomotion de-recruits V2a interneurons and strongly influences locomotor circuit function. Rather than acting as separate units, gap junctions unite motor neurons and V2a interneurons into functional ensembles endowed with a retrograde analogue computation essential for locomotor rhythm generation. These results show that motor neurons are not a passive recipient of motor commands but an integral component of the neural circuits responsible for motor behaviour.
C1 [Song, Jianren; Ampatzis, Konstantinos; Bjoernfors, E. Rebecka; El Manira, Abdeljabbar] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
C3 Karolinska Institutet
RP El Manira, A (corresponding author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
EM Abdel.ElManira@ki.se
FU Swedish Research Council; Karolinska Institute; Swedish Brain Foundation
NR 42
TC 104
Z9 121
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 399
EP +
DI 10.1038/nature16497
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800047
PM 26760208
DA 2026-03-09
ER

PT J
AU Wang, T
   Liang, L
   Xue, Y
   Jia, PF
   Chen, W
   Zhang, MX
   Wang, YC
   Li, HJ
   Yang, WC
AF Wang, Tong
   Liang, Liang
   Xue, Yong
   Jia, Peng-Fei
   Chen, Wei
   Zhang, Meng-Xia
   Wang, Ying-Chun
   Li, Hong-Ju
   Yang, Wei-Cai
TI A receptor heteromer mediates the male perception of female attractants in plants
SO NATURE
LA English
DT Article
ID pollen-tube guidance; gene-expression; arabidopsis; kinase; activation; protein; cells; transcription; regulator; peptides
AB Sexual reproduction requires recognition between the male and female gametes. In flowering plants, the immobile sperms are delivered to the ovule-enclosed female gametophyte by guided pollen tube growth. Although the female gametophyte-secreted peptides have been identified to be the chemotactic attractant to the pollen tube(1-3), the male receptor(s) is still unknown. Here we identify a cell-surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives female attractant LURE1 in Arabidopsis thaliana. MDIS1, MIK1 and MIK2 are plasma-membrane-localized receptor-like kinases with extracellular leucine-rich repeats and an intracellular kinase domain. LURE1 specifically binds the extracellular domains of MDIS1, MIK1 and MIK2, whereas mdis1 and mik1 mik2 mutant pollen tubes respond less sensitively to LURE1. Furthermore, LURE1 triggers dimerization of the receptors and activates the kinase activity of MIK1. Importantly, transformation of AtMDIS1 to the sister species Capsella rubella can partially break down the reproductive isolation barrier. Our findings reveal a new mechanism of the male perception of the female attracting signals.
C1 [Wang, Tong; Liang, Liang; Xue, Yong; Jia, Peng-Fei; Chen, Wei; Zhang, Meng-Xia; Wang, Ying-Chun; Li, Hong-Ju; Yang, Wei-Cai] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China.
   [Wang, Tong; Liang, Liang; Xue, Yong; Chen, Wei; Zhang, Meng-Xia] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
RP Li, HJ; Yang, WC (corresponding author), Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China.
EM hjli@genetics.ac.cn; wcyang@genetics.ac.cn
FU Ministry of Science and Technology of China [2013CB945103, 2015CB910202]; National Natural Science Foundation of China [31330053, 31221063]
NR 29
TC 188
Z9 233
U1 12
U2 208
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 241
EP +
DI 10.1038/nature16975
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100043
PM 26863186
DA 2026-03-09
ER

PT J
AU Fujita, D
   Ueda, Y
   Sato, S
   Mizuno, N
   Kumasaka, T
   Fujita, M
AF Fujita, Daishi
   Ueda, Yoshihiro
   Sato, Sota
   Mizuno, Nobuhiro
   Kumasaka, Takashi
   Fujita, Makoto
TI Self-assembly of tetravalent Goldberg polyhedra from 144 small components
SO NATURE
LA English
DT Article
ID structural switch; principles; topology; design
AB Rational control of the self-assembly of large structures is one of the key challenges in chemistry(1-9), and is believed to become increasingly difficult and ultimately impossible as the number of components involved increases. So far, it has not been possible to design a self-assembled discrete molecule made up of more than 100 components. Such molecules-for example, spherical virus capsids(10)-are prevalent in nature, which suggests that the difficulty in designing these very large self-assembled molecules is due to a lack of understanding of the underlying design principles. For example, the targeted assembly of a series of large spherical structures containing up to 30 palladium ions coordinated by up to 60 bent organic ligands(11-16) was achieved by considering their topologies(17). Here we report the self-assembly of a spherical structure that also contains 30 palladium ions and 60 bent ligands, but belongs to a shape family that has not previously been observed experimentally(17). The new structure consists of a combination of 8 triangles and 24 squares, and has the symmetry of a tetravalent Goldberg polyhedron(18,19). Platonic and Archimedean solids have previously been prepared through self-assembly, as have trivalent Goldberg polyhedra, which occur naturally in the form of virus capsids(20) and fullerenes(21). But tetravalent Goldberg polyhedra have not previously been reported at the molecular level, although their topologies have been predicted using graph theory. We use graph theory to predict the self-assembly of even larger tetravalent Goldberg polyhedra, which should be more stable, enabling another member of this polyhedron family to be assembled from 144 components: 48 palladium ions and 96 bent ligands.
C1 [Fujita, Daishi; Ueda, Yoshihiro; Fujita, Makoto] Univ Tokyo, Grad Sch Engn, Dept Appl Chem, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
   [Fujita, Daishi] Japan Sci & Technol Agcy, PRESTO Precursory Res Embryon Sci & Technol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
   [Fujita, Daishi; Ueda, Yoshihiro; Fujita, Makoto] Japan Sci & Technol Agcy, ACCEL, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
   [Sato, Sota] Tohoku Univ, Adv Inst Mat Res, Aoba Ku, 2-1-1 Katahira, Sendai, Miyagi 9808577, Japan.
   [Sato, Sota] Japan Sci & Technol Agcy, ERATO, Aoba Ku, 2-1-1 Katahira, Sendai, Miyagi 9808577, Japan.
   [Mizuno, Nobuhiro; Kumasaka, Takashi] Japan Synchrotron Radiat Res Inst JASRI, SPring 8,1-1-1 Kouto, Sayo, Hyogo 6795198, Japan.
C3 University of Tokyo; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST); Tohoku University; Japan Science & Technology Agency (JST); Japan Synchrotron Radiation Research Institute
RP Fujita, D; Fujita, M (corresponding author), Univ Tokyo, Grad Sch Engn, Dept Appl Chem, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.; Fujita, D (corresponding author), Japan Sci & Technol Agcy, PRESTO Precursory Res Embryon Sci & Technol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.; Fujita, D; Fujita, M (corresponding author), Japan Sci & Technol Agcy, ACCEL, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM fujitadaishi@appchem.t.u-tokyo.ac.jp; mfujita@appchem.t.u-tokyo.ac.jp
FU JST-PRESTO programme; ACCEL programme; KAKENHI [25102007]; Grants-in-Aid for Scientific Research [25102001, 24000009, 25102007] Funding Source: KAKEN
NR 35
TC 555
Z9 596
U1 11
U2 369
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 563
EP +
DI 10.1038/nature20771
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500047
PM 30905932
DA 2026-03-09
ER

PT J
AU Rouse, GW
   Wilson, NG
   Carvajal, JI
   Vrijenhoek, RC
AF Rouse, Greg W.
   Wilson, Nerida G.
   Carvajal, Jose I.
   Vrijenhoek, Robert C.
TI New deep-sea species of Xenoturbella and the position of Xenacoelomorpha
SO NATURE
LA English
DT Article
ID bocki phylum xenoturbellida; mitochondrial genome; animal phylogeny; sequence; deuterostome; uncertain; indicate; program; sister; tree
AB The discovery of four new Xenoturbella species from deep waters of the eastern Pacific Ocean is reported here. The genus and two nominal species were described from the west coast of Sweden(1,2), but their taxonomic placement remains unstable(3,4). Limited evidence placed Xenoturbella with molluscs(5,6), but the tissues can be contaminated with prey(7,8). They were then considered deuterostomes(9-13). Further taxon sampling and analysis have grouped Xenoturbella with acoelomorphs (= Xenacoelomorpha) as sister to all other Bilateria (= Nephrozoa)(14,15), or placed Xenacoelomorpha inside Deuterostomia with Ambulacraria (Hemichordata + Echinodermata)(16). Here we describe four new species of Xenoturbella and reassess those hypotheses. A large species (> 20 cm long) was found at cold-water hydrocarbon seeps at 2,890 m depth in Monterey Canyon and at 1,722 m in the Gulf of California (Mexico). A second large species (similar to 10 cm long) also occurred at 1,722 m in the Gulf of California. The third large species (similar to 15 cm long) was found at similar to 3,700 m depth near a newly discovered carbonate-hosted hydrothermal vent in the Gulf of California. Finally, a small species (similar to 2.5 cm long), found near a whale carcass at 631 m depth in Monterey Submarine Canyon (California), resembles the two nominal species from Sweden. Analysis of whole mitochondrial genomes places the three larger species as a sister clade to the smaller Atlantic and Pacific species. Phylogenomic analyses of transcriptomic sequences support placement of Xenacoelomorpha as sister to Nephrozoa or Protostomia.
C1 [Rouse, Greg W.; Wilson, Nerida G.; Carvajal, Jose I.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92037 USA.
   [Wilson, Nerida G.] Western Australian Museum, Locked Bag 49, Welshpool Dc, WA 6986, Australia.
   [Wilson, Nerida G.] Univ Western Australia, Sch Anim Biol, Crawley, WA 6009, Australia.
   [Vrijenhoek, Robert C.] Monterey Bay Aquarium & Res Inst, Moss Landing, CA 95039 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Western Australian Museum; University of Western Australia; Monterey Bay Aquarium Research Institute
RP Rouse, GW (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92037 USA.
EM grouse@ucsd.edu
FU David and Lucile Packard Foundation via the Monterey Bay Aquarium Research Institute; Scripps Institution of Oceanography; National Science Foundation [DEB1036368]; Division Of Environmental Biology; Direct For Biological Sciences [1036368] Funding Source: National Science Foundation
NR 37
TC 99
Z9 110
U1 0
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 94
EP +
DI 10.1038/nature16545
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500039
PM 26842060
DA 2026-03-09
ER

PT J
AU De Henau, O
   Rausch, M
   Winkler, D
   Campesato, LF
   Liu, CL
   Hirschhorn-Cymerman, D
   Budhu, S
   Ghosh, A
   Pink, M
   Tchaicha, J
   Douglas, M
   Tibbitts, T
   Sharma, S
   Proctor, J
   Kosmider, N
   White, K
   Stern, H
   Soglia, J
   Adams, J
   Palombella, VJ
   McGovern, K
   Kutok, JL
   Wolchok, JD
   Merghoub, T
AF De Henau, Olivier
   Rausch, Matthew
   Winkler, David
   Campesato, Luis Felipe
   Liu, Cailian
   Hirschhorn-Cymerman, Daniel
   Budhu, Sadna
   Ghosh, Arnab
   Pink, Melissa
   Tchaicha, Jeremy
   Douglas, Mark
   Tibbitts, Thomas
   Sharma, Sujata
   Proctor, Jennifer
   Kosmider, Nicole
   White, Kerry
   Stern, Howard
   Soglia, John
   Adams, Julian
   Palombella, Vito J.
   McGovern, Karen
   Kutok, Jeffery L.
   Wolchok, Jedd D.
   Merghoub, Taha
TI Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells
SO NATURE
LA English
DT Article
ID suppressor-cells; tumor; inflammation; macrophages
AB Recent clinical trials using immunotherapy have demonstrated its potential to control cancer by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against cytotoxic-T-lymphocyte-associated protein 4 or programmed cell death protein 1/programmed death-ligand 1 have displayed durable clinical responses in various cancers(1). Although these new immunotherapies have had a notable effect on cancer treatment, multiple mechanisms of immune resistance exist in tumours. Among the key mechanisms, myeloid cells have a major role in limiting effective tumour immunity(2-4). Growing evidence suggests that high infiltration of immune-suppressive myeloid cells correlates with poor prognosis and ICB resistance(5,6). These observations suggest a need for a precision medicine approach in which the design of the immunotherapeutic combination is modified on the basis of the tumour immune landscape to overcome such resistance mechanisms. Here we employ a pre-clinical mouse model system and show that resistance to ICB is directly mediated by the suppressive activity of infiltrating myeloid cells in various tumours. Furthermore, selective pharmacologic targeting of the gamma isoform of phosphoinositide 3-kinase (PI3K gamma), highly expressed in myeloid cells, restores sensitivity to ICB. We demonstrate that targeting PI3K gamma with a selective inhibitor, currently being evaluated in a phase 1 clinical trial (NCT02637531), can reshape the tumour immune microenvironment and promote cytotoxic-T-cell-mediated tumour regression without targeting cancer cells directly. Our results introduce opportunities for new combination strategies using a selective small molecule PI3K gamma inhibitor, such as IPI-549, to overcome-resistance to ICB in patients with high levels of suppressive myeloid cell infiltration in tumours.
C1 [De Henau, Olivier; Campesato, Luis Felipe; Liu, Cailian; Hirschhorn-Cymerman, Daniel; Budhu, Sadna; Ghosh, Arnab; Wolchok, Jedd D.; Merghoub, Taha] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, New York, NY 10065 USA.
   [De Henau, Olivier; Campesato, Luis Felipe; Liu, Cailian; Hirschhorn-Cymerman, Daniel; Budhu, Sadna; Ghosh, Arnab; Wolchok, Jedd D.; Merghoub, Taha] Swim Across Amer, Ludwig Collaborat Lab, New York, NY 10065 USA.
   [Rausch, Matthew; Winkler, David; Pink, Melissa; Tchaicha, Jeremy; Douglas, Mark; Tibbitts, Thomas; Sharma, Sujata; Proctor, Jennifer; Kosmider, Nicole; White, Kerry; Stern, Howard; Soglia, John; Adams, Julian; Palombella, Vito J.; McGovern, Karen; Kutok, Jeffery L.] Infin Pharmaceut Inc, Cambridge, MA 02139 USA.
   [Wolchok, Jedd D.] Weill Cornell Med Sch, New York, NY 10065 USA.
   [Wolchok, Jedd D.] Weill Cornell Grad Sch, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Infinity Pharmaceuticals, Inc.; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine
RP Wolchok, JD; Merghoub, T (corresponding author), Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy, New York, NY 10065 USA.; Wolchok, JD; Merghoub, T (corresponding author), Swim Across Amer, Ludwig Collaborat Lab, New York, NY 10065 USA.; Wolchok, JD (corresponding author), Weill Cornell Med Sch, New York, NY 10065 USA.
EM wolchokj@mskcc.org; merghout@mskcc.org
FU Swim Across America; Ludwig Institute for Cancer Research; Parker Institute for Cancer Immunotherapy; Center for Experimental Therapeutics at MSKCC (ETC); Breast Cancer Research Foundation; MSKCC [P30 CA008748]; J. Houtard foundation; Nuovo Soldati Foundation; Wallonie-Bruxelles International; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 11
TC 705
Z9 784
U1 3
U2 190
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 443
EP 447
DI 10.1038/nature20554
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700057
PM 27828943
DA 2026-03-09
ER

PT J
AU Knowles, B
   Silveira, CB
   Bailey, BA
   Barott, K
   Cantu, VA
   Cobián-Güemes, AG
   Coutinho, FH
   Dinsdale, EA
   Felts, B
   Furby, KA
   George, EE
   Green, KT
   Gregoracci, GB
   Haas, AF
   Haggerty, JM
   Hester, ER
   Hisakawa, N
   Kelly, LW
   Lim, YW
   Little, M
   Luque, A
   McDole-Somera, T
   McNair, K
   de Oliveira, LS
   Quistad, SD
   Robinett, NL
   Sala, E
   Salamon, P
   Sanchez, SE
   Sandin, S
   Silva, GGZ
   Smith, J
   Sullivan, C
   Thompson, C
   Vermeij, MJA
   Youle, M
   Young, C
   Zgliczynski, B
   Brainard, R
   Edwards, RA
   Nulton, J
   Thompson, F
   Rohwer, F
AF Knowles, B.
   Silveira, C. B.
   Bailey, B. A.
   Barott, K.
   Cantu, V. A.
   Cobian-Gueemes, A. G.
   Coutinho, F. H.
   Dinsdale, E. A.
   Felts, B.
   Furby, K. A.
   George, E. E.
   Green, K. T.
   Gregoracci, G. B.
   Haas, A. F.
   Haggerty, J. M.
   Hester, E. R.
   Hisakawa, N.
   Kelly, L. W.
   Lim, Y. W.
   Little, M.
   Luque, A.
   McDole-Somera, T.
   McNair, K.
   de Oliveira, L. S.
   Quistad, S. D.
   Robinett, N. L.
   Sala, E.
   Salamon, P.
   Sanchez, S. E.
   Sandin, S.
   Silva, G. G. Z.
   Smith, J.
   Sullivan, C.
   Thompson, C.
   Vermeij, M. J. A.
   Youle, M.
   Young, C.
   Zgliczynski, B.
   Brainard, R.
   Edwards, R. A.
   Nulton, J.
   Thompson, F.
   Rohwer, F.
TI Lytic to temperate switching of viral communities
SO NATURE
LA English
DT Article
ID virus-like particles; life strategy; cystic-fibrosis; metagenomic analysis; respiratory-tract; bacterial-virus; marine-bacteria; growth-rate; coral; diversity
AB Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.
C1 [Knowles, B.; Silveira, C. B.; Cobian-Gueemes, A. G.; Dinsdale, E. A.; George, E. E.; Green, K. T.; Haas, A. F.; Haggerty, J. M.; Hester, E. R.; Hisakawa, N.; Kelly, L. W.; Lim, Y. W.; Little, M.; Quistad, S. D.; Robinett, N. L.; Sanchez, S. E.; Rohwer, F.] San Diego State Univ, Dept Biol, 5500 Campanile Dr, San Diego, CA 92182 USA.
   [Silveira, C. B.; Coutinho, F. H.; de Oliveira, L. S.; Thompson, C.; Thompson, F.] Univ Fed Rio de Janeiro, Inst Biol, Ave Carlos Chagas Filho 373, BR-21941599 Rio De Janeiro, Brazil.
   [Bailey, B. A.; Felts, B.; Luque, A.; Salamon, P.; Nulton, J.] San Diego State Univ, Dept Math & Stat, 5500 Campanile Dr, San Diego, CA 92182 USA.
   [Barott, K.] Univ Hawaii Manoa, Hawaii Inst Marine Biol, 46-007 Lilipuna Rd, Kaneohe, HI 96744 USA.
   [Cantu, V. A.; Luque, A.; McNair, K.; Silva, G. G. Z.; Edwards, R. A.] San Diego State Univ, Computat Sci Res Ctr, 5500 Campanile Dr, San Diego, CA 92182 USA.
   [Coutinho, F. H.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Ctr Mol & Biomol Informat, NL-6525 HP Nijmegen, Netherlands.
   [Dinsdale, E. A.; Luque, A.; Salamon, P.; Edwards, R. A.; Rohwer, F.] San Diego State Univ, Viral Informat Inst, 5500 Campanile Dr, San Diego, CA 92182 USA.
   [Furby, K. A.; McDole-Somera, T.; Sandin, S.; Smith, J.; Zgliczynski, B.] Scripps Inst Oceanog, 8622 Kennel Way, La Jolla, CA 92037 USA.
   [Gregoracci, G. B.] Sao Paulo Fed Univ Baixada Santista, Marine Sci Dept, Ave Alm Saldanha da Gama 89, BR-11030400 Sao Paulo, Brazil.
   [Sala, E.] Natl Geog Soc, 1145 17th St NW, Washington, DC 20036 USA.
   [Sullivan, C.] Univ Calif San Diego, Dept Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Vermeij, M. J. A.] CARMABI Fdn, Piscaderabaai Z-N, Willemstad, Curacao, Netherlands.
   [Vermeij, M. J. A.] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, Aquat Microbiol, NL-1098 XH Amsterdam, Netherlands.
   [Youle, M.] Rainbow Rock, Ocean View, HI 96737 USA.
   [Young, C.; Brainard, R.] NOAA, Coral Reef Ecosyst Div, PIFSC, 1845 Wasp Blvd, Honolulu, HI 96818 USA.
   [Edwards, R. A.] San Diego State Univ, Dept Comp Sci, 5500 Campanile Dr, San Diego, CA 92182 USA.
C3 California State University System; San Diego State University; Universidade Federal do Rio de Janeiro; California State University System; San Diego State University; University of Hawaii System; University of Hawaii Manoa; California State University System; San Diego State University; Radboud University Nijmegen; California State University System; San Diego State University; University of California System; University of California San Diego; Scripps Institution of Oceanography; National Geographic Society; University of California System; University of California San Diego; University of Amsterdam; National Oceanic Atmospheric Admin (NOAA) - USA; California State University System; San Diego State University
RP Knowles, B; Rohwer, F (corresponding author), San Diego State Univ, Dept Biol, 5500 Campanile Dr, San Diego, CA 92182 USA.; Rohwer, F (corresponding author), San Diego State Univ, Viral Informat Inst, 5500 Campanile Dr, San Diego, CA 92182 USA.
EM benjaminwilliamknowles@gmail.com; frohwer@gmail.com
FU Canadian Institute for Advanced Research Integrated Microbial Biodiversity Program Fellowship Award [141679]; National Science Foundation [OISE-1243541, DEB-1046413, CNS-1305112, MCB-1330800, DUE-1323809]; Gordon and Betty Moore Foundation Investigator Award [GBMF-3781]; Brazilian National Research Council (CNPq); Brazilian National Research Council Science Without Borders Program (CNPq/CAPES); Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1330800] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1107046] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Ocean Sciences [1538567] Funding Source: National Science Foundation; Division Of Undergraduate Education; Direct For Education and Human Resources [1323809] Funding Source: National Science Foundation
NR 79
TC 456
Z9 534
U1 17
U2 373
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 466
EP +
DI 10.1038/nature17193
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300032
PM 26982729
DA 2026-03-09
ER

PT J
AU Carpenter, B
   Nehmé, R
   Warne, T
   Leslie, AGW
   Tate, CG
AF Carpenter, Byron
   Nehme, Rony
   Warne, Tony
   Leslie, Andrew G. W.
   Tate, Christopher G.
TI Structure of the adenosine A2A receptor bound to an engineered G protein
SO NATURE
LA English
DT Article
ID crystal-structure; coupled receptor; agonist; insights; activation; binding
AB G-protein-coupled receptors (GPCRs) are essential components of the signalling network throughout the body. To understand the molecular mechanism of G-protein-mediated signalling, solved structures of receptors in inactive conformations and in the active conformation coupled to a G protein are necessary(1,2). Here we present the structure of the adenosine A(2A) receptor (A(2A)R) bound to an engineered G protein, mini-G(s), at 3.4 angstrom resolution. Mini-G(s) binds to A(2A)R through an extensive interface (1,048 angstrom(2)) that is similar, but not identical, to the interface between G(s) and the beta(2)-adrenergic receptor(3). The transition of the receptor from an agonist-bound active-intermediate state(4,5) to an active G-protein-bound state is characterized by a 14 angstrom shift of the cytoplasmic end of transmembrane helix 6 (H6) away from the receptor core, slight changes in the positions of the cytoplasmic ends of H5 and H7 and rotamer changes of the amino acid side chains Arg(3.50), Tyr(5.58) and Tyr(7.53). There are no substantial differences in the extracellular half of the receptor around the ligand binding pocket. The A(2A)R-mini-G(s) structure highlights both the diversity and similarity in G-protein coupling to GPCRs(6) and hints at the potential complexity of the molecular basis for G-protein specificity.
C1 [Carpenter, Byron; Nehme, Rony; Warne, Tony; Leslie, Andrew G. W.; Tate, Christopher G.] MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Tate, CG (corresponding author), MRC, Mol Biol Lab, Francis Crick Ave, Cambridge CB2 0QH, England.
EM cgt@mrc-lmb.cam.ac.uk
FU Heptares Therapeutics Ltd.; ERC [EMPSI 339995]; Medical Research Council [MC_U105197215, MC_U105184325]; BBSRC [BB/M017982/1] Funding Source: UKRI; MRC [MC_U105184325, MC_U105197215] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/M017982/1] Funding Source: researchfish; Medical Research Council [MC_U105197215, MC_U105184325] Funding Source: researchfish
NR 24
TC 342
Z9 409
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 104
EP +
DI 10.1038/nature18966
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200039
PM 27462812
DA 2026-03-09
ER

PT J
AU Chaudhuri, AR
   Callen, E
   Ding, X
   Gogola, E
   Duarte, AA
   Lee, JE
   Wong, N
   Lafarga, V
   Calvo, JA
   Panzarino, NJ
   John, S
   Day, A
   Crespo, AV
   Shen, BH
   Starnes, LM
   de Ruiter, JR
   Daniel, JA
   Konstantinopoulos, PA
   Cortez, D
   Cantor, SB
   Fernandez-Capetillo, O
   Ge, K
   Jonkers, J
   Rottenberg, S
   Sharan, SK
   Nussenzweig, A
AF Chaudhuri, Arnab Ray
   Callen, Elsa
   Ding, Xia
   Gogola, Ewa
   Duarte, Alexandra A.
   Lee, Ji-Eun
   Wong, Nancy
   Lafarga, Vanessa
   Calvo, Jennifer A.
   Panzarino, Nicholas J.
   John, Sam
   Day, Amanda
   Crespo, Anna Vidal
   Shen, Binghui
   Starnes, Linda M.
   de Ruiter, Julian R.
   Daniel, Jeremy A.
   Konstantinopoulos, Panagiotis A.
   Cortez, David
   Cantor, Sharon B.
   Fernandez-Capetillo, Oscar
   Ge, Kai
   Jonkers, Jos
   Rottenberg, Sven
   Sharan, Shyam K.
   Nussenzweig, Andre
TI Replication fork stability confers chemoresistance in BRCA-deficient cells
SO NATURE
LA English
DT Article
ID homology-directed repair; conditional mouse model; mutant-cells; dna-damage; 53bp1; recombination; resistance; resection; rif1; ptip
AB Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.
C1 [Chaudhuri, Arnab Ray; Callen, Elsa; Wong, Nancy; John, Sam; Day, Amanda; Crespo, Anna Vidal; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
   [Ding, Xia; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
   [Gogola, Ewa; Duarte, Alexandra A.; de Ruiter, Julian R.; Jonkers, Jos; Rottenberg, Sven] Netherlands Canc Inst, Div Mol Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Ding, Xia; Gogola, Ewa; de Ruiter, Julian R.; Jonkers, Jos; Rottenberg, Sven] Netherlands Canc Inst, Canc Genom Ctr, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Lee, Ji-Eun; Ge, Kai] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
   [Lafarga, Vanessa; Fernandez-Capetillo, Oscar] Spanish Natl Canc Res Ctr CNIO, Genom Instabil Grp, Madrid 28029, Spain.
   [Calvo, Jennifer A.; Panzarino, Nicholas J.; Cantor, Sharon B.] Univ Massachusetts, Sch Med, UMASS Mem Canc Ctr, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA.
   [Shen, Binghui] City Hope Natl Med Ctr, Beckman Res Inst, Dept Radiat Biol, 1500 East Duarte Rd, Duarte, CA 91010 USA.
   [Starnes, Linda M.; Daniel, Jeremy A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Prot Res, DK-2200 Copenhagen, Denmark.
   [Konstantinopoulos, Panagiotis A.] Harvard Med Sch, Dana Farber Canc Inst, Dept Gynecol Med Oncol, Boston, MA 02215 USA.
   [Cortez, David] Vanderbilt Univ, Dept Biochem, Sch Med, 2215 Garland Ave, Nashville, TN 37232 USA.
   [Rottenberg, Sven] Univ Bern, Vetsuisse Fac, Inst Anim Pathol, Langgassstr 122, CH-3012 Bern, Switzerland.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Netherlands Cancer Institute; Netherlands Cancer Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Centro Nacional de Investigaciones Oncologicas (CNIO); University of Massachusetts System; University of Massachusetts Worcester; University Massachusetts Worcester Hospital; City of Hope; Beckman Research Institute of City of Hope; University of Copenhagen; Novo Nordisk Foundation; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Vanderbilt University; University of Bern
RP Nussenzweig, A (corresponding author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH), the National Cancer Institute; Center for Cancer Research; Department of Defense [11557134]; Netherlands Organization for Scientific Research; Dutch Cancer Society; Swiss National Science Foundation; Swiss National Science Foundation [PBZHP3 147302]; Human Frontier Science Program Long-Term Fellowship [LT000393/2013]; NIH [R01 CA176166-01A1, R01CA085344]; Novo Nordisk Foundation [NNF14CC0001]; Swiss National Science Foundation (SNF) [PBZHP3_147302] Funding Source: Swiss National Science Foundation (SNF); National Cancer Institute [R01CA085344, ZIABC011311, ZIABC010959, ZIABC010283] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK075003, ZIADK075017] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM116616] Funding Source: NIH RePORTER
NR 44
TC 746
Z9 830
U1 2
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 382
EP +
DI 10.1038/nature18325
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200032
PM 27443740
DA 2026-03-09
ER

PT J
AU Roettenbacher, RM
   Monnier, JD
   Korhonen, H
   Aarnio, AN
   Baron, F
   Che, X
   Harmon, RO
   Kovári, Z
   Kraus, S
   Schaefer, GH
   Torres, G
   Zhao, M
   ten Brummelaar, TA
   Sturmann, J
   Sturmann, L
AF Roettenbacher, R. M.
   Monnier, J. D.
   Korhonen, H.
   Aarnio, A. N.
   Baron, F.
   Che, X.
   Harmon, R. O.
   Kovari, Zs.
   Kraus, S.
   Schaefer, G. H.
   Torres, G.
   Zhao, M.
   ten Brummelaar, T. A.
   Sturmann, J.
   Sturmann, L.
TI No Sun-like dynamo on the active star ζ Andromedae from starspot asymmetry
SO NATURE
LA English
DT Article
ID low-mass stars; brown dwarfs; light-curve; chara array; interferometry; surface; spots; controversy; evolution; radii
AB Sunspots are cool areas caused by strong surface magnetic fields that inhibit convection(1,2). Moreover, strong magnetic fields can alter the average atmospheric structure(3), degrading our ability to measure stellar masses and ages. Stars that are more active than the Sun have more and stronger dark spots than does the Sun, including on the rotational pole(4). Doppler imaging, which has so far produced the most detailed images of surface structures on other stars, cannot always distinguish the hemisphere in which the starspots are located, especially in the equatorial region and if the data quality is not optimal(5). This leads to problems in investigating the north-south distribution of starspot active latitudes (those latitudes with more starspot activity); this distribution is a crucial constraint of dynamo theory. Polar spots, whose existence is inferred from Doppler tomography, could plausibly be observational artefacts(6). Here we report imaging of the old, magnetically active star zeta Andromedae using long-baseline infrared interferometry. In our data, a dark polar spot is seen in each of two observation epochs, whereas lower-latitude spot structures in both hemispheres do not persist between observations, revealing global starspot asymmetries. The north-south symmetry of active latitudes observed on the Sun(7) is absent on zeta And, which hosts global spot patterns that cannot be produced by solar-type dynamos(8).
C1 [Roettenbacher, R. M.; Monnier, J. D.; Aarnio, A. N.; Baron, F.; Che, X.; Kraus, S.; Zhao, M.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Korhonen, H.] Univ Turku, Finnish Ctr Astron ESO FINCA, FI-21500 Piikkio, Finland.
   [Korhonen, H.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
   [Baron, F.] Georgia State Univ, Dept Phys & Astron, Atlanta, GA 30303 USA.
   [Harmon, R. O.] Ohio Wesleyan Univ, Dept Phys & Astron, Delaware, OH USA.
   [Kovari, Zs.] Hungarian Acad Sci, Konkoly Observ, Res Ctr Astron & Earth Sci, H-1121 Budapest, Hungary.
   [Kraus, S.] Univ Exeter, Sch Phys, Exeter EX4 4QL, Devon, England.
   [Schaefer, G. H.; ten Brummelaar, T. A.; Sturmann, J.; Sturmann, L.] Georgia State Univ, Ctr High Angular Resolut Astron, Mt Wilson, CA 91023 USA.
   [Torres, G.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Zhao, M.] Penn State Univ, Dept Astron & Astrophys, State Coll, PA 16802 USA.
C3 University of Michigan System; University of Michigan; University of Turku; University of Copenhagen; Niels Bohr Institute; University System of Georgia; Georgia State University; University System of Ohio; Ohio Wesleyan University; Hungarian Academy of Sciences; HUN-REN; HUN-REN Research Centre for Astronomy & Earth Sciences; Konkoly Thege Miklos Astronomical Institute; University of Exeter; University System of Georgia; Georgia State University; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Roettenbacher, RM (corresponding author), Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
EM rmroett@umich.edu
FU National Science Foundation [AST-1211929, AST-1411654]; University of Michigan; National Science Foundation (NSF) [AST-1108963]; Hungarian Scientific Research Fund [OTKA K-109276]; Hungarian Academy of Sciences; STFC [ST/J004030/1, ST/K003445/1]; ERC [639889]; Science and Technology Facilities Council [ST/K003445/1, ST/J004030/1] Funding Source: researchfish; STFC [ST/J004030/1, ST/K003445/1] Funding Source: UKRI; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1211929, 1509375, 1445935] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1411654] Funding Source: National Science Foundation
NR 42
TC 95
Z9 100
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 217
EP +
DI 10.1038/nature17444
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200043
PM 27144357
DA 2026-03-09
ER

PT J
AU Wang, ZJ
   Alexandradinata, A
   Cava, RJ
   Bernevig, BA
AF Wang, Zhijun
   Alexandradinata, A.
   Cava, R. J.
   Bernevig, B. Andrei
TI Hourglass fermions
SO NATURE
LA English
DT Article
ID topological crystalline insulator; energy-bands; phase-transition; polarization; realization
AB Spatial symmetries in crystals may be distinguished by whether they preserve the spatial origin. Here we study spatial symmetries that translate the origin by a fraction of the lattice period, and find that these non-symmorphic symmetries protect an exotic surface fermion whose dispersion relation is shaped like an hourglass; surface bands connect one hourglass to the next in an unbreakable zigzag pattern. These 'hourglass' fermions are formed in the large-gap insulators, KHgX (X = As, Sb, Bi), which we propose as the first material class whose band topology relies on non-symmorphic symmetries. Besides the hourglass fermion, another surface of KHgX manifests a three-dimensional generalization of the quantum spin Hall effect, which has previously been observed only in two-dimensional crystals. To describe the bulk topology of non-symmorphic crystals, we propose a non-Abelian generalization of the geometric theory of polarization. Our non-trivial topology originates from an inversion of the rotational quantum numbers, which we propose as a criterion in the search for topological materials.
C1 [Wang, Zhijun; Alexandradinata, A.; Bernevig, B. Andrei] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Alexandradinata, A.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Cava, R. J.] Princeton Univ, Dept Chem, Princeton, NJ 08540 USA.
C3 Princeton University; Yale University; Princeton University
RP Bernevig, BA (corresponding author), Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
EM bernevig@princeton.edu
FU NSF CAREER [DMR-095242, ONR-N00014-11-1-0635]; TI MURI [W911NF-12-1-0461]; NSF-MRSEC [DMR-1420541]; Packard Foundation; Keck grant; ONR [25812-G0001-10006242-101]; Schmidt fund [23800-E2359-FB625]; Yale Fellowship in Condensed Matter Physics
NR 51
TC 378
Z9 410
U1 3
U2 184
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 189
EP 194
DI 10.1038/nature17410
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100030
PM 27075096
DA 2026-03-09
ER

PT J
AU Boettiger, AN
   Bintu, B
   Moffitt, JR
   Wang, SY
   Beliveau, BJ
   Fudenberg, G
   Imakaev, M
   Mirny, LA
   Wu, CT
   Zhuang, XW
AF Boettiger, Alistair N.
   Bintu, Bogdan
   Moffitt, Jeffrey R.
   Wang, Siyuan
   Beliveau, Brian J.
   Fudenberg, Geoffrey
   Imakaev, Maxim
   Mirny, Leonid A.
   Wu, Chao-ting
   Zhuang, Xiaowei
TI Super-resolution imaging reveals distinct chromatin folding for different epigenetic states
SO NATURE
LA English
DT Article
ID 3d genome; organization; visualization; principles; domains
AB Metazoan genomes are spatially organized at multiple scales, from packaging of DNA around individual nucleosomes to segregation of whole chromosomes into distinct territories1-5. At the intermediate scale of kilobases to megabases, which encompasses the sizes of genes, gene clusters and regulatory domains, the three-dimensional (3D) organization of DNA is implicated in multiple gene regulatory mechanisms(2-4,6-8), but understanding this organization remains a challenge. At this scale, the genome is partitioned into domains of different epigenetic states that are essential for regulating gene expression(9-11). Here we investigate the 3D organization of chromatin in different epigenetic states using super-resolution imaging. We classified genomic domains in Drosophila cells into transcriptionally active, inactive or Polycomb-repressed states, and observed distinct chromatin organizations for each state. All three types of chromatin domains exhibit power-law scaling between their physical sizes in 3D and their domain lengths, but each type has a distinct scaling exponent. Polycomb-repressed domains show the densest packing and most intriguing chromatin folding behaviour, in which chromatin packing density increases with domain length. Distinct from the self-similar organization displayed by transcriptionally active and inactive chromatin, the Polycomb-repressed domains are characterized by a high degree of chromatin intermixing within the domain. Moreover, compared to inactive domains, Polycomb-repressed domains spatially exclude neighbouring active chromatin to a much stronger degree. Computational modelling and knockdown experiments suggest that reversible chromatin interactions mediated by Polycomb-group proteins play an important role in these unique packaging properties of the repressed chromatin. Taken together, our super-resolution images reveal distinct chromatin packaging for different epigenetic states at the kilobase-to-megabase scale, a length scale that is directly relevant to genome regulation.
C1 [Boettiger, Alistair N.; Bintu, Bogdan; Moffitt, Jeffrey R.; Wang, Siyuan; Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Dept Phys, Cambridge, MA 02138 USA.
   [Beliveau, Brian J.; Wu, Chao-ting] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
   [Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A.] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Zhuang, XW (corresponding author), Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Dept Phys, Cambridge, MA 02138 USA.
EM zhuang@chemistry.harvard.edu
FU National Institutes of Health; Damon Runyon Foundation postdoctoral fellowship; Helen Hay Whitney Foundation postdoctoral fellowship; Jane Coffin Childs Foundation; National Institute of General Medical Sciences [R01GM114190] Funding Source: NIH RePORTER
NR 30
TC 634
Z9 770
U1 1
U2 313
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 418
EP +
DI 10.1038/nature16496
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800051
PM 26760202
DA 2026-03-09
ER

PT J
AU Reimer, JM
   Aloise, MN
   Harrison, PM
   Schmeing, TM
AF Reimer, Janice M.
   Aloise, Martin N.
   Harrison, Paul M.
   Schmeing, T. Martin
TI Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase
SO NATURE
LA English
DT Article
ID x-ray-scattering; crystal-structure; structural-characterization; biological macromolecules; diffraction data; biosynthesis; gramicidin; domain; antibiotics; adenylation
AB Nonribosomal peptide synthetases (NRPSs) are very large proteins that produce small peptide molecules with wide-ranging biological activities, including environmentally friendly chemicals and many widely used therapeutics(1). NRPSs are macromolecular machines, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites(2,3). In addition to the core domains required to link the substrates, they often include specialized tailoring domains, which introduce chemical modifications and allow the product to access a large expanse of chemical space(3,4). It is still unknown how the NRPS tailoring domains are structurally accommodated into megaenzymes or how they have adapted to function in nonribosomal peptide synthesis. Here we present a series of crystal structures of the initiation module of an antibiotic-producing NRPS, linear gramicidin synthetase(5,6). This module includes the specialized tailoring formylation domain, and states are captured that represent every major step of the assembly-line synthesis in the initiation module. The transitions between conformations are large in scale, with both the peptidyl carrier protein domain and the adenylation subdomain undergoing huge movements to transport substrate between distal active sites. The structures highlight the great versatility of NRPSs, as small domains repurpose and recycle their limited interfaces to interact with their various binding partners. Understanding tailoring domains is important if NRPSs are to be utilized in the production of novel therapeutics.
C1 [Reimer, Janice M.; Aloise, Martin N.; Schmeing, T. Martin] McGill Univ, Dept Biochem, Montreal, PQ H3G 0B1, Canada.
   [Harrison, Paul M.] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
C3 McGill University; McGill University
RP Schmeing, TM (corresponding author), McGill Univ, Dept Biochem, 3649 Promenade Sir William Osler, Montreal, PQ H3G 0B1, Canada.
EM martin.schmeing@mcgill.ca
FU CIHR [106615]; HFSP CDA; Canada Research Chair in Macromolecular Machines; NSERC Alexander Graham Bell studentship; CIHR Training Grant in Chemical Biology
NR 57
TC 129
Z9 173
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 239
EP U305
DI 10.1038/nature16503
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700043
PM 26762462
DA 2026-03-09
ER

PT J
AU Radha, B
   Esfandiar, A
   Wang, FC
   Rooney, AP
   Gopinadhan, K
   Keerthi, A
   Mishchenko, A
   Janardanan, A
   Blake, P
   Fumagalli, L
   Lozada-Hidalgo, M
   Garaj, S
   Haigh, SJ
   Grigorieva, IV
   Wu, HA
   Geim, AK
AF Radha, B.
   Esfandiar, A.
   Wang, F. C.
   Rooney, A. P.
   Gopinadhan, K.
   Keerthi, A.
   Mishchenko, A.
   Janardanan, A.
   Blake, P.
   Fumagalli, L.
   Lozada-Hidalgo, M.
   Garaj, S.
   Haigh, S. J.
   Grigorieva, I. V.
   Wu, H. A.
   Geim, A. K.
TI Molecular transport through capillaries made with atomic-scale precision
SO NATURE
LA English
DT Article
ID carbon nanotube membranes; der-waals heterostructures; fast water transport; porous graphene; mass-transport; graphite; dynamics; flow; nanofluidics; interfaces
AB Nanometre-scale pores and capillaries have long been studied because of their importance in many natural phenomena and their use in numerous applications(1). A more recent development is the ability to fabricate artificial capillaries with nanometre dimensions, which has enabled new research on molecular transport and led to the emergence of nanofluidics(2-4). But surface roughness in particular makes it challenging to produce capillaries with precisely controlled dimensions at this spatial scale. Here we report the fabrication of narrow and smooth capillaries through van der Waals assembly(5), with atomically flat sheets at the top and bottom separated by spacers made of two-dimensional crystals(6) with a precisely controlled number of layers. We use graphene and its multilayers as archetypal two-dimensional materials to demonstrate this technology, which produces structures that can be viewed as if individual atomic planes had been removed from a bulk crystal to leave behind flat voids of a height chosen with atomic-scale precision. Water transport through the channels, ranging in height from one to several dozen atomic planes, is characterized by unexpectedly fast flow (up to 1 metre per second) that we attribute to high capillary pressures (about 1,000 bar) and large slip lengths. For channels that accommodate only a few layers of water, the flow exhibits a marked enhancement that we associate with an increased structural order in nanoconfined water. Our work opens up an avenue to making capillaries and cavities with sizes tunable to angstrom precision, and with permeation properties further controlled through a wide choice of atomically flat materials available for channel walls.
C1 [Radha, B.; Esfandiar, A.; Gopinadhan, K.; Keerthi, A.; Mishchenko, A.; Janardanan, A.; Fumagalli, L.; Lozada-Hidalgo, M.; Grigorieva, I. V.; Geim, A. K.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Wang, F. C.; Wu, H. A.] Chinese Acad Sci, Univ Sci & Technol China, Dept Modern Mech, Key Lab Mech Behav & Design Mat, Hefei 230027, Anhui, Peoples R China.
   [Rooney, A. P.; Haigh, S. J.] Univ Manchester, Sch Mat, Manchester M13 9PL, Lancs, England.
   [Blake, P.; Fumagalli, L.] Univ Manchester, Natl Graphene Inst, Booth St East, Manchester M13 9PL, Lancs, England.
   [Garaj, S.] Natl Univ Singapore, Dept Phys, Singapore 117542, Singapore.
C3 University of Manchester; Chinese Academy of Sciences; University of Science & Technology of China, CAS; University of Manchester; University of Manchester; National University of Singapore
RP Radha, B; Geim, AK (corresponding author), Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.; Wang, FC (corresponding author), Chinese Acad Sci, Univ Sci & Technol China, Dept Modern Mech, Key Lab Mech Behav & Design Mat, Hefei 230027, Anhui, Peoples R China.
EM radha.boya@manchester.ac.uk; wangfc@ustc.edu.cn; andre.k.geim@manchester.ac.uk
FU Lloyd's Register Foundation; European Research Council; Royal Society; EPSRC NowNANO programme [EP/M022498/1, EP/K016946/1]; DTRA [HDTRA1-12-1-0013]; Engineering and Physical Sciences Research Council [EP/M022498/1, EP/N010345/1, EP/K016946/1, EP/N007131/1, EP/K005014/1] Funding Source: researchfish; EPSRC [EP/K005014/1, EP/N007131/1, EP/N010345/1] Funding Source: UKRI
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NR 53
TC 620
Z9 682
U1 35
U2 1001
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 222
EP +
DI 10.1038/nature19363
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000040
PM 27602512
DA 2026-03-09
ER

PT J
AU Potvin-Trottier, L
   Lord, ND
   Vinnicombe, G
   Paulsson, J
AF Potvin-Trottier, Laurent
   Lord, Nathan D.
   Vinnicombe, Glenn
   Paulsson, Johan
TI Synchronous long-term oscillations in a synthetic gene circuit
SO NATURE
LA English
DT Article
ID expression; cyanobacteria; fluctuations; network; robust; noise; cells
AB Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator(1), and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.
C1 [Potvin-Trottier, Laurent; Lord, Nathan D.; Paulsson, Johan] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
   [Potvin-Trottier, Laurent] Harvard Univ, Biophys Program, Cambridge, MA 02138 USA.
   [Lord, Nathan D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Vinnicombe, Glenn] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; University of Cambridge
RP Paulsson, J (corresponding author), Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
EM johan_paulsson@harvard.edu
FU NSF [ECS-0335765, 1517372]; Natural Sciences and Engineering Research Council of Canada (NSERC); Fonds de recherche du Quebec - Nature et technologies; National Institutes of Health (NIH) [GM081563, GM095784]; National Institute of General Medical Sciences [R01GM081563] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1517372] Funding Source: National Science Foundation
NR 36
TC 219
Z9 291
U1 5
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 514
EP +
DI 10.1038/nature19841
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400059
PM 27732583
DA 2026-03-09
ER

PT J
AU Baden, T
   Berens, P
   Franke, K
   Rosón, MR
   Bethge, M
   Euler, T
AF Baden, Tom
   Berens, Philipp
   Franke, Katrin
   Roson, Miroslav Roman
   Bethge, Matthias
   Euler, Thomas
TI The functional diversity of retinal ganglion cells in the mouse
SO NATURE
LA English
DT Article
ID receptive-fields; classification; identification; representations; organization; responses; pathways; parallel; subtypes; spikes
AB In the vertebrate visual system, all output of the retina is carried by retinal ganglion cells. Each type encodes distinct visual features in parallel for transmission to the brain. How many such 'output channels' exist and what each encodes are areas of intense debate. In the mouse, anatomical estimates range from 15 to 20 channels, and only a handful are functionally understood. By combining two-photon calcium imaging to obtain dense retinal recordings and unsupervised clustering of the resulting sample of more than 11,000 cells, here we show that the mouse retina harbours substantially more than 30 functional output channels. These include all known and several new ganglion cell types, as verified by genetic and anatomical criteria. Therefore, information channels from the mouse eye to the mouse brain are considerably more diverse than shown thus far by anatomical studies, suggesting an encoding strategy resembling that used in state-of-the-art artificial vision systems.
C1 [Baden, Tom; Berens, Philipp; Franke, Katrin; Roson, Miroslav Roman; Bethge, Matthias; Euler, Thomas] Bernstein Ctr Computat Neurosci, D-72076 Tubingen, Germany.
   [Baden, Tom; Berens, Philipp; Franke, Katrin; Roson, Miroslav Roman; Bethge, Matthias; Euler, Thomas] Univ Tubingen, Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
   [Baden, Tom; Berens, Philipp; Franke, Katrin; Roson, Miroslav Roman; Euler, Thomas] Inst Ophthalm Res, D-72076 Tubingen, Germany.
   [Berens, Philipp] Baylor Coll Med, Houston, TX 77030 USA.
   [Berens, Philipp; Bethge, Matthias] Univ Tubingen, Inst Theoret Phys, D-72076 Tubingen, Germany.
   [Franke, Katrin; Roson, Miroslav Roman] Univ Tubingen, Grad Training Ctr Neurosci, D-72074 Tubingen, Germany.
   [Bethge, Matthias] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Baylor College of Medicine; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Max Planck Society
RP Euler, T (corresponding author), Bernstein Ctr Computat Neurosci, D-72076 Tubingen, Germany.
EM thomas.euler@cin.uni-tuebingen.de
FU Deutsche Forschungsgemeinschaft (DFG) (Werner Reichardt Centre for Integrative Neuroscience Tubingen) [EXC 307, BA 5283/1-1, BE 5601/1-1]; German Federal Ministry of Education and Research (BMBF) (BCCN Tubingen) [FKZ 01GQ1002]; BW-Stiftung [AZ 1.16101.09]; intramural fortune program of the University of Tubingen [2125-0-0]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [U01NS090562]
NR 55
TC 700
Z9 843
U1 8
U2 200
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 345
EP +
DI 10.1038/nature16468
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800036
PM 26735013
DA 2026-03-09
ER

PT J
AU Gautam, R
   Nishimura, Y
   Pegu, A
   Nason, MC
   Klein, F
   Gazumyan, A
   Golijanin, J
   Buckler-White, A
   Sadjadpour, R
   Wang, KY
   Mankoff, Z
   Schmidt, SD
   Lifson, JD
   Mascola, JR
   Nussenzweig, MC
   Martin, MA
AF Gautam, Rajeev
   Nishimura, Yoshiaki
   Pegu, Amarendra
   Nason, Martha C.
   Klein, Florian
   Gazumyan, Anna
   Golijanin, Jovana
   Buckler-White, Alicia
   Sadjadpour, Reza
   Wang, Keyun
   Mankoff, Zachary
   Schmidt, Stephen D.
   Lifson, Jeffrey D.
   Mascola, John R.
   Nussenzweig, Michel C.
   Martin, Malcolm A.
TI A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges
SO NATURE
LA English
DT Article
ID simian/human immunodeficiency virus; broadly neutralizing antibody; hiv-1/siv chimeric virus; monoclonal-antibody; improves protection; passive transfer; potent; macaques; infection; transmission
AB Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively(1-8), the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9-12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.
C1 [Gautam, Rajeev; Nishimura, Yoshiaki; Buckler-White, Alicia; Sadjadpour, Reza; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Pegu, Amarendra; Wang, Keyun; Mankoff, Zachary; Schmidt, Stephen D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
   [Klein, Florian; Gazumyan, Anna; Golijanin, Jovana; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Klein, Florian] Univ Cologne, Lab Expt Immunol, CMMC, D-50931 Cologne, Germany.
   [Klein, Florian] Univ Hosp Cologne, Ctr Integrated Oncol Cologne Bonn, Dept Internal Med 1, D-50937 Cologne, Germany.
   [Lifson, Jeffrey D.] Frederick Natl Lab Canc Res, Leidos Biomed Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
   [Nussenzweig, Michel C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Rockefeller University; University of Cologne; University of Cologne; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Howard Hughes Medical Institute
RP Martin, MA (corresponding author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM malm@nih.gov
FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; National Cancer Institute, NIH [HHSN261200800001E]; Bill and Melinda Gates Foundation [OPP1033115, OPP1092074]; NIH [AI-100148, UM1 AI100663-01]; Robertson Foundation; Howard Hughes Medical Institute; Bill and Melinda Gates Foundation [OPP1092074, OPP1033115] Funding Source: Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [ZIAAI001213, P01AI100148] Funding Source: NIH RePORTER
NR 33
TC 267
Z9 324
U1 0
U2 56
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 105
EP +
DI 10.1038/nature17677
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900048
PM 27120156
DA 2026-03-09
ER

PT J
AU Thienpont, B
   Steinbacher, J
   Zhao, H
   D'Anna, F
   Kuchnio, A
   Ploumakis, A
   Ghesquière, B
   Van Dyck, L
   Boeckx, B
   Schoonjans, L
   Hermans, E
   Amant, F
   Kristensen, VN
   Koh, KP
   Mazzone, M
   Coleman, ML
   Carell, T
   Carmeliet, P
   Lambrechts, D
AF Thienpont, Bernard
   Steinbacher, Jessica
   Zhao, Hui
   D'Anna, Flora
   Kuchnio, Anna
   Ploumakis, Athanasios
   Ghesquiere, Bart
   Van Dyck, Laurien
   Boeckx, Bram
   Schoonjans, Luc
   Hermans, Els
   Amant, Frederic
   Kristensen, Vessela N.
   Koh, Kian Peng
   Mazzone, Massimiliano
   Coleman, Mathew L.
   Carell, Thomas
   Carmeliet, Peter
   Lambrechts, Diether
TI Tumour hypoxia causes DNA hyper-methylation by reducing TET activity
SO NATURE
LA English
DT Article
ID cancer; 5-methylcytosine; 5-hydroxymethylcytosine; hydroxylases; metastasis; expression; mutations; phenotype; succinate; fumarate
AB Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylation.
C1 [Thienpont, Bernard; Zhao, Hui; D'Anna, Flora; Kuchnio, Anna; Ghesquiere, Bart; Van Dyck, Laurien; Boeckx, Bram; Schoonjans, Luc; Mazzone, Massimiliano; Carmeliet, Peter; Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium.
   [Thienpont, Bernard; Zhao, Hui; D'Anna, Flora; Van Dyck, Laurien; Boeckx, Bram; Lambrechts, Diether] Katholieke Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
   [Steinbacher, Jessica; Carell, Thomas] Univ Munich, Dept Chem & Pharm, Ctr Integrat Prot Sci, Marchioninistr 15, D-81377 Munich, Germany.
   [Kuchnio, Anna; Schoonjans, Luc; Carmeliet, Peter] Katholieke Univ Leuven, Dept Oncol, Lab Angiogenesis & Vasc Metab, B-3000 Leuven, Belgium.
   [Ploumakis, Athanasios; Coleman, Mathew L.] Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England.
   [Hermans, Els; Amant, Frederic] Katholieke Univ Leuven, Dept Oncol, Univ Hosp Leuven, Gynecol Oncol, B-3000 Leuven, Belgium.
   [Kristensen, Vessela N.] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway.
   [Kristensen, Vessela N.] Univ Oslo, Akershus Univ Hosp, Dept Clin Mol Biol EpiGen, N-0318 Oslo, Norway.
   [Kristensen, Vessela N.] Univ Oslo, Fac Med, Inst Clin Med, Postboks 1171, N-0318 Oslo, Norway.
   [Koh, Kian Peng] Katholieke Univ Leuven, Dept Dev & Regenerat, B-3000 Leuven, Belgium.
   [Koh, Kian Peng] Katholieke Univ Leuven, Stem Cell Inst Leuven, B-3000 Leuven, Belgium.
   [Mazzone, Massimiliano] Katholieke Univ Leuven, Dept Oncol, Lab Mol Oncol & Angiogenesis, B-3000 Leuven, Belgium.
C3 Flanders Institute for Biotechnology (VIB); KU Leuven; University of Munich; KU Leuven; University of Birmingham; KU Leuven; University Hospital Leuven; University of Oslo; University of Oslo; University of Oslo; KU Leuven; KU Leuven; KU Leuven
RP Thienpont, B; Lambrechts, D (corresponding author), VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium.; Thienpont, B; Lambrechts, D (corresponding author), Katholieke Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
EM bernard.thienpont@vib-kuleuven.be; diether.lambrechts@vib-kuleuven.be
FU FWO-F; ERC [CHAMELEON 617595, EU-ERC269073, CHAMELEO 334420]; FWO-F [G065615N, G070615N]; IUAP [P7/03]; Flemish Government (Methusalem); DFG [EXC114, CA275/8-5, GRK2062/1, SPP1784]; Biotechnology and Biological Sciences Research Council [1734215] Funding Source: researchfish; Medical Research Council [MR/N021053/1] Funding Source: researchfish; MRC [MR/N021053/1] Funding Source: UKRI
NR 32
TC 502
Z9 573
U1 1
U2 210
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 63
EP 68
DI 10.1038/nature19081
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900038
PM 27533040
DA 2026-03-09
ER

PT J
AU Biard, T
   Stemmann, L
   Picheral, M
   Mayot, N
   Vandromme, P
   Hauss, H
   Gorsky, G
   Guidi, L
   Kiko, R
   Not, F
AF Biard, Tristan
   Stemmann, Lars
   Picheral, Marc
   Mayot, Nicolas
   Vandromme, Pieter
   Hauss, Helena
   Gorsky, Gabriel
   Guidi, Lionel
   Kiko, Rainer
   Not, Fabrice
TI In situ imaging reveals the biomass of giant protists in the global ocean
SO NATURE
LA English
DT Article
ID planktonic sarcodines acantharia; surface waters; zooplankton; radiolaria; photosynthesis; phytoplankton; foraminifera; abundance; pacific
AB Planktonic organisms play crucial roles in oceanic food webs and global biogeochemical cycles(1,2). Most of our knowledge about the ecological impact of large zooplankton stems from research on abundant and robust crustaceans, and in particular copepods(3,4). A number of the other organisms that comprise planktonic communities are fragile, and therefore hard to sample and quantify, meaning that their abundances and effects on oceanic ecosystems are poorly understood. Here, using data from a worldwide in situ imaging survey of plankton larger than 600 mu m, we show that a substantial part of the biomass of this size fraction consists of giant protists belonging to the Rhizaria, a super-group of mostly fragile unicellular marine organisms that includes the taxa Phaeodaria and Radiolaria ( for example, orders Collodaria and Acantharia). Globally, we estimate that rhizarians in the top 200 m of world oceans represent a standing stock of 0.089 Pg carbon, equivalent to 5.2% of the total oceanic biota carbon reservoir(5). In the vast oligotrophic intertropical open oceans, rhizarian biomass is estimated to be equivalent to that of all other mesozooplankton ( plankton in the size range 0.2-20 mm). The photosymbiotic association of many rhizarians with microalgae may be an important factor in explaining their distribution. The previously overlooked importance of these giant protists across the widest ecosystem on the planet(6) changes our understanding of marine planktonic ecosystems.
C1 [Biard, Tristan; Not, Fabrice] Univ Paris 06, Sorbonne Univ, Lab Adaptat & Divers Milieu Marin, CNRS,UMR7144,Stn Biol Roscoff, F-29688 Roscoff, France.
   [Biard, Tristan; Stemmann, Lars; Picheral, Marc; Mayot, Nicolas; Gorsky, Gabriel; Guidi, Lionel] Univ Paris 06, Sorbonne Univ, Observ Oceanol, CNRS,LOV,UMR7093, F-06230 Villefranche Sur Mer, France.
   [Vandromme, Pieter; Hauss, Helena; Kiko, Rainer] GEOMAR Helmholtz Ctr Ocean Res Kiel, Wischhofstr 1-3, D-24148 Kiel, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel
RP Not, F (corresponding author), Univ Paris 06, Sorbonne Univ, Lab Adaptat & Divers Milieu Marin, CNRS,UMR7144,Stn Biol Roscoff, F-29688 Roscoff, France.; Stemmann, L (corresponding author), Univ Paris 06, Sorbonne Univ, Observ Oceanol, CNRS,LOV,UMR7093, F-06230 Villefranche Sur Mer, France.
EM stemmann@obs-vlfr.fr; not@sb-roscoff.fr
FU U.S. National Science Foundation; DESIR project Emergence-UPMC from Universite Pierre et Marie Curie; JST-CNRS exchange program; CHAIRE CNRS/UPMC Vision; Investissements d'Avenir' programmes OCEANOMICS [ANR-11-BTBR-0008]; DFG [SFB754]; Future Ocean (Kiel University); Future Ocean (GEOMAR)
NR 43
TC 194
Z9 215
U1 5
U2 199
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 504
EP +
DI 10.1038/nature17652
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900048
PM 27096373
DA 2026-03-09
ER

PT J
AU Cannon, JT
   Vellutini, BC
   Smith, J
   Onquist, FR
   Jondelius, U
   Hejnol, A
AF Cannon, Johanna Taylor
   Vellutini, Bruno Cossermelli
   Smith, Julian, III
   Onquist, Fredrik R.
   Jondelius, Ulf
   Hejnol, Andreas
TI Xenacoelomorpha is the sister group to Nephrozoa
SO NATURE
LA English
DT Article
ID mitochondrial genome; xenoturbella-bocki; phylogenetic position; evolution; selection; tree; resolution; flatworms; software; supports
AB The position of Xenacoelomorpha in the tree of life remains a major unresolved question in the study of deep animal relationships(1). Xenacoelomorpha, comprising Acoela, Nemertodermatida, and Xenoturbella, are bilaterally symmetrical marine worms that lack several features common to most other bilaterians, for example an anus, nephridia, and a circulatory system. Two conflicting hypotheses are under debate: Xenacoelomorpha is the sister group to all remaining Bilateria (= Nephrozoa, namely protostomes and deuterostomes)(2,3) or is a clade inside Deuterostomia(4). Thus, determining the phylogenetic position of this clade is pivotal for understanding the early evolution of bilaterian features, or as a case of drastic secondary loss of complexity. Here we show robust phylogenomic support for Xenacoelomorpha as the sister taxon of Nephrozoa. Our phylogenetic analyses, based on 11 novel xenacoelomorph transcriptomes and using different models of evolution under maximum likelihood and Bayesian inference analyses, strongly corroborate this result. Rigorous testing of 25 experimental data sets designed to exclude data partitions and taxa potentially prone to reconstruction biases indicates that long-branch attraction, saturation, and missing data do not influence these results. The sister group relationship between Nephrozoa and Xenacoelomorpha supported by our phylogenomic analyses implies that the last common ancestor of bilaterians was probably a benthic, ciliated acoelomate worm with a single opening into an epithelial gut, and that excretory organs, coelomic cavities, and nerve cords evolved after xenacoelomorphs separated from the stem lineage of Nephrozoa.
C1 [Cannon, Johanna Taylor; Onquist, Fredrik R.; Jondelius, Ulf] Nat Hist Riksmuseet, POB 50007, SE-10405 Stockholm, Sweden.
   [Vellutini, Bruno Cossermelli; Hejnol, Andreas] Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5008 Bergen, Norway.
   [Smith, Julian, III] Winthrop Univ, Dept Biol, 701 Oakland Ave, Rock Hill, SC 29733 USA.
C3 University of Bergen; Winthrop University
RP Cannon, JT (corresponding author), Nat Hist Riksmuseet, POB 50007, SE-10405 Stockholm, Sweden.; Hejnol, A (corresponding author), Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5008 Bergen, Norway.
EM joie.cannon@gmail.com; andreas.hejnol@uib.no
FU Swedish Research Council [2012-3913, 2014-5901]; Sars Core budget; Marie Curie Innovative Training Networks 'NEPTUNE' [FP7-PEOPLE-2012-ITN 317172, FP7-PEOPLE-2009-RG 256450]; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) [b2013077];  [snic2014-1-323]; National Institute of General Medical Sciences [P20GM103499] Funding Source: NIH RePORTER
NR 45
TC 256
Z9 288
U1 3
U2 116
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 89
EP +
DI 10.1038/nature16520
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500038
PM 26842059
DA 2026-03-09
ER

PT J
AU Osteen, JD
   Herzig, V
   Gilchrist, J
   Emrick, JJ
   Zhang, CC
   Wang, XD
   Castro, J
   Garcia-Caraballo, S
   Grundy, L
   Rychkov, GY
   Weyer, AD
   Dekan, Z
   Undheim, EAB
   Alewood, P
   Stucky, CL
   Brierley, SM
   Basbaum, AI
   Bosmans, F
   King, GF
   Julius, D
AF Osteen, Jeremiah D.
   Herzig, Volker
   Gilchrist, John
   Emrick, Joshua J.
   Zhang, Chuchu
   Wang, Xidao
   Castro, Joel
   Garcia-Caraballo, Sonia
   Grundy, Luke
   Rychkov, Grigori Y.
   Weyer, Andy D.
   Dekan, Zoltan
   Undheim, Eivind A. B.
   Alewood, Paul
   Stucky, Cheryl L.
   Brierley, Stuart M.
   Basbaum, Allan I.
   Bosmans, Frank
   King, Glenn F.
   Julius, David
TI Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
SO NATURE
LA English
DT Article
ID rat dorsal-root; sensitive sodium-channels; antiepileptic drugs; neuropathic pain; receptor; expression; neurons; mutations; migraine; mouse
AB Voltage-gated sodium (Na-v) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Na-v channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Na(v)1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Na(v)1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Na(v)1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Na(v)1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.
C1 [Osteen, Jeremiah D.; Emrick, Joshua J.; Zhang, Chuchu; Julius, David] Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA 94143 USA.
   [Herzig, Volker; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; King, Glenn F.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
   [Gilchrist, John; Bosmans, Frank] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
   [Gilchrist, John; Bosmans, Frank] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Wang, Xidao; Basbaum, Allan I.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   [Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Brierley, Stuart M.] Flinders Univ S Australia, Visceral Pain Grp, Bedford Pk, SA 5042, Australia.
   [Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Brierley, Stuart M.] Univ Adelaide, SAHMRI, Ctr Nutr & Gastrointestinal Dis, Discipline Med, N Terrace, Adelaide, SA 5000, Australia.
   [Weyer, Andy D.; Stucky, Cheryl L.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
C3 University of California System; University of California San Francisco; University of Queensland; Johns Hopkins University; Johns Hopkins University; University of California System; University of California San Francisco; Flinders University; South Australian Health & Medical Research Institute (SAHMRI); Adelaide University; University of Adelaide; Medical College of Wisconsin
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA 94143 USA.; King, GF (corresponding author), Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.; Bosmans, F (corresponding author), Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.; Bosmans, F (corresponding author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
EM frankbosmans@jhmi.edu; glenn.king@imb.uq.edu.au; david.julius@ucsf.edu
FU UCSF CVRI; Ruth Kirschstein NIH [F32NS081907, F31NS084646, F30DE023476]; National Institutes of Health [R37NS065071, R01NS081115, R01NS091352, R01NS040538, R01NS070711, R37NS014627, R01DA29204]; National Health and Medical Research Council of Australia [APP1083480, APP1072113, APP1044414]; Wellcome Trust; Wellcome Trust [102645/Z/13/Z] Funding Source: researchfish; National Heart Lung and Blood Institute [T32HL007731] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS070711] Funding Source: NIH RePORTER
NR 65
TC 249
Z9 280
U1 4
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 494
EP +
DI 10.1038/nature17976
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300042
PM 27281198
DA 2026-03-09
ER

PT J
AU Singh, SR
   Zeng, XK
   Zhao, JS
   Liu, Y
   Hou, G
   Liu, HH
   Hou, SX
AF Singh, Shree Ram
   Zeng, Xiankun
   Zhao, Jiangsha
   Liu, Ying
   Hou, Gerald
   Liu, Hanhan
   Hou, Steven X.
TI The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila
SO NATURE
LA English
DT Article
ID engulfment; activation; inhibition; receptor; dysfunction; homeostasis; regulator; oxidation; apoptosis; division
AB Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients(1). In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)-Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper-myoblast city-Rac1-basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers.
C1 [Singh, Shree Ram; Zeng, Xiankun; Zhao, Jiangsha; Liu, Ying; Hou, Gerald; Liu, Hanhan; Hou, Steven X.] Natl Canc Inst Frederick, Basic Res Lab, NIH, Frederick, MD 21702 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Hou, SX (corresponding author), Natl Canc Inst Frederick, Basic Res Lab, NIH, Frederick, MD 21702 USA.
EM hous@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; National Cancer Institute [ZIABC010738] Funding Source: NIH RePORTER
NR 56
TC 80
Z9 88
U1 3
U2 72
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 109
EP +
DI 10.1038/nature19788
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900044
PM 27680705
DA 2026-03-09
ER

PT J
AU Sanchez, S
   Tafforeau, P
   Clack, JA
   Ahlberg, PE
AF Sanchez, Sophie
   Tafforeau, Paul
   Clack, Jennifer A.
   Ahlberg, Per E.
TI Life history of the stem tetrapod Acanthostega revealed by synchrotron microtomography
SO NATURE
LA English
DT Article
ID early evolution; east greenland; pectoral fin; origin; competition; patterns; skeleton; gunnari; bone
AB The transition from fish to tetrapod was arguably the most radical series of adaptive shifts in vertebrate evolutionary history. Data are accumulating rapidly for most aspects of these events(1-5), but the life histories of the earliest tetrapods remain completely unknown, leaving a major gap in our understanding of these organisms as living animals. Symptomatic of this problem is the unspoken assumption that the largest known Devonian tetrapod fossils represent adult individuals. Here we present the first, to our knowledge, life history data for a Devonian tetrapod, from the Acanthostega mass-death deposit of Stensio Bjerg, East Greenland(6,7). Using propagation phase-contrast synchrotron microtomography (PPC-SR mu CT)(8) to visualize the histology of humeri (upper arm bones) and infer their growth histories, we show that even the largest individuals from this deposit are juveniles. A long early juvenile stage with unossified limb bones, during which individuals grew to almost final size, was followed by a slow-growing late juvenile stage with ossified limbs that lasted for at least six years in some individuals. The late onset of limb ossification suggests that the juveniles were exclusively aquatic, and the predominance of juveniles in the sample suggests segregated distributions of juveniles and adults at least at certain times. The absolute size at which limb ossification began differs greatly between individuals, suggesting the possibility of sexual dimorphism, adaptive strategies or competition-related size variation.
C1 [Sanchez, Sophie; Ahlberg, Per E.] Sci Life Lab, Norbyvagen 18A, S-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Ahlberg, Per E.] Uppsala Univ, Subdept Evolut & Dev, Dept Organismal Biol, Evolutionary Biol Ctr, Norbyvagen 18A, S-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Tafforeau, Paul] European Synchrotron Radiat Facil, 71 Ave Martyrs,CS 40220, F-38043 Grenoble, France.
   [Clack, Jennifer A.] Univ Cambridge, Univ Museum Zool, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
C3 Uppsala University; European Synchrotron Radiation Facility (ESRF); University of Cambridge
RP Sanchez, S (corresponding author), Sci Life Lab, Norbyvagen 18A, S-75236 Uppsala, Sweden.; Sanchez, S (corresponding author), Uppsala Univ, Subdept Evolut & Dev, Dept Organismal Biol, Evolutionary Biol Ctr, Norbyvagen 18A, S-75236 Uppsala, Sweden.; Sanchez, S (corresponding author), European Synchrotron Radiat Facil, 71 Ave Martyrs,CS 40220, F-38043 Grenoble, France.
EM sophie.sanchez@ebc.uu.se
FU ERC [233111]; Vetenskapsradet [201504335]; European Research Council (ERC) [233111] Funding Source: European Research Council (ERC)
NR 33
TC 36
Z9 43
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 408
EP +
DI 10.1038/nature19354
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000055
PM 27602519
DA 2026-03-09
ER

PT J
AU Itkin, T
   Gur-Cohen, S
   Spencer, JA
   Schajnovitz, A
   Ramasamy, SK
   Kusumbe, AP
   Ledergor, G
   Jung, Y
   Milo, I
   Poulos, MG
   Kalinkovich, A
   Ludin, A
   Kollet, O
   Shakhar, G
   Butler, JM
   Rafii, S
   Adams, RH
   Scadden, DT
   Lin, CP
   Lapidot, T
AF Itkin, Tomer
   Gur-Cohen, Shiri
   Spencer, Joel A.
   Schajnovitz, Amir
   Ramasamy, Saravana K.
   Kusumbe, Anjali P.
   Ledergor, Guy
   Jung, Yookyung
   Milo, Idan
   Poulos, Michael G.
   Kalinkovich, Alexander
   Ludin, Aya
   Kollet, Orit
   Shakhar, Guy
   Butler, Jason M.
   Rafii, Shahin
   Adams, Ralf H.
   Scadden, David T.
   Lin, Charles P.
   Lapidot, Tsvee
TI Distinct bone marrow blood vessels differentially regulate haematopoiesis
SO NATURE
LA English
DT Article
ID stem-cell quiescence; progenitor cells; rapid mobilization; niche; megakaryocytes; murine; angiogenesis; regeneration; maintenance; recruitment
AB Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.
C1 [Itkin, Tomer; Gur-Cohen, Shiri; Ledergor, Guy; Milo, Idan; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Lapidot, Tsvee] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Spencer, Joel A.; Jung, Yookyung; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Spencer, Joel A.; Jung, Yookyung; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
   [Schajnovitz, Amir; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Schajnovitz, Amir; Scadden, David T.] Harvard Stem Cell Inst, Boston, MA 02114 USA.
   [Schajnovitz, Amir; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Schajnovitz, Amir; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Ramasamy, Saravana K.; Kusumbe, Anjali P.; Adams, Ralf H.] Univ Munster, Dept Tissue Morphogenesis, Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
   [Ramasamy, Saravana K.; Kusumbe, Anjali P.; Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
   [Ledergor, Guy] Tel Aviv Sourasky Med Ctr, Dept Internal Med, IL-64239 Tel Aviv, Israel.
   [Poulos, Michael G.; Butler, Jason M.; Rafii, Shahin] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA.
C3 Weizmann Institute of Science; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Max Planck Society; University of Munster; University of Munster; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Cornell University; Weill Cornell Medicine
RP Lapidot, T (corresponding author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.; Lin, CP (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.; Lin, CP (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
EM charles_lin@hms.harvard.edu; tsvee.lapidot@weizmann.ac.il
FU Ministry of Science, Technology Space, Israel; DKFZ, Germany; Israel Science Foundation [851/13]; Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine; EU [261387]; European Research Council [339409]; NIH [EB017274, HL100402]; European Research Council (ERC) [339409] Funding Source: European Research Council (ERC)
NR 50
TC 568
Z9 655
U1 1
U2 183
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 323
EP +
DI 10.1038/nature17624
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700024
PM 27074509
DA 2026-03-09
ER

PT J
AU Masuti, S
   Barbot, SD
   Karato, S
   Feng, LJ
   Banerjee, P
AF Masuti, Sagar
   Barbot, Sylvain D.
   Karato, Shun-ichiro
   Feng, Lujia
   Banerjee, Paramesh
TI Upper-mantle water stratification inferred from observations of the 2012 Indian Ocean earthquake
SO NATURE
LA English
DT Article
ID plastic-deformation; shear localization; dislocation creep; transient creep; rheology; lithosphere; mechanisms; kinematics; inversion; afterslip
AB Water, the most abundant volatile in Earth's interior, preserves the young surface of our planet by catalysing mantle convection, lubricating plate tectonics and feeding arc volcanism. Since planetary accretion, water has been exchanged between the hydrosphere and the geosphere, but its depth distribution in the mantle remains elusive. Water drastically reduces the strength of olivine(1) and this effect can be exploited to estimate the water content of olivine from the mechanical response of the asthenosphere to stress perturbations such as the ones following large earthquakes. Here, we exploit the sensitivity to water of the strength of olivine(2), the weakest and most abundant mineral in the upper mantle, and observations of the exceptionally large (moment magnitude 8.6) 2012 Indian Ocean earthquake(3) to constrain the stratification of water content in the upper mantle. Taking into account a wide range of temperature conditions and the transient creep of olivine, we explain the transient deformation in the aftermath of the earthquake that was recorded by continuous geodetic stations along Sumatra as the result of water-and stress-activated creep of olivine. This implies a minimum water content of about 0.01 per cent by weight-or 1,600 H atoms per million Si atoms-in the asthenosphere (the part of the upper mantle below the lithosphere). The earthquake ruptured conjugate faults down to great depths(4), compatible with dry olivine in the oceanic lithosphere. We attribute the steep rheological contrast to dehydration across the lithosphere-asthenosphere boundary, presumably by buoyant melt migration to form the oceanic crust.
C1 [Masuti, Sagar; Barbot, Sylvain D.; Feng, Lujia; Banerjee, Paramesh] Nanyang Technol Univ, Asian Sch Environm, Earth Observ Singapore, Singapore, Singapore.
   [Karato, Shun-ichiro] Yale Univ, Dept Geol & Geophys, New Haven, CT USA.
C3 Nanyang Technological University; Yale University
RP Barbot, SD (corresponding author), Nanyang Technol Univ, Asian Sch Environm, Earth Observ Singapore, Singapore, Singapore.
EM sbarbot@ntu.edu.sg
FU National Research Foundation of Singapore [NRF-NRFF2013-04, NRF-NRFF2010-064]; Earth Observatory of Singapore; National Research Foundation; Singapore Ministry of Education under the Research Centres of Excellence initiative
NR 53
TC 76
Z9 84
U1 0
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 373
EP +
DI 10.1038/nature19783
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100037
PM 27723743
DA 2026-03-09
ER

PT J
AU Tsujino, N
   Nishihara, Y
   Yamazaki, D
   Seto, Y
   Higo, Y
   Takahashi, E
AF Tsujino, Noriyoshi
   Nishihara, Yu
   Yamazaki, Daisuke
   Seto, Yusuke
   Higo, Yuji
   Takahashi, Eiichi
TI Mantle dynamics inferred from the crystallographic preferred orientation of bridgmanite
SO NATURE
LA English
DT Article
ID in-situ observation; x-ray-diffraction; seismic anisotropy; mgsio3 perovskite; high-pressure; high-temperature; phase-boundary; subducted slab; earths mantle; 30 gpa
AB Seismic shear wave anisotropy(1-6) is observed in Earth's uppermost lower mantle around several subducted slabs. The anisotropy caused by the deformation-induced crystallographic preferred orientation (CPO) of bridgmanite (perovskite-structured (Mg, Fe) SiO3) is the most plausible explanation for these seismic observations. However, the rheological properties of bridgmanite are largely unknown. Uniaxial deformation experiments(7-9) have been carried out to determine the deformation texture of bridgmanite, but the dominant slip system (the slip direction and plane) has not been determined. Here we report the CPO pattern and dominant slip system of bridgmanite under conditions that correspond to the uppermost lower mantle (25 gigapascals and 1,873 kelvin) obtained through simple shear deformation experiments using the Kawaitype deformation-DIA apparatus(10.) The fabrics obtained are characterized by [100] perpendicular to the shear plane and [001] parallel to the shear direction, implying that the dominant slip system of bridgmanite is [001](100). The observed seismic shear-wave anisotropies near several subducted slabs(1-4) (Tonga-Kermadec, Kurile, Peru and Java) can be explained in terms of the CPO of bridgmanite as induced by mantle flow parallel to the direction of subduction.
C1 [Tsujino, Noriyoshi; Yamazaki, Daisuke] Okayama Univ, Inst Planetary Mat, 827 Yamada, Misasa, Tottori 6820193, Japan.
   [Nishihara, Yu] Ehime Univ, Geodynam Res Ctr, 2-5 Bunkyo Cho, Matsuyama, Ehime 7908577, Japan.
   [Seto, Yusuke] Kobe Univ, Dept Planetol, Kobe, Hyogo 6578501, Japan.
   [Higo, Yuji] Japan Synchrotron Radiat Res Inst, 1-1-1 Kouto, Sayo, Hyogo 6895198, Japan.
   [Takahashi, Eiichi] Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, 2-12-1 Ookayama, Tokyo 1528551, Japan.
C3 Okayama University; Ehime University; Kobe University; Japan Synchrotron Radiation Research Institute; Institute of Science Tokyo; Tokyo Institute of Technology
RP Tsujino, N (corresponding author), Okayama Univ, Inst Planetary Mat, 827 Yamada, Misasa, Tottori 6820193, Japan.
EM tsujino@okayama-u.ac.jp
FU JSPS KAKENHI [15J09669, 25247088, 21109001]; Grants-in-Aid for Scientific Research [15H03749, 25247088, 26287136, 21109001, 15J09669, 15H05829, 16K13907, 15H05827] Funding Source: KAKEN
NR 42
TC 59
Z9 72
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 81
EP +
DI 10.1038/nature19777
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100033
PM 27750277
DA 2026-03-09
ER

PT J
AU Zanos, P
   Moaddel, R
   Morris, PJ
   Georgiou, P
   Fischell, J
   Elmer, GI
   Alkondon, M
   Yuan, PX
   Pribut, HJ
   Singh, NS
   Dossou, KSS
   Fang, YH
   Huang, XP
   Mayo, CL
   Wainer, IW
   Albuquerque, EX
   Thompson, SM
   Thomas, CJ
   Zarate, CA
   Gould, TD
AF Zanos, Panos
   Moaddel, Ruin
   Morris, Patrick J.
   Georgiou, Polymnia
   Fischell, Jonathan
   Elmer, Greg I.
   Alkondon, Manickavasagom
   Yuan, Peixiong
   Pribut, Heather J.
   Singh, Nagendra S.
   Dossou, Katina S. S.
   Fang, Yuhong
   Huang, Xi-Ping
   Mayo, Cheryl L.
   Wainer, Irving W.
   Albuquerque, Edson X.
   Thompson, Scott M.
   Thomas, Craig J.
   Zarate, Carlos A., Jr.
   Gould, Todd D.
TI NMDAR inhibition-independent antidepressant actions of ketamine metabolites
SO NATURE
LA English
DT Article
ID d-aspartate antagonist; star-asterisk-d; sustained antidepressant; receptor antagonist; sex-differences; ampa receptor; depression; stress; cortex; rat
AB Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist(R,S)-ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Here we show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice. These antidepressant actions are independent of NMDAR inhibition but involve early and sustained activation of AMPARs (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors). We also establish that (2R,6R)-HNK lacks ketamine-related side effects. Our data implicate a novel mechanism underlying the antidepressant properties of (R,S)-ketamine and have relevance for the development of next-generation, rapid-acting antidepressants.
C1 [Zanos, Panos; Georgiou, Polymnia; Elmer, Greg I.; Pribut, Heather J.; Thompson, Scott M.; Gould, Todd D.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
   [Moaddel, Ruin; Singh, Nagendra S.; Dossou, Katina S. S.; Wainer, Irving W.] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
   [Morris, Patrick J.; Fang, Yuhong; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
   [Fischell, Jonathan; Thompson, Scott M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
   [Elmer, Greg I.; Albuquerque, Edson X.; Gould, Todd D.] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA.
   [Elmer, Greg I.; Mayo, Cheryl L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
   [Alkondon, Manickavasagom; Albuquerque, Edson X.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Translat Toxicol, Baltimore, MD 21201 USA.
   [Yuan, Peixiong; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Huang, Xi-Ping] Univ N Carolina, Sch Med, Dept Pharmacol, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27516 USA.
   [Huang, Xi-Ping] Univ N Carolina, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27516 USA.
   [Albuquerque, Edson X.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
   [Gould, Todd D.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
   [Wainer, Irving W.] Mitchell Woods Pharmaceut, Shelton, CT 06484 USA.
C3 University System of Maryland; University of Maryland Baltimore; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS); University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore County; University System of Maryland; University of Maryland Baltimore; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore
RP Gould, TD (corresponding author), Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.; Gould, TD (corresponding author), Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA.; Gould, TD (corresponding author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
EM gouldlab@me.com
FU NIMH [MH099345, MH107615, MH086828, HHSN-271-2008-025C]; NIA, NIH; NIMH, NIH; NCATS, NIH; NIA [HHSN271201000008I]; National Center for Advancing Translational Sciences [ZIATR000042] Funding Source: NIH RePORTER; National Institute of Mental Health [R01MH107615] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000297] Funding Source: NIH RePORTER
NR 39
TC 1257
Z9 1450
U1 7
U2 381
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 481
EP +
DI 10.1038/nature17998
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100030
PM 27144355
DA 2026-03-09
ER

PT J
AU Muñoz-Darias, T
   Casares, J
   Sánchez, DM
   Fender, RP
   Padilla, MA
   Linares, M
   Ponti, G
   Charles, PA
   Mooley, KP
   Rodriguez, J
AF Munoz-Darias, T.
   Casares, J.
   Mata Sanchez, D.
   Fender, R. P.
   Armas Padilla, M.
   Linares, M.
   Ponti, G.
   Charles, P. A.
   Mooley, K. P.
   Rodriguez, J.
TI Regulation of black-hole accretion by a disk wind during a violent outburst of V404 Cygni
SO NATURE
LA English
DT Article
ID x-ray; light curves; stellar; spectroscopy; mechanism; feedback
AB Accretion of matter onto black holes is universally associated with strong radiative feedback(1) and powerful outflows(2). In particular, black-hole transients(3) have outflows whose properties(4) are strongly coupled to those of the accretion flow. This includes X-ray winds of ionized material, expelled from the accretion disk encircling the black hole, and collimated radio jets(5,6). Very recently, a distinct optical variability pattern has been reported in the transient stellar-mass black hole V404 Cygni, and interpreted as disrupted mass flow into the inner regions of its large accretion disk(7). Here we report observations of a sustained outer accretion disk wind in V404 Cyg, which is unlike any seen hitherto. We find that the outflowing wind is neutral, has a large covering factor, expands at one per cent of the speed of light and triggers a nebular phase once accretion drops sharply and the ejecta become optically thin. The large expelled mass (> 10(-8) solar masses) indicates that the outburst was prematurely ended when a sizeable fraction of the outer disk was depleted by the wind, detaching the inner regions from the rest of the disk. The luminous, but brief, accretion phases shown by transients with large accretion disks(2) imply that this outflow is probably a fundamental ingredient in regulating mass accretion onto black holes.
C1 [Munoz-Darias, T.; Casares, J.; Mata Sanchez, D.; Armas Padilla, M.; Linares, M.] Inst Astrofis Canarias, E-38205 San Cristobal la Laguna, Santa Cruz De T, Spain.
   [Munoz-Darias, T.; Casares, J.; Mata Sanchez, D.; Armas Padilla, M.; Linares, M.] Univ La Laguna, Dept Astrofis, E-38206 San Cristobal la Laguna, Santa Cruz De T, Spain.
   [Casares, J.; Fender, R. P.; Charles, P. A.; Mooley, K. P.] Univ Oxford, Dept Phys, Astrophys, Denys Wilkinson Bldg,Keble Rd, Oxford OX1 3RH, England.
   [Armas Padilla, M.] Kyoto Univ, Dept Astron, Kyoto 6068502, Japan.
   [Linares, M.] NTNU, Inst Fys, Trondheim, Norway.
   [Ponti, G.] Max Planck Inst Extraterr Phys, Giessenbachstr 1, D-85748 Garching, Germany.
   [Charles, P. A.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Rodriguez, J.] Univ Paris Diderot, CEA CNRS,CEA DRF IRFU SAp, UMR 7158, Lab Astrophys Instrumentat Modelisat AIM, F-91191 Gif Sur Yvette, France.
C3 Instituto de Astrofisica de Canarias; Universidad de la Laguna; University of Oxford; Kyoto University; Norwegian University of Science & Technology (NTNU); Max Planck Society; University of Southampton; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Muñoz-Darias, T (corresponding author), Inst Astrofis Canarias, E-38205 San Cristobal la Laguna, Santa Cruz De T, Spain.; Muñoz-Darias, T (corresponding author), Univ La Laguna, Dept Astrofis, E-38206 San Cristobal la Laguna, Santa Cruz De T, Spain.
EM teo.munoz-darias@iac.es
FU Spanish Ministerio de Economia y competitividad [AYA2013-42627, PSR2015-00397]; Leverhulme Trust [VP2-2015-046]; International Research Fellowship program of the Japan Society for the Promotion of Science [PE15024]; Bundesministerium fur Wirtschaft und Technologie (BMWI/DLR) [FKZ 50 OR 1408]; French Research National Agency's CHAOS project [ANR-12-BS05-0009]; STFC [ST/N000919/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/N000919/1] Funding Source: researchfish
NR 52
TC 113
Z9 117
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 75
EP +
DI 10.1038/nature17446
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300035
PM 27251277
DA 2026-03-09
ER

PT J
AU Li, B
   Wang, F
   Zhou, D
   Peng, Y
   Ni, R
   Han, YL
AF Li, Bo
   Wang, Feng
   Zhou, Di
   Peng, Yi
   Ni, Ran
   Han, Yilong
TI Modes of surface premelting in colloidal crystals composed of attractive particles
SO NATURE
LA English
DT Article
ID 2 dimensions; transitions; ice; simulation; interface; dynamics; disorder; phase
AB Crystal surfaces typically melt into a thin liquid layer at temperatures slightly below the melting point of the crystal. Such surface premelting is prevalent in all classes of solids and is important in a variety of metallurgical, geological and meteorological phenomena(1). Premelting has been studied using X-ray diffraction(2) and differential scanning calorimetry(3), but the lack of single-particle resolution makes it hard to elucidate the underlying mechanisms. Colloids are good model systems for studying phase transitions(4) because the thermal motions of individual micrometre-sized particles can be tracked directly using optical microscopy(5). Here we use colloidal spheres with tunable attractions to form equilibrium crystal-vapour interfaces, and study their surface premelting behaviour at the single-particle level. We find that monolayer colloidal crystals exhibit incomplete premelting at their perimeter, with a constant liquid-layer thickness. In contrast, two-and three-layer crystals exhibit conventional complete melting, with the thickness of the surface liquid diverging as the melting point is approached. The microstructures of the surface liquids differ in certain aspects from what would be predicted by conventional premelting theories. Incomplete premelting in the monolayer crystals is triggered by a bulk isostructural solid-solid transition and truncated by a mechanical instability that separately induces homogeneous melting within the bulk. This finding is in contrast to the conventional assumption that two-dimensional crystals melt heterogeneously from their free surfaces(3,6) (that is, at the solid-vapour interface). The unexpected bulk melting that we observe for the monolayer crystals is accompanied by the formation of grain boundaries, which supports a previously proposed grain-boundary-mediated two-dimensional melting theory(7). The observed interplay between surface premelting, bulk melting and solid-solid transitions challenges existing theories of surface premelting and two-dimensional melting.
C1 [Li, Bo; Wang, Feng; Zhou, Di; Peng, Yi; Han, Yilong] Hong Kong Univ Sci & Technol, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
   [Ni, Ran] Nanyang Technol Univ, Sch Chem & Biomed Engn, 62 Nanyang Dr, Singapore 637459, Singapore.
   [Ni, Ran] Univ Amsterdam, Vant Hoff Inst Mol Sci, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
C3 Hong Kong University of Science & Technology; Nanyang Technological University; University of Amsterdam
RP Han, YL (corresponding author), Hong Kong Univ Sci & Technol, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
EM yilong@ust.hk
FU RGC [GRF601911, GRF16301514, C6004-14G]; NWO VENI grant [680-47-441]; Nanyang Technological University
NR 31
TC 77
Z9 92
U1 1
U2 183
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 485
EP 488
DI 10.1038/nature16987
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300036
PM 26976448
DA 2026-03-09
ER

PT J
AU Huth, AG
   de Heer, WA
   Griffiths, TL
   Theunissen, FE
   Gallant, JL
AF Huth, Alexander G.
   de Heer, Wendy A.
   Griffiths, Thomas L.
   Theunissen, Frederic E.
   Gallant, Jack L.
TI Natural speech reveals the semantic maps that tile human cerebral cortex
SO NATURE
LA English
DT Article
ID human brain; representation; space; organization; knowledge; concrete; systems; object; areas
AB The meaning of language is represented in regions of the cerebral cortex collectively known as the 'semantic system'. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modelling of functional MRI (fMRI) data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that seem to be consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods-commonplace in studies of human neuroanatomy and functional connectivity-provide a powerful and efficient means for mapping functional representations in the brain.
C1 [Huth, Alexander G.; Griffiths, Thomas L.; Theunissen, Frederic E.; Gallant, Jack L.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [de Heer, Wendy A.; Griffiths, Thomas L.; Theunissen, Frederic E.; Gallant, Jack L.] Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Gallant, JL (corresponding author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.; Gallant, JL (corresponding author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA.
EM gallant@berkeley.edu
FU National Science Foundation (NSF) [IIS1208203]; National Eye Institute [EY019684]; Center for Science of Information (CSoI), an NSF Science and Technology Center [CCF-0939370]; William Orr Dingwall Neurolinguistics Fellowship; Direct For Computer & Info Scie & Enginr [1208203] Funding Source: National Science Foundation; Div Of Information & Intelligent Systems [1208203] Funding Source: National Science Foundation
NR 38
TC 983
Z9 1182
U1 16
U2 377
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 453
EP +
DI 10.1038/nature17637
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900037
PM 27121839
DA 2026-03-09
ER

PT J
AU Galvez, ME
   Connolly, JAD
   Manning, CE
AF Galvez, Matthieu E.
   Connolly, James A. D.
   Manning, Craig E.
TI Implications for metal and volatile cycles from the pH of subduction zone fluids
SO NATURE
LA English
DT Article
ID degrees-c; elevated-temperatures; dielectric-constant; mantle fluids; deep earth; water; pressures; solubility; evolution; deposits
AB The chemistry of aqueous fluids controls the transport and exchange the cycles of metals(1-5) and volatile elements(3,6,7) on Earth. Subduction zones, where oceanic plates sink into the Earth's interior, are the most important geodynamic setting for this fluid-mediated chemical exchange(2,6-10). Characterizing the ionic speciation and pH of fluids equilibrated with rocks at subduction zone conditions has long been a major challenge in Earth sciences(11,12). Here we report thermodynamic predictions of fluid-rock equilibria that tie together models of the thermal structure, mineralogy and fluid speciation of subduction zones. We find that the pH of fluids in subducted crustal lithologies is confined to a mildly alkaline range, modulated by rock volatile and chlorine contents. Cold subduction typical of the Phanerozoic eon(13) favours the preservation of oxidized carbon in subducting slabs. In contrast, the pH of mantle wedge fluids is very sensitive to minor variations in rock composition. These variations may be caused by intramantle differentiation, or by infiltration of fluids enriched in alkali components extracted from the subducted crust. The sensitivity of pH to soluble elements in low abundance in the host rocks, such as carbon, alkali metals and halogens, illustrates a feedback between the chemistry of the Earth's atmosphere-ocean system(14,15) and the speciation of subduction zone fluids via the composition of the seawater-altered oceanic lithosphere. Our findings provide a perspective on the controlling reactions that have coupled metal and volatile cycles in subduction zones for more than 3 billion years(7).
C1 [Galvez, Matthieu E.; Connolly, James A. D.] Swiss Fed Inst Technol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
   [Manning, Craig E.] Univ Calif Los Angeles, Dept Earth Planetary & Space Sci, Los Angeles, CA 90095 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of California System; University of California Los Angeles
RP Galvez, ME (corresponding author), Swiss Fed Inst Technol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
EM matthieu.galvez@erdw.ethz.ch
FU ETH fellowship ETH/CoFUND [Fel-06 13-2]; Carnegie; Society in Science/Branco-Weiss fellowships; Swiss National Science Foundation [200021_146872]; Deep Carbon Observatory; National Science Fundation [EAR 1347987]; Swiss National Science Foundation (SNF) [200021_146872] Funding Source: Swiss National Science Foundation (SNF); Directorate For Geosciences; Division Of Earth Sciences [1347987] Funding Source: National Science Foundation
NR 33
TC 108
Z9 122
U1 3
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 420
EP 424
DI 10.1038/nature20103
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700052
PM 27853207
DA 2026-03-09
ER

PT J
AU Brouwer, I
   Sitters, G
   Candelli, A
   Heerema, SJ
   Heller, I
   de Melo, AJ
   Zhang, HS
   Normanno, D
   Modesti, M
   Peterman, EJG
   Wuite, GJL
AF Brouwer, Ineke
   Sitters, Gerrit
   Candelli, Andrea
   Heerema, Stephanie J.
   Heller, Iddo
   de Melo, Abinadabe J.
   Zhang, Hongshan
   Normanno, Davide
   Modesti, Mauro
   Peterman, Erwin J. G.
   Wuite, Gijs J. L.
TI Sliding sleeves of XRCC4-XLF bridge DNA and connect fragments of broken DNA
SO NATURE
LA English
DT Article
ID strand break repair; optical tweezers; protein interactions; complex; xlf; ligation; dynamics; ends
AB Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in mammalian cells(1). Such breaks are formed, for example, during gene-segment rearrangements in the adaptive immune system or by cancer therapeutic agents. Although the core components of the NHEJ machinery are known, it has remained difficult to assess the specific roles of these components and the dynamics of bringing and holding the fragments of broken DNA together. The structurally similar XRCC4 and XLF proteins are proposed to assemble as highly dynamic filaments at (or near) DSBs(2). Here we show, using dual-and quadruple-trap optical tweezers combined with fluorescence microscopy, how human XRCC4, XLF and XRCC4-XLF complexes interact with DNA in real time. We find that XLF stimulates the binding of XRCC4 to DNA, forming heteromeric complexes that diffuse swiftly along the DNA. Moreover, we find that XRCC4-XLF complexes robustly bridge two independent DNA molecules and that these bridges are able to slide along the DNA. These observations suggest that XRCC4-XLF complexes form mobile sleeve-like structures around DNA that can reconnect the broken ends very rapidly and hold them together. Understanding the dynamics and regulation of this mechanism will lead to clarification of how NHEJ proteins are involved in generating chromosomal translocations(3,4).
C1 [Brouwer, Ineke; Sitters, Gerrit; Candelli, Andrea; Heerema, Stephanie J.; Heller, Iddo; Peterman, Erwin J. G.; Wuite, Gijs J. L.] Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands.
   [Brouwer, Ineke; Sitters, Gerrit; Candelli, Andrea; Heerema, Stephanie J.; Heller, Iddo; Peterman, Erwin J. G.; Wuite, Gijs J. L.] Vrije Univ Amsterdam, LaserLab, NL-1081 HV Amsterdam, Netherlands.
   [de Melo, Abinadabe J.; Zhang, Hongshan; Normanno, Davide; Modesti, Mauro] Aix Marseille Univ, Canc Res Ctr Marseille, Inst Paoli Calmettes, CNRS,UMR7258,Inserm,U1068,UM105, F-13273 Marseilles, France.
   [Sitters, Gerrit; Candelli, Andrea] LUMICKS BV, NL-1081 HV Amsterdam, Netherlands.
   [Heerema, Stephanie J.] Delft Univ Technol, Kavli Inst Nanosci, NL-2628 CJ Delft, Netherlands.
C3 Vrije Universiteit Amsterdam; Vrije Universiteit Amsterdam; UNICANCER; Institut Paoli-Calmette (IPC); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Delft University of Technology
RP Wuite, GJL (corresponding author), Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands.; Wuite, GJL (corresponding author), Vrije Univ Amsterdam, LaserLab, NL-1081 HV Amsterdam, Netherlands.; Modesti, M (corresponding author), Aix Marseille Univ, Canc Res Ctr Marseille, Inst Paoli Calmettes, CNRS,UMR7258,Inserm,U1068,UM105, F-13273 Marseilles, France.
EM mauro.modesti@inserm.fr; g.j.l.wuite@vu.nl
FU VICI; VENI; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, a European Research Council; French National Cancer Institute [PLBIO13-103]; ARC Foundation for Cancer Research; A*MIDEX project [ANR-11-IDEX-0001-02]; 'Investissements d'Avenir' French Government program; Brazilian program for Coordination for the Improvement of Higher Education Personnel [0558/12-5]; College of Aix-Marseille Universite
NR 25
TC 126
Z9 148
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 566
EP +
DI 10.1038/nature18643
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600032
PM 27437582
DA 2026-03-09
ER

PT J
AU Bakken, TE
   Miller, JA
   Ding, SL
   Sunkin, SM
   Smith, KA
   Ng, L
   Szafer, A
   Dalley, RA
   Royall, JJ
   Lemon, T
   Shapouri, S
   Aiona, K
   Arnold, J
   Bennett, JL
   Bertagnolli, D
   Bickley, K
   Boe, A
   Brouner, K
   Butler, S
   Byrnes, E
   Caldejon, S
   Carey, A
   Cate, S
   Chapin, M
   Chen, J
   Dee, N
   Desta, T
   Dolbeare, TA
   Dotson, N
   Ebbert, A
   Fulfs, E
   Gee, G
   Gilbert, TL
   Goldy, J
   Gourley, L
   Gregor, B
   Gu, GY
   Hall, J
   Haradon, Z
   Haynor, DR
   Hejazinia, N
   Hoerder-Suabedissen, A
   Howard, R
   Jochim, J
   Kinnunen, M
   Kriedberg, A
   Kuan, CL
   Lau, C
   Lee, CK
   Lee, F
   Luong, L
   Mastan, N
   May, R
   Melchor, J
   Mosqueda, N
   Mott, E
   Ngo, K
   Nyhus, J
   Oldre, A
   Olson, E
   Parente, J
   Parker, PD
   Parry, S
   Pendergraft, J
   Potekhina, L
   Reding, M
   Riley, ZL
   Roberts, T
   Rogers, B
   Roll, K
   Rosen, D
   Sandman, D
   Sarreal, M
   Shapovalova, N
   Shi, S
   Sjoquist, N
   Sodt, AJ
   Townsend, R
   Velasquez, L
   Wagley, U
   Wakeman, WB
   White, C
   Bennett, C
   Wu, J
   Young, R
   Youngstrom, BL
   Wohnoutka, P
   Gibbs, RA
   Rogers, J
   Hohmann, JG
   Hawrylycz, MJ
   Hevner, RF
   Molnár, Z
   Phillips, JW
   Dang, C
   Jones, AR
   Amaral, DG
   Bernard, A
   Lein, ES
AF Bakken, Trygve E.
   Miller, Jeremy A.
   Ding, Song-Lin
   Sunkin, Susan M.
   Smith, Kimberly A.
   Ng, Lydia
   Szafer, Aaron
   Dalley, Rachel A.
   Royall, Joshua J.
   Lemon, Tracy
   Shapouri, Sheila
   Aiona, Kaylynn
   Arnold, James
   Bennett, Jeffrey L.
   Bertagnolli, Darren
   Bickley, Kristopher
   Boe, Andrew
   Brouner, Krissy
   Butler, Stephanie
   Byrnes, Emi
   Caldejon, Shiella
   Carey, Anita
   Cate, Shelby
   Chapin, Mike
   Chen, Jefferey
   Dee, Nick
   Desta, Tsega
   Dolbeare, Tim A.
   Dotson, Nadia
   Ebbert, Amanda
   Fulfs, Erich
   Gee, Garrett
   Gilbert, Terri L.
   Goldy, Jeff
   Gourley, Lindsey
   Gregor, Ben
   Gu, Guangyu
   Hall, Jon
   Haradon, Zeb
   Haynor, David R.
   Hejazinia, Nika
   Hoerder-Suabedissen, Anna
   Howard, Robert
   Jochim, Jay
   Kinnunen, Marty
   Kriedberg, Ali
   Kuan, Chihchau L.
   Lau, Christopher
   Lee, Chang-Kyu
   Lee, Felix
   Luong, Lon
   Mastan, Naveed
   May, Ryan
   Melchor, Jose
   Mosqueda, Nerick
   Mott, Erika
   Ngo, Kiet
   Nyhus, Julie
   Oldre, Aaron
   Olson, Eric
   Parente, Jody
   Parker, Patrick D.
   Parry, Sheana
   Pendergraft, Julie
   Potekhina, Lydia
   Reding, Melissa
   Riley, Zackery L.
   Roberts, Tyson
   Rogers, Brandon
   Roll, Kate
   Rosen, David
   Sandman, David
   Sarreal, Melaine
   Shapovalova, Nadiya
   Shi, Shu
   Sjoquist, Nathan
   Sodt, Andy J.
   Townsend, Robbie
   Velasquez, Lissette
   Wagley, Udi
   Wakeman, Wayne B.
   White, Cassandra
   Bennett, Crissa
   Wu, Jennifer
   Young, Rob
   Youngstrom, Brian L.
   Wohnoutka, Paul
   Gibbs, Richard A.
   Rogers, Jeffrey
   Hohmann, John G.
   Hawrylycz, Michael J.
   Hevner, Robert F.
   Molnar, Zoltn
   Phillips, John W.
   Dang, Chinh
   Jones, Allan R.
   Amaral, David G.
   Bernard, Amy
   Lein, Ed S.
TI A comprehensive transcriptional map of primate brain development
SO NATURE
LA English
DT Article
ID human prefrontal cortex; human cerebral-cortex; adult human brain; gene-expression; rhesus-monkey; visual-cortex; synaptic development; positive selection; molecular pathways; rna-seq
AB The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.
C1 [Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Hejazinia, Nika; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Hohmann, John G.; Hawrylycz, Michael J.; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Bernard, Amy; Lein, Ed S.] Allen Inst Brain Sci, Seattle, WA 98109 USA.
   [Bennett, Jeffrey L.; Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Calif Natl Primate Res Ctr, MIND Inst, Sacramento, CA 95817 USA.
   [Haynor, David R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
   [Hoerder-Suabedissen, Anna; Molnar, Zoltn] Univ Oxford, Dept Physiol Anat & Genet, South Pk Rd, Oxford OX1 3QX, England.
   [Gibbs, Richard A.; Rogers, Jeffrey] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Gibbs, Richard A.; Rogers, Jeffrey] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Hevner, Robert F.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 USA.
C3 Allen Institute for Brain Science; University of California System; University of California Davis; University of Washington; University of Washington Seattle; University of Oxford; Baylor College of Medicine; Baylor College of Medicine; Seattle Children's Hospital
RP Lein, ES (corresponding author), Allen Inst Brain Sci, Seattle, WA 98109 USA.
EM EdL@alleninstitute.org
FU California National Primate Research Center (NIH) [RR00169]; NIH from National Institute of Mental Health [HHSN-271-2008-0047]; Biotechnology and Biological Sciences Research Council [BB/I021833/1] Funding Source: researchfish; Medical Research Council [G0500180, MR/N026039/1, G0700377] Funding Source: researchfish; BBSRC [BB/I021833/1] Funding Source: UKRI; MRC [G0700377, MR/N026039/1] Funding Source: UKRI
NR 83
TC 285
Z9 314
U1 1
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 367
EP +
DI 10.1038/nature18637
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200030
PM 27409810
DA 2026-03-09
ER

PT J
AU Park, CH
   Lee, SY
   Hwang, DS
   Shin, DW
   Cho, DH
   Lee, KH
   Kim, TW
   Kim, TW
   Lee, M
   Kim, DS
   Doherty, CM
   Thornton, AW
   Hill, AJ
   Guiver, MD
   Lee, YM
AF Park, Chi Hoon
   Lee, So Young
   Hwang, Doo Sung
   Shin, Dong Won
   Cho, Doo Hee
   Lee, Kang Hyuck
   Kim, Tae-Woo
   Kim, Tae-Wuk
   Lee, Mokwon
   Kim, Deok-Soo
   Doherty, Cara M.
   Thornton, Aaron W.
   Hill, Anita J.
   Guiver, Michael D.
   Lee, Young Moo
TI Nanocrack-regulated self-humidifying membranes
SO NATURE
LA English
DT Article
ID proton-exchange membrane; medium-temperature; fuel-cells; water; transport; nanochannels; chemistry; nafion; state
AB The regulation of water content in polymeric membranes is important in a number of applications, such as reverse electrodialysis and proton-exchange fuel-cell membranes. External thermal and water management systems add both mass and size to systems, and so intrinsic mechanisms of retaining water and maintaining ionic transport(1-3) in such membranes are particularly important for applications where small system size is important. For example, in proton-exchange membrane fuel cells, where water retention in the membrane is crucial for efficient transport of hydrated ions(1,4-7), by operating the cells at higher temperatures without external humidification, the membrane is self-humidified with water generated by electrochemical reactions(5,8). Here we report an alternative solution that does not rely on external regulation of water supply or high temperatures. Water content in hydrocarbon polymer membranes is regulated through nanometre-scale cracks ('nanocracks') in a hydrophobic surface coating. These cracks work as nanoscale valves to retard water desorption and to maintain ion conductivity in the membrane on dehumidification. Hydrocarbon fuel-cell membranes with surface nanocrack coatings operated at intermediate temperatures show improved electrochemical performance, and coated reverse-electrodialysis membranes show enhanced ionic selectivity with low bulk resistance.
C1 [Park, Chi Hoon; Lee, So Young; Hwang, Doo Sung; Shin, Dong Won; Cho, Doo Hee; Lee, Kang Hyuck; Lee, Young Moo] Hanyang Univ, Coll Engn, Dept Energy Engn, Seoul 133791, South Korea.
   [Kim, Tae-Woo; Kim, Tae-Wuk] Hanyang Univ, Dept Life Sci, Coll Nat Sci, Seoul 133791, South Korea.
   [Lee, Mokwon; Kim, Deok-Soo] Hanyang Univ, Sch Mech Engn, Coll Engn, Seoul 133791, South Korea.
   [Doherty, Cara M.; Thornton, Aaron W.; Hill, Anita J.] CSIRO, Mfg Flagship, Clayton, Vic 3168, Australia.
   [Guiver, Michael D.] Tianjin Univ, State Key Lab Engines, Tianjin 300072, Peoples R China.
   [Guiver, Michael D.] Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300072, Peoples R China.
   [Park, Chi Hoon] Gyeongnam Natl Univ Sci & Technol, Dept Energy Engn, Jinju 660758, South Korea.
   [Lee, So Young] Korea Inst Sci & Technol, Fuel Cell Res Ctr, 39-1 Hawolgok Dong, Seoul 136791, South Korea.
   [Hwang, Doo Sung] Univ Illinois, Dept Chem Engn, Chicago, IL 60607 USA.
   [Shin, Dong Won] Korea Inst Energy Res, Fuel Cell Lab, Daejeon 34129, South Korea.
C3 Hanyang University; Hanyang University; Hanyang University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Tianjin University; Nankai University; Tianjin University; Collaborative Innovation Center of Chemical Science & Engineering Tianjin; Gyeongnam National University of Science and Technology; Korea Institute of Science & Technology (KIST); University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Korea Institute of Energy Research (KIER)
RP Lee, YM (corresponding author), Hanyang Univ, Coll Engn, Dept Energy Engn, Seoul 133791, South Korea.; Guiver, MD (corresponding author), Tianjin Univ, State Key Lab Engines, Tianjin 300072, Peoples R China.; Guiver, MD (corresponding author), Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300072, Peoples R China.
EM guiver@tju.edu.cn; ymlee@hanyang.ac.kr
FU Nano-Material Technology Development Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2012M3A7B4049745]; Australian Research Council [DE40101359]; CSIRO Julius Career award; CSIRO Office of the Chief Executive Science Leader Scheme; Australia-Korea Foundation Early Career Researchers Program
NR 26
TC 395
Z9 423
U1 21
U2 862
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 480
EP +
DI 10.1038/nature17634
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900042
PM 27121841
DA 2026-03-09
ER

PT J
AU Rantakari, P
   Jäppinen, N
   Lokka, E
   Mokkala, E
   Gerke, H
   Peuhu, E
   Ivaska, J
   Elima, K
   Auvinen, K
   Salmi, M
AF Rantakari, Pia
   Jappinen, Norma
   Lokka, Emmi
   Mokkala, Elias
   Gerke, Heidi
   Peuhu, Emilia
   Ivaska, Johanna
   Elima, Kati
   Auvinen, Kaisa
   Salmi, Marko
TI Fetal liver endothelium regulates the seeding of tissue-resident macrophages
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; yolk-sac; heparin-binding; haemogenic endothelium; circulating monocytes; myeloid progenitors; mammalian embryo; iron homeostasis; spi-c; microglia
AB Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours(1-4). Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow(4,5). Although fate-mapping studies have uncovered a great amount of detail on the origin and kinetics of fetal macrophage development in the yolk sac and liver(6-11), the molecules that govern the tissue-specific migration of these cells remain completely unknown. Here we show that an endothelium-specific molecule, plasmalemma vesicle-associated protein (PLVAP), regulates the seeding of fetal monocyte-derived macrophages to tissues in mice. We found that PLVAP-deficient mice have completely normal levels of both yolk-sac-and bone-marrow-derived macrophages, but that fetal liver monocyte-derived macrophage populations were practically missing from tissues. Adult PLVAP-deficient mice show major alterations in macrophage-dependent iron recycling and mammary branching morphogenesis. PLVAP forms diaphragms in the fenestrae of liver sinusoidal endothelium during embryogenesis, interacts with chemoattractants and adhesion molecules and regulates the egress of fetal liver monocytes to the systemic vasculature. Thus, PLVAP selectively controls the exit of macrophage precursors from the fetal liver and, to our knowledge, is the first molecule identified in any organ as regulating the migratory events during embryonic macrophage ontogeny.
C1 [Rantakari, Pia; Jappinen, Norma; Lokka, Emmi; Mokkala, Elias; Gerke, Heidi; Elima, Kati; Auvinen, Kaisa; Salmi, Marko] Univ Turku, MediCity Res Lab, FI-20520 Turku, Finland.
   [Peuhu, Emilia; Ivaska, Johanna] Univ Turku, Turku Ctr Biotechnol, FI-20520 Turku, Finland.
   [Ivaska, Johanna] Univ Turku, Dept Biochem, FI-20500 Turku, Finland.
   [Elima, Kati] Univ Turku, Dept Med Biochem & Genet, FI-20520 Turku, Finland.
   [Salmi, Marko] Univ Turku, Dept Med Microbiol & Immunol, FI-20520 Turku, Finland.
C3 University of Turku; University of Turku; University of Turku; Finland National Institute for Health & Welfare; University of Turku; University of Turku
RP Salmi, M (corresponding author), Univ Turku, MediCity Res Lab, FI-20520 Turku, Finland.; Salmi, M (corresponding author), Univ Turku, Dept Med Microbiol & Immunol, FI-20520 Turku, Finland.
EM marko.salmi@utu.fi
FU Academy of Finland; Juselius Foundation; Cancer Foundation; South-Western Regional Fund of the Finnish Cultural Foundation; Foundation of Turku University; Satakunta Regional Fund of the Finnish Cultural Foundation
NR 49
TC 71
Z9 82
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 392
EP +
DI 10.1038/nature19814
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100041
PM 27732581
DA 2026-03-09
ER

PT J
AU Stroustrup, N
   Anthony, WE
   Nash, ZM
   Gowda, V
   Gomez, A
   López-Moyado, IF
   Apfeld, J
   Fontana, W
AF Stroustrup, Nicholas
   Anthony, Winston E.
   Nash, Zachary M.
   Gowda, Vivek
   Gomez, Adam
   Lopez-Moyado, Isaac F.
   Apfeld, Javier
   Fontana, Walter
TI The temporal scaling of Caenorhabditis elegans ageing
SO NATURE
LA English
DT Article
ID life-span; dietary restriction; genetic-analysis; c. elegans; daf-16; temperature; mutants; stress; damage
AB The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations(1,2). The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.
C1 [Stroustrup, Nicholas; Anthony, Winston E.; Nash, Zachary M.; Gowda, Vivek; Gomez, Adam; Lopez-Moyado, Isaac F.; Apfeld, Javier; Fontana, Walter] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Nash, Zachary M.] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Gomez, Adam] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Lopez-Moyado, Isaac F.] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA.
   [Apfeld, Javier] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of California System; University of California Los Angeles; La Jolla Institute for Immunology; Northeastern University
RP Stroustrup, N; Fontana, W (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM nstroustrup@post.harvard.edu; walter@hms.harvard.edu
FU US National Institutes of Health (NIH) Office of Research Infrastructure Programs [P40 OD010440]; NIH [R01 AG034994]; Glenn Foundation for Medical Research; NIH Office of the Director; National Institute of General Medical Sciences [P40OD010440] Funding Source: NIH RePORTER
NR 35
TC 135
Z9 173
U1 1
U2 94
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 103
EP +
DI 10.1038/nature16550
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500041
PM 26814965
DA 2026-03-09
ER

PT J
AU Frangeul, L
   Pouchelon, G
   Telley, L
   Lefort, S
   Luscher, C
   Jabaudon, D
AF Frangeul, Laura
   Pouchelon, Gabrielle
   Telley, Ludovic
   Lefort, Sandrine
   Luscher, Christian
   Jabaudon, Denis
TI A cross-modal genetic framework for the development and plasticity of sensory pathways
SO NATURE
LA English
DT Article
ID cytochrome-oxidase; geniculate-nucleus; neurons; mouse; projections; inputs; expression; neocortex; system; cortex
AB Modality-specific sensory inputs from individual sense organs are processed in parallel in distinct areas of the neocortex. For each sensory modality, input follows a cortico-thalamo-cortical loop in which a 'first-order' exteroceptive thalamic nucleus sends peripheral input to the primary sensory cortex, which projects back to a 'higher order' thalamic nucleus that targets a secondary sensory cortex(1-6). This conserved circuit motif raises the possibility that shared genetic programs exist across sensory modalities. Here we report that, despite their association with distinct sensory modalities, first-order nuclei in mice are genetically homologous across somatosensory, visual, and auditory pathways, as are higher order nuclei. We further reveal peripheral input-dependent control over the transcriptional identity and connectivity of first-order nuclei by showing that input ablation leads to induction of higher-order-type transcriptional programs and rewiring of higher-order-directed descending cortical input to deprived first-order nuclei. These findings uncover an input-dependent genetic logic for the design and plasticity of sensory pathways, in which conserved developmental programs lead to conserved circuit motifs across sensory modalities.
C1 [Frangeul, Laura; Pouchelon, Gabrielle; Telley, Ludovic; Lefort, Sandrine; Luscher, Christian; Jabaudon, Denis] Univ Geneva, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Luscher, Christian; Jabaudon, Denis] Univ Hosp Geneva, Clin Neurol, CH-1211 Geneva, Switzerland.
   [Pouchelon, Gabrielle] NYU, Langone Med Ctr, New York, NY 10016 USA.
C3 University of Geneva; University of Geneva; NYU Langone Medical Center; New York University
RP Jabaudon, D (corresponding author), Univ Geneva, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.; Jabaudon, D (corresponding author), Univ Hosp Geneva, Clin Neurol, CH-1211 Geneva, Switzerland.
EM denis.jabaudon@unige.ch
FU Swiss National Science Foundation (SNF) [PP00P3_123447]; Leenaards Foundation; Synapsis Foundation; NARSAD Foundation; Swiss National Science Foundation (SNF) [PP00P3_123447] Funding Source: Swiss National Science Foundation (SNF)
NR 32
TC 61
Z9 68
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 96
EP +
DI 10.1038/nature19770
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900041
PM 27669022
DA 2026-03-09
ER

PT J
AU Kirchdoerfer, RN
   Cottrell, CA
   Wang, NS
   Pallesen, J
   Yassine, HM
   Turner, HL
   Corbett, KS
   Graham, BS
   McLellan, JS
   Ward, AB
AF Kirchdoerfer, Robert N.
   Cottrell, Christopher A.
   Wang, Nianshuang
   Pallesen, Jesper
   Yassine, Hadi M.
   Turner, Hannah L.
   Corbett, Kizzmekia S.
   Graham, Barney S.
   McLellan, Jason S.
   Ward, Andrew B.
TI Pre-fusion structure of a human coronavirus spike protein
SO NATURE
LA English
DT Article
ID receptor-binding domain; cryo-em structure; crystal-structure; electron-microscope; virus; glycoprotein; hemagglutinin; visualization; validation; mechanisms
AB HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease1, and is related to the zoonotic SARS(2) and MERS3 betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein(4), which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 resolution structure of the trimeric HKU1 S protein determined using singleparticle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.
C1 [Kirchdoerfer, Robert N.; Cottrell, Christopher A.; Pallesen, Jesper; Turner, Hannah L.; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Wang, Nianshuang; McLellan, Jason S.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
   [Yassine, Hadi M.; Corbett, Kizzmekia S.; Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA.
   [Yassine, Hadi M.] Qatar Univ, Biomed Res Ctr, QU NRC, Zone 5,Room D130, Doha, Qatar.
C3 Scripps Research Institute; Dartmouth College; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Qatar University
RP Ward, AB (corresponding author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.; McLellan, JS (corresponding author), Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
EM Jason.S.McLellan@Dartmouth.edu; ABWard@Scripps.edu
FU Scripps Research Institute; Geisel School of Medicine at Dartmouth; intramural NIAID; NIH [R56 AI118016]; National Institute of Allergy and Infectious Diseases [ZIAAI005125] Funding Source: NIH RePORTER
NR 57
TC 528
Z9 647
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 118
EP 121
DI 10.1038/nature17200
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900052
PM 26935699
DA 2026-03-09
ER

PT J
AU Schaefer, JM
   Finkel, RC
   Balco, G
   Alley, RB
   Caffee, MW
   Briner, JP
   Young, NE
   Gow, AJ
   Schwartz, R
AF Schaefer, Joerg M.
   Finkel, Robert C.
   Balco, Greg
   Alley, Richard B.
   Caffee, Marc W.
   Briner, Jason P.
   Young, Nicolas E.
   Gow, Anthony J.
   Schwartz, Roseanne
TI Greenland was nearly ice-free for extended periods during the Pleistocene
SO NATURE
LA English
DT Article
ID elastic recoil detection; cosmogenic radionuclides; half-life; sheet; be-10; climate; al-26; sensitivity; burial; muons
AB The Greenland Ice Sheet (GIS) contains the equivalent of 7.4 metres of global sea-level rise(1). Its stability in our warming climate is therefore a pressing concern. However, the sparse proxy evidence of the palaeo-stability of the GIS means that its history is controversial (compare refs 2 and 3 to ref. 4). Here we show that Greenland was deglaciated for extended periods during the Pleistocene epoch (from 2.6 million years ago to 11,700 years ago), based on new measurements of cosmic-ray-produced beryllium and aluminium isotopes (Be-10 and Al-26) in a bedrock core from beneath an ice core near the GIS summit. Models indicate that when this bedrock site is ice-free, any remaining ice is concentrated in the eastern Greenland highlands and the GIS is reduced to less than ten per cent of its current volume. Our results narrow the spectrum of possible GIS histories: the longest period of stability of the present ice sheet that is consistent with the measurements is 1.1 million years, assuming that this was preceded by more than 280,000 years of ice-free conditions. Other scenarios, in which Greenland was ice-free during any or all Pleistocene interglacials, may be more realistic. Our observations are incompatible with most existing model simulations that present a continuously existing Pleistocene GIS. Future simulations of the GIS should take into account that Greenland was nearly ice-free for extended periods under Pleistocene climate forcing.
C1 [Schaefer, Joerg M.; Finkel, Robert C.; Young, Nicolas E.; Schwartz, Roseanne] Lamont Doherty Earth Observ, Geochem, Palisades, NY 10964 USA.
   [Schaefer, Joerg M.] Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
   [Finkel, Robert C.] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 95064 USA.
   [Balco, Greg] Berkeley Geochronol Ctr, 2455 Ridge Rd, Berkeley, CA 94709 USA.
   [Alley, Richard B.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Caffee, Marc W.] Purdue Univ, Dept Phys & Astron, 525 Northwestern Ave, W Lafayette, IN 47907 USA.
   [Briner, Jason P.] SUNY Buffalo, Dept Otolaryngol, Buffalo, NY 14260 USA.
   [Gow, Anthony J.] US Army Cold Reg Res & Engn Lab, Hanover, NH 03755 USA.
C3 Columbia University; Columbia University; University of California System; University of California Berkeley; Berkeley Geochronolgy Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Purdue University System; Purdue University; State University of New York (SUNY) System; University at Buffalo, SUNY; United States Department of Defense; United States Army; U.S. Army Corps of Engineers; U.S. Army Engineer Research & Development Center (ERDC); Cold Regions Research & Engineering Laboratory (CRREL)
RP Schaefer, JM (corresponding author), Lamont Doherty Earth Observ, Geochem, Palisades, NY 10964 USA.; Schaefer, JM (corresponding author), Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
EM schaefer@ldeo.columbia.edu
FU Lamont Climate Center; Corner Family Foundation; NSF [AGS 1338832]; PLR Arctic System Science Program [1503959]; Ann and Gordon Getty Foundation; US National Science Foundation [EAR-1153689]; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1338832] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1560658] Funding Source: National Science Foundation
NR 43
TC 111
Z9 129
U1 1
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 252
EP +
DI 10.1038/nature20146
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700053
PM 27929018
DA 2026-03-09
ER

PT J
AU Kerr, EM
   Gaude, E
   Turrell, FK
   Frezza, C
   Martins, CP
AF Kerr, Emma M.
   Gaude, Edoardo
   Turrell, Frances K.
   Frezza, Christian
   Martins, Carla P.
TI Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities
SO NATURE
LA English
DT Article
ID k-ras; oncogene; cancer; p53; dysfunction; mutations; glucose; mouse
AB The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations(1-3). A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations(4-7.) We recently showed that advanced lung tumours from KrasG12D/+; p53-null mice frequently exhibit KrasG12D allelic enrichment (KrasG12D/Kraswild-type > 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, KrasG12D/G12D cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous nonsmall- cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of KrasG12D copy gain), but not in the corresponding early tumours (KrasG12D heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.
C1 [Kerr, Emma M.; Gaude, Edoardo; Turrell, Frances K.; Frezza, Christian; Martins, Carla P.] Univ Cambridge, MRC, Canc Unit, Box 197,Cambridge Biomed Campus, Cambridge CB2 0XZ, England.
C3 University of Cambridge
RP Martins, CP (corresponding author), Univ Cambridge, MRC, Canc Unit, Box 197,Cambridge Biomed Campus, Cambridge CB2 0XZ, England.
EM c.martins@mrc-cu.cam.ac.uk
FU Medical Research Council; Medical Research Council [MC_UU_12022/6, MC_UU_12022/4, 1390328, MC_UP_1101/1] Funding Source: researchfish; MRC [MC_UP_1101/1, MC_UU_12022/6, MC_UU_12022/4] Funding Source: UKRI
NR 29
TC 260
Z9 302
U1 2
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 110
EP +
DI 10.1038/nature16967
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900050
PM 26909577
DA 2026-03-09
ER

PT J
AU Saredi, G
   Huang, HD
   Hammond, CM
   Alabert, C
   Bekker-Jensen, S
   Forne, I
   Reverón-Gómez, N
   Foster, BM
   Mlejnkova, L
   Bartke, T
   Cejka, P
   Mailand, N
   Imhof, A
   Patel, DJ
   Groth, A
AF Saredi, Giulia
   Huang, Hongda
   Hammond, Colin M.
   Alabert, Constance
   Bekker-Jensen, Simon
   Forne, Ignasi
   Reveron-Gomez, Nazaret
   Foster, Benjamin M.
   Mlejnkova, Lucie
   Bartke, Till
   Cejka, Petr
   Mailand, Niels
   Imhof, Axel
   Patel, Dinshaw J.
   Groth, Anja
TI H4K20me0 marks post-replicative chromatin and recruits the TONSL-MMS22L DNA repair complex
SO NATURE
LA English
DT Article
ID homologous recombination; mms22l-nfkbil2 complex; mms22l-tonsl complex; cell-cycle; methylation; chaperone; binding; bard1; stability; proteins
AB After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL-MMS22L(1-4) homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL-MMS22L binds new histones H3-H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL-MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.
C1 [Saredi, Giulia; Hammond, Colin M.; Alabert, Constance; Reveron-Gomez, Nazaret; Groth, Anja] Univ Copenhagen, BRIC, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
   [Saredi, Giulia; Hammond, Colin M.; Alabert, Constance; Reveron-Gomez, Nazaret; Groth, Anja] Univ Copenhagen, Ctr Epigenet, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
   [Huang, Hongda; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Bekker-Jensen, Simon; Mailand, Niels] Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, DK-2200 Copenhagen, Denmark.
   [Forne, Ignasi; Imhof, Axel] Univ Munich, Dept Mol Biol, Biomed Ctr, D-80336 Munich, Germany.
   [Forne, Ignasi; Imhof, Axel] Univ Munich, Ctr Integrated Prot Sci Munich, D-80336 Munich, Germany.
   [Foster, Benjamin M.; Bartke, Till] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, CSC, Du Cane Rd, London W12 0NN, England.
   [Foster, Benjamin M.; Bartke, Till] Univ London Imperial Coll Sci Technol & Med, Fac Med, ICS, Du Cane Rd, London W12 0NN, England.
   [Mlejnkova, Lucie; Cejka, Petr] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland.
C3 University of Copenhagen; University of Copenhagen; Memorial Sloan Kettering Cancer Center; University of Copenhagen; Novo Nordisk Foundation; University of Munich; University of Munich; Imperial College London; Imperial College London; University of Zurich
RP Groth, A (corresponding author), Univ Copenhagen, BRIC, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.; Groth, A (corresponding author), Univ Copenhagen, Ctr Epigenet, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.; Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pateld@mskcc.org; anja.groth@bric.ku.dk
FU European Commission; Leukemia and Lymphoma Society; STARR foundation; European Research Council (ERC) [281765]; Danish National Research Foundation to the Center for Epigenetics [DNRF82]; Danish Cancer Society; Danish Medical Research Council; Novo Nordisk Foundation; Lundbeck Foundation; European Commission [257082]; DFG Excellence Clusters CIPSM; SyNergy; DFG Collaborative Research Center [1064]; Medical Research Council and the European Research Council (ERC) [309952]; MRC [MC_UP_1102/2] Funding Source: UKRI; Medical Research Council [MC_UP_1102/2] Funding Source: researchfish; Novo Nordisk Fonden [NNF14OC0012839] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Niels Mailand] Funding Source: researchfish; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; European Research Council (ERC) [281765] Funding Source: European Research Council (ERC)
NR 41
TC 172
Z9 201
U1 0
U2 33
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 714
EP +
DI 10.1038/nature18312
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000043
PM 27338793
DA 2026-03-09
ER

PT J
AU Vourekas, A
   Alexiou, P
   Vrettos, N
   Maragkakis, M
   Mourelatos, Z
AF Vourekas, Anastassios
   Alexiou, Panagiotis
   Vrettos, Nicholas
   Maragkakis, Manolis
   Mourelatos, Zissimos
TI Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm
SO NATURE
LA English
DT Article
ID drosophila-melanogaster; structural basis; piwi proteins; clip-seq; reveals; localization; oskar; tudor; aubergine; identification
AB The conserved Piwi family of proteins and piwi-interacting RNAs (piRNAs) have a central role in genomic stability, which is inextricably linked to germ-cell formation, by forming Piwi ribonucleoproteins (piRNPs) that silence transposable elements(1). In Drosophila melanogaster and other animals, primordial germ-cell specification in the developing embryo is driven by maternal messenger RNAs and proteins that assemble into specialized messenger ribonucleoproteins (mRNPs) localized in the germ (pole) plasm at the posterior of the oocyte(2,3). Maternal piRNPs, especially those loaded on the Piwi protein Aubergine (Aub), are transmitted to the germ plasm to initiate transposon silencing in the offspring germ line(4-7). The transport of mRNAs to the oocyte by midoogenesis is an active, microtubule-dependent process(8); mRNAs necessary for primordial germ-cell formation are enriched in the germ plasm at late oogenesis via a diffusion and entrapment mechanism, the molecular identity of which remains unknown(8,9). Aub is a central component of germ granule RNPs, which house mRNAs in the germ plasm(10-12), and interactions between Aub and Tudor are essential for the formation of germ granules(13-16). Here we show that Aub-loaded piRNAs use partial base-pairing characteristics of Argonaute RNPs to bind mRNAs randomly in Drosophila, acting as an adhesive trap that captures mRNAs in the germ plasm, in a Tudor-dependent manner. Notably, germ plasm mRNAs in drosophilids are generally longer and more abundant than other mRNAs, suggesting that they provide more target sites for piRNAs to promote their preferential tethering in germ granules. Thus, complexes containing Tudor, Aub piRNPs and mRNAs couple piRNA inheritance with germline specification. Our findings reveal an unexpected function for piRNP complexes in mRNA trapping that may be generally relevant to the function of animal germ granules.
C1 [Vourekas, Anastassios; Alexiou, Panagiotis; Vrettos, Nicholas; Maragkakis, Manolis; Mourelatos, Zissimos] Univ Penn, Perelman Sch Med, Inst Translat Med & Therapeut, Dept Pathol & Lab Med,Div Neuropathol, Philadelphia, PA 19104 USA.
   [Vourekas, Anastassios; Alexiou, Panagiotis; Vrettos, Nicholas; Maragkakis, Manolis; Mourelatos, Zissimos] Univ Penn, PENN Genome Frontiers Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania
RP Mourelatos, Z (corresponding author), Univ Penn, Perelman Sch Med, Inst Translat Med & Therapeut, Dept Pathol & Lab Med,Div Neuropathol, Philadelphia, PA 19104 USA.; Mourelatos, Z (corresponding author), Univ Penn, PENN Genome Frontiers Inst, Philadelphia, PA 19104 USA.
EM mourelaz@uphs.upenn.edu
FU Brody family fellowship; National Institutes of Health (NIH) [GM072777]
NR 44
TC 103
Z9 121
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 390
EP +
DI 10.1038/nature17150
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300057
PM 26950602
DA 2026-03-09
ER

PT J
AU Lorenzo-Redondo, R
   Fryer, HR
   Bedford, T
   Kim, EY
   Archer, J
   Pond, SLK
   Chung, YS
   Penugonda, S
   Chipman, JG
   Fletcher, CV
   Schacker, TW
   Malim, MH
   Rambaut, A
   Haase, AT
   McLean, AR
   Wolinsky, SM
AF Lorenzo-Redondo, Ramon
   Fryer, Helen R.
   Bedford, Trevor
   Kim, Eun-Young
   Archer, John
   Pond, Sergei L. Kosakovsky
   Chung, Yoon-Seok
   Penugonda, Sudhir
   Chipman, Jeffrey G.
   Fletcher, Courtney V.
   Schacker, Timothy W.
   Malim, Michael H.
   Rambaut, Andrew
   Haase, Ashley T.
   McLean, Angela R. .
   Wolinsky, Steven M.
TI Persistent HIV-1 replication maintains the tissue reservoir during therapy
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; active antiretroviral therapy; cd4(+) t-cells; in-vivo; peripheral-blood; evolution; dna; sequences; dynamics; accurate
AB Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.
C1 [Lorenzo-Redondo, Ramon; Kim, Eun-Young; Penugonda, Sudhir; Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60011 USA.
   [Fryer, Helen R.; McLean, Angela R. .] Univ Oxford, Inst Emerging Infect, Dept Zool, Oxford OX1 3PS, England.
   [Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
   [Archer, John] Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, P-4485661 Vairao, Portugal.
   [Pond, Sergei L. Kosakovsky] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA.
   [Chung, Yoon-Seok] Korea Natl Inst Hlth, Div Aids, Ctr Immunol & Pathol, Chungju Si 28159, Chungcheongbuk, South Korea.
   [Chipman, Jeffrey G.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
   [Fletcher, Courtney V.] Univ Nebraska Med Ctr, Coll Pharm, Antiviral Pharmacol Lab, Omaha, NE 68198 USA.
   [Schacker, Timothy W.] Univ Minnesota, Div Infect Dis, Minneapolis, MN 55455 USA.
   [Malim, Michael H.] Kings Coll London, Guys Hosp, Dept Infect Dis, London SE21 7DN, England.
   [Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland.
   [Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Pond, Sergei L. Kosakovsky] Temple Univ, Inst Genom & Evolutionary Med, Philadelphia, PA 19122 USA.
C3 Northwestern University; Feinberg School of Medicine; University of Oxford; Fred Hutchinson Cancer Center; Universidade do Porto; University of California System; University of California San Diego; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Immunology & Pathology; University of Minnesota System; University of Minnesota Twin Cities; University of Nebraska System; University of Nebraska Medical Center; University of Minnesota System; University of Minnesota Twin Cities; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; University of Edinburgh; University of Minnesota System; University of Minnesota Twin Cities; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University
RP Wolinsky, SM (corresponding author), Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60011 USA.
EM s-wolinsky@northwestern.edu
FU National Institutes of Health [DA033773, AI1074340, GM110749]; Medical Research Council [G1000196]; Framework Programme for Research and Technological Development [278433-PREDEMICS]; European Research Council [260864]; Oxford Martin School; All Souls College; Royal Society; Wellcome Trust; MRC [G1000196] Funding Source: UKRI; Medical Research Council [G1000196] Funding Source: researchfish; Wellcome Trust [106223/Z/14/Z] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [UM1AI106701] Funding Source: NIH RePORTER
NR 50
TC 521
Z9 620
U1 1
U2 145
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 51
EP +
DI 10.1038/nature16933
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500030
PM 26814962
DA 2026-03-09
ER

PT J
AU Goldberg, A
   Mychajliw, AM
   Hadly, EA
AF Goldberg, Amy
   Mychajliw, Alexis M.
   Hadly, Elizabeth A.
TI Post-invasion demography of prehistoric humans in South America
SO NATURE
LA English
DT Article
ID human-population; radiocarbon-dates; history; climate; north; distributions; calibration; impact; growth
AB As the last habitable continent colonized by humans, the site of multiple domestication hotspots, and the location of the largest Pleistocene megafaunal extinction, South America is central to human prehistory(1-7). Yet remarkably little is known about human population dynamics during colonization, subsequent expansions, and domestication(2-5). Here we reconstruct the spatiotemporal patterns of human population growth in South America using a newly aggregated database of 1,147 archaeological sites and 5,464 calibrated radiocarbon dates spanning fourteen thousand to two thousand years ago (ka). We demonstrate that, rather than a steady exponential expansion, the demographic history of South Americans is characterized by two distinct phases. First, humans spread rapidly throughout the continent, but remained at low population sizes for 8,000 years, including a 4,000-year period of 'boom-and-bust' oscillations with no net growth. Supplementation of hunting with domesticated crops and animals(4,8) had a minimal impact on population carrying capacity. Only with widespread sedentism, beginning similar to 5 ka(4,8), did a second demographic phase begin, with evidence for exponential population growth in cultural hotspots, characteristic of the Neolithic transition worldwide(9). The unique extent of humanity's ability to modify its environment to markedly increase carrying capacity in South America is therefore an unexpectedly recent phenomenon.
C1 [Goldberg, Amy; Mychajliw, Alexis M.; Hadly, Elizabeth A.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Hadly, Elizabeth A.] Stanford Univ, Woods Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Goldberg, A (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM agoldb@stanford.edu
FU NSF [EAR 1148181, BCS 1515127]; NSF Graduate Research fellowship; ARCS fellowship; Stanford Interdisciplinary Graduate Fellowship; Gabilan Fellowship; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1515127] Funding Source: National Science Foundation; Directorate For Geosciences [1148181] Funding Source: National Science Foundation; Division Of Earth Sciences [1148181] Funding Source: National Science Foundation
NR 53
TC 164
Z9 186
U1 1
U2 55
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 232
EP +
DI 10.1038/nature17176
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100039
PM 27049941
DA 2026-03-09
ER

PT J
AU Kostyuchenko, VA
   Lim, EXY
   Zhang, SJ
   Fibriansah, G
   Ng, TS
   Ooi, JSG
   Shi, J
   Lok, SM
AF Kostyuchenko, Victor A.
   Lim, Elisa X. Y.
   Zhang, Shuijun
   Fibriansah, Guntur
   Ng, Thiam-Seng
   Ooi, Justin S. G.
   Shi, Jian
   Lok, Shee-Mei
TI Structure of the thermally stable Zika virus
SO NATURE
LA English
DT Article
ID dengue virus; envelope glycoprotein; encephalitis-virus; crystal-structure; maturation; infection
AB Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses(1), and with Guillian-Barre syndrome in adults(2). Here we present the 3.7 angstrom resolution cryoelectron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 degrees C, in sharp contrast to the less thermally stable DENV3. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryoelectron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen(4), saliva(5) and urine(6). Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.
C1 [Kostyuchenko, Victor A.; Lim, Elisa X. Y.; Zhang, Shuijun; Fibriansah, Guntur; Ng, Thiam-Seng; Ooi, Justin S. G.; Lok, Shee-Mei] Duke Natl Univ Singapore, Sch Med, Program Emerging Infect Dis, Singapore 169857, Singapore.
   [Kostyuchenko, Victor A.; Lim, Elisa X. Y.; Zhang, Shuijun; Fibriansah, Guntur; Ng, Thiam-Seng; Ooi, Justin S. G.; Shi, Jian; Lok, Shee-Mei] Natl Univ Singapore, Dept Biol Sci, Ctr BioImaging Sci, Singapore 117557, Singapore.
   [Shi, Jian] Natl Univ Singapore, Dept Biol Sci, CryoEM Unit, Singapore 117557, Singapore.
C3 National University of Singapore; National University of Singapore; National University of Singapore
RP Lok, SM (corresponding author), Duke Natl Univ Singapore, Sch Med, Program Emerging Infect Dis, Singapore 169857, Singapore.; Lok, SM (corresponding author), Natl Univ Singapore, Dept Biol Sci, Ctr BioImaging Sci, Singapore 117557, Singapore.
EM sheemei.lok@duke-nus.edu.sg
FU Singapore Ministry of Education Tier 3 grant [MOE2012-T3-1-008]; National Research Foundation [NRF-NRFI2016-01]; Duke-NUS Signature Research Programme - Ministry of Health, Singapore
NR 29
TC 376
Z9 493
U1 2
U2 151
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 425
EP +
DI 10.1038/nature17994
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300055
PM 27093288
DA 2026-03-09
ER

PT J
AU Kintzer, AF
   Stroud, RM
AF Kintzer, Alexander F.
   Stroud, Robert M.
TI Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana
SO NATURE
LA English
DT Article
ID ion-channel; crystal-structure; sequence alignment; naadp; calcium; prediction; shaker; activation; mechanism; proteins
AB Two-pore channels (TPCs) comprise a subfamily (TPC1-3) of eukaryotic voltage-and ligand-gated cation channels(1,2) with two non-equivalent tandem pore-forming subunits that dimerize to form quasi-tetramers. Found in vacuolar(3) or endolysosomal(4) membranes, they regulate the conductance of sodium(5) and calcium(3,6) ions, intravesicular pH(5), trafficking(7) and excitability(8,9). TPCs are activated by a decrease in transmembrane potential(1,3,9,10) and an increase in cytosolic calcium concentrations(1,10), are inhibited by low luminal pH and calcium(11), and are regulated by phosphorylation(12,13). Here we report the crystal structure of TPC1 from Arabidopsis thaliana at 2.87 angstrom resolution as a basis for understanding ion permeation(3,4,10), channel activation(1,5,10), the location of voltage-sensing domains(1,9,10) and regulatory ion-binding sites(11,14). We determined sites of phosphorylation3,4 in the amino-terminal and carboxy-terminal domains that are positioned to allosterically modulate cytoplasmic Ca2+ activation. One of the two voltage-sensing domains (VSD2) encodes voltage sensitivity and inhibition by luminal Ca2+ and adopts a conformation distinct from the activated state observed in structures of other voltage-gated ion channels(15,16). The structure shows that potent pharmacophore trans-Ned-19 (ref. 17) acts allosterically by clamping the pore domains to VSD2. In animals, Ned-19 prevents infection by Ebola virus and other filoviruses, presumably by altering their fusion with the endolysosome and delivery of their contents into the cytoplasm(7).
C1 [Kintzer, Alexander F.; Stroud, Robert M.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco
RP Stroud, RM (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM stroud@msg.ucsf.edu
FU NIH [GM24485]; Sandler Foundation; NIGMS [P41-GM103311, P41-RR001614]; National Institutes of Health, National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]; DOE Office of Biological and Environmental Research; National Institutes of Health, National Institute of General Medical Sciences [P41GM103393];  [MR-15-328599]; National Institute of General Medical Sciences [R01GM024485] Funding Source: NIH RePORTER
NR 51
TC 146
Z9 164
U1 0
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 258
EP +
DI 10.1038/nature17194
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100047
PM 26961658
DA 2026-03-09
ER

PT J
AU Bailey, P
   Chang, DK
   Nones, K
   Johns, AL
   Patch, AM
   Gingras, MC
   Miller, DK
   Christ, AN
   Bruxner, TJC
   Quinn, MC
   Nourse, C
   Murtaugh, LC
   Harliwong, I
   Idrisoglu, S
   Manning, S
   Nourbakhsh, E
   Wani, S
   Fink, L
   Holmes, O
   Chin, V
   Anderson, MJ
   Kazakoff, S
   Leonard, C
   Newell, F
   Waddell, N
   Wood, S
   Xu, QY
   Wilson, PJ
   Cloonan, N
   Kassahn, KS
   Taylor, D
   Quek, K
   Robertson, A
   Pantano, L
   Mincarelli, L
   Sanchez, LN
   Evers, L
   Wu, JM
   Pinese, M
   Cowley, MJ
   Jones, MD
   Colvin, EK
   Nagrial, AM
   Humphrey, ES
   Chantrill, LA
   Mawson, A
   Humphris, J
   Chou, A
   Pajic, M
   Scarlett, CJ
   Pinho, AV
   Giry-Laterriere, M
   Rooman, I
   Samra, JS
   Kench, JG
   Lovell, JA
   Merrett, ND
   Toon, CW
   Epari, K
   Nguyen, NQ
   Barbour, A
   Zeps, N
   Moran-Jones, K
   Jamieson, NB
   Graham, JS
   Duthie, F
   Oien, K
   Hair, J
   Grützmann, R
   Maitra, A
   Iacobuzio-Donahue, CA
   Wolfgang, CL
   Morgan, RA
   Lawlor, RT
   Corbo, V
   Bassi, C
   Rusev, B
   Capelli, P
   Salvia, R
   Tortora, G
   Mukhopadhyay, D
   Petersen, GM
   Munzy, DM
   Fisher, WE
   Karim, SA
   Eshleman, JR
   Hruban, RH
   Pilarsky, C
   Morton, JR
   Sansom, OJ
   Scarpa, A
   Musgrove, EA
   Bailey, UMH
   Hofmann, O
   Sutherland, RL
   Wheeler, DA
   Gill, AJ
   Gibbs, RA
   Pearson, JV
   Waddell, N
   Biankin, AV
   Grimmond, SM
AF Bailey, Peter
   Chang, David K.
   Nones, Katia
   Johns, Amber L.
   Patch, Ann-Marie
   Gingras, Marie-Claude
   Miller, David K.
   Christ, Angelika N.
   Bruxner, Tim J. C.
   Quinn, Michael C.
   Nourse, Craig
   Murtaugh, L. Charles
   Harliwong, Ivon
   Idrisoglu, Senel
   Manning, Suzanne
   Nourbakhsh, Ehsan
   Wani, Shivangi
   Fink, Lynn
   Holmes, Oliver
   Chin, Vencssa
   Anderson, Matthew J.
   Kazakoff, Stephen
   Leonard, Conrad
   Newell, Felicity
   Waddell, Nick
   Wood, Scott
   Xu, Qinying
   Wilson, Peter J.
   Cloonan, Nicole
   Kassahn, Karin S.
   Taylor, Darrin
   Quek, Kelly
   Robertson, Alan
   Pantano, Lorena
   Mincarelli, Laura
   Sanchez, Luis N.
   Evers, Lisa
   Wu, Jianmin
   Pinese, Mark
   Cowley, Mark J.
   Jones, Marc D.
   Colvin, Emily K.
   Nagrial, Adnan M.
   Humphrey, Emily S.
   Chantrill, Lorraine A.
   Mawson, Amanda
   Humphris, Jeremy
   Chou, Angela
   Pajic, Marina
   Scarlett, Christopher J.
   Pinho, Andreia V.
   Giry-Laterriere, Marc
   Rooman, Ilse
   Samra, Jaswinder S.
   Kench, James G.
   Lovell, Jessica A.
   Merrett, Neil D.
   Toon, Christopher W.
   Epari, Krishna
   Nguyen, Nam Q.
   Barbour, Andrew
   Zeps, Nikolajs
   Moran-Jones, Kim
   Jamieson, Nigel B.
   Graham, Janet S.
   Duthie, Fraser
   Oien, Karin
   Hair, Jane
   Gruetzmann, Robert
   Maitra, Anirban
   Iacobuzio-Donahue, Christine A.
   Wolfgang, Christopher L.
   Morgan, Richard A.
   Lawlor, Rita T.
   Corbo, Vincenzo
   Bassi, Claudio
   Rusev, Borislav
   Capelli, Paola
   Salvia, Roberto
   Tortora, Giampaolo
   Mukhopadhyay, Debabrata
   Petersen, Gloria M.
   Munzy, Donna M.
   Fisher, William E.
   Karim, Saadia A.
   Eshleman, James R.
   Hruban, Ralph H.
   Pilarsky, Christian
   Morton, Jennifer R.
   Sansom, Owen J.
   Scarpa, Aldo
   Musgrove, Elizabeth A.
   Bailey, Ulla-Maja Hagbo
   Hofmann, Oliver
   Sutherland, Robert L.
   Wheeler, David A.
   Gill, Anthony J.
   Gibbs, Richard A.
   Pearson, John V.
   Waddell, Nicola
   Biankin, Andrew V.
   Grimmond, Sean M.
TI Genomic analyses identify molecular subtypes of pancreatic cancer
SO NATURE
LA English
DT Article
ID ductal adenocarcinoma; mutations; package; tumor; differentiation; metastasis; pathways
AB Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63 Delta N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.
C1 [Bailey, Peter; Nones, Katia; Patch, Ann-Marie; Miller, David K.; Christ, Angelika N.; Bruxner, Tim J. C.; Quinn, Michael C.; Nourse, Craig; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Anderson, Matthew J.; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J.; Cloonan, Nicole; Kassahn, Karin S.; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pearson, John V.; Waddell, Nicola; Grimmond, Sean M.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4072, Australia.
   [Bailey, Peter; Chang, David K.; Nourse, Craig; Mincarelli, Laura; Sanchez, Luis N.; Evers, Lisa; Jones, Marc D.; Moran-Jones, Kim; Jamieson, Nigel B.; Graham, Janet S.; Musgrove, Elizabeth A.; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Biankin, Andrew V.; Grimmond, Sean M.] Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.
   [Chang, David K.; Johns, Amber L.; Miller, David K.; Chin, Vencssa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Jones, Marc D.; Colvin, Emily K.; Nagrial, Adnan M.; Humphrey, Emily S.; Chantrill, Lorraine A.; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Kench, James G.; Lovell, Jessica A.; Toon, Christopher W.; Oien, Karin; Sutherland, Robert L.; Gill, Anthony J.; Biankin, Andrew V.] Kinghorn Canc Ctr, 370 Victoria St, Darlinghurst, NSW 2010, Australia.
   [Chang, David K.; Johns, Amber L.; Miller, David K.; Chin, Vencssa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Jones, Marc D.; Colvin, Emily K.; Nagrial, Adnan M.; Humphrey, Emily S.; Chantrill, Lorraine A.; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Kench, James G.; Lovell, Jessica A.; Toon, Christopher W.; Oien, Karin; Sutherland, Robert L.; Gill, Anthony J.; Biankin, Andrew V.] Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Sydney, NSW 2010, Australia.
   [Chang, David K.; Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Eldridge Rd, Sydney, NSW 2200, Australia.
   [Chang, David K.; Merrett, Neil D.; Biankin, Andrew V.] Univ New S Wales, Fac Med, South Western Sydney Clin Sch, Liverpool, Merseyside 2170, England.
   [Nones, Katia; Patch, Ann-Marie; Quinn, Michael C.; Wani, Shivangi; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Wood, Scott; Xu, Qinying; Cloonan, Nicole; Pearson, John V.; Waddell, Nicola] QIMR Berghofer Med Res Inst, Herston, Qld 4006, Australia.
   [Gingras, Marie-Claude; Munzy, Donna M.; Wheeler, David A.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Gingras, Marie-Claude; Munzy, Donna M.; Wheeler, David A.; Gibbs, Richard A.] Baylor Coll Med, Michael DeBakey Dept Surg, Houston, TX 77030 USA.
   [Gingras, Marie-Claude] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Murtaugh, L. Charles] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
   [Kassahn, Karin S.] SA Pathol, Genet & Mol Pathol, Adelaide, SA 5000, Australia.
   [Kassahn, Karin S.] Univ Adelaide, Sch Biol Sci, Adelaide, SA 5000, Australia.
   [Pantano, Lorena; Hofmann, Oliver] Harvard Univ, TH Chan Sch Publ Hlth, Harvard Chan Bioinformat Core, Boston, MA 02115 USA.
   [Chantrill, Lorraine A.] Campbelltown Hosp, Macarthur Canc Therapy Ctr, Campbelltown, NSW 2560, Australia.
   [Chou, Angela] St Vincents Hosp, SydPath, Dept Pathol, Sydney, NSW 2010, Australia.
   [Pajic, Marina] Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW 2052, Australia.
   [Scarlett, Christopher J.] Univ Newcastle, Sch Environm & Life Sci, Ourimbah, NSW 2258, Australia.
   [Samra, Jaswinder S.] Royal N Shore Hosp, Dept Surg, Sydney, NSW 2065, Australia.
   [Samra, Jaswinder S.; Kench, James G.; Gill, Anthony J.] Univ Sydney, Sydney, NSW 2006, Australia.
   [Kench, James G.] Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Camperdown, NSW 2050, Australia.
   [Merrett, Neil D.] Univ Western Sydney, Sch Med, Penrith, NSW 2175, Australia.
   [Epari, Krishna] Fiona Stanley Hosp, Robin Warren Dr, Murdoch, WA 6150, Australia.
   [Nguyen, Nam Q.] Royal Adelaide Hosp, Dept Gastroenterol, Adelaide, SA 5000, Australia.
   [Barbour, Andrew] Princess Alexandra Hosp, Dept Surg, Ipswich Rd, Woollongabba, Qld 4102, Australia.
   [Zeps, Nikolajs] Univ Western Australia, Sch Surg M507, 35 Stirling Hwy, Nedlands, WA 6009, Australia.
   [Zeps, Nikolajs] St John God Pathol, 12 Salvado Rd, Subiaco, WA 6008, Australia.
   [Jamieson, Nigel B.] Univ Glasgow, Glasgow Royal Infirm, Coll Med Vet & Life Sci, Sch Med,Acad Unit Surg, Glasgow G4 OSF, Lanark, Scotland.
   [Jamieson, Nigel B.; Biankin, Andrew V.] Glasgow Royal Infirm, West Scotland Pancreat Unit, Glasgow G31 2ER, Lanark, Scotland.
   [Graham, Janet S.] Beatson West Scotland Canc Ctr, Dept Med Oncol, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
   [Duthie, Fraser; Oien, Karin] Greater Glasgow & Clyde NHS, So Gen Hosp, Dept Pathol, Glasgow G51 4TF, Lanark, Scotland.
   [Hair, Jane] So Gen Hosp, Dept Pathol, GGC Biorepository, 1345 Govan Rd, Glasgow G51 4TY, Lanark, Scotland.
   [Gruetzmann, Robert; Pilarsky, Christian] Tech Univ Dresden, Dept Surg, Fetscherstr 74, D-01307 Dresden, Germany.
   [Maitra, Anirban] UT MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Maitra, Anirban] UT MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
   [Iacobuzio-Donahue, Christine A.] Mem Sloan Kettering Canc Ctr, David M Rubenstein Pancreat Canc Res Ctr, New York, NY 10065 USA.
   [Iacobuzio-Donahue, Christine A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Wolfgang, Christopher L.; Morgan, Richard A.; Eshleman, James R.; Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA.
   [Wolfgang, Christopher L.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21231 USA.
   [Lawlor, Rita T.; Corbo, Vincenzo; Rusev, Borislav; Scarpa, Aldo] Univ & Hosp Trust Verona, ARC Net Appl Res Canc Ctr, I-37134 Verona, Italy.
   [Lawlor, Rita T.; Capelli, Paola; Scarpa, Aldo] Univ Verona, Dept Pathol & Diagnost, I-37134 Verona, Italy.
   [Bassi, Claudio; Salvia, Roberto] Univ & Hosp Trust Verona, Pancreas Inst, Dept Surg, I-37134 Verona, Italy.
   [Tortora, Giampaolo] Univ & Hosp Trust Verona, Ctr Comprehens Canc, Dept Med Oncol, I-37134 Verona, Italy.
   [Mukhopadhyay, Debabrata; Petersen, Gloria M.] Mayo Clin, Rochester, MN 55905 USA.
   [Fisher, William E.] Baylor Coll Med, Elkins Pancreas Ctr, One Baylor Plaza,MS226, Houston, TX 77030 USA.
   [Karim, Saadia A.; Morton, Jennifer R.; Sansom, Owen J.] Canc Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland.
   [Sansom, Owen J.] Univ Glasgow, Inst Canc Sci, Glasgow G12 8QQ, Lanark, Scotland.
   [Grimmond, Sean M.] Univ Melbourne, Melbourne, Vic 3010, Australia.
   [Gruetzmann, Robert] Univ Klinikum Erlangen, Dept Surg, D-91054 Erlangen, Germany.
C3 University of Queensland; University of Glasgow; The Kinghorn Cancer Centre; Garvan Institute of Medical Research; NSW Health; Bankstown Lidcombe Hospital; University of Liverpool; QIMR Berghofer Medical Research Institute; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Utah System of Higher Education; University of Utah; SA Pathology; Adelaide University; University of Adelaide; Harvard University; Harvard T.H. Chan School of Public Health; NSW Health; Campbelltown Hospital; NSW Health; St Vincents Hospital Sydney; University of New South Wales Sydney; University of Newcastle; Royal North Shore Hospital; University of Sydney; University of Sydney; NSW Health; Royal Prince Alfred Hospital; University of Sydney; Western Sydney University; South Metropolitan Health Service; Fiona Stanley Fremantle Hospitals Group; Fiona Stanley Hospital; Royal Adelaide Hospital; Princess Alexandra Hospital; University of Western Australia; St John of God Health Care; University of Glasgow; University of Glasgow; Beatson Oncology Centre; University of Glasgow; University of Glasgow; Technische Universitat Dresden; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Johns Hopkins University; Johns Hopkins University; University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; University of Verona; University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; Mayo Clinic; Baylor College of Medicine; Beatson Institute; University of Glasgow; University of Melbourne; University of Erlangen Nuremberg
RP Grimmond, SM (corresponding author), Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4072, Australia.; Biankin, AV; Grimmond, SM (corresponding author), Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.; Biankin, AV (corresponding author), Kinghorn Canc Ctr, 370 Victoria St, Darlinghurst, NSW 2010, Australia.; Biankin, AV (corresponding author), Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Sydney, NSW 2010, Australia.; Biankin, AV (corresponding author), Bankstown Hosp, Dept Surg, Eldridge Rd, Sydney, NSW 2200, Australia.; Biankin, AV (corresponding author), Univ New S Wales, Fac Med, South Western Sydney Clin Sch, Liverpool, Merseyside 2170, England.; Biankin, AV (corresponding author), Glasgow Royal Infirm, West Scotland Pancreat Unit, Glasgow G31 2ER, Lanark, Scotland.; Grimmond, SM (corresponding author), Univ Melbourne, Melbourne, Vic 3010, Australia.
EM andrew.biankin@glasgow.ac.uk; sean.grimmond@unimelb.edu.au
FU National Health and Medical Research Council of Australia (NHMRC) [631701, 535903, 427601]; Queensland Government (NIRAP); University of Queensland; Australian Government: Department of Innovation, Industry, Science and Research (DIISR); Australian Cancer Research Foundation (ACRF); Cancer Council NSW [SRP06-01, SRP11-01. ICGC]; Cancer Institute NSW [10/ECF/2-26, 06/ECF/1-24, 09/CDF/2-40, 07/CDF/1-03, 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26, 10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26]; Garvan Institute of Medical Research; Cancer Research UK Glasgow Centre Program [A18076]; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Philip Hemstritch Foundation; Gastroenterological Society of Australia (GESA); American Association for Cancer Research (AACR) Landon Foundation-INNOVATOR Award; Wellcome Trust Senior Investigator Award [103721/Z/14/Z]; Cancer Research UK Programme Grant [C29717/A17263, A12481]; Pancreatic Cancer UK; Howat Foundation; University of Glasgow; European Research Council Starting Grant [311301]; Italian Ministry of University and Research (Cancer Genome Project) [FIRB RBAP10AHJB]; Associazione Italiana Ricerca Cancro [12182]; Fondazione Italiana Malattie Pancreas - Ministry of Health [CUP_J33G13000210001]; European Community Grant FP7 Cam-Pac [602783]; MRC [MR/N005813/1] Funding Source: UKRI; Academy of Medical Sciences (AMS) [AMS-SGCL9-Jamieson] Funding Source: researchfish; Cancer Research UK [11650, 17263, 22533, 12946] Funding Source: researchfish; Medical Research Council [MR/N005813/1] Funding Source: researchfish; Pancreatic Cancer UK [RIF2015_A06_Jamieson] Funding Source: researchfish; Versus Arthritis; Cancer Research UK [20409, 21139] Funding Source: researchfish; Wellcome Trust [103721/Z/14/Z] Funding Source: researchfish; Wellcome Trust [103721/Z/14/Z] Funding Source: Wellcome Trust; National Cancer Institute [P50CA062924] Funding Source: NIH RePORTER; National Health and Medical Research Council (NHMRC) [427601] Funding Source: National Health and Medical Research Council (NHMRC)
NR 50
TC 2794
Z9 3181
U1 13
U2 657
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 47
EP +
DI 10.1038/nature16965
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900037
PM 26909576
DA 2026-03-09
ER

PT J
AU Facon, A
   Dietsche, EK
   Grosso, D
   Haroche, S
   Raimond, JM
   Brune, M
   Gleyzes, S
AF Facon, Adrien
   Dietsche, Eva-Katharina
   Grosso, Dorian
   Haroche, Serge
   Raimond, Jean-Michel
   Brune, Michel
   Gleyzes, Sebastien
TI A sensitive electrometer based on a Rydberg atom in a Schrodinger-cat state
SO NATURE
LA English
DT Article
ID standard quantum limit; entanglement; oscillator; motion
AB Fundamental quantum fluctuations caused by the Heisenberg principle limit measurement precision(1). If the uncertainty is distributed equally between conjugate variables of the meter system, the measurement precision cannot exceed the standard quantum limit. When the meter is a large angular momentum, going beyond the standard quantum limit requires non-classical states such as squeezed states(2-4) or Schrodinger-cat-like states(5-7). However, the metrological use of the latter(8-10) has been so far restricted to meters with a relatively small total angular momentum because the experimental preparation of these non-classical states is very challenging(11,12). Here we report a measurement of an electric field based on an electrometer consisting of a large angular momentum (quantum number J approximate to 25) carried by a single atom in a high-energy Rydberg state. We show that the fundamental Heisenberg limit(13) can be approached when the Rydberg atom undergoes a non-classical evolution through Schrodinger-cat states. Using this method, we reach a single-shot sensitivity of 1.2 millivolts per centimetre for a 100-nanosecond interaction time, corresponding to 30 microvolts per centimetre per square root hertz at our 3 kilohertz repetition rate. This highly sensitive, non-invasive space-and time-resolved field measurement extends the realm of electrometric techniques(14-17) and could have important practical applications: detection of individual electrons in mesoscopic devices(18-21) at a distance of about 100 micrometres with a megahertz bandwidth is within reach.
C1 [Facon, Adrien; Dietsche, Eva-Katharina; Grosso, Dorian; Haroche, Serge; Raimond, Jean-Michel; Brune, Michel; Gleyzes, Sebastien] UPMC, Univ Paris 04, ENS PSL Res Univ, Lab Kastler Brossel,Coll France,CNRS, 11 Pl Marcelin Berthelot, F-75231 Paris 05, France.
C3 Sorbonne Universite; Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS)
RP Gleyzes, S (corresponding author), UPMC, Univ Paris 04, ENS PSL Res Univ, Lab Kastler Brossel,Coll France,CNRS, 11 Pl Marcelin Berthelot, F-75231 Paris 05, France.
EM gleyzes@lkb.ens.fr
FU EU under ERC project 'DECLIC'; EU under RIA project 'RYSQ'
NR 35
TC 186
Z9 213
U1 2
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 262
EP +
DI 10.1038/nature18327
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600052
PM 27411632
DA 2026-03-09
ER

PT J
AU Lyons, SK
   Amatangelo, KL
   Behrenstneyer, AK
   Bercovici, A
   Blois, JL
   Davis, M
   DiMichele, WA
   Du, A
   Eronen, JT
   Faith, JT
   Graves, GR
   Jud, N
   Labandeira, C
   Looy, CM
   McGill, B
   Miller, JH
   Patterson, D
   Pineda-Munoz, S
   Potts, R
   Riddle, B
   Terry, R
   Tóth, A
   Ulrich, W
   Villaseñor, A
   Wing, S
   Anderson, H
   Anderson, J
   Waller, D
   Gotelli, NJ
AF Lyons, S. Kathleen
   Amatangelo, Kathryn L.
   Behrenstneyer, Anna K.
   Bercovici, Antoine
   Blois, Jessica L.
   Davis, Matt
   DiMichele, William A.
   Du, Andrew
   Eronen, Jussi T.
   Faith, J. Tyler
   Graves, Gary R.
   Jud, Nathan
   Labandeira, Conrad
   Looy, Cindy M.
   McGill, Brian
   Miller, Joshua H.
   Patterson, David
   Pineda-Munoz, Silvia
   Potts, Richard
   Riddle, Brett
   Terry, Rebecca
   Toth, Aniko
   Ulrich, Werner
   Villasenor, Amelia
   Wing, Scott
   Anderson, Heidi
   Anderson, John
   Waller, Donald
   Gotelli, Nicholas J.
TI Holocene shifts in the assembly of plant and animal communities implicate human impacts
SO NATURE
LA English
DT Article
ID null model analysis; species cooccurrence; associations; quaternary; dispersal; record
AB Understanding how ecological communities are organized and how they change through time is critical to predicting the effects of climate change(1). Recent work documenting the co-occurrence structure of modern communities found that most significant species pairs co-occur less frequently than would be expected by chance(2,3). However, little is known about how co-occurrence structure changes through time. Here we evaluate changes in plant and animal community organization over geological time by quantifying the co-occurrence structure of 359,896 unique taxon pairs in 80 assemblages spanning the past 300 million years. Co-occurrences of most taxon pairs were statistically random, but a significant fraction were spatially aggregated or segregated. Aggregated pairs dominated from the Carboniferous period (307 million years ago) to the early Holocene epoch (11,700 years before present), when there was a pronounced shift to more segregated pairs, a trend that continues in modern assemblages. The shift began during the Holocene and coincided with increasing human population size(4,5) and the spread of agriculture in North America(6,7). Before the shift, an average of 64% of significant pairs were aggregated; after the shift, the average dropped to 37%. The organization of modern and late Holocene plant and animal assemblages differs fundamentally from that of assemblages over the past 300 million years that predate the large-scale impacts of humans. Our results suggest that the rules governing the assembly of communities have recently been changed by human activity.
C1 [Lyons, S. Kathleen; Behrenstneyer, Anna K.; Bercovici, Antoine; Davis, Matt; DiMichele, William A.; Labandeira, Conrad; Toth, Aniko; Wing, Scott] Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA.
   [Amatangelo, Kathryn L.] SUNY Coll Brockport, Dept Environm Sci & Biol, Brockport, NY 14420 USA.
   [Blois, Jessica L.] Univ Calif Merced, Sch Nat Sci, 5200 North Lake Rd, Merced, CA 95343 USA.
   [Davis, Matt] Yale Univ, Dept Geol & Geophys, POB 6666, New Haven, CT 06520 USA.
   [Du, Andrew; Patterson, David; Villasenor, Amelia] George Washington Univ, Dept Anthropol, Ctr Adv Study Hominid Paleobiol, Hominid Paleobiol Doctoral Program, Washington, DC 20052 USA.
   [Eronen, Jussi T.] Univ Helsinki, Dept Geosci & Geog, POB 64, FIN-00014 Helsinki, Finland.
   [Faith, J. Tyler] Univ Queensland, Sch Social Sci, Brisbane, Qld 4072, Australia.
   [Graves, Gary R.] Smithsonian Inst, Natl Museum Nat Hist, Dept Vertebrate Zool, Washington, DC 20013 USA.
   [Graves, Gary R.] Univ Copenhagen, Ctr Macroecol Evolut & Climate, DK-2100 Copenhagen, Denmark.
   [Jud, Nathan] Univ Maryland, Biol Sci Grad Program, College Pk, MD 20742 USA.
   [Jud, Nathan] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [Labandeira, Conrad] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Labandeira, Conrad] Capital Normal Univ, Key Lab Insect Evolut & Environm Changes, Beijing 100048, Peoples R China.
   [Looy, Cindy M.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Looy, Cindy M.] Univ Calif Berkeley, Museum Paleontol, Berkeley, CA 94720 USA.
   [McGill, Brian] Univ Maine, Sch Biol & Ecol, Orono, ME 04469 USA.
   [McGill, Brian] Univ Maine, Sustainabil Solut Initiat, Orono, ME 04469 USA.
   [Miller, Joshua H.] Univ Cincinnati, Dept Geol, Cincinnati, OH 45221 USA.
   [Pineda-Munoz, Silvia] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [Potts, Richard] Smithsonian Inst, Natl Museum Nat Hist, Human Origins Program, Dept Anthropol, Washington, DC 20013 USA.
   [Riddle, Brett] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA.
   [Terry, Rebecca] Oregon State Univ, Dept Integrat Biol, Corvallis, OR 97331 USA.
   [Ulrich, Werner] Nicholas Copernicus Univ, Chair Ecol & Biogeog, Lwowska 1, PL-87100 Torun, Poland.
   [Anderson, Heidi; Anderson, John] Univ Witwatersrand, Evolutionary Studies Inst, Jorissen St, ZA-2001 Johannesburg, South Africa.
   [Waller, Donald] Univ Wisconsin, Dept Bot, Madison, WI 53706 USA.
   [Gotelli, Nicholas J.] Univ Vermont, Dept Biol, Burlington, VT 05405 USA.
C3 Smithsonian Institution; Smithsonian National Museum of Natural History; State University of New York (SUNY) System; State University of New York (SUNY) Brockport; University of California System; University of California Merced; Yale University; George Washington University; University of Helsinki; University of Queensland; Smithsonian Institution; Smithsonian National Museum of Natural History; University of Copenhagen; University System of Maryland; University of Maryland College Park; State University System of Florida; University of Florida; University System of Maryland; University of Maryland College Park; Capital Normal University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Maine System; University of Maine Orono; University of Maine System; University of Maine Orono; University System of Ohio; University of Cincinnati; Macquarie University; Smithsonian Institution; Smithsonian National Museum of Natural History; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; Oregon State University; Nicolaus Copernicus University; University of Witwatersrand; University of Wisconsin System; University of Wisconsin Madison; University of Vermont
RP Lyons, SK (corresponding author), Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA.
EM lyonss2@si.edu
FU National Museum of Natural History Program grant [NSF-DEB 1257625]; Direct For Biological Sciences; Division Of Environmental Biology [1257033] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1046355, 1257625] Funding Source: National Science Foundation
NR 39
TC 145
Z9 165
U1 0
U2 153
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 80
EP U183
DI 10.1038/nature16447
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900030
PM 26675730
DA 2026-03-09
ER

PT J
AU Brune, S
   Williams, SE
   Butterworth, NP
   Müller, RD
AF Brune, Sascha
   Williams, Simon E.
   Butterworth, Nathaniel P.
   Mueller, R. Dietmar
TI Abrupt plate accelerations shape rifted continental margins
SO NATURE
LA English
DT Article
ID gulf-of-california; south china sea; tectonic evolution; central atlantic; break-up; basin; transition; mantle; ocean; north
AB Rifted margins are formed by persistent stretching of continental lithosphere until breakup is achieved. It is well known that strain-rate-dependent processes control rift evolution(1,2), yet quantified extension histories of Earth's major passive margins have become available only recently. Here we investigate rift kinematics globally by applying a new geotectonic analysis technique to revised global plate reconstructions. We find that rifted margins feature an initial, slow rift phase (less than ten millimetres per year, full rate) and that an abrupt increase of plate divergence introduces a fast rift phase. Plate acceleration takes place before continental rupture and considerable margin area is created during each phase. We reproduce the rapid transition from slow to fast extension using analytical and numerical modelling with constant force boundary conditions. The extension models suggest that the two-phase velocity behaviour is caused by a rift-intrinsic strength-velocity feedback, which can be robustly inferred for diverse lithosphere configurations and rheologies. Our results explain differences between proximal and distal margin areas(3) and demonstrate that abrupt plate acceleration during continental rifting is controlled by the nonlinear decay of the resistive rift strength force. This mechanism provides an explanation for several previously unexplained rapid absolute plate motion changes, offering new insights into the balance of plate driving forces through time.
C1 [Brune, Sascha] GFZ German Res Ctr Geosci, D-14473 Potsdam, Germany.
   [Brune, Sascha; Williams, Simon E.; Butterworth, Nathaniel P.; Mueller, R. Dietmar] Univ Sydney, Sch Geosci, EarthByte Res Grp, Sydney, NSW 2006, Australia.
C3 Helmholtz Association; GFZ Helmholtz Centre for Geosciences; University of Sydney
RP Brune, S (corresponding author), GFZ German Res Ctr Geosci, D-14473 Potsdam, Germany.; Brune, S (corresponding author), Univ Sydney, Sch Geosci, EarthByte Res Grp, Sydney, NSW 2006, Australia.
EM sascha.brune@gfz-potsdam.de
FU Marie Curie International Outgoing Fellowship [326115]; German Research Foundation Priority Program 1375 SAMPLE; Helmholtz Young Investigators Group CRYSTALS; Science and Industry Endowment Fund project [RP 04-174]; Australian Research Council [IH130200012]
NR 70
TC 178
Z9 197
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 201
EP +
DI 10.1038/nature18319
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100034
PM 27437571
DA 2026-03-09
ER

PT J
AU Liu, Z
   Li, X
   Zhang, JT
   Cai, YJ
   Cheng, TL
   Cheng, C
   Wang, Y
   Zhang, CC
   Nie, YH
   Chen, ZF
   Bian, WJ
   Zhang, L
   Xiao, JQ
   Lu, B
   Zhang, YF
   Zhang, XD
   Sang, X
   Wu, JJ
   Xu, X
   Xiong, ZQ
   Zhang, F
   Yu, X
   Gong, N
   Zhou, WH
   Sun, Q
   Qiu, ZL
AF Liu, Zhen
   Li, Xiao
   Zhang, Jun-Tao
   Cai, Yi-Jun
   Cheng, Tian-Lin
   Cheng, Cheng
   Wang, Yan
   Zhang, Chen-Chen
   Nie, Yan-Hong
   Chen, Zhi-Fang
   Bian, Wen-Jie
   Zhang, Ling
   Xiao, Jianqiu
   Lu, Bin
   Zhang, Yue-Fang
   Zhang, Xiao-Di
   Sang, Xiao
   Wu, Jia-Jia
   Xu, Xiu
   Xiong, Zhi-Qi
   Zhang, Feng
   Yu, Xiang
   Gong, Neng
   Zhou, Wen-Hao
   Sun, Qiang
   Qiu, Zilong
TI Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2
SO NATURE
LA English
DT Article
ID macaque macaca-fascicularis; transcriptional repressor; nonhuman-primates; rhesus-monkeys; generation; cynomolgus; amygdala; infant; disease; anxiety
AB Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing(1-4). Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes(5). Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders(6). Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression(7,8). Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test(9). The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F-1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F-0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F-1 progeny. Moreover, F-1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.
C1 [Liu, Zhen; Li, Xiao; Zhang, Jun-Tao; Cai, Yi-Jun; Cheng, Tian-Lin; Cheng, Cheng; Wang, Yan; Zhang, Chen-Chen; Nie, Yan-Hong; Chen, Zhi-Fang; Bian, Wen-Jie; Lu, Bin; Zhang, Yue-Fang; Zhang, Xiao-Di; Sang, Xiao; Wu, Jia-Jia; Xiong, Zhi-Qi; Yu, Xiang; Gong, Neng; Sun, Qiang; Qiu, Zilong] Chinese Acad Sci, CAS Key Lab Primate Neurobiol, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci,State Key Lab Neurosci,Shanghai Ins, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
   [Zhang, Ling; Xiao, Jianqiu; Zhang, Feng] Fudan Univ, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
   [Zhang, Ling; Xiao, Jianqiu; Zhang, Feng] Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, Collaborat Innovat Ctr Genet & Dev,Sch Life Sci, Shanghai 200438, Peoples R China.
   [Xu, Xiu] Fudan Univ, Childrens Hosp, Dept Child Healthcare, Shanghai 201102, Peoples R China.
   [Zhou, Wen-Hao] Fudan Univ, Childrens Hosp, Dept Neonatol, Shanghai 201102, Peoples R China.
C3 Chinese Academy of Sciences; Center for Excellence in Brain Science and Intelligence Technology, CAS; Fudan University; Fudan University; Fudan University; Fudan University
RP Sun, Q; Qiu, ZL (corresponding author), Chinese Acad Sci, CAS Key Lab Primate Neurobiol, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci,State Key Lab Neurosci,Shanghai Ins, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
EM qsun@ion.ac.cn; zqiu@ion.ac.cn
FU CAS Strategic Priority Research Program [XDB02050400]; MoST 973 Program [2011CBA00400]; NSFC [91432111, 91232712, 81527901]; National Key Technology R&D Program of China [2014BAI03B00]; Shanghai City Committee of Science and Technology Project [14140900100]
NR 44
TC 255
Z9 297
U1 1
U2 231
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 98
EP +
DI 10.1038/nature16533
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500040
PM 26808898
DA 2026-03-09
ER

PT J
AU Kleinstiver, BP
   Pattanayak, V
   Prew, MS
   Tsai, SQ
   Nguyen, NT
   Zheng, ZL
   Joung, JK
AF Kleinstiver, Benjamin P.
   Pattanayak, Vikram
   Prew, Michelle S.
   Tsai, Shengdar Q.
   Nguyen, Nhu T.
   Zheng, Zongli
   Joung, J. Keith
TI High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
SO NATURE
LA English
DT Article
ID rna-guided endonuclease; crispr/cas9 systems; dual-rna; cas9; dna; specificity; cleavage; talens; interrogation; complex
AB CRISPR-Cas9 nucleases are widely used for genome editing but can induce unwanted off-target mutations. Existing strategies for reducing genome-wide off-target effects of the widely used Streptococcus pyogenes Cas9 (SpCas9) are imperfect, possessing only partial or unproven efficacies and other limitations that constrain their use. Here we describe SpCas9-HF1, a high-fidelity variant harbouring alterations designed to reduce non-specific DNA contacts. SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with > 85% of single-guide RNAs (sgRNAs) tested in human cells. Notably, with sgRNAs targeted to standard non-repetitive sequences, SpCas9-HF1 rendered all or nearly all off-target events undetectable by genome-wide break capture and targeted sequencing methods. Even for atypical, repetitive target sites, the vast majority of off-target mutations induced by wild-type SpCas9 were not detected with SpCas9-HF1. With its exceptional precision, SpCas9-HF1 provides an alternative to wild-type SpCas9 for research and therapeutic applications. More broadly, our results suggest a general strategy for optimizing genome-wide specificities of other CRISPR-RNA-guided nucleases.
C1 [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.
   [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA.
   [Kleinstiver, Benjamin P.; Pattanayak, Vikram; Tsai, Shengdar Q.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Zheng, Zongli] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; City University of Hong Kong
RP Joung, JK (corresponding author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.; Joung, JK (corresponding author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA.; Joung, JK (corresponding author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM jjoung@mgh.harvard.edu
FU Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship; Massachusetts General Hospital (MGH) Department of Pathology; MGH Tosteson; Fund for Medical Discovery Fellowship; US National Institutes of Health (NIH) Director's Pioneer Award [DP1 GM105378]; NIH [R01 GM107427, R01 GM088040]; Jim and Ann Orr MGH Research Scholar Award
NR 45
TC 2068
Z9 2790
U1 22
U2 893
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 490
EP +
DI 10.1038/nature16526
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800029
PM 26735016
DA 2026-03-09
ER

PT J
AU Howe, MW
   Dombeck, DA
AF Howe, M. W.
   Dombeck, D. A.
TI Rapid signalling in distinct dopaminergic axons during locomotion and reward
SO NATURE
LA English
DT Article
AB Dopaminergic projection axons from the midbrain to the striatum are crucial for motor control, as their degeneration in Parkinson disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signalling (similar to 100-ms bursts) in response to unpredicted rewards, with little evidence for movement-related signalling. The leading model posits that phasic signalling in striatum-targeting dopamine neurons drives reward-based learning, whereas slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, current methods have provided little evidence to support or refute this model. Here, using new optical recording methods, we report the discovery of rapid phasic signalling in striatum-targeting dopaminergic axons that is associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those that responded to unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision, and indicate that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders.
C1 [Howe, M. W.; Dombeck, D. A.] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
C3 Northwestern University
RP Howe, MW (corresponding author), Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
EM markhowe72@gmail.com; d-dombeck@northwestern.edu
FU Klingenstein Foundation; McKnight Foundation; Whitehall Foundation; Chicago Biomedical Consortium; Searle Funds at Chicago Community Trust; Northwestern University; National Institutes of Health [T32 AG20506]; National Institute of Mental Health [R01MH101297] Funding Source: NIH RePORTER; National Institute on Aging [T32AG020506] Funding Source: NIH RePORTER
NR 57
TC 427
Z9 540
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 505
EP 510
DI 10.1038/nature18942
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600040
PM 27398617
DA 2026-03-09
ER

PT J
AU Liu, X
   Zhang, ZB
   Ruan, JB
   Pan, YD
   Magupalli, VG
   Wu, H
   Lieberman, J
AF Liu, Xing
   Zhang, Zhibin
   Ruan, Jianbin
   Pan, Youdong
   Magupalli, Venkat Giri
   Wu, Hao
   Lieberman, Judy
TI Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
SO NATURE
LA English
DT Article
ID mixed lineage kinase; listeria-monocytogenes; intracellular bacteria; caspase-1 activation; nlrp3 inflammasome; cell-death; interleukin-1-beta; granulysin; granzymes; perforin
AB Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1 beta(1,2). Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined.
C1 [Liu, Xing; Zhang, Zhibin; Ruan, Jianbin; Magupalli, Venkat Giri; Wu, Hao; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Liu, Xing; Zhang, Zhibin; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Ruan, Jianbin; Magupalli, Venkat Giri; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Pan, Youdong] Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA.
   [Pan, Youdong] Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, 75 Francis St, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Wu, H; Lieberman, J (corresponding author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Lieberman, J (corresponding author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.; Wu, H (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM wu@crystal.harvard.edu; judy.lieberman@childrens.harvard.edu
FU US NIH [R01AI123265]; National Institute of Allergy and Infectious Diseases [R01AI124491] Funding Source: NIH RePORTER
NR 29
TC 2565
Z9 2952
U1 14
U2 554
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 153
EP +
DI 10.1038/nature18629
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600043
PM 27383986
DA 2026-03-09
ER

PT J
AU Kunstler, G
   Falster, D
   Coomes, DA
   Hui, F
   Kooyman, RM
   Laughlin, DC
   Poorter, L
   Vanderwel, M
   Vieilledent, G
   Wright, SJ
   Aiba, M
   Baraloto, C
   Caspersen, J
   Cornelissen, JHC
   Gourlet-Fleury, S
   Hanewinkel, M
   Herault, B
   Kattge, J
   Kurokawa, H
   Onoda, Y
   Peñuelas, J
   Poorter, H
   Uriarte, M
   Richardson, S
   Ruiz-Benito, P
   Sun, IF
   Ståhl, G
   Swenson, NG
   Thompson, J
   Westerlund, B
   Wirth, C
   Zavala, MA
   Zeng, HC
   Zimmerman, JK
   Zimmermann, NE
   Westoby, M
AF Kunstler, Georges
   Falster, Daniel
   Coomes, David A.
   Hui, Francis
   Kooyman, Robert M.
   Laughlin, Daniel C.
   Poorter, Lourens
   Vanderwel, Mark
   Vieilledent, Ghislain
   Wright, S. Joseph
   Aiba, Masahiro
   Baraloto, Christopher
   Caspersen, John
   Cornelissen, J. Hans C.
   Gourlet-Fleury, Sylvie
   Hanewinkel, Marc
   Herault, Bruno
   Kattge, Jens
   Kurokawa, Hiroko
   Onoda, Yusuke
   Penuelas, Josep
   Poorter, Hendrik
   Uriarte, Maria
   Richardson, Sarah
   Ruiz-Benito, Paloma
   Sun, I-Fang
   Stahl, Goeran
   Swenson, Nathan G.
   Thompson, Jill
   Westerlund, Bertil
   Wirth, Christian
   Zavala, Miguel A.
   Zeng, Hongcheng
   Zimmerman, Jess K.
   Zimmermann, Niklaus E.
   Westoby, Mark
TI Plant functional traits have globally consistent effects on competition
SO NATURE
LA English
DT Article
ID hawaiian metrosideros-polymorpha; leaf dry mass; wide-range; elevated co2; wood density; quercus-ilex; long-term; phosphorus stoichiometry; photosynthetic capacity; litter decomposability
AB Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions(1-3), but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear (4). Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits-wood density, specific leaf area and maximum height-consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies(5). Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.
C1 [Kunstler, Georges] Irstea, UR EMGR, F-38402 St Martin Dheres, France.
   [Kunstler, Georges] Univ Grenoble Alpes, F-38402 Grenoble, France.
   [Kunstler, Georges; Falster, Daniel; Kooyman, Robert M.; Westoby, Mark] Macquarie Univ, Dept Biol Sci, N Ryde, NSW 2109, Australia.
   [Coomes, David A.] Univ Cambridge, Dept Plant Sci, Forest Ecol & Conservat Grp, Cambridge CB2 3EA, England.
   [Hui, Francis] Australian Natl Univ, Inst Math Sci, Canberra, ACT 0200, Australia.
   [Kooyman, Robert M.] Royal Bot Gardens & Domain Trust, Natl Herbarium New South Wales, Sydney, NSW 2000, Australia.
   [Laughlin, Daniel C.] Univ Waikato, Environm Res Inst, Sch Sci, Hamilton 3240, New Zealand.
   [Poorter, Lourens] Wageningen Univ, Forest Ecol & Forest Management Grp, NL-6708 PB Wageningen, Netherlands.
   [Vanderwel, Mark] Univ Regina, Dept Biol, Regina, SK S4S 0A2, Canada.
   [Vieilledent, Ghislain; Gourlet-Fleury, Sylvie] Cirad, UPR BSEF, F-34398 Montpellier, France.
   [Wright, S. Joseph] Smithsonian Trop Res Inst, Balboa, Panama.
   [Aiba, Masahiro; Kurokawa, Hiroko] Tohoku Univ, Sch Life Sci, Sendai, Miyagi 9808578, Japan.
   [Baraloto, Christopher] INRA, UMR Ecol Forets Guyane, F-97387 Kourou, France.
   [Baraloto, Christopher] Florida Int Univ, Dept Biol Sci, Int Ctr Trop Bot, Miami, FL 33199 USA.
   [Caspersen, John; Zeng, Hongcheng] Univ Toronto, Fac Forestry, Toronto, ON M5S 3B3, Canada.
   [Caspersen, John; Zimmermann, Niklaus E.] Swiss Fed Res Inst WSL, Landscape Dynam Unit, CH-8903 Birmensdorf, Switzerland.
   [Cornelissen, J. Hans C.] Vrije Univ, Dept Ecol Sci, Syst Ecol, NL-1081 HV Amsterdam, Netherlands.
   [Hanewinkel, Marc] Swiss Fed Res Inst WSL, Forest Resources & Management Unit, CH-8903 Birmensdorf, Switzerland.
   [Hanewinkel, Marc] Univ Freiburg, Chair Forestry Econ & Planning, D-79106 Freiburg, Germany.
   [Herault, Bruno] Cirad, UMR Ecol Forets Guyane, F-97387 Kourou, France.
   [Kattge, Jens] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Kattge, Jens; Wirth, Christian] German Ctr Integrat Biodivers Res iDiv, D-04103 Leipzig, Germany.
   [Onoda, Yusuke] Kyoto Univ, Sch Agr, Kyoto 6068502, Japan.
   [Penuelas, Josep] UAB, CSIC, CREAF, Global Ecol Unit, Catalonia 08193, Spain.
   [Penuelas, Josep] CREAF, Barcelona 08193, Catalonia, Spain.
   [Poorter, Hendrik] Forschungszentrum Julich GmbH, Plant Sci IBG 2, D-52425 Julich, Germany.
   [Uriarte, Maria] Columbia Univ, Dept Ecol Evolut & Environm Biol, New York, NY 10027 USA.
   [Richardson, Sarah] Landcare Res, Lincoln 7640, New Zealand.
   [Ruiz-Benito, Paloma] Univ Stirling, Sch Nat Sci, Biol & Environm Sci, Stirling FK9 4LA, Scotland.
   [Ruiz-Benito, Paloma; Zavala, Miguel A.] Univ Alcala, Dept Life Sci, Forest Ecol & Restorat Grp, Alcala De Henares 28805, Madrid, Spain.
   [Sun, I-Fang] Natl Dong Hwa Univ, Dept Nat Resources & Environm Studies, Hualien 97401, Taiwan.
   [Stahl, Goeran; Westerlund, Bertil] Swedish Univ Agr Sci SLU, Dept Forest Resource Management, S-90183 Umea, Sweden.
   [Swenson, Nathan G.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Thompson, Jill] Ctr Ecol & Hydrol, Penicuik EH26 0QB, Midlothian, Scotland.
   [Thompson, Jill; Zimmerman, Jess K.] Univ Puerto Rico, Dept Environm Sci, San Juan, PR 00936 USA.
   [Wirth, Christian] Univ Leipzig, Inst Systemat Bot & Funct Biodivers, D-04103 Leipzig, Germany.
C3 INRAE; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Macquarie University; University of Cambridge; Australian National University; University of Waikato; Wageningen University & Research; University of Regina; CIRAD; Smithsonian Institution; Smithsonian Tropical Research Institute; Tohoku University; AgroParisTech; CIRAD; Centre National de la Recherche Scientifique (CNRS); Universite des Antilles; INRAE; State University System of Florida; Florida International University; University of Toronto; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Vrije Universiteit Amsterdam; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Freiburg; AgroParisTech; CIRAD; Centre National de la Recherche Scientifique (CNRS); Universite des Antilles; Max Planck Society; German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); Kyoto University; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Helmholtz Association; Julich Research Centre; Columbia University; Landcare Research - New Zealand; University of Stirling; Universidad de Alcala; National Dong Hwa University; Swedish University of Agricultural Sciences; University System of Maryland; University of Maryland College Park; UK Centre for Ecology & Hydrology (UKCEH); University of Puerto Rico; University of Puerto Rico Rio Piedras; Leipzig University
RP Kunstler, G (corresponding author), Irstea, UR EMGR, 2 Rue Papeterie BP 76, F-38402 St Martin Dheres, France.
EM georges.kunstler@irstea.fr
FU CEBA [ANR-10-LABX-25-01]; IGBP; DIVERSITAS; GLP; NERC; QUEST; FRB; GIS Climate; Marie Curie International Outgoing Fellowship within European Community [299340]; Macquarie University; Australian Research Council; Grants-in-Aid for Scientific Research [26660126, 26711025] Funding Source: KAKEN; Division Of Environmental Biology; Direct For Biological Sciences [1546686] Funding Source: National Science Foundation; Natural Environment Research Council [ceh020002] Funding Source: researchfish; NERC [ceh020002] Funding Source: UKRI
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   Adams TP, 2007, P ROY SOC B-BIOL SCI, V274, P3039, DOI 10.1098/rspb.2007.0891
   Adler PB, 2013, ECOL LETT, V16, P1294, DOI 10.1111/ele.12157
   Aiba M, 2009, FUNCT ECOL, V23, P265, DOI 10.1111/j.1365-2435.2008.01500.x
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   Bagchi R, 2014, NATURE, V506, P85, DOI 10.1038/nature12911
   Baraloto C, 2010, ECOL LETT, V13, P1338, DOI 10.1111/j.1461-0248.2010.01517.x
   Bates D, 2014, NO TITLE CAPTURED, V0, P1
   Burnham KP, 1998, MODEL SELECTION MULT, V2nd, P0, DOI 10.1007/978-0-387-22456-5_5
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NR 129
TC 742
Z9 880
U1 56
U2 1316
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 204
EP U174
DI 10.1038/nature16476
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700035
PM 26700807
DA 2026-03-09
ER

PT J
AU Lin, CY
   Erkek, S
   Tong, YA
   Yin, LL
   Federation, AJ
   Zapatka, M
   Haldipur, P
   Kawauchi, D
   Risch, T
   Warnatz, HJ
   Worst, BC
   Ju, BS
   Orr, BA
   Zeid, R
   Polaski, DR
   Segura-Wang, M
   Waszak, SM
   Jones, DTW
   Kool, M
   Hovestadt, V
   Buchhalter, I
   Sieber, L
   Johann, P
   Chavez, L
   Gröschel, S
   Ryzhova, M
   Korshunov, A
   Chen, WB
   Chizhikov, VV
   Millen, KJ
   Amstislavskiy, V
   Lehrach, H
   Yaspo, ML
   Eils, R
   Lichter, P
   Korbel, JO
   Pfister, SM
   Bradner, JE
   Northcott, PA
AF Lin, Charles Y.
   Erkek, Serap
   Tong, Yiai
   Yin, Linlin
   Federation, Alexander J.
   Zapatka, Marc
   Haldipur, Parthiv
   Kawauchi, Daisuke
   Risch, Thomas
   Warnatz, Hans-Joerg
   Worst, Barbara C.
   Ju, Bensheng
   Orr, Brent A.
   Zeid, Rhamy
   Polaski, Donald R.
   Segura-Wang, Maia
   Waszak, Sebastian M.
   Jones, David T. W.
   Kool, Marcel
   Hovestadt, Volker
   Buchhalter, Ivo
   Sieber, Laura
   Johann, Pascal
   Chavez, Lukas
   Groeschel, Stefan
   Ryzhova, Marina
   Korshunov, Andrey
   Chen, Wenbiao
   Chizhikov, Victor V.
   Millen, Kathleen J.
   Amstislavskiy, Vyacheslav
   Lehrach, Hans
   Yaspo, Marie-Laure
   Eils, Roland
   Lichter, Peter
   Korbel, Jan O.
   Pfister, Stefan M.
   Bradner, James E.
   Northcott, Paul A.
TI Active medulloblastoma enhancers reveal subgroup-specific cellular origins
SO NATURE
LA English
DT Article
ID library preparation protocol; transcription factors; super-enhancers; identity; expression; landscape; oncogenes; rna
AB Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.
C1 [Lin, Charles Y.; Federation, Alexander J.; Zeid, Rhamy; Polaski, Donald R.; Bradner, James E.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02215 USA.
   [Erkek, Serap; Segura-Wang, Maia; Waszak, Sebastian M.; Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Erkek, Serap; Kawauchi, Daisuke; Worst, Barbara C.; Jones, David T. W.; Kool, Marcel; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Pfister, Stefan M.; Northcott, Paul A.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Tong, Yiai; Northcott, Paul A.] St Jude Childrens Res Hosp, Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Yin, Linlin; Chen, Wenbiao] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
   [Zapatka, Marc; Hovestadt, Volker; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Haldipur, Parthiv; Millen, Kathleen J.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98105 USA.
   [Risch, Thomas; Warnatz, Hans-Joerg; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany.
   [Ju, Bensheng] St Jude Childrens Res Hosp, Dept Bone Marrow Transplantat & Cellular Therapy, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Orr, Brent A.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Jones, David T. W.; Kool, Marcel; Lichter, Peter; Pfister, Stefan M.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
   [Buchhalter, Ivo; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Groeschel, Stefan] NCT Heidelberg, Dept Translat Oncol, D-69120 Heidelberg, Germany.
   [Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow 125047, Russia.
   [Korshunov, Andrey] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany.
   [Korshunov, Andrey] Univ Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Chizhikov, Victor V.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
   [Millen, Kathleen J.] Univ Washington, Div Genet, Dept Pediat, Seattle, WA 98195 USA.
   [Eils, Roland] Heidelberg Univ, Inst Pharm & Mol Biotechnol & BioQuant, D-69117 Heidelberg, Germany.
   [Pfister, Stefan M.] Heidelberg Univ, Dept Pediat, D-69117 Heidelberg, Germany.
   [Lin, Charles Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; European Molecular Biology Laboratory (EMBL); Helmholtz Association; German Cancer Research Center (DKFZ); St Jude Children's Research Hospital; Vanderbilt University; Helmholtz Association; German Cancer Research Center (DKFZ); Seattle Children's Hospital; Max Planck Society; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Russian Academy of Medical Sciences; N.N.Burdenko National Medical Research Center of Neurosurgery; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; University of Tennessee System; University of Tennessee Health Science Center; University of Washington; University of Washington Seattle; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Baylor College of Medicine
RP Bradner, JE (corresponding author), Dana Farber Canc Inst, Med Oncol, Boston, MA 02215 USA.; Northcott, PA (corresponding author), German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.; Pfister, SM (corresponding author), Heidelberg Univ, Dept Pediat, D-69117 Heidelberg, Germany.
EM s.pfister@dkfz-heidelberg.de; james_bradner@dfci.harvard.edu; paul.northcott@stjude.org
FU Human Frontiers Science Program [LT000432/2014]; SNSF [P2ELP3_155365]; EMBO Long-Term Fellowship [ALTF 755-2014]; US Department of Defense CDMRP [CA120184]; Swiss National Science Foundation (SNF) [P2ELP3_155365] Funding Source: Swiss National Science Foundation (SNF)
NR 55
TC 298
Z9 368
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 57
EP +
DI 10.1038/nature16546
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500031
PM 26814967
DA 2026-03-09
ER

PT J
AU Li, N
   Daie, K
   Svoboda, K
   Druckmann, S
AF Li, Nuo
   Daie, Kayvon
   Svoboda, Karel
   Druckmann, Shaul
TI Robust neuronal dynamics in premotor cortex during motor planning
SO NATURE
LA English
DT Article
ID short-term-memory; prefrontal cortex; neural-networks; working-memory; cortical activity; decision-making; movement; circuits; system; chaos
AB Neural activity maintains representations that bridge past and future events, often over many seconds. Network models can produce persistent and ramping activity, but the positive feedback that is critical for these slow dynamics can cause sensitivity to perturbations. Here we use electrophysiology and optogenetic perturbations in the mouse premotor cortex to probe the robustness of persistent neural representations during motor planning. We show that preparatory activity is remarkably robust to large-scale unilateral silencing: detailed neural dynamics that drive specific future movements were quickly and selectively restored by the network. Selectivity did not recover after bilateral silencing of the premotor cortex. Perturbations to one hemisphere are thus corrected by information from the other hemisphere. Corpus callosum bisections demonstrated that premotor cortex hemispheres can maintain preparatory activity independently. Redundancy across selectively coupled modules, as we observed in the premotor cortex, is a hallmark of robust control systems. Network models incorporating these principles show robustness that is consistent with data.
C1 [Li, Nuo; Daie, Kayvon; Svoboda, Karel; Druckmann, Shaul] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Svoboda, K; Druckmann, S (corresponding author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
EM svobodak@janelia.hhmi.org; druckmanns@janelia.hhmi.org
FU Howard Hughes Medical Institute
NR 50
TC 317
Z9 404
U1 3
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 459
EP +
DI 10.1038/nature17643
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900038
PM 27074502
DA 2026-03-09
ER

PT J
AU Liu, S
   Grinberg, I
   Rappe, AM
AF Liu, Shi
   Grinberg, Ilya
   Rappe, Andrew M.
TI Intrinsic ferroelectric switching from first principles
SO NATURE
LA English
DT Article
ID domain-wall motion; oxides; mechanism; dynamics; titanate; field
AB The existence of domain walls, which separate regions of different polarization, can influence the dielectric(1), piezoelectric(2), pyroelectric(3) and electronic properties(4,5) of ferroelectric materials. In particular, domain-wall motion is crucial for polarization switching, which is characterized by the hysteresis loop that is a signature feature of ferroelectric materials(6). Experimentally, the observed dynamics of polarization switching and domain-wall motion are usually explained as the behaviour of an elastic interface pinned by a random potential that is generated by defects(7,8), which appear to be strongly sample-dependent and affected by various elastic, microstructural and other extrinsic effects(9-12). Theoretically, connecting the zero-kelvin, first-principles-based, microscopic quantities of a sample with finite-temperature, macroscopic properties such as the coercive field is critical for material design and device performance; and the lack of such a connection has prevented the use of techniques based on ab initio calculations for high-throughput computational materials discovery. Here we use molecular dynamics simulations(13) of 90 degrees domain walls (separating domains with orthogonal polarization directions) in the ferroelectric material PbTiO3 to provide microscopic insights that enable the construction of a simple, universal, nucleation-and-growth-based analytical model that quantifies the dynamics of many types of domain walls in various ferroelectrics. We then predict the temperature and frequency dependence of hysteresis loops and coercive fields at finite temperatures from first principles. We find that, even in the absence of defects, the intrinsic temperature and field dependence of the domain-wall velocity can be described with a nonlinear creep-like region and a depinning-like region. Our model enables quantitative estimation of coercive fields, which agree well with experimental results for ceramics and thin films. This agreement between model and experiment suggests that, despite the complexity of ferroelectric materials, typical ferroelectric switching is largely governed by a simple, universal mechanism of intrinsic domain-wall motion, providing an efficient framework for predicting and optimizing the properties of ferroelectric materials.
C1 [Liu, Shi] Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
   [Grinberg, Ilya; Rappe, Andrew M.] Univ Penn, Dept Chem, Makineni Theoret Labs, Philadelphia, PA 19104 USA.
   [Grinberg, Ilya] Bar Ilan Univ, Dept Chem, IL-5290002 Ramat Gan, Israel.
C3 Carnegie Institution for Science; University of Pennsylvania; Bar Ilan University
RP Liu, S (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.; Rappe, AM (corresponding author), Univ Penn, Dept Chem, Makineni Theoret Labs, Philadelphia, PA 19104 USA.
EM sliu@carnegiescience.edu; rappe@sas.upenn.edu
FU NSF [DMR-1124696, CBET-1159736]; Carnegie Institution for Science; US ONR [N00014-12-1-1033]; US DOE [DE-FG02-07ER46431]; HPCMO; Direct For Mathematical & Physical Scien; Division Of Materials Research [1124696] Funding Source: National Science Foundation
NR 39
TC 218
Z9 240
U1 13
U2 458
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 360
EP +
DI 10.1038/nature18286
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800030
PM 27306186
DA 2026-03-09
ER

PT J
AU Steinke, S
   van Tilborg, J
   Benedetti, C
   Geddes, CGR
   Schroeder, CB
   Daniels, J
   Swanson, KK
   Gonsalves, AJ
   Nakamura, K
   Matlis, NH
   Shaw, BH
   Esarey, E
   Leemans, WP
AF Steinke, S.
   van Tilborg, J.
   Benedetti, C.
   Geddes, C. G. R.
   Schroeder, C. B.
   Daniels, J.
   Swanson, K. K.
   Gonsalves, A. J.
   Nakamura, K.
   Matlis, N. H.
   Shaw, B. H.
   Esarey, E.
   Leemans, W. P.
TI Multistage coupling of independent laser-plasma accelerators
SO NATURE
LA English
DT Article
ID electron-beams; intensity; physics; pulses
AB Laser-plasma accelerators (LPAs) are capable of accelerating charged particles to very high energies in very compact structures(1). In theory, therefore, they offer advantages over conventional, large-scale particle accelerators. However, the energy gain in a single-stage LPA can be limited by laser diffraction, dephasing, electron-beam loading and laser-energy depletion(1). The problem of laser diffraction can be addressed by using laser-pulse guiding(2) and preformed plasma waveguides to maintain the required laser intensity over distances of many Rayleigh lengths(3); dephasing can be mitigated by longitudinal tailoring of the plasma density(4); and beam loading can be controlled by proper shaping of the electron beam(5). To increase the beam energy further, it is necessary to tackle the problem of the depletion of laser energy, by sequencing the accelerator into stages, each powered by a separate laser pulse(6). Here, we present results from an experiment that demonstrates such staging. Two LPA stages were coupled over a short distance (as is needed to preserve the average acceleration gradient) by a plasma mirror. Stable electron beams from a first LPA were focused to a twenty-micrometre radius-by a discharge capillary-based(7) active plasma lens(8)-into a second LPA, such that the beams interacted with the wakefield excited by a separate laser. Staged acceleration by the wakefield of the second stage is detected via an energy gain of 100 megaelectronvolts for a subset of the electron beam. Changing the arrival time of the electron beam with respect to the second-stage laser pulse allowed us to reconstruct the temporal wakefield structure and to determine the plasma density. Our results indicate that the fundamental limitation to energy gain presented by laser depletion can be overcome by using staged acceleration, suggesting a way of reaching the electron energies required for collider applications(6,9).
C1 [Steinke, S.; van Tilborg, J.; Benedetti, C.; Geddes, C. G. R.; Schroeder, C. B.; Daniels, J.; Swanson, K. K.; Gonsalves, A. J.; Nakamura, K.; Matlis, N. H.; Shaw, B. H.; Esarey, E.; Leemans, W. P.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Swanson, K. K.; Shaw, B. H.; Leemans, W. P.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Daniels, J.] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Eindhoven University of Technology
RP Leemans, WP (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, 1 Cyclotron Rd, Berkeley, CA 94720 USA.
EM wpleemans@lbl.gov
FU US Department of Energy, Office of Science, Office of High Energy Physics [DE-AC02-05CH11231]; US Department of Energy National Nuclear Security Administration, Defense Nuclear Nonproliferation RD [NA22]; National Science Foundation (NSF) [0917687, 0935197, PHY-1415596]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Direct For Mathematical & Physical Scien [0917687] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1415596] Funding Source: National Science Foundation; Division Of Physics [0917687] Funding Source: National Science Foundation
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NR 34
TC 264
Z9 325
U1 6
U2 202
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 190
EP +
DI 10.1038/nature16525
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700032
PM 26829223
DA 2026-03-09
ER

PT J
AU Clemente-Casares, X
   Blanco, J
   Ambalavanan, P
   Yamanouchi, J
   Singha, S
   Fandos, C
   Tsai, S
   Wang, JG
   Garabatos, N
   Izquierdo, C
   Agrawal, S
   Keough, MB
   Yong, VW
   James, E
   Moore, A
   Yang, Y
   Stratmann, T
   Serra, P
   Santamaria, P
AF Clemente-Casares, Xavier
   Blanco, Jesus
   Ambalavanan, Poornima
   Yamanouchi, Jun
   Singha, Santiswarup
   Fandos, Cesar
   Tsai, Sue
   Wang, Jinguo
   Garabatos, Nahir
   Izquierdo, Cristina
   Agrawal, Smriti
   Keough, Michael B.
   Yong, V. Wee
   James, Eddie
   Moore, Anna
   Yang, Yang
   Stratmann, Thomas
   Serra, Pau
   Santamaria, Pere
TI Expanding antigen-specific regulatory networks to treat autoimmunity
SO NATURE
LA English
DT Article
ID subunit-related protein; cd8(+) t-cells; c-maf; tolerance; differentiation; autoantigen; instability; activation; generation; arthritis
AB Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (T(R)1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII-based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into T(R)1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner.
C1 [Clemente-Casares, Xavier; Ambalavanan, Poornima; Yamanouchi, Jun; Singha, Santiswarup; Tsai, Sue; Yang, Yang; Santamaria, Pere] Univ Calgary, Snyder Inst Chron Dis & Hotchkiss Brain Inst, Cumming Sch Med, JMDRC, Calgary, AB T2N 4N1, Canada.
   [Clemente-Casares, Xavier; Ambalavanan, Poornima; Yamanouchi, Jun; Singha, Santiswarup; Tsai, Sue; Wang, Jinguo; Yang, Yang; Santamaria, Pere] Univ Calgary, Snyder Inst Chron Dis & Hotchkiss Brain Inst, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 4N1, Canada.
   [Blanco, Jesus; Fandos, Cesar; Serra, Pau; Santamaria, Pere] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.
   [Blanco, Jesus] Inst Salud Carlos III, Ctr Invest Biomed Red Diabet & Enfermedades, Metab Asociadas CIBERDEM, Madrid 28029, Spain.
   [Garabatos, Nahir; Izquierdo, Cristina; Stratmann, Thomas] Univ Barcelona, Fac Biol, Dept Physiol & Immunol, E-08028 Barcelona, Spain.
   [Agrawal, Smriti; Keough, Michael B.; Yong, V. Wee] Univ Calgary, Fac Med, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada.
   [Agrawal, Smriti; Keough, Michael B.; Yong, V. Wee] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada.
   [James, Eddie] Virginia Mason, Benaroya Res Inst, Seattle, WA 98101 USA.
   [Moore, Anna] Massachusetts Gen Hosp, Dept Radiol, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
   [Yang, Yang] Univ Calgary, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada.
C3 University of Calgary; University of Calgary; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBERDEM; University of Barcelona; University of Calgary; University of Calgary; Benaroya Research Institute; Virginia Mason Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Calgary
RP Santamaria, P (corresponding author), Univ Calgary, Snyder Inst Chron Dis & Hotchkiss Brain Inst, Cumming Sch Med, JMDRC, Calgary, AB T2N 4N1, Canada.; Santamaria, P (corresponding author), Univ Calgary, Snyder Inst Chron Dis & Hotchkiss Brain Inst, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 4N1, Canada.; Santamaria, P (corresponding author), Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.
EM psantama@ucalgary.ca
FU Canadian Institutes of Health Research (CIHR); Diabetes Research Foundation; Juvenile Diabetes Research Foundation (JDRF); Canadian Diabetes Association (CDA); Multiple Sclerosis Society of Canada (MSSC); Brawn Family Foundation; National Research Council of Canada-Industrial Research Assistance Program (NRC-IRAP); Instituto de Investigaciones Sanitarias Carlos III (ISCIII) Integrated Project of Excellence; Instituto de Investigaciones Sanitarias Carlos III (ISCIII) Integrated Project of FEDER; Ministerio de Economia y Competitividad of Spain (MINECO); European Association for the study of diabetes (EASD); Sarda Farriol Research Programme; European Community; AXA Research Fund; endMS network; Rio Hortega fellowship; Spanish Society for Diabetes; Alberta Heritage Foundation of Medical Research (AHFMR); CDA; JDRF Career Development Award; Diabetes Association (Foothills)
NR 31
TC 414
Z9 476
U1 1
U2 158
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 434
EP +
DI 10.1038/nature16962
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800026
PM 26886799
DA 2026-03-09
ER

PT J
AU Powers, JT
   Tsanov, KM
   Pearson, DS
   Roels, F
   Spina, CS
   Ebright, R
   Seligson, M
   de Soysa, Y
   Cahan, P
   Theissen, J
   Tu, HC
   Han, A
   Kurek, KC
   LaPier, GS
   Osborne, JK
   Ross, SJ
   Cesana, M
   Collins, JJ
   Berthold, F
   Daley, GQ
AF Powers, John T.
   Tsanov, Kaloyan M.
   Pearson, Daniel S.
   Roels, Frederik
   Spina, Catherine S.
   Ebright, Richard
   Seligson, Marc
   de Soysa, Yvanka
   Cahan, Patrick
   Theissen, Jessica
   Tu, Ho-Chou
   Han, Areum
   Kurek, Kyle C.
   LaPier, Grace S.
   Osborne, Jihan K.
   Ross, Samantha J.
   Cesana, Marcella
   Collins, James J.
   Berthold, Frank
   Daley, George Q.
TI Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma
SO NATURE
LA English
DT Article
ID comparative genomic hybridization; competitive endogenous rna; gene-expression; n-myc; cancer; tumor; lin28b; cells; mirna; amplification
AB Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.
C1 [Powers, John T.; Tsanov, Kaloyan M.; Pearson, Daniel S.; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Tu, Ho-Chou; Han, Areum; LaPier, Grace S.; Osborne, Jihan K.; Ross, Samantha J.; Cesana, Marcella; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Roels, Frederik; Theissen, Jessica; Berthold, Frank] Univ Hosp Koln, Dept Pediat Oncol, D-50937 Cologne, Germany.
   [Spina, Catherine S.; Collins, James J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
   [Kurek, Kyle C.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02215 USA.
   [Collins, James J.] Broad Inst MIT & Harvard, MIT, Dept Biol Engn, Cambridge, MA 02142 USA.
   [Daley, George Q.] Dana Farber Canc Inst, Stem Cell Transplantat Program, Boston, MA 02115 USA.
   [Daley, George Q.] Boston Childrens Hosp, Boston, MA 02115 USA.
   [Daley, George Q.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Cologne; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University
RP Daley, GQ (corresponding author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.; Daley, GQ (corresponding author), Dana Farber Canc Inst, Stem Cell Transplantat Program, Boston, MA 02115 USA.; Daley, GQ (corresponding author), Boston Childrens Hosp, Boston, MA 02115 USA.; Daley, GQ (corresponding author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Daley, GQ (corresponding author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
EM george.daley@childrens.harvard.edu
FU National Institutes of Health [R01GM107536]; Alex's Lemonade Stand Foundation; Ellison Medical Foundation; National Institute of General Medical Sciences [T32GM007753]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 58
TC 157
Z9 177
U1 0
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 246
EP U112
DI 10.1038/nature18632
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600049
PM 27383785
DA 2026-03-09
ER

PT J
AU Lee, SB
   Frattini, V
   Bansal, M
   Castano, AM
   Sherman, D
   Hutchinson, K
   Bruce, JN
   Califano, A
   Liu, GC
   Cardozo, T
   Iavarone, A
   Lasorella, A
AF Lee, Sang Bae
   Frattini, Veronique
   Bansal, Mukesh
   Castano, Angelica M.
   Sherman, Dan
   Hutchinson, Keino
   Bruce, Jeffrey N.
   Califano, Andrea
   Liu, Guangchao
   Cardozo, Timothy
   Iavarone, Antonio
   Lasorella, Anna
TI An ID2-dependent mechanism for VHL inactivation in cancer
SO NATURE
LA English
DT Article
ID protein-kinase dyrk1a; ubiquitin ligase huwe1; loop-helix proteins; neural stem-cells; down-syndrome; neuronal differentiation; transcriptional activity; inhibits proliferation; progenitor cells; expression
AB Mechanisms that maintain cancer stem cells are crucial to tumour progression. The ID2 protein supports cancer hallmarks including the cancer stem cell state. HIF alpha transcription factors, most notably HIF2 alpha (also known as EPAS1), are expressed in and required for maintenance of cancer stem cells (CSCs). However, the pathways that are engaged by ID2 or drive HIF2 alpha accumulation in CSCs have remained unclear. Here we report that DYRK1A and DYRK1B kinases phosphorylate ID2 on threonine 27 (Thr27). Hypoxia downregulates this phosphorylation via inactivation of DYRK1A and DYRK1B. The activity of these kinases is stimulated in normoxia by the oxygen-sensing prolyl hydroxylase PHD1 (also known as EGLN2). ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2 alpha ubiquitylation and degradation. Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2 alpha ubiquitylation. In glioblastoma, ID2 positively modulates HIF2 alpha activity. Conversely, elevated expression of DYRK1 phosphorylates Thr27 of ID2, leading to HIF2 alpha destabilization, loss of glioma stemness, inhibition of tumour growth, and a more favourable outcome for patients with glioblastoma.
C1 [Lee, Sang Bae; Frattini, Veronique; Castano, Angelica M.; Liu, Guangchao; Iavarone, Antonio; Lasorella, Anna] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
   [Bansal, Mukesh; Califano, Andrea] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA.
   [Bansal, Mukesh; Califano, Andrea] Columbia Univ, Med Ctr, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Sherman, Dan; Hutchinson, Keino; Cardozo, Timothy] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10014 USA.
   [Bruce, Jeffrey N.] Columbia Univ, Med Ctr, Dept Neurosurg, New York, NY 10032 USA.
   [Iavarone, Antonio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA.
   [Iavarone, Antonio; Lasorella, Anna] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA.
   [Lasorella, Anna] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; New York University; Columbia University; Columbia University; Columbia University; Columbia University
RP Lasorella, A (corresponding author), Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
EM ai2102@columbia.edu; al2179@columbia.edu
FU National Institute of Health [R01CA101644, R01CA131126]; Chemotherapy Foundation; American Brain Tumor Association (ABTA);  [R01CA178546 and R01NS061776];  [NRF-2013R1A6A3A03063888]
NR 53
TC 104
Z9 118
U1 2
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 172
EP U93
DI 10.1038/nature16475
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700028
PM 26735018
DA 2026-03-09
ER

PT J
AU Anderson, TM
   Garcia, AJ
   Baertsch, NA
   Pollak, J
   Bloom, JC
   Wei, AD
   Rai, KG
   Ramirez, JM
AF Anderson, Tatiana M.
   Garcia, Alfredo J., III
   Baertsch, Nathan A.
   Pollak, Julia
   Bloom, Jacob C.
   Wei, Aguan D.
   Rai, Karan G.
   Ramirez, Jan-Marino
TI A novel excitatory network for the control of breathing
SO NATURE
LA English
DT Article
ID respiratory rhythm; functional architecture; neuronal control; complex; reconfiguration; expiration; medulla; mice
AB Breathing must be tightly coordinated with other behaviours such as vocalization, swallowing, and coughing. These behaviours occur after inspiration, during a respiratory phase termed postinspiration(1). Failure to coordinate postinspiration with inspiration can result in aspiration pneumonia, the leading cause of death in Alzheimer's disease, Parkinson's disease, dementia, and other neurodegenerative diseases(2). Here we describe an excitatory network that generates the neuronal correlate of postinspiratory activity in mice. Glutamatergic-cholinergic neurons form the basis of this network, and GABA (gamma-aminobutyric acid)-mediated inhibition establishes the timing and coordination relative to inspiration. We refer to this network as the postinspiratory complex (PiCo). The PiCo has autonomous rhythm-generating properties and is necessary and sufficient for postinspiratory activity in vivo. The PiCo also shows distinct responses to neuromodulators when compared to other excitatory brainstem networks. On the basis of the discovery of the PiCo, we propose that each of the three phases of breathing is generated by a distinct excitatory network: the pre-Botzinger complex, which has been linked to inspiration(3,4); the PiCo, as described here for the neuronal control of postinspiration; and the lateral parafacial region (pF(L)), which has been associated with active expiration, a respiratory phase that is recruited during high metabolic demand(4,5).
C1 [Anderson, Tatiana M.; Garcia, Alfredo J., III; Baertsch, Nathan A.; Pollak, Julia; Bloom, Jacob C.; Wei, Aguan D.; Rai, Karan G.; Ramirez, Jan-Marino] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 USA.
   [Anderson, Tatiana M.] Univ Washington, Sch Med, Grad Program Neurosci, Seattle, WA 98195 USA.
   [Ramirez, Jan-Marino] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98105 USA.
C3 Seattle Children's Hospital; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Ramirez, JM (corresponding author), Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 USA.; Ramirez, JM (corresponding author), Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98105 USA.
EM nino1@uw.edu
FU National Institute of Health [NS087828-01, HL090554, HL126523-01]; National Heart Lung and Blood Institute [R01HL126523] Funding Source: NIH RePORTER
NR 30
TC 183
Z9 220
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 76
EP +
DI 10.1038/nature18944
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200033
PM 27462817
DA 2026-03-09
ER

PT J
AU Seo, JS
   Rhie, A
   Kim, J
   Lee, S
   Sohn, MH
   Kim, CU
   Hastie, A
   Cao, H
   Yun, JY
   Kim, J
   Kuk, J
   Park, GH
   Kim, J
   Ryu, H
   Kim, J
   Roh, M
   Baek, J
   Hunkapiller, MW
   Korlach, J
   Shin, JY
   Kim, C
AF Seo, Jeong-Sun
   Rhie, Arang
   Kim, Junsoo
   Lee, Sangjin
   Sohn, Min-Hwan
   Kim, Chang-Uk
   Hastie, Alex
   Cao, Han
   Yun, Ji-Young
   Kim, Jihye
   Kuk, Junho
   Park, Gun Hwa
   Kim, Juhyeok
   Ryu, Hanna
   Kim, Jongbum
   Roh, Mira
   Baek, Jeonghun
   Hunkapiller, Michael W.
   Korlach, Jonas
   Shin, Jong-Yeon
   Kim, Changhoon
TI De novo assembly and phasing of a Korean human genome
SO NATURE
LA English
DT Article
ID structural variation; sequence; mutations; alignment; gene
AB Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing(2), next-generation mapping(3), microfluidics-based linked reads(4), and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.
C1 [Seo, Jeong-Sun; Rhie, Arang; Kim, Junsoo; Lee, Sangjin; Sohn, Min-Hwan; Kim, Chang-Uk; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok; Shin, Jong-Yeon] Seoul Natl Univ, Med Res Ctr, GMI, Seoul 110799, South Korea.
   [Seo, Jeong-Sun; Rhie, Arang; Sohn, Min-Hwan; Kim, Chang-Uk] Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea.
   [Seo, Jeong-Sun; Rhie, Arang; Sohn, Min-Hwan; Kim, Chang-Uk] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 110799, South Korea.
   [Seo, Jeong-Sun; Kim, Junsoo; Ryu, Hanna; Kim, Jongbum; Roh, Mira; Baek, Jeonghun; Kim, Changhoon] Macrogen Inc, Bioinformat Inst, Seoul 153023, South Korea.
   [Seo, Jeong-Sun; Lee, Sangjin; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok] Macrogen Inc, Genome Inst, Seoul 153023, South Korea.
   [Cao, Han] BioNano Genom, San Diego, CA 92121 USA.
   [Hunkapiller, Michael W.; Korlach, Jonas] Pacific Biosci Calif Inc, Menlo Pk, CA 94025 USA.
C3 Seoul National University (SNU); Seoul National University (SNU); Seoul National University (SNU); Macrogen, Inc.; Macrogen, Inc.
RP Seo, JS (corresponding author), Seoul Natl Univ, Med Res Ctr, GMI, Seoul 110799, South Korea.; Seo, JS (corresponding author), Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea.; Seo, JS (corresponding author), Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 110799, South Korea.; Seo, JS; Kim, C (corresponding author), Macrogen Inc, Bioinformat Inst, Seoul 153023, South Korea.; Seo, JS (corresponding author), Macrogen Inc, Genome Inst, Seoul 153023, South Korea.
EM jeongsun@snu.ac.kr; kimchan@macrogen.com
FU Macrogen Inc. [SNU RNDB 0411-20160001, MGR14-01]; Post-Genome Technology Development Program - Ministry of Trade, Industry & Energy (MOTIE, Korea) [10050164]
NR 33
TC 226
Z9 276
U1 0
U2 50
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 243
EP +
DI 10.1038/nature20098
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000045
PM 27706134
DA 2026-03-09
ER

PT J
AU Siegler, MA
   Miller, RS
   Keane, JT
   Laneuville, M
   Paige, DA
   Matsuyama, I
   Lawrence, DJ
   Crotts, A
   Poston, MJ
AF Siegler, M. A.
   Miller, R. S.
   Keane, J. T.
   Laneuville, M.
   Paige, D. A.
   Matsuyama, I.
   Lawrence, D. J.
   Crotts, A.
   Poston, M. J.
TI Lunar true polar wander inferred from polar hydrogen
SO NATURE
LA English
DT Article
ID gravity-field; water ice; surface; moon; prospector; fines; constraints; temperature; evolution; deposits
AB The earliest dynamic and thermal history of the Moon is not well understood. The hydrogen content of deposits near the lunar poles may yield insight into this history, because these deposits (which are probably composed of water ice) survive only if they remain in permanent shadow. If the orientation of the Moon has changed, then the locations of the shadowed regions will also have changed. The polar hydrogen deposits have been mapped by orbiting neutron spectrometers(1-3), and their observed spatial distribution does not match the expected distribution of water ice inferred from present-day lunar temperatures(4,5). This finding is in contrast to the distribution of volatiles observed in similar thermal environments at Mercury's poles(6). Here we show that polar hydrogen preserves evidence that the spin axis of the Moon has shifted: the hydrogen deposits are antipodal and displaced equally from each pole along opposite longitudes. From the direction and magnitude of the inferred reorientation, and from analysis of the moments of inertia of the Moon, we hypothesize that this change in the spin axis, known as true polar wander, was caused by a low-density thermal anomaly beneath the Procellarum region. Radiogenic heating within this region resulted in the bulk of lunar mare volcanism(7-11) and altered the density structure of the Moon, changing its moments of inertia. This resulted in true polar wander consistent with the observed remnant polar hydrogen. This thermal anomaly still exists and, in part, controls the current orientation of the Moon. The Procellarum region was most geologically active early in lunar history(7-9), which implies that polar wander initiated billions of years ago and that a large portion of the measured polar hydrogen is ancient, recording early delivery of water to the inner Solar System. Our hypothesis provides an explanation for the antipodal distribution of lunar polar hydrogen, and connects polar volatiles to the geologic and geophysical evolution of the Moon and the bombardment history of the early Solar System.
C1 [Siegler, M. A.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Siegler, M. A.] So Methodist Univ, Dallas, TX 75275 USA.
   [Miller, R. S.] Univ Alabama, Huntsville, AL 35899 USA.
   [Keane, J. T.; Matsuyama, I.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Laneuville, M.] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, Tokyo 1528551, Japan.
   [Paige, D. A.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Lawrence, D. J.] Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
   [Crotts, A.] Columbia Univ, New York, NY 10027 USA.
   [Poston, M. J.] CALTECH, Pasadena, CA 91125 USA.
C3 Southern Methodist University; University of Alabama System; University of Alabama Huntsville; University of Arizona; Institute of Science Tokyo; Tokyo Institute of Technology; University of California System; University of California Los Angeles; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; Columbia University; California Institute of Technology
RP Siegler, MA (corresponding author), Planetary Sci Inst, Tucson, AZ 85719 USA.; Siegler, MA (corresponding author), So Methodist Univ, Dallas, TX 75275 USA.
EM msiegler@psi.edu
FU NASA's SSERVI VORTICES node; Lunar Reconnaissance Orbiter; NASA Lunar Advanced Science and Exploration Research (LASER) programme
NR 94
TC 102
Z9 116
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 480
EP +
DI 10.1038/nature17166
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300035
PM 27008966
DA 2026-03-09
ER

PT J
AU Keane, EF
   Johnston, S
   Bhandari, S
   Barr, E
   Bhat, NDR
   Burgay, M
   Caleb, M
   Flynn, C
   Jameson, A
   Kramer, M
   Petroff, E
   Possenti, A
   van Straten, W
   Bailes, M
   Burke-Spolaor, S
   Eatough, RP
   Stappers, BW
   Totani, T
   Honma, M
   Furusawa, H
   Hattori, T
   Morokuma, T
   Niino, Y
   Sugai, H
   Terai, T
   Tominaga, N
   Yamasaki, S
   Yasuda, N
   Allen, R
   Cooke, J
   Jencson, J
   Kasliwal, MM
   Kaplan, DL
   Tingay, SJ
   Williams, A
   Wayth, R
   Chandra, P
   Perrodin, D
   Berezina, M
   Mickaliger, M
   Bassa, C
AF Keane, E. F.
   Johnston, S.
   Bhandari, S.
   Barr, E.
   Bhat, N. D. R.
   Burgay, M.
   Caleb, M.
   Flynn, C.
   Jameson, A.
   Kramer, M.
   Petroff, E.
   Possenti, A.
   van Straten, W.
   Bailes, M.
   Burke-Spolaor, S.
   Eatough, R. P.
   Stappers, B. W.
   Totani, T.
   Honma, M.
   Furusawa, H.
   Hattori, T.
   Morokuma, T.
   Niino, Y.
   Sugai, H.
   Terai, T.
   Tominaga, N.
   Yamasaki, S.
   Yasuda, N.
   Allen, R.
   Cooke, J.
   Jencson, J.
   Kasliwal, M. M.
   Kaplan, D. L.
   Tingay, S. J.
   Williams, A.
   Wayth, R.
   Chandra, P.
   Perrodin, D.
   Berezina, M.
   Mickaliger, M.
   Bassa, C.
TI The host galaxy of a fast radio burst
SO NATURE
LA English
DT Article
ID gamma-ray burst; reionization history; dispersion measure; missing baryons; search; constraints; afterglows; energetics; emission
AB In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts(1-9). These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations(10,11). Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates. Here we report the discovery of a fast radio burst and the identification of a fading radio transient lasting similar to 6 days after the event, which we use to identify the host galaxy; we measure the galaxy's redshift to be z = 0.492 +/- 0.008. The dispersion measure and redshift, in combination, provide a direct measurement of the cosmic density of ionized baryons in the intergalactic medium of Omega(IGM) = 4.9 +/- 1.3 per cent, in agreement with the expectation from the Wilkinson Microwave Anisotropy Probe(12), and including all of the so-called 'missing baryons'. The similar to 6-day radio transient is largely consistent with the radio afterglow of a short gamma-ray burst(13), and its existence and timescale do not support progenitor models such as giant pulses from pulsars, and supernovae. This contrasts with the interpretation(8) of another recently discovered fast radio burst, suggesting that there are at least two classes of bursts.
C1 [Keane, E. F.] Jodrell Bank Observ, Square Kilometre Array Org, Macclesfield SK11 9DL, Cheshire, England.
   [Keane, E. F.; Bhandari, S.; Barr, E.; Caleb, M.; Flynn, C.; Jameson, A.; Petroff, E.; van Straten, W.; Bailes, M.; Allen, R.; Cooke, J.] Swinburne Univ Technol, Ctr Astrophys & Supercomputing, Mail H29 POB 218, Victoria 3122, Australia.
   [Keane, E. F.; Bhandari, S.; Bhat, N. D. R.; Caleb, M.; Flynn, C.; Jameson, A.; Petroff, E.; Bailes, M.; Cooke, J.; Tingay, S. J.; Wayth, R.] Australian Res Council Ctr Excellence All Sky Ast, Sydney, NSW, Australia.
   [Johnston, S.; Petroff, E.] CSIRO, Australia Telescope Natl Facil, Astron & Space Sci, POB 76, Epping, NSW 1710, Australia.
   [Bhat, N. D. R.; Tingay, S. J.; Williams, A.; Wayth, R.] Curtin Univ Technol, Int Ctr Radio Astron Res, Bentley, WA 6102, Australia.
   [Burgay, M.; Possenti, A.; Perrodin, D.] INAF, Osservat Astronomico Cagliari, Via Sci 5, I-09047 Selargius, CA, Italy.
   [Caleb, M.] Australian Capital Terr, Australian Natl Univ Canberra, Res Sch Astron & Astrophys, Canberra, ACT 2611, Australia.
   [Kramer, M.; Eatough, R. P.; Berezina, M.] Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
   [Kramer, M.; Stappers, B. W.; Mickaliger, M.] Univ Manchester, Sch Phys & Astron, Jodrell Bank Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Burke-Spolaor, S.] Natl Radio Astron Observ, Socorro, NM, Mexico.
   [Totani, T.; Yamasaki, S.] Univ Tokyo, Dept Astron, Hongo, Tokyo 1130033, Japan.
   [Honma, M.; Furusawa, H.; Niino, Y.] Natl Astron Observ Japan, 2 Chome 21-1, Mitaka, Tokyo 1818588, Japan.
   [Honma, M.] SOKENDAI, Grad Univ Adv Study, Dept Astron Sci, Mitaka, Tokyo 1818588, Japan.
   [Hattori, T.; Terai, T.] Subaru Telescope, Natl Astron Observ Japan, 650 N Aohoku Pl, Hilo, HI 96720 USA.
   [Morokuma, T.] Univ Tokyo, Grad Sch Sci, Inst Astron, Mitaka, Tokyo 1810015, Japan.
   [Morokuma, T.; Sugai, H.; Tominaga, N.; Yasuda, N.] Univ Tokyo, Inst Adv Study, Kavli Inst Phys & Math Univ WPI, Kashiwa, Chiba 2778583, Japan.
   [Tominaga, N.] Konan Univ, Fac Sci & Engn, Dept Phys, 8-9-1 Okamoto, Kobe, Hyogo 6588501, Japan.
   [Jencson, J.; Kasliwal, M. M.] CALTECH, Cahill Ctr Astrophys, 1200 East Calif Blvd, Pasadena, CA 91125 USA.
   [Kaplan, D. L.] Univ Wisconsin, Dept Phys, Milwaukee, WI 53201 USA.
   [Chandra, P.] Tata Inst Fundamental Res, Natl Ctr Radio Astrophys, Pune 411007, Maharashtra, India.
   [Bassa, C.] ASTRON, Netherlands Inst Radio Astron, NL-7990 AA Dwingeloo, Netherlands.
C3 University of Manchester; Jodrell Bank Centre for Astrophysics; Swinburne University of Technology; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; Australia Telescope National Facility; University of Western Australia; Curtin University; Istituto Nazionale Astrofisica (INAF); Australian National University; Max Planck Society; University of Manchester; Jodrell Bank Centre for Astrophysics; National Radio Astronomy Observatory (NRAO); University of Tokyo; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Graduate University for Advanced Studies - Japan; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); University of Tokyo; University of Tokyo; Konan University; California Institute of Technology; University of Wisconsin System; University of Wisconsin Milwaukee; Tata Institute of Fundamental Research (TIFR); National Centre for Radio Astrophysics (NCRA), Pune
RP Keane, EF (corresponding author), Jodrell Bank Observ, Square Kilometre Array Org, Macclesfield SK11 9DL, Cheshire, England.
EM e.keane@skatelescope.org
FU Commonwealth of Australia; Science and Technology Facilities Council [ST/L000768/1] Funding Source: researchfish; STFC [ST/L000768/1] Funding Source: UKRI; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1412421] Funding Source: National Science Foundation; Grants-in-Aid for Scientific Research [24000004, 13J06603, 15H05440, 15K05018] Funding Source: KAKEN
NR 49
TC 223
Z9 260
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 453
EP +
DI 10.1038/nature17140
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800029
PM 26911781
DA 2026-03-09
ER

PT J
AU Bertrand, T
   Forget, F
AF Bertrand, Tanguy
   Forget, Francois
TI Observed glacier and volatile distribution on Pluto from atmosphere-topography processes
SO NATURE
LA English
DT Article
ID charon; methane; maps
AB Pluto has a variety of surface frosts and landforms as well as a complex atmosphere(1). There is ongoing geological activity related to the massive Sputnik Planitia glacier, mostly made of nitrogen (N-2) ice mixed with solid carbon monoxide and methane(2), covering the 4-kilometre-deep, 1,000-kilometre-wide basin of Sputnik Planitia(1,3) near the anti-Charon point. The glacier has been suggested to arise from a source region connected to the deep interior, or from a sink collecting the volatiles released planetwide(1). Thin deposits of N-2 frost, however, were also detected at mid-northern latitudes and methane ice was observed to cover most of Pluto except for the darker, frost-free equatorial regions(2). Here we report numerical simulations of the evolution of N-2, methane and carbon monoxide on Pluto over thousands of years. The model predicts N-2 ice accumulation in the deepest low-latitude basin and the threefold increase in atmospheric pressure that has been observed to occur since 1988(4-6). This points to atmospheric-topographic processes as the origin of Sputnik Planitia's N-2 glacier. The same simulations also reproduce the observed quantities of volatiles in the atmosphere and show frosts of methane, and sometimes N-2, that seasonally cover the mid-and high latitudes, explaining the bright northern polar cap reported in the 1990s(7,8) and the observed ice distribution in 2015(2). The model also predicts that most of these seasonal frosts should disappear in the next decade.
C1 [Bertrand, Tanguy; Forget, Francois] UPMC Univ Paris 06, Sorbonne Univ, CNRS, Lab Meteorol Dynam,IPSL, BP99,4 Pl Jussieu, F-75005 Paris, France.
C3 Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Institut Polytechnique de Paris; Ecole Polytechnique; Sorbonne Universite
RP Forget, F (corresponding author), UPMC Univ Paris 06, Sorbonne Univ, CNRS, Lab Meteorol Dynam,IPSL, BP99,4 Pl Jussieu, F-75005 Paris, France.
EM forget@lmd.jussieu.fr
FU Institut de Formation Doctorale
NR 23
TC 76
Z9 82
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 86
EP +
DI 10.1038/nature19337
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600052
PM 27629517
DA 2026-03-09
ER

PT J
AU Yan, LJ
   Wang, L
   Tian, YY
   Xia, X
   Chen, ZC
AF Yan, Lijuan
   Wang, Li
   Tian, Yuanyuan
   Xia, Xian
   Chen, Zhucheng
TI Structure and regulation of the chromatin remodeller ISWI
SO NATURE
LA English
DT Article
ID histone h4 tail; dna translocation; concerted action; atpase; swi2/snf2; swi/snf; domain; family; recognition; requires
AB ISWI is a member of the SWI2/SNF2 family of chromatin remodellers(1,2), which also includes Snf2, Chd1, and Ino80. ISWI is the catalytic subunit of several chromatin remodelling complexes, which mobilize nucleosomes along genomic DNA, promoting replication progression, transcription repression, heterochromatin formation, and many other nuclear processes(3-5). The ATPase motor of ISWI is an autonomous remodelling machine(6), whereas its carboxy (C)-terminal HAND-SAND-SLIDE (HSS) domain functions in binding extranucleosomal linker DNA(7-10). The activity of the catalytic core of ISWI is inhibited by the regulatory AutoN and NegC domains, which are in turn antagonized by the H4 tail and extranucleosomal DNA, respectively, to ensure the appropriate chromatin landscape in cells(11). How AutoN and NegC inhibit ISWI and regulate its nucleosome-centring activity remains elusive. Here we report the crystal structures of ISWI from the thermophilic yeast Myceliophthora thermophila and its complex with a histone H4 peptide. Our data show the amino (N)-terminal AutoN domain contains two inhibitory elements, which collectively bind the second RecA-like domain (core2), holding the enzyme in an inactive conformation. The H4 peptide binds to the core2 domain coincident with one of the AutoN-binding sites, explaining the ISWI activation by H4. The H4-binding surface is conserved in Snf2 and functions beyond AutoN regulation. The C-terminal NegC domain is involved in binding to the core2 domain and functions as an allosteric element for ISWI to respond to the extranucleosomal DNA length.
C1 [Yan, Lijuan; Wang, Li; Tian, Yuanyuan; Xia, Xian; Chen, Zhucheng] Tsinghua Univ, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Yan, Lijuan; Wang, Li; Tian, Yuanyuan; Xia, Xian; Chen, Zhucheng] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University
RP Chen, ZC (corresponding author), Tsinghua Univ, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.; Chen, ZC (corresponding author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
EM Zhucheng_chen@tsinghua.edu.cn
FU Chinese Key Research Plan-Protein Sciences [2014CB910100]; National Natural Science Foundation of China [31570731, 31270762]; 'Junior One Thousand Talents' program
NR 31
TC 76
Z9 93
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 466
EP +
DI 10.1038/nature20590
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800049
PM 27919072
DA 2026-03-09
ER

PT J
AU Kojima, Y
   Volkmer, JP
   McKenna, K
   Civelek, M
   Lusis, AJ
   Miller, CL
   Direnzo, D
   Nanda, V
   Ye, JQ
   Connolly, AJ
   Schadt, EE
   Quertermous, T
   Betancur, P
   Maegdefessel, L
   Matic, LP
   Hedin, U
   Weissman, IL
   Leeper, NJ
AF Kojima, Yoko
   Volkmer, Jens-Peter
   McKenna, Kelly
   Civelek, Mete
   Lusis, Aldons Jake
   Miller, Clint L.
   Direnzo, Daniel
   Nanda, Vivek
   Ye, Jianqin
   Connolly, Andrew J.
   Schadt, Eric E.
   Quertermous, Thomas
   Betancur, Paola
   Maegdefessel, Lars
   Matic, Ljubica Perisic
   Hedin, Ulf
   Weissman, Irving L.
   Leeper, Nicholas J.
TI CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis
SO NATURE
LA English
DT Article
ID smooth-muscle-cells; apoptotic cells; plaque instability; mertk receptor; lesions; gene; cd47; transdifferentiation; efferocytosis; macrophages
AB Atherosclerosis is the disease process that underlies heart attack and stroke(1). Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris(2). Why these cells are not cleared remains unknown(3). Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or 'efferocytosis'(4-7). We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models. Mechanistic studies implicate the pro-atherosclerotic factor TNF-alpha as a fundamental driver of impaired programmed cell removal, explaining why this process is compromised in vascular disease. Similar to recent observations in cancer(5), impaired efferocytosis appears to play a pathogenic role in cardiovascular disease, but is not a fixed defect and may represent a novel therapeutic target.
C1 [Kojima, Yoko; Direnzo, Daniel; Nanda, Vivek; Ye, Jianqin; Leeper, Nicholas J.] Stanford Univ, Dept Surg, Sch Med, Div Vasc Surg, Stanford, CA 94305 USA.
   [Volkmer, Jens-Peter; McKenna, Kelly; Betancur, Paola; Weissman, Irving L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Civelek, Mete; Lusis, Aldons Jake] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
   [Miller, Clint L.; Quertermous, Thomas; Leeper, Nicholas J.] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
   [Connolly, Andrew J.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Maegdefessel, Lars] Karolinska Inst, Dept Med, Stockholm, Sweden.
   [Matic, Ljubica Perisic; Hedin, Ulf] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
C3 Stanford University; Stanford University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Stanford University; Stanford University; Icahn School of Medicine at Mount Sinai; Karolinska Institutet; Karolinska Institutet
RP Leeper, NJ (corresponding author), Stanford Univ, Dept Surg, Sch Med, Div Vasc Surg, Stanford, CA 94305 USA.; Leeper, NJ (corresponding author), Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
EM nleeper@stanford.edu
FU National Institutes of Health [R01HL12522401, R01HL12337001, U01HL099999]; Ludwig Center at Stanford; National Heart Lung and Blood Institute [T32HL098049, T32HL094274] Funding Source: NIH RePORTER
NR 42
TC 549
Z9 646
U1 12
U2 281
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 86
EP +
DI 10.1038/nature18935
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200035
PM 27437576
DA 2026-03-09
ER

PT J
AU Latorre-Pellicer, A
   Moreno-Loshuertos, R
   Lechuga-Vieco, AV
   Sánchez-Cabo, F
   Torroja, C
   Acín-Pérez, R
   Calvo, E
   Aix, E
   González-Guerra, A
   Logan, A
   Bernad-Miana, ML
   Romanos, E
   Cruz, R
   Cogliati, S
   Sobrino, B
   Carracedo, A
   Pérez-Martos, A
   Fernández-Silva, P
   Ruíz-Cabello, J
   Murphy, MP
   Flores, I
   Vázquez, J
   Enríquez, JA
AF Latorre-Pellicer, Ana
   Moreno-Loshuertos, Raquel
   Victoria Lechuga-Vieco, Ana
   Sanchez-Cabo, Fatima
   Torroja, Carlos
   Acin-Perez, Rebeca
   Calvo, Enrique
   Aix, Esther
   Gonzalez-Guerra, Andres
   Logan, Angela
   Luisa Bernad-Miana, Maria
   Romanos, Eduardo
   Cruz, Raquel
   Cogliati, Sara
   Sobrino, Beatriz
   Carracedo, Angel
   Perez-Martos, Acisclo
   Fernandez-Silva, Patricio
   Ruiz-Cabello, Jesus
   Murphy, Michael P.
   Flores, Ignacio
   Vazquez, Jesus
   Antonio Enriquez, Jose
TI Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing
SO NATURE
LA English
DT Article
ID disease; expression; mtdna; cognition; genome; cells; chain
AB Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability(1). Many studies suggest that mtDNA variants may be associated with ageing or diseases(2-4), although mechanistic evidence at the molecular level is lacking(5,6). Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals(7-9) allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains.
C1 [Latorre-Pellicer, Ana; Victoria Lechuga-Vieco, Ana; Sanchez-Cabo, Fatima; Torroja, Carlos; Acin-Perez, Rebeca; Calvo, Enrique; Aix, Esther; Gonzalez-Guerra, Andres; Cogliati, Sara; Ruiz-Cabello, Jesus; Flores, Ignacio; Vazquez, Jesus; Antonio Enriquez, Jose] Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain.
   [Latorre-Pellicer, Ana; Cruz, Raquel; Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Grp Med Xenom, Santiago De Compostela 15782, Spain.
   [Moreno-Loshuertos, Raquel; Perez-Martos, Acisclo; Fernandez-Silva, Patricio; Antonio Enriquez, Jose] Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain.
   [Victoria Lechuga-Vieco, Ana; Ruiz-Cabello, Jesus] CIBERES, C Melchor Fernandez Almagro 3, Madrid 28029, Spain.
   [Logan, Angela; Murphy, Michael P.] MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.
   [Luisa Bernad-Miana, Maria; Romanos, Eduardo] Inst Aragones Ciencias Salud, SAI Biomed & Biomat & Phenotyp Unit, Zaragoza 50009, Spain.
   [Sobrino, Beatriz; Carracedo, Angel] Complexo Hosp Univ Santiago, SERGAS, Fdn Publ Gallega Med Xenom, Santiago De Compostela 15706, Spain.
   [Carracedo, Angel] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia.
   [Ruiz-Cabello, Jesus] Univ Complutense Madrid, Madrid 28606, Spain.
C3 Centro Nacional de Investigaciones Cardiovasculares (CNIC); CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Universidade de Santiago de Compostela; University of Zaragoza; CIBER - Centro de Investigacion Biomedica en Red; CIBERES; Complexo Hospitalario Universitario de Santiago de Compostela; King Abdulaziz University; Complutense University of Madrid
RP Enríquez, JA (corresponding author), Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain.; Enríquez, JA (corresponding author), Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain.
EM jaenriquez@cnic.es
FU MEyC [SAF2015-65633-R, CSD2007-00020, SAF2012-38449, BIO2012-37926, BIO2015-67580-P]; Madrid [CAM/P2010/BMD-2402]; EU [PCIG10-GA-2011-304217, FP7-PEOPLE-2012-ITN-GA-317433]; ISC III [PI09-00946, PI12/01297, PI13-01136, PI11-00078, PRB2 (IPT13/0001), RIC ((RD12/0042/0045), RETICS (RD12/0042/00056)]; MEyC; Pro-CNIC Foundation; SO-Center of Excellence [SEV-2015-0505]; MRC [MC_U105663142] Funding Source: UKRI; Medical Research Council [MC_U105663142] Funding Source: researchfish
NR 30
TC 307
Z9 335
U1 3
U2 171
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 561
EP +
DI 10.1038/nature18618
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600031
PM 27383793
DA 2026-03-09
ER

PT J
AU Wright, NJ
   Drake, JJ
AF Wright, Nicholas J.
   Drake, Jeremy J.
TI Solar-type dynamo behaviour in fully convective stars without a tachocline
SO NATURE
LA English
DT Article
ID activity-rotation relationship; main-sequence stars; x-ray-emission; m-dwarf stars; magnetic-fields; stellar-activity; cool neighbors; generation; models; flux
AB In solar-type stars (with radiative cores and convective envelopes like our Sun), the magnetic field powers star spots, flares and other solar phenomena, as well as chromospheric and coronal emission at ultraviolet to X-ray wavelengths. The dynamo responsible for generating the field depends on the shearing of internal magnetic fields by differential rotation(1,2). The shearing has long been thought to take place in a boundary layer known as the tachocline between the radiative core and the convective envelope(3). Fully convective stars do not have a tachocline and their dynamo mechanism is expected to be very different(4), although its exact form and physical dependencies are not known. Here we report observations of four fully convective stars whose X-ray emission correlates with their rotation periods in the same way as in solar-type stars. As the X-ray activity-rotation relationship is a well-established proxy for the behaviour of the magnetic dynamo, these results imply that fully convective stars also operate a solar-type dynamo. The lack of a tachocline in fully convective stars therefore suggests that this is not a critical ingredient in the solar dynamo and supports models in which the dynamo originates throughout the convection zone.
C1 [Wright, Nicholas J.] Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
   [Drake, Jeremy J.] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
C3 Keele University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University
RP Wright, NJ (corresponding author), Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
EM nick.nwright@gmail.com
FU Royal Astronomical Society; STFC Ernest Rutherford Fellowship; NASA [NAS8-03060]; STFC [ST/M005569/1] Funding Source: UKRI
NR 46
TC 167
Z9 186
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 526
EP +
DI 10.1038/nature18638
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600023
PM 27466124
DA 2026-03-09
ER

PT J
AU Schmidt, HR
   Zheng, SD
   Gurpinar, E
   Koehl, A
   Manglik, A
   Kruse, AC
AF Schmidt, Hayden R.
   Zheng, Sanduo
   Gurpinar, Esin
   Koehl, Antoine
   Manglik, Aashish
   Kruse, Andrew C.
TI Crystal structure of the human σ1 receptor
SO NATURE
LA English
DT Article
ID amino-acid-residues; ligand; pharmacology; proteins; conservation; activation; expression; mutation; binding; domain
AB The human sigma 1 receptor is an enigmatic endoplasmic-reticulumresident transmembrane protein implicated in a variety of disorders including depression, drug addiction, and neuropathic pain(1). Recently, an additional connection to amyotrophic lateral sclerosis has emerged from studies of human genetics and mouse models(2). Unlike many transmembrane receptors that belong to large, extensively studied families such as G-protein- coupled receptors or ligand-gated ion channels, the sigma 1 receptor is an evolutionary isolate with no discernible similarity to any other human protein. Despite its increasingly clear importance in human physiology and disease, the molecular architecture of the s1 receptor and its regulation by drug-like compounds remain poorly defined. Here we report crystal structures of the human sigma 1 receptor in complex with two chemically divergent ligands, PD144418 and 4-IBP. The structures reveal a trimeric architecture with a single transmembrane domain in each protomer. The carboxy-terminal domain of the receptor shows an extensive flat, hydrophobic membrane-proximal surface, suggesting an intimate association with the cytosolic surface of the endoplasmic reticulum membrane in cells. This domain includes a cupin-like beta-barrel with the ligand-binding site buried at its centre. This large, hydrophobic ligand-binding cavity shows remarkable plasticity in ligand recognition, binding the two ligands in similar positions despite dissimilar chemical structures. Taken together, these results reveal the overall architecture, oligomerization state, and molecular basis for ligand recognition by this important but poorly understood protein.
C1 [Schmidt, Hayden R.; Zheng, Sanduo; Gurpinar, Esin; Kruse, Andrew C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Koehl, Antoine; Manglik, Aashish] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
C3 Harvard University; Harvard Medical School; Stanford University
RP Kruse, AC (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM andrew_kruse@hms.harvard.edu
FU Merck Postdoctoral Fellowship in Biological Chemistry and Molecular Pharmacology; National Institutes of Health Cellular and Developmental Biology training grant at Harvard Medical School [T32GM007226]; National Institute of General Medical Sciences [T32GM007226] Funding Source: NIH RePORTER
NR 44
TC 410
Z9 447
U1 3
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 527
EP +
DI 10.1038/nature17391
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900053
PM 27042935
DA 2026-03-09
ER

PT J
AU Münch, C
   Harper, JW
AF Munch, Christian
   Harper, J. Wade
TI Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation
SO NATURE
LA English
DT Article
ID cancer-cell line; stress-response; activation; expression; pathways; elegans; element; hsp90; upr
AB The mitochondrial matrix is unique in that it must integrate the folding and assembly of proteins derived from the nuclear and mitochondrial genomes. In Caenorhabditis elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis(1-3). While misfolded mitochondrial-matrix-localized ornithine transcarbamylase induces chaperonin expression(4-6), our understanding of mammalian UPRmt is rudimentary(7), reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 (ref. 8) or LON protease(9), which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response encompasses widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing caused by transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3 (ref. 10). This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.
C1 [Munch, Christian; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Harper, JW (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM wade_harper@hms.harvard.edu
FU National Institutes of Health [R37NS083524]; Biogen, Inc.; EMBO Fellowship
NR 28
TC 242
Z9 288
U1 3
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 710
EP +
DI 10.1038/nature18302
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000042
PM 27350246
DA 2026-03-09
ER

PT J
AU Tyrakis, PA
   Palazon, A
   Macias, D
   Lee, KL
   Phan, AT
   Veliça, P
   You, J
   Chia, GS
   Sim, J
   Doedens, A
   Abelanet, A
   Evans, CE
   Griffiths, JR
   Poellinger, L
   Goldrath, AW
   Johnson, RS
AF Tyrakis, Petros A.
   Palazon, Asis
   Macias, David
   Lee, Kian L.
   Phan, Anthony T.
   Velica, Pedro
   You, Jia
   Chia, Grace S.
   Sim, Jingwei
   Doedens, Andrew
   Abelanet, Alice
   Evans, Colin E.
   Griffiths, John R.
   Poellinger, Lorenz
   Goldrath, Ananda W.
   Johnson, Randall S.
TI S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate
SO NATURE
LA English
DT Article
ID cell-differentiation; alpha-ketoglutarate; oncometabolite 2-hydroxyglutarate; gene-expression; mutant idh; memory; effector; cancer; metabolism; antigen
AB R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8(+) T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1 alpha)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8(+) T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1 alpha stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8(+) T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function.
C1 [Tyrakis, Petros A.; Palazon, Asis; Macias, David; Sim, Jingwei; Abelanet, Alice; Evans, Colin E.; Johnson, Randall S.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England.
   [Tyrakis, Petros A.; Griffiths, John R.] Univ Cambridge, Cambridge Inst, Canc Res UK, Cambridge, England.
   [Lee, Kian L.; You, Jia; Chia, Grace S.; Poellinger, Lorenz] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore.
   [Phan, Anthony T.; Doedens, Andrew; Goldrath, Ananda W.] Univ Calif San Diego, Mol Biol Sect, La Jolla, CA USA.
   [Velica, Pedro; Poellinger, Lorenz; Johnson, Randall S.] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
C3 University of Cambridge; Cancer Research UK; University of Cambridge; CRUK Cambridge Institute; National University of Singapore; University of California System; University of California San Diego; Karolinska Institutet
RP Johnson, RS (corresponding author), Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England.; Johnson, RS (corresponding author), Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
EM rsj33@cam.ac.uk
FU CRUK; MRC [1495954]; Wellcome Trust [WT092738MA]; Marie-Curie IEF; UCSD NIH Grant [5T32GM007240-36]; NIH [A1096852, A1072117]; Leukemia and Lymphoma Society; Pew Scholars Fund; Singapore National Research Foundation; Singapore Ministry of Education; NMRC [NMRC/CIRG/1389/2014]; Swedish Research Council; Swedish Cancer Foundation (Cancerfonden); Swedish Research Council (Vetenskapsradet); National Institute of Allergy and Infectious Diseases [R01AI072117] Funding Source: NIH RePORTER; Cancer Research UK [11562] Funding Source: researchfish; Medical Research Council [1495954] Funding Source: researchfish; Wellcome Trust [092738/Z/10/Z] Funding Source: researchfish
NR 50
TC 353
Z9 383
U1 2
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 236
EP +
DI 10.1038/nature20165
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700050
PM 27798602
DA 2026-03-09
ER

PT J
AU Greene, JS
   Brown, M
   Dobosiewicz, M
   Ishida, IG
   Macosko, EZ
   Zhang, XX
   Butcher, RA
   Cline, DJ
   McGrath, PT
   Bargmann, CI
AF Greene, Joshua S.
   Brown, Maximillian
   Dobosiewicz, May
   Ishida, Itzel G.
   Macosko, Evan Z.
   Zhang, Xinxing
   Butcher, Rebecca A.
   Cline, Devin J.
   McGrath, Patrick T.
   Bargmann, Cornelia I. .
TI Balancing selection shapes density-dependent foraging behaviour
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; c-elegans; protein-kinase; pheromone; gene; evolution; cgmp; polymorphism; drosophila; diversity
AB The optimal foraging strategy in a given environment depends on the number of competing individuals and their behavioural strategies. Little is known about the genes and neural circuits that integrate social information into foraging decisions. Here we show that ascaroside pheromones, small glycolipids that signal population density, suppress exploratory foraging in Caenorhabditis elegans, and that heritable variation in this behaviour generates alternative foraging strategies. We find that natural C. elegans isolates differ in their sensitivity to the potent ascaroside icas#9 (IC-asc-C5). A quantitative trait locus (QTL) regulating icas#9 sensitivity includes srx-43, a G-protein-coupled icas#9 receptor that acts in the ASI class of sensory neurons to suppress exploration. Two ancient haplotypes associated with this QTL confer competitive growth advantages that depend on ascaroside secretion, its detection by srx-43 and the distribution of food. These results suggest that balancing selection at the srx-43 locus generates alternative density-dependent behaviours, fulfilling a prediction of foraging game theory.
C1 [Greene, Joshua S.; Brown, Maximillian; Dobosiewicz, May; Ishida, Itzel G.; Macosko, Evan Z.; Bargmann, Cornelia I. .] Rockefeller Univ, Howard Hughes Med Inst, Lulu & Anthony Wang Lab Neural Circuits & Behav, New York, NY 10065 USA.
   [Zhang, Xinxing; Butcher, Rebecca A.] Univ Florida, Dept Chem, Gainesville, FL 32611 USA.
   [Cline, Devin J.; McGrath, Patrick T.] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA.
C3 Rockefeller University; Howard Hughes Medical Institute; State University System of Florida; University of Florida; University System of Georgia; Georgia Institute of Technology
RP Bargmann, CI (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lulu & Anthony Wang Lab Neural Circuits & Behav, New York, NY 10065 USA.
EM cori@rockefeller.edu
FU Research Corporation for Science Advancement [22844]; NIH [R01GM114170, F30 MH101931-03]; Ellison Medical Foundation
NR 38
TC 94
Z9 115
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 254
EP +
DI 10.1038/nature19848
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500037
PM 27799655
DA 2026-03-09
ER

PT J
AU Taylor-Weiner, A
   Zack, T
   O'Donnell, E
   Guerriero, JL
   Bernard, B
   Reddy, A
   Han, GC
   AlDubayan, S
   Amin-Mansour, A
   Schumacher, SE
   Litchfield, K
   Turnbull, C
   Gabriel, S
   Beroukhim, R
   Getz, G
   Carter, SL
   Hirsch, MS
   Letai, A
   Sweeney, C
   Van Allen, EM
AF Taylor-Weiner, Amaro
   Zack, Travis
   O'Donnell, Elizabeth
   Guerriero, Jennifer L.
   Bernard, Brandon
   Reddy, Anita
   Han, G. Celine
   AlDubayan, Saud
   Amin-Mansour, Ali
   Schumacher, Steven E.
   Litchfield, Kevin
   Turnbull, Clare
   Gabriel, Stacey
   Beroukhim, Rameen
   Getz, Gad
   Carter, Scott L.
   Hirsch, Michelle S.
   Letai, Anthony
   Sweeney, Christopher
   Van Allen, Eliezer M. .
TI Genomic evolution and chemoresistance in germ-cell tumours
SO NATURE
LA English
DT Article
ID dna-damage; cancer; mutations; reveals; quantification; association; discovery; culture; samples
AB Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes(1,2). GCTs are histologically heterogeneous and distinctly curable with chemotherapy(3). Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs(4-6), but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue(7), we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1)(8,9) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.
C1 [Taylor-Weiner, Amaro; Zack, Travis] Harvard Univ, Div Med Sci, Boston, MA 02115 USA.
   [Taylor-Weiner, Amaro; Han, G. Celine; Amin-Mansour, Ali; Schumacher, Steven E.; Gabriel, Stacey; Beroukhim, Rameen; Getz, Gad; Carter, Scott L.; Van Allen, Eliezer M. .] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.
   [Zack, Travis] Harvard Med Sch, Hlth Sci & Technol, Boston, MA 02115 USA.
   [O'Donnell, Elizabeth; Guerriero, Jennifer L.; Bernard, Brandon; Han, G. Celine; Beroukhim, Rameen; Letai, Anthony; Sweeney, Christopher; Van Allen, Eliezer M. .] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [O'Donnell, Elizabeth] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
   [Reddy, Anita] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
   [AlDubayan, Saud] Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA.
   [AlDubayan, Saud] King Saud bin Abdulaziz Univ Hlth Sci, Dept Med, Riyadh, Saudi Arabia.
   [Schumacher, Steven E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Litchfield, Kevin; Turnbull, Clare] Inst Canc Res, Div Genet & Epidemiol, Fulham Rd, London SW3 6JB, England.
   [Litchfield, Kevin; Turnbull, Clare] Queen Mary Univ London, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England.
   [Getz, Gad] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA.
   [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Carter, Scott L.; Van Allen, Eliezer M. .] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA.
   [Carter, Scott L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Carter, Scott L.] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
   [Hirsch, Michelle S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; King Saud Bin Abdulaziz University for Health Sciences; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; University of London; Queen Mary University London; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Van Allen, EM (corresponding author), Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.; Van Allen, EM (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Van Allen, EM (corresponding author), Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA.
EM eliezerm_vanallen@dfci.harvard.edu
FU NIH [U54 HG003067, 1K08 CA188615]; Damon Runyon Clinical Investigator Award; Shawmut Design and Construction Pan Mass Challenge Team; Giovino Jimmy Fund Golf Tournament; NIH Office of the Director; National Human Genome Research Institute [T32HG002295] Funding Source: NIH RePORTER
NR 43
TC 139
Z9 149
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 114
EP +
DI 10.1038/nature20596
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600059
PM 27905446
DA 2026-03-09
ER

PT J
AU Nuttle, X
   Giannuzzi, G
   Duyzend, MH
   Schraiber, JG
   Narvaiza, I
   Sudmant, PH
   Penn, O
   Chiatante, G
   Malig, M
   Huddleston, J
   Benner, C
   Camponeschi, F
   Ciofi-Baffoni, S
   Stessman, HAF
   Marchetto, MCN
   Denman, L
   Harshman, L
   Baker, C
   Raja, A
   Penewit, K
   Janke, N
   Tang, WJ
   Ventura, M
   Banci, L
   Antonacci, F
   Akey, JM
   Amemiya, CT
   Gage, FH
   Reymond, A
   Eichler, EE
AF Nuttle, Xander
   Giannuzzi, Giuliana
   Duyzend, Michael H.
   Schraiber, Joshua G.
   Narvaiza, Inigo
   Sudmant, Peter H.
   Penn, Osnat
   Chiatante, Giorgia
   Malig, Maika
   Huddleston, John
   Benner, Chris
   Camponeschi, Francesca
   Ciofi-Baffoni, Simone
   Stessman, Holly A. F.
   Marchetto, Maria C. N.
   Denman, Laura
   Harshman, Lana
   Baker, Carl
   Raja, Archana
   Penewit, Kelsi
   Janke, Nicolette
   Tang, W. Joyce
   Ventura, Mario
   Banci, Lucia
   Antonacci, Francesca
   Akey, Joshua M.
   Amemiya, Chris T.
   Gage, Fred H.
   Reymond, Alexandre
   Eichler, Evan E.
TI Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility
SO NATURE
LA English
DT Article
ID genome sequence; positive selection; humans; identification; microdeletion; neanderthal; population; diversity; evolution; dna
AB Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates(1), including more recently the genomes of archaic hominins(2,3). Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism(4,5) and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair segment containing BOLA2 duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage-a pattern unlikely to have arisen so rapidly in the absence of selection (P < 0.0097). We show that the duplication of BOLA2 led to a novel, human-specific in-frame fusion transcript and that BOLA2 copy number correlates with both RNA expression (r = 0.36) and protein level (r = 0.65), with the greatest expression difference between human and chimpanzee in experimentally derived stem cells. Analyses of 152 patients carrying a chromosome 16p11.2 rearrangement show that more than 96% of breakpoints occur within the H. sapiens-specific duplication. In summary, the duplicative transposition of BOLA2 at the root of the H. sapiens lineage about 282 ka simultaneously increased copy number of a gene associated with iron homeostasis and predisposed our species to recurrent rearrangements associated with disease.
C1 [Nuttle, Xander; Duyzend, Michael H.; Schraiber, Joshua G.; Sudmant, Peter H.; Penn, Osnat; Malig, Maika; Huddleston, John; Stessman, Holly A. F.; Denman, Laura; Harshman, Lana; Baker, Carl; Raja, Archana; Penewit, Kelsi; Janke, Nicolette; Akey, Joshua M.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Giannuzzi, Giuliana; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Narvaiza, Inigo; Benner, Chris; Marchetto, Maria C. N.; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Chiatante, Giorgia; Ventura, Mario; Antonacci, Francesca] Univ Bari Aldo Moro, Dipartimento Biol, I-70125 Bari, Italy.
   [Huddleston, John; Raja, Archana; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Camponeschi, Francesca; Ciofi-Baffoni, Simone; Banci, Lucia] Univ Florence, Dept Chem, Via Lastruccia 3, I-50019 Florence, Italy.
   [Ciofi-Baffoni, Simone; Banci, Lucia] Univ Florence, Magnet Resonance Ctr CERM, Via Luigi Sacconi 6, I-50019 Florence, Italy.
   [Tang, W. Joyce; Amemiya, Chris T.] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA.
   [Gage, Fred H.] Ctr Acad Res & Training Anthropogeny, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Sudmant, Peter H.] MIT, Program Computat & Syst Biol, Cambridge, MA 02142 USA.
C3 University of Washington; University of Washington Seattle; University of Lausanne; Salk Institute; Universita degli Studi di Bari Aldo Moro; Howard Hughes Medical Institute; University of Florence; University of Florence; Virginia Mason Medical Center; Benaroya Research Institute; Massachusetts Institute of Technology (MIT)
RP Eichler, EE (corresponding author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.; Reymond, A (corresponding author), Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.; Eichler, EE (corresponding author), Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM alexandre.reymond@unil.ch; eee@gs.washington.edu
FU Paul G. Allen Foundation [11631]; Simons Foundation Autism Research Initiative (SFARI) [303241, 274424]; US National Institutes of Health (NIH) [2R01HG002385]; Swiss National Science Foundation [31003A_160203, CRSII33-133044]; NIH [TR01 MH095741]; Helmsley Charitable Fund; Mathers Foundation; JPB Foundation; US National Science Foundation [DGE-1256082]; Faculty of Biology and Medicine, University of Lausanne; US National Institute of Mental Health [1F30MH105055-01]; Human Frontier Science Program postdoctoral fellowship; EC [N653706]; Ente Cassa di Risparmio grant [2013/7201]; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG002385] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER
NR 39
TC 96
Z9 115
U1 1
U2 42
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 205
EP +
DI 10.1038/nature19075
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100035
PM 27487209
DA 2026-03-09
ER

PT J
AU Letts, JA
   Fiedorczuk, K
   Sazanov, LA
AF Letts, James A.
   Fiedorczuk, Karol
   Sazanov, Leonid A.
TI The architecture of respiratory supercomplexes
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; mitochondrial electron-transport; em structure determination; bovine heart-mitochondria; complex-i; cryo-em; mammalian mitochondria; chain supercomplexes; crystal-structures; kinetic evidence
AB Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII2CIV (the respirasome)-a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.8 angstrom and 6.7 angstrom, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII2 at 7.8 resolution. All observed density can be attributed to the known 80 subunitsof the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain.
C1 [Letts, James A.; Fiedorczuk, Karol; Sazanov, Leonid A.] IST Austria, A-3400 Klosterneuburg, Austria.
   [Fiedorczuk, Karol] MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
C3 Institute of Science & Technology - Austria
RP Sazanov, LA (corresponding author), IST Austria, A-3400 Klosterneuburg, Austria.
EM sazanov@ist.ac.at
FU FEBS; MRC UK; MRC [MC_U105674180] Funding Source: UKRI; Medical Research Council [1601061, 1373852, MC_U105674180] Funding Source: researchfish
NR 69
TC 416
Z9 452
U1 2
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 644
EP +
DI 10.1038/nature19774
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700042
PM 27654913
DA 2026-03-09
ER

PT J
AU Saxton, RA
   Chantranupong, L
   Knockenhauer, KE
   Schwartz, TU
   Sabatini, DM
AF Saxton, Robert A.
   Chantranupong, Lynne
   Knockenhauer, Kevin E.
   Schwartz, Thomas U.
   Sabatini, David M.
TI Mechanism of arginine sensing by CASTOR1 upstream of mTORC1
SO NATURE
LA English
DT Article
ID signal integration; tumor-suppressor; rag gtpases; act domain; kinase; complex; sufficiency; evolution; proteins; raptor
AB The mechanistic Target of Rapamycin Complex 1 (mTORC1) is a major regulator of eukaryotic growth that coordinates anabolic and catabolic cellular processes with inputs such as growth factors and nutrients, including amino acids(1-3). In mammals arginine is particularly important, promoting diverse physiological effects such as immune cell activation, insulin secretion, and muscle growth, largely mediated through activation of mTORC1 (refs 4-7). Arginine activates mTORC1 upstream of the Rag family of GTPases(8), through either the lysosomal amino acid transporter SLC38A9 or the GATOR2-interacting Cellular Arginine Sensor for mTORC1 (CASTOR1)(9-12). However, the mechanism by which the mTORC1 pathway detects and transmits this arginine signal has been elusive. Here, we present the 1.8 angstrom crystal structure of arginine-bound CASTOR1. Homodimeric CASTOR1 binds arginine at the interface of two Aspartate kinase, Chorismate mutase, TyrA (ACT) domains, enabling allosteric control of the adjacent GATOR2-binding site to trigger dissociation from GATOR2 and downstream activation of mTORC1. Our data reveal that CASTOR1 shares substantial structural homology with the lysine-binding regulatory domain of prokaryotic aspartate kinases, suggesting that the mTORC1 pathway exploited an ancient, amino-acid-dependent allosteric mechanism to acquire arginine sensitivity. Together, these results establish a structural basis for arginine sensing by the mTORC1 pathway and provide insights into the evolution of a mammalian nutrient sensor.
C1 [Saxton, Robert A.; Chantranupong, Lynne; Knockenhauer, Kevin E.; Schwartz, Thomas U.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Saxton, Robert A.; Chantranupong, Lynne; Sabatini, David M.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
   [Saxton, Robert A.; Chantranupong, Lynne; Sabatini, David M.] Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Saxton, Robert A.; Chantranupong, Lynne; Sabatini, David M.] Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Saxton, Robert A.; Chantranupong, Lynne; Sabatini, David M.] Harvard & Massachusetts Inst Technol, Broad Inst, 415 Main St, Cambridge, MA 02142 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Schwartz, TU; Sabatini, DM (corresponding author), MIT, Dept Biol, Cambridge, MA 02139 USA.; Sabatini, DM (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.; Sabatini, DM (corresponding author), Howard Hughes Med Inst, Cambridge, MA 02139 USA.; Sabatini, DM (corresponding author), Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Sabatini, DM (corresponding author), Harvard & Massachusetts Inst Technol, Broad Inst, 415 Main St, Cambridge, MA 02142 USA.
EM tus@mit.edu; sabatini@wi.mit.edu
FU National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]; NIH-ORIP HEI grant [S10 RR029205]; DOE Office of Science [DE-AC02-06CH11357]; NIH [R01CA103866, AI47389, F31 CA180271]; US Department of Defense [W81XWH-07-0448]; National Cancer Institute [R01CA103866, P30CA014051] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI047389] Funding Source: NIH RePORTER
NR 41
TC 257
Z9 322
U1 2
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 229
EP +
DI 10.1038/nature19079
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100040
PM 27487210
DA 2026-03-09
ER

PT J
AU Tao, L
   Zhang, J
   Meraner, P
   Tovaglieri, A
   Wu, XQ
   Gerhard, R
   Zhang, XJ
   Stallcup, WB
   Miao, J
   He, X
   Hurdle, JG
   Breault, DT
   Brass, AL
   Dong, M
AF Tao, Liang
   Zhang, Jie
   Meraner, Paul
   Tovaglieri, Alessio
   Wu, Xiaoqian
   Gerhard, Ralf
   Zhang, Xinjun
   Stallcup, William B.
   Miao, Ji
   He, Xi
   Hurdle, Julian G.
   Breault, David T.
   Brass, Abraham L.
   Dong, Min
TI Frizzled proteins are colonic epithelial receptors for C. difficile toxin B
SO NATURE
LA English
DT Article
ID udp-glucose deficiency; clostridium-difficile; stem-cells; in-vitro; infection; model; identification; translocation; expression; virulence
AB Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.
C1 [Tao, Liang; Zhang, Jie; Dong, Min] Harvard Med Sch, Boston Childrens Hosp, Dept Urol, Boston, MA 02115 USA.
   [Tao, Liang; Zhang, Jie; Dong, Min] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Tao, Liang; Zhang, Jie; Dong, Min] Harvard Med Sch, Dept Surg, Boston, MA 02115 USA.
   [Meraner, Paul; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst MaPS, Worcester, MA 01655 USA.
   [Tovaglieri, Alessio; Miao, Ji; Breault, David T.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
   [Wu, Xiaoqian; Hurdle, Julian G.] Texas A&M Hlth Sci Ctr, Ctr Infect & Inflammatory Dis, Houston, TX 77030 USA.
   [Gerhard, Ralf] Hannover Med Sch, Inst Toxicol, D-30625 Hannover, Germany.
   [Zhang, Xinjun; He, Xi] Harvard Med Sch, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Zhang, Xinjun; He, Xi] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA.
   [Stallcup, William B.] Sanford Burnham Prebys Med Discovery Inst, Tumor Microenvironm & Canc Immunol Program, La Jolla, CA 92037 USA.
   [Miao, Ji; Breault, David T.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
   [Breault, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Med, Gastroenterol Div, Worcester, MA 01655 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; University of Massachusetts System; University of Massachusetts Worcester; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Texas A&M University System; Texas A&M University College Station; Texas A&M Health Science Center; Hannover Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Sanford Burnham Prebys Medical Discovery Institute; Harvard University; Harvard Medical School; Harvard University; University of Massachusetts System; University of Massachusetts Worcester
RP Dong, M (corresponding author), Harvard Med Sch, Boston Childrens Hosp, Dept Urol, Boston, MA 02115 USA.; Dong, M (corresponding author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Dong, M (corresponding author), Harvard Med Sch, Dept Surg, Boston, MA 02115 USA.
EM min.dong@childrens.harvard.edu
FU National Institutes of Health (NIH) [R01NS080833, R01AI091786, R01AT006732, R01DK084056, R01CA095287, K99DK100539, R01GM057603, R01GM074241, R01AR060359]; Bill and Melinda Gates Foundation; Timothy Murphy Fund; Harvard Digestive Diseases Center [NIH P30DK034854]; Boston Children's Hospital Intellectual and Developmental Disabilities Research Center [NIH P30HD18655]; Burroughs Wellcome Fund; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS080833] Funding Source: NIH RePORTER
NR 54
TC 230
Z9 286
U1 6
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 350
EP +
DI 10.1038/nature19799
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100032
PM 27680706
DA 2026-03-09
ER

PT J
AU Gerbe, F
   Sidot, E
   Smyth, DJ
   Ohmoto, M
   Matsumoto, I
   Dardalhon, V
   Cesses, P
   Garnier, L
   Pouzolles, M
   Brulin, B
   Bruschi, M
   Harcus, Y
   Zimmermann, VS
   Taylor, N
   Maizels, RM
   Jay, P
AF Gerbe, Francois
   Sidot, Emmanuelle
   Smyth, Danielle J.
   Ohmoto, Makoto
   Matsumoto, Ichiro
   Dardalhon, Valerie
   Cesses, Pierre
   Garnier, Laure
   Pouzolles, Marie
   Brulin, Benedicte
   Bruschi, Marco
   Harcus, Yvonne
   Zimmermann, Valerie S.
   Taylor, Naomi
   Maizels, Rick M.
   Jay, Philippe
TI Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites
SO NATURE
LA English
DT Article
ID nippostrongylus-brasiliensis; stem-cells; differentiation; generation; expulsion; il-13; sox9
AB Helminth parasitic infections are a major global health and social burden(1). The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity(2). Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion(3,4). However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium(5), are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature(6) and we demonstrate that they undergo a rapid and extensive IL-4R alpha-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that the Pou2f3 gene is essential for tuft cell specification. Pou2f3(-/-) mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4R alpha signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection.
C1 [Gerbe, Francois; Sidot, Emmanuelle; Cesses, Pierre; Garnier, Laure; Brulin, Benedicte; Bruschi, Marco; Jay, Philippe] CNRS, UMR 5203, Inst Genom Fonct, F-34094 Montpellier, France.
   [Gerbe, Francois; Sidot, Emmanuelle; Cesses, Pierre; Garnier, Laure; Brulin, Benedicte; Bruschi, Marco; Jay, Philippe] INSERM, U1191, F-34094 Montpellier, France.
   [Gerbe, Francois; Sidot, Emmanuelle; Dardalhon, Valerie; Cesses, Pierre; Garnier, Laure; Pouzolles, Marie; Brulin, Benedicte; Bruschi, Marco; Zimmermann, Valerie S.; Taylor, Naomi; Jay, Philippe] Univ Montpellier, F-34000 Montpellier, France.
   [Smyth, Danielle J.; Harcus, Yvonne; Maizels, Rick M.] Univ Edinburgh, Inst Immunol & Infect Res, Sch Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Smyth, Danielle J.; Harcus, Yvonne; Maizels, Rick M.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Ohmoto, Makoto; Matsumoto, Ichiro] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
   [Dardalhon, Valerie; Pouzolles, Marie; Zimmermann, Valerie S.; Taylor, Naomi] CNRS, UMR5535, Inst Genet Mol Montpellier, F-34293 Montpellier, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Universite de Montpellier; University of Edinburgh; University of Edinburgh; Monell Chemical Senses Center; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Jay, P (corresponding author), CNRS, UMR 5203, Inst Genom Fonct, F-34094 Montpellier, France.
EM philippe.jay@igf.cnrs.fr
FU Association pour la Recherche contre le Cancer (ARC) [SL220110603456]; Agence Nationale de la Recherche [ANR-09-BLAN-0368-01, ANR-14-CE14-0025-01]; Institut National du Cancer [INCa 2014-174]; CNRS-NIH International Laboratory grant from the CNRS (LIA-BAGEL); Welcome Trust [106122]; Monell Chemical Senses Center; Ligue Nationale contre le Cancer; LabEx EpiGenMed; Inserm; NIH [P30DC011735]; Agence Nationale de la Recherche (ANR) [ANR-14-CE14-0025, ANR-09-BLAN-0368] Funding Source: Agence Nationale de la Recherche (ANR)
NR 30
TC 727
Z9 906
U1 6
U2 138
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 226
EP U260
DI 10.1038/nature16527
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700040
PM 26762460
DA 2026-03-09
ER

PT J
AU Matyskiela, ME
   Lu, G
   Ito, T
   Pagarigan, B
   Lu, CC
   Miller, K
   Fang, W
   Wang, NY
   Nguyen, D
   Houston, J
   Carmel, G
   Tran, T
   Riley, M
   Nosaka, L
   Lander, GC
   Gaidarova, S
   Xu, SC
   Ruchelman, AL
   Handa, H
   Carmichael, J
   Daniel, TO
   Cathers, BE
   Lopez-Girona, A
   Chamberlain, PP
AF Matyskiela, Mary E.
   Lu, Gang
   Ito, Takumi
   Pagarigan, Barbra
   Lu, Chin-Chun
   Miller, Karen
   Fang, Wei
   Wang, Nai-Yu
   Nguyen, Derek
   Houston, Jack
   Carmel, Gilles
   Tran, Tam
   Riley, Mariko
   Nosaka, Lyn'Al
   Lander, Gabriel C.
   Gaidarova, Svetlana
   Xu, Shuichan
   Ruchelman, Alexander L.
   Handa, Hiroshi
   Carmichael, James
   Daniel, Thomas O.
   Cathers, Brian E.
   Lopez-Girona, Antonia
   Chamberlain, Philip P.
TI A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
SO NATURE
LA English
DT Article
ID lenalidomide; target; degradation; proteins; complex; ikaros; pomalidomide; recognition; thalidomide; hydroxyproline
AB Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4(CRBN) E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity. The anti-tumour activity of CC-885 is mediated through the cereblon-dependent ubiquitination and degradation of the translation termination factor GSPT1. Patient-derived acute myeloid leukaemia tumour cells exhibit high sensitivity to CC-885, indicating the clinical potential of this mechanism. Crystallographic studies of the CRBN-DDB1-CC-885-GSPT1 complex reveal that GSPT1 binds to cereblon through a surface turn containing a glycine residue at a key position, interacting with both CC-885 and a 'hotspot' on the cereblon surface. Although GSPT1 possesses no obvious structural, sequence or functional homology to previously known cereblon substrates, mutational analysis and modelling indicate that the cereblon substrate Ikaros uses a similar structural feature to bind cereblon, suggesting a common motif for substrate recruitment. These findings define a structural degron underlying cereblon 'neosubstrate' selectivity, and identify an anti-tumour target rendered druggable by cereblon modulation.
C1 [Matyskiela, Mary E.; Lu, Gang; Pagarigan, Barbra; Lu, Chin-Chun; Miller, Karen; Fang, Wei; Wang, Nai-Yu; Nguyen, Derek; Houston, Jack; Carmel, Gilles; Tran, Tam; Riley, Mariko; Gaidarova, Svetlana; Xu, Shuichan; Ruchelman, Alexander L.; Carmichael, James; Daniel, Thomas O.; Cathers, Brian E.; Lopez-Girona, Antonia; Chamberlain, Philip P.] Celgene Corp, 10300 Campus Point Dr,Suite 100, San Diego, CA 92121 USA.
   [Ito, Takumi; Handa, Hiroshi] Tokyo Med Univ, Dept Nanoparticle Translat Res, Shinjuku Ku, Tokyo 1608402, Japan.
   [Nosaka, Lyn'Al; Lander, Gabriel C.] Scripps Res Inst, San Diego, CA 92121 USA.
C3 Bristol-Myers Squibb; Celgene Corporation; Tokyo Medical University; Scripps Research Institute
RP Lu, G; Chamberlain, PP (corresponding author), Celgene Corp, 10300 Campus Point Dr,Suite 100, San Diego, CA 92121 USA.
EM glu@celgene.com; pchamberlain@celgene.com
FU National Institutes of Health, National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Ministry of Education, Culture, Sports, Science and Technology (MEXT) [23102002]; JST, PRESTO; MEXT [26750374]; Grants-in-Aid for Scientific Research [26750374, 23102002] Funding Source: KAKEN
NR 34
TC 525
Z9 626
U1 8
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 252
EP +
DI 10.1038/nature18611
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600050
PM 27338790
DA 2026-03-09
ER

PT J
AU Decorsiere, A
   Mueller, H
   Van Breugel, PC
   Abdul, F
   Gerossier, L
   Beran, RK
   Livingston, CM
   Niu, CR
   Fletcher, SP
   Hantz, O
   Strubin, M
AF Decorsiere, Adrien
   Mueller, Henrik
   Van Breugel, Pieter C.
   Abdul, Fabien
   Gerossier, Laetitia
   Beran, Rudolf K.
   Livingston, Christine M.
   Niu, Congrong
   Fletcher, Simon P.
   Hantz, Olivier
   Strubin, Michel
TI Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor
SO NATURE
LA English
DT Article
ID in-vivo; human hepatocytes; hbv replication; cell-death; dna; infection; binding; chromosome; expression; cohesin
AB Chronic hepatitis B virus infection is a leading cause of cirrhosis and liver cancer(1,2). Hepatitis B virus encodes the regulatory HBx protein whose primary role is to promote transcription of the viral genome, which persists as an extrachromosomal DNA circle in infected cells(3-5). HBx accomplishes this task by an unusual mechanism, enhancing transcription only from extrachromosomal DNA templates(6). Here we show that HBx achieves this by hijacking the cellular DDB1-containing E3 ubiquitin ligase to target the 'structural maintenance of chromosomes' (Smc) complex Smc5/6 for degradation. Blocking this event inhibits the stimulatory effect of HBx both on extrachromosomal reporter genes and on hepatitis B virus transcription. Conversely, silencing the Smc5/6 complex enhances extrachromosomal reporter gene transcription in the absence of HBx, restores replication of an HBx-deficient hepatitis B virus, and rescues wild-type hepatitis B virus in a DDB1-knockdown background. The Smc5/6 complex associates with extrachromosomal reporters and the hepatitis B virus genome, suggesting a direct mechanism of transcriptional inhibition. These results uncover a novel role for the Smc5/6 complex as a restriction factor selectively blocking extrachromosomal DNA transcription. By destroying this complex, HBx relieves the inhibition to allow productive hepatitis B virus gene expression.
C1 [Decorsiere, Adrien; Mueller, Henrik; Van Breugel, Pieter C.; Abdul, Fabien; Strubin, Michel] Univ Med Ctr CMU, Dept Microbiol & Mol Med, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.
   [Gerossier, Laetitia; Hantz, Olivier] Univ Lyon, CRCL, INSERM U1052, CNRS 5286, 151 Cours A Thomas, F-69424 Lyon, France.
   [Beran, Rudolf K.; Livingston, Christine M.; Niu, Congrong; Fletcher, Simon P.] Gilead Sci Inc, 333 Lakeside Dr, Foster City, CA 94404 USA.
   [Mueller, Henrik] F Hoffmann La Roche Ltd, Infect Dis Discovery & Translat Area, Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev, Grenzacherstr 124, CH-4070 Basel, Switzerland.
   [Van Breugel, Pieter C.] Netherlands Canc Inst, Div Biol Stress Response, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
C3 UNICANCER; Centre Leon Berard; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Lyon 1; Gilead Sciences; Roche Holding; Netherlands Cancer Institute
RP Strubin, M (corresponding author), Univ Med Ctr CMU, Dept Microbiol & Mol Med, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland.; Hantz, O (corresponding author), Univ Lyon, CRCL, INSERM U1052, CNRS 5286, 151 Cours A Thomas, F-69424 Lyon, France.; Fletcher, SP (corresponding author), Gilead Sci Inc, 333 Lakeside Dr, Foster City, CA 94404 USA.
EM Simon.Fletcher@gilead.com; olivier.hantz@inserm.fr; michel.strubin@unige.ch
FU CLARA (Lyon); French National Agency for Research against AIDS and viral hepatitis (ANRS); Swiss National Science Foundation [31003A-127384, 310030-149626]; Canton of Geneva; Swiss National Science Foundation (SNF) [31003A_127384, 310030_149626] Funding Source: Swiss National Science Foundation (SNF)
NR 44
TC 439
Z9 498
U1 2
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 386
EP +
DI 10.1038/nature17170
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300056
PM 26983541
DA 2026-03-09
ER

PT J
AU Veedu, DM
   Barbot, S
AF Veedu, Deepa Mele
   Barbot, Sylvain
TI The Parkfield tremors reveal slow and fast ruptures on the same asperity
SO NATURE
LA English
DT Article
ID san-andreas fault; postseismic relaxation; friction; earthquakes; complexity; stability; zone
AB The deep extension of the San Andreas Fault is believed to be creeping, but the recent observations of tectonic tremors from these depths indicate a complex deformation style1. In particular, an isolated tremor source near Parkfield has been producing a sequence of low-frequency earthquakes2 that indicates an uncommon mechanism of stress accumulation and release. The tremor pattern regularly oscillated between three and six days from mid-2003 until it was disrupted by the 2004 magnitude 6.0 Parkfield earthquake. After that event, the tremor source ruptured only about every three days, but over the next two years it gradually returned to its initial alternating recurrence pattern. The mechanism that drives this recurrence pattern is unknown. Here we use physics-based models to show that the same tremor asperity-the region from which the low-frequency earthquakes radiate-can regularly slip in slow and fast ruptures, naturally resulting in recurrence intervals alternating between three and six days. This unusual slip behaviour occurs when the tremor asperity size is close to the critical nucleation size of earthquakes. We also show that changes in pore pressure following the Parkfield earthquake can explain the sudden change and gradual recovery of the recurrence intervals. Our findings suggest a framework for fault deformation in which the same asperity can release tectonic stress through both slow and fast ruptures.
C1 [Veedu, Deepa Mele; Barbot, Sylvain] Nanyang Technol Univ, Earth Observat Singapore, Asian Sch Environm, 50 Nanyang Ave, Singapore 639798, Singapore.
C3 Nanyang Technological University
RP Barbot, S (corresponding author), Nanyang Technol Univ, Earth Observat Singapore, Asian Sch Environm, 50 Nanyang Ave, Singapore 639798, Singapore.
EM deepa004@e.ntu.edu.sg; sbarbot@ntu.edu.sg
FU National Research Foundation Singapore under its Singapore NRF Fellowship scheme [NRF-NRFF2013-04]; Earth Observatory of Singapore; National Research Foundation Singapore; Singapore Ministry of Education under the Research Centres of Excellence initiative; Division Of Earth Sciences; Directorate For Geosciences [1261833] Funding Source: National Science Foundation
NR 46
TC 65
Z9 65
U1 0
U2 24
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 
EP 
DI 10.1038/nature17190
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700048
DA 2026-03-09
ER

PT J
AU Olsen, JL
   Rouzé, P
   Verhelst, B
   Lin, YC
   Bayer, T
   Collen, J
   Dattolo, E
   De Paoli, E
   Dittami, S
   Maumus, F
   Michel, G
   Kersting, A
   Lauritano, C
   Lohaus, R
   Töpel, M
   Tonon, T
   Vanneste, K
   Amirebrahimi, M
   Brakel, J
   Boström, C
   Chovatia, M
   Grimwood, J
   Jenkins, JW
   Jueterbock, A
   Mraz, A
   Stam, WT
   Tice, H
   Bornberg-Bauer, E
   Green, PJ
   Pearson, GA
   Procaccini, G
   Duarte, CM
   Schmutz, J
   Reusch, TBH
   Van de Peer, Y
AF Olsen, Jeanine L.
   Rouze, Pierre
   Verhelst, Brain
   Lin, Yao-Cheng
   Bayer, Till
   Collen, Jonas
   Dattolo, Emanuela
   De Paoli, Emanuele
   Dittami, Simon
   Maumus, Florian
   Michel, Gurvan
   Kersting, Anna
   Lauritano, Chiara
   Lohaus, Rolf
   Topel, Mats
   Tonon, Thierry
   Vanneste, Kevin
   Amirebrahimi, Mojgan
   Brakel, Janina
   Bostrom, Christoffer
   Chovatia, Mansi
   Grimwood, Jane
   Jenkins, Jerry W.
   Jueterbock, Alexander
   Mraz, Amy
   Stam, Wytze T.
   Tice, Hope
   Bornberg-Bauer, Erich
   Green, Pamela J.
   Pearson, Gareth A.
   Procaccini, Gabriele
   Duarte, Carlos M.
   Schmutz, Jeremy
   Reusch, Thorsten B. H.
   Van de Peer, Yves
TI The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea
SO NATURE
LA English
DT Article
ID chromosome-numbers; new-jersey; evolution; annotation; protein; algorithms; resource; program; history; origin
AB Seagrasses colonized the sea(1) on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet(2). Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes(3), genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae(4) and that is important for ion homoeostasis, nutrient uptake and O-2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming(5,6), to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants(7).
C1 [Olsen, Jeanine L.; Stam, Wytze T.] Univ Groningen, Groningen Inst Evolutionary Life Sci GELIFES, POB 11103, NL-9700 CC Groningen, Netherlands.
   [Rouze, Pierre; Verhelst, Brain; Lin, Yao-Cheng; Lohaus, Rolf; Vanneste, Kevin] VIB, Dept Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.
   [Rouze, Pierre; Verhelst, Brain; Lin, Yao-Cheng; Lohaus, Rolf; Vanneste, Kevin] Univ Ghent, Dept Plant Biotechnol & Bioinformat, Technol Pk 927, B-9052 Ghent, Belgium.
   [Bayer, Till; Brakel, Janina; Reusch, Thorsten B. H.] GEOMAR Helmholtz Ctr Ocean Res Kiel, Evolutionary Ecol, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
   [Collen, Jonas; Dittami, Simon; Michel, Gurvan; Tonon, Thierry] Univ Paris 06, Sorbonne Univ, Stn Biol Roscoff, Integrat Biol Marine Models, CS 90074, F-29688 Roscoff, France.
   [Dattolo, Emanuela; Lauritano, Chiara; Procaccini, Gabriele] Stn Zool Anton Dohrn, I-80121 Naples, Italy.
   [De Paoli, Emanuele] Univ Udine, Dipartimento Sci Agr & Ambientali, Via Sci 206, I-33100 Udine, Italy.
   [Maumus, Florian] INRA Versailles Grignon, INRA, URGI Res Unit Genom Info UR1164, Route St Cyr, F-78026 Versailles, France.
   [Kersting, Anna; Bornberg-Bauer, Erich] Univ Munster, Inst Evolut & Biodivers, Hufferstr 1, D-48149 Munster, Germany.
   [Kersting, Anna] Univ Dusseldorf, Inst Comp Sci, D-40255 Dusseldorf, Germany.
   [Topel, Mats] Univ Gothenburg, BILS, Dept Biol & Environm Sci, Med Gatan 18A, S-40530 Gothenburg, Sweden.
   [Amirebrahimi, Mojgan; Chovatia, Mansi; Grimwood, Jane; Jenkins, Jerry W.; Tice, Hope; Schmutz, Jeremy] Joint Genome Inst, Dept Energy, 2800 Mitchell Dr 100, Walnut Creek, CA 94598 USA.
   [Bostrom, Christoffer] Abo Akad Univ, Fac Sci & Engn, Environm & Marine Biol, Artillerigatan 6, FI-20520 Turku, Finland.
   [Grimwood, Jane; Jenkins, Jerry W.; Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, 601 Genome Way NW, Huntsville, AL 35806 USA.
   [Jueterbock, Alexander] Nord Univ, Marine Ecol Grp, Postbox 1490, N-8049 Bodo, Norway.
   [Mraz, Amy] Amplicon Express, 2345 NE Hopkins Ct, Pullman, WA 99163 USA.
   [Green, Pamela J.] Univ Delaware, Delaware Biotechnol Inst, Dept Plant & Soil Sci, Sch Marine Sci & Policy, 15 Innovat Way, Newark, DE 19711 USA.
   [Pearson, Gareth A.] Univ Algarve, Ctr Marine Sci CCMAR, Marine Ecol & Evolut, P-8005139 Faro, Portugal.
   [Duarte, Carlos M.] KAUST, RSRC, Thuwal 239556900, Saudi Arabia.
   [Reusch, Thorsten B. H.] Univ Kiel, Fac Math & Nat Sci, Christian Albrechts Pl 4, D-24118 Kiel, Germany.
   [Van de Peer, Yves] Univ Pretoria, Genom Res Inst, Hatfield Campus, ZA-0028 Pretoria, South Africa.
   [Van de Peer, Yves] Univ Ghent, Bioinformat Inst, B-9000 Ghent, Belgium.
C3 University of Groningen; Flanders Institute for Biotechnology (VIB); Ghent University; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Sorbonne Universite; Stazione Zoologica Anton Dohrn; University of Udine; INRAE; Universite Paris Saclay; University of Munster; Heinrich Heine University Dusseldorf; University of Gothenburg; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; Abo Akademi University; HudsonAlpha Institute for Biotechnology; Nord University; University of Delaware; Universidade do Algarve; King Abdullah University of Science & Technology; University of Kiel; University of Pretoria; Ghent University
RP Olsen, JL (corresponding author), Univ Groningen, Groningen Inst Evolutionary Life Sci GELIFES, POB 11103, NL-9700 CC Groningen, Netherlands.; Van de Peer, Y (corresponding author), VIB, Dept Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.; Van de Peer, Y (corresponding author), Univ Ghent, Dept Plant Biotechnol & Bioinformat, Technol Pk 927, B-9052 Ghent, Belgium.; Van de Peer, Y (corresponding author), Univ Pretoria, Genom Res Inst, Hatfield Campus, ZA-0028 Pretoria, South Africa.; Van de Peer, Y (corresponding author), Univ Ghent, Bioinformat Inst, B-9000 Ghent, Belgium.
EM j.l.olsen@rug.nl; yves.vandepeer@psb.vib-ugent.be
NR 87
TC 414
Z9 475
U1 13
U2 423
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 331
EP +
DI 10.1038/nature16548
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100036
PM 26814964
DA 2026-03-09
ER

PT J
AU Guo, F
   Yu, JW
   Jung, HJ
   Abruzzi, KC
   Luo, WF
   Riffith, LCG
   Rosbash, M
AF Guo, Fang
   Yu, Junwei
   Jung, Hyung Jae
   Abruzzi, Katharine C.
   Luo, Weifei
   Riffith, Leslie C. G.
   Rosbash, Michael
TI Circadian neuron feedback controls the Drosophila sleep-activity profile
SO NATURE
LA English
DT Article
ID clock neurons; pacemaker neurons; rhythms; gene; light; temperature; glutamate; circuits; mutation; output
AB Little is known about the ability of Drosophila circadian neurons to promote sleep. Here we show, using optogenetic manipulation and video recording, that a subset of dorsal clock neurons (DN1s) are potent sleep-promoting cells that release glutamate to directly inhibit key pacemaker neurons. The pacemakers promote morning arousal by activating these DN1s, implying that a late-day feedback circuit drives midday siesta and night-time sleep. To investigate more plastic aspects of the sleep program, we used a calcium assay to monitor and compare the real-time activity of DN1 neurons in freely behaving males and females. Our results revealed that DN1 neurons were more active in males than in females, consistent with the finding that male flies sleep more during the day. DN1 activity is also enhanced by elevated temperature, consistent with the ability of higher temperatures to increase sleep. These new approaches indicate that DN1s have a major effect on the fly sleep-wake profile and integrate environmental information with the circadian molecular program.
C1 [Guo, Fang; Jung, Hyung Jae; Abruzzi, Katharine C.; Luo, Weifei; Rosbash, Michael] Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA.
   [Guo, Fang; Jung, Hyung Jae; Abruzzi, Katharine C.; Luo, Weifei; Rosbash, Michael] Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
   [Guo, Fang; Yu, Junwei; Jung, Hyung Jae; Abruzzi, Katharine C.; Luo, Weifei; Riffith, Leslie C. G.; Rosbash, Michael] Brandeis Univ, Dept Biol, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
   [Guo, Fang; Yu, Junwei; Jung, Hyung Jae; Abruzzi, Katharine C.; Luo, Weifei; Riffith, Leslie C. G.; Rosbash, Michael] Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA 02454 USA.
C3 Brandeis University; Howard Hughes Medical Institute; Brandeis University; Brandeis University; Brandeis University
RP Rosbash, M (corresponding author), Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA.; Rosbash, M (corresponding author), Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.; Rosbash, M (corresponding author), Brandeis Univ, Dept Biol, Natl Ctr Behav Genom, Waltham, MA 02454 USA.; Rosbash, M (corresponding author), Brandeis Univ, Volen Natl Ctr Complex Syst, Waltham, MA 02454 USA.
EM rosbash@brandeis.edu
FU NIH [R01 MH067284]; National Institute of Mental Health [R01MH067284] Funding Source: NIH RePORTER
NR 52
TC 219
Z9 268
U1 0
U2 114
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 292
EP +
DI 10.1038/nature19097
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900027
PM 27479324
DA 2026-03-09
ER

PT J
AU Zhong, LS
   Yu, F
   An, YL
   Zhao, YH
   Sun, YH
   Li, ZJ
   Lin, TJ
   Lin, YJ
   Qi, XZ
   Dai, YY
   Gu, L
   Hu, JS
   Jin, SF
   Shen, Q
   Wang, H
AF Zhong, Liangshu
   Yu, Fei
   An, Yunlei
   Zhao, Yonghui
   Sun, Yuhan
   Li, Zhengjia
   Lin, Tiejun
   Lin, Yanjun
   Qi, Xingzhen
   Dai, Yuanyuan
   Gu, Lin
   Hu, Jinsong
   Jin, Shifeng
   Shen, Qun
   Wang, Hui
TI Cobalt carbide nanoprisms for direct production of lower olefins from syngas
SO NATURE
LA English
DT Article
ID fischer-tropsch synthesis; augmented-wave method; minimum energy paths; elastic band method; synthesis gas; light olefins; catalytic performance; selective conversion; iron catalysts; saddle-points
AB Lower olefins-generally referring to ethylene, propylene and butylene-are basic carbon-based building blocks that are widely used in the chemical industry, and are traditionally produced through thermal or catalytic cracking of a range of hydrocarbon feedstocks, such as naphtha, gas oil, condensates and light alkanes(1,2). With the rapid depletion of the limited petroleum reserves that serve as the source of these hydrocarbons, there is an urgent need for processes that can produce lower olefins from alternative feedstocks(3-9). The 'Fischer-Tropsch to olefins' (FTO) process has long offered a way of producing lower olefins directly from syngas-a mixture of hydrogen and carbon monoxide that is readily derived from coal, biomass and natural gas(3-7). But the hydrocarbons obtained with the FTO process typically follow the so-called Anderson-Schulz-Flory distribution, which is characterized by a maximum C-2-C-4 hydrocarbon fraction of about 56.7 per cent and an undesired methane fraction of about 29.2 per cent (refs 1, 10-12). Here we show that, under mild reaction conditions, cobalt carbide quadrangular nanoprisms catalyse the FTO conversion of syngas with high selectivity for the production of lower olefins (constituting around 60.8 per cent of the carbon products), while generating little methane (about 5.0 per cent), with the ratio of desired unsaturated hydrocarbons to less valuable saturated hydrocarbons amongst the C-2-C-4 products being as high as 30. Detailed catalyst characterization during the initial reaction stage and theoretical calculations indicate that preferentially exposed {101} and {020} facets play a pivotal role during syngas conversion, in that they favour olefin production and inhibit methane formation, and thereby render cobalt carbide nanoprisms a promising new catalyst system for directly converting syngas into lower olefins.
C1 [Zhong, Liangshu; Yu, Fei; An, Yunlei; Zhao, Yonghui; Sun, Yuhan; Li, Zhengjia; Lin, Tiejun; Lin, Yanjun; Qi, Xingzhen; Dai, Yuanyuan; Shen, Qun; Wang, Hui] Chinese Acad Sci, Shanghai Adv Res Inst, CAS Key Lab Low Carbon Convers Sci & Engn, Shanghai 201203, Peoples R China.
   [Yu, Fei; An, Yunlei] Shanghai Univ, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China.
   [Sun, Yuhan] ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201203, Peoples R China.
   [Li, Zhengjia] East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China.
   [Dai, Yuanyuan; Hu, Jinsong] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Gu, Lin; Jin, Shifeng] Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Inst Phys, Beijing 100190, Peoples R China.
   [Hu, Jinsong] Chinese Acad Sci, Beijing Natl Lab Mol Sci, Inst Chem, Key Lab Mol Nanostruct & Nanotechnol, Beijing 100190, Peoples R China.
C3 Chinese Academy of Sciences; Shanghai Advanced Research Institute, CAS; Shanghai University; ShanghaiTech University; East China Normal University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Institute of Physics, CAS; Chinese Academy of Sciences; Institute of Chemistry, CAS
RP Zhong, LS; Sun, YH (corresponding author), Chinese Acad Sci, Shanghai Adv Res Inst, CAS Key Lab Low Carbon Convers Sci & Engn, Shanghai 201203, Peoples R China.; Sun, YH (corresponding author), ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201203, Peoples R China.
EM zhongls@sari.ac.cn; sunyh@sari.ac.cn
FU Natural Science Foundation of China [21403278, 21403277, 21573271, 91545112]; Shanghai Municipal Science and Technology Commission, China [15DZ1170500, 14ZR1444600]; Shanxi Lu'an Coal Corporation Limited; Ministry of Science and Technology of China [2016YFA0202802]; Chinese Academy of Sciences [QYZDB-SSW-SLH035]; Chinese Academy of Sciences (Youth Innovation Promotion Association of CAS)
NR 37
TC 767
Z9 871
U1 35
U2 1650
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 84
EP +
DI 10.1038/nature19786
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900038
PM 27708303
DA 2026-03-09
ER

PT J
AU Clements, T
   Dolocan, A
   Martin, P
   Purnell, MA
   Vinther, J
   Gabbott, SE
AF Clements, Thomas
   Dolocan, Andrei
   Martin, Peter
   Purnell, Mark A.
   Vinther, Jakob
   Gabbott, Sarah E.
TI The eyes of Tullimonstrum reveal a vertebrate affinity
SO NATURE
LA English
DT Article
ID fossil; illinois; pigment; record; characters; components; evolution; feathers; lamprey; hagfish
AB Tullimonstrum gregarium is an iconic soft-bodied fossil from the Carboniferous Mazon Creek Lagerstatte ( Illinois, USA)(1). Despite a large number of specimens and distinct anatomy, various analyses over the past five decades have failed to determine the phylogenetic affinities of the 'Tully monster', and although it has been allied to such disparate phyla as the Mollusca(2), Annelida(3),(4) or Chordata(5), it remains enigmatic(1-5). The nature and phylogenetic affinities of Tullimonstrum have defied confident systematic placement because none of its preserved anatomy provides unequivocal evidence of homology, without which comparative analysis fails. Here we show that the eyes of Tullimonstrum possess ultrastructural details indicating homology with vertebrate eyes. Anatomical analysis using scanning electron microscopy reveals that the eyes of Tullimonstrum preserve a retina defined by a thick sheet comprising distinct layers of spheroidal and cylindrical melanosomes. Time-offlight secondary ion mass spectrometry and multivariate statistics provide further evidence that these microbodies are melanosomes. A range of animals have melanin in their eyes, but the possession of melanosomes of two distinct morphologies arranged in layers, forming retinal pigment epithelium, is a synapomorphy of vertebrates. Our analysis indicates that in addition to evidence of colour patterning(6), ecology(7) and thermoregulation(8), fossil melanosomes can also carry a phylogenetic signal. Identification in Tullimonstrum of spheroidal and cylindrical melanosomes forming the remains of retinal pigment epithelium indicates that it is a vertebrate; considering its body parts in this new light suggests
C1 [Clements, Thomas; Purnell, Mark A.; Gabbott, Sarah E.] Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
   [Dolocan, Andrei] Univ Texas Austin, Texas Mat Inst, Austin, TX 78712 USA.
   [Martin, Peter; Vinther, Jakob] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Martin, Peter] Univ Bristol, HH Wills Phys Lab, Interface Anal Ctr, Bristol BS8 1TQ, Avon, England.
   [Vinther, Jakob] Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.
C3 University of Leicester; University of Texas System; University of Texas Austin; University of Bristol; University of Bristol; University of Bristol
RP Gabbott, SE (corresponding author), Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.; Vinther, J (corresponding author), Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.; Vinther, J (corresponding author), Univ Bristol, Sch Biol Sci, Bristol BS8 1TQ, Avon, England.
EM jakob.vinther@bristol.ac.uk; sg21@le.ac.uk
FU Natural Environment Research Council [P14DF19, NE/K004557/1]; National Science Foundation [DMR-0923096]; EPSRC [EP/K035746/1] Funding Source: UKRI; NERC [NE/E015336/1, NE/K004557/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/K035746/1] Funding Source: researchfish; Natural Environment Research Council [NE/E015336/1, NE/K004557/1, 1357873] Funding Source: researchfish
NR 30
TC 55
Z9 65
U1 3
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 500
EP +
DI 10.1038/nature17647
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900047
PM 27074512
DA 2026-03-09
ER

PT J
AU Huff, JT
   Zilberman, D
   Roy, SW
AF Huff, Jason T.
   Zilberman, Daniel
   Roy, Scott W.
TI Mechanism for DNA transposons to generate introns on genomic scales
SO NATURE
LA English
DT Article
ID evolution; sequence; alignment; origin; duplication; discovery; chromatin; elements; genes
AB The discovery of introns four decades ago was one of the most unexpected findings in molecular biology(1). Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many(2,3). Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain(2,3). However, although several detailed mechanisms for such episodic intron generation have been proposed(4-8), none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases(2) and prevalence of nucleosome-sized exons(9) observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution(2,3).
C1 [Huff, Jason T.; Zilberman, Daniel] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Huff, Jason T.] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA.
   [Roy, Scott W.] San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; California State University System; San Francisco State University
RP Zilberman, D (corresponding author), Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.; Roy, SW (corresponding author), San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA.
EM danielz@berkeley.edu; scottwroy@gmail.com
FU NIH [T32HG000047]; Beckman Young Investigator Award; National Human Genome Research Institute [T32HG000047] Funding Source: NIH RePORTER
NR 38
TC 63
Z9 74
U1 0
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 533
EP +
DI 10.1038/nature20110
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400063
PM 27760113
DA 2026-03-09
ER

PT J
AU Franke, M
   Ibrahim, DM
   Andrey, G
   Schwarzer, W
   Heinrich, V
   Schöpflin, R
   Kraft, K
   Kempfer, R
   Jerkovic, I
   Chan, WL
   Spielmann, M
   Timmermann, B
   Wittler, L
   Kurth, I
   Cambiaso, P
   Zuffardi, O
   Houge, G
   Lambie, L
   Brancati, F
   Pombo, A
   Vingron, M
   Spitz, F
   Mundlos, S
AF Franke, Martin
   Ibrahim, Daniel M.
   Andrey, Guillaume
   Schwarzer, Wibke
   Heinrich, Verena
   Schoepflin, Robert
   Kraft, Katerina
   Kempfer, Rieke
   Jerkovic, Ivana
   Chan, Wing-Lee
   Spielmann, Malte
   Timmermann, Bernd
   Wittler, Lars
   Kurth, Ingo
   Cambiaso, Paola
   Zuffardi, Orsetta
   Houge, Gunnar
   Lambie, Lindsay
   Brancati, Francesco
   Pombo, Ana
   Vingron, Martin
   Spitz, Francois
   Mundlos, Stefan
TI Formation of new chromatin domains determines pathogenicity of genomic duplications
SO NATURE
LA English
DT Article
ID campomelic dysplasia; noncoding elements; read alignment; sox9; upstream; generation; sry
AB Chromosome conformation capture methods have identified subchromosomal structures of higher-order chromatin interactions called topologically associated domains (TADs) that are separated from each other by boundary regions(1,2). By subdividing the genome into discrete regulatory units, TADs restrict the contacts that enhancers establish with their target genes(3-5). However, the mechanisms that underlie partitioning of the genome into TADs remain poorly understood. Here we show by chromosome conformation capture (capture Hi-C and 4C-seq methods) that genomic duplications in patient cells and genetically modified mice can result in the formation of new chromatin domains (neo-TADs) and that this process determines their molecular pathology. Duplications of non-coding DNA within the mouse Sox9 TAD (intra-TAD) that cause female to male sex reversal in humans(6), showed increased contact of the duplicated regions within the TAD, but no change in the overall TAD structure. In contrast, overlapping duplications that extended over the next boundary into the neighbouring TAD (inter-TAD), resulted in the formation of a new chromatin domain (neo-TAD) that was isolated from the rest of the genome. As a consequence of this insulation, inter-TAD duplications had no phenotypic effect. However, incorporation of the next flanking gene, Kcnj2, in the neo-TAD resulted in ectopic contacts of Kcnj2 with the duplicated part of the Sox9 regulatory region, consecutive misexpression of Kcnj2, and a limb malformation phenotype. Our findings provide evidence that TADs are genomic regulatory units with a high degree of internal stability that can be sculptured by structural genomic variations. This process is important for the interpretation of copy number variations, as these variations are routinely detected in diagnostic tests for genetic disease and cancer. This finding also has relevance in an evolutionary setting because copy-number differences are thought to have a crucial role in the evolution of genome complexity.
C1 [Franke, Martin; Ibrahim, Daniel M.; Andrey, Guillaume; Kraft, Katerina; Kempfer, Rieke; Jerkovic, Ivana; Spielmann, Malte; Mundlos, Stefan] Max Planck Inst Mol Genet, RG Dev & Dis, D-14195 Berlin, Germany.
   [Franke, Martin; Ibrahim, Daniel M.; Heinrich, Verena; Kraft, Katerina; Jerkovic, Ivana; Chan, Wing-Lee; Spielmann, Malte; Mundlos, Stefan] Charite Univ Med Berlin, Inst Med & Human Genet, D-13353 Berlin, Germany.
   [Ibrahim, Daniel M.; Pombo, Ana; Mundlos, Stefan] Berlin Inst Hlth, D-10117 Berlin, Germany.
   [Schwarzer, Wibke; Spitz, Francois] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
   [Heinrich, Verena; Schoepflin, Robert; Vingron, Martin] Max Planck Inst Mol Genet, Dept Computat Mol Biol, D-14195 Berlin, Germany.
   [Timmermann, Bernd] Sequencing Core Facil, Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Wittler, Lars] Max Planck Inst Mol Genet, Dept Dev Genet, D-14195 Berlin, Germany.
   [Kurth, Ingo] Jena Univ Hosp, Inst Human Genet, D-07743 Jena, Germany.
   [Kurth, Ingo] Uniklin RWTH Aachen, Inst Human Genet, D-52074 Aachen, Germany.
   [Cambiaso, Paola] Bambino Gesu Childrens Hosp IRCCS, I-00165 Rome, Italy.
   [Zuffardi, Orsetta] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy.
   [Houge, Gunnar] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway.
   [Lambie, Lindsay] Univ Witwatersrand, Div Human Genet, Natl Hlth Lab Serv, ZA-2000 Johannesburg, South Africa.
   [Brancati, Francesco] Univ Aquila, Dept Life Hlth & Environm Sci, I-67100 Laquila, Italy.
   [Brancati, Francesco] IRCCS, IDI, I-00167 Rome, Italy.
   [Pombo, Ana] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13125 Berlin, Germany.
   [Mundlos, Stefan] Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, D-13353 Berlin, Germany.
C3 Max Planck Society; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; European Molecular Biology Laboratory (EMBL); Max Planck Society; Max Planck Society; Max Planck Society; Friedrich Schiller University of Jena; RWTH Aachen University; RWTH Aachen University Hospital; IRCCS Bambino Gesu; University of Pavia; University of Bergen; Haukeland University Hospital; National Health Laboratory Service; University of Witwatersrand; University of L'Aquila; IRCCS Istituto Dermopatico dell'Immacolata (IDI); Helmholtz Association; Max Delbruck Center for Molecular Medicine; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Mundlos, S (corresponding author), Max Planck Inst Mol Genet, RG Dev & Dis, D-14195 Berlin, Germany.; Mundlos, S (corresponding author), Charite Univ Med Berlin, Inst Med & Human Genet, D-13353 Berlin, Germany.; Mundlos, S (corresponding author), Berlin Inst Hlth, D-10117 Berlin, Germany.; Mundlos, S (corresponding author), Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, D-13353 Berlin, Germany.
EM mundlos@molgen.mpg.de
FU Deutsche Forschungsgemeinschaft; BIH; Max Planck Foundation
NR 37
TC 491
Z9 589
U1 0
U2 108
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 265
EP +
DI 10.1038/nature19800
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000049
PM 27706140
DA 2026-03-09
ER

PT J
AU Hsieh, J
   Koseki, M
   Molusky, MM
   Yakushiji, E
   Ichi, I
   Westerterp, M
   Iqbal, J
   Chan, RB
   Abramowicz, S
   Tascau, L
   Takiguchi, S
   Yamashita, S
   Welch, CL
   Di Paolo, G
   Hussain, MM
   Lefkowitch, JH
   Rader, DJ
   Tall, AR
AF Hsieh, Joanne
   Koseki, Masahiro
   Molusky, Matthew M.
   Yakushiji, Emi
   Ichi, Ikuyo
   Westerterp, Marit
   Iqbal, Jahangir
   Chan, Robin B.
   Abramowicz, Sandra
   Tascau, Liana
   Takiguchi, Shunichi
   Yamashita, Shizuya
   Welch, Carrie L.
   Di Paolo, Gilbert
   Hussain, M. Mahmood
   Lefkowitch, Jay H.
   Rader, Daniel J.
   Tall, Alan R.
TI TTC39B deficiency stabilizes LXR reducing both atherosclerosis and steatohepatitis
SO NATURE
LA English
DT Article
ID liver-x-receptor; reverse cholesterol transport; oxidation-products; er stress; in-vivo; insulin; alpha; mouse; mice; metabolism
AB Cellular mechanisms that mediate steatohepatitis, an increasingly prevalent condition in the Western world for which no therapies are available(1), are poorly understood. Despite the fact that its synthetic agonists induce fatty liver, the liver X receptor (LXR) transcription factor remains a target of interest because of its anti-atherogenic, cholesterol removal, and anti-inflammatory activities. Here we show that tetratricopeptide repeat domain protein 39B (Ttc39b, C9orf52) (T39), a high-density lipoprotein gene discovered in human genome-wide association studies(2), promotes the ubiquitination and degradation of LXR. Chow-fed mice lacking T39 (T39(-/-)) display increased high-density lipoprotein cholesterol levels associated with increased enterocyte ATP-binding cassette transporter A1 (Abca1) expression and increased LXR protein without change in LXR messenger RNA. When challenged with a high fat/high cholesterol/bile salt diet, T39(-/-) mice or mice with hepatocyte-specific T39 deficiency show increased hepatic LXR protein and target gene expression, and unexpectedly protection from steatohepatitis and death. Mice fed a Western-type diet and lacking low-density lipoprotein receptor (Ldlr(-/-)T39(-/-)) show decreased fatty liver, increased high-density lipoprotein, decreased low-density lipoprotein, and reduced atherosclerosis. In addition to increasing hepatic Abcg5/8 expression and limiting dietary cholesterol absorption, T39 deficiency inhibits hepatic sterol regulatory elementbinding protein 1 (SREBP-1, ADD1) processing. This is explained by an increase in microsomal phospholipids containing polyunsaturated fatty acids, linked to an LXRa-dependent increase in expression of enzymes mediating phosphatidylcholine biosynthesis and incorporation of polyunsaturated fatty acids into phospholipids. The preservation of endogenous LXR protein activates a beneficial profile of gene expression that promotes cholesterol removal and inhibits lipogenesis. T39 inhibition could be an effective strategy for reducing both steatohepatitis and atherosclerosis.
C1 [Hsieh, Joanne; Koseki, Masahiro; Molusky, Matthew M.; Yakushiji, Emi; Westerterp, Marit; Abramowicz, Sandra; Tascau, Liana; Welch, Carrie L.; Tall, Alan R.] Columbia Univ, Dept Med, Div Mol Med, New York, NY 10032 USA.
   [Koseki, Masahiro; Yamashita, Shizuya] Osaka Univ, Grad Sch Med, Cardiovasc Med, Suita, Osaka 5650871, Japan.
   [Ichi, Ikuyo] Ochanomizu Univ, Fac Core Res, Bunkyo Ku, Tokyo 1128610, Japan.
   [Iqbal, Jahangir; Hussain, M. Mahmood] Suny Downstate Med Ctr, Hlth Sci Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
   [Chan, Robin B.; Di Paolo, Gilbert; Lefkowitch, Jay H.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Takiguchi, Shunichi; Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Takiguchi, Shunichi; Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
C3 Columbia University; University of Osaka; Ochanomizu University; State University of New York (SUNY) System; SUNY Downstate Health Sciences University; Columbia University; University of Pennsylvania; University of Pennsylvania
RP Hsieh, J (corresponding author), Columbia Univ, Dept Med, Div Mol Med, New York, NY 10032 USA.
FU Manpei Suzuki Diabetes Foundation; Netherlands Organization of Sciences [91715350]; Rosalind Franklin Fellowship from the University Medical Center Groningen; JSPS [15K160203]; Fondation Leducq; National Institutes of Health [HL007343, HL087123, HL119830, HL101864, HL111398, DK46900]; National Heart Lung and Blood Institute [T32HL007343, R01HL119830, P01HL087123] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [15K16203] Funding Source: KAKEN
NR 38
TC 80
Z9 89
U1 1
U2 61
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 303
EP U282
DI 10.1038/nature18628
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600061
PM 27383786
DA 2026-03-09
ER

PT J
AU Zoued, A
   Durand, E
   Brunet, YR
   Spinelli, S
   Douzi, B
   Guzzo, M
   Flaugnatti, N
   Legrand, P
   Journet, L
   Fronzes, R
   Mignot, T
   Cambillau, C
   Cascales, E
AF Zoued, Abdelrahim
   Durand, Eric
   Brunet, Yannick R.
   Spinelli, Silvia
   Douzi, Badreddine
   Guzzo, Mathilde
   Flaugnatti, Nicolas
   Legrand, Pierre
   Journet, Laure
   Fronzes, Remi
   Mignot, Tam
   Cambillau, Christian
   Cascales, Eric
TI Priming and polymerization of a bacterial contractile tail structure
SO NATURE
LA English
DT Article
ID vi secretion system; small-angle scattering; escherichia-coli; antifeeding prophage; high-resolution; reveals; visualization; architecture; complexes; mechanism
AB Contractile tails are composed of an inner tube wrapped by an outer sheath assembled in an extended, metastable conformation that stores mechanical energy necessary for its contraction. Contraction is used to propel the rigid inner tube towards target cells for DNA or toxin delivery. Although recent studies have revealed the structure of the contractile sheath of the type VI secretion system, the mechanisms by which its polymerization is controlled and coordinated with the assembly of the inner tube remain unknown. Here we show that the starfish-like TssA dodecameric complex interacts with tube and sheath components. Fluorescence microscopy experiments in enteroaggregative Escherichia coli reveal that TssA binds first to the type VI secretion system membrane core complex and then initiates tail polymerization. TssA remains at the tip of the growing structure and incorporates new tube and sheath blocks. On the basis of these results, we propose that TssA primes and coordinates tail tube and sheath biogenesis.
C1 [Zoued, Abdelrahim; Durand, Eric; Brunet, Yannick R.; Douzi, Badreddine; Flaugnatti, Nicolas; Journet, Laure; Cascales, Eric] Aix Marseille Univ, CNRS, UMR7255, Lab Ingn Syst Macromol,Inst Microbiol Mediterrane, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France.
   [Durand, Eric; Spinelli, Silvia; Douzi, Badreddine; Cambillau, Christian] CNRS, UMR 7257, Architecture & Fonct Macromol Biol, Campus Luminy,Case 932, F-13288 Marseille 09, France.
   [Durand, Eric; Spinelli, Silvia; Douzi, Badreddine; Cambillau, Christian] Aix Marseille Univ, UMR 7257, Architecture & Fonct Macromol Biol, Campus Luminy,Case 932, F-13288 Marseille 09, France.
   [Durand, Eric; Fronzes, Remi] Inst Pasteur, Biol Struct Secret Bacterienne G5, 25-28 Rue Docteur Roux, F-75015 Paris, France.
   [Durand, Eric; Fronzes, Remi] Inst Pasteur, CNRS, UMR 3528, 25-28 Rue Docteur Roux, F-75015 Paris, France.
   [Guzzo, Mathilde; Mignot, Tam] Aix Marseille Univ, CNRS, UMR7283, Lab Chim Bacterienne,Inst Microbiol Mediterranee, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France.
   [Legrand, Pierre] Synchrotron Soleil, BP48, F-91192 Gif Sur Yvette, France.
   [Brunet, Yannick R.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); SOLEIL Synchrotron; Harvard University; Harvard Medical School
RP Durand, E; Cambillau, C; Cascales, E (corresponding author), Aix Marseille Univ, CNRS, UMR7255, Lab Ingn Syst Macromol,Inst Microbiol Mediterrane, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France.; Durand, E; Cambillau, C (corresponding author), CNRS, UMR 7257, Architecture & Fonct Macromol Biol, Campus Luminy,Case 932, F-13288 Marseille 09, France.; Durand, E; Cambillau, C (corresponding author), Aix Marseille Univ, UMR 7257, Architecture & Fonct Macromol Biol, Campus Luminy,Case 932, F-13288 Marseille 09, France.; Durand, E (corresponding author), Inst Pasteur, Biol Struct Secret Bacterienne G5, 25-28 Rue Docteur Roux, F-75015 Paris, France.; Durand, E (corresponding author), Inst Pasteur, CNRS, UMR 3528, 25-28 Rue Docteur Roux, F-75015 Paris, France.
EM edurand@imm.cnrs.fr; cambillau@afmb.univ-mrs.fr; cascales@imm.cnrs.fr
FU Centre National de la Recherche Scientifique; Aix-Marseille Universite; Agence Nationale de la Recherche [ANR-10-JCJC-1303-03, ANR-14-CE14-0006-02]; Fondation pour la Recherche Medicale [FRM DEQ2011-0421282, FDT20140931060, SPF20101221116]; French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01]; French Ministry of Research
NR 56
TC 111
Z9 131
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 59
EP +
DI 10.1038/nature17182
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900039
PM 26909579
DA 2026-03-09
ER

PT J
AU Ibiza, S
   García-Cassani, B
   Ribeiro, H
   Carvalho, T
   Almeida, L
   Marques, R
   Misic, AM
   Bartow-McKenney, C
   Larson, DM
   Pavan, WJ
   Eberl, G
   Grice, EA
   Veiga-Fernandes, H
AF Ibiza, Sales
   Garcia-Cassani, Bethania
   Ribeiro, Helder
   Carvalho, Tania
   Almeida, Luis
   Marques, Rute
   Misic, Ana M.
   Bartow-McKenney, Casey
   Larson, Denise M.
   Pavan, William J.
   Eberl, Gerard
   Grice, Elizabeth A.
   Veiga-Fernandes, Henrique
TI Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence
SO NATURE
LA English
DT Article
ID inflammatory-bowel-disease; toll-like receptors; citrobacter-rodentium; transgenic mice; sequencing data; lamina propria; enteric glia; ret; microbiota; immunity
AB Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers(1). ILC3 development is thought to be programmed(1), but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial-ILC3-epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals.
C1 [Ibiza, Sales; Garcia-Cassani, Bethania; Ribeiro, Helder; Carvalho, Tania; Almeida, Luis; Veiga-Fernandes, Henrique] Fac Med Lisbon, Inst Med Mol, Ave Prof Egas Moniz,Edificio Egas Moniz, P-1649028 Lisbon, Portugal.
   [Marques, Rute; Eberl, Gerard] Inst Pasteur, Microenvironm & Immun Unit, 25 Rue Docteur Roux, F-75724 Paris, France.
   [Misic, Ana M.; Bartow-McKenney, Casey; Grice, Elizabeth A.] Univ Penn, Dept Dermatol, Perelman Sch Med, 421 Curie Blvd,1007 Biomed Res Bldg, Philadelphia, PA 19104 USA.
   [Larson, Denise M.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   [Veiga-Fernandes, Henrique] Champalimaud Ctr Unknown, Champalimaud Res, P-1400038 Lisbon, Portugal.
   [Marques, Rute] INSERM, U1163, Lab Intestinal Immun, Paris, France.
   [Marques, Rute] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
   [Marques, Rute] Inst Imagine, Paris, France.
   [Misic, Ana M.] Univ Penn, Sch Vet Med, Dept Pathobiol, Ctr Host Microbial Interact, Philadelphia, PA 19104 USA.
C3 Instituto Superior de Ciencias da Saude Egas Moniz; Universidade de Lisboa; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; University of Pennsylvania; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Fundacao Champalimaud; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; University of Pennsylvania
RP Veiga-Fernandes, H (corresponding author), Fac Med Lisbon, Inst Med Mol, Ave Prof Egas Moniz,Edificio Egas Moniz, P-1649028 Lisbon, Portugal.; Veiga-Fernandes, H (corresponding author), Champalimaud Ctr Unknown, Champalimaud Res, P-1400038 Lisbon, Portugal.
EM jhfernandes@medicina.ulisboa.pt
FU MEC, Spain; FCT, Portugal; EU [289720]; EMBO [1648]; ERC, EU [647274]; Kenneth Rainin Foundation, US; Crohn's and Colitis Foundation of America, US; Institut Pasteur; ANR, France; NIH NIAMS [R01 AR060873, T32 AR007465]; Morris Animal Foundation [D14CA-404]; European Research Council (ERC) [647274] Funding Source: European Research Council (ERC); National Human Genome Research Institute [ZIAHG000070] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007465] Funding Source: NIH RePORTER
NR 60
TC 320
Z9 361
U1 2
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 440
EP +
DI 10.1038/nature18644
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200044
PM 27409807
DA 2026-03-09
ER

PT J
AU Manchado, E
   Weissmueller, S
   Morris, JP
   Chen, CC
   Wullenkord, R
   Lujambio, A
   de Stanchina, E
   Poirier, JT
   Gainor, JF
   Corcoran, RB
   Engelman, JA
   Rudin, CM
   Rosen, N
   Lowe, SW
AF Manchado, Eusebio
   Weissmueller, Susann
   Morris, John P.
   Chen, Chi-Chao
   Wullenkord, Ramona
   Lujambio, Amaia
   de Stanchina, Elisa
   Poirier, John T.
   Gainor, Justin F.
   Corcoran, Ryan B.
   Engelman, Jeffrey A.
   Rudin, Charles M.
   Rosen, Neal
   Lowe, Scott W.
TI A combinatorial strategy for treating KRAS-mutant lung cancer
SO NATURE
LA English
DT Article
ID mek inhibition; mediated reactivation; selective inhibitor; feedback activation; acquired-resistance; colon-cancer; ras; potent; braf; discovery
AB Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by the US Food and Drug Administration, which acts downstream of KRAS to suppress signalling through the mitogen-activated protein kinase (MAPK) cascade. Informed by a short-hairpin RNA screen, we show that trametinib provokes a compensatory response involving the fibroblast growth factor receptor 1 (FGFR1) that leads to signalling rebound and adaptive drug resistance. As a consequence, genetic or pharmacological inhibition of FGFR1 in combination with trametinib enhances tumour cell death in vitro and in vivo. This compensatory response shows distinct specificities: it is dominated by FGFR1 in KRAS-mutant lung and pancreatic cancer cells, but is not activated or involves other mechanisms in KRAS wild-type lung and KRAS-mutant colon cancer cells. Importantly, KRAS-mutant lung cancer cells and patients' tumours treated with trametinib show an increase in FRS2 phosphorylation, a biomarker of FGFR activation; this increase is abolished by FGFR1 inhibition and correlates with sensitivity to trametinib and FGFR inhibitor combinations. These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer.
C1 [Manchado, Eusebio; Weissmueller, Susann; Morris, John P.; Chen, Chi-Chao; Wullenkord, Ramona; Lujambio, Amaia; Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10065 USA.
   [Weissmueller, Susann] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Chen, Chi-Chao] Cornell Univ, Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA.
   [Lujambio, Amaia] Icahn Sch Med Mt Sinai, Dept Oncol Sci, Liver Canc Program, Tisch Canc Inst, New York, NY 10029 USA.
   [de Stanchina, Elisa; Poirier, John T.; Rudin, Charles M.; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10065 USA.
   [Poirier, John T.; Rudin, Charles M.; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Gainor, Justin F.; Corcoran, Ryan B.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA.
   [Gainor, Justin F.; Corcoran, Ryan B.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Lowe, Scott W.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cold Spring Harbor Laboratory; Cornell University; Icahn School of Medicine at Mount Sinai; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Lowe, SW (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10065 USA.; Rosen, N (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10065 USA.; Rosen, N (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.; Lowe, SW (corresponding author), Howard Hughes Med Inst, New York, NY 10065 USA.
EM rosenn@mskcc.org; lowes@mskcc.org
FU National Cancer Institute; Center of Experimental Therapeutics; Stand Up To Cancer grant from the American Association for Cancer Research; Cancer Center Support grant; Jane Coffin Childs Memorial Fund for Medical Research; National Institutes of Health/National Cancer Institute [K99/R00]; Watson School of Biological Sciences; Bayer Foundation; EMBO Long-Term fellowship; Geoffrey Beene Cancer Research Center; National Cancer Institute [P30CA008748, P50CA127003, P01CA129243] Funding Source: NIH RePORTER
NR 36
TC 339
Z9 398
U1 2
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 647
EP +
DI 10.1038/nature18600
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000028
PM 27338794
DA 2026-03-09
ER

PT J
AU Grundy, WM
   Cruikshank, DP
   Gladstone, GR
   Howett, CJA
   Lauer, TR
   Spencer, JR
   Summers, ME
   Buie, MW
   Earle, AM
   Ennico, K
   Parker, JW
   Porter, SB
   Singer, KN
   Stern, SA
   Verbiscer, AJ
   Beyer, RA
   Binzel, RP
   Buratti, BJ
   Cook, JC
   Ore, CMD
   Olkin, CB
   Parker, AH
   Protopapa, S
   Quirico, E
   Retherford, KD
   Robbins, SJ
   Schmitt, B
   Stansberry, JA
   Umurhan, OM
   Weaver, HA
   Young, LA
   Zangari, AM
   Bray, VJ
   Cheng, AF
   McKinnon, WB
   McNutt, RL
   Moore, JM
   Nimmo, F
   Reuter, DC
   Schenk, PM
AF Grundy, W. M.
   Cruikshank, D. P.
   Gladstone, G. R.
   Howett, C. J. A.
   Lauer, T. R.
   Spencer, J. R.
   Summers, M. E.
   Buie, M. W.
   Earle, A. M.
   Ennico, K.
   Parker, J. Wm.
   Porter, S. B.
   Singer, K. N.
   Stern, S. A.
   Verbiscer, A. J.
   Beyer, R. A.
   Binzel, R. P.
   Buratti, B. J.
   Cook, J. C.
   Ore, C. M. Dalle
   Olkin, C. B.
   Parker, A. H.
   Protopapa, S.
   Quirico, E.
   Retherford, K. D.
   Robbins, S. J.
   Schmitt, B.
   Stansberry, J. A.
   Umurhan, O. M.
   Weaver, H. A.
   Young, L. A.
   Zangari, A. M.
   Bray, V. J.
   Cheng, A. F.
   McKinnon, W. B.
   McNutt, R. L., Jr.
   Moore, J. M.
   Nimmo, F.
   Reuter, D. C.
   Schenk, P. M.
TI The formation of Charon's red poles from seasonally cold-trapped volatiles
SO NATURE
LA English
DT Article
ID pluto; irradiation; surface; system; imager; ices; ch4
AB A unique feature of Pluto's large satellite Charon is its dark red northern polar cap(1). Similar colours on Pluto's surface have been attributed(2) to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon's high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry(3,4). Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed(1,2) as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.
C1 [Grundy, W. M.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [Cruikshank, D. P.; Ennico, K.; Beyer, R. A.; Ore, C. M. Dalle; Umurhan, O. M.; Moore, J. M.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Gladstone, G. R.; Retherford, K. D.] Southwest Res Inst, San Antonio, TX USA.
   [Howett, C. J. A.; Spencer, J. R.; Buie, M. W.; Parker, J. Wm.; Porter, S. B.; Singer, K. N.; Stern, S. A.; Cook, J. C.; Olkin, C. B.; Parker, A. H.; Robbins, S. J.] Southwest Res Inst, Boulder, CO USA.
   [Lauer, T. R.] Natl Opt Astron Observ, Tucson, AZ 85726 USA.
   [Summers, M. E.] George Mason Univ, Fairfax, VA 22030 USA.
   [Earle, A. M.; Binzel, R. P.] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Verbiscer, A. J.] Univ Virginia, Charlottesville, VA USA.
   [Beyer, R. A.; Ore, C. M. Dalle] SETI Inst, Carl Sagan Ctr, Mountain View, CA USA.
   [Buratti, B. J.] NASA, Jet Prop Lab, La Canada Flintridge, CA USA.
   [Protopapa, S.] Univ Maryland, College Pk, MD 20742 USA.
   [Quirico, E.; Schmitt, B.] Univ Grenoble Alpes, CNRS, IPAG, Grenoble, France.
   [Stansberry, J. A.] Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
   [Weaver, H. A.; Cheng, A. F.; McNutt, R. L., Jr.] Johns Hopkins Univ, Appl Phys Lab, Columbia, MD USA.
   [Bray, V. J.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ USA.
   [McKinnon, W. B.] Washington Univ, St Louis, MO USA.
   [Nimmo, F.] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
   [Reuter, D. C.] NASA, Goddard Space Flight Ctr, Greenbelt, MD USA.
   [Schenk, P. M.] Lunar & Planetary Inst, Houston, TX USA.
C3 National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Southwest Research Institute; Southwest Research Institute; National Optical Astronomy Observatory; George Mason University; Massachusetts Institute of Technology (MIT); University of Virginia; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University System of Maryland; University of Maryland College Park; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); Space Telescope Science Institute; Johns Hopkins University; University of Arizona; Washington University (WUSTL); University of California System; University of California Santa Cruz; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Grundy, WM (corresponding author), Lowell Observ, Flagstaff, AZ 86001 USA.
EM w.grundy@lowell.edu
FU NASA's New Horizons Project; Centre National d'Etudes Spatiales (CNES) through its 'Systeme Solaire' programme
NR 43
TC 51
Z9 54
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 65
EP +
DI 10.1038/nature19340
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100029
PM 27626378
DA 2026-03-09
ER

PT J
AU Cummings, RJ
   Barbet, G
   Bongers, G
   Hartmann, BM
   Gettler, K
   Muniz, L
   Furtado, GC
   Cho, J
   Lira, SA
   Blander, JM
AF Cummings, Ryan J.
   Barbet, Gaetan
   Bongers, Gerold
   Hartmann, Boris M.
   Gettler, Kyle
   Muniz, Luciana
   Furtado, Glaucia C.
   Cho, Judy
   Lira, Sergio A.
   Blander, J. Magarian
TI Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs
SO NATURE
LA English
DT Article
ID regulatory t-cells; inflammatory-bowel-disease; dendritic cells; mucosal immunity; transgenic mice; expression; intestine; gene; macrophages; responses
AB Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies(1,2). The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions(3), are not merely extruded to maintain homeostatic cell numbers(4), but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria(5,6). Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease(7). Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.
C1 [Cummings, Ryan J.; Barbet, Gaetan; Bongers, Gerold; Muniz, Luciana; Furtado, Glaucia C.; Cho, Judy; Lira, Sergio A.; Blander, J. Magarian] Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA.
   [Cummings, Ryan J.; Barbet, Gaetan; Bongers, Gerold; Muniz, Luciana; Furtado, Glaucia C.; Cho, Judy; Lira, Sergio A.; Blander, J. Magarian] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
   [Hartmann, Boris M.] Icahn Sch Med Mt Sinai, Ctr Translat Syst Biol, Dept Neurol, New York, NY 10029 USA.
   [Gettler, Kyle] Yale Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Muniz, Luciana; Blander, J. Magarian] Icahn Sch Med Mt Sinai, Grad Sch Biol Sci, New York, NY 10029 USA.
   [Cho, Judy] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Lira, Sergio A.; Blander, J. Magarian] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
   [Blander, J. Magarian] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
   [Blander, J. Magarian] Cornell Univ, Weill Cornell Med, Dept Microbiol & Immunol,Jill Roberts Inst Inflam, Joan & Sanford I Weill Dept Med,Div Gastroenterol, New York, NY 10021 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Yale University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Cornell University; Weill Cornell Medicine
RP Lira, SA; Blander, JM (corresponding author), Icahn Sch Med Mt Sinai, Inst Immunol, New York, NY 10029 USA.; Lira, SA; Blander, JM (corresponding author), Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.; Blander, JM (corresponding author), Icahn Sch Med Mt Sinai, Grad Sch Biol Sci, New York, NY 10029 USA.; Lira, SA; Blander, JM (corresponding author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.; Blander, JM (corresponding author), Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.; Blander, JM (corresponding author), Cornell Univ, Weill Cornell Med, Dept Microbiol & Immunol,Jill Roberts Inst Inflam, Joan & Sanford I Weill Dept Med,Div Gastroenterol, New York, NY 10021 USA.
EM Sergio.lira@mssm.edu; JMBlander@med.cornell.edu
FU NIH [AI095245, AI123284, DK072201, 2T32A1007605-11, 5T32DK007792-12, 5P01DK072201-09, 5R01CA161373-04]; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Crohn's and Colitis Foundation of America (CCFA) Research Fellowship Award; NIAID [HHSN272201000054C, U19 AI117873, R01 DK092235, U01 DK62429, U01 DK062422]; philanthropic SUCCESS; Sanford J. Grossman Charitable Trust; CCFA [330239]; SUCCESS; Jenna and Paul Segal grant; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK062422] Funding Source: NIH RePORTER
NR 35
TC 185
Z9 209
U1 2
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 565
EP +
DI 10.1038/nature20138
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600044
PM 27828940
DA 2026-03-09
ER

PT J
AU Isogai, S
   Deupi, X
   Opitz, C
   Heydenreich, FM
   Tsai, CJ
   Rueckner, FB
   Schertler, GFX
   Veprintsev, DB
   Grzesiek, S
AF Isogai, Shin
   Deupi, Xavier
   Opitz, Christian
   Heydenreich, Franziska M.
   Tsai, Ching-Ju
   Rueckner, Florian B.
   Schertler, Gebhard F. X.
   Veprintsev, Dmitry B.
   Grzesiek, Stephan
TI Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor
SO NATURE
LA English
DT Article
ID beta(2)-adrenergic receptor; crystal-structure; structural insights; dynamic process; active state; protein; activation; agonist
AB G protein-coupled receptors (GPCRs) are physiologically important transmembrane signalling proteins that trigger intracellular responses upon binding of extracellular ligands. Despite recent breakthroughs in GPCR crystallography(1-3), the details of ligand-induced signal transduction are not well understood owing to missing dynamical information. In principle, such information can be provided by NMR4, but so far only limited data of functional relevance on few side-chain sites of eukaryotic GPCRs have been obtained(5-9). Here we show that receptor motions can be followed at virtually any backbone site in a thermostabilized mutant of the turkey beta(1)-adrenergic receptor (beta(1)AR)(10-12). Labelling with [N-15] valine in a eukaryotic expression system provides over twenty resolved resonances that report on structure and dynamics in six ligand complexes and the apo form. The response to the various ligands is heterogeneous in the vicinity of the binding pocket, but gets transformed into a homogeneous readout at the intracellular side of helix 5 (TM5), which correlates linearly with ligand efficacy for the G protein pathway. The effect of several pertinent, thermostabilizing point mutations was assessed by reverting them to the native sequence. Whereas the response to ligands remains largely unchanged, binding of the G protein mimetic nanobody NB80 and G protein activation are only observed when two conserved tyrosines (Y227 and Y343) are restored. Binding of NB80 leads to very strong spectral changes throughout the receptor, including the extracellular ligand entrance pocket. This indicates that even the fully thermostabilized receptor undergoes activating motions in TM5, but that the fully active state is only reached in presence of Y227 and Y343 by stabilization with a G protein-like partner. The combined analysis of chemical shift changes from the point mutations and ligand responses identifies crucial connections in the allosteric activation pathway, and presents a general experimental method to delineate signal transmission networks at high resolution in GPCRs.
C1 [Isogai, Shin; Opitz, Christian; Grzesiek, Stephan] Univ Basel, Focal Area Struct Biol & Biophys, Biozentrum, CH-4056 Basel, Switzerland.
   [Deupi, Xavier; Heydenreich, Franziska M.; Tsai, Ching-Ju; Rueckner, Florian B.; Schertler, Gebhard F. X.; Veprintsev, Dmitry B.] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
   [Schertler, Gebhard F. X.; Veprintsev, Dmitry B.] Swiss Fed Inst Technol, Dept Biol, CH-8093 Zurich, Switzerland.
C3 University of Basel; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Grzesiek, S (corresponding author), Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
EM gebhard.schertler@psi.ch; dmitry.veprintsev@psi.ch; stephan.grzesiek@unibas.ch
FU Marie Curie postdoctoral fellowship; EMBO postdoctoral fellowship; Swiss National Science Foundation [31-132857]; Sinergia [141898, 31-135754, 31-153145, 31-146520]; European Union [242135]; COST Action [CM1207]
NR 31
TC 148
Z9 166
U1 0
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 237
EP +
DI 10.1038/nature16577
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700043
PM 26840483
DA 2026-03-09
ER

PT J
AU Scheid, JF
   Horwitz, JA
   Bar-On, Y
   Kreider, EF
   Lu, CL
   Lorenzi, JCC
   Feldmann, A
   Braunschweig, M
   Nogueira, L
   Oliveira, T
   Shimeliovich, I
   Patel, R
   Burke, L
   Cohen, YZ
   Hadrigan, S
   Settler, A
   Witmer-Pack, M
   West, AP
   Juelg, B
   Keler, T
   Hawthorne, T
   Zingman, B
   Gulick, RM
   Pfeifer, N
   Learn, GH
   Seaman, MS
   Bjorkman, PJ
   Klein, F
   Schlesinger, SJ
   Walker, BD
   Hahn, BH
   Nussenzweig, MC
   Caskey, M
AF Scheid, Johannes F.
   Horwitz, Joshua A.
   Bar-On, Yotam
   Kreider, Edward F.
   Lu, Ching-Lan
   Lorenzi, Julio C. C.
   Feldmann, Anna
   Braunschweig, Malte
   Nogueira, Lilian
   Oliveira, Thiago
   Shimeliovich, Irina
   Patel, Roshni
   Burke, Leah
   Cohen, Yehuda Z.
   Hadrigan, Sonya
   Settler, Allison
   Witmer-Pack, Maggi
   West, Anthony P., Jr.
   Juelg, Boris
   Keler, Tibor
   Hawthorne, Thomas
   Zingman, Barry
   Gulick, Roy M.
   Pfeifer, Nico
   Learn, Gerald H.
   Seaman, Michael S.
   Bjorkman, Pamela J.
   Klein, Florian
   Schlesinger, Sarah J.
   Walker, Bruce D.
   Hahn, Beatrice H.
   Nussenzweig, Michel C.
   Caskey, Marina
TI HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption
SO NATURE
LA English
DT Article
ID broadly neutralizing antibody; antiretroviral therapy; monoclonal-antibody; genetic-determinants; passive transfer; potent; sequence; replication; responses; immunotherapy
AB Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117, a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein(1), during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions, separated by 3 or 2 weeks, respectively, are generally well tolerated. Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals, emerging viruses show increased resistance, indicating escape. However, 30% of participants remained suppressed until antibody concentrations waned below 20 mu g ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks. We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.
C1 [Scheid, Johannes F.; Horwitz, Joshua A.; Bar-On, Yotam; Lu, Ching-Lan; Lorenzi, Julio C. C.; Braunschweig, Malte; Nogueira, Lilian; Oliveira, Thiago; Shimeliovich, Irina; Patel, Roshni; Cohen, Yehuda Z.; Hadrigan, Sonya; Settler, Allison; Witmer-Pack, Maggi; Klein, Florian; Schlesinger, Sarah J.; Nussenzweig, Michel C.; Caskey, Marina] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Scheid, Johannes F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Scheid, Johannes F.] Harvard Med Sch, Boston, MA 02114 USA.
   [Kreider, Edward F.; Learn, Gerald H.; Hahn, Beatrice H.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Kreider, Edward F.; Learn, Gerald H.; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Feldmann, Anna; Pfeifer, Nico] Max Planck Inst Informat, Dept Computat Biol & Appl Algorithm, Campus E1 4, D-66123 Saarbrcken, Germany.
   [Burke, Leah; Gulick, Roy M.] Cornell Univ, Div Infect Dis, Weill Med Coll, New York, NY 10065 USA.
   [West, Anthony P., Jr.; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Juelg, Boris; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
   [Keler, Tibor; Hawthorne, Thomas] Celldex Therapeut Inc, Hampton, NJ 08827 USA.
   [Zingman, Barry] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
   [Klein, Florian] Univ Cologne, Ctr Mol Med Cologne CMMC, Lab Expt Immunol, D-50931 Cologne, Germany.
   [Klein, Florian] Univ Hosp Cologne, Ctr Integrated Oncol Cologne Bonn, Dept Internal Med 1, D-50937 Cologne, Germany.
   [Walker, Bruce D.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Rockefeller University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Pennsylvania; University of Pennsylvania; Max Planck Society; Cornell University; Weill Cornell Medicine; California Institute of Technology; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Celldex Therapeutics, Inc.; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; University of Cologne; University of Cologne; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Howard Hughes Medical Institute; Rockefeller University
RP Nussenzweig, MC; Caskey, M (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.; Nussenzweig, MC (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
EM nussen@rockefeller.edu; mcaskey@rockefeller.edu
FU Rockefeller University Hospital Clinical Research Support Office; AIDS Clinical Trials Group grant [UM1 AI068636]; Statistical and Data Management Center [UM1 AI068634]; Collaboration for AIDS Vaccine Discovery grant [OPP1033115, OPP1032144]; National Center for Advancing Translational Sciences (NCATS) [8 UL1 TR000043]; NIH Clinical and Translational Science Award (CTSA) program; NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663-01, 5UM1 AI100645-03, 1UM1 AI00645]; Bill and Melinda Gates Foundation [OPP1092074, OPP1124068]; NIH HIVRAD [P01 AI100148]; Robertson Foundation; Ruth L. Kirschstein National Research Service Award [F30 AI112426, F31 AI118555]; University of Pennsylvania Center for AIDS Research (CFAR) Single Genome Amplification Service Center [P30 AI045008]; NIH Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1-AI100663]; Bill and Melinda Gates Foundation [OPP1124068, OPP1092074, OPP1033115] Funding Source: Bill and Melinda Gates Foundation; National Center for Advancing Translational Sciences [UL1TR001866] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [P01AI100148, UM1AI068634] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse [UM1AI068636] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [UM1AI068636] Funding Source: NIH RePORTER; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; National Institute of Dental and Craniofacial Research; National Heart Lung and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Nursing Research; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse [P30AI045008] Funding Source: NIH RePORTER
NR 52
TC 396
Z9 474
U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 556
EP +
DI 10.1038/nature18929
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600030
PM 27338952
DA 2026-03-09
ER

PT J
AU Hyslop, LA
   Blakeley, P
   Craven, L
   Richardson, J
   Fogarty, NME
   Fragouli, E
   Lamb, M
   Wamaitha, SE
   Prathalingam, N
   Zhang, Q
   O'Keefe, H
   Takeda, Y
   Arizzi, L
   Alfarawati, S
   Tuppen, HA
   Irving, L
   Kalleas, D
   Choudhary, M
   Wells, D
   Murdoch, AP
   Turnbull, DM
   Niakan, KK
   Herbert, M
AF Hyslop, Louise A.
   Blakeley, Paul
   Craven, Lyndsey
   Richardson, Jessica
   Fogarty, Norah M. E.
   Fragouli, Elpida
   Lamb, Mahdi
   Wamaitha, Sissy E.
   Prathalingam, Nilendran
   Zhang, Qi
   O'Keefe, Hannah
   Takeda, Yuko
   Arizzi, Lucia
   Alfarawati, Samer
   Tuppen, Helen A.
   Irving, Laura
   Kalleas, Dimitrios
   Choudhary, Meenakshi
   Wells, Dagan
   Murdoch, Alison P.
   Turnbull, Douglass M.
   Niakan, Kathy K.
   Herbert, Mary
TI Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease
SO NATURE
LA English
DT Article
ID preimplantation genetic diagnosis; point mutations; human embryos; transmission; transcriptm; pluripotent; segregation; blastocyst; aneuploidy; disorders
AB Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases(1). Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes(2) were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention.
C1 [Hyslop, Louise A.; Richardson, Jessica; Lamb, Mahdi; Prathalingam, Nilendran; Zhang, Qi; O'Keefe, Hannah; Takeda, Yuko; Arizzi, Lucia; Irving, Laura; Kalleas, Dimitrios; Herbert, Mary] Wellcome Trust Ctr Mitochondrial Res, Inst Med Genet, Ctr Life, Biomed West Wing,Times Sq, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Hyslop, Louise A.; Prathalingam, Nilendran; Arizzi, Lucia; Choudhary, Meenakshi; Murdoch, Alison P.; Herbert, Mary] Newcastle Fertil Ctr, Ctr Life, Biomed West Wing,Times Sq, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
   [Blakeley, Paul; Fogarty, Norah M. E.; Wamaitha, Sissy E.; Niakan, Kathy K.] Francis Crick Inst, Human Embryo & Stem Cell Lab, Mill Hill Lab, Mill Hill, London NW7 1AA, England.
   [Craven, Lyndsey; Tuppen, Helen A.; Turnbull, Douglass M.] Newcastle Univ, Wellcome Trust Ctr Mitochondrial Res, Inst Neurosci, Sch Med, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Fragouli, Elpida; Alfarawati, Samer] Reprogenet UK, Inst Reprod Sci, Oxford Business Pk North, Oxford OX4 2HW, England.
   [Wells, Dagan] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England.
   [Zhang, Qi] Acad Mil Med Sci, Dept Cell Biol, 27th Taiping Rd, Beijing 100850, Peoples R China.
   [Irving, Laura] Gateshead Hlth NHS Trust, Queen Elizabeth Hosp, Gateshead Fertil Unit, Sheriff Hill, Gateshead NE9 6SX, England.
   [Kalleas, Dimitrios] Old St Marys Hosp, St Marys Hosp, Dept Reprod Med, Oxford Rd, Manchester M13 9WL, Lancs, England.
C3 Newcastle University - UK; Newcastle University - UK; University of Oxford; Academy of Military Medical Sciences - China; University of Manchester
RP Herbert, M (corresponding author), Wellcome Trust Ctr Mitochondrial Res, Inst Med Genet, Ctr Life, Biomed West Wing,Times Sq, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.; Herbert, M (corresponding author), Newcastle Fertil Ctr, Ctr Life, Biomed West Wing,Times Sq, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
EM mary.herbert@ncl.ac.uk
FU Wellcome Trust [096919]; National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre; Barbour Foundation; Francis Crick Institute - Cancer Research UK; UK Medical Research Council [MC_UP_1202/9]; Wellcome Trust; March of Dimes Foundation [FY11-436]; NIHR Oxford Biomedical Research Centre; Medical Research Council [MR/J003603/1, MR/L016354/1, MC_UP_1202/9] Funding Source: researchfish; The Francis Crick Institute [10120] Funding Source: researchfish; MRC [MR/L016354/1, MR/J003603/1, MC_UP_1202/9] Funding Source: UKRI
NR 42
TC 233
Z9 276
U1 0
U2 72
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 383
EP +
DI 10.1038/nature183030
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800035
PM 27281217
DA 2026-03-09
ER

PT J
AU Cai, DJ
   Aharoni, D
   Shuman, T
   Shobe, J
   Biane, J
   Song, WL
   Wei, B
   Veshkini, M
   La-Vu, M
   Lou, J
   Flores, SE
   Kim, I
   Sano, Y
   Zhou, M
   Baumgaertel, K
   Lavi, A
   Kamata, M
   Tuszynski, M
   Mayford, M
   Golshani, P
   Silva, AJ
AF Cai, Denise J.
   Aharoni, Daniel
   Shuman, Tristan
   Shobe, Justin
   Biane, Jeremy
   Song, Weilin
   Wei, Brandon
   Veshkini, Michael
   La-Vu, Mimi
   Lou, Jerry
   Flores, Sergio E.
   Kim, Isaac
   Sano, Yoshitake
   Zhou, Miou
   Baumgaertel, Karsten
   Lavi, Ayal
   Kamata, Masakazu
   Tuszynski, Mark
   Mayford, Mark
   Golshani, Peyman
   Silva, Alcino J.
TI A shared neural ensemble links distinct contextual memories encoded close in time
SO NATURE
LA English
DT Article
ID intrinsic neuronal excitability; fear memory; allocation; mice; place; trace; hippocampus; environment; system; recall
AB Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time(1-12). According to the memory allocation hypothesis(1,2), learning triggers a temporary increase in neuronal excitability(13-15) that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability(15,16), do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information.
C1 [Cai, Denise J.; Aharoni, Daniel; Shobe, Justin; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Lavi, Ayal; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Neurobiol, Los Angeles, CA 90025 USA.
   [Cai, Denise J.; Aharoni, Daniel; Shuman, Tristan; Shobe, Justin; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Lou, Jerry; Flores, Sergio E.; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Lavi, Ayal; Golshani, Peyman; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90025 USA.
   [Cai, Denise J.; Aharoni, Daniel; Shobe, Justin; Song, Weilin; Wei, Brandon; Veshkini, Michael; La-Vu, Mimi; Kim, Isaac; Sano, Yoshitake; Zhou, Miou; Lavi, Ayal; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Psychol, Los Angeles, CA 90025 USA.
   [Aharoni, Daniel; Shuman, Tristan; Lou, Jerry; Flores, Sergio E.; Golshani, Peyman] Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Neurol, Los Angeles, CA 90025 USA.
   [Aharoni, Daniel; Shuman, Tristan; Lou, Jerry; Flores, Sergio E.; Golshani, Peyman] West Los Angeles VA Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
   [Biane, Jeremy; Tuszynski, Mark] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Biane, Jeremy; Tuszynski, Mark] Vet Affairs Med Ctr, San Diego, CA 92161 USA.
   [Baumgaertel, Karsten; Mayford, Mark] Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Cell Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Baumgaertel, Karsten; Mayford, Mark] Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Neurosci, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Kamata, Masakazu] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; US Department of Veterans Affairs; Veterans Health Administration (VHA); West Los Angeles VA Medical Center; University of California System; University of California San Diego; US Department of Veterans Affairs; Veterans Health Administration (VHA); Scripps Research Institute; Scripps Research Institute; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Silva, AJ (corresponding author), Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Neurobiol, Los Angeles, CA 90025 USA.; Golshani, P; Silva, AJ (corresponding author), Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90025 USA.; Silva, AJ (corresponding author), Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Psychol, Los Angeles, CA 90025 USA.; Golshani, P (corresponding author), Univ Calif Los Angeles, Brain Res Inst, Integrat Ctr Learning & Memory, Dept Neurol, Los Angeles, CA 90025 USA.; Golshani, P (corresponding author), West Los Angeles VA Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM pgolshani@mednet.ucla.edu; silvaa@mednet.ucla.edu
FU National Institute on Aging [R37 AG013622]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; National Institutes of Health [RO1 MH101198, 1U54 HD087101, U01 NS094286-01]; VA Merit Award [BX00152401A1]; National Research Service Award [F32 MH97413]; Behavioral Neuroscience Training Grant [T32 MH15795]; Neurobehavioral Genetics Training Grant [T32 NS048004]; Neural Microcircuits Training Grant [T32 NS058280]; Cellular Neurobiology Training Grant [T32 NS710133]; Epilepsy Foundation; David Geffen School of Medicine Dean's Fund for development of open-source miniaturized microscopes; Grants-in-Aid for Scientific Research [15K21013] Funding Source: KAKEN; National Institute of Mental Health [T32NS048004] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32NS048004] Funding Source: NIH RePORTER
NR 33
TC 642
Z9 808
U1 1
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 115
EP +
DI 10.1038/nature17955
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300045
PM 27251287
DA 2026-03-09
ER

PT J
AU Schläger, C
   Körner, H
   Krueger, M
   Vidoli, S
   Haberl, M
   Mielke, D
   Brylla, E
   Issekutz, T
   Cabañas, C
   Nelsons, PJ
   Ziemssen, T
   Rohde, V
   Bechmann, I
   Lodygin, D
   Odoardi, F
   Flügel, A
AF Schlaeger, Christian
   Koerner, Henrike
   Krueger, Martin
   Vidoli, Stefano
   Haberl, Michael
   Mielke, Dorothee
   Brylla, Elke
   Issekutz, Thomas
   Cabanas, Carlos
   Nelsons, Peter J.
   Ziemssen, Tjalf
   Rohde, Veit
   Bechmann, Ingo
   Lodygin, Dmitri
   Odoardi, Francesca
   Fluegel, Alexander
TI Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid
SO NATURE
LA English
DT Article
ID experimental autoimmune encephalomyelitis; choroid-plexus; real-time; in-vivo; cns; activation; migration; system; antigen; inflammation
AB In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue(1,2). How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical(3-6). Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen availability and tissue damage.
C1 [Schlaeger, Christian; Koerner, Henrike; Haberl, Michael; Lodygin, Dmitri; Odoardi, Francesca; Fluegel, Alexander] Univ Med Ctr Gottingen, Inst Multiple Sclerosis Res, Inst Neuroimmunol, D-37073 Gottingen, Germany.
   [Fluegel, Alexander] Max Planck Inst Expt Med, D-37075 Gottingen, Germany.
   [Krueger, Martin; Brylla, Elke; Bechmann, Ingo] Univ Leipzig, Inst Anat, D-04103 Leipzig, Germany.
   [Vidoli, Stefano] Univ Roma La Sapienza, Dept Struct & Geotech Engn, I-00135 Rome, Italy.
   [Mielke, Dorothee; Rohde, Veit] Univ Med Ctr Gottingen, Dept Neurosurg, D-37075 Gottingen, Germany.
   [Issekutz, Thomas] Dalhousie Univ, Dept Pediat, Div Immunol, Halifax, NS B3H 4R2, Canada.
   [Cabanas, Carlos] Ctr Biol Mol Severo Ochoa, Dept Biol Celular & Inmunol, Madrid 28049, Spain.
   [Nelsons, Peter J.] Univ Munich, Med Clin & Policlin 4, D-80336 Munich, Germany.
   [Ziemssen, Tjalf] Univ Hosp, Dept Neurol, D-01307 Dresden, Germany.
C3 University of Gottingen; University of Gottingen Hospital; Max Planck Society; Leipzig University; Sapienza University Rome; University of Gottingen; University of Gottingen Hospital; Dalhousie University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM); University of Munich; Technische Universitat Dresden; Carl Gustav Carus University Hospital
RP Flügel, A (corresponding author), Univ Med Ctr Gottingen, Inst Multiple Sclerosis Res, Inst Neuroimmunol, D-37073 Gottingen, Germany.; Flügel, A (corresponding author), Max Planck Inst Expt Med, D-37075 Gottingen, Germany.
EM fluegel@med.uni-goettingen.de
NR 53
TC 306
Z9 360
U1 0
U2 66
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 349
EP +
DI 10.1038/nature16939
PG 28
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100040
PM 26863192
DA 2026-03-09
ER

PT J
AU Bosveld, F
   Markova, O
   Guirao, B
   Martin, C
   Wang, ZM
   Pierre, A
   Balakireva, M
   Gaugue, I
   Ainslie, A
   Christophorou, N
   Lubensky, DK
   Minc, N
   Bellaïche, Y
AF Bosveld, Floris
   Markova, Olga
   Guirao, Boris
   Martin, Charlotte
   Wang, Zhimin
   Pierre, Anaelle
   Balakireva, Maria
   Gaugue, Isabelle
   Ainslie, Anna
   Christophorou, Nicolas
   Lubensky, David K.
   Minc, Nicolas
   Bellaiche, Yohanns
TI Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis
SO NATURE
LA English
DT Article
ID regulates spindle orientation; mitotic spindle; drosophila-melanogaster; polarity pathway; cleavage plane; protein; divisions; tissue; morphogenesis; localization
AB The orientation of cell division along the long axis of the interphase cell-the century-old Hertwig's rule-has profound roles in tissue proliferation, morphogenesis, architecture and mechanics(1,2). In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbour topology, and planar polarity pathways(3-12). At mitosis, epithelial cells usually adopt a rounded shape to ensure faithful chromosome segregation and to promote morphogenesis(1). The mechanisms underlying interphase cell shape sensing in tissues are therefore unknown. Here we show that in Drosophila epithelia, tricellular junctions (TCJs) localize force generators, pulling on astral microtubules and orienting cell division via the Dynein-associated protein Mud independently of the classical Pins/G alpha(i) pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJs emerge from a general geometric property of TCJ distributions in epithelial tissues. Thus, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues.
C1 [Bosveld, Floris; Markova, Olga; Guirao, Boris; Martin, Charlotte; Wang, Zhimin; Balakireva, Maria; Gaugue, Isabelle; Ainslie, Anna; Christophorou, Nicolas; Lubensky, David K.; Bellaiche, Yohanns] Inst Curie, CNRS UMR 3215, INSERM U934, Polar,Div & Morphogenesis Team, 26 Rue Ulm, F-75248 Paris 05, France.
   [Pierre, Anaelle; Minc, Nicolas] Inst Jacques Monod, CNRS UMR7592, 15 Rue Helene Brion, F-75205 Paris 13, France.
   [Lubensky, David K.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
   [Martin, Charlotte] Univ Paris Sud, CNRS UMR 3348, Inst Curie, Batiment 110, F-91405 Orsay, France.
   [Christophorou, Nicolas] Inst Jean Pierre Bourgin, INRA, UMR 1318, ERL CNRS 3559,Saclay Plant Sci,RD10, Versailles, France.
   [Ainslie, Anna] Lincolns Inn Fields Lab, Francis Crick Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England.
C3 Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; University of Michigan System; University of Michigan; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Saclay; UNICANCER; Universite PSL; Institut Curie; AgroParisTech; Universite Paris Saclay; INRAE; Francis Crick Institute
RP Bosveld, F (corresponding author), Inst Curie, CNRS UMR 3215, INSERM U934, Polar,Div & Morphogenesis Team, 26 Rue Ulm, F-75248 Paris 05, France.
EM floris.bosveld@curie.fr; yohanns.bellaiche@curie.fr
FU CePoDro ANR; MorphoDro ERC Advanced; ARC [SL220130607097]; Curie Mayent-Rothschild; Labex DEEP; NSF [DMR1056456]; ICAM; Direct For Mathematical & Physical Scien [1056456] Funding Source: National Science Foundation; Division Of Materials Research [1056456] Funding Source: National Science Foundation
NR 60
TC 182
Z9 222
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 495
EP +
DI 10.1038/nature16970
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800039
PM 26886796
DA 2026-03-09
ER

PT J
AU Farin, HF
   Jordens, I
   Mosa, MH
   Basak, O
   Korving, J
   Tauriello, DVF
   de Punder, K
   Angers, S
   Peters, PJ
   Maurice, MM
   Clevers, H
AF Farin, Homier F.
   Jordens, Ingrid
   Mosa, Mohammed H.
   Basak, Onur
   Korving, Jeroen
   Tauriello, Daniele V. F.
   de Punder, Karin
   Angers, Stephane
   Peters, Peter J.
   Maurice, Madelon M.
   Clevers, Hans
TI Visualization of a short-range Wnt gradient in the intestinal stem-cell niche
SO NATURE
LA English
DT Article
ID morphogen gradient; drosophila embryos; structural basis; in-vitro; wingless; lgr5; expression; crypt; recombinase; recognition
AB Mammalian Wnt proteins are believed to act as short-range signals(1-4), yet have not been previously visualized in vivo. Selfrenewal, proliferation and differentiation are coordinated along a putative Wnt gradient in the intestinal crypt(5). Wnt3 is produced specifically by Paneth cells(6,7). Here we have generated an epitopetagged, functional Wnt3 knock-in allele. Wnt3 covers basolateral membranes of neighbouring stem cells. In intestinal organoids, Wnt3-transfer involves direct contact between Paneth cells and stem cells. Plasma membrane localization requires surface expression of Frizzled receptors, which in turn is regulated by the transmembrane E3 ligases Rnf43/Znrf3 and their antagonists Lgr4-5/R-spondin. By manipulating Wnt3 secretion and by arresting stem-cell proliferation, we demonstrate that Wnt3 mainly travels away from its source in a cell-bound manner through cell division, and not through diffusion. We conclude that stem-cell membranes constitute a reservoir for Wnt proteins, while Frizzled receptor turnover and ` plasma membrane dilution' through cell division shape the epithelial Wnt3 gradient.
C1 [Farin, Homier F.; Basak, Onur; Korving, Jeroen; Clevers, Hans] Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [Farin, Homier F.; Basak, Onur; Korving, Jeroen; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Farin, Homier F.; Mosa, Mohammed H.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
   [Farin, Homier F.; Mosa, Mohammed H.] Georg Speyer Haus Inst Tumor Biol & Expt Therapy, D-60596 Frankfurt, Germany.
   [Farin, Homier F.; Mosa, Mohammed H.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Jordens, Ingrid; Tauriello, Daniele V. F.; Maurice, Madelon M.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
   [de Punder, Karin; Peters, Peter J.] Maastricht Univ, Maastricht Multimodal Mol Imaging Inst, NL-6229 ER Maastricht, Netherlands.
   [Angers, Stephane] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Utrecht University; Utrecht University Medical Center; Maastricht University; University of Toronto
RP Farin, HF; Clevers, H (corresponding author), Royal Netherlands Acad Arts & Sci KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.; Farin, HF; Clevers, H (corresponding author), Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.; Farin, HF (corresponding author), German Canc Consortium DKTK, D-69120 Heidelberg, Germany.; Farin, HF (corresponding author), Georg Speyer Haus Inst Tumor Biol & Expt Therapy, D-60596 Frankfurt, Germany.; Farin, HF (corresponding author), German Canc Res Ctr, D-69120 Heidelberg, Germany.
EM farin@gsh.uni-frankfurt.de; h.clevers@hubrecht.eu
NR 38
TC 419
Z9 526
U1 0
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 340
EP +
DI 10.1038/nature16937
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100038
PM 26863187
DA 2026-03-09
ER

PT J
AU Ahmadi, M
   Baquero-Ruiz, M
   Bertsche, W
   Butler, E
   Capra, A
   Carruth, C
   Cesar, CL
   Charlton, M
   Charman, AE
   Eriksson, S
   Evans, LT
   Evetts, N
   Fajans, J
   Friesen, T
   Fujiwara, MC
   Gill, DR
   Gutierrez, A
   Hangst, JS
   Hardy, WN
   Hayden, ME
   Isaac, CA
   Ishida, A
   Jones, SA
   Jonsell, S
   Kurchaninov, L
   Madsen, N
   Maxwell, D
   McKenna, JTK
   Menary, S
   Michan, JM
   Momose, T
   Munich, JJ
   Nolan, P
   Olchanski, K
   Olin, A
   Povilus, A
   Pusa, P
   Rasmussen, CO
   Robicheaux, F
   Sacramento, RL
   Sameed, M
   Sarid, E
   Silveira, DM
   So, C
   Tharp, TD
   Thompson, RI
   van der Werf, DP
   Wurtele, JS
   Zhmoginov, AI
AF Ahmadi, M.
   Baquero-Ruiz, M.
   Bertsche, W.
   Butler, E.
   Capra, A.
   Carruth, C.
   Cesar, C. L.
   Charlton, M.
   Charman, A. E.
   Eriksson, S.
   Evans, L. T.
   Evetts, N.
   Fajans, J.
   Friesen, T.
   Fujiwara, M. C.
   Gill, D. R.
   Gutierrez, A.
   Hangst, J. S.
   Hardy, W. N.
   Hayden, M. E.
   Isaac, C. A.
   Ishida, A.
   Jones, S. A.
   Jonsell, S.
   Kurchaninov, L.
   Madsen, N.
   Maxwell, D.
   McKenna, J. T. K.
   Menary, S.
   Michan, J. M.
   Momose, T.
   Munich, J. J.
   Nolan, P.
   Olchanski, K.
   Olin, A.
   Povilus, A.
   Pusa, P.
   Rasmussen, C. O.
   Robicheaux, F.
   Sacramento, R. L.
   Sameed, M.
   Sarid, E.
   Silveira, D. M.
   So, C.
   Tharp, T. D.
   Thompson, R. I.
   van der Werf, D. P.
   Wurtele, J. S.
   Zhmoginov, A. I.
TI An improved limit on the charge of antihydrogen from stochastic acceleration
SO NATURE
LA English
DT Article
ID electron
AB Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms(1-4) of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of vertical bar Q vertical bar < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement(5) of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known(6) to be no greater than about 10(-21)e for a diverse range of species including H-2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation(7) demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge(8), then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement(8),(9).
C1 [Ahmadi, M.; Nolan, P.; Pusa, P.] Univ Liverpool, Dept Phys, Liverpool L69 7ZE, Merseyside, England.
   [Baquero-Ruiz, M.; Carruth, C.; Charman, A. E.; Evans, L. T.; Fajans, J.; Povilus, A.; So, C.; Wurtele, J. S.; Zhmoginov, A. I.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Baquero-Ruiz, M.] Ecole Polytech Fed Lausanne, CRPP, CH-1015 Lausanne, Switzerland.
   [Bertsche, W.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Bertsche, W.] Sci Tech Daresbury, Cockcroft Inst, Warrington WA4 4AD, Cheshire, England.
   [Butler, E.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Ctr Cold Matter, London SW7 2AZ, England.
   [Butler, E.; Ishida, A.] European Org Nucl Res CERN, Dept Phys, CH-1211 Geneva 23, Switzerland.
   [Capra, A.; Menary, S.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Cesar, C. L.; Sacramento, R. L.; Silveira, D. M.] Univ Fed Rio de Janeiro, Inst Fis, BR-21941972 Rio De Janeiro, Brazil.
   [Charlton, M.; Eriksson, S.; Isaac, C. A.; Jones, S. A.; Madsen, N.; Maxwell, D.; Sameed, M.; van der Werf, D. P.] Swansea Univ, Dept Phys, Swansea SA2 8PP, W Glam, Wales.
   [Evetts, N.; Gutierrez, A.; Hardy, W. N.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z4, Canada.
   [Friesen, T.; Hangst, J. S.; Rasmussen, C. O.; Tharp, T. D.] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Fujiwara, M. C.; Gill, D. R.; Kurchaninov, L.; McKenna, J. T. K.; Michan, J. M.; Olchanski, K.; Olin, A.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Hayden, M. E.; Munich, J. J.] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada.
   [Jonsell, S.] Stockholm Univ, Dept Phys, SE-10691 Stockholm, Sweden.
   [Momose, T.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
   [Olin, A.] Univ Victoria, Dept Phys & Astron, Victoria, BC V8P 5C2, Canada.
   [Robicheaux, F.] Purdue Univ, Dept Phys & Astron, W Lafayette, IN 47907 USA.
   [Sarid, E.] Soreq Nucl Res Ctr, IL-81800 Yavne, Israel.
   [Thompson, R. I.] Univ Calgary, Dept Phys & Astron, Calgary, AB T2N 1N4, Canada.
   [Wurtele, J. S.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, ATAP, Berkeley, CA 94720 USA.
C3 University of Liverpool; University of California System; University of California Berkeley; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Manchester; STFC Daresbury Laboratory; Imperial College London; York University - Canada; Universidade Federal do Rio de Janeiro; Swansea University; University of British Columbia; Aarhus University; University of British Columbia; Simon Fraser University; Stockholm University; University of British Columbia; University of Victoria; Purdue University System; Purdue University; University of Calgary; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Fajans, J (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM joel@physics.berkeley.edu; wurtele@berkeley.edu
FU CNPq (Brazil); FINEP-RENAFAE (Brazil); NSERC, (Canada); NRC/TRIUMF, (Canada); AITF, (Canada); FQRNT (Canada); FNU, (Denmark); Carlsberg Foundation (Denmark); JSPS Postdoctoral Fellowships for Research Abroad (Japan); ISF (Israel); STFC (UK); EPSRC (UK); Royal Society (UK); Leverhulme Trust (UK); DOE (USA); NSF (USA); VR (Sweden); EPSRC [EP/L014734/1, EP/K017373/1, EP/E048951/1, EP/L014769/1, EP/H02431X/1, EP/K040235/1, EP/H026932/1, EP/L005522/1, EP/L014718/1] Funding Source: UKRI; STFC [ST/G008248/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/K040235/1, EP/H026932/1, EP/L005522/1, 1422853, EP/L014718/1, EP/K017373/1, EP/L014734/1, EP/L014769/1, EP/H02431X/1, EP/E048951/1, 1510926] Funding Source: researchfish; Science and Technology Facilities Council [ST/G008248/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Physics [1500538] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1500470] Funding Source: National Science Foundation
NR 35
TC 47
Z9 58
U1 0
U2 43
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 373
EP +
DI 10.1038/nature16491
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800041
PM 26791725
DA 2026-03-09
ER

PT J
AU Pätzold, M
   Andert, T
   Hahn, M
   Asmar, SW
   Barriot, JP
   Bird, MK
   Häusler, B
   Peter, K
   Tellmann, S
   Grün, E
   Weissman, PR
   Sierks, H
   Jorda, L
   Gaskell, R
   Preusker, F
   Scholten, F
AF Paetzold, M.
   Andert, T.
   Hahn, M.
   Asmar, S. W.
   Barriot, J. -P.
   Bird, M. K.
   Haeusler, B.
   Peter, K.
   Tellmann, S.
   Gruen, E.
   Weissman, P. R.
   Sierks, H.
   Jorda, L.
   Gaskell, R.
   Preusker, F.
   Scholten, F.
TI A homogeneous nucleus for comet 67P/Churyumov-Gerasimenko from its gravity field
SO NATURE
LA English
DT Article
ID mass; express
AB Cometary nuclei consist mostly of dust and water ice(1). Previous observations have found nuclei to be low-density and highly porous bodies(2-4), but have only moderately constrained the range of allowed densities because of the measurement uncertainties. Here we report the precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov-Gerasimenko on the basis of its gravity field. The mass and gravity field are derived from measured spacecraft velocity perturbations at fly-by distances between 10 and 100 kilometres. The gravitational point mass is GM = 666.2 +/- 0.2 cubic metres per second squared, giving a mass M = (9,982 +/- 3) x 10(9) kilograms. Together with the current estimate of the volume of the nucleus(5), the average bulk density of the nucleus is 533 +/- 6 kilograms per cubic metre. The nucleus appears to be a low-density, highly porous (72-74 per cent) dusty body, similar to that of comet 9P/Tempel 1(2,3). The most likely composition mix has approximately four times more dust than ice by mass and two times more dust than ice by volume. We conclude that the interior of the nucleus is homogeneous and constant in density on a global scale without large voids. The high porosity seems to be an inherent property of the nucleus material.
C1 [Paetzold, M.; Hahn, M.; Bird, M. K.; Peter, K.; Tellmann, S.] Univ Cologne, Rhein Inst Umweltforsch, Abt Planetenforsch, D-50931 Cologne, Germany.
   [Andert, T.; Haeusler, B.] Univ Bundeswehr Munchen, Inst Raumfahrttech & Weltraumnutzung, D-85577 Neubiberg, Germany.
   [Asmar, S. W.] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
   [Barriot, J. -P.] Univ Polynesie Francaise, Faaa, Tahiti, France.
   [Gruen, E.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Weissman, P. R.; Gaskell, R.] Planetary Sci Inst, 1700 East Ft Lowell,Suite 106, Tucson, AZ 85719 USA.
   [Sierks, H.] Max Planck Inst Sonnensyst Forsch, D-37077 Gottingen, Germany.
   [Jorda, L.] Aix Marseille Univ, Lab Astrophys Marseille, F-13388 Marseille, France.
   [Preusker, F.; Scholten, F.] Deutsch Zentrum Luft & Raumfahrt DLR Berlin Adler, Inst Planetenforsch, D-12489 Berlin, Germany.
C3 University of Cologne; Bundeswehr University Munich; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Max Planck Society; Max Planck Society; Aix-Marseille Universite; Helmholtz Association; German Aerospace Centre (DLR)
RP Pätzold, M (corresponding author), Univ Cologne, Rhein Inst Umweltforsch, Abt Planetenforsch, D-50931 Cologne, Germany.
EM martin.paetzold@uni-koeln.de
FU Bundesministerium fur Wirtschaft BMWi, Berlin, via the German Space Agency DLR, Bonn [50QM1401, 50QM1002]; CNES, Paris; NASA/JPL
NR 29
TC 262
Z9 277
U1 1
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 63
EP +
DI 10.1038/nature16535
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500032
PM 26842054
DA 2026-03-09
ER

PT J
AU Beyaz, S
   Mana, MD
   Roper, J
   Kedrin, D
   Saadatpour, A
   Hong, SJ
   Bauer-Rowe, KE
   Xifaras, ME
   Akkad, A
   Arias, E
   Pinello, L
   Katz, Y
   Shinagare, S
   Abu-Remaileh, M
   Mihaylova, MM
   Lamming, DW
   Dogum, R
   Guo, GJ
   Bell, GW
   Selig, M
   Nielsen, GP
   Gupta, N
   Ferrone, CR
   Deshpande, V
   Yuan, GC
   Orkin, SH
   Sabatini, DM
   Yilmaz, ÖH
AF Beyaz, Semir
   Mana, Miyeko D.
   Roper, Jatin
   Kedrin, Dmitriy
   Saadatpour, Assieh
   Hong, Sue Jean
   Bauer-Rowe, Khristian E.
   Xifaras, Michael E.
   Akkad, Adam
   Arias, Erika
   Pinello, Luca
   Katz, Yarden
   Shinagare, Shweta
   Abu-Remaileh, Monther
   Mihaylova, Maria M.
   Lamming, Dudley W.
   Dogum, Rizkullah
   Guo, Guoji
   Bell, George W.
   Selig, Martin
   Nielsen, G. Petur
   Gupta, Nitin
   Ferrone, Cristina R.
   Deshpande, Vikram
   Yuan, Guo-Cheng
   Orkin, Stuart H.
   Sabatini, David M.
   Yilmaz, Oemer H.
TI High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
SO NATURE
LA English
DT Article
ID activated-receptor-delta; genetic disruption; in-vitro; cancer; cells; expression; exercise; obesity; mouse; model
AB Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-delta recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-delta-dependent manner. Notably, HFD- and agonist-activated PPAR-delta signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-delta signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.
C1 [Beyaz, Semir; Mana, Miyeko D.; Roper, Jatin; Kedrin, Dmitriy; Bauer-Rowe, Khristian E.; Xifaras, Michael E.; Akkad, Adam; Arias, Erika; Shinagare, Shweta; Abu-Remaileh, Monther; Mihaylova, Maria M.; Dogum, Rizkullah; Sabatini, David M.; Yilmaz, Oemer H.] MIT, Dept Biol, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Beyaz, Semir; Guo, Guoji; Orkin, Stuart H.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   [Beyaz, Semir; Guo, Guoji; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Howard Hughes Med Inst,Harvard, 44 Binney St, Boston, MA 02115 USA.
   [Roper, Jatin] Tufts Med Ctr, Div Gastroenterol, Boston, MA 02111 USA.
   [Roper, Jatin] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.
   [Kedrin, Dmitriy; Selig, Martin; Nielsen, G. Petur; Ferrone, Cristina R.; Deshpande, Vikram; Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Kedrin, Dmitriy; Selig, Martin; Nielsen, G. Petur; Ferrone, Cristina R.; Deshpande, Vikram; Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
   [Kedrin, Dmitriy; Selig, Martin; Nielsen, G. Petur; Ferrone, Cristina R.; Deshpande, Vikram; Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   [Kedrin, Dmitriy; Selig, Martin; Nielsen, G. Petur; Ferrone, Cristina R.; Deshpande, Vikram; Yilmaz, Oemer H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Saadatpour, Assieh; Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Saadatpour, Assieh; Pinello, Luca; Yuan, Guo-Cheng] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
   [Hong, Sue Jean; Abu-Remaileh, Monther; Mihaylova, Maria M.; Bell, George W.; Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Whitehead Inst Biomed Res, 77 Massachusetts Ave, Cambridge, MA 02142 USA.
   [Katz, Yarden; Sabatini, David M.; Yilmaz, Oemer H.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA.
   [Gupta, Nitin] Univ Mississippi, Med Ctr, Div Digest Dis, Jackson, MS 39216 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Tufts Medical Center; Tufts Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Wisconsin System; University of Wisconsin Madison; University of Mississippi Medical Center; University of Mississippi
RP Sabatini, DM; Yilmaz, ÖH (corresponding author), MIT, Dept Biol, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Yilmaz, ÖH (corresponding author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Yilmaz, ÖH (corresponding author), Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.; Yilmaz, ÖH (corresponding author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.; Sabatini, DM (corresponding author), MIT, Dept Biol, Howard Hughes Med Inst, Whitehead Inst Biomed Res, 77 Massachusetts Ave, Cambridge, MA 02142 USA.; Sabatini, DM; Yilmaz, ÖH (corresponding author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu; ohyilmaz@mit.edu
FU Howard Hughes Medical Institute; Ellison Medical Foundation Aging; NIH [R01 CA103866, A147389, K08 CA198002, ROD AG045144, ROD AG041765]; Department of Defense PRCRP Career Development Award [CA120198]; Center for the Study of Inflammatory Bowel Diseases from the Massachusetts General Hospital NIH [DK043351]; NIH Cancer Center Support [P30-CA14051]; Kathy and Curt Marble Cancer Research Fund; American Federation of Aging Research (AFAR); V Foundation Scholar grant; Koch MIT Ludwig Center; MGH [T32DK007191]; Damon Runyon Cancer Research Foundation; Hope Babette Tang Histology Facility and Kathleen Cormier; CDMRP [542403, CA120198] Funding Source: Federal RePORTER; National Cancer Institute [R01CA103866, R01CA129105, P30CA014051] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI047389] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007191, P30DK043351] Funding Source: NIH RePORTER
NR 48
TC 657
Z9 748
U1 13
U2 296
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 53
EP +
DI 10.1038/nature17173
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900038
PM 26935695
DA 2026-03-09
ER

PT J
AU Bashan, A
   Gibson, TE
   Friedman, J
   Carey, VJ
   Weiss, ST
   Hohmann, EL
   Liu, YY
AF Bashan, Amir
   Gibson, Travis E.
   Friedman, Jonathan
   Carey, Vincent J.
   Weiss, Scott T.
   Hohmann, Elizabeth L.
   Liu, Yang-Yu
TI Universality of human microbial dynamics
SO NATURE
LA English
DT Article
ID gut microbiota; transplantation; diversity; health
AB Human-associated microbial communities have a crucial role in determining our health and well-being(1,2), and this has led to the continuing development of microbiome-based therapies(3) such as faecal microbiota transplantation(4,5). These microbial communities are very complex, dynamic(6) and highly personalized ecosystems(3,7), exhibiting a high degree of inter-individual variability in both species assemblages(8) and abundance profiles(9). It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra-and inter-species interactions in population dynamics models(10), are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle(11), physiology(12) or genetics(13), then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species(7,14). Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studiesthe Human Microbiome Project(9,15) and the Student Microbiome Project(16)-we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection(17) but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiomebased therapies(18).
C1 [Bashan, Amir; Gibson, Travis E.; Carey, Vincent J.; Weiss, Scott T.; Liu, Yang-Yu] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
   [Bashan, Amir; Gibson, Travis E.; Carey, Vincent J.; Weiss, Scott T.; Hohmann, Elizabeth L.; Liu, Yang-Yu] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Friedman, Jonathan] MIT, Dept Phys, Phys Living Syst, Cambridge, MA 02139 USA.
   [Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA.
   [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Liu, YY (corresponding author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Liu, YY (corresponding author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Liu, YY (corresponding author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
EM yyl@channing.harvard.edu
FU John Templeton Foundation [51977]; National Institutes of Health [R01 HL091528]
NR 38
TC 197
Z9 231
U1 2
U2 220
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 259
EP +
DI 10.1038/nature18301
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100043
PM 27279224
DA 2026-03-09
ER

PT J
AU Lesk, C
   Rowhani, P
   Ramankutty, N
AF Lesk, Corey
   Rowhani, Pedram
   Ramankutty, Navin
TI Influence of extreme weather disasters on global crop production
SO NATURE
LA English
DT Article
ID climate-change; drought; maize; heat; trends
AB In recent years, several extreme weather disasters have partially or completely damaged regional crop production(1-5). While detailed regional accounts of the effects of extreme weather disasters exist, the global scale effects of droughts, floods and extreme temperature on crop production are yet to be quantified. Here we estimate for the first time, to our knowledge, national cereal production losses across the globe resulting from reported extreme weather disasters during 1964-2007. We show that droughts and extreme heat significantly reduced national cereal production by 9-10%, whereas our analysis could not identify an effect from floods and extreme cold in the national data. Analysing the underlying processes, we find that production losses due to droughts were associated with a reduction in both harvested area and yields, whereas extreme heat mainly decreased cereal yields. Furthermore, the results highlight similar to 7% greater production damage from more recent droughts and 8-11% more damage in developed countries than in developing ones. Our findings may help to guide agricultural priorities in international disaster risk reduction and adaptation efforts.
C1 [Lesk, Corey; Ramankutty, Navin] McGill Univ, Dept Geog, Montreal, PQ H3A 0B9, Canada.
   [Rowhani, Pedram] Univ Sussex, Dept Geog, Brighton BN1 9QJ, E Sussex, England.
   [Ramankutty, Navin] Univ British Columbia, Liu Inst Global Issues, Vancouver, BC V6T 1Z2, Canada.
   [Ramankutty, Navin] Univ British Columbia, Inst Resources Environm & Sustainabil, Vancouver, BC V6T 1Z2, Canada.
C3 McGill University; University of Sussex; University of British Columbia; University of British Columbia
RP Ramankutty, N (corresponding author), McGill Univ, Dept Geog, Montreal, PQ H3A 0B9, Canada.; Ramankutty, N (corresponding author), Univ British Columbia, Liu Inst Global Issues, Vancouver, BC V6T 1Z2, Canada.; Ramankutty, N (corresponding author), Univ British Columbia, Inst Resources Environm & Sustainabil, Vancouver, BC V6T 1Z2, Canada.
EM navin.ramankutty@ubc.ca
FU Natural Science and Engineering Research Council of Canada; Natural Science and Engineering Research Council of Canada
NR 28
TC 2715
Z9 3140
U1 162
U2 2263
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 84
EP +
DI 10.1038/nature16467
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900031
PM 26738594
DA 2026-03-09
ER

PT J
AU Tenaillon, O
   Barrick, JE
   Ribeck, N
   Deatherage, DE
   Blanchard, JL
   Dasgupta, A
   Wu, GC
   Wielgoss, S
   Cruveiller, S
   Médigue, C
   Schneider, D
   Lenski, RE
AF Tenaillon, Olivier
   Barrick, Jeffrey E.
   Ribeck, Noah
   Deatherage, Daniel E.
   Blanchard, Jeffrey L.
   Dasgupta, Aurko
   Wu, Gabriel C.
   Wielgoss, Sebastien
   Cruveiller, Stephane
   Medigue, Claudine
   Schneider, Dominique
   Lenski, Richard E.
TI Tempo and mode of genome evolution in a 50,000-generation experiment
SO NATURE
LA English
DT Article
ID term experimental evolution; escherichia-coli; beneficial mutations; bacterial population; adapting populations; molecular evolution; clonal interference; positive selection; genetic draft; codon bias
AB Adaptation by natural selection depends on the rates, effects and interactions of many mutations, making it difficult to determine what proportion of mutations in an evolving lineage are beneficial. Here we analysed 264 complete genomes from 12 Escherichia coli populations to characterize their dynamics over 50,000 generations. The populations that retained the ancestral mutation rate support a model in which most fixed mutations are beneficial, the fraction of beneficial mutations declines as fitness rises, and neutral mutations accumulate at a constant rate. We also compared these populations to mutation-accumulation lines evolved under a bottlenecking regime that minimizes selection. Nonsynonymous mutations, intergenic mutations, insertions and deletions are overrepresented in the long-term populations, further supporting the inference that most mutations that reached high frequency were favoured by selection. These results illuminate the shifting balance of forces that govern genome evolution in populations adapting to a new environment.
C1 [Tenaillon, Olivier] Univ Paris Diderot, Sorbonne Paris Cite, INSERM, IAME,UMR 1137, F-75018 Paris, France.
   [Barrick, Jeffrey E.; Deatherage, Daniel E.; Dasgupta, Aurko; Wu, Gabriel C.] Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Syst & Synthet Biol, Dept Mol Biosci,Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
   [Barrick, Jeffrey E.; Ribeck, Noah; Lenski, Richard E.] Michigan State Univ, BEACON Ctr Study Evolut Act, E Lansing, MI 48824 USA.
   [Ribeck, Noah; Lenski, Richard E.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
   [Blanchard, Jeffrey L.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
   [Wielgoss, Sebastien] ETH, Inst Integrat Biol, Univ Str 16, CH-8092 Zurich, Switzerland.
   [Wielgoss, Sebastien; Schneider, Dominique] Univ Grenoble Alpes, Lab Technol Ingn Med & Complexite Informat Math &, F-38000 Grenoble, France.
   [Cruveiller, Stephane; Medigue, Claudine] Univ Evry Val dEssonne, CEA, Lab Anal Bioinformat Genom & Metabol, Inst Genom,CNRS,UMR 8030, F-91000 Evry, France.
   [Schneider, Dominique] CNRS, TIMC IMAG, F-38000 Grenoble, France.
   [Dasgupta, Aurko] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
C3 Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Texas System; University of Texas Austin; Michigan State University; Michigan State University; University of Massachusetts System; University of Massachusetts Amherst; Swiss Federal Institutes of Technology Domain; ETH Zurich; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA; Universite Paris Saclay; Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Washington University (WUSTL)
RP Lenski, RE (corresponding author), Michigan State Univ, BEACON Ctr Study Evolut Act, E Lansing, MI 48824 USA.; Lenski, RE (corresponding author), Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
EM lenski@msu.edu
FU US National Science Foundation [DEB-1451740]; BEACON Center for the Study of Evolution in Action [DBI-0939454]; European Research Council [310944]; European Union [610427]; French National Funding Agency [ANR-08-GENM-023-001]; French CNRS International Associated Laboratory; US National Institutes of Health [R00-GM087550]; Cancer Prevention and Research Institute of Texas; Division Of Environmental Biology; Direct For Biological Sciences [1451740] Funding Source: National Science Foundation; European Research Council (ERC) [310944] Funding Source: European Research Council (ERC)
NR 50
TC 316
Z9 362
U1 5
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 165
EP +
DI 10.1038/nature18959
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100027
PM 27479321
DA 2026-03-09
ER

PT J
AU Ding, JJ
   Wang, K
   Liu, W
   She, Y
   Sun, Q
   Shi, JJ
   Sun, HZ
   Wang, DC
   Shao, F
AF Ding, Jingjin
   Wang, Kun
   Liu, Wang
   She, Yang
   Sun, Qi
   Shi, Jianjin
   Sun, Hanzi
   Wang, Da-Cheng
   Shao, Feng
TI Pore-forming activity and structural autoinhibition of the gasdermin family
SO NATURE
LA English
DT Article
ID noncanonical inflammasome activation; cell-death; caspases; mutation; protein; gene; lps; conservation; mechanisms; receptors
AB Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10-14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases.
C1 [Ding, Jingjin; She, Yang; Wang, Da-Cheng; Shao, Feng] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Ding, Jingjin; Wang, Kun; Liu, Wang; She, Yang; Sun, Qi; Shi, Jianjin; Sun, Hanzi; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Wang, Da-Cheng] Foshan Univ, Foshan 528000, Guangdong, Peoples R China.
   [Shao, Feng] Natl Inst Biol Sci, Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; National Institute of Biological Sciences, Beijing; Foshan University; National Institute of Biological Sciences, Beijing
RP Wang, DC; Shao, F (corresponding author), Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.; Shao, F (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.; Wang, DC (corresponding author), Foshan Univ, Foshan 528000, Guangdong, Peoples R China.; Shao, F (corresponding author), Natl Inst Biol Sci, Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
EM dcwang@sun5.ibp.ac.cn; shaofeng@nibs.ac.cn
FU Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08020202]; China National Science Foundation Program for Distinguished Young Scholars [31225002]; Program for International Collaborations [31461143006]; National Basic Research Program of China 973 Program [2012CB518700, 2014CB849602]; International Early Career Scientist grant from Howard Hughes Medical Institute; Beijing Scholar Program
NR 42
TC 2193
Z9 2485
U1 21
U2 744
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 111
EP +
DI 10.1038/nature18590
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600034
PM 27281216
DA 2026-03-09
ER

PT J
AU Filiano, AJ
   Xu, Y
   Tustison, NJ
   Marsh, RL
   Baker, W
   Smirnov, I
   Overall, CC
   Gadani, SP
   Turner, SD
   Weng, ZP
   Peerzade, SN
   Chen, H
   Lee, KS
   Scott, MM
   Beenhakker, MP
   Litvak, V
   Kipnis, J
AF Filiano, Anthony J.
   Xu, Yang
   Tustison, Nicholas J.
   Marsh, Rachel L.
   Baker, Wendy
   Smirnov, Igor
   Overall, Christopher C.
   Gadani, Sachin P.
   Turner, Stephen D.
   Weng, Zhiping
   Peerzade, Sayeda Najamussahar
   Chen, Hao
   Lee, Kevin S.
   Scott, Michael M.
   Beenhakker, Mark P.
   Litvak, Vladimir
   Kipnis, Jonathan
TI Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour
SO NATURE
LA English
DT Article
ID choroid-plexus; mouse models; brain; zebrafish; responses; activation; expression; evolution; children; immunity
AB Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory(1). Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-gamma (IFN-gamma)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-gamma and increase GABAergic (gamma-aminobutyric-acid) currents in projection neurons, suggesting that IFN-gamma is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-gamma/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-gamma signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-gamma, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-gamma signalling.
C1 [Filiano, Anthony J.; Marsh, Rachel L.; Baker, Wendy; Smirnov, Igor; Overall, Christopher C.; Gadani, Sachin P.; Lee, Kevin S.; Kipnis, Jonathan] Univ Virginia, Sch Med, Ctr Brain Immunol & Glia, Charlottesville, VA 22908 USA.
   [Filiano, Anthony J.; Marsh, Rachel L.; Baker, Wendy; Smirnov, Igor; Overall, Christopher C.; Gadani, Sachin P.; Lee, Kevin S.; Kipnis, Jonathan] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.
   [Xu, Yang; Peerzade, Sayeda Najamussahar; Litvak, Vladimir] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA.
   [Tustison, Nicholas J.] Univ Virginia, Sch Med, Dept Radiol & Med Imaging, Charlottesville, VA 22908 USA.
   [Gadani, Sachin P.; Lee, Kevin S.; Scott, Michael M.; Beenhakker, Mark P.; Kipnis, Jonathan] Univ Virginia, Sch Med, Neurosci Grad Program, Charlottesville, VA 22908 USA.
   [Gadani, Sachin P.; Kipnis, Jonathan] Univ Virginia, Sch Med, Med Scientist Training Program, Charlottesville, VA 22908 USA.
   [Turner, Stephen D.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
   [Weng, Zhiping; Chen, Hao] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01655 USA.
   [Lee, Kevin S.] Univ Virginia, Sch Med, Dept Neurosurg, Charlottesville, VA 22908 USA.
   [Scott, Michael M.; Beenhakker, Mark P.] Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Massachusetts System; University of Massachusetts Worcester; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Massachusetts System; University of Massachusetts Worcester; University of Virginia; University of Virginia
RP Filiano, AJ; Kipnis, J (corresponding author), Univ Virginia, Sch Med, Ctr Brain Immunol & Glia, Charlottesville, VA 22908 USA.; Filiano, AJ; Kipnis, J (corresponding author), Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.; Litvak, V (corresponding author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA.; Kipnis, J (corresponding author), Univ Virginia, Sch Med, Neurosci Grad Program, Charlottesville, VA 22908 USA.; Kipnis, J (corresponding author), Univ Virginia, Sch Med, Med Scientist Training Program, Charlottesville, VA 22908 USA.
EM afiliano@virginia.edu; Vladimir.Litvak@umassmed.edu; kipnis@virginia.edu
FU National Institutes of Health [AG034113, NS081026, T32-AI007496]; Hartwell Foundation; National Institute of Allergy and Infectious Diseases [T32AI007496] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007267] Funding Source: NIH RePORTER
NR 66
TC 555
Z9 664
U1 3
U2 157
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 425
EP +
DI 10.1038/nature18626
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200041
PM 27409813
DA 2026-03-09
ER

PT J
AU Shen, Y
   Li, YD
   Wo, HL
   Li, YS
   Shen, SD
   Pan, BY
   Wang, QS
   Walker, HC
   Steffens, P
   Boehm, M
   Hao, YQ
   Quintero-Castro, DL
   Harriger, LW
   Frontzek, MD
   Hao, LJ
   Meng, SQ
   Zhang, QM
   Chen, G
   Zhao, J
AF Shen, Yao
   Li, Yao-Dong
   Wo, Hongliang
   Li, Yuesheng
   Shen, Shoudong
   Pan, Bingying
   Wang, Qisi
   Walker, H. C.
   Steffens, P.
   Boehm, M.
   Hao, Yiqing
   Quintero-Castro, D. L.
   Harriger, L. W.
   Frontzek, M. D.
   Hao, Lijie
   Meng, Siqin
   Zhang, Qingming
   Chen, Gang
   Zhao, Jun
TI Evidence for a spinon Fermi surface in a triangular-lattice quantum-spin-liquid candidate
SO NATURE
LA English
DT Article
ID valence-bond state; kagome-lattice; ground-state; excitations; topology; physics
AB A quantum spin liquid is an exotic quantum state of matter in which spins are highly entangled and remain disordered down to zero temperature. Such a state of matter is potentially relevant to high-temperature superconductivity and quantum-information applications, and experimental identification of a quantum spin liquid state is of fundamental importance for our understanding of quantum matter. Theoretical studies have proposed various quantum-spin-liquid ground states1-4, most of which are characterized by exotic spin excitations with fractional quantum numbers (termed 'spinons'). Here we report neutron scattering measurements of the triangular-lattice antiferromagnet YbMgGaO4 that reveal broad spin excitations covering a wide region of the Brillouin zone. The observed diffusive spin excitation persists at the lowest measured energy and shows a clear upper excitation edge, consistent with the particle-hole excitation of a spinon Fermi surface. Our results therefore point to the existence of a quantum spin liquid state with a spinon Fermi surface in YbMgGaO4, which has a perfect spin-1/2 triangular lattice as in the original proposal(4) of quantum spin liquids.
C1 [Shen, Yao; Wo, Hongliang; Shen, Shoudong; Pan, Bingying; Wang, Qisi; Hao, Yiqing; Chen, Gang; Zhao, Jun] Fudan Univ, State Key Lab Surface Phys, Shanghai 200433, Peoples R China.
   [Shen, Yao; Wo, Hongliang; Shen, Shoudong; Pan, Bingying; Wang, Qisi; Hao, Yiqing; Chen, Gang; Zhao, Jun] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
   [Li, Yao-Dong] Fudan Univ, Sch Comp Sci, Shanghai 200433, Peoples R China.
   [Li, Yuesheng; Zhang, Qingming] Renmin Univ China, Beijing Key Lab Optoelect Funct Mat & Micronano D, Dept Phys, Beijing 100872, Peoples R China.
   [Walker, H. C.] STFC, Rutherford Appleton Lab, ISIS Facil, Didcot OX11 0QX, Oxon, England.
   [Steffens, P.; Boehm, M.] Inst Laue Langevin, 71 Ave Martyrs, F-38042 Grenoble 9, France.
   [Quintero-Castro, D. L.] Helmholtz Zentrum Berlin Mat & Energie, D-14109 Berlin, Germany.
   [Harriger, L. W.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Frontzek, M. D.] Oak Ridge Natl Lab, Quantum Condensed Matter Div, Oak Ridge, TN 37831 USA.
   [Hao, Lijie; Meng, Siqin] China Inst Atom Energy, Neutron Scattering Lab, Beijing 102413, Peoples R China.
   [Zhang, Qingming] Shanghai Jiao Tong Univ, Dept Phys & Astron, Shanghai 200240, Peoples R China.
   [Zhang, Qingming; Chen, Gang; Zhao, Jun] Collaborat Innovat Ctr Adv Microstruct, Nanjing 210093, Jiangsu, Peoples R China.
   [Chen, Gang] Fudan Univ, Ctr Field Theory & Particle Phys, Shanghai 200433, Peoples R China.
C3 Fudan University; Fudan University; Fudan University; Renmin University of China; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Institut Laue-Langevin (ILL); Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); National Institute of Standards & Technology (NIST) - USA; United States Department of Energy (DOE); Oak Ridge National Laboratory; China Institute of Atomic Energy; Shanghai Jiao Tong University; Collaborative Innovation Center of Advanced Microstructures (CICAM); Fudan University
RP Chen, G; Zhao, J (corresponding author), Fudan Univ, State Key Lab Surface Phys, Shanghai 200433, Peoples R China.; Chen, G; Zhao, J (corresponding author), Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.; Chen, G; Zhao, J (corresponding author), Collaborat Innovat Ctr Adv Microstruct, Nanjing 210093, Jiangsu, Peoples R China.; Chen, G (corresponding author), Fudan Univ, Ctr Field Theory & Particle Phys, Shanghai 200433, Peoples R China.
EM gchen_physics@fudan.edu.cn; zhaoj@fudan.edu.cn
FU National Key RAMP;D Program of the MOST of China [2016YFA0300203]; Ministry of Science and Technology of China (Program 973) [2015CB921302]; National Natural Science Foundation of China [91421106]; Thousand Youth Talent Program of China; NSF of China; Ministry of Science and Technology of China [2016YFA0300504]
NR 38
TC 318
Z9 349
U1 10
U2 389
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 559
EP +
DI 10.1038/nature20614
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500046
PM 27919078
DA 2026-03-09
ER

PT J
AU Harward, SC
   Hedrick, NG
   Hall, CE
   Parra-Bueno, P
   Milner, TA
   Pan, EH
   Laviv, T
   Hempstead, BL
   Yasuda, R
   McNamara, JO
AF Harward, Stephen C.
   Hedrick, Nathan G.
   Hall, Charles E.
   Parra-Bueno, Paula
   Milner, Teresa A.
   Pan, Enhui
   Laviv, Tal
   Hempstead, Barbara L.
   Yasuda, Ryohei
   McNamara, James O.
TI Autocrine BDNF-TrkB signalling within a single dendritic spine
SO NATURE
LA English
DT Article
ID long-term potentiation; dependent structural plasticity; neurotrophic factor; genetic approach; ampa receptors; activation; secretion; hippocampus; synapses; dynamics
AB Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity(1-6), including structural long-term potentiation (sLTP)(7,8), which is a correlate of an animal's learning(7,9-12). However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where. Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy(13-16), we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices. In response to sLTP induction(9,14-16), we find fast (onset < 1 min) and sustained (>20 min) activation of TrkB in the stimulated spine that depends on NMDAR (N-methyl-D-aspartate receptor) and CaMKII signalling and on postsynaptically synthesized BDNF. We confirm the presence of postsynaptic BDNF using electron microscopy to localize endogenous BDNF to dendrites and spines of hippocampal CA1 pyramidal neurons. Consistent with these findings, we also show rapid, glutamate-uncaging-evoked, time-locked BDNF release from single dendritic spines using BDNF fused to superecliptic pHluorin(17-19). We demonstrate that this postsynaptic BDNF-TrkB signalling pathway is necessary for both structural and functional LTP20. Together, these findings reveal a spine-autonomous, autocrine signalling mechanism involving NMDAR-CaMKII-dependent BDNF release from stimulated dendritic spines and subsequent TrkB activation on these same spines that is crucial for structural and functional plasticity.
C1 [Harward, Stephen C.; Hedrick, Nathan G.; Hall, Charles E.; Pan, Enhui; Yasuda, Ryohei; McNamara, James O.] Duke Univ, Med Ctr, Dept Neurobiol, Res Dr, Durham, NC 27710 USA.
   [Parra-Bueno, Paula; Laviv, Tal; Yasuda, Ryohei] Max Planck Florida Inst Neurosci, 1 Max Planck Way, Jupiter, FL 33458 USA.
   [Milner, Teresa A.; Hempstead, Barbara L.] Weill Cornell Med, Feil Family Brain & Mind Res Inst, 407 East 61st St, New York, NY 10065 USA.
   [Milner, Teresa A.] Rockefeller Univ, Lab Neuroendocrinol, 1230 York Ave, New York, NY 10065 USA.
   [Hempstead, Barbara L.] Weill Cornell Med, Dept Med, 1300 York Ave, New York, NY 10065 USA.
   [Hedrick, Nathan G.] Univ Calif San Diego, Ctr Neural Circuits & Behav, Neurobiol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA.
   [Hedrick, Nathan G.] Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr, La Jolla, CA 92093 USA.
C3 Duke University; Max Planck Society; Cornell University; Weill Cornell Medicine; Rockefeller University; Cornell University; Weill Cornell Medicine; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Yasuda, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Res Dr, Durham, NC 27710 USA.; Yasuda, R (corresponding author), Max Planck Florida Inst Neurosci, 1 Max Planck Way, Jupiter, FL 33458 USA.
EM Ryohei.Yasuda@mpfi.org
FU National Institutes of Health [F31NS078847, R01NS068410, DP1NS096787, R01NS05621, R01MH080047, R01DA08259, R01HL098351, P01HL096571, RO1NS030687]; Wakeman Fellowship; Human Frontier Science Program; National Institute of Mental Health [R01MH080047] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS056217] Funding Source: NIH RePORTER
NR 40
TC 254
Z9 289
U1 2
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 99
EP +
DI 10.1038/nature19766
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900042
PM 27680698
DA 2026-03-09
ER

PT J
AU Sugahara, F
   Pascual-Anaya, J
   Oisi, Y
   Kuraku, S
   Aota, S
   Adachi, N
   Takagi, W
   Hirai, T
   Sato, N
   Murakami, Y
   Kuratani, S
AF Sugahara, Fumiaki
   Pascual-Anaya, Juan
   Oisi, Yasuhiro
   Kuraku, Shigehiro
   Aota, Shin-ichi
   Adachi, Noritaka
   Takagi, Wataru
   Hirai, Tamami
   Sato, Noboru
   Murakami, Yasunori
   Kuratani, Shigeru
TI Evidence from cyclostomes for complex regionalization of the ancestral vertebrate brain
SO NATURE
LA English
DT Article
ID prosomeric model; pacific hagfish; growth changes; evolution; gene; telencephalon; forebrain; lamprey; stouti; organization
AB The vertebrate brain is highly complex, but its evolutionary origin remains elusive. Because of the absence of certain developmental domains generally marked by the expression of regulatory genes, the embryonic brain of the lamprey, a jawless vertebrate, had been regarded as representing a less complex, ancestral state of the vertebrate brain. Specifically, the absence of a Hedgehog- and Nkx2.1-positive domain in the lamprey subpallium was thought to be similar to mouse mutants in which the suppression of Nkx2-1 leads to a loss of the medial ganglionic eminence1,2. Here we show that the brain of the inshore hagfish (Eptatretus burgeri), another cyclostome group, develops domains equivalent to the medial ganglionic eminence and rhombic lip, resembling the gnathostome brain. Moreover, further investigation of lamprey larvae revealed that these domains are also present, ruling out the possibility of convergent evolution between hagfish and gnathostomes. Thus, brain regionalization as seen in crown gnathostomes is not an evolutionary innovation of this group, but dates back to the latest vertebrate ancestor before the divergence of cyclostomes and gnathostomes more than 500 million years ago.
C1 [Sugahara, Fumiaki; Pascual-Anaya, Juan; Aota, Shin-ichi; Takagi, Wataru; Hirai, Tamami; Kuratani, Shigeru] RIKEN, Evolutionary Morphol Lab, Kobe, Hyogo 6500047, Japan.
   [Sugahara, Fumiaki] Hyogo Coll Med, Div Biol, Nishinomiya, Hyogo 6638501, Japan.
   [Oisi, Yasuhiro] Max Planck Florida Inst Neurosci, Dev & Funct Inhibitory Neural Circuits, Jupiter, FL 33458 USA.
   [Kuraku, Shigehiro] RIKEN, Ctr Life Sci Technol, Phyloinformat Unit, Kobe, Hyogo 6500047, Japan.
   [Adachi, Noritaka] Univ Chicago, Dept Organismal Biol & Anat, 1025 E 57Th St, Chicago, IL 60637 USA.
   [Sato, Noboru] Niigata Univ, Grad Sch Med & Dent Sci, Div Gross Anat & Morphogenesis, Niigata 9508510, Japan.
   [Murakami, Yasunori] Ehime Univ, Grad Sch Sci & Engn, Matsuyama, Ehime 7908577, Japan.
C3 RIKEN; Hyogo Medical University; Max Planck Society; RIKEN; University of Chicago; Niigata University; Ehime University
RP Kuratani, S (corresponding author), RIKEN, Evolutionary Morphol Lab, Kobe, Hyogo 6500047, Japan.
EM saizo@cdb.riken.jp
FU Centre for Developmental Biology, RIKEN, JSPS KAKENHI [15H02416, 25840133]; Hyogo Science and Technology Association; Grants-in-Aid for Scientific Research [25840133, 15H02416, 26291065] Funding Source: KAKEN
NR 47
TC 75
Z9 79
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 97
EP +
DI 10.1038/nature16518
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900047
PM 26878236
DA 2026-03-09
ER

PT J
AU Garg, M
   Zhan, M
   Luu, TT
   Lakhotia, H
   Klostermann, T
   Guggenmos, A
   Goulielmakis, E
AF Garg, M.
   Zhan, M.
   Luu, T. T.
   Lakhotia, H.
   Klostermann, T.
   Guggenmos, A.
   Goulielmakis, E.
TI Multi-petahertz electronic metrology
SO NATURE
LA English
DT Article
ID high-harmonic generation; nonlinear response; solids; optics; plasma
AB The frequency of electric currents associated with charge carriers moving in the electronic bands of solids determines the speed limit of electronics and thereby that of information and signal processing(1). The use of light fields to drive electrons promises access to vastly higher frequencies than conventionally used, as electric currents can be induced and manipulated on timescales faster than that of the quantum dephasing of charge carriers in solids(2). This forms the basis of terahertz (10(12) hertz) electronics in artificial superlattices(2), and has enabled light-based switches(3-5) and sampling of currents extending in frequency up to a few hundred terahertz. Here we demonstrate the extension of electronic metrology to the multi-petahertz (10(15) hertz) frequency range. We use single-cycle intense optical fields (about one volt per angstrom) to drive electron motion in the bulk of silicon dioxide, and then probe its dynamics by using attosecond (10(-18) seconds) streaking(6,7) to map the time structure of emerging isolated attosecond extreme ultraviolet transients and their optical driver. The data establish a firm link between the emission of the extreme ultraviolet radiation and the light-induced intraband, phase-coherent electric currents that extend in frequency up to about eight petahertz, and enable access to the dynamic nonlinear conductivity of silicon dioxide. Direct probing, confinement and control of the waveform of intraband currents inside solids on attosecond timescales establish a method of realizing multi-petahertz coherent electronics. We expect this technique to enable new ways of exploring the interplay between electron dynamics and the structure of condensed matter on the atomic scale.
C1 [Garg, M.; Zhan, M.; Luu, T. T.; Lakhotia, H.; Klostermann, T.; Guggenmos, A.; Goulielmakis, E.] Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
C3 Max Planck Society
RP Goulielmakis, E (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM elgo@mpq.mpg.de
FU European Research Council [Attoelectronics-258501]; Deutsche Forschungsgemeinschaft Cluster of Excellence; Munich Centre for Advanced Photonics; Max Planck Society; European Research Training Network MEDEA
NR 30
TC 287
Z9 310
U1 2
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 359
EP 363
DI 10.1038/nature19821
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100034
PM 27762353
DA 2026-03-09
ER

PT J
AU Anagnostou, E
   John, EH
   Edgar, KM
   Foster, GL
   Ridgwell, A
   Inglis, GN
   Pancost, RD
   Lunt, DJ
   Pearson, PN
AF Anagnostou, Eleni
   John, Eleanor H.
   Edgar, Kirsty M.
   Foster, Gavin L.
   Ridgwell, Andy
   Inglis, Gordon N.
   Pancost, Richard D.
   Lunt, Daniel J.
   Pearson, Paul N.
TI Changing atmospheric CO2 concentration was the primary driver of early Cenozoic climate
SO NATURE
LA English
DT Article
ID boron isotopic composition; carbon-dioxide; planktonic-foraminifera; seawater ph; stable-isotopes; kilwa group; oxygen; sea; paleogene; evolution
AB The Early Eocene Climate Optimum (EECO, which occurred about 51 to 53 million years ago)(1), was the warmest interval of the past 65 million years, with mean annual surface air temperature over ten degrees Celsius warmer than during the pre-industrial period(2-4). Subsequent global cooling in the middle and late Eocene epoch, especially at high latitudes, eventually led to continental ice sheet development in Antarctica in the early Oligocene epoch (about 33.6 million years ago). However, existing estimates place atmospheric carbon dioxide (CO2) levels during the Eocene at 500-3,000 parts per million(5-7), and in the absence of tighter constraints carbon-climate interactions over this interval remain uncertain. Here we use recent analytical and methodological developments(8-11) to generate a new high-fidelity record of CO2 concentrations using the boron isotope (delta B-11) composition of well preserved planktonic foraminifera from the Tanzania Drilling Project, revising previous estimates(6). Although species-level uncertainties make absolute values difficult to constrain, CO2 concentrations during the EECO were around 1,400 parts per million. The relative decline in CO2 concentration through the Eocene is more robustly constrained at about fifty per cent, with a further decline into the Oligocene(12). Provided the latitudinal dependency of sea surface temperature change for a given climate forcing in the Eocene was similar to that of the late Quaternary period(13), this CO2 decline was sufficient to drive the well documented high-and low-latitude cooling that occurred through the Eocene(14). Once the change in global temperature between the pre-industrial period and the Eocene caused by the action of all known slow feedbacks (apart from those associated with the carbon cycle) is removed(2-4), both the EECO and the late Eocene exhibit an equilibrium climate sensitivity relative to the pre-industrial period of 2.1 to 4.6 degrees Celsius per CO2 doubling (66 per cent confidence), which is similar to the canonical range (1.5 to 4.5 degrees Celsius(15)), indicating that a large fraction of the warmth of the early Eocene greenhouse was driven by increased CO2 concentrations, and that climate sensitivity was relatively constant throughout this period.
C1 [Anagnostou, Eleni; Foster, Gavin L.] Univ Southampton, Natl Oceanog Ctr Southampton, Ocean & Earth Sci, Waterfront Campus, Southampton SO14 3ZH, Hants, England.
   [John, Eleanor H.; Edgar, Kirsty M.; Pearson, Paul N.] Cardiff Univ, Sch Earth & Ocean Sci, Pk Pl, Cardiff CF10 3AT, S Glam, Wales.
   [Edgar, Kirsty M.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Ridgwell, Andy; Lunt, Daniel J.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Ridgwell, Andy; Lunt, Daniel J.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Inglis, Gordon N.; Pancost, Richard D.] Univ Bristol, Sch Chem, Organ Geochem Unit, Cantocks Close, Bristol BS8 1TS, Avon, England.
   [Inglis, Gordon N.; Pancost, Richard D.] Univ Bristol, Cabot Inst, Bristol BS8 1UJ, Avon, England.
   [John, Eleanor H.] Univ S Pacific, Sch Geog Earth Sci & Environm, Suva, Fiji.
   [Edgar, Kirsty M.] Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.
C3 University of Southampton; NERC National Oceanography Centre; Cardiff University; University of Bristol; University of Bristol; University of California System; University of California Riverside; University of Bristol; University of Bristol; University of the South Pacific; University of Birmingham
RP Anagnostou, E (corresponding author), Univ Southampton, Natl Oceanog Ctr Southampton, Ocean & Earth Sci, Waterfront Campus, Southampton SO14 3ZH, Hants, England.
EM e.anagnostou@noc.soton.ac.uk
FU NERC [NE/H017356/1, NE/I005595/1, NE/H016457/1]; UK NERC [NE/I005595/1]; Royal Society Wolfson Research Merit Award; Advanced ERC Grant T-GRES [340923]; Tanzania Petroleum Development Corporation; Tanzania Commission for Science and Technology; Tanzania Drilling Project field team; NERC [NE/I005714/1, NE/H017356/1, NE/H016457/1, NE/I005870/1, NE/I005595/1] Funding Source: UKRI; Natural Environment Research Council [NE/I005714/1, NE/H017356/1, NE/I005870/1, NE/H016457/1, NE/I005595/1] Funding Source: researchfish
NR 95
TC 360
Z9 417
U1 17
U2 418
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 380
EP +
DI 10.1038/nature17423
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300045
PM 27111509
DA 2026-03-09
ER

PT J
AU Fuchsberger, C
   Flannick, J
   Teslovich, TM
   Mahajan, A
   Agarwala, V
   Gaulton, KJ
   Ma, C
   Fontanillas, P
   Moutsianas, L
   McCarthy, DJ
   Rivas, MA
   Perry, JRB
   Sim, X
   Blackwell, TW
   Robertson, NR
   Rayner, NW
   Cingolani, P
   Locke, AE
   Tajes, JF
   Highland, HM
   Dupuis, J
   Chines, PS
   Lindgren, CM
   Hartl, C
   Jackson, AU
   Chen, H
   Huyghe, JR
   van de Bunt, M
   Pearson, RD
   Kumar, A
   Müller-Nurasyid, M
   Grarup, N
   Stringham, HM
   Gamazon, ER
   Lee, J
   Chen, YH
   Scott, RA
   Below, JE
   Chen, P
   Huang, J
   Go, MJ
   Stitzel, ML
   Pasko, D
   Parker, SCJ
   Varga, TV
   Green, T
   Beer, NL
   Day-Williams, AG
   Ferreira, T
   Fingerlin, T
   Horikoshi, M
   Hu, C
   Huh, I
   Ikram, MK
   Kim, BJ
   Kim, Y
   Kim, YJ
   Kwon, MS
   Lee, J
   Lee, S
   Lin, KH
   Maxwell, TJ
   Nagai, Y
   Wang, X
   Welch, RP
   Yoon, J
   Zhang, W
   Barzilai, N
   Voight, BF
   Han, BG
   Jenkinson, CP
   Kuulasmaa, T
   Kuusisto, J
   Manning, A
   Ng, MCY
   Palmer, ND
   Balkau, B
   Stancáková, A
   Abboud, HE
   Boeing, H
   Giedraitis, V
   Prabhakaran, D
   Gottesman, O
   Scott, J
   Carey, J
   Kwan, P
   Grant, G
   Smith, JD
   Neale, BM
   Purcell, S
   Butterworth, AS
   Howson, JMM
   Lee, HM
   Lu, YC
   Kwak, SH
   Zhao, W
   Danesh, J
   Lam, VKL
   Park, KS
   Saleheen, D
   So, WY
   Tam, CHT
   Afzal, U
   Aguilar, D
   Arya, R
   Aung, T
   Chan, E
   Navarro, C
   Cheng, CY
   Palli, D
   Correa, A
   Curran, JE
   Rybin, D
   Farook, VS
   Fowler, SP
   Freedman, BI
   Griswold, M
   Hale, DE
   Hicks, PJ
   Khor, CC
   Kumar, S
   Lehne, B
   Thuillier, D
   Lim, WY
   Liu, J
   van der Schouw, YT
   Loh, M
   Musani, SK
   Puppala, S
   Scott, WR
   Yengo, L
   Tan, ST
   Taylor, HA
   Thameem, F
   Wilson, G
   Wong, TY
   Njolstad, PR
   Levy, JC
   Mangino, M
   Bonnycastle, LL
   Schwarzmayr, T
   Fadista, J
   Surdulescu, GL
   Herder, C
   Groves, CJ
   Wieland, T
   Bork-Jensen, J
   Brandslund, I
   Christensen, C
   Koistinen, HA
   Doney, ASF
   Kinnunen, L
   Esko, T
   Farmer, AJ
   Hakaste, L
   Hodgkiss, D
   Kravic, J
   Lyssenko, V
   Hollensted, M
   Jorgensen, ME
   Jorgensen, T
   Ladenvall, C
   Justesen, JM
   Karajamaki, A
   Kriebel, J
   Rathmann, W
   Lannfelt, L
   Lauritzen, T
   Narisu, N
   Linneberg, A
   Melander, O
   Milani, L
   Neville, M
   Orho-Melander, M
   Qi, L
   Qi, QB
   Roden, M
   Rolandsson, O
   Swift, A
   Rosengren, AH
   Stirrups, K
   Wood, AR
   Mihailov, E
   Blancher, C
   Carneiro, MO
   Maguire, J
   Poplin, R
   Shakir, K
   Fennell, T
   DePristo, M
   de Angelis, MH
   Deloukas, P
   Gjesing, AP
   Jun, G
   Nilsson, P
   Murphy, J
   Onofrio, R
   Thorand, B
   Hansen, T
   Meisinger, C
   Hu, FB
   Isomaa, B
   Karpe, F
   Liang, LM
   Peters, A
   Huth, C
   O'Rahilly, SP
   Palmer, CNA
   Pedersen, O
   Rauramaa, R
   Tuomilehto, J
   Salomaa, V
   Watanabe, RM
   Syvänen, AC
   Bergman, RN
   Bharadwaj, D
   Bottinger, EP
   Cho, YS
   Chandak, GR
   Chan, JCN
   Chia, KS
   Daly, MJ
   Ebrahim, SB
   Langenberg, C
   Elliott, P
   Jablonski, KA
   Lehman, DM
   Jia, WP
   Ma, RCW
   Pollin, TI
   Sandhu, M
   Tandon, N
   Froguel, P
   Barroso, I
   Teo, YY
   Zeggini, E
   Loos, RJF
   Small, KS
   Ried, JS
   DeFronzo, RA
   Grallert, H
   Glaser, B
   Metspalu, A
   Wareham, NJ
   Walker, M
   Banks, E
   Gieger, C
   Ingelsson, E
   Im, HK
   Illig, T
   Franks, PW
   Buck, G
   Trakalo, J
   Buck, D
   Prokopenko, I
   Mägi, R
   Lind, L
   Farjoun, Y
   Owen, KR
   Gloyn, AL
   Strauch, K
   Tuomi, T
   Kooner, JS
   Lee, JY
   Park, T
   Donnelly, P
   Morris, AD
   Hattersley, AT
   Bowden, DW
   Collins, FS
   Atzmon, G
   Chambers, JC
   Spector, TD
   Laakso, M
   Strom, TM
   Bell, GI
   Blangero, J
   Duggirala, R
   Tai, ES
   McVean, G
   Hanis, CL
   Wilson, JG
   Seielstad, M
   Frayling, TM
   Meigs, JB
   Cox, NJ
   Sladek, R
   Lander, ES
   Gabriel, S
   Burtt, NP
   Mohlke, KL
   Meitinger, T
   Groop, L
   Abecasis, G
   Florez, JC
   Scott, LJ
   Morris, AP
   Kang, HM
   Boehnke, M
   Altshuler, D
   McCarthy, MI
AF Fuchsberger, Christian
   Flannick, Jason
   Teslovich, Tanya M.
   Mahajan, Anubha
   Agarwala, Vineeta
   Gaulton, Kyle J.
   Ma, Clement
   Fontanillas, Pierre
   Moutsianas, Loukas
   McCarthy, Davis J.
   Rivas, Manuel A.
   Perry, John R. B.
   Sim, Xueling
   Blackwell, Thomas W.
   Robertson, Neil R.
   Rayner, N. William
   Cingolani, Pablo
   Locke, Adam E.
   Tajes, Juan Fernandez
   Highland, Heather M.
   Dupuis, Josee
   Chines, Peter S.
   Lindgren, Cecilia M.
   Hartl, Christopher
   Jackson, Anne U.
   Chen, Han
   Huyghe, Jeroen R.
   van de Bunt, Martijn
   Pearson, Richard D.
   Kumar, Ashish
   Mueller-Nurasyid, Martina
   Grarup, Niels
   Stringham, Heather M.
   Gamazon, Eric R.
   Lee, Jaehoon
   Chen, Yuhui
   Scott, Robert A.
   Below, Jennifer E.
   Chen, Peng
   Huang, Jinyan
   Go, Min Jin
   Stitzel, Michael L.
   Pasko, Dorota
   Parker, Stephen C. J.
   Varga, Tibor V.
   Green, Todd
   Beer, Nicola L.
   Day-Williams, Aaron G.
   Ferreira, Teresa
   Fingerlin, Tasha
   Horikoshi, Momoko
   Hu, Cheng
   Huh, Iksoo
   Ikram, Mohammad Kamran
   Kim, Bong-Jo
   Kim, Yongkang
   Kim, Young Jin
   Kwon, Min-Seok
   Lee, Juyoung
   Lee, Selyeong
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TI The genetic architecture of type 2 diabetes
SO NATURE
LA English
DT Article
ID genome-wide association; protein complexes; rare variants; low-frequency; risk; susceptibility; loci; heritability; metaanalysis; annotation
AB The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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   [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
   [Lauritzen, Torsten] Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark.
   [Linneberg, Allan] Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.
   [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
   [Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden.
   [Neville, Matt; Karpe, Fredrik; Owen, Katharine R.; Gloyn, Anna L.; McCarthy, Mark I.] Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
   [Orho-Melander, Marju] Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden.
   [Qi, Lu; Qi, Qibin; Hu, Frank B.; Franks, Paul W.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.
   [Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
   [Qi, Lu] Harvard Med Sch, Boston, MA USA.
   [Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
   [Roden, Michael] Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany.
   [Rolandsson, Olov; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
   [Blancher, Christine; Buck, Gemma; Trakalo, Joseph; Buck, David] Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England.
   [de Angelis, Martin Hrabe] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.
   [de Angelis, Martin Hrabe] Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany.
   [Deloukas, Panos] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
   [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
   [Nilsson, Peter] Lund Univ, Dept Clin Sci, Med, Malmo, Sweden.
   [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
   [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
   [O'Rahilly, Stephen P.; Barroso, Ines] Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England.
   [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
   [Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
   [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
   [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
   [Tuomilehto, Jaakko] Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain.
   [Tuomilehto, Jaakko; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland.
   [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
   [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.
   [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dabet & Obes Res Inst, Los Angeles, CA USA.
   [Syvanen, Ann-Christine] Uppsala Univ, Mol Med & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
   [Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA.
   [Bharadwaj, Dwaipayan] CSIR IGIB, Funct Genom Unit, New Delhi, India.
   [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
   [Chandak, Giriraj R.] CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India.
   [Chan, Juliana C. N.; Ma, Ronald C. W.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.
   [Chan, Juliana C. N.; Ma, Ronald C. W.] Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China.
   [Elliott, Paul] Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
   [Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
   [Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
   [Pollin, Toni I.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
   [Tandon, Nikhil] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India.
   [Froguel, Philippe; Prokopenko, Inga] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
   [Teo, Yik Ying] Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.
   [Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore.
   [Glaser, Benjamin] Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel.
   [Walker, Mark] Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England.
   [Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
   [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.
   [Illig, Thomas] Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany.
   [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
   [Farjoun, Yossi] Broad Inst, Data Sci & Data Engn, Cambridge, MA USA.
   [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, FIMM, Helsinki, Finland.
   [Kooner, Jaspal Singh; Chambers, John C.] Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
   [Morris, Andrew D.] Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.
   [Morris, Andrew D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
   [Hattersley, Andrew T.] Univ Exeter, Sch Med, Exeter, Devon, England.
   [Atzmon, Gil] Univ Haifa, Dept Nat Sci, Haifa, Israel.
   [Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany.
   [Bell, Graeme I.] Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA.
   [Bell, Graeme I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Tai, E. Shyong] Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore.
   [McVean, Gilean] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
   [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
   [Seielstad, Mark] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA.
   [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
   [Meigs, James B.] Harvard Med Sch, Dept Med, Boston, MA USA.
   [Sladek, Rob] McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
   [Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge, MA USA.
   [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
   [Florez, Jose C.; Altshuler, David] Harvard Med Sch, Dept Med, Boston, MA USA.
   [Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
   [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
   [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA.
C3 University of Michigan System; University of Michigan; Medical University of Innsbruck; European Academy of Bozen-Bolzano; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Oxford; Wellcome Centre for Human Genetics; Harvard University; Massachusetts Institute of Technology (MIT); University of Oxford; University of Exeter; University of Cambridge; University of London; King's College London; University of Oxford; Wellcome Trust Sanger Institute; McGill University; McGill University; University of Texas System; University of Texas Health Science Center Houston; University of Texas Graduate School of Biomedical Sciences; Boston University; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Framingham Heart Study; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Harvard University; Harvard T.H. Chan School of Public Health; Swiss School of Public Health (SSPH+); University of Basel; Swiss Tropical & Public Health Institute; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; University of Munich; Munich Heart Alliance; German Centre for Cardiovascular Research; Novo Nordisk Foundation; University of Copenhagen; University of Chicago; Seoul National University (SNU); University of Texas System; University of Texas Health Science Center Houston; University of Texas School Public Health; National University of Singapore; Harvard University; Harvard T.H. Chan School of Public Health; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Genome Science; Jackson Laboratory; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Lund University; University of Colorado System; University of Colorado Anschutz Medical Campus; Colorado School of Public Health; Shanghai Jiao Tong University; Singapore National Eye Center; National University of Singapore; National University of Singapore; National University of Singapore; Seoul National University (SNU); McGill University; McGill University; Imperial College London; Yeshiva University; Yeshiva University; University of Pennsylvania; University of Pennsylvania; University of Texas System; University of Texas at San Antonio; US Department of Veterans Affairs; Veterans Health Administration (VHA); Audie L. Murphy Memorial Veterans Hospital; University of Eastern Finland; Kuopio University Hospital; University of Eastern Finland; University of Eastern Finland Hospital; Wake Forest University; Wake Forest University; Wake Forest University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Leibniz Association; Deutsches Institut fur Ernahrungsforschung Potsdam-Rehbrucke (DIfE); Uppsala University; Icahn School of Medicine at Mount Sinai; Imperial College London; University of Washington; University of Washington Seattle; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; University of Cambridge; Chinese University of Hong Kong; Seoul National University (SNU); University of Pennsylvania; University of Cambridge; Seoul National University (SNU); Seoul National University (SNU); University of Pennsylvania; Baylor College of Medicine; University of Texas System; University of Texas at San Antonio; National University of Singapore; Murcia Regional Health Council; Hospital Clinico Universitario Virgen de la Arrixaca; University of Murcia; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; University of Murcia; ISPRO Istituto per lo studio, la prevenzione e la rete oncologica; University of Mississippi; University of Mississippi Medical Center; University of Texas System; University of Texas Rio Grande Valley; Texas Biomedical Research Institute; Wake Forest University; University of Mississippi; University of Mississippi Medical Center; National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite de Lille; Institut Pasteur Lille; Utrecht University; Utrecht University Medical Center; University of Oulu; Agency for Science Technology & Research (A*STAR); University of Mississippi; University of Mississippi Medical Center; Jackson State University; University of Bergen; University of Bergen; Haukeland University Hospital; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Lund University; Heinrich Heine University Dusseldorf; Leibniz Association; Deutsches Diabetes-Zentrum (DDZ); German Center for Diabetes Research (DZD); University of Southern Denmark; University of Southern Denmark; Lillebaelt Hospital; University of Southern Denmark; Lillebaelt Hospital; Finland National Institute for Health & Welfare; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; University of Helsinki; University of Dundee; University of Tartu; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Oxford; Folkhalsan Research Center; University of Helsinki; Steno Diabetes Center; University of Copenhagen; Aalborg University; Vaasa Central Hospital; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Leibniz Association; Deutsches Diabetes-Zentrum (DDZ); Heinrich Heine University Dusseldorf; Aarhus University; Rigshospitalet; University of Copenhagen; Lund University; Oxford University Hospitals NHS Foundation Trust; University of Oxford; Lund University; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Yeshiva University; Heinrich Heine University Dusseldorf; Umea University; University of Oxford; Wellcome Centre for Human Genetics; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; University of London; Queen Mary University London; King Abdulaziz University; Lund University; University of Southern Denmark; University of Cambridge; University of Dundee; Danube University Krems; King Abdulaziz University; Autonomous University of Madrid; Finland National Institute for Health & Welfare; University of Southern California; University of Southern California; University of Southern California; Uppsala University; Cedars Sinai Medical Center; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Institute of Genomics & Integrative Biology (IGIB); Hallym University; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); Chinese University of Hong Kong; Chinese University of Hong Kong; Imperial College London; George Washington University; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; All India Institute of Medical Sciences (AIIMS) New Delhi; Imperial College London; National University of Singapore; National University of Singapore; Hebrew University of Jerusalem; Hadassah University Hospital; Newcastle University - UK; Uppsala University; Hannover Medical School; Hannover Medical School; Uppsala University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Helsinki; Imperial College London; University of Dundee; University of Edinburgh; University of Exeter; University of Haifa; Technical University of Munich; University of Chicago; University of Chicago; National University of Singapore; University of Oxford; University of Mississippi Medical Center; University of Mississippi; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Vitalant; Vitalant Research Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; McGill University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Liverpool; Massachusetts Institute of Technology (MIT)
RP Boehnke, M (corresponding author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.; McCarthy, MI (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.; McCarthy, MI (corresponding author), Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
EM boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk
FU MRC [G0601966, G0800270, MC_U106179472, G0601261, MR/L01341X/1, MC_UU_12015/1, MC_UU_12015/2, G0700931, MC_UU_12012/5, MC_PC_13046, MR/K013491/1, MR/K002414/1] Funding Source: UKRI; British Heart Foundation [RG/14/5/30893] Funding Source: researchfish; Lundbeck Foundation [R16-2007-1691] Funding Source: researchfish; Medical Research Council [MR/L01341X/1, G0801566, MR/K013491/1, MC_UU_12012/5/B, MC_UU_12012/5, MC_PC_13046, MC_U106179472, G0601966, G0800270, G0700931, MC_UU_12015/1, MR/K002414/1, G0901213, MC_UU_12015/2, G0601261] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10219, ACF-2009-18-005, NF-SI-0507-10380, NF-SI-0514-10027, NF-SI-0611-10099, NF-SI-0512-10077, NF-SI-0507-10228, NF-SI-0513-10109, NF-SI-0611-10136] Funding Source: researchfish; NNF Center for Basic Metabolic Research [Grarup Group, Pedersen Group, Hansen Group] Funding Source: researchfish; Novo Nordisk Fonden [NNF14OC0011039, NNF13OC0005781, NNF11OC1014855, NNF15OC0016416, NNF12OC1016167] Funding Source: researchfish; Wellcome Trust [100956/Z/13/Z, 095552/Z/11/Z] Funding Source: researchfish; National Cancer Institute [K12CA139160] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL007055] Funding Source: NIH RePORTER; National Human Genome Research Institute [ZIAHG000024] Funding Source: NIH RePORTER; National Institute of Biomedical Imaging and Bioengineering [R01EB015611] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK072193, P30DK020595, P30DK020572, R01DK093757, U01DK062370, R01DK062370] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER; National Institute on Aging [P30AG038072] Funding Source: NIH RePORTER; British Heart Foundation [SP/04/002, SP/09/002, RG/14/5/30893] Funding Source: Medline; CIHR Funding Source: Medline; Medical Research Council [G0900747-­‐91070, G0901213, MC_UU_12012/5, MR/K013491/1, G0700931, G0601261, MR/L01341X/1, G0801566, MC_UU_12015/1, MR/K002414/1, G0800270, G0601966] Funding Source: Medline; NCI NIH HHS [K12CA139160] Funding Source: Medline; NHGRI NIH HHS [U01HG005773, R01 HG000376, T32 HG000040, R56 HG000376, U54HG003067, U54 HG003067, U01 HG005773] Funding Source: Medline; NHLBI NIH HHS [HHSN268201300049C, HHSN268201300048C, T32 HL007055, HHSN268201300047C, R01 HL102830, R01HL102830, HHSN268201300046C, HHSN268201300050C] Funding Source: Medline; NIA NIH HHS [P01 AG027734, P30AG038072, R01 AG046949, R01AG046949, P01AG027734, P30 AG038072, 1R01AG042188, R01 AG042188] Funding Source: Medline; NIDDK NIH HHS [R01DK062370, R01 DK093757, P30DK020595, 1RC2DK088389, P60DK20595, U01DK085501, DK093757, K24 DK110550, RC2 DK088389, R00 DK099240, R00 DK092251, RC2DK088389, DK085526, DK088389, DK098032, U01 DK062370, U01 DK085584, R01 DK072193, U01 DK078616, RC2-­‐DK088389, P60 DK020595, P30 DK020572, DK085545, DK085584, K24 DK080140, DK085501, R01DK073541, R01DK098032, R01 DK101478, P30 DK020595, DK072193, R00DK092251, R01 DK073541, R01 DK066358, U01 DK085526, U01 DK085524, U01 DK085545, K24DK080140, R01DK066358, R01 DK106236, DK085524, R01 DK098032, U01DK085526, U01 DK085501] Funding Source: Medline; NIGMS NIH HHS [T32 GM007753, T32GM007753] Funding Source: Medline; NIH HHS [S10 OD018522] Funding Source: Medline; NIMHD NIH HHS [U54 MD007588] Funding Source: Medline; NIMH NIH HHS [R01 MH090937, R01MH090937, R01 MH101820, R01MH101820] Funding Source: Medline; Wellcome Trust [085475, 083948, 086596, 098381, 090532, 200837/Z/16/Z, 100956, 098051, 064890, 084723, 095101, 092447, 090367, 095552, 098017] Funding Source: Medline
NR 68
TC 826
Z9 926
U1 4
U2 352
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 41
EP +
DI 10.1038/nature18642
PG 29
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200026
PM 27398621
DA 2026-03-09
ER

PT J
AU Zhao, YG
   Ren, JS
   Harlos, K
   Jones, DM
   Zeltina, A
   Bowden, TA
   Padilla-Parra, S
   Fry, EE
   Stuart, DI
AF Zhao, Yuguang
   Ren, Jingshan
   Harlos, Karl
   Jones, Daniel M.
   Zeltina, Antra
   Bowden, Thomas A.
   Padilla-Parra, Sergi
   Fry, Elizabeth E.
   Stuart, David I.
TI Toremifene interacts with and destabilizes the Ebola virus glycoprotein
SO NATURE
LA English
DT Article
ID niemann-pick c1; small-molecule inhibitors; hiv-1 virion fusion; crystal-structure; entry; infection; antibody; receptor; cholesterol; system
AB Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion(1-7). GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered(8-10). Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein-drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14 degrees C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs.
C1 [Zhao, Yuguang; Ren, Jingshan; Harlos, Karl; Jones, Daniel M.; Zeltina, Antra; Bowden, Thomas A.; Padilla-Parra, Sergi; Fry, Elizabeth E.; Stuart, David I.] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Padilla-Parra, Sergi] Univ Oxford, Cellular Imaging Core, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Stuart, David I.] Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England.
C3 University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; Wellcome Centre for Human Genetics; Diamond Light Source
RP Stuart, DI (corresponding author), Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.; Stuart, DI (corresponding author), Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England.
EM dave@strubi.ox.ac.uk
FU Biostruct-X project by the EU seventh Framework Programme (FP7) [283570]; Wellcome Trust; UK Medical Research Council [MR/N00065X/1]; Wellcome Trust [090532/Z/09/Z]; Marie Curie Fellowship [658363]; MRC [MR/L009528/1]; Nuffield Department of Medicine Leadership Fellowship; Medical Research Council [G1000099, G1100525, MR/L009528/1, MR/N00065X/1] Funding Source: researchfish; MRC [G1000099, MR/N00065X/1, MR/L009528/1] Funding Source: UKRI; Marie Curie Actions (MSCA) [658363] Funding Source: Marie Curie Actions (MSCA)
NR 41
TC 194
Z9 235
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 169
EP +
DI 10.1038/nature18615
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600046
PM 27362232
DA 2026-03-09
ER

PT J
AU Celia, H
   Noinaj, N
   Zakharov, SD
   Bordignon, E
   Botos, I
   Santamaria, M
   Barnard, TJ
   Cramer, WA
   Lloubes, R
   Buchanan, SK
AF Celia, Herve
   Noinaj, Nicholas
   Zakharov, Stanislav D.
   Bordignon, Enrica
   Botos, Istvan
   Santamaria, Monica
   Barnard, Travis J.
   Cramer, William A.
   Lloubes, Roland
   Buchanan, Susan K.
TI Structural insight into the role of the Ton complex in energy transduction
SO NATURE
LA English
DT Article
ID escherichia-coli; outer-membrane; periplasmic domain; pseudomonas-aeruginosa; conformational-changes; protonmotive force; crystal-structure; flagellar motor; terminal domain; exbb-exbd
AB In Gram-negative bacteria, outer membrane transporters import nutrients by coupling to an inner membrane protein complex called the Ton complex. The Ton complex consists of TonB, ExbB, and ExbD, and uses the proton motive force at the inner membrane to transduce energy to the outer membrane via TonB. Here, we structurally characterize the Ton complex from Escherichia coli using X-ray crystallography, electron microscopy, double electron-electron resonance (DEER) spectroscopy, and crosslinking. Our results reveal a stoichiometry consisting of a pentamer of ExbB, a dimer of ExbD, and at least one TonB. Electrophysiology studies show that the Ton subcomplex forms pH-sensitive cation-selective channels and provide insight into the mechanism by which it may harness the proton motive force to produce energy.
C1 [Celia, Herve; Lloubes, Roland] Aix Marseille Univ, CNRS, UMR7255, Inst Microbiol Mediterranee,Lab Ingn Syst Macromo, F-13402 Marseille 20, France.
   [Celia, Herve; Botos, Istvan; Barnard, Travis J.; Buchanan, Susan K.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
   [Noinaj, Nicholas; Zakharov, Stanislav D.; Cramer, William A.] Purdue Univ, Markey Ctr Struct Biol, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Noinaj, Nicholas; Zakharov, Stanislav D.; Cramer, William A.] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
   [Bordignon, Enrica] Free Univ Berlin, Fachbereich Phys, D-14195 Berlin, Germany.
   [Bordignon, Enrica] Ruhr Univ Bochum, Fac Chem & Biochem, D-45810 Bochum, Germany.
   [Santamaria, Monica] Hosp La Paz IdiPAZ, Inst Invest, Dept Cirugia Expt, Paseo Castellana 261, Madrid 28046, Spain.
C3 Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Purdue University System; Purdue University; Purdue University System; Purdue University; Free University of Berlin; Ruhr University Bochum
RP Lloubes, R (corresponding author), Aix Marseille Univ, CNRS, UMR7255, Inst Microbiol Mediterranee,Lab Ingn Syst Macromo, F-13402 Marseille 20, France.; Buchanan, SK (corresponding author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.; Noinaj, N (corresponding author), Purdue Univ, Markey Ctr Struct Biol, Dept Biol Sci, W Lafayette, IN 47907 USA.; Noinaj, N (corresponding author), Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA.
EM nnoinaj@purdue.edu; lloubes@imm.cnrs.fr; skbuchan@helix.nih.gov
FU US DOE, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; US DOE, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; Office of Science, Office of Basic Energy Sciences, of the US DOE [DE-AC02-05CH11231]; Deutsche Forschungsgemeinschaft [INST 130/972-1 FUGG]; Department of Biological Sciences, Purdue University; National Institute of Allergy and Infectious Diseases [1K22AI113078-01]; Cluster of Excellence RESOLV - Deutsche Forschungsgemeinschaft [EXC 1069]; NIH [NIH GM 038323]; Henry Koffler Professorship at Purdue University; Centre National de la Recherche Scientifique; Aix-Marseille Universite; Agence National de la Recherche (BACMOLMOT) [ANR-14-CE09-0023]; Projets internationaux de cooperation scientifique [PICS05853]; NIH, NIDDK; Agence Nationale de la Recherche (ANR) [ANR-14-CE09-0023] Funding Source: Agence Nationale de la Recherche (ANR); National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK011011] Funding Source: NIH RePORTER
NR 56
TC 131
Z9 156
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 60
EP +
DI 10.1038/nature19757
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900033
PM 27654919
DA 2026-03-09
ER

PT J
AU Louder, RK
   He, Y
   López-Blance, JR
   Fang, J
   Chacon, P
   Nogales, E
AF Louder, Robert K.
   He, Yuan
   Ramon Lopez-Blance, Jose
   Fang, Jie
   Chacon, Pablo
   Nogales, Eva
TI Structure of promoter-bound TFIID and model of human pre-initiation complex assembly
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; tata-binding protein; core promoter; transcription initiation; electron-microscopy; crystal-structure; human genome; cryo-em; tafs; architecture
AB The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II (Pol II)-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy at sub-nanometre resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo-electron microscopy reconstruction of a fully assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation.
C1 [Louder, Robert K.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [He, Yuan; Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, Inst QB3, Berkeley, CA 94720 USA.
   [He, Yuan; Chacon, Pablo; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrat Bioimaging Div, Berkeley, CA 94720 USA.
   [Ramon Lopez-Blance, Jose] CSIC, Dept Biol Phys Chem, Rocasolano Phys Chem Inst, Serrano 119, Madrid 28006, Spain.
   [Fang, Jie; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [He, Yuan] Northwestern Univ, Interdisciplinary Biol Sci Program, Evanston, IL 60208 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Quimica Fisica Blas Cabrera (IQF-CSIC); Howard Hughes Medical Institute; University of California System; University of California Berkeley; Northwestern University
RP Nogales, E (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Inst QB3, Berkeley, CA 94720 USA.; Nogales, E (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrat Bioimaging Div, Berkeley, CA 94720 USA.; Nogales, E (corresponding author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
EM ENogales@lbl.gov
FU National Energy Research Scientific Computing Center [DE-AC02-05CH11231]; NIGMS [GM63072]; Spanish Ministry of Economy and Competitiveness [BFU2013-44306P]; NIGMS Molecular Biophysics Training Grant [GM008295]; National Institute of General Medical Sciences [T32GM008295] Funding Source: NIH RePORTER
NR 73
TC 182
Z9 234
U1 0
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 604
EP +
DI 10.1038/nature17394
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400031
PM 27007846
DA 2026-03-09
ER

PT J
AU Badran, AH
   Guzov, VM
   Huai, Q
   Kemp, MM
   Vishwanath, P
   Kain, W
   Nance, AM
   Evdokimov, A
   Moshiri, F
   Turner, KH
   Wang, P
   Malvar, T
   Liu, DR
AF Badran, Ahmed H.
   Guzov, Victor M.
   Huai, Qing
   Kemp, Melissa M.
   Vishwanath, Prashanth
   Kain, Wendy
   Nance, Autumn M.
   Evdokimov, Artem
   Moshiri, Farhad
   Turner, Keith H.
   Wang, Ping
   Malvar, Thomas
   Liu, David R.
TI Continuous evolution of Bacillus thuringiensis toxins overcomes insect resistance
SO NATURE
LA English
DT Article
ID continuous directed evolution; protein evolution; crystal protein; cabbage-looper; bt crops; in-vivo; cadherin; binding; cry1ac; population
AB The Bacillus thuringiensis d-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits. The development of insect resistance to Bt toxins endangers their long-term effectiveness. Here we have developed a phage-assisted continuous evolution selection that rapidly evolves high-affinity protein-protein interactions, and applied this system to evolve variants of the Bt toxin Cry1Ac that bind a cadherin-like receptor from the insect pest Trichoplusia ni (TnCAD) that is not natively bound by wild-type Cry1Ac. The resulting evolved Cry1Ac variants bind TnCAD with high affinity (dissociation constant K-d = 11-41 nM), kill TnCAD-expressing insect cells that are not susceptible to wild-type Cry1Ac, and kill Cry1Ac-resistant T. ni insects up to 335-fold more potently than wild-type Cry1Ac. Our findings establish that the evolution of Bt toxins with novel insect cell receptor affinity can overcome insect Bt toxin resistance and confer lethality approaching that of the wild-type Bt toxin against non-resistant insects.
C1 [Badran, Ahmed H.; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Badran, Ahmed H.; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Guzov, Victor M.; Huai, Qing; Kemp, Melissa M.; Vishwanath, Prashanth] Monsanto Co, 245 First St,Suite 200, Cambridge, MA 02142 USA.
   [Kain, Wendy; Wang, Ping] Cornell Univ, Dept Entomol, Geneva, NY 14456 USA.
   [Nance, Autumn M.; Evdokimov, Artem; Moshiri, Farhad; Turner, Keith H.; Malvar, Thomas] Monsanto Co, 700 Chesterfield Pkwy West, Chesterfield, MO 63017 USA.
   [Evdokimov, Artem] HarkerBIO, 700 Ellicott St, Buffalo, NY 14023 USA.
C3 Harvard University; Howard Hughes Medical Institute; Harvard University; Monsanto; Cornell University; Monsanto
RP Liu, DR (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.; Liu, DR (corresponding author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM drliu@fas.harvard.edu
FU National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering [R01EB022376]; DARPA [HR0011-11-2-0003, N66001-12-C-4207]; Howard Hughes Medical Institute; US Department of Agriculture National Institute of Food and Agriculture and Agricultural Research Service Biotechnology Risk Assessment [2012-33522-19791]; Harvard Chemical Biology Program; National Science Foundation Graduate Research Fellowship
NR 42
TC 162
Z9 247
U1 6
U2 230
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 58
EP +
DI 10.1038/nature17938
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900038
PM 27120167
DA 2026-03-09
ER

PT J
AU Dickinson, ME
   Flenniken, AM
   Ji, X
   Teboul, L
   Wong, MD
   White, JK
   Meehan, TF
   Weninger, WJ
   Westerberg, H
   Adissu, H
   Baker, CN
   Bower, L
   Brown, JM
   Caddle, LB
   Chiani, F
   Clary, D
   Cleak, J
   Daly, MJ
   Denegre, JM
   Doe, B
   Dolan, ME
   Edie, SM
   Fuchs, H
   Gailus-Durner, V
   Galli, A
   Gambadoro, A
   Gallegos, J
   Guo, SY
   Horner, NR
   Hsu, CW
   Johnson, SJ
   Kalaga, S
   Keith, LC
   Lanoue, L
   Lawson, TN
   Lek, M
   Mark, M
   Arschall, SM
   Mason, J
   McElwee, ML
   Newbigging, S
   Nutter, LMJ
   Peterson, KA
   Ramirez-Solis, R
   Rowland, DJ
   Ryder, E
   Samocha, KE
   Seavitt, JR
   Selloum, M
   Szoke-Kovacs, Z
   Tamura, M
   Trainor, AG
   Tudose, I
   Wakana, S
   Warren, J
   Wendling, O
   West, DB
   Wong, L
   Yoshiki, A
   MacArthur, DG
   Tocchini-Valentini, GP
   Gao, X
   Flicek, P
   Bradley, A
   Skarnes, WC
   Justice, MJ
   Parkinson, HE
   Moore, M
   Wells, S
   Braun, RE
   Svenson, KL
   de Angelis, MH
   Herault, Y
   Mohun, T
   Mallon, AM
   Henkelman, RM
   Brown, SDM
   Adams, DJ
   Lloyd, KCK
   McKerlie, C
   Beaudet, AL
   Bucan, M
   Murray, SA
AF Dickinson, Mary E.
   Flenniken, Ann M.
   Ji, Xiao
   Teboul, Lydia
   Wong, Michael D.
   White, Jacqueline K.
   Meehan, Terrence F.
   Weninger, Wolfgang J.
   Westerberg, Henrik
   Adissu, Hibret
   Baker, Candice N.
   Bower, Lynette
   Brown, James M.
   Caddle, L. Brianna
   Chiani, Francesco
   Clary, Dave
   Cleak, James
   Daly, Mark J.
   Denegre, James M.
   Doe, Brendan
   Dolan, Mary E.
   Edie, Sarah M.
   Fuchs, Helmut
   Gailus-Durner, Valerie
   Galli, Antonella
   Gambadoro, Alessia
   Gallegos, Juan
   Guo, Shiying
   Horner, Neil R.
   Hsu, Chih-Wei
   Johnson, Sara J.
   Kalaga, Sowmya
   Keith, Lance C.
   Lanoue, Louise
   Lawson, Thomas N.
   Lek, Monkol
   Mark, Manuel
   Arschall, Susan M.
   Mason, Jeremy
   McElwee, Melissa L.
   Newbigging, Susan
   Nutter, Lauryl M. J.
   Peterson, Kevin A.
   Ramirez-Solis, Ramiro
   Rowland, Douglas J.
   Ryder, Edward
   Samocha, Kaitlin E.
   Seavitt, John R.
   Selloum, Mohammed
   Szoke-Kovacs, Zsombor
   Tamura, Masaru
   Trainor, Amanda G.
   Tudose, Ilinca
   Wakana, Shigeharu
   Warren, Jonathan
   Wendling, Olivia
   West, David B.
   Wong, Leeyean
   Yoshiki, Atsushi
   MacArthur, Daniel G.
   Tocchini-Valentini, Glauco P.
   Gao, Xiang
   Flicek, Paul
   Bradley, Allan
   Skarnes, William C.
   Justice, Monica J.
   Parkinson, Helen E.
   Moore, Mark
   Wells, Sara
   Braun, Robert E.
   Svenson, Karen L.
   de Angelis, Martin Hrabe
   Herault, Yann
   Mohun, Tim
   Mallon, Ann-Marie
   Henkelman, R. Mark
   Brown, Steve D. M.
   Adams, David J.
   Lloyd, K. C. Kent
   McKerlie, Colin
   Beaudet, Arthur L.
   Bucan, Maja
   Murray, Stephen A.
TI High-throughput discovery of novel developmental phenotypes
SO NATURE
LA English
DT Article
ID mammalian gene-function; mouse embryo; glycogenin-1 deficiency; genome-wide; micro-ct; screens; disease; expression; resource; identification
AB Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.
C1 [Dickinson, Mary E.; Hsu, Chih-Wei; Kalaga, Sowmya; Keith, Lance C.; McElwee, Melissa L.; Wong, Leeyean] Dept Mol Physiol & Biophys, Houston, TX 77030 USA.
   [Flenniken, Ann M.; Wong, Michael D.; Adissu, Hibret; Newbigging, Susan; Nutter, Lauryl M. J.; Henkelman, R. Mark; McKerlie, Colin] Toronto Ctr Phenogen, Toronto, ON M5T 3H7, Canada.
   [Flenniken, Ann M.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
   [Ji, Xiao] Univ Penn, Perelman Sch Med, Genom & Computat Biol Program, Philadelphia, PA 19104 USA.
   [Teboul, Lydia; Westerberg, Henrik; Brown, James M.; Cleak, James; Horner, Neil R.; Johnson, Sara J.; Lawson, Thomas N.; Szoke-Kovacs, Zsombor; Wells, Sara; Mallon, Ann-Marie; Brown, Steve D. M.] Med Res Council Harwell, Mammalian Genet Unit, Harwell OX11 0RD, Oxon, England.
   [Teboul, Lydia; Westerberg, Henrik; Brown, James M.; Cleak, James; Horner, Neil R.; Johnson, Sara J.; Lawson, Thomas N.; Szoke-Kovacs, Zsombor; Wells, Sara; Mallon, Ann-Marie; Brown, Steve D. M.] Mary Lyon Ctr, Harwell OX11 0RD, Oxon, England.
   [Wong, Michael D.; Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5T 3H7, Canada.
   [White, Jacqueline K.; Doe, Brendan; Galli, Antonella; Ramirez-Solis, Ramiro; Ryder, Edward; Bradley, Allan; Skarnes, William C.; Adams, David J.] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
   [Meehan, Terrence F.; Clary, Dave; Mason, Jeremy; Tudose, Ilinca; Warren, Jonathan; Flicek, Paul; Parkinson, Helen E.] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
   [Weninger, Wolfgang J.] Med Univ Vienna, Ctr Anat & Cell Biol, A-1090 Vienna, Austria.
   [Adissu, Hibret; Newbigging, Susan; Nutter, Lauryl M. J.; Justice, Monica J.; McKerlie, Colin] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
   [Baker, Candice N.; Caddle, L. Brianna; Denegre, James M.; Dolan, Mary E.; Edie, Sarah M.; Peterson, Kevin A.; Braun, Robert E.; Svenson, Karen L.; Murray, Stephen A.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
   [Bower, Lynette; Clary, Dave; Lanoue, Louise; Rowland, Douglas J.; Trainor, Amanda G.; Lloyd, K. C. Kent] Univ Calif Davis, Mouse Biol Program, Davis, CA 95618 USA.
   [Chiani, Francesco; Gambadoro, Alessia; Tocchini-Valentini, Glauco P.] Italian Natl Res Council CNR, Inst Cell Biol & Neurobiol, Monterotondo Mouse Clin, I-00015 Monterotondo, Italy.
   [Daly, Mark J.; Lek, Monkol; Samocha, Kaitlin E.; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Daly, Mark J.; Lek, Monkol; Samocha, Kaitlin E.; MacArthur, Daniel G.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Fuchs, Helmut; Gailus-Durner, Valerie; Arschall, Susan M.; de Angelis, Martin Hrabe] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.
   [Fuchs, Helmut; Gailus-Durner, Valerie; Arschall, Susan M.; de Angelis, Martin Hrabe] German Mouse Clin, D-85764 Neuherberg, Germany.
   [Gallegos, Juan; Seavitt, John R.; Justice, Monica J.; Beaudet, Arthur L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Guo, Shiying; Gao, Xiang] Nanjing Univ, Nanjing Biomed Res Inst, Collaborat Innovat Ctr Genet & Dev, SKL Pharmaceut Biotechnol & Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China.
   [Mark, Manuel; Selloum, Mohammed; Wendling, Olivia; Herault, Yann] Univ Strasbourg, ICS, Infrastruct Natl PHENOMIN, F-67404 Illkirch Graffenstaden, France.
   [Mark, Manuel; Selloum, Mohammed; Wendling, Olivia; Herault, Yann] Univ Strasbourg, INSERM, CNRS, IGBMC, F-67404 Illkirch Graffenstaden, France.
   [Tamura, Masaru; Wakana, Shigeharu; Yoshiki, Atsushi] RIKEN, BioResource Ctr, Tsukuba, Ibaraki 3050074, Japan.
   [West, David B.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Moore, Mark] IMPC, San Anselmo, CA 94960 USA.
   [de Angelis, Martin Hrabe] Tech Univ Munich, Sch Life Sci Weihenstephan, Chair Expt Genet, D-81675 Freising Weihenstephan, Germany.
   [de Angelis, Martin Hrabe] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.
   [Mohun, Tim] Francis Crick Inst, Mill Hill Lab, Mill Hill, London NW1 1AT, England.
   [Bucan, Maja] Univ Penn, Perlman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Bucan, Maja] Univ Penn, Dept Psychiat, Perlman Sch Med, Philadelphia, PA 19104 USA.
C3 University of Toronto; Sinai Health System Toronto; University of Pennsylvania; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); University of Toronto; Hospital for Sick Children (SickKids); Wellcome Trust Sanger Institute; Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Medical University of Vienna; University of Toronto; Hospital for Sick Children (SickKids); Jackson Laboratory; University of California System; University of California Davis; Consiglio Nazionale delle Ricerche (CNR); Istituto di Biologia Cellulare e Neurobiologia (IBCN-CNR); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Baylor College of Medicine; Nanjing University; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; RIKEN; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; Technical University of Munich; German Center for Diabetes Research (DZD); University of Pennsylvania; University of Pennsylvania
RP Murray, SA (corresponding author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM steve.murray@jax.org
FU NIH [U42 OD011185, U54 HG006332, U54 HG006348-S1, OD011174, HG006364-03S1, U42 OD011175, U54 HG006370]; Wellcome Trust; Medical Research Council Strategic Award; Government of Canada through Genome Canada; Ontario Genomics [OGI-051]; Wellcome Trust Strategic Award " Deciphering the Mechanisms of Developmental Disorders (DMDD)" [WT100160]; National Centre for Scientific Research (CNRS); French National Institute of Health and Medical Research (INSERM); University of Strasbourg (UDS); Centre Europeen de Recherche en Biologie et en Medecine; Agence Nationale de la Recherche [ANR-10-IDEX-0002-02, ANR-10-INBS- 07 PHENOMIN]; German Federal Ministry of Education and Research [01KX1012]; Grants-in-Aid for Scientific Research [26250024, 15K06815] Funding Source: KAKEN; National Cancer Institute [P30CA093373, P30CA034196] Funding Source: NIH RePORTER; National Eye Institute [P30EY002520] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [U2CDK092993] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Dental and Craniofacial Research; National Heart Lung and Blood Institute; National Eye Institute; National Institute of Environmental Health Sciences; NIH Office of the Director [UM1OD023222] Funding Source: NIH RePORTER; National Institute on Aging; National Center for Complementary and Integrative Health; National Human Genome Research Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UM1HG006348] Funding Source: NIH RePORTER; National Institute on Drug Abuse; National Cancer Institute; National Institute of Environmental Health Sciences; National Institute on Alcohol Abuse and Alcoholism; National Institute of Neurological Disorders and Stroke; NIH Office of the Director; National Institute of Allergy and Infectious Diseases [UM1OD023221] Funding Source: NIH RePORTER; NIH Office of the Director [U42OD012210] Funding Source: NIH RePORTER; NIH Office of the Director; National Human Genome Research Institute; National Institute on Deafness and Other Communication Disorders [UM1HG006370] Funding Source: NIH RePORTER; Cancer Research UK [13031] Funding Source: researchfish; Medical Research Council [MC_U142684171, MC_UP_1502/3, MC_U142684172] Funding Source: researchfish; MRC [MC_U142684171, MC_U142684172, MC_UP_1502/3] Funding Source: UKRI
NR 59
TC 904
Z9 1020
U1 2
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 508
EP +
DI 10.1038/nature19356
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900047
PM 27626380
DA 2026-03-09
ER

PT J
AU Verdegaal, EME
   de Miranda, NFCC
   Visser, M
   Harryvan, T
   van Buuren, MM
   Andersen, RS
   Hadrup, SR
   van der Minne, CE
   Schotte, R
   Spits, H
   Haanen, JBAG
   Kapiteijn, EHW
   Schumacher, TN
   van der Burg, SH
AF Verdegaal, Els M. E.
   de Miranda, Noel F. C. C.
   Visser, Marten
   Harryvan, Tom
   van Buuren, Marit M.
   Andersen, Rikke S.
   Hadrup, Sine R.
   van der Minne, Caroline E.
   Schotte, Remko
   Spits, Hergen
   Haanen, John B. A. G.
   Kapiteijn, Ellen H. W.
   Schumacher, Ton N.
   van der Burg, Sjoerd H.
TI Neoantigen landscape dynamics during human melanoma-T cell interactions
SO NATURE
LA English
DT Article
ID exome analysis reveals; pd-1 blockade; antigens; therapy; lymphocytes; responses; recognition; mutations; patient; tumors
AB Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T-cell checkpoint blockade and adoptive T-cell therapy(1-7). Therefore, strategies to selectively enhance T-cell reactivity against genetically defined neoantigens(1,8-11) are currently under development. In mouse models, T-cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens(12,13). However, whether the T-cell-recognized neoantigen repertoire in human cancers is constant over time is unclear. Here we analyse the stability of neoantigen-specific T-cell responses and the antigens they recognize in two patients with stage IV melanoma treated by adoptive T-cell transfer. The T-cell-recognized neoantigens can be selectively lost from the tumour cell population, either by overall reduced expression of the genes or loss of the mutant alleles. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of neoantigen-specific T-cell reactivity in tumour-infiltrating lymphocytes. These data demonstrate the dynamic interactions between cancer cells and T cells, which suggest that T cells mediate neoantigen immunoediting, and indicate that the therapeutic induction of broad neoantigen-specific T-cell responses should be used to avoid tumour resistance.
C1 [Verdegaal, Els M. E.; Visser, Marten; Harryvan, Tom; van der Minne, Caroline E.; Haanen, John B. A. G.; Kapiteijn, Ellen H. W.; van der Burg, Sjoerd H.] Leiden Univ, Med Ctr, Dept Med Oncol, NL-2300 RC Leiden, Netherlands.
   [de Miranda, Noel F. C. C.] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands.
   [van Buuren, Marit M.; Haanen, John B. A. G.; Schumacher, Ton N.] Netherlands Canc Inst, Dept Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
   [Andersen, Rikke S.; Hadrup, Sine R.] Herlev Univ Hosp, Dept Hematol, Ctr Canc Immune Therapy, DK-2730 Herlev, Denmark.
   [Schotte, Remko; Spits, Hergen] AIMM Therapeut, NL-1105 BA Amsterdam, Netherlands.
   [Spits, Hergen] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands.
   [van Buuren, Marit M.] Neon Therapeut, Cambridge, MA 02142 USA.
   [Andersen, Rikke S.] Univ Southern Denmark, Inst Mol Med, Dept Canc & Inflammat Res, DK-5000 Odense, Denmark.
   [Hadrup, Sine R.] Tech Univ Denmark, Natl Vet Inst, Sect Immunol & Vaccinol, DK-1870 Copenhagen, Denmark.
C3 Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Netherlands Cancer Institute; University of Copenhagen; Herlev & Gentofte Hospital; University of Amsterdam; Academic Medical Center Amsterdam; University of Southern Denmark; Technical University of Denmark
RP Verdegaal, EME (corresponding author), Leiden Univ, Med Ctr, Dept Med Oncol, NL-2300 RC Leiden, Netherlands.
EM E.Verdegaal@lumc.nl
FU Dutch Cancer Society [UL 2012-5544, NKI 2012-5463, UVA 2010-4822]; Anticancer Fund; Dutch Cancer Society Queen Wilhelmina Award NKI [2013-6122]; Fight Colorectal Cancer-Michael's Mission-AACR Fellowship; Alpe d'HuZes/KWF Bas Mulder Award
NR 29
TC 368
Z9 429
U1 2
U2 113
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 91
EP +
DI 10.1038/nature18945
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200036
PM 27350335
DA 2026-03-09
ER

PT J
AU Myung, JH
   Neagu, D
   Miller, DN
   Irvine, JTS
AF Myung, Jae-ha
   Neagu, Dragos
   Miller, David N.
   Irvine, John T. S.
TI Switching on electrocatalytic activity in solid oxide cells
SO NATURE
LA English
DT Article
ID in-situ; performance; nickel
AB Solid oxide cells (SOCs) can operate with high efficiency in two ways-as fuel cells, oxidizing a fuel to produce electricity, and as electrolysis cells, electrolysing water to produce hydrogen and oxygen gases. Ideally, SOCs should perform well, be durable and be inexpensive, but there are often competitive tensions, meaning that, for example, performance is achieved at the expense of durability. SOCs consist of porous electrodes-the fuel and air electrodes-separated by a dense electrolyte. In terms of the electrodes, the greatest challenge is to deliver high, long-lasting electrocatalytic activity while ensuring cost-and time-efficient manufacture(1). This has typically been achieved through lengthy and intricate ex situ procedures. These often require dedicated precursors and equipment(1-3); moreover, although the degradation of such electrodes associated with their reversible operation can be mitigated(4), they are susceptible to many other forms of degradation(5). An alternative is to grow appropriate electrode nanoarchitectures under operationally relevant conditions, for example, via redox exsolution(6-10). Here we describe the growth of a finely dispersed array of anchored metal nanoparticles on an oxide electrode through electrochemical poling of a SOC at 2 volts for a few seconds. These electrode structures perform well as both fuel cells and electrolysis cells (for example, at 900 degrees C they deliver 2 watts per square centimetre of power in humidified hydrogen gas, and a current of 2.75 amps per square centimetre at 1.3 volts in 50% water/nitrogen gas). The nanostructures and corresponding electrochemical activity do not degrade in 150 hours of testing. These results not only prove that in operando methods can yield emergent nanomaterials, which in turn deliver exceptional performance, but also offer proof of concept that electrolysis and fuel cells can be unified in a single, high-performance, versatile and easily manufactured device. This opens up the possibility of simple, almost instantaneous production of highly active nanostructures for reinvigorating SOCs during operation.
C1 [Myung, Jae-ha; Neagu, Dragos; Miller, David N.; Irvine, John T. S.] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
C3 University of St Andrews
RP Myung, JH; Neagu, D; Irvine, JTS (corresponding author), Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
EM jm297@st-andrews.ac.uk; dn67@st-andrews.ac.uk; jtsi@st-andrews.ac.uk
FU Engineering and Physical Sciences Research Council (EPSRC) [EP/K015540/1]; EPSRC Material World Network [EP/J018414/1]; EPSRC [EP/K021036/1, EP/G01244X/1, EP/L017008/1]; Royal Society Wolfson Merit Award [WRMA 2012/R2]; EPSRC [EP/K021036/2, EP/L017008/1, EP/G01244X/1, EP/J018414/1, EP/K015540/1, EP/K021036/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/K015540/1, EP/G01244X/1, EP/L017008/1, EP/K021036/2, EP/J018414/1, EP/K021036/1] Funding Source: researchfish
NR 14
TC 523
Z9 563
U1 17
U2 589
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 528
EP +
DI 10.1038/nature19090
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900051
PM 27548878
DA 2026-03-09
ER

PT J
AU Leucci, E
   Vendramin, R
   Spinazzi, M
   Laurette, P
   Fiers, M
   Wouters, J
   Radaelli, E
   Eyckerman, S
   Leonelli, C
   Vanderheyden, K
   Rogiers, A
   Hermans, E
   Baatsen, P
   Aerts, S
   Amant, F
   Van Aelst, S
   van den Oord, J
   de Strooper, B
   Davidson, I
   Lafontaine, DLJ
   Gevaert, K
   Vandesompele, J
   Mestdagh, P
   Marine, JC
AF Leucci, Eleonora
   Vendramin, Roberto
   Spinazzi, Marco
   Laurette, Patrick
   Fiers, Mark
   Wouters, Jasper
   Radaelli, Enrico
   Eyckerman, Sven
   Leonelli, Carina
   Vanderheyden, Katrien
   Rogiers, Aljosja
   Hermans, Els
   Baatsen, Pieter
   Aerts, Stein
   Amant, Frederic
   Van Aelst, Stefan
   van den Oord, Joost
   de Strooper, Bart
   Davidson, Irwin
   Lafontaine, Denis L. J.
   Gevaert, Kris
   Vandesompele, Jo
   Mestdagh, Pieter
   Marine, Jean-Christophe
TI Melanoma addiction to the long non-coding RNA SAMMSON
SO NATURE
LA English
DT Article
ID p-32 protein; mitochondrial translation; oxidative-phosphorylation; metabolism; proliferation; pgc1-alpha; morphology; p32/gc1qr; survival; target
AB Focal amplifications of chromosome 3p13-3p14 occur in about 10% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon(1). However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.
C1 [Leucci, Eleonora; Vendramin, Roberto; Rogiers, Aljosja; Marine, Jean-Christophe] KULeuven, Lab Mol Canc Biol, Ctr Human Genet, Herestr 49, B-3000 Leuven, Belgium.
   [Leucci, Eleonora; Vendramin, Roberto; Spinazzi, Marco; Fiers, Mark; Rogiers, Aljosja; Baatsen, Pieter; de Strooper, Bart; Marine, Jean-Christophe] VIB, Ctr Biol Dis, Herestr 49, B-3000 Leuven, Belgium.
   [Laurette, Patrick; Davidson, Irwin] IGBMC, Rue Laurent Fries 1, F-67404 Illkirch Graffenstaden, France.
   [Wouters, Jasper; van den Oord, Joost] KULeuven, Dept Pathol, Lab Translat Cell & Tissue Res, Herestr 49, B-3000 Leuven, Belgium.
   [Wouters, Jasper; van den Oord, Joost] UZ Leuven, Herestr 49, B-3000 Leuven, Belgium.
   [Radaelli, Enrico] VIB KULeuven, Ctr Biol Dis, Mouse Histopathol Core Facil, Herestr 49, B-3000 Leuven, Belgium.
   [Eyckerman, Sven; Gevaert, Kris] VIB, Ctr Med Biotechnol, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium.
   [Eyckerman, Sven; Gevaert, Kris] Univ Ghent, Dept Biochem, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium.
   [Leonelli, Carina; Vanderheyden, Katrien; Vandesompele, Jo; Mestdagh, Pieter] Univ Ghent, Ctr Med Genet, De Pintelaan 185, B-9000 Ghent, Belgium.
   [Leonelli, Carina; Vanderheyden, Katrien; Vandesompele, Jo; Mestdagh, Pieter] Univ Ghent, Canc Res Inst Gent, De Pintelaan 185, B-9000 Ghent, Belgium.
   [Hermans, Els; Amant, Frederic] Katholieke Univ Leuven, Gynaecol Oncol, Herestr 49, B-3000 Leuven, Belgium.
   [Aerts, Stein] KULeuven, Ctr Human Genet, Lab Computat Biol, Herestr 49, B-3000 Leuven, Belgium.
   [Van Aelst, Stefan] Univ Ghent, Dept Appl Math Comp Sci & Stat, De Pintelaan 185, B-9000 Ghent, Belgium.
   [Van Aelst, Stefan] Katholieke Univ Leuven, Dept Math, Celestijnenlann 200B, B-3001 Leuven, Belgium.
   [Lafontaine, Denis L. J.] Univ Libre Bruxelles, Ctr Microscopy & Mol Imaging, RNA Mol Biol, Rue Prof Jeener & Brachet 12, B-6041 Charleroi, Belgium.
C3 KU Leuven; Flanders Institute for Biotechnology (VIB); Institut National de la Sante et de la Recherche Medicale (Inserm); KU Leuven; KU Leuven; University Hospital Leuven; Flanders Institute for Biotechnology (VIB); KU Leuven; Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University; Ghent University Hospital; Ghent University; Ghent University Hospital; KU Leuven; KU Leuven; Ghent University; Ghent University Hospital; KU Leuven; Universite Libre de Bruxelles
RP Marine, JC (corresponding author), KULeuven, Lab Mol Canc Biol, Ctr Human Genet, Herestr 49, B-3000 Leuven, Belgium.; Marine, JC (corresponding author), VIB, Ctr Biol Dis, Herestr 49, B-3000 Leuven, Belgium.
EM JeanChristophe.Marine@cme.vib-kuleuven.be
FU Fonds Wetenschappelijk Onderzoek (FWO) [G.0646.14N, 3G056613]; Foundation Against Cancer (STK) [2014-126]; UGent-IOF [F2013/IOF-Advanced/676]; STK grant [F/2014/376]; KULeuven [GOA/14/012]; Belgian Ministries of Health [KPC_29_005]; Marie-Curie/VIB OMICS program; EMBO fellowship [ALTF 648-2013]; FWO; Fonds National de la Recherche (FRS/FNRS); Institut National du Cancer PAIR melanoma [MELA13-002]; "France Genomique" consortium [ANR10-INBS-09-08];  [ANR-10-LABX-0030-INRT]
NR 30
TC 463
Z9 516
U1 1
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 518
EP +
DI 10.1038/nature17161
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300044
PM 27008969
DA 2026-03-09
ER

PT J
AU Beal, LM
   Elipot, S
AF Beal, Lisa M.
   Elipot, Shane
TI Broadening not strengthening of the Agulhas Current since the early 1990s
SO NATURE
LA English
DT Article
ID western boundary currents; wind-driven circulation; east australian current; climate-change; variability; pacific; sea; intensification; transport; project
AB Western boundary currents-such as the Agulhas Current in the Indian Ocean-carry heat poleward, moderating Earth's climate and fuelling the mid-latitude storm tracks(1,2). They could exacerbate or mitigate warming and extreme weather events in the future, depending on their response to anthropogenic climate change. Climate models show an ongoing poleward expansion and intensification of the global wind systems, most robustly in the Southern Hemisphere(3-5), and linear dynamical theory(6,7) suggests that western boundary currents will intensify and shift poleward as a result(3,8). Observational evidence of such changes comes from accelerated warming and air-sea heat flux rates within all western boundary currents, which are two or three times faster than global mean rates(5,9,10). Here we show that, despite these expectations, the Agulhas Current has not intensified since the early 1990s. Instead, we find that it has broadened as a result of more eddy activity. Recent analyses of other western boundary currents-the Kuroshio and East Australia currents-hint at similar trends(11-15). These results indicate that intensifying winds may be increasing the eddy kinetic energy of boundary currents, rather than their mean flow. This could act to decrease poleward heat transport and increase cross-frontal exchange of nutrients and pollutants between the coastal ocean and the deep ocean. Sustained in situ measurements are needed to properly understand the role of these current systems in a changing climate.
C1 [Beal, Lisa M.; Elipot, Shane] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, 4600 Rickenbacker Causeway, Miami, FL 33149 USA.
C3 University of Miami
RP Beal, LM (corresponding author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, 4600 Rickenbacker Causeway, Miami, FL 33149 USA.
EM lbeal@rsmas.miami.edu
FU US National Science Foundation [OCE-0850891]; Cnes; Division Of Ocean Sciences; Directorate For Geosciences [1459543] Funding Source: National Science Foundation
NR 37
TC 125
Z9 135
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 570
EP +
DI 10.1038/nature19853
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500049
PM 27828944
DA 2026-03-09
ER

PT J
AU Abramowski, A
   Aharonian, F
   Benkhali, FA
   Akhperjanian, AG
   Angüner, EO
   Backes, M
   Balzer, A
   Becherini, Y
   Tjus, JB
   Berge, D
   Bernhard, S
   Bernlöhr, K
   Birsin, E
   Blackwell, R
   Böttcher, M
   Boisson, C
   Bolmont, J
   Bordas, P
   Bregeon, J
   Brun, F
   Brun, P
   Bryan, M
   Bulik, T
   Carr, J
   Casanova, S
   Chakraborty, N
   Chalme-Calvet, R
   Chaves, RCG
   Chen, A
   Chrétien, M
   Colafrancesco, S
   Cologna, G
   Conrad, J
   Couturier, C
   Cui, Y
   Davids, ID
   Degrange, B
   Deil, C
   deWilt, P
   Djannati-Ata, A
   Domainko, W
   Donath, A
   Drury, LO
   Dubus, G
   Dutson, K
   Dyks, J
   Dyrda, M
   Edwards, T
   Egberts, K
   Eger, P
   Ernenwein, JP
   Espigat, P
   Farnier, C
   Fegan, S
   Feinstein, F
   Fernandes, MV
   Fernandez, D
   Fiasson, A
   Fontaine, G
   Förster, A
   Füessling, M
   Gabici, S
   Gajdus, M
   Gallant, YA
   Garrigoux, T
   Giavitto, G
   Giebels, B
   Glicenstein, JF
   Gottschall, D
   Goyal, A
   Grondin, MH
   Grudzinska, M
   Hadasch, D
   Häffner, S
   Hahn, J
   Hawkes, J
   Heinzelmann, G
   Henri, G
   Hermann, G
   Hervet, O
   Hillert, A
   Hinton, JA
   Hofmann, W
   Hofverberg, P
   Hoischen, C
   Holler, M
   Horns, D
   Ivascenko, A
   Jacholkowska, A
   Jamrozy, M
   Janiak, M
   Jankowsky, F
   Jung-Richardt, I
   Kastendieck, MA
   Katarzynski, K
   Katz, U
   Kerszberg, D
   Khélifi, B
   Kieffer, M
   Klepser, S
   Klochkov, D
   Kluzniak, W
   Kolitzus, D
   Komin, N
   Kosack, K
   Krakau, S
   Krayzel, F
   Krüger, PP
   Laffon, H
   Lamanna, G
   Lau, J
   Lefaucheur, J
   Lefranc, V
   Lemiére, A
   Lemoine-Goumard, M
   Lenain, JP
   Lohse, T
   Lopatin, A
   Lu, CC
   Lui, R
   Marandon, V
   Marcowith, A
   Mariaud, C
   Marx, R
   Maurin, G
   Maxted, N
   Mayer, M
   Meintjes, PJ
   Menzler, U
   Meyer, M
   Mitchell, AMW
   Moderski, R
   Mohamed, M
   Morå, K
   Moulin, E
   Murach, T
   de Naurois, M
   Niemiec, J
   Oakes, L
   Odaka, H
   Öttl, S
   Ohm, S
   Opitz, B
   Ostrowski, M
   Oya, I
   Panter, M
   Parsons, RD
   Arribas, MP
   Pekeur, NW
   Pelletier, G
   Petrucci, PO
   Peyaud, B
   Pita, S
   Poon, H
   Prokoph, H
   Pühlhofer, G
   Punch, M
   Quirrenbach, A
   Raab, S
   Reichardt, I
   Reimer, A
   Reimer, O
   Renaud, M
   de los Reyes, R
   Rieger, F
   Romoli, C
   Rosier-Lees, S
   Rowell, G
   Rudak, B
   Rulten, CB
   Sahakian, V
   Salek, D
   Sanchez, DA
   Santangelo, A
   Sasaki, M
   Schlickeiser, R
   Schüssler, F
   Schulz, A
   Schwanke, U
   Schwemmer, S
   Seyffert, AS
   Simoni, R
   Sol, H
   Spanier, F
   Spengler, G
   Spies, F
   Stawarz, L
   Steenkamp, R
   Stegmann, C
   Stinzing, F
   Stycz, K
   Sushch, I
   Tavernet, JP
   Tavernier, T
   Taylor, AM
   Terrier, R
   Tluczykont, M
   Trichard, C
   Tuffs, R
   Valerius, K
   van der Walt, J
   van Eldik, C
   van Soelen, B
   Vasileiadis, G
   Veh, J
   Venter, C
   Viana, A
   Vincent, P
   Vink, J
   Voisin, F
   Völk, HJ
   Vuillaume, T
   Wagner, SJ
   Wagner, P
   Wagner, RM
   Weidinger, M
   Weitzel, Q
   White, R
   Wierzcholska, A
   Willmann, P
   Wörnlein, A
   Wouters, D
   Yang, R
   Zabalza, V
   Zaborov, D
   Zacharias, M
   Zdziarski, AA
   Zech, A
   Zefi, F
   Zywucka, N
AF Abramowski, A.
   Aharonian, F.
   Benkhali, F. Ait
   Akhperjanian, A. G.
   Anguener, E. O.
   Backes, M.
   Balzer, A.
   Becherini, Y.
   Tjus, J. Becker
   Berge, D.
   Bernhard, S.
   Bernloehr, K.
   Birsin, E.
   Blackwell, R.
   Boettcher, M.
   Boisson, C.
   Bolmont, J.
   Bordas, P.
   Bregeon, J.
   Brun, F.
   Brun, P.
   Bryan, M.
   Bulik, T.
   Carr, J.
   Casanova, S.
   Chakraborty, N.
   Chalme-Calvet, R.
   Chaves, R. C. G.
   Chen, A.
   Chretien, M.
   Colafrancesco, S.
   Cologna, G.
   Conrad, J.
   Couturier, C.
   Cui, Y.
   Davids, I. D.
   Degrange, B.
   Deil, C.
   deWilt, P.
   Djannati-Ata, A.
   Domainko, W.
   Donath, A.
   Drury, L. O'C.
   Dubus, G.
   Dutson, K.
   Dyks, J.
   Dyrda, M.
   Edwards, T.
   Egberts, K.
   Eger, P.
   Ernenwein, J-P.
   Espigat, P.
   Farnier, C.
   Fegan, S.
   Feinstein, F.
   Fernandes, M. V.
   Fernandez, D.
   Fiasson, A.
   Fontaine, G.
   Foerster, A.
   Fuessling, M.
   Gabici, S.
   Gajdus, M.
   Gallant, Y. A.
   Garrigoux, T.
   Giavitto, G.
   Giebels, B.
   Glicenstein, J. F.
   Gottschall, D.
   Goyal, A.
   Grondin, M-H.
   Grudzinska, M.
   Hadasch, D.
   Haeffner, S.
   Hahn, J.
   Hawkes, J.
   Heinzelmann, G.
   Henri, G.
   Hermann, G.
   Hervet, O.
   Hillert, A.
   Hinton, J. A.
   Hofmann, W.
   Hofverberg, P.
   Hoischen, C.
   Holler, M.
   Horns, D.
   Ivascenko, A.
   Jacholkowska, A.
   Jamrozy, M.
   Janiak, M.
   Jankowsky, F.
   Jung-Richardt, I.
   Kastendieck, M. A.
   Katarzynski, K.
   Katz, U.
   Kerszberg, D.
   Khelifi, B.
   Kieffer, M.
   Klepser, S.
   Klochkov, D.
   Kluzniak, W.
   Kolitzus, D.
   Komin, Nu.
   Kosack, K.
   Krakau, S.
   Krayzel, F.
   Krueger, P. P.
   Laffon, H.
   Lamanna, G.
   Lau, J.
   Lefaucheur, J.
   Lefranc, V.
   Lemiere, A.
   Lemoine-Goumard, M.
   Lenain, J-P.
   Lohse, T.
   Lopatin, A.
   Lu, C-C.
   Lui, R.
   Marandon, V.
   Marcowith, A.
   Mariaud, C.
   Marx, R.
   Maurin, G.
   Maxted, N.
   Mayer, M.
   Meintjes, P. J.
   Menzler, U.
   Meyer, M.
   Mitchell, A. M. W.
   Moderski, R.
   Mohamed, M.
   Mora, K.
   Moulin, E.
   Murach, T.
   de Naurois, M.
   Niemiec, J.
   Oakes, L.
   Odaka, H.
   Oettl, S.
   Ohm, S.
   Opitz, B.
   Ostrowski, M.
   Oya, I.
   Panter, M.
   Parsons, R. D.
   Arribas, M. Paz
   Pekeur, N. W.
   Pelletier, G.
   Petrucci, P-O.
   Peyaud, B.
   Pita, S.
   Poon, H.
   Prokoph, H.
   Puehlhofer, G.
   Punch, M.
   Quirrenbach, A.
   Raab, S.
   Reichardt, I.
   Reimer, A.
   Reimer, O.
   Renaud, M.
   de los Reyes, R.
   Rieger, F.
   Romoli, C.
   Rosier-Lees, S.
   Rowell, G.
   Rudak, B.
   Rulten, C. B.
   Sahakian, V.
   Salek, D.
   Sanchez, D. A.
   Santangelo, A.
   Sasaki, M.
   Schlickeiser, R.
   Schuessler, F.
   Schulz, A.
   Schwanke, U.
   Schwemmer, S.
   Seyffert, A. S.
   Simoni, R.
   Sol, H.
   Spanier, F.
   Spengler, G.
   Spies, F.
   Stawarz, L.
   Steenkamp, R.
   Stegmann, C.
   Stinzing, F.
   Stycz, K.
   Sushch, I.
   Tavernet, J-P.
   Tavernier, T.
   Taylor, A. M.
   Terrier, R.
   Tluczykont, M.
   Trichard, C.
   Tuffs, R.
   Valerius, K.
   van der Walt, J.
   van Eldik, C.
   van Soelen, B.
   Vasileiadis, G.
   Veh, J.
   Venter, C.
   Viana, A.
   Vincent, P.
   Vink, J.
   Voisin, F.
   Voelk, H. J.
   Vuillaume, T.
   Wagner, S. J.
   Wagner, P.
   Wagner, R. M.
   Weidinger, M.
   Weitzel, Q.
   White, R.
   Wierzcholska, A.
   Willmann, P.
   Woernlein, A.
   Wouters, D.
   Yang, R.
   Zabalza, V.
   Zaborov, D.
   Zacharias, M.
   Zdziarski, A. A.
   Zech, A.
   Zefi, F.
   Zywucka, N.
TI Acceleration of petaelectronvolt protons in the Galactic Centre
SO NATURE
LA English
DT Article
ID gamma-ray emission; massive black-hole; center region; cosmic-rays; x-ray; supernova-remnants; molecular clouds; magnetic-field; origin; propagation
AB Galactic cosmic rays reach energies of at least a few petaelectronvolts(1) (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators ('PeVatrons'), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies(2). Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 10(13) electronvolts) were inferred from recent gamma-ray observations(3). However, none of the currently known accelerators-not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays-has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of.-rays extending without a cut-off or a spectral break to tens of teraelectronvolts(4). Here we report deep.-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts(5) and an outflow from the Galactic Centre(6). Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 10(6)-10(7) years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
C1 [Abramowski, A.; Fernandes, M. V.; Heinzelmann, G.; Horns, D.; Kastendieck, M. A.; Opitz, B.; Spies, F.; Tluczykont, M.] Univ Hamburg, Inst Expt Phys, Luruper Chaussee 149, D-22761 Hamburg, Germany.
   [Aharonian, F.; Benkhali, F. Ait; Bernloehr, K.; Bordas, P.; Casanova, S.; Chakraborty, N.; Deil, C.; Domainko, W.; Donath, A.; Edwards, T.; Eger, P.; Foerster, A.; Hahn, J.; Hermann, G.; Hillert, A.; Hinton, J. A.; Hofmann, W.; Hofverberg, P.; Lu, C-C.; Lui, R.; Marandon, V.; Marx, R.; Mitchell, A. M. W.; Odaka, H.; Panter, M.; Parsons, R. D.; Poon, H.; de los Reyes, R.; Rieger, F.; Tuffs, R.; Viana, A.; Voelk, H. J.; Weitzel, Q.; Yang, R.] Max Planck Inst Kernphys, POB 103980, D-69029 Heidelberg, Germany.
   [Aharonian, F.; Drury, L. O'C.; Romoli, C.; Taylor, A. M.] Dublin Inst Adv Studies, 31 Fitzwilliam Pl, Dublin 2, Ireland.
   [Aharonian, F.; Akhperjanian, A. G.; Sahakian, V.] Natl Acad Sci Republ Armenia, Marshall Baghramian Ave 24, Yerevan 0019, Armenia.
   [Akhperjanian, A. G.; Sahakian, V.] Yerevan Phys Inst, 2 Alikhanian Bros St, Yerevan 375036, Armenia.
   [Anguener, E. O.; Birsin, E.; Gajdus, M.; Lohse, T.; Mayer, M.; Murach, T.; Oakes, L.; Arribas, M. Paz; Schwanke, U.; Wagner, P.] Humboldt Univ, Inst Phys, Newtonstr 15, D-12489 Berlin, Germany.
   [Backes, M.; Davids, I. D.; Steenkamp, R.] Univ Namibia, Dept Phys, Private Bag 13301, Windhoek, Namibia.
   [Balzer, A.; Berge, D.; Bryan, M.; Simoni, R.; Vink, J.] Univ Amsterdam, Astron Inst Anton Pannekoek, GRAPPA, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
   [Becherini, Y.; Prokoph, H.] Linnaeus Univ, Dept Phys & Elect Engn, S-35195 Vaxjo, Sweden.
   [Tjus, J. Becker; Krakau, S.; Menzler, U.; Schlickeiser, R.; Weidinger, M.] Ruhr Univ Bochum, Inst Theoret Phys, Lehrstuhl Weltraum & Astrophys 4, D-44780 Bochum, Germany.
   [Berge, D.] Univ Amsterdam, Inst High Energy Phys, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
   [Bernhard, S.; Hadasch, D.; Kolitzus, D.; Oettl, S.; Reimer, A.; Reimer, O.] Leopold Franzens Univ Innsbruck, Inst Astro Teilchenphys, A-6020 Innsbruck, Austria.
   [Blackwell, R.; deWilt, P.; Hawkes, J.; Lau, J.; Rowell, G.; Voisin, F.] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia.
   [Boettcher, M.; Davids, I. D.; Ivascenko, A.; Krueger, P. P.; Pekeur, N. W.; Seyffert, A. S.; Spanier, F.; Sushch, I.; van der Walt, J.; Venter, C.] North West Univ, Ctr Space Res, ZA-2520 Potchefstroom, South Africa.
   [Boisson, C.; Hervet, O.; Rulten, C. B.; Sol, H.; Zech, A.] Univ Paris Diderot, LUTH, Observ Paris, CNRS, 5 Pl Jules Janssen, F-92190 Meudon, France.
   [Bolmont, J.; Chalme-Calvet, R.; Chretien, M.; Couturier, C.; Garrigoux, T.; Jacholkowska, A.; Kerszberg, D.; Kieffer, M.; Lenain, J-P.; Tavernet, J-P.; Vincent, P.] Univ Paris 06, Univ Paris 07, LPNHE, CNRS,IN2P3, 4 Pl Jussieu, F-75252 Paris 5, France.
   [Bregeon, J.; Chaves, R. C. G.; Feinstein, F.; Fernandez, D.; Gallant, Y. A.; Marcowith, A.; Maxted, N.; Renaud, M.; Vasileiadis, G.] Univ Montpellier 2, Lab Universe & Particules Montpellier, CNRS, IN2P3, CC 72,Pl Eugene Bataillon, F-34095 Montpellier 5, France.
   [Brun, F.; Brun, P.; Glicenstein, J. F.; Kosack, K.; Lefranc, V.; Moulin, E.; Peyaud, B.; Schuessler, F.; Wouters, D.] CEA Saclay, DSM, Irfu, F-91191 Gif Sur Yvette, France.
   [Bulik, T.; Grudzinska, M.] Univ Warsaw, Astron Observ, Al Ujazdowskie 4, PL-00478 Warsaw, Poland.
   [Carr, J.; Ernenwein, J-P.] Aix Marseille Univ, CNRS, IN2P3, CPPM,UMR 7346, F-13288 Marseille, France.
   [Casanova, S.; Dyrda, M.; Niemiec, J.; Wierzcholska, A.] Inst Fizyki Jadrowej PAN, Ul Radzikowskiego 152, PL-31342 Krakow, Poland.
   [Chen, A.; Colafrancesco, S.; Komin, Nu.] Univ Witwatersrand, Sch Phys, 1 Jan Smuts Ave, ZA-2050 Johannesburg, South Africa.
   [Cologna, G.; Jankowsky, F.; Mohamed, M.; Quirrenbach, A.; Schwemmer, S.; Wagner, S. J.; Wierzcholska, A.; Zacharias, M.] Heidelberg Univ, Landessternwarte, D-69117 Heidelberg, Germany.
   [Conrad, J.; Farnier, C.; Meyer, M.; Mora, K.; Spengler, G.; Wagner, R. M.] Stockholm Univ, Albanova Univ Ctr, Dept Phys, Oskar Klein Ctr, SE-10691 Stockholm, Sweden.
   [Cui, Y.; Gottschall, D.; Klochkov, D.; Puehlhofer, G.; Santangelo, A.; Sasaki, M.] Univ Tubingen, Inst Astron & Astrophys, Sand 1, D-72076 Tubingen, Germany.
   [Degrange, B.; Fegan, S.; Fontaine, G.; Giebels, B.; Holler, M.; Mariaud, C.; de Naurois, M.; Zaborov, D.; Zefi, F.] Ecole Polytech, CNRS, IN2P3, Lab Leprince Ringuet, F-91128 Palaiseau, France.
   [Djannati-Ata, A.; Espigat, P.; Gabici, S.; Khelifi, B.; Lefaucheur, J.; Lemiere, A.; Pita, S.; Punch, M.; Reichardt, I.; Tavernier, T.; Terrier, R.] Univ Paris Diderot, APC, AstroParticule & Cosmol, CNRS,IN2P3,CEA,Irfu,Observ Paris,Sorbonne Paris C, 10 Rue Alice Domon & Leonie Duquet, F-75205 Paris 13, France.
   [Dubus, G.; Henri, G.; Pelletier, G.; Petrucci, P-O.; Vuillaume, T.] Univ Grenoble Alpes, IPAG, F-38000 Grenoble, France.
   [Dubus, G.; Henri, G.; Pelletier, G.; Petrucci, P-O.; Vuillaume, T.] CNRS, IPAG, F-38000 Grenoble, France.
   [Dutson, K.; Hinton, J. A.; White, R.; Zabalza, V.] Univ Leicester, Dept Phys & Astron, Univ Rd, Leicester LE1 7RH, Leics, England.
   [Dyks, J.; Janiak, M.; Kluzniak, W.; Moderski, R.; Rudak, B.; Zdziarski, A. A.] Nicolaus Copernicus Astron Ctr, Ul Bartycka 18, PL-00716 Warsaw, Poland.
   [Egberts, K.; Hoischen, C.; Stegmann, C.] Univ Potsdam, Inst Phys & Astron, Karl Liebknecht Str 24-25, D-14476 Golm, Germany.
   [Fiasson, A.; Krayzel, F.; Lamanna, G.; Maurin, G.; Rosier-Lees, S.; Sanchez, D. A.; Trichard, C.] Univ Savoie Mt Blanc, Lab Annecy le Vieux Phys Particules, CNRS, IN2P3, F-74941 Annecy Le Vieux, France.
   [Fuessling, M.; Giavitto, G.; Klepser, S.; Ohm, S.; Oya, I.; Schulz, A.; Stegmann, C.; Stycz, K.] DESY, D-15738 Zeuthen, Germany.
   [Goyal, A.; Jamrozy, M.; Ostrowski, M.; Stawarz, L.; Zywucka, N.] Uniwersytet Jagiellonski, Obserwatorium Astron, Ul Orla 171, PL-30244 Krakow, Poland.
   [Grondin, M-H.; Laffon, H.; Lemoine-Goumard, M.] Univ Bordeaux, CNRS, IN2P3, Ctr Etud Nucl Bordeaux Gradignan, F-33175 Gradignan, France.
   [Haeffner, S.; Jung-Richardt, I.; Katz, U.; Lopatin, A.; Raab, S.; Stinzing, F.; Valerius, K.; van Eldik, C.; Veh, J.; Willmann, P.; Woernlein, A.] Univ Erlangen Nurnberg, Phys Inst, Erwin Rommel Str 1, D-91058 Erlangen, Germany.
   [Katarzynski, K.] Nicolaus Copernicus Univ, Fac Phys Astron & Informat, Ctr Astron, Grudziadzka 5, PL-87100 Torun, Poland.
   [Meintjes, P. J.; van Soelen, B.] Univ Orange Free State, Dept Phys, POB 339, ZA-9300 Bloemfontein, South Africa.
   [Rieger, F.] ITA Univ Heidelberg, Heidelberg, Germany.
   [Salek, D.] Univ Amsterdam, Inst High Energy Phys, GRAPPA, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands.
C3 University of Hamburg; Max Planck Society; Dublin Institute for Advanced Studies; National Academy of Sciences of Armenia; Yerevan Physics Institute; Humboldt University of Berlin; University of Namibia; University of Amsterdam; Linnaeus University; Ruhr University Bochum; University of Amsterdam; University of Innsbruck; Adelaide University; University of Adelaide; North West University - South Africa; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Sorbonne Universite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite de Montpellier; CEA; Universite Paris Saclay; University of Warsaw; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Polish Academy of Sciences; Institute of Nuclear Physics - Polish Academy of Sciences; University of Witwatersrand; Ruprecht Karls University Heidelberg; Stockholm University; Oskar Klein Centre; Eberhard Karls University of Tubingen; Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite PSL; Observatoire de Paris; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); University of Leicester; Polish Academy of Sciences; Nicolaus Copernicus Astronomical Center of the Polish Academy of Sciences; University of Potsdam; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite Savoie Mont Blanc; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Jagiellonian University; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Erlangen Nuremberg; Nicolaus Copernicus University; University of the Free State; University of Amsterdam
RP Abramowski, A (corresponding author), Univ Hamburg, Inst Expt Phys, Luruper Chaussee 149, D-22761 Hamburg, Germany.
EM contact.hess@hess-experiment.eu
FU German Ministry for Education and Research (BMBF); Max Planck Society; German Research Foundation (DFG); French Ministry for Research; CNRS-IN2P3; Astroparticle Interdisciplinary Programme of the CNRS; UK Science and Technology Facilities Council (STFC); IPNP of the Charles University; Czech Science Foundation; Polish Ministry of Science and Higher Education; South African Department of Science and Technology; National Research Foundation; University of Namibia; EU FP7 Marie Curie grant [PIEF-GA-2012-332350]; Economic and Social Research Council [ES/N013956/1] Funding Source: researchfish; ESRC [ES/N013956/1] Funding Source: UKRI; STFC [ST/N002881/1] Funding Source: UKRI
NR 47
TC 370
Z9 412
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 476
EP +
DI 10.1038/nature17147
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300034
PM 26982725
DA 2026-03-09
ER

PT J
AU von der Wense, L
   Seiferle, B
   Laatiaoui, M
   Neumayr, JB
   Maier, HJ
   Wirth, HF
   Mokry, C
   Runke, J
   Eberhardt, K
   Düllmann, CE
   Trautmann, NG
   Thirolf, PG
AF von der Wense, Lars
   Seiferle, Benedict
   Laatiaoui, Mustapha
   Neumayr, Juergen B.
   Maier, Hans-Joerg
   Wirth, Hans-Friedrich
   Mokry, Christoph
   Runke, Joerg
   Eberhardt, Klaus
   Duellmann, Christoph E.
   Trautmann, Norbert G.
   Thirolf, Peter G.
TI Direct detection of the 229Th nuclear clock transition
SO NATURE
LA English
DT Article
ID energy; search; decay; spectroscopy; efficiency; level
AB Today's most precise time and frequency measurements are performed with optical atomic clocks. However, it has been proposed that they could potentially be outperformed by a nuclear clock, which employs a nuclear transition instead of an atomic shell transition. There is only one known nuclear state that could serve as a nuclear clock using currently available technology, namely, the isomeric first excited state of Th-229 (denoted Th-229m). Here we report the direct detection of this nuclear state, which is further confirmation of the existence of the isomer and lays the foundation for precise studies of its decay parameters. On the basis of this direct detection, the isomeric energy is constrained to between 6.3 and 18.3 electronvolts, and the half-life is found to be longer than 60 seconds for Th-229m(2+). More precise determinations appear to be within reach, and would pave the way to the development of a nuclear frequency standard.
C1 [von der Wense, Lars; Seiferle, Benedict; Neumayr, Juergen B.; Maier, Hans-Joerg; Wirth, Hans-Friedrich; Thirolf, Peter G.] Univ Munich, D-85748 Garching, Germany.
   [Laatiaoui, Mustapha; Runke, Joerg; Duellmann, Christoph E.] GSI Helmholtzzentrum Schwerionenforsch GmbH, D-64291 Darmstadt, Germany.
   [Laatiaoui, Mustapha; Mokry, Christoph; Eberhardt, Klaus; Duellmann, Christoph E.] Helmholtz Inst Mainz, D-55099 Mainz, Germany.
   [Mokry, Christoph; Runke, Joerg; Eberhardt, Klaus; Duellmann, Christoph E.; Trautmann, Norbert G.] Johannes Gutenberg Univ Mainz, D-55099 Mainz, Germany.
C3 University of Munich; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Johannes Gutenberg University of Mainz
RP von der Wense, L (corresponding author), Univ Munich, D-85748 Garching, Germany.
EM L.Wense@physik.uni-muenchen.de
FU DFG [Th956/3-1]; European Union [664732]; LMU department of Medical Physics via the Maier-Leibnitz Laboratory
NR 64
TC 204
Z9 231
U1 2
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 47
EP +
DI 10.1038/nature17669
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900036
PM 27147026
DA 2026-03-09
ER

PT J
AU Chailangkarn, T
   Trujillo, CA
   Freitas, BC
   Hrvoj-Mihic, B
   Herai, RH
   Yu, DN
   Brown, TT
   Marchetto, MC
   Bardy, C
   McHenry, L
   Stefanacci, L
   Järvinen, A
   Searcy, YM
   DeWitt, M
   Wong, W
   Lai, P
   Ard, MC
   Hanson, KL
   Romero, S
   Jacobs, B
   Dale, AM
   Dai, L
   Korenberg, JR
   Gage, FH
   Bellugi, U
   Halgren, E
   Semendeferi, K
   Muotri, AR
AF Chailangkarn, Thanathom
   Trujillo, Cleber A.
   Freitas, Beatriz C.
   Hrvoj-Mihic, Branka
   Herai, Roberto H.
   Yu, Diana N.
   Brown, Timothy T.
   Marchetto, Maria C.
   Bardy, Cedric
   McHenry, Lauren
   Stefanacci, Lisa
   Jarvinen, Anna
   Searcy, Yvonne M.
   DeWitt, Michelle
   Wong, Wenny
   Lai, Philip
   Ard, M. Colin
   Hanson, Kari L.
   Romero, Sarah
   Jacobs, Bob
   Dale, Anders M.
   Dai, Li
   Korenberg, Julie R.
   Gage, Fred H.
   Bellugi, Ursula
   Halgren, Eric
   Semendeferi, Katerina
   Muotri, Alysson R.
TI A human neurodevelopmental model for Williams syndrome
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; prospective motion correction; human cerebral-cortex; surface-based analysis; human-fetus; gene; brain; mri; frizzled-9; neurons
AB Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome(6,7), we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of postmortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells(8) fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.
C1 [Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Herai, Roberto H.; Stefanacci, Lisa; Romero, Sarah; Muotri, Alysson R.] Univ Calif San Diego, Sch Med, UCSD Stem Cell Program, Dept Pediat,Rady Childrens Hosp San Diego, La Jolla, CA 92037 USA.
   [Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Herai, Roberto H.; Stefanacci, Lisa; Romero, Sarah; Muotri, Alysson R.] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.
   [Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Herai, Roberto H.; Stefanacci, Lisa; Romero, Sarah; Muotri, Alysson R.] CARTA, La Jolla, CA 92093 USA.
   [Chailangkarn, Thanathom] Natl Ctr Genet Engn & Biotechnol BIOTEC, Virol & Cell Technol Lab, Pathum Thani 12120, Thailand.
   [Hrvoj-Mihic, Branka; Stefanacci, Lisa; Hanson, Kari L.; Semendeferi, Katerina] Univ Calif San Diego, Dept Anthropol, La Jolla, CA 92093 USA.
   [Herai, Roberto H.] Pontificia Univ Catolica Parana PUCPR, Grad Program Hlth Sci, Sch Med, Curitiba, Parana, Brazil.
   [Yu, Diana N.; Marchetto, Maria C.; Bardy, Cedric; McHenry, Lauren; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Brown, Timothy T.; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 USA.
   [Brown, Timothy T.; Ard, M. Colin; Halgren, Eric] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA.
   [Brown, Timothy T.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA.
   [Bardy, Cedric] Flinders Univ S Australia, SAHMRI Mind & Brain Theme, Sch Med, Lab Human Neurophysiol & Genet, Adelaide, SA 5000, Australia.
   [Jarvinen, Anna; Searcy, Yvonne M.; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Bellugi, Ursula] Salk Inst Biol Studies, Lab Cognit Neurosci, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Jacobs, Bob] Colorado Coll, Dept Psychol, Colorado Springs, CO 80903 USA.
   [Dale, Anders M.] Univ Calif San Diego, Sch Med, Dept Radiol, La Jolla, CA 92093 USA.
   [Dale, Anders M.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
   [Dai, Li; Korenberg, Julie R.] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA.
   [Dai, Li; Korenberg, Julie R.] Univ Utah, Inst Brain, Salt Lake City, UT 84108 USA.
   [Gage, Fred H.; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R.] Univ Calif San Diego, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.
   [Semendeferi, Katerina; Muotri, Alysson R.] Univ Calif San Diego, Neurosci Grad Program, Sch Med, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Rady Childrens Hospital San Diego; University of California System; University of California San Diego; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); University of California System; University of California San Diego; Pontificia Universidade Catolica do Parana; Salk Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Flinders University; South Australian Health & Medical Research Institute (SAHMRI); Salk Institute; Colorado College; University of California System; University of California San Diego; University of California System; University of California San Diego; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Muotri, AR (corresponding author), Univ Calif San Diego, Sch Med, UCSD Stem Cell Program, Dept Pediat,Rady Childrens Hosp San Diego, La Jolla, CA 92037 USA.; Muotri, AR (corresponding author), Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.; Muotri, AR (corresponding author), CARTA, La Jolla, CA 92093 USA.; Semendeferi, K (corresponding author), Univ Calif San Diego, Dept Anthropol, La Jolla, CA 92093 USA.; Semendeferi, K; Muotri, AR (corresponding author), Univ Calif San Diego, Kavli Inst Brain & Mind, La Jolla, CA 92093 USA.; Semendeferi, K; Muotri, AR (corresponding author), Univ Calif San Diego, Neurosci Grad Program, Sch Med, La Jolla, CA 92093 USA.
EM ksemende@ucsd.edu; muotri@ucsd.edu
FU California Institute for Regenerative Medicine (CIRM) [TR2-01814, TR4-06747]; National Institutes of Health (NIH) [P01 NICHD033113]; NIH Director's New Innovator Award Program [1-DP2-OD006495-01, R01MH094753, R01MH103134, U19MH107367, U19MH106434, R01MH095741]; National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Grant; JPB Foundation; Paul G. Allen Family Foundation; Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]; G. Harold & Leila Y. Mathers Foundation; Royal Thai Government Scholarship; CIRM postdoctoral fellowship; Rita L. Atkinson Graduate fellowship; University of California San Diego Kavli Institute for Brain and Mind; National Institute of Mental Health [R01MH100175] Funding Source: NIH RePORTER; National Institute on Deafness and Other Communication Disorders [T32DC007361] Funding Source: NIH RePORTER
NR 59
TC 139
Z9 179
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 338
EP +
DI 10.1038/nature19067
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900037
PM 27509850
DA 2026-03-09
ER

PT J
AU Hacker, B
   Welte, S
   Rempe, G
   Ritter, S
AF Hacker, Bastian
   Welte, Stephan
   Rempe, Gerhard
   Ritter, Stephan
TI A photon-photon quantum gate based on a single atom in an optical resonator
SO NATURE
LA English
DT Article
ID switch
AB That two photons pass each other undisturbed in free space is ideal for the faithful transmission of information, but prohibits an interaction between the photons. Such an interaction is, however, required for a plethora of applications in optical quantum information processing(1). The long-standing challenge here is to realize a deterministic photon-photon gate, that is, a mutually controlled logic operation on the quantum states of the photons. This requires an interaction so strong that each of the two photons can shift the other's phase by pi radians. For polarization qubits, this amounts to the conditional flipping of one photon's polarization to an orthogonal state. So far, only probabilistic gates(2) based on linear optics and photon detectors have been realized(3), because "no known or foreseen material has an optical nonlinearity strong enough to implement this conditional phase shift"(4). Meanwhile, tremendous progress in the development of quantum-nonlinear systems has opened up new possibilities for single-photon experiments(5). Platforms range from Rydberg blockade in atomic ensembles(6) to single-atom cavity quantum electrodynamics(7). Applications such as single-photon switches(8) and transistors(9,10), two-photon gateways(11), nondestructive photon detectors(12), photon routers(13) and nonlinear phase shifters(14-18) have been demonstrated, but none of them with the ideal information carriers: optical qubits in discriminable modes. Here we use the strong light-matter coupling provided by a single atom in a high-finesse optical resonator to realize the Duan-Kimble protocol(19) of a universal controlled phase flip (p phase shift) photon-photon quantum gate. We achieve an average gate fidelity of (76.2 +/- 3.6) per cent and specifically demonstrate the capability of conditional polarization flipping as well as entanglement generation between independent input photons. This photon-photon quantum gate is a universal quantum logic element, and therefore could perform most existing two-photon operations. The demonstrated feasibility of deterministic protocols for the optical processing of quantum information could lead to new applications in which photons are essential, especially long-distance quantum communication and scalable quantum computing.
C1 [Hacker, Bastian; Welte, Stephan; Rempe, Gerhard; Ritter, Stephan] Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
C3 Max Planck Society
RP Ritter, S (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM stephan.ritter@mpq.mpg.de
FU European Union (Collaborative Project SIQS); Bundesministerium fur Bildung und Forschung [IKT 2020]; Deutsche Forschungsgemeinschaft via the excellence cluster Nanosystems Initiative Munich (NIM); doctorate programme Exploring Quantum Matter (ExQM)
NR 30
TC 278
Z9 324
U1 8
U2 244
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 193
EP +
DI 10.1038/nature18592
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100032
PM 27383791
DA 2026-03-09
ER

PT J
AU Saotome, K
   Singh, AK
   Yelshanskaya, MV
   Sobolevsky, AI
AF Saotome, Kei
   Singh, Appu K.
   Yelshanskaya, Maria V.
   Sobolevsky, Alexander I.
TI Crystal structure of the epithelial calcium channel TRPV6
SO NATURE
LA English
DT Article
ID cryoelectron microscopy structure; membrane; calmodulin; identification; activation; proteins
AB Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca2+-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca2+ uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca2+ permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 angstrom resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K+ channel-like transmembrane domain, Ca2+ selectivity is determined by direct coordination of Ca2+ by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca2+ permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca2+ uptake and its role in pathophysiology.
C1 [Saotome, Kei; Singh, Appu K.; Yelshanskaya, Maria V.; Sobolevsky, Alexander I.] Columbia Univ, Dept Biochem & Mol Biophys, 680 West 168th St, New York, NY 10032 USA.
C3 Columbia University
RP Sobolevsky, AI (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 680 West 168th St, New York, NY 10032 USA.
EM as4005@cumc.columbia.edu
FU National Institutes of Health [R01 NS083660, T32 GM008281]; Pew Scholar Award in Biomedical Sciences; Schaefer Research Scholar Award; Klingenstein Fellowship Award in the Neurosciences; Irma T. Hirschl Career Scientist Award; National Institute of Neurological Disorders and Stroke [R01NS083660] Funding Source: NIH RePORTER
NR 48
TC 189
Z9 217
U1 1
U2 59
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 506
EP +
DI 10.1038/nature17975
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300044
PM 27296226
DA 2026-03-09
ER

PT J
AU Sapparapu, G
   Fernandez, E
   Kose, N
   Cao, B
   Fox, JM
   Bombardi, RG
   Zhao, HY
   Nelson, CA
   Bryan, AL
   Barnes, T
   Davidson, E
   Mysorekar, IU
   Fremont, DH
   Doranz, BJ
   Diamond, MS
   Crowe, JE
AF Sapparapu, Gopal
   Fernandez, Estefania
   Kose, Nurgun
   Cao, Bin
   Fox, Julie M.
   Bombardi, Robin G.
   Zhao, Haiyan
   Nelson, Christopher A.
   Bryan, Aubrey L.
   Barnes, Trevor
   Davidson, Edgar
   Mysorekar, Indira U.
   Fremont, Daved H.
   Doranz, Benjamin J.
   Diamond, Michael S.
   Crowe, James E., Jr.
TI Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice
SO NATURE
LA English
DT Article
ID west-nile-virus; monoclonal-antibody; cross-reactivity; infection; pregnancy; enhancement; protection; exposure
AB Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy(1). To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.
C1 [Sapparapu, Gopal; Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
   [Sapparapu, Gopal; Kose, Nurgun; Bombardi, Robin G.; Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA.
   [Fernandez, Estefania; Zhao, Haiyan; Nelson, Christopher A.; Mysorekar, Indira U.; Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
   [Cao, Bin; Mysorekar, Indira U.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
   [Fox, Julie M.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Bryan, Aubrey L.; Barnes, Trevor; Davidson, Edgar; Doranz, Benjamin J.] Integral Mol, Philadelphia, PA USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.
   [Crowe, James E., Jr.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA.
C3 Vanderbilt University; Vanderbilt University; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Vanderbilt University
RP Crowe, JE (corresponding author), Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.; Crowe, JE (corresponding author), Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37232 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.; Diamond, MS (corresponding author), Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA.; Crowe, JE (corresponding author), Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM diamond@wusm.wustl.edu; james.crowe@vanderbilt.edu
FU US N.I.H. [R01 AI073755, R01 AI104972, HHSN272201400024C, HHSN272201400058C, HHSN272201400018C, HHSN272201200026C]; Preventing Prematurity Initiative grant from the Burroughs Wellcome Fund; March of Dimes; N.I.H. [T32 AI007163]; National Institute of Allergy and Infectious Diseases [R01AI073755] Funding Source: NIH RePORTER
NR 33
TC 336
Z9 411
U1 1
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 443
EP +
DI 10.1038/nature20564
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800044
PM 27819683
DA 2026-03-09
ER

PT J
AU Cho, SH
   Raybuck, AL
   Stengel, K
   Wei, M
   Beck, TC
   Volanakis, E
   Thomas, JW
   Hiebert, S
   Haase, VH
   Boothby, MR
AF Cho, Sung Hoon
   Raybuck, Ariel L.
   Stengel, Kristy
   Wei, Mei
   Beck, Thomas C.
   Volanakis, Emmanuel
   Thomas, James W.
   Hiebert, Scott
   Haase, Volker H.
   Boothby, Mark R.
TI Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system
SO NATURE
LA English
DT Article
ID class switch recombination; inducible factor-i; flow-cytometry; mtor; inflammation; disease; cells; activation; expression; selection
AB Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory(1,2). Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class(3,4), both cell-autonomous5 and extrinsic(6,7) metabolic programming have emerged as modulators of T-cell-mediated immunity(8). Here we show in mice that GC light zones are hypoxic, and that low oxygen tension (p(O2)) alters B cell physiology and function. In addition to reduced proliferation and increased B cell death, low p(O2) impairs antibody class switching to the pro-inflammatory IgG2c antibody isotype by limiting the expression of activation-induced cytosine deaminase (AID). Hypoxia induces HIF transcription factors by restricting the activity of prolyl hydroxyl dioxygenase enzymes, which hydroxylate HIF-1 alpha and HIF-2 alpha to destabilize HIF by binding the von Hippel-Landau tumour suppressor protein (pVHL)(7). B-cell-specific depletion of pVHL leads to constitutive HIF stabilization, decreases antigen-specific GC B cells and undermines the generation of high-affinity IgG, switching to IgG2c, early memory B cells, and recall antibody responses. HIF induction can reprogram metabolic and growth factor gene expression. Sustained hypoxia or HIF induction by pVHL deficiency inhibits mTOR complex 1 (mTORC1) activity in B lymphoblasts, and mTORC1-haploinsufficient B cells have reduced clonal expansion, AID expression, and capacities to yield IgG2c and high-affinity antibodies. Thus, the normal physiology of GCs involves regional variegation of hypoxia, and HIF-dependent oxygen sensing regulates vital functions of B cells. We propose that the restriction of oxygen in lymphoid organs, which can be altered in pathophysiological states, modulates humoral immunity.
C1 [Cho, Sung Hoon; Raybuck, Ariel L.; Wei, Mei; Beck, Thomas C.; Thomas, James W.; Boothby, Mark R.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
   [Stengel, Kristy; Hiebert, Scott] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
   [Volanakis, Emmanuel] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA.
   [Thomas, James W.; Haase, Volker H.; Boothby, Mark R.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA.
   [Hiebert, Scott; Haase, Volker H.; Boothby, Mark R.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA.
   [Hiebert, Scott; Haase, Volker H.; Boothby, Mark R.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
   [Haase, Volker H.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Med & Res Serv, Nashville, TN 37212 USA.
C3 Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Tennessee Valley Healthcare System
RP Boothby, MR (corresponding author), Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.; Boothby, MR (corresponding author), Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA.; Boothby, MR (corresponding author), Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA.; Boothby, MR (corresponding author), Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
EM mark.boothby@vanderbilt.edu
FU National Institutes of Health (NIH) [R01 AI113292, HL106812, CA164605]; Veterans Affairs Merit award [I01 BX002348]; American Cancer Society [PF-13-303-01-DMC]; Cancer Center Support Grant [CA068485]; Diabetes Research Center [DK0205930];  [T32 DK007563]; National Cancer Institute [P30CA068485, T32CA009582, R01CA164605] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI051448] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK081646, T32DK007563] Funding Source: NIH RePORTER
NR 35
TC 249
Z9 279
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 234
EP +
DI 10.1038/nature19334
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100048
PM 27501247
DA 2026-03-09
ER

PT J
AU Zhao, MT
   Yuan, K
   Wang, Y
   Li, GD
   Guo, J
   Gu, L
   Hu, WP
   Zhao, HJ
   Tang, ZY
AF Zhao, Meiting
   Yuan, Kuo
   Wang, Yun
   Li, Guodong
   Guo, Jun
   Gu, Lin
   Hu, Wenping
   Zhao, Huijun
   Tang, Zhiyong
TI Metal-organic frameworks as selectivity regulators for hydrogenation reactions
SO NATURE
LA English
DT Article
ID generation vibrational spectroscopy; alpha,beta-unsaturated aldehydes; chemoselective hydrogenation; catalysts; nanoparticles; oxidation; crotonaldehyde; nanostructure; nanocrystals; oxygen
AB Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them from alpha,beta-unsaturated aldehydes, through the selective hydrogenation of the carbon-oxygen group (in preference to the carboncarbon group)(1). However, developing effective catalysts for this transformation is challenging(2-7), because hydrogenation of the carbon-carbon group is thermodynamically favoured(8). This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not(9-14). This has inspired the use of metal-organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material(15-18). Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of alpha,beta-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe3+, Cr3+ or both (known as MIL-101; refs 19-21) results in stable catalysts that convert a range of alpha,beta-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon-oxygen rather than the carboncarbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.
C1 [Zhao, Meiting; Yuan, Kuo; Li, Guodong; Guo, Jun; Tang, Zhiyong] Chinese Acad Sci, CAS Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, Key Lab Nanosyst & Hierarchy Fabricat, Beijing 100190, Peoples R China.
   [Yuan, Kuo; Hu, Wenping] Tianjin Univ, Sch Sci, Tianjin 300072, Peoples R China.
   [Wang, Yun; Zhao, Huijun] Griffith Univ, Ctr Clean Environm & Energy, Gold Coast Campus, Nathan, Qld 4222, Australia.
   [Gu, Lin] Chinese Acad Sci, Inst Phys, Beijing 100190, Peoples R China.
   [Hu, Wenping] Chinese Acad Sci, Inst Chem, Beijing 100190, Peoples R China.
C3 Chinese Academy of Sciences; National Center for Nanoscience & Technology, CAS; Tianjin University; Griffith University; Chinese Academy of Sciences; Institute of Physics, CAS; Chinese Academy of Sciences; Institute of Chemistry, CAS
RP Li, GD; Tang, ZY (corresponding author), Chinese Acad Sci, CAS Ctr Excellence Nanosci, Natl Ctr Nanosci & Technol, Key Lab Nanosyst & Hierarchy Fabricat, Beijing 100190, Peoples R China.; Zhao, HJ (corresponding author), Griffith Univ, Ctr Clean Environm & Energy, Gold Coast Campus, Nathan, Qld 4222, Australia.
EM liguodong@nanoctr.cn; h.zhao@griffith.edu.au; zytang@nanoctr.cn
FU National Research Fund for Fundamental Key Project [2014CB931801]; National Natural Science Foundation of China [21475029, 91427302, 21303029]; Instrument Developing Project of the Chinese Academy of Sciences [YZ201311]; CAS-CSIRO Cooperative Research Program [GJHZ1503]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA09040100]; Youth Innovation Promotion Association CAS [2016036]
NR 30
TC 1356
Z9 1430
U1 49
U2 3126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 76
EP 80
DI 10.1038/nature19763
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100032
PM 27706142
DA 2026-03-09
ER

PT J
AU Huang, XH
   Yang, SH
   Gong, JY
   Zhao, Q
   Feng, Q
   Zhan, QL
   Zhao, Y
   Li, WJ
   Cheng, BY
   Xia, JH
   Chen, N
   Huang, T
   Zhang, L
   Fan, DL
   Chen, JY
   Zhou, CC
   Lu, YQ
   Weng, QJ
   Han, B
AF Huang, Xuehui
   Yang, Shihua
   Gong, Junyi
   Zhao, Qiang
   Feng, Qi
   Zhan, Qilin
   Zhao, Yan
   Li, Wenjun
   Cheng, Benyi
   Xia, Junhui
   Chen, Neng
   Huang, Tao
   Zhang, Lei
   Fan, Danlin
   Chen, Jiaying
   Zhou, Congcong
   Lu, Yiqi
   Weng, Qijun
   Han, Bin
TI Genomic architecture of heterosis for yield traits in rice
SO NATURE
LA English
DT Article
ID cytoplasmic male-sterility; hybrid rice; wide association; gene; locus; maize; component; osspl14; system; allele
AB Increasing grain yield is a long-term goal in crop breeding to meet the demand for global food security. Heterosis, when a hybrid shows higher performance for a trait than both parents, offers an important strategy for crop breeding. To examine the genetic basis of heterosis for yield in rice, here we generate, sequence and record the phenotypes of 10,074 F-2 lines from 17 representative hybrid rice crosses. We classify modern hybrid rice varieties into three groups, representing different hybrid breeding systems. Although we do not find any heterosis-associated loci shared across all lines, within each group, a small number of genomic loci from female parents explain a large proportion of the yield advantage of hybrids over their male parents. For some of these loci, we find support for partial dominance of heterozygous locus for yield-related traits and better-parent heterosis for overall performance when all of the grain-yield traits are considered together. These results inform on the genomic architecture of heterosis and rice hybrid breeding.
C1 [Huang, Xuehui; Zhao, Qiang; Feng, Qi; Zhan, Qilin; Zhao, Yan; Li, Wenjun; Huang, Tao; Zhang, Lei; Fan, Danlin; Chen, Jiaying; Zhou, Congcong; Lu, Yiqi; Weng, Qijun; Han, Bin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Natl Ctr Gene Res,CAS Ctr Excellence Mol Plant Sc, Shanghai 200233, Peoples R China.
   [Yang, Shihua; Gong, Junyi; Cheng, Benyi; Xia, Junhui; Chen, Neng] Chinese Acad Agr Sci, China Natl Rice Res Inst, Key Lab Rice Biol, Hangzhou 310006, Zhejiang, Peoples R China.
C3 Chinese Academy of Sciences; Chinese Academy of Agricultural Sciences; China National Rice Research Institute, CAAS
RP Huang, XH; Han, B (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Natl Ctr Gene Res,CAS Ctr Excellence Mol Plant Sc, Shanghai 200233, Peoples R China.
EM xhhuang@ncgr.ac.cn; bhan@ncgr.ac.cn
FU Chinese Academy of Sciences [XDA08020101]; National Natural Science Foundation of China [31322028, 91535202, 31421093, 31301302]
NR 45
TC 357
Z9 420
U1 8
U2 402
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 629
EP +
DI 10.1038/nature19760
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700039
PM 27602511
DA 2026-03-09
ER

PT J
AU Wang, KH
   Fredens, J
   Brunner, SF
   Kim, SH
   Chia, TS
   Chin, JW
AF Wang, Kaihang
   Fredens, Julius
   Brunner, Simon F.
   Kim, Samuel H.
   Chia, Tiongsun
   Chin, Jason W.
TI Defining synonymous codon compression schemes by genome recoding
SO NATURE
LA English
DT Article
ID unnatural amino-acids; escherichia-coli; chemical-synthesis; protein-synthesis; gene-expression; synthetic dna; cell-division; translation; cloning; rates
AB Synthetic recoding of genomes, to remove targeted sense codons, may facilitate the encoded cellular synthesis of unnatural polymers by orthogonal translation systems. However, our limited understanding of allowed synonymous codon substitutions, and the absence of methods that enable the stepwise replacement of the Escherichia coli genome with long synthetic DNA and provide feedback on allowed and disallowed design features in synthetic genomes, have restricted progress towards this goal. Here we endow E. coli with a system for efficient, programmable replacement of genomic DNA with long (>100-kb) synthetic DNA, through the in vivo excision of double-stranded DNA from an episomal replicon by CRISPR/Cas9, coupled to lambda-red-mediated recombination and simultaneous positive and negative selection. We iterate the approach, providing a basis for stepwise whole-genome replacement. We attempt systematic recoding in an essential operon using eight synonymous recoding schemes. Each scheme systematically replaces target codons with defined synonyms and is compatible with codon reassignment. Our results define allowed and disallowed synonymous recoding schemes, and enable the identification and repair of recoding at idiosyncratic positions in the genome.
C1 [Wang, Kaihang; Fredens, Julius; Brunner, Simon F.; Kim, Samuel H.; Chia, Tiongsun; Chin, Jason W.] Med Res Council Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
   [Kim, Samuel H.; Chin, Jason W.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
C3 UK Research & Innovation (UKRI); Medical Research Council UK (MRC); MRC Laboratory Molecular Biology; University of Cambridge
RP Wang, KH; Chin, JW (corresponding author), Med Res Council Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM kaihang@mrc-lmb.cam.ac.uk; chin@mrc-lmb.cam.ac.uk
FU Medical Research Council, UK [MC_U105181009, MC_UP_A024_1008]; Danish Council for Independent Research [DFF - 4090-00289]; Boehringer Ingelheim Fonds PhD fellowship; Gates-Cambridge Scholarship; ERC Advanced Grant; Medical Research Council [MC_UP_A024_1008, MC_U105181009] Funding Source: researchfish; MRC [MC_U105181009] Funding Source: UKRI
NR 47
TC 136
Z9 175
U1 4
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 59
EP +
DI 10.1038/nature20124
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100028
PM 27776354
DA 2026-03-09
ER

PT J
AU Irwin, JA
   Maksym, WP
   Sivakoff, GR
   Romanowsky, AJ
   Lin, DC
   Speegle, T
   Prado, I
   Mildebrath, D
   Strader, J
   Liu, JF
   Miller, JM
AF Irwin, Jimmy A.
   Maksym, W. Peter
   Sivakoff, Gregory R.
   Romanowsky, Aaron J.
   Lin, Dacheng
   Speegle, Tyler
   Prado, Ian
   Mildebrath, David
   Strader, Jay
   Liu, Jifeng
   Miller, Jon M.
TI Ultraluminous X-ray bursts in two ultracompact companions to nearby elliptical galaxies
SO NATURE
LA English
DT Article
ID globular-cluster system; acs virgo cluster; dwarf galaxy; ngc-5128; field; binary; distance; flares; population; centaurus
AB A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares(1), but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 10(39) erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares. We found two ultraluminous flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 x 10(40) erg per second; the other flared five times to 10(40) erg per second. The rise times of all of the flares were less than one minute, and the flares then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron-star or black-hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft gamma repeaters that have repetitive flares of similar luminosities.
C1 [Irwin, Jimmy A.; Speegle, Tyler; Prado, Ian; Mildebrath, David] Univ Alabama, Dept Phys & Astron, Box 870324, Tuscaloosa, AL 35487 USA.
   [Maksym, W. Peter] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
   [Sivakoff, Gregory R.] Univ Alberta, Dept Phys, CCIS 4-181, Edmonton, AB T6G 2E1, Canada.
   [Romanowsky, Aaron J.] San Jose State Univ, Dept Phys & Astron, One Washington Sq, San Jose, CA 95192 USA.
   [Romanowsky, Aaron J.] Univ Calif Observ, 1156 High St, Santa Cruz, CA 95064 USA.
   [Lin, Dacheng] Univ New Hampshire, Ctr Space Sci, Durham, NH 03824 USA.
   [Strader, Jay] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Liu, Jifeng] Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, 20A Datun Rd, Beijing 100012, Peoples R China.
   [Liu, Jifeng] Univ Chinese Acad Sci, Coll Astron & Space Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China.
   [Miller, Jon M.] Univ Michigan, Dept Astron, 1085 South Univ Ave, Ann Arbor, MI 48103 USA.
C3 University of Alabama System; University of Alabama Tuscaloosa; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of Alberta; California State University System; San Jose State University; University of California System; University of California Santa Cruz; University System Of New Hampshire; University of New Hampshire; Michigan State University; Chinese Academy of Sciences; National Astronomical Observatory, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; University of Michigan System; University of Michigan
RP Irwin, JA (corresponding author), Univ Alabama, Dept Phys & Astron, Box 870324, Tuscaloosa, AL 35487 USA.
EM jairwin@ua.edu
FU Chandra grant [AR6-17010X]; NASA ADAP [NNX10AE15G]; NSERC; National Science Foundation [AST-1515084]; NSF [AST-1308124, AST-1514763]; Packard Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1514763] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1515084] Funding Source: National Science Foundation; NASA [135153, NNX10AE15G] Funding Source: Federal RePORTER
NR 33
TC 54
Z9 59
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 356
EP +
DI 10.1038/nature19822
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100033
PM 27762351
DA 2026-03-09
ER

PT J
AU Ohto, U
   Ishida, H
   Krayukhina, E
   Uchiyama, S
   Inoue, N
   Shimizu, T
AF Ohto, Umeharu
   Ishida, Hanako
   Krayukhina, Elena
   Uchiyama, Susumu
   Inoue, Naokazu
   Shimizu, Toshiyuki
TI Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization
SO NATURE
LA English
DT Article
ID crystal-structure; protein izumo; egg fusion; ultracentrifugation; folate; juno
AB Fertilization is a fundamental process in sexual reproduction, creating a new individual through the combination of male and female gametes(1-4). The IZUMO1 sperm membrane protein(5) and its counterpart oocyte receptor JUNO(6) have been identified as essential factors for sperm-oocyte interaction and fusion. However, the mechanism underlying their specific recognition remains poorly defined. Here, we show the crystal structures of human IZUMO1, JUNO and the IZUMO1-JUNO complex, establishing the structural basis for the IZUMO1-JUNO-mediated sperm-oocyte interaction. IZUMO1 exhibits an elongated rod-shaped structure comprised of a helical bundle IZUMO domain and an immunoglobulin-like domain that are each firmly anchored to an intervening beta-hairpin region through conserved disulfide bonds. The central beta-hairpin region of IZUMO1 provides the main platform for JUNO binding, while the surface located behind the putative JUNO ligand binding pocket is involved in IZUMO1 binding. Structure-based mutagenesis analysis confirms the biological importance of the IZUMO1-JUNO interaction. This structure provides a major step towards elucidating an essential phase of fertilization and it will contribute to the development of new therapeutic interventions for fertility, such as contraceptive agents.
C1 [Ohto, Umeharu; Ishida, Hanako; Shimizu, Toshiyuki] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Krayukhina, Elena; Uchiyama, Susumu] Osaka Univ, Grad Sch Engn, 2-1 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Uchiyama, Susumu] Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan.
   [Inoue, Naokazu] Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Cell Sci, 1 Hikarigaoka, Fukushima, Fukushima 9601295, Japan.
C3 University of Tokyo; University of Osaka; National Institutes of Natural Sciences (NINS) - Japan; Okazaki Institute for Integrative Bioscience (OIIB); Fukushima Medical University
RP Ohto, U; Shimizu, T (corresponding author), Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan.
EM umeji@mol.f.u-tokyo.ac.jp; shimizu@mol.f.u-tokyo.ac.jp
FU Japan Agency for Medical Research and Development (AMED); Japanese Ministry of Education, Culture, Sports, Science, and Technology; CREST, JST; Takeda Science Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Daiichi Sankyo Foundation of Life Science; Grants-in-Aid for Scientific Research [26291052] Funding Source: KAKEN
NR 29
TC 117
Z9 135
U1 1
U2 53
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 566
EP +
DI 10.1038/nature18596
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300057
PM 27309808
DA 2026-03-09
ER

PT J
AU Forbes, JC
   Krumholz, MR
   Goldbaum, NJ
   Dekel, A
AF Forbes, John C.
   Krumholz, Mark R.
   Goldbaum, Nathan J.
   Dekel, Avishai
TI Suppression of star formation in dwarf galaxies by photoelectric grain heating feedback
SO NATURE
LA English
DT Article
ID adaptive mesh refinement; cold dark-matter; interstellar-medium; molecular-hydrogen; stellar feedback; formation law; mass function; high-redshift; h i; evolution
AB Photoelectric heating-heating of dust grains by far-ultraviolet photons-has long been recognized as the primary source of heating for the neutral interstellar medium(1). Simulations of spiral galaxies(2) have shown some indication that photoelectric heating could suppress star formation; however, simulations that include photoelectric heating have typically shown that it has little effect on the rate of star formation in either spiral galaxies(3,4) or dwarf galaxies(5), which suggests that supernovae are responsible for setting the gas depletion time in galaxies(6-8). This result is in contrast with recent work(9-13) indicating that a star formation law that depends on galaxy metallicity-as is expected with photoelectric heating, but not with supernovae-reproduces the present-day galaxy population better than does a metallicity-independent one. Here we report a series of simulations of dwarf galaxies, the class of galaxy in which the effects of both photoelectric heating and supernovae are expected to be strongest. We simultaneously include space-and time-dependent photoelectric heating in our simulations, and we resolve the energy-conserving phase of every supernova blast wave, which allows us to directly measure the relative importance of feedback by supernovae and photoelectric heating in suppressing star formation. We find that supernovae are unable to account for the observed(14) large gas depletion times in dwarf galaxies. Instead, photoelectric heating is the dominant means by which dwarf galaxies regulate their star formation rate at any given time, suppressing the rate by more than an order of magnitude relative to simulations with only supernovae.
C1 [Forbes, John C.; Krumholz, Mark R.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Krumholz, Mark R.] Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2611, Australia.
   [Goldbaum, Nathan J.] Univ Illinois, Natl Ctr Supercomp Applicat, 1205 West Clark St, Urbana, IL 61820 USA.
   [Dekel, Avishai] Hebrew Univ Jerusalem, Racah Inst Phys, Ctr Astrophys & Planetary Sci, IL-91904 Jerusalem, Israel.
C3 University of California System; University of California Santa Cruz; Australian National University; University of Illinois System; University of Illinois Urbana-Champaign; Hebrew University of Jerusalem
RP Forbes, JC (corresponding author), Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
EM jcforbes@ucsc.edu
FU Hubble Archival Research grant [HST-AR-13909]; NSF [AST-09553300, AST-1405962, AST-1229745]; NASA ATP grant [NNX13AB84G]; NASA TCAN grant [NNX14AB52G]; Australian Research Council [DP160100695]; ISF [124/12]; I-CORE Program of the PBC/ISF [1829/12]; BSF [2014-273]; NASA [476434, NNX13AB84G, 686542, NNX14AB52G] Funding Source: Federal RePORTER; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1405962] Funding Source: National Science Foundation; Office of Advanced Cyberinfrastructure (OAC); Direct For Computer & Info Scie & Enginr [1535651] Funding Source: National Science Foundation
NR 43
TC 56
Z9 63
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 523
EP +
DI 10.1038/nature18292
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600022
PM 27350244
DA 2026-03-09
ER

PT J
AU Morgan, JLW
   McNamara, JT
   Fischer, M
   Rich, J
   Chen, HM
   Withers, SG
   Zimmer, J
AF Morgan, Jacob L. W.
   McNamara, Joshua T.
   Fischer, Michael
   Rich, Jamie
   Chen, Hong-Ming
   Withers, Stephen G.
   Zimmer, Jochen
TI Observing cellulose biosynthesis and membrane translocation in crystallo
SO NATURE
LA English
DT Article
ID neisseria-meningitidis; synthase; dynamics; glycosyltransferases; polymerization; stabilization; mechanism; protein; system
AB Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. Here, in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA-BcsB complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate-and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a 'finger helix' that contacts the polymer's terminal glucose. Cooperating with BcsA's gating loop, the finger helix moves 'up' and 'down' in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA's transmembrane channel. This mechanism is validated experimentally by tethering BcsA's finger helix, which inhibits polymer translocation but not elongation.
C1 [Morgan, Jacob L. W.; McNamara, Joshua T.; Zimmer, Jochen] Univ Virginia, Sch Med, Ctr Membrane Biol Mol Physiol & Biol Phys, 480 Ray C Hunt Dr, Charlottesville, VA 22908 USA.
   [Fischer, Michael; Rich, Jamie; Chen, Hong-Ming; Withers, Stephen G.] Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
   [Fischer, Michael] Sandoz GmbH, Biochem Str 10, A-6250 Kundl, Austria.
   [Rich, Jamie] Kairos Therapeut, 2405 Wesbrook Mall,Fourth Floor, Vancouver, BC V6T 1Z3, Canada.
C3 University of Virginia; University of British Columbia; Novartis; NOVARTIS AUSTRIA; Sandoz
RP Zimmer, J (corresponding author), Univ Virginia, Sch Med, Ctr Membrane Biol Mol Physiol & Biol Phys, 480 Ray C Hunt Dr, Charlottesville, VA 22908 USA.
EM jochen_zimmer@virginia.edu
FU Federal funds from the National Cancer Institute [ACB-12002]; National Institute of General Medical Sciences [AGM-12006]; National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]; NIH-ORIP HEI grant [S10 RR029205]; DOE Office of Science [DE-AC02-06CH11357]; National Science Foundation Graduate Research Fellowship [DGE-1315231]; Austrian Science Fund (FWF) [J3293-B21]; National Institutes of Health [1R01GM101001]; Natural Sciences and Engineering Research Council of Canada; National Institute of General Medical Sciences [R01GM101001] Funding Source: NIH RePORTER
NR 36
TC 129
Z9 145
U1 4
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 329
EP +
DI 10.1038/nature16966
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300044
PM 26958837
DA 2026-03-09
ER

PT J
AU Katmis, F
   Lauter, V
   Nogueira, FS
   Assaf, BA
   Jamer, ME
   Wei, P
   Satpati, B
   Freeland, JW
   Eremin, I
   Heiman, D
   Jarillo-Herrero, P
   Moodera, JS
AF Katmis, Ferhat
   Lauter, Valeria
   Nogueira, Flavio S.
   Assaf, Badih A.
   Jamer, Michelle E.
   Wei, Peng
   Satpati, Biswarup
   Freeland, John W.
   Eremin, Ilya
   Heiman, Don
   Jarillo-Herrero, Pablo
   Moodera, Jagadeesh S.
TI A high-temperature ferromagnetic topological insulating phase by proximity coupling
SO NATURE
LA English
DT Article
ID majorana fermions; surface
AB Topological insulators are insulating materials that display conducting surface states protected by time-reversal symmetry(1,)2, wherein electron spins are locked to their momentum. This unique property opens up new opportunities for creating next-generation electronic, spintronic and quantum computation devices(3-5). Introducing ferromagnetic order into a topological insulator system without compromising its distinctive quantum coherent features could lead to the realization of several predicted physical phenomena(6,7). In particular, achieving robust long-range magnetic order at the surface of the topological insulator at specific locations without introducing spin-scattering centres could open up new possibilities for devices. Here we use spin-polarized neutron reflectivity experiments to demonstrate topologically enhanced interface magnetism by coupling a ferromagnetic insulator (EuS) to a topological insulator (Bi2Se3) in a bilayer system. This interfacial ferromagnetism persists up to room temperature, even though the ferromagnetic insulator is known to order ferromagnetically only at low temperatures (<17 K). The magnetism induced at the interface resulting from the large spin-orbit interaction and the spin-momentum locking of the topological insulator surface greatly enhances the magnetic ordering (Curie) temperature of this bilayer system. The ferromagnetism extends similar to 2 nm into the Bi2Se3 from the interface. Owing to the short-range nature of the ferromagnetic exchange interaction, the time-reversal symmetry is broken only near the surface of a topological insulator, while leaving its bulk states unaffected. The topological magneto-electric response originating in such an engineered topological insulator(2,8) could allow efficient manipulation of the magnetization dynamics by an electric field, providing an energy-efficient topological control mechanism for future spin-based technologies.
C1 [Katmis, Ferhat; Wei, Peng; Jarillo-Herrero, Pablo; Moodera, Jagadeesh S.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Katmis, Ferhat; Wei, Peng; Moodera, Jagadeesh S.] MIT, Francis Bitter Magnet Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Katmis, Ferhat; Wei, Peng; Moodera, Jagadeesh S.] MIT, Plasma Sci & Fus Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Lauter, Valeria] Oak Ridge Natl Lab, Neutron Sci Directorate, Quantum Condensed Matter Div, Oak Ridge, TN 37831 USA.
   [Nogueira, Flavio S.; Eremin, Ilya] Ruhr Univ Bochum, Inst Theoret Phys 3, D-44801 Bochum, Germany.
   [Nogueira, Flavio S.] Inst Festkoerper & Werkstoffforsch Dresden, Inst Theoret Solid State Phys, D-01069 Dresden, Germany.
   [Assaf, Badih A.; Jamer, Michelle E.; Heiman, Don] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
   [Assaf, Badih A.] Paris Sci & Lettres Res Univ, CNRS, Ecole Normale Super, Dept Phys, F-75005 Paris, France.
   [Satpati, Biswarup] Saha Inst Nucl Phys, 1-AF Bidhannagar, Kolkata 64, India.
   [Freeland, John W.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); United States Department of Energy (DOE); Oak Ridge National Laboratory; Ruhr University Bochum; Northeastern University; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Ecole Normale Superieure (ENS); Saha Institute of Nuclear Physics; United States Department of Energy (DOE); Argonne National Laboratory
RP Katmis, F; Moodera, JS (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.; Katmis, F; Moodera, JS (corresponding author), MIT, Francis Bitter Magnet Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Katmis, F; Moodera, JS (corresponding author), MIT, Plasma Sci & Fus Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM katmis@mit.edu; moodera@mit.edu
FU Scientific User Facilities Division, Office of Basic Energy Sciences; US Department of Energy; MIT MRSEC through the MRSEC Program of the National Science Foundation [DMR-0819762]; National Science Foundation [DMR-1207469, DMR-0907007, ECCS-1402738]; Office of Naval Research [N00014-13-1-0301]; STC Center for Integrated Quantum Materials under National Science Foundation [DMR-1231319]; US Department of Energy, Basic Energy Sciences Office, Division of Material Sciences and Engineering [DE-SC0006418]; Agence Nationale de la Recherche LabEx grants ENS-ICFP [ANR-10-LABX-0010/ANR-10-IDEX-0001-02 PSL]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; German Research Council (DFG) under the collaborative research centre [SFB TR 12]; German Research Council (DFG) under the priority programme SPP 1666 [ER 463/9]; Division Of Materials Research; Direct For Mathematical & Physical Scien [1207469] Funding Source: National Science Foundation; Div Of Electrical, Commun & Cyber Sys; Directorate For Engineering [1402738] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0006418] Funding Source: U.S. Department of Energy (DOE)
NR 36
TC 406
Z9 474
U1 11
U2 471
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 513
EP +
DI 10.1038/nature17635
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100036
PM 27225124
DA 2026-03-09
ER

PT J
AU Jee, J
   Rasouly, A
   Shamovsky, I
   Akivis, Y
   Steinman, SR
   Mishra, B
   Nudler, E
AF Jee, Justin
   Rasouly, Aviram
   Shamovsky, Ilya
   Akivis, Yonatan
   Steinman, Susan R.
   Mishra, Bud
   Nudler, Evgeny
TI Rates and mechanisms of bacterial mutagenesis from maximum-depth sequencing
SO NATURE
LA English
DT Article
ID escherichia-coli; mutation-rate; rare mutations; antibiotics; sensitivity; selection; gene
AB In 1943, Luria and Delbruck used a phage-resistance assay to establish spontaneous mutation as a driving force of microbial diversity(1). Mutation rates are still studied using such assays, but these can only be used to examine the small minority of mutations conferring survival in a particular condition. Newer approaches, such as long-term evolution followed by whole-genome sequencing(2,3), may be skewed by mutational 'hot' or 'cold' spots(3,4). Both approaches are affected by numerous caveats(5-7). Here we devise a method, maximum-depth sequencing (MDS), to detect extremely rare variants in a population of cells through error-corrected, high-throughput sequencing. We directly measure locus-specific mutation rates in Escherichia coli and show that they vary across the genome by at least an order of magnitude. Our data suggest that certain types of nucleotide misincorporation occur 10(4)-fold more frequently than the basal rate of mutations, but are repaired in vivo. Our data also suggest specific mechanisms of antibiotic-induced mutagenesis, including downregulation of mismatch repair via oxidative stress, transcription-replication conflicts, and, in the case of fluoroquinolones, direct damage to DNA.
C1 [Jee, Justin; Rasouly, Aviram; Shamovsky, Ilya; Akivis, Yonatan; Steinman, Susan R.; Nudler, Evgeny] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [Jee, Justin; Mishra, Bud] NYU, Courant Inst Math Sci, New York, NY 10016 USA.
   [Rasouly, Aviram; Nudler, Evgeny] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
C3 New York University; New York University; New York University; Howard Hughes Medical Institute
RP Nudler, E (corresponding author), NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.; Mishra, B (corresponding author), NYU, Courant Inst Math Sci, New York, NY 10016 USA.; Nudler, E (corresponding author), NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
EM mishra@nyu.edu; evgeny.nudler@nyumc.org
FU Cancer Center Support Grant [P30CA016087]; NIH [R01GM107329]; HHMI; NCI PSOC grant [U54 CA193313]; NYU Medical Scientist Training Program; National Defense Science and Engineering Graduate Fellowship; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 34
TC 97
Z9 124
U1 0
U2 63
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 693
EP +
DI 10.1038/nature18313
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000038
PM 27338792
DA 2026-03-09
ER

PT J
AU Fu, QM
   Posth, C
   Hajdinjak, M
   Petr, M
   Mallick, S
   Fernandes, D
   Furtwängler, A
   Haak, W
   Meyer, M
   Mittnik, A
   Nickel, B
   Peltzer, A
   Rohland, N
   Slon, V
   Talamo, S
   Lazaridis, I
   Lipson, M
   Mathieson, I
   Schiffels, S
   Skoglund, P
   Derevianko, AP
   Drozdov, N
   Slavinsky, V
   Tsybankov, A
   Cremonesi, RG
   Mallegni, F
   Gély, B
   Vacca, E
   Morales, MRG
   Straus, LG
   Neugebauer-Maresch, C
   Teschler-Nicola, M
   Constantin, S
   Moldovan, OT
   Benazzi, S
   Peresani, M
   Coppola, D
   Lari, M
   Ricci, S
   Ronchitelli, A
   Valentin, F
   Thevenet, C
   Wehrberger, K
   Grigorescu, D
   Rougier, H
   Crevecoeur, I
   Flas, D
   Semal, P
   Mannino, MA
   Cupillard, C
   Bocherens, H
   Conard, NJ
   Harvati, K
   Moiseyev, V
   Drucker, DG
   Svoboda, J
   Richards, MP
   Caramelli, D
   Pinhasi, R
   Kelso, J
   Patterson, N
   Krause, J
   Pääbo, S
   Reich, D
AF Fu, Qiaomei
   Posth, Cosimo
   Hajdinjak, Mateja
   Petr, Martin
   Mallick, Swapan
   Fernandes, Daniel
   Furtwangler, Anja
   Haak, Wolfgang
   Meyer, Matthias
   Mittnik, Alissa
   Nickel, Birgit
   Peltzer, Alexander
   Rohland, Nadin
   Slon, Viviane
   Talamo, Sahra
   Lazaridis, Iosif
   Lipson, Mark
   Mathieson, Iain
   Schiffels, Stephan
   Skoglund, Pontus
   Derevianko, Anatoly P.
   Drozdov, Nikolai
   Slavinsky, Vyacheslav
   Tsybankov, Alexander
   Cremonesi, Renata Grifoni
   Mallegni, Francesco
   Gely, Bernard
   Vacca, Eligio
   Gonzalez Morales, Manuel R.
   Straus, Lawrence G.
   Neugebauer-Maresch, Christine
   Teschler-Nicola, Maria
   Constantin, Silviu
   Moldovan, Oana Teodora
   Benazzi, Stefano
   Peresani, Marco
   Coppola, Donato
   Lari, Martina
   Ricci, Stefano
   Ronchitelli, Annamaria
   Valentin, Frederique
   Thevenet, Corinne
   Wehrberger, Kurt
   Grigorescu, Dan
   Rougier, Helene
   Crevecoeur, Isabelle
   Flas, Damien
   Semal, Patrick
   Mannino, Marcello A.
   Cupillard, Christophe
   Bocherens, Herve
   Conard, Nicholas J.
   Harvati, Katerina
   Moiseyev, Vyacheslav
   Drucker, Dorothee G.
   Svoboda, Jiri
   Richards, Michael P.
   Caramelli, David
   Pinhasi, Ron
   Kelso, Janet
   Patterson, Nick
   Krause, Johannes
   Paeaebo, Svante
   Reich, David
TI The genetic history of Ice Age Europe
SO NATURE
LA English
DT Article
ID genome sequence; radiocarbon-dates; hunter-gatherers; neanderthal; morphology; cave; dispersal; admixture; ancestry; suggest
AB Modern humans arrived in Europe similar to 45,000 years ago, but little is known about their genetic composition before the start of farming similar to 8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from similar to 45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between similar to 37,000 and similar to 14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An similar to 35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age similar to 19,000 years ago. During the major warming period after similar to 14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.
C1 [Fu, Qiaomei] Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Fu, Qiaomei; Mallick, Swapan; Rohland, Nadin; Lazaridis, Iosif; Lipson, Mark; Mathieson, Iain; Skoglund, Pontus; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Fu, Qiaomei; Hajdinjak, Mateja; Petr, Martin; Meyer, Matthias; Nickel, Birgit; Slon, Viviane; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Posth, Cosimo; Furtwangler, Anja; Mittnik, Alissa; Peltzer, Alexander; Krause, Johannes] Univ Tubingen, Inst Archaeol Sci Archaeo & Palaeogenet, D-72070 Tubingen, Germany.
   [Posth, Cosimo; Haak, Wolfgang; Mittnik, Alissa; Schiffels, Stephan; Krause, Johannes] Max Planck Inst Sci Human Hist, Dept Archaeogenet, D-07745 Jena, Germany.
   [Mallick, Swapan; Patterson, Nick; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Mallick, Swapan; Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Fernandes, Daniel; Pinhasi, Ron] Univ Coll Dublin, Sch Archaeol, Dublin 4, Ireland.
   [Fernandes, Daniel; Pinhasi, Ron] Univ Coll Dublin, Earth Inst, Dublin 4, Ireland.
   [Fernandes, Daniel] Univ Coimbra, Dept Life Sci, CIAS, P-3000456 Coimbra, Portugal.
   [Haak, Wolfgang] Univ Adelaide, Sch Biol Sci, Australian Ctr Ancient DNA, Adelaide, SA 5005, Australia.
   [Talamo, Sahra; Benazzi, Stefano; Mannino, Marcello A.; Richards, Michael P.] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Derevianko, Anatoly P.; Drozdov, Nikolai; Slavinsky, Vyacheslav; Tsybankov, Alexander] Russian Acad Sci, Siberian Branch, Inst Archaeol & Ethnog, RU-630090 Novosibirsk 17, Russia.
   [Derevianko, Anatoly P.] Altai State Univ, RU-656049 Barnaul, Russia.
   [Cremonesi, Renata Grifoni] Univ Pisa, Dipartimento Civilta & Forme Sapere, I-56126 Pisa, Italy.
   [Mallegni, Francesco] Univ Pisa, Dept Biol, I-56126 Pisa, Italy.
   [Gely, Bernard] Direct Reg Affaires Culturelles Rhone Alpes, F-69283 Lyon 01, France.
   [Vacca, Eligio] Univ Bari Aldo Moro, Dipartimento Biol, I-70125 Bari, Italy.
   [Gonzalez Morales, Manuel R.; Straus, Lawrence G.] Univ Cantabria, Inst Int Invest Prehist, E-39005 Santander, Spain.
   [Straus, Lawrence G.] Univ New Mexico, Dept Anthropol, MSC01 1040, Albuquerque, NM 87131 USA.
   [Neugebauer-Maresch, Christine] Austrian Acad Sci, Inst Oriental & European Archaeol, Quaternary Archaeol, A-1010 Vienna, Austria.
   [Teschler-Nicola, Maria] Nat Hist Museum Vienna, Dept Anthropol, A-1010 Vienna, Austria.
   [Teschler-Nicola, Maria] Univ Vienna, Dept Anthropol, A-1090 Vienna, Austria.
   [Constantin, Silviu] Emil Racovita Inst Speleol, Bucharest 010986 12, Romania.
   [Moldovan, Oana Teodora] Emil Racovita Inst Speleol, Cluj Branch, Cluj Napoca 400006, Romania.
   [Benazzi, Stefano] Univ Bologna, Dept Cultural Heritage, I-48121 Ravenna, Italy.
   [Peresani, Marco] Univ Ferrara, Dipartimento Studi Umanist, Sez Sci Preistor & Antropol, I-44100 Ferrara, Italy.
   [Coppola, Donato] Univ Bari Aldo Moro, I-70125 Bari, Italy.
   [Coppola, Donato] Museo Civilta Preclassiche Murgia Merid, I-72017 Ostuni, Italy.
   [Lari, Martina; Caramelli, David] Univ Firenze, Dipartimento Biol, I-50122 Florence, Italy.
   [Ricci, Stefano; Ronchitelli, Annamaria] Univ Siena, UR Preistoria Antropol, Dipartimento Sci Fis Terra & Ambiente, I-53100 Siena, Italy.
   [Valentin, Frederique] CNRS UMR 7041 ArScAn, F-92023 Nanterre, France.
   [Thevenet, Corinne] INRAP UMR 8215, Trajectoires 21, F-92023 Nanterre, France.
   [Wehrberger, Kurt] Ulmer Museum, D-89073 Ulm, Germany.
   [Grigorescu, Dan] Univ Bucharest, Fac Geol & Geophys, Dept Geol, Bucharest 01041, Romania.
   [Rougier, Helene] Calif State Univ Northridge, Dept Anthropol, Northridge, CA 91330 USA.
   [Crevecoeur, Isabelle] Univ Bordeaux, CNRS, UMR PACEA 5199, F-33615 Pessac, France.
   [Flas, Damien] Univ Toulouse Jean Jaures, Maison Rech, TRACES UMR 5608, F-31058 Toulouse 9, France.
   [Semal, Patrick] Royal Belgian Inst Nat Sci, B-1000 Brussels, Belgium.
   [Mannino, Marcello A.] Aarhus Univ, Sch Culture & Soc, Dept Archaeol, DK-8270 Hojbjerg, Denmark.
   [Cupillard, Christophe] Serv Reg Archeol Franche Comte, F-25043 Besancon, France.
   [Cupillard, Christophe] CNRS, UMR 6249, UFR Sci & Tech, Lab Chronoenvironm, F-25030 Besancon, France.
   [Bocherens, Herve; Drucker, Dorothee G.] Univ Tubingen, Biogeol, Dept Geosci, D-72074 Tubingen, Germany.
   [Bocherens, Herve; Conard, Nicholas J.; Harvati, Katerina; Krause, Johannes] Univ Tubingen, Senckenberg Ctr Human Evolut & Palaeoenvironm, D-72072 Tubingen, Germany.
   [Conard, Nicholas J.] Univ Tubingen, Dept Early Prehist & Quaternary Ecol, D-72070 Tubingen, Germany.
   [Harvati, Katerina] Univ Tubingen, Inst Archaeol Sci Paleoanthropol, D-72070 Tubingen, Germany.
   [Moiseyev, Vyacheslav] Museum Anthropol & Ethnog, St Petersburg 34, Russia.
   [Svoboda, Jiri] Masaryk Univ, Fac Sci, Dept Anthropol, CS-61137 Brno, Czech Republic.
   [Svoboda, Jiri] Acad Sci Czech Republ, Inst Archaeol Brno, Dolni Vestonice 69129, Czech Republic.
   [Richards, Michael P.] Simon Fraser Univ, Dept Archaeol, Burnaby, BC V5A 1S6, Canada.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Harvard University; Harvard Medical School; Max Planck Society; Eberhard Karls University of Tubingen; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; University College Dublin; University College Dublin; Universidade de Coimbra; Adelaide University; University of Adelaide; Max Planck Society; Russian Academy of Sciences; Altai State University; University of Pisa; University of Pisa; Universita degli Studi di Bari Aldo Moro; Universidad de Cantabria; Instituto Internacional de Investigaciones Prehistoricas de Cantabria (IIIPC); University of New Mexico; Austrian Academy of Sciences; University of Vienna; Emil Racovita Institute of Speleology; Emil Racovita Institute of Speleology; Romanian Academy; University of Bologna; University of Ferrara; Universita degli Studi di Bari Aldo Moro; University of Florence; University of Siena; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social Sciences (INSHS); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Humanities & Social Sciences (INSHS); University of Bucharest; California State University System; California State University Northridge; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Bordeaux; Universite de Toulouse; Universite de Toulouse - Jean Jaures; Royal Belgian Institute of Natural Sciences; Aarhus University; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite Marie et Louis Pasteur; Eberhard Karls University of Tubingen; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Masaryk University; Czech Academy of Sciences; Institute of Archaeology of the Czech Academy of Sciences - Brno; Simon Fraser University
RP Reich, D (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.; Reich, D (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Reich, D (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM reich@genetics.med.harvard.edu
FU Wenner-Gren Foundation [7837]; College of Social and Behavioral Sciences of CSUN; CSUN Competition for Research, Scholarship and Creative Activity Awards; RBINS; Gobierno de Cantabria; L.S.B. Leakey Foundation; University of New Mexico; Stone Age Research Fund; town of Ramales de la Victoria; Universidad de Cantabria; MIBACT; Veneto Region; Special Foundation of the President of the Chinese Academy of Sciences; Bureau of International Cooperation of the Chinese Academy of Sciences; Chinese Academy of Sciences [XDA05130202]; National Natural Science Foundation of China [L1524016]; Chinese Academy of Sciences Discipline Development Strategy Project [2015-DX-C-03]; Irish Research Council [GOIPG/2013/36]; Human Frontier Science Program [LT001095/2014-L]; Swedish Research Council [VR 2014-453]; Max Planck Society; FWF [P-17258, P-19347, P-21660, P-23612]; 'Karsthives' Grant [PCCE 31/2010]; Russian Science Foundation [14-50-00036]; European Community [PIEF-GA-2008-219965]; Collective Research Program (PCR); European Research Council [ERC StG 283503]; Deutsche Forschungsgemeinschaft [DFG INST37/706-1FUGG, DFG FOR2237, SFB1052]; European Social Fund; Ministry of Science, Research and Arts of Baden-Wurttemberg; ERC starting grant ADNABIOARC [263441]; DFG [KR 4015/1-1]; Baden Wurttemberg Foundation; Krekeler Foundation; NSF HOMINID [BCS-1032255]; NIH (NIGMS) [GM100233]; Howard Hughes Medical Institute;  [2010EL8TXP_003]; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1032255] Funding Source: National Science Foundation; Austrian Science Fund (FWF) [P 23612] Funding Source: researchfish; European Research Council (ERC) [263441] Funding Source: European Research Council (ERC)
NR 65
TC 677
Z9 768
U1 6
U2 374
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 200
EP +
DI 10.1038/nature17993
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100031
PM 27135931
DA 2026-03-09
ER

PT J
AU Larocca, RA
   Abbink, P
   Peron, JPS
   Zanotto, PMD
   Iampietro, MJ
   Badamchi-Zadeh, A
   Boyd, M
   Ng'ang'a, D
   Kirilova, M
   Nityanandam, R
   Mercado, NB
   Li, ZF
   Moseley, ET
   Bricault, CA
   Borducchi, EN
   Giglio, PB
   Jetton, D
   Neubauer, G
   Nkolola, JP
   Maxfield, LF
   De La Barrera, RA
   Jarman, RG
   Eckels, KH
   Michael, NL
   Thomas, SJ
   Barouch, DH
AF Larocca, Rafael A.
   Abbink, Peter
   Peron, Jean Pierre S.
   Zanotto, Paolo M. de A.
   Iampietro, M. Justin
   Badamchi-Zadeh, Alexander
   Boyd, Michael
   Ng'ang'a, David
   Kirilova, Marinela
   Nityanandam, Ramya
   Mercado, Noe B.
   Li, Zhenfeng
   Moseley, Edward T.
   Bricault, Christine A.
   Borducchi, Erica N.
   Giglio, Patricia B.
   Jetton, David
   Neubauer, George
   Nkolola, Joseph P.
   Maxfield, Lori F.
   De La Barrera, Rafael A.
   Jarman, Richard G.
   Eckels, Kenneth H.
   Michael, Nelson L.
   Thomas, Stephen J.
   Barouch, Dan H.
TI Vaccine protection against Zika virus from Brazil
SO NATURE
LA English
DT Article
ID neutralizing antibody; healthy-adults; challenge; immunogenicity; infection; america; safety; model; mice
AB Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas(1,2). ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans(3-8) and mice(9-11). The rapid development of a safe and effective ZIKV vaccine is a global health priority(1,2), but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice(11). We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.
C1 [Larocca, Rafael A.; Abbink, Peter; Iampietro, M. Justin; Badamchi-Zadeh, Alexander; Boyd, Michael; Ng'ang'a, David; Kirilova, Marinela; Nityanandam, Ramya; Mercado, Noe B.; Li, Zhenfeng; Moseley, Edward T.; Bricault, Christine A.; Borducchi, Erica N.; Giglio, Patricia B.; Jetton, David; Neubauer, George; Nkolola, Joseph P.; Maxfield, Lori F.; Barouch, Dan H.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
   [Peron, Jean Pierre S.; Zanotto, Paolo M. de A.] Univ Sao Paulo, BR-05508000 Sao Paulo, Brazil.
   [De La Barrera, Rafael A.; Jarman, Richard G.; Eckels, Kenneth H.; Michael, Nelson L.; Thomas, Stephen J.] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
   [Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Universidade de Sao Paulo; Walter Reed Army Institute of Research (WRAIR); United States Department of Defense; United States Army; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School
RP Barouch, DH (corresponding author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.; Barouch, DH (corresponding author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
EM dbarouch@bidmc.harvard.edu
FU Ragon Institute of MGH, MIT, and Harvard; National Institutes of Health [AI095985, AI096040, AI100663, AI124377]; Sao Paulo Research Foundation [FAPESP 2011/18703-2, 2014/17766-9]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [14/17766-9, 11/18703-2] Funding Source: FAPESP
NR 30
TC 424
Z9 527
U1 2
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 474
EP +
DI 10.1038/nature18952
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600045
PM 27355570
DA 2026-03-09
ER

PT J
AU Zhou, Y
   Guan, XF
   Zhou, H
   Ramadoss, K
   Adam, S
   Liu, HJ
   Lee, S
   Shi, J
   Tsuchiya, M
   Fong, DD
   Ramanathan, S
AF Zhou, You
   Guan, Xiaofei
   Zhou, Hua
   Ramadoss, Koushik
   Adam, Suhare
   Liu, Huajun
   Lee, Sungsik
   Shi, Jian
   Tsuchiya, Masaru
   Fong, Dillon D.
   Ramanathan, Shriram
TI Strongly correlated perovskite fuel cells
SO NATURE
LA English
DT Article
ID quantum molecular-dynamics; proton conduction; transport-property; temperature; diffusion; design; nickel; srtio3
AB Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines(1-4). Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number(5). Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes(6). Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations.
C1 [Zhou, You; Guan, Xiaofei; Ramadoss, Koushik; Adam, Suhare; Shi, Jian; Ramanathan, Shriram] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Zhou, Hua; Lee, Sungsik] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
   [Liu, Huajun; Fong, Dillon D.] Argonne Natl Lab, Div Mat Sci, 9700 S Cass Ave, Argonne, IL 60439 USA.
   [Shi, Jian] Rensselaer Polytech Inst, Dept Mat Sci & Engn, Troy, NY 12180 USA.
   [Tsuchiya, Masaru] SiEnergy Syst, Cambridge, MA 02140 USA.
   [Ramanathan, Shriram] Purdue Univ, Sch Mat Engn, W Lafayette, IN 47907 USA.
C3 Harvard University; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Rensselaer Polytechnic Institute; Purdue University System; Purdue University
RP Zhou, Y; Ramanathan, S (corresponding author), Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.; Ramanathan, S (corresponding author), Purdue Univ, Sch Mat Engn, W Lafayette, IN 47907 USA.
EM youzhou@fas.harvard.edu; shriram@purdue.edu
FU Army Research Office [W911NF-14-1-0348, W911NF-14-1-0669]; Air Force Office of Scientific Research [FA9550-12-1-0189]; Advanced Research Projects Agency-Energy (ARPA-E); IBM PhD Fellowship; National Academy of Sciences; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division
NR 33
TC 476
Z9 524
U1 23
U2 1043
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 231
EP +
DI 10.1038/nature17653
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100037
PM 27279218
DA 2026-03-09
ER

PT J
AU Joesch, M
   Meister, M
AF Joesch, Maximilian
   Meister, Markus
TI A neuronal circuit for colour vision based on rod-cone opponency
SO NATURE
LA English
DT Article
ID mouse retina; horizontal cells; ganglion-cells; mammalian retina; mice; photoreceptors; light; sensitivity; responses
AB In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour(1). In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals(2). Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC)(3), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.
C1 [Joesch, Maximilian] Harvard Univ, 52 Oxford St, Cambridge, MA 02138 USA.
   [Meister, Markus] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
C3 Harvard University; California Institute of Technology
RP Joesch, M (corresponding author), Harvard Univ, 52 Oxford St, Cambridge, MA 02138 USA.; Meister, M (corresponding author), CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
EM joeschkrotki@fas.harvard.edu; meister@caltech.edu
FU NIH; International Human Frontier Science Program Organization
NR 36
TC 111
Z9 141
U1 5
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 236
EP +
DI 10.1038/nature17158
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100040
PM 27049951
DA 2026-03-09
ER

PT J
AU Gies, E
AF Gies, Erica
TI Can wind and solar fuel Africa's future?
SO NATURE
LA English
DT Article
NR 9
TC 10
Z9 12
U1 1
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 20
EP +
DI 10.1038/539020a
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100008
PM 27808213
DA 2026-03-09
ER

PT J
AU Xin, XF
   Nomura, K
   Aung, K
   Velásquez, AC
   Yao, J
   Boutrot, F
   Chang, JH
   Zipfel, C
   He, SY
AF Xin, Xiu-Fang
   Nomura, Kinya
   Aung, Kyaw
   Velasquez, Andre C.
   Yao, Jian
   Boutrot, Freddy
   Chang, Jeff H.
   Zipfel, Cyril
   He, Sheng Yang
TI Bacteria establish an aqueous living space in plants crucial for virulence
SO NATURE
LA English
DT Article
ID lysm receptor kinase; triggered immunity; innate immune; secretion; arabidopsis; effectors; avirulence; disease; growth; mutant
AB High humidity has a strong influence on the development of numerous diseases affecting the above-ground parts of plants (the phyllosphere) in crop fields and natural ecosystems, but the molecular basis of this humidity effect is not understood. Previous studies have emphasized immune suppression as a key step in bacterial pathogenesis. Here we show that humidity-dependent, pathogen-driven establishment of an aqueous intercellular space (apoplast) is another important step in bacterial infection of the phyllosphere. Bacterial effectors, such as Pseudomonas syringae HopM1, induce establishment of the aqueous apoplast and are sufficient to transform non-pathogenic P. syringae strains into virulent pathogens in immunodeficient Arabidopsis thaliana under high humidity. Arabidopsis quadruple mutants simultaneously defective in a host target (AtMIN7) of HopM1 and in pattern-triggered immunity could not only be used to reconstitute the basic features of bacterial infection, but also exhibited humidity-dependent dyshomeostasis of the endophytic commensal bacterial community in the phyllosphere. These results highlight a new conceptual framework for understanding diverse phyllosphere-bacterial interactions.
C1 [Xin, Xiu-Fang; Nomura, Kinya; Aung, Kyaw; Velasquez, Andre C.; Yao, Jian; He, Sheng Yang] Michigan State Univ, Plant Res Lab, Dept Energy, E Lansing, MI 48824 USA.
   [Nomura, Kinya; He, Sheng Yang] Michigan State Univ, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, E Lansing, MI 48824 USA.
   [Boutrot, Freddy; Zipfel, Cyril] Sainsbury Lab, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England.
   [Chang, Jeff H.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
   [Chang, Jeff H.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
   [He, Sheng Yang] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.
   [He, Sheng Yang] Michigan State Univ, Plant Resilience Inst, E Lansing, MI 48824 USA.
   [Yao, Jian] Western Michigan Univ, Dept Biol Sci, Kalamazoo, MI 49008 USA.
C3 Michigan State University; Michigan State University; Howard Hughes Medical Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Oregon State University; Oregon State University; Michigan State University; Michigan State University; Western Michigan University
RP He, SY (corresponding author), Michigan State Univ, Plant Res Lab, Dept Energy, E Lansing, MI 48824 USA.; He, SY (corresponding author), Michigan State Univ, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, E Lansing, MI 48824 USA.; He, SY (corresponding author), Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.; He, SY (corresponding author), Michigan State Univ, Plant Resilience Inst, E Lansing, MI 48824 USA.
EM hes@msu.edu
FU Gordon and Betty Moore Foundation [GBMF3037]; National Institutes of Health [GM109928]; Department of Energy (the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science) [DE-FG02-91ER20021]; Gatsby Charitable Foundation; BBSRC [BB/G024936/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/G024936/1] Funding Source: researchfish
NR 33
TC 352
Z9 408
U1 8
U2 348
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 524
EP +
DI 10.1038/nature20166
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600036
PM 27882964
DA 2026-03-09
ER

PT J
AU Albright, R
   Caldeira, L
   Hosfelt, J
   Kwiatkowski, L
   Maclaren, JK
   Mason, BM
   Nebuchina, Y
   Ninokawa, A
   Pongratz, J
   Ricke, KL
   Rivlin, T
   Schneider, K
   Sesboüe, M
   Shamberger, K
   Silverman, J
   Wolfe, K
   Zhu, K
   Caldeira, K
AF Albright, Rebecca
   Caldeira, Lilian
   Hosfelt, Jessica
   Kwiatkowski, Lester
   Maclaren, Jana K.
   Mason, Benjamin M.
   Nebuchina, Yana
   Ninokawa, Aaron
   Pongratz, Julia
   Ricke, Katharine L.
   Rivlin, Tanya
   Schneider, Kenneth
   Sesbouee, Marine
   Shamberger, Kathryn
   Silverman, Jacob
   Wolfe, Kennedy
   Zhu, Kai
   Caldeira, Ken
TI Reversal of ocean acidification enhances net coral reef calcification
SO NATURE
LA English
DT Article
ID massive porites; carbonic-acid; growth-rates; seawater; dissociation; marine; chemistry; constants; dynamics; island
AB Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([CO32-]), and saturation state of carbonate minerals (Omega)(1). This process, referred to as ocean acidification, represents a major threat to marine ecosystems, in particular marine calcifiers such as oysters, crabs, and corals. Laboratory and field studies(2,3) have shown that calcification rates of many organisms decrease with declining pH, [CO32-], and Omega. Coral reefs are widely regarded as one of the most vulnerable marine ecosystems to ocean acidification, in part because the very architecture of the ecosystem is reliant on carbonate-secreting organisms(4). Acidification-induced reductions in calcification are projected to shift coral reefs from a state of net accretion to one of net dissolution this century(5). While retrospective studies show large-scale declines in coral, and community, calcification over recent decades(6-12), determining the contribution of ocean acidification to these changes is difficult, if not impossible, owing to the confounding effects of other environmental factors such as temperature. Here we quantify the net calcification response of a coral reef flat to alkalinity enrichment, and show that, when ocean chemistry is restored closer to pre-industrial conditions, net community calcification increases. In providing results from the first seawater chemistry manipulation experiment of a natural coral reef community, we provide evidence that net community calcification is depressed compared with values expected for pre-industrial conditions, indicating that ocean acidification may already be impairing coral reef growth.
C1 [Albright, Rebecca; Caldeira, Lilian; Kwiatkowski, Lester; Maclaren, Jana K.; Nebuchina, Yana; Pongratz, Julia; Ricke, Katharine L.; Schneider, Kenneth; Sesbouee, Marine; Zhu, Kai; Caldeira, Ken] Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
   [Hosfelt, Jessica; Ninokawa, Aaron] Univ Calif Davis, Bodega Marine Lab, Bodega Bay, CA 94923 USA.
   [Maclaren, Jana K.] Stanford Univ, Stanford Nano Shared Facil, Stanford, CA 94305 USA.
   [Mason, Benjamin M.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
   [Pongratz, Julia] Max Planck Inst Meteorol, Bundesstr 53, D-20146 Hamburg, Germany.
   [Ricke, Katharine L.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA.
   [Rivlin, Tanya] Hebrew Univ Jerusalem, Interuniv Inst Marine Sci, H Steinitz Marine Biol Lab, Elat, Israel.
   [Rivlin, Tanya] Hebrew Univ Jerusalem, Fredy & Nadine Herrman Inst Earth Sci, Edmond J Safra Campus, Jerusalem, Israel.
   [Schneider, Kenneth] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, Israel.
   [Shamberger, Kathryn] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [Shamberger, Kathryn] Texas A&M Univ, College Stn, TX 77843 USA.
   [Silverman, Jacob] Inst Oceanog & Limnol Res, Haifa, Israel.
   [Wolfe, Kennedy] Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia.
   [Zhu, Kai] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Zhu, Kai] Rice Univ, Dept BioSci, Houston, TX 77005 USA.
C3 Carnegie Institution for Science; University of California System; University of California Davis; Stanford University; Stanford University; Max Planck Society; Cornell University; The Inter-University Institute for Marine Sciences; Hebrew University of Jerusalem; Hebrew University of Jerusalem; Hebrew University of Jerusalem; Woods Hole Oceanographic Institution; Texas A&M University System; Texas A&M University College Station; University of Sydney; Stanford University; Rice University
RP Albright, R (corresponding author), Carnegie Inst Sci, Dept Global Ecol, Stanford, CA 94305 USA.
EM ralbright@carnegiescience.edu
FU Fund for Innovative Climate and Energy Research
NR 43
TC 248
Z9 291
U1 27
U2 877
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 362
EP +
DI 10.1038/nature17155
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300051
PM 26909578
DA 2026-03-09
ER

PT J
AU Luchsinger, LL
   de Almeida, MJ
   Corrigan, DJ
   Mumau, M
   Snoeck, HW
AF Luchsinger, Larry L.
   de Almeida, Mariana Justino
   Corrigan, David J.
   Mumau, Melanie
   Snoeck, Hans-Willem
TI Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential
SO NATURE
LA English
DT Article
ID mitochondrial fission; endoplasmic-reticulum; fusion; expression; inhibitor
AB Haematopoietic stem cells (HSCs), which sustain production of all blood cell lineages(1), rely on glycolysis for ATP production(2,3), yet little attention has been paid to the role of mitochondria. Here we show in mice that the short isoform of a critical regulator of HSCs, Prdm16 (refs 4, 5), induces mitofusin 2 (Mfn2), a protein involved in mitochondrial fusion and in tethering of mitochondria to the endoplasmic reticulum. Overexpression and deletion studies, including single-cell transplantation assays, revealed that Mfn2 is specifically required for the maintenance of HSCs with extensive lymphoid potential, but not, or less so, for the maintenance of myeloid-dominant HSCs. Mfn2 increased buffering of intracellular Ca2+, an effect mediated through its endoplasmic reticulum-mitochondria tethering activity(6,7), thereby negatively regulating nuclear translocation and transcriptional activity of nuclear factor of activated T cells (Nfat). Nfat inhibition rescued the effects of Mfn2 deletion in HSCs, demonstrating that negative regulation of Nfat is the prime downstream mechanism of Mfn2 in the maintenance of HSCs with extensive lymphoid potential. Mitochondria therefore have an important role in HSCs. These findings provide a mechanism underlying clonal heterogeneity among HSCs8-11 and may lead to the design of approaches to bias HSC differentiation into desired lineages after transplantation.
C1 [Luchsinger, Larry L.; de Almeida, Mariana Justino; Corrigan, David J.; Mumau, Melanie; Snoeck, Hans-Willem] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA.
   [Luchsinger, Larry L.; Snoeck, Hans-Willem] Columbia Univ, Dept Med, Med Ctr, New York, NY 10032 USA.
   [de Almeida, Mariana Justino; Corrigan, David J.; Mumau, Melanie; Snoeck, Hans-Willem] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University
RP Snoeck, HW (corresponding author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA.; Snoeck, HW (corresponding author), Columbia Univ, Dept Med, Med Ctr, New York, NY 10032 USA.; Snoeck, HW (corresponding author), Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
EM hs2680@columbia.edu
FU Druckenmiller Fellowship from the New York Stem Cell Foundation; Ruth L. Kirschstein fellowship [F31 CA196045]; NIH National Center for Research Resources [1S10RR027050-01]; NIH Office of the Director [1S10OD020056-01];  [NIH RO1 CA167286];  [RO1 AG029262]; National Institute of Allergy and Infectious Diseases [T32AI106711] Funding Source: NIH RePORTER
NR 35
TC 200
Z9 236
U1 0
U2 38
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 528
EP +
DI 10.1038/nature16500
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800037
PM 26789249
DA 2026-03-09
ER

PT J
AU Hamilton, DP
   Stern, SA
   Moore, JM
   Young, LA
AF Hamilton, Douglas P.
   Stern, S. A.
   Moore, J. M.
   Young, L. A.
TI The rapid formation of Sputnik Planitia early in Pluto's history
SO NATURE
LA English
DT Article
ID insolation; charon; obliquity; evolution
AB Pluto's Sputnik Planitia is a bright, roughly circular feature that resembles a polar ice cap. It is approximately 1,000 kilometres across and is centred on a latitude of 25 degrees north and a longitude of 175 degrees, almost directly opposite the side of Pluto that always faces Charon as a result of tidal locking(1). One explanation for its location includes the formation of a basin in a giant impact, with subsequent upwelling of a dense interior ocean(2). Once the basin was established, ice would naturally have accumulated there(3). Then, provided that the basin was a positive gravity anomaly (with or without the ocean), true polar wander could have moved the feature towards the Pluto-Charon tidal axis, on the far side of Pluto from Charon(2,4). Here we report modelling that shows that ice quickly accumulates on Pluto near latitudes of 30 degrees north and south, even in the absence of a basin, because, averaged over its orbital period, those are Pluto's coldest regions. Within a million years of Charon's formation, ice deposits on Pluto concentrate into a single cap centred near a latitude of 30 degrees, owing to the runaway albedo effect. This accumulation of ice causes a positive gravity signature that locks, as Pluto's rotation slows, to a longitude directly opposite Charon. Once locked, Charon raises a permanent tidal bulge on Pluto, which greatly enhances the gravity signature of the ice cap. Meanwhile, the weight of the ice in Sputnik Planitia causes the crust under it to slump, creating its own basin (as has happened on Earth in Greenland(5)). Even if the feature is now a modest negative gravity anomaly, it remains locked in place because of the permanent tidal bulge raised by Charon. Any movement of the feature away from 30 degrees latitude is countered by the preferential recondensation of ices near the coldest extremities of the cap. Therefore, our modelling suggests that Sputnik Planitia formed shortly after Charon did and has been stable, albeit gradually losing volume, over the age of the Solar System.
C1 [Hamilton, Douglas P.] Univ Maryland, College Pk, MD 20742 USA.
   [Stern, S. A.; Young, L. A.] SWRI, Boulder, CO USA.
   [Moore, J. M.] NASA Ames, Mountain View, CA USA.
C3 University System of Maryland; University of Maryland College Park; Southwest Research Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP Hamilton, DP (corresponding author), Univ Maryland, College Pk, MD 20742 USA.
EM dphamil@umd.edu
FU NASA; NASA Origins
NR 34
TC 29
Z9 32
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 97
EP +
DI 10.1038/nature20586
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600055
PM 27905411
DA 2026-03-09
ER

PT J
AU Graves, A
   Wayne, G
   Eynolds, MR
   Harley, T
   Danihelka, I
   Grabska-Barwinska, A
   Colmenarejo, SG
   Grefenstette, E
   Amalho, TR
   Agapiou, J
   Badia, AP
   Hermann, KM
   Zwols, Y
   Strovski, GO
   Ain, AC
   King, H
   Summerfield, C
   Lunsom, PB
   Kavukcuoglu, K
   Hassabis, D
AF Graves, Alex
   Wayne, Greg
   Eynolds, Malcolm R.
   Harley, Tim
   Danihelka, Ivo
   Grabska-Barwinska, Agnieszka
   Colmenarejo, Sergio Gomez
   Grefenstette, Edward
   Amalho, Tiago R.
   Agapiou, John
   Badia, Adria Puigdomenech
   Hermann, Karl Moritz
   Zwols, Yori
   Strovski, Georg O.
   Ain, Adam C.
   King, Helen
   Summerfield, Christopher
   Lunsom, Phil B.
   Kavukcuoglu, Koray
   Hassabis, Demis
TI Hybrid computing using a neural network with dynamic external memory
SO NATURE
LA English
DT Article
ID complementary learning-systems; hippocampus; models
AB Artificial neural networks are remarkably adept at sensory processing, sequence learning and reinforcement learning, but are limited in their ability to represent variables and data structures and to store data over long timescales, owing to the lack of an external memory. Here we introduce a machine learning model called a differentiable neural computer (DNC), which consists of a neural network that can read from and write to an external memory matrix, analogous to the random-access memory in a conventional computer. Like a conventional computer, it can use its memory to represent and manipulate complex data structures, but, like a neural network, it can learn to do so from data. When trained with supervised learning, we demonstrate that a DNC can successfully answer synthetic questions designed to emulate reasoning and inference problems in natural language. We show that it can learn tasks such as finding the shortest path between specified points and inferring the missing links in randomly generated graphs, and then generalize these tasks to specific graphs such as transport networks and family trees. When trained with reinforcement learning, a DNC can complete a moving blocks puzzle in which changing goals are specified by sequences of symbols. Taken together, our results demonstrate that DNCs have the capacity to solve complex, structured tasks that are inaccessible to neural networks without external read-write memory.
C1 [Graves, Alex; Wayne, Greg; Eynolds, Malcolm R.; Harley, Tim; Danihelka, Ivo; Grabska-Barwinska, Agnieszka; Colmenarejo, Sergio Gomez; Grefenstette, Edward; Amalho, Tiago R.; Agapiou, John; Badia, Adria Puigdomenech; Hermann, Karl Moritz; Zwols, Yori; Strovski, Georg O.; Ain, Adam C.; King, Helen; Summerfield, Christopher; Lunsom, Phil B.; Kavukcuoglu, Koray; Hassabis, Demis] Google DeepMind, 5 New St Sq, London EC4A 3TW, England.
C3 Alphabet Inc.; Google Incorporated; DeepMind
RP Graves, A; Wayne, G; Hassabis, D (corresponding author), Google DeepMind, 5 New St Sq, London EC4A 3TW, England.
EM gravesa@google.com; gregwayne@google.com; demishassabis@google.com
NR 51
TC 914
Z9 1222
U1 4
U2 226
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 471
EP +
DI 10.1038/nature20101
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400049
PM 27732574
DA 2026-03-09
ER

PT J
AU Seiple, IB
   Zhang, ZY
   Jakubec, P
   Langlois-Mercier, A
   Wright, PM
   Hog, DT
   Yabu, K
   Allu, SR
   Fukuzaki, T
   Carlsen, PN
   Kitamura, Y
   Zhou, X
   Condakes, ML
   Szczypinski, FT
   Green, WD
   Myers, AG
AF Seiple, Ian B.
   Zhang, Ziyang
   Jakubec, Pavol
   Langlois-Mercier, Audrey
   Wright, Peter M.
   Hog, Daniel T.
   Yabu, Kazuo
   Allu, Senkara Rao
   Fukuzaki, Takehiro
   Carlsen, Peter N.
   Kitamura, Yoshiaki
   Zhou, Xiang
   Condakes, Matthew L.
   Szczypinski, Filip T.
   Green, William D.
   Myers, Andrew G.
TI A platform for the discovery of new macrolide antibiotics
SO NATURE
LA English
DT Article
ID asymmetric total-synthesis; azithromycin cp-62,993; erythromycin-b; efficient; resistance; telithromycin; derivatives; ketolides; ribosome; binding
AB The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.
C1 [Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypinski, Filip T.; Green, William D.; Myers, Andrew G.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Seiple, Ian B.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Langlois-Mercier, Audrey] Novartis Pharma AG, Chem & Analyt Dev, CH-4002 Basel, Switzerland.
   [Wright, Peter M.] McKinsey & Co Inc, 55 East 52nd St,21st Floor, New York, NY 10022 USA.
   [Hog, Daniel T.] Bayer Pharma AG, Med Chem, Mullerstr 178, D-13353 Berlin, Germany.
   [Yabu, Kazuo] Daiichi Sankyo Co Ltd, Med Chem Res Labs, Shinagawa R&D Ctr, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan.
   [Kitamura, Yoshiaki] Gifu Univ, Dept Chem & Biomol Sci, 1-1 Yanagido, Gifu 5011193, Japan.
   [Condakes, Matthew L.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Szczypinski, Filip T.] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
   [Green, William D.] Univ Cambridge Trinity Coll, Cambridge CB2 1TQ, England.
C3 Harvard University; University of California System; University of California San Francisco; Novartis; McKinsey & Company; Bayer AG; Bayer Healthcare Pharmaceuticals; Daiichi Sankyo Company Limited; Gifu University; University of California System; University of California Berkeley; University of Cambridge; University of Cambridge
RP Myers, AG (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM myers@chemistry.harvard.edu
FU Gustavus and Louise Pfeiffer Research Foundation; Blavatnik Biomedical Accelerator Program at Harvard University; NERCE (NIH) [U54 AI057159]; National Institutes of Health [F32GM099233]; Swiss National Science Foundation [PBGEPE2-139864]; Novartis Foundation; Deutsche Forschungsgemeinschaft (DFG) [HO 5326/1-1]; Daiichi-Sankyo Co., Ltd; Engineering Promotion Fund of Gifu University
NR 50
TC 279
Z9 348
U1 3
U2 260
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 338
EP +
DI 10.1038/nature17967
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300038
PM 27193679
DA 2026-03-09
ER

PT J
AU Mallarino, R
   Henegar, C
   Mirasierra, M
   Manceau, M
   Schradin, C
   Vallejo, M
   Beronja, S
   Barsh, GS
   Hoekstra, HE
AF Mallarino, Ricardo
   Henegar, Corneliu
   Mirasierra, Mercedes
   Manceau, Marie
   Schradin, Carsten
   Vallejo, Mario
   Beronja, Slobodan
   Barsh, Gregory S.
   Hoekstra, Hopi E.
TI Developmental mechanisms of stripe patterns in rodents
SO NATURE
LA English
DT Article
ID color pattern; mouse coat; expression; alx3; pigmentation; evolution; genetics; binding; sox10; promoter
AB Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator of this process. In embryonic dorsal skin, patterned expression of Alx3 precedes pigment stripes and acts to directly repress Mitf, a master regulator of melanocyte differentiation, thereby giving rise to light-coloured hair. Moreover, Alx3 is upregulated in the light stripes of chipmunks, which have independently evolved a similar dorsal pattern. Our results show a previously undescribed mechanism for modulating spatial variation in hair colour and provide insights into how phenotypic novelty evolves.
C1 [Mallarino, Ricardo; Hoekstra, Hopi E.] Harvard Univ, Museum Comparat Zool, Howard Hughes Med Inst, Dept Cellular Biol, Cambridge, MA 02138 USA.
   [Mallarino, Ricardo; Hoekstra, Hopi E.] Harvard Univ, Museum Comparat Zool, Howard Hughes Med Inst, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Henegar, Corneliu; Barsh, Gregory S.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Henegar, Corneliu; Barsh, Gregory S.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
   [Mirasierra, Mercedes; Vallejo, Mario] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain.
   [Mirasierra, Mercedes; Vallejo, Mario] Ciber Diabet & Enfermedades Metabol Asociadas Cib, Madrid 28029, Spain.
   [Manceau, Marie] Coll France, Ctr Interdisciplinary Res Biol, F-75005 Paris, France.
   [Schradin, Carsten] Univ Strasbourg, CNRS, IPHC, UMR 7178, F-67000 Strasbourg, France.
   [Schradin, Carsten] Univ Witwatersrand, Sch Anim Plant & Environm Sci, ZA-2000 Johannesburg, South Africa.
   [Beronja, Slobodan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
C3 Howard Hughes Medical Institute; Harvard University; Howard Hughes Medical Institute; Harvard University; HudsonAlpha Institute for Biotechnology; Stanford University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Investigaciones Biomedicas Alberto Sols (IIBM); CIBER - Centro de Investigacion Biomedica en Red; CIBERDEM; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; College de France; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Witwatersrand; Fred Hutchinson Cancer Center
RP Hoekstra, HE (corresponding author), Harvard Univ, Museum Comparat Zool, Howard Hughes Med Inst, Dept Cellular Biol, Cambridge, MA 02138 USA.; Hoekstra, HE (corresponding author), Harvard Univ, Museum Comparat Zool, Howard Hughes Med Inst, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
EM hoekstra@oeb.harvard.edu
FU Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2011-24245, BFU2014-52149-R]; Instituto de Salud Carlos III
NR 47
TC 96
Z9 110
U1 2
U2 72
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 518
EP +
DI 10.1038/nature20109
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600035
PM 27806375
DA 2026-03-09
ER

PT J
AU Bhardwaj, G
   Mulligan, VK
   Bahl, CD
   Gilmore, JM
   Harvey, PJ
   Cheneval, O
   Buchko, GW
   Pulavarti, SVSRK
   Kaas, Q
   Eletsky, A
   Huang, PS
   Johnsen, WA
   Greisen, PJ
   Rocklin, GJ
   Song, YF
   Linsky, TW
   Watkins, A
   Rettie, SA
   Xu, XZ
   Carter, LP
   Bonneau, R
   Olson, JM
   Coutsias, E
   Correnti, CE
   Szyperski, T
   Craik, DJ
   Baker, D
AF Bhardwaj, Gaurav
   Mulligan, Vikram Khipple
   Bahl, Christopher D.
   Gilmore, Jason M.
   Harvey, Peta J.
   Cheneval, Olivier
   Buchko, Garry W.
   Pulavarti, Surya V. S. R. K.
   Kaas, Quentin
   Eletsky, Alexander
   Huang, Po-Ssu
   Johnsen, William A.
   Greisen, Per Jr
   Rocklin, Gabriel J.
   Song, Yifan
   Linsky, Thomas W.
   Watkins, Andrew
   Rettie, Stephen A.
   Xu, Xianzhong
   Carter, Lauren P.
   Bonneau, Richard
   Olson, James M.
   Coutsias, Evangelos
   Correnti, Colin E.
   Szyperski, Thomas
   Craik, David J.
   Baker, David
TI Accurate de novo design of hyperstable constrained peptides
SO NATURE
LA English
DT Article
ID nmr chemical-shifts; molecular-dynamics; protein structures; computational design; structure prediction; torsion angles; loop closure; crystallography; stabilization; simulations
AB Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18-47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N-C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.
C1 [Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Bahl, Christopher D.; Gilmore, Jason M.; Huang, Po-Ssu; Greisen, Per Jr; Rocklin, Gabriel J.; Song, Yifan; Linsky, Thomas W.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Bahl, Christopher D.; Gilmore, Jason M.; Huang, Po-Ssu; Greisen, Per Jr; Rocklin, Gabriel J.; Song, Yifan; Linsky, Thomas W.; Rettie, Stephen A.; Carter, Lauren P.; Baker, David] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
   [Harvey, Peta J.; Cheneval, Olivier; Kaas, Quentin; Craik, David J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Buchko, Garry W.] Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Seattle Struct Genom Ctr Infect Dis, Richland, WA 99352 USA.
   [Pulavarti, Surya V. S. R. K.; Eletsky, Alexander; Xu, Xianzhong; Szyperski, Thomas] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA.
   [Johnsen, William A.; Olson, James M.; Correnti, Colin E.] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA.
   [Greisen, Per Jr] Novo Nordisk AS, Global Res, DK-2760 Malov, Denmark.
   [Song, Yifan] Cyrus Biotechnol, Seattle, WA 98109 USA.
   [Watkins, Andrew] NYU, Dept Chem, New York, NY 10003 USA.
   [Bonneau, Richard] NYU, Dept Biol, New York, NY 10003 USA.
   [Bonneau, Richard] Simons Fdn, Ctr Computat Biol, New York, NY 10010 USA.
   [Coutsias, Evangelos] SUNY Stony Brook, Appl Math & Stat, Stony Brook, NY 11794 USA.
   [Coutsias, Evangelos] SUNY Stony Brook, Laufer Ctr Phys & Quantitat Biol, Stony Brook, NY 11794 USA.
   [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Queensland; United States Department of Energy (DOE); Pacific Northwest National Laboratory; State University of New York (SUNY) System; University at Buffalo, SUNY; Fred Hutchinson Cancer Center; Novo Nordisk; New York University; New York University; Simons Foundation; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.; Baker, D (corresponding author), Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.; Baker, D (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM dabaker@uw.edu
FU NIH [P50 AG005136, T32-H600035, GM094597]; Howard Hughes Medical Institute; Australian Research Council [FL150100146]; NESG; NIGMS [GM090205]; National Institute of Allergy and Infectious Diseases, National Institute of Health, Department of Health and Human Services [HHSN272201200025C]; Office of Biological and Environmental Research;  [DE-AC02-06CH11357]
NR 58
TC 339
Z9 424
U1 6
U2 336
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 329
EP +
DI 10.1038/nature19791
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100029
PM 27626386
DA 2026-03-09
ER

PT J
AU Zhao, Y
   Chen, SS
   Yoshioka, C
   Baconguis, I
   Gouaux, E
AF Zhao, Yan
   Chen, Shanshuang
   Yoshioka, Craig
   Baconguis, Isabelle
   Gouaux, Eric
TI Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM
SO NATURE
LA English
DT Article
ID 2 distinct mechanisms; ligand-binding core; glutamate-receptor; auxiliary subunits; activation; stargazin; desensitization; channels; states
AB Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors(1). Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates receptor trafficking and the kinetics of receptor gating and pharmacology(2). Here we report the cryo-electron microscopy (cryo-EM) structure of the homomeric rat GluA2 AMPA receptor saturated with TARP gamma 2 subunits, which shows how the TARPs are arranged with four-fold symmetry around the ion channel domain and make extensive interactions with the M1, M2 and M4 transmembrane helices. Poised like partially opened 'hands' underneath the two-fold symmetric ligand-binding domain (LBD) 'clamshells', one pair of TARPs is juxtaposed near the LBD dimer interface, whereas the other pair is near the LBD dimer-dimer interface. The extracellular 'domains' of TARP are positioned to not only modulate LBD clamshell closure, but also affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane domains buttress the ion channel pore.
C1 [Zhao, Yan; Chen, Shanshuang; Baconguis, Isabelle; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Yoshioka, Craig] Oregon Hlth & Sci Univ, Dept Biomed Engn, 2730 SW Moody Ave, Portland, OR 97201 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.; Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU American Heart Association [16POST27790099]; NIH [NS038631]; National Institute of Neurological Disorders and Stroke [R01NS038631] Funding Source: NIH RePORTER; American Heart Association (AHA) [16POST27790099] Funding Source: American Heart Association (AHA)
NR 48
TC 96
Z9 117
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 108
EP +
DI 10.1038/nature18961
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200040
PM 27368053
DA 2026-03-09
ER

PT J
AU Tröstl, J
   Chuang, WK
   Gordon, H
   Heinritzi, M
   Yan, C
   Molteni, U
   Ahlm, L
   Frege, C
   Bianchi, F
   Wagner, R
   Simon, M
   Lehtipalo, K
   Williamson, C
   Craven, JS
   Duplissy, J
   Adamov, A
   Almeida, J
   Bernhammer, AK
   Breitenlechner, M
   Brilke, S
   Dias, A
   Ehrhart, S
   Flagan, RC
   Franchin, A
   Fuchs, C
   Guida, R
   Gysel, M
   Hansel, A
   Hoyle, CR
   Jokinen, T
   Junninen, H
   Kangasluoma, J
   Keskinen, H
   Kim, J
   Krapf, M
   Kürten, A
   Laaksonen, A
   Lawler, M
   Leiminger, M
   Mathot, S
   Möhler, O
   Nieminen, T
   Onnela, A
   Petäjä, T
   Piel, FM
   Miettinen, P
   Rissanen, MP
   Rondo, L
   Sarnela, N
   Schobesberger, S
   Sengupta, K
   Sipilä, M
   Smith, JN
   Steiner, G
   Tomè, A
   Virtanen, A
   Wagner, AC
   Weingartner, E
   Wimmer, D
   Winkler, PM
   Ye, PL
   Carslaw, KS
   Curtius, J
   Dommen, J
   Kirkby, J
   Kulmala, M
   Riipinen, I
   Worsnop, DR
   Donahue, NM
   Baltensperger, U
AF Troestl, Jasmin
   Chuang, Wayne K.
   Gordon, Hamish
   Heinritzi, Martin
   Yan, Chao
   Molteni, Ugo
   Ahlm, Lars
   Frege, Carla
   Bianchi, Federico
   Wagner, Robert
   Simon, Mario
   Lehtipalo, Katrianne
   Williamson, Christina
   Craven, Jill S.
   Duplissy, Jonathan
   Adamov, Alexey
   Almeida, Joao
   Bernhammer, Anne-Kathrin
   Breitenlechner, Martin
   Brilke, Sophia
   Dias, Antonio
   Ehrhart, Sebastian
   Flagan, Richard C.
   Franchin, Alessandro
   Fuchs, Claudia
   Guida, Roberto
   Gysel, Martin
   Hansel, Armin
   Hoyle, Christopher R.
   Jokinen, Tuija
   Junninen, Heikki
   Kangasluoma, Juha
   Keskinen, Helmi
   Kim, Jaeseok
   Krapf, Manuel
   Kuerten, Andreas
   Laaksonen, Ari
   Lawler, Michael
   Leiminger, Markus
   Mathot, Serge
   Moehler, Ottmar
   Nieminen, Tuomo
   Onnela, Antti
   Petaejae, Tuukka
   Piel, Felix M.
   Miettinen, Pasi
   Rissanen, Matti P.
   Rondo, Linda
   Sarnela, Nina
   Schobesberger, Siegfried
   Sengupta, Kamalika
   Sipila, Mikko
   Smith, James N.
   Steiner, Gerhard
   Tome, Antonio
   Virtanen, Annele
   Wagner, Andrea C.
   Weingartner, Ernest
   Wimmer, Daniela
   Winkler, Paul M.
   Ye, Penglin
   Carslaw, Kenneth S.
   Curtius, Joachim
   Dommen, Josef
   Kirkby, Jasper
   Kulmala, Markku
   Riipinen, Ilona
   Worsnop, Douglas R.
   Donahue, Neil M.
   Baltensperger, Urs
TI The role of low-volatility organic compounds in initial particle growth in the atmosphere
SO NATURE
LA English
DT Article
ID differential mobility analyzer; oxidized ro2 radicals; sulfuric-acid; aerosol formation; alpha-pinene; oxidation-products; mass-spectrometer; size; nucleation; ozonolysis
AB About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday(1). Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres(2,3). In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles(4), thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth(5,6), leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer(7-10). Although recent studies(11-13) predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon(2), and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Kohler theory)(2,14), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown(15) that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
C1 [Troestl, Jasmin; Molteni, Ugo; Frege, Carla; Bianchi, Federico; Lehtipalo, Katrianne; Franchin, Alessandro; Fuchs, Claudia; Gysel, Martin; Hoyle, Christopher R.; Krapf, Manuel; Weingartner, Ernest; Dommen, Josef; Baltensperger, Urs] Paul Scherrer Inst, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
   [Chuang, Wayne K.; Ye, Penglin; Donahue, Neil M.] Carnegie Mellon Univ, Ctr Atmospher Particle Studies, Pittsburgh, PA 15213 USA.
   [Gordon, Hamish; Almeida, Joao; Dias, Antonio; Ehrhart, Sebastian; Franchin, Alessandro; Guida, Roberto; Mathot, Serge; Onnela, Antti; Kirkby, Jasper] CERN, CH-1211 Geneva, Switzerland.
   [Heinritzi, Martin; Simon, Mario; Williamson, Christina; Brilke, Sophia; Kuerten, Andreas; Leiminger, Markus; Piel, Felix M.; Rondo, Linda; Wagner, Andrea C.; Wimmer, Daniela; Curtius, Joachim; Kirkby, Jasper] Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.
   [Yan, Chao; Bianchi, Federico; Wagner, Robert; Lehtipalo, Katrianne; Duplissy, Jonathan; Adamov, Alexey; Franchin, Alessandro; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Keskinen, Helmi; Nieminen, Tuomo; Petaejae, Tuukka; Rissanen, Matti P.; Sarnela, Nina; Schobesberger, Siegfried; Sipila, Mikko; Steiner, Gerhard; Wimmer, Daniela; Kulmala, Markku; Worsnop, Douglas R.; Donahue, Neil M.] Univ Helsinki, Dept Phys, POB 64, FI-00014 Helsinki, Finland.
   [Ahlm, Lars; Riipinen, Ilona] Univ Stockholm, Dept Appl Environm Sci, SE-10961 Stockholm, Sweden.
   [Bianchi, Federico] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Williamson, Christina] NOAA, Div Chem Sci, Earth Syst Res Lab, Boulder, CO USA.
   [Craven, Jill S.; Flagan, Richard C.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Duplissy, Jonathan; Nieminen, Tuomo; Worsnop, Douglas R.] Univ Helsinki, Helsinki Inst Phys, POB 64, FI-00014 Helsinki, Finland.
   [Bernhammer, Anne-Kathrin; Breitenlechner, Martin; Hansel, Armin; Steiner, Gerhard] Univ Innsbruck, Inst Ion & Appl Phys, A-6020 Innsbruck, Austria.
   [Bernhammer, Anne-Kathrin; Breitenlechner, Martin; Hansel, Armin] Ionicon Analyt GmbH, A-6020 Innsbruck, Austria.
   [Hoyle, Christopher R.] SLF, WSL Inst Snow & Avalanche Res, CH-7260 Davos, Switzerland.
   [Keskinen, Helmi; Kim, Jaeseok; Laaksonen, Ari; Lawler, Michael; Miettinen, Pasi; Smith, James N.; Virtanen, Annele] Univ Eastern Finland, Kuopio 70211, Finland.
   [Laaksonen, Ari] Finnish Meteorol Inst, Helsinki 00101, Finland.
   [Lawler, Michael] Natl Ctr Atmospher Res, Atmospher Chem Observat & Modeling Lab, Boulder, CO 80301 USA.
   [Moehler, Ottmar] Karlsruhe Inst Technol, Inst Meteorol & Climate Res, D-76021 Karlsruhe, Germany.
   [Sengupta, Kamalika; Carslaw, Kenneth S.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Smith, James N.] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
   [Steiner, Gerhard; Winkler, Paul M.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Tome, Antonio] Univ Lisbon, SIM, P-1849016 Lisbon, Portugal.
   [Tome, Antonio] Univ Beira Interior, P-1849016 Lisbon, Portugal.
   [Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Williamson, Christina; Keskinen, Helmi; Kim, Jaeseok; Schobesberger, Siegfried; Weingartner, Ernest] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Williamson, Christina] NOAA, Div Chem Sci, Earth Syst Res Lab, Boulder, CO USA.
   [Keskinen, Helmi] Univ Helsinki, SMEAR II, Hyytiala Forestry Field Stn, Hyytialantie 124, FI-35500 Korkeakoski, Finland.
   [Kim, Jaeseok] Korea Polar Res Inst, Arct Res Ctr, Inchon 21990, South Korea.
   [Schobesberger, Siegfried] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Weingartner, Ernest] Univ Appl Sci Northwestern Switzerland, Inst Aerosol & Sensor Technol, CH-5210 Windisch, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Carnegie Mellon University; European Organization for Nuclear Research (CERN); Goethe University Frankfurt; University of Helsinki; Stockholm University; Swiss Federal Institutes of Technology Domain; ETH Zurich; National Oceanic Atmospheric Admin (NOAA) - USA; California Institute of Technology; University of Helsinki; Helsinki Institute of Physics; University of Innsbruck; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Eastern Finland; Finnish Meteorological Institute; National Center Atmospheric Research (NCAR) - USA; Helmholtz Association; Karlsruhe Institute of Technology; University of Leeds; University of California System; University of California Irvine; University of Vienna; Universidade de Lisboa; Universidade da Beira Interior; Aerodyne Research; University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA; University of Helsinki; Korea Polar Research Institute (KOPRI); University of Washington; University of Washington Seattle; FHNW University of Applied Sciences & Arts Northwestern Switzerland
RP Baltensperger, U (corresponding author), Paul Scherrer Inst, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
EM urs.baltensperger@psi.ch
FU CERN; EC (Marie Curie Initial Training Network 'CLOUD-ITN') [215072]; EC (MC-ITN 'CLOUD-TRAIN') [316662]; EC (ERC-StG-ATMOGAIN) [278277]; EC (ERC-Advanced 'ATMNUCLE') [227463]; German Federal Ministry of Education and Research [01LK0902A, 01LK1222A]; Swiss National Science Foundation [200020_135307, 200020_152907, 20FI20_149002, 200021_140663]; Academy of Finland Center of Excellence [1118615]; Academy of Finland (CoE) [1118615]; Academy of Finland (LASTU) [135054]; Nessling Foundation; Austrian Science Fund (FWF) [J3198-N21]; EU [656994]; Swedish Research Council, Vetenskapsradet [2011-5120]; Portuguese Foundation for Science and Technology [CERN/FP/116387/2010]; Presidium of the Russian Academy of Sciences; Russian Foundation for Basic Research [08-02-91006-CERN, 12-02-91522-CERN]; Dreyfus Award [EP-11-117]; Davidow Foundation; US National Science Foundation [AGS1136479, AGS1447056, AGS1439551, CHE1012293]; US Department of Energy [DE-SC00014469]; FP7 project BACCHUS [603445]; Swiss National Science Foundation (SNF) [20FI20_149002, 200020_152907, 200021_140663] Funding Source: Swiss National Science Foundation (SNF); Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1439551] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1447056] Funding Source: National Science Foundation; Academy of Finland (AKA) [215072] Funding Source: Academy of Finland (AKA); European Research Council (ERC) [278277] Funding Source: European Research Council (ERC)
NR 74
TC 593
Z9 671
U1 20
U2 691
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 527
EP +
DI 10.1038/nature18271
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100039
PM 27225126
DA 2026-03-09
ER

PT J
AU Ding, Y
   Berrocal, A
   Morita, T
   Longden, KD
   Stern, DL
AF Ding, Yun
   Berrocal, Augusto
   Morita, Tomoko
   Longden, Kit D.
   Stern, David L.
TI Natural courtship song variation caused by an intronic retroelement in an ion channel gene
SO NATURE
LA English
DT Article
ID activated potassium channels; tissue-specific expression; drosophila-melanogaster; c. elegans; behavior; evolution; locus; mice
AB Animal species display enormous variation for innate behaviours, but little is known about how this diversity arose. Here, using an unbiased genetic approach, we map a courtship song difference between wild isolates of Drosophila simulans and Drosophila mauritiana to a 966 base pair region within the slowpoke (slo) locus, which encodes a calcium-activated potassium channel(1). Using the reciprocal hemizygosity test(2), we confirm that slo is the causal locus and resolve the causal mutation to the evolutionarily recent insertion of a retroelement in a slo intron within D. simulans. Targeted deletion of this retroelement reverts the song phenotype and alters slo splicing. Like many ion channel genes, slo is expressed widely in the nervous system and influences a variety of behaviours(3,4); slo-null males sing little song with severely disrupted features. By contrast, the natural variant of slo alters a specific component of courtship song, illustrating that regulatory evolution of a highly pleiotropic ion channel gene can cause modular changes in behaviour.
C1 [Ding, Yun; Berrocal, Augusto; Morita, Tomoko; Longden, Kit D.; Stern, David L.] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
   [Berrocal, Augusto] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California Berkeley
RP Stern, DL (corresponding author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
EM sternd@janelia.hhmi.org
NR 30
TC 103
Z9 114
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 329
EP +
DI 10.1038/nature19093
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900035
PM 27509856
DA 2026-03-09
ER

PT J
AU Guo, JT
   Zeng, WZ
   Chen, QF
   Lee, C
   Chen, LP
   Yang, Y
   Cang, CL
   Ren, DJ
   Jiang, YX
AF Guo, Jiangtao
   Zeng, Weizhong
   Chen, Qingfeng
   Lee, Changkeun
   Chen, Liping
   Yang, Yi
   Cang, Chunlei
   Ren, Dejian
   Jiang, Youxing
TI Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana
SO NATURE
LA English
DT Article
ID of-function allele; shaker k+ channel; gating-charge; crystal-structure; ion channels; wild-type; calcium; sodium; naadp; perspective
AB Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here we present the crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain, the conformational changes of which are coupled to the pair of inner helices from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing the second voltage-sensing domain in the resting state and shift voltage activation towards more positive potentials. Our Ba-2-bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels.
C1 [Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Cang, Chunlei; Ren, Dejian] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Pennsylvania
RP Jiang, YX (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.; Jiang, YX (corresponding author), Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
EM youxing.jiang@utsouthwestern.edu
FU US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; National Institutes of Health, National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; National Institutes of Health [GM079179, NS055293, NS074257]; Welch Foundation [I-1578]
NR 57
TC 200
Z9 227
U1 1
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 196
EP +
DI 10.1038/nature16446
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100033
PM 26689363
DA 2026-03-09
ER

PT J
AU Morrissy, AS
   Garzia, L
   Shih, DJH
   Zuyderduyn, S
   Huang, X
   Skowron, P
   Remke, M
   Cavalli, FMG
   Ramaswamy, V
   Lindsay, PE
   Jelveh, S
   Donovan, LK
   Wang, X
   Luu, B
   Zayne, K
   Li, YS
   Mayoh, C
   Thiessen, N
   Mercier, E
   Mungall, KL
   Ma, Y
   Tse, K
   Zeng, T
   Shumansky, K
   Roth, AJL
   Shah, S
   Farooq, H
   Kijima, N
   Holgado, BL
   Lee, JJY
   Matan-Lithwick, S
   Liu, J
   Mack, SC
   Manno, A
   Michealraj, KA
   Nor, C
   Peacock, J
   Qin, L
   Reimand, J
   Rolider, A
   Thompson, YY
   Wu, XC
   Pugh, T
   Ally, A
   Bilenky, M
   Butterfield, YSN
   Carlsen, R
   Cheng, Y
   Chuah, E
   Corbett, RD
   Dhalla, N
   He, A
   Lee, D
   Li, HYI
   Long, W
   Mayo, M
   Plettner, P
   Qian, JQ
   Schein, JE
   Tam, A
   Wong, T
   Birol, I
   Zhao, YJ
   Faria, CC
   Pimentel, J
   Nunes, S
   Shalaby, T
   Grotzer, M
   Pollack, IF
   Hamilton, RL
   Li, XN
   Bendel, AE
   Fults, DW
   Walter, AW
   Kumabe, T
   Tominaga, T
   Collins, VP
   Cho, YJ
   Hoffman, C
   Lyden, D
   Wisoff, JH
   Garvin, JH
   Stearns, DS
   Massimi, L
   Schüller, U
   Sterba, J
   Zitterbart, K
   Puget, S
   Ayrault, O
   Dunn, SE
   Tirapelli, DPC
   Carlotti, CG
   Wheeler, H
   Hallahan, AR
   Ingram, W
   MacDonald, TJ
   Olson, JJ
   Van Meir, EG
   Lee, JY
   Wang, KC
   Kim, SK
   Cho, BK
   Pietsch, T
   Fleischhack, G
   Tippelt, S
   Ra, YS
   Bailey, S
   Lindsey, JC
   Clifford, SC
   Eberhart, CG
   Cooper, MK
   Packer, RJ
   Massimino, M
   Garre, ML
   Bartels, U
   Tabori, U
   Hawkins, CE
   Dirks, P
   Bouffet, E
   Rutka, JT
   Wechsler-Reya, RJ
   Weiss, WA
   Collier, LS
   Dupuy, AJ
   Korshunov, A
   Jones, DTW
   Kool, M
   Northcott, PA
   Pfister, SM
   Largaespada, DA
   Mungall, AJ
   Moore, RA
   Jabado, N
   Bader, GD
   Jones, SJM
   Malkin, D
   Marra, MA
   Taylor, MD
AF Morrissy, A. Sorana
   Garzia, Livia
   Shih, David J. H.
   Zuyderduyn, Scott
   Huang, Xi
   Skowron, Patryk
   Remke, Marc
   Cavalli, Florence M. G.
   Ramaswamy, Vijay
   Lindsay, Patricia E.
   Jelveh, Salomeh
   Donovan, Laura K.
   Wang, Xin
   Luu, Betty
   Zayne, Kory
   Li, Yisu
   Mayoh, Chelsea
   Thiessen, Nina
   Mercier, Eloi
   Mungall, Karen L.
   Ma, Yusanne
   Tse, Kane
   Zeng, Thomas
   Shumansky, Karey
   Roth, Andrew J. L.
   Shah, Sohrab
   Farooq, Hamza
   Kijima, Noriyuki
   Holgado, Borja L.
   Lee, John J. Y.
   Matan-Lithwick, Stuart
   Liu, Jessica
   Mack, Stephen C.
   Manno, Alex
   Michealraj, K. A.
   Nor, Carolina
   Peacock, John
   Qin, Lei
   Reimand, Juri
   Rolider, Adi
   Thompson, Yuan Y.
   Wu, Xiaochong
   Pugh, Trevor
   Ally, Adrian
   Bilenky, Mikhail
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Cheng, Young
   Chuah, Eric
   Corbett, Richard D.
   Dhalla, Noreen
   He, An
   Lee, Darlene
   Li, Haiyan I.
   Long, William
   Mayo, Michael
   Plettner, Patrick
   Qian, Jenny Q.
   Schein, Jacqueline E.
   Tam, Angela
   Wong, Tina
   Birol, Inanc
   Zhao, Yongjun
   Faria, Claudia C.
   Pimentel, Jose
   Nunes, Sofia
   Shalaby, Tarek
   Grotzer, Michael
   Pollack, Ian F.
   Hamilton, Ronald L.
   Li, Xiao-Nan
   Bendel, Anne E.
   Fults, Daniel W.
   Walter, Andrew W.
   Kumabe, Toshihiro
   Tominaga, Teiji
   Collins, V. Peter
   Cho, Yoon-Jae
   Hoffman, Caitlin
   Lyden, David
   Wisoff, Jeffrey H.
   Garvin, James H., Jr.
   Stearns, Duncan S.
   Massimi, Luca
   Schueller, Ulrich
   Sterba, Jaroslav
   Zitterbart, Karel
   Puget, Stephanie
   Ayrault, Olivier
   Dunn, Sandra E.
   Tirapelli, Daniela P. C.
   Carlotti, Carlos G.
   Wheeler, Helen
   Hallahan, Andrew R.
   Ingram, Wendy
   MacDonald, Tobey J.
   Olson, Jeffrey J.
   Van Meir, Erwin G.
   Lee, Ji-Yeoun
   Wang, Kyu-Chang
   Kim, Seung-Ki
   Cho, Byung-Kyu
   Pietsch, Torsten
   Fleischhack, Gudrun
   Tippelt, Stephan
   Ra, Young Shin
   Bailey, Simon
   Lindsey, Janet C.
   Clifford, Steven C.
   Eberhart, Charles G.
   Cooper, Michael K.
   Packer, Roger J.
   Massimino, Maura
   Garre, Maria Luisa
   Bartels, Ute
   Tabori, Uri
   Hawkins, Cynthia E.
   Dirks, Peter
   Bouffet, Eric
   Rutka, James T.
   Wechsler-Reya, Robert J.
   Weiss, William A.
   Collier, Lara S.
   Dupuy, Adam J.
   Korshunov, Andrey
   Jones, David T. W.
   Kool, Marcel
   Northcott, Paul A.
   Pfister, Stefan M.
   Largaespada, David A.
   Mungall, Andrew J.
   Moore, Richard A.
   Jabado, Nada
   Bader, Gary D.
   Jones, Steven J. M.
   Malkin, David
   Marra, Marco A.
   Taylor, Michael D.
TI Divergent clonal selection dominates medulloblastoma at recurrence
SO NATURE
LA English
DT Article
ID evolution; heterogeneity; mutations; dynamics; impact; mutagenesis; subgroups; inference; relapse; cells
AB The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
C1 [Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Huang, Xi; Skowron, Patryk; Cavalli, Florence M. G.; Ramaswamy, Vijay; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Taylor, Michael D.] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 0A4, Canada.
   [Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Skowron, Patryk; Cavalli, Florence M. G.; Ramaswamy, Vijay; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Reimand, Juri; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Tabori, Uri; Hawkins, Cynthia E.; Dirks, Peter; Bouffet, Eric; Rutka, James T.; Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
   [Shih, David J. H.; Skowron, Patryk; Ramaswamy, Vijay; Wang, Xin; Lee, John J. Y.; Peacock, John; Thompson, Yuan Y.; Rutka, James T.; Taylor, Michael D.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 0A4, Canada.
   [Zuyderduyn, Scott; Reimand, Juri; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Remke, Marc] Univ Hosp Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, Dusseldorf, Germany.
   [Ramaswamy, Vijay; Hoffman, Caitlin; Dirks, Peter; Rutka, James T.; Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5S 3E1, Canada.
   [Lindsay, Patricia E.] Univ Toronto, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada.
   [Lindsay, Patricia E.; Jelveh, Salomeh] Univ Hlth Network, Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON M5G 2M9, Canada.
   [Li, Yisu; Mayoh, Chelsea; Thiessen, Nina; Mercier, Eloi; Mungall, Karen L.; Ma, Yusanne; Tse, Kane; Zeng, Thomas; Ally, Adrian; Bilenky, Mikhail; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Young; Chuah, Eric; Corbett, Richard D.; Dhalla, Noreen; He, An; Lee, Darlene; Li, Haiyan I.; Long, William; Mayo, Michael; Plettner, Patrick; Qian, Jenny Q.; Schein, Jacqueline E.; Tam, Angela; Wong, Tina; Birol, Inanc; Zhao, Yongjun; Mungall, Andrew J.; Moore, Richard A.; Jones, Steven J. M.; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
   [Shumansky, Karey; Roth, Andrew J. L.; Shah, Sohrab] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada.
   [Mack, Stephen C.] Cleveland Clin Fdn, Ctr Stem Cell & Regenerat Med, Cleveland, OH 44195 USA.
   [Pugh, Trevor] Univ Hlth Network, Princess Margaret Canc Ctr, Clin Genom Res Program, Toronto, ON, Canada.
   [Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
   [Birol, Inanc] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada.
   [Faria, Claudia C.] Hosp Santa Maria, Ctr Hosp Lisboa Norte, Div Neurosurg, P-1649035 Lisbon, Portugal.
   [Pimentel, Jose] Hosp Santa Maria, Ctr Hosp Lisboa Norte, Div Pathol, P-1649035 Lisbon, Portugal.
   [Nunes, Sofia] Inst Portugues Oncol Francisco Gentil, Unidade Neurooncol Pediat, P-1099023 Lisbon, Portugal.
   [Shalaby, Tarek; Grotzer, Michael] Univ Childrens Hosp Zurich, Dept Oncol, CH-8032 Zurich, Switzerland.
   [Shalaby, Tarek; Grotzer, Michael] Univ Childrens Hosp Zurich, Dept Neurooncol, CH-8032 Zurich, Switzerland.
   [Pollack, Ian F.] Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15224 USA.
   [Hamilton, Ronald L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Li, Xiao-Nan] Baylor Coll Med, Brain Tumor Program, Childrens Canc Ctr, Houston, TX 77030 USA.
   [Li, Xiao-Nan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Bendel, Anne E.] Childrens Hosp & Clin Minnesota, Pediat Hematol Oncol, Minneapolis, MN 55404 USA.
   [Fults, Daniel W.] Univ Utah, Clin Neurosci Ctr, Dept Neurosurg, Salt Lake City, UT 84132 USA.
   [Walter, Andrew W.] Alfred I DuPont Hosp Children, Wilmington, DE 19803 USA.
   [Kumabe, Toshihiro] Kitasato Univ, Sch Med, Dept Neurosurg, Sagamihara, Kanagawa 2520374, Japan.
   [Tominaga, Teiji] Tohoku Univ, Grad Sch Med, Dept Neurosurg, Sendai, Miyagi 9808574, Japan.
   [Collins, V. Peter] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol Sci, Stanford, CA 94305 USA.
   [Lyden, David] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10065 USA.
   [Lyden, David] Cornell Univ, Weill Med Coll, Dept Cell Biol, New York, NY 10065 USA.
   [Lyden, David] Cornell Univ, Weill Med Coll, Dept Dev Biol, New York, NY 10065 USA.
   [Wisoff, Jeffrey H.] NYU Langone Med Ctr, Dept Neurosurg, New York, NY 10016 USA.
   [Garvin, James H., Jr.] Columbia Univ, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY 10032 USA.
   [Stearns, Duncan S.] Rainbow Babies & Childrens Hosp, Dept Pediat Hematol & Oncol, Cleveland, OH 44106 USA.
   [Stearns, Duncan S.] Case Western Reserve, Dept Pediat Hematol & Oncol, Cleveland, OH 44106 USA.
   [Massimi, Luca] Catholic Univ, Sch Med, Pediat Neurosurg, I-00198 Rome, Italy.
   [Schueller, Ulrich] Univ Munich, Ctr Neuropathol, D-81377 Munich, Germany.
   [Sterba, Jaroslav; Zitterbart, Karel] Masaryk Univ, Sch Med, Dept Pediat Oncol, Brno 62500, Czech Republic.
   [Puget, Stephanie] Univ Paris 05, Necker Enfants Malad Hosp, AP HP, Dept Neurosurg, F-75743 Paris, France.
   [Ayrault, Olivier] Inst Curie, Signaling Dev & Brain Tumors, CNRS, UMR 3347,INSERM,U1021, F-91405 Orsay 5, France.
   [Dunn, Sandra E.] British Columbia Childrens Hosp, Div Hematol Oncol, Vancouver, BC V6H 3V4, Canada.
   [Tirapelli, Daniela P. C.; Carlotti, Carlos G.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, BR-14049900 Sao Paulo, Brazil.
   [Wheeler, Helen] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2065, Australia.
   [Hallahan, Andrew R.; Ingram, Wendy] Childrens Hlth Queensland, Queensland Childrens Med Res Inst, Brisbane, Qld 4029, Australia.
   [Hallahan, Andrew R.] Childrens Hlth Queensland, Div Oncol, Brisbane, Qld 4029, Australia.
   [Ingram, Wendy] Univ Queensland, UQ Child Hlth Res Ctr, Brisbane, Qld 4029, Australia.
   [MacDonald, Tobey J.] Emory Univ, Sch Med, Pediat Neurooncol Program, Atlanta, GA 30307 USA.
   [MacDonald, Tobey J.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30307 USA.
   [Olson, Jeffrey J.] Emory Univ, Dept Neurosurg, Sch Med, Atlanta, GA 30322 USA.
   [Olson, Jeffrey J.; Van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Van Meir, Erwin G.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
   [Lee, Ji-Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki; Cho, Byung-Kyu] Seoul Natl Univ, Childrens Hosp, Div Pediat Neurosurg, Dept Neurosurg, Seoul 30322, South Korea.
   [Pietsch, Torsten] Univ Bonn, Inst Neuropathol, D-53105 Bonn, Germany.
   [Fleischhack, Gudrun; Tippelt, Stephan] Childrens Univ Hosp Essen, D-45147 Essen, Germany.
   [Ra, Young Shin] Univ Ulsan, Asan Med Ctr, Dept Neurosurg, Seoul 05505, South Korea.
   [Bailey, Simon; Lindsey, Janet C.; Clifford, Steven C.] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
   [Cooper, Michael K.] Vanderbilt Univ Sch Med, Dept Neurol, Nashville, TN 37232 USA.
   [Packer, Roger J.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
   [Massimino, Maura] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy.
   [Garre, Maria Luisa] Ist Giannina Gaslini, UO Neurochirurg, I-16147 Genoa, Italy.
   [Bartels, Ute; Tabori, Uri; Bouffet, Eric; Malkin, David] Hosp Sick Children, Dept Haematol & Oncol, Toronto, ON M5G 1X8, Canada.
   [Hawkins, Cynthia E.] Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada.
   [Wechsler-Reya, Robert J.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94158 USA.
   [Collier, Lara S.] Univ Wisconsin, Sch Pharmacol, Madison, WI 53715 USA.
   [Dupuy, Adam J.] Univ Iowa, Mol & Cellular Biol Program, Iowa City, IA 52242 USA.
   [Korshunov, Andrey] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany.
   [Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol, D-69120 Heidelberg, Germany.
   [Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Jabado, Nada] McGill Univ, Div Hematol Oncol, Montreal, PQ H2W 1S6, Canada.
   [Bader, Gary D.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5G 1L7, Canada.
   [Bader, Gary D.] Univ Toronto, Dept Mol Genet, Banting & Best Dept Med Res, Toronto, ON M5G 1L7, Canada.
   [Bader, Gary D.] Univ Toronto, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON M5G 1L7, Canada.
   [Jones, Steven J. M.] Simon Fraser Univ, Dept Mol Biol & Biochem, Toronto, ON M5G 1L7, Canada.
   [Malkin, David] Univ Toronto, Dept Pediat, Toronto, ON M5G 1X8, Canada.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; British Columbia Cancer Agency; British Columbia Cancer Agency; Cleveland Clinic Foundation; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of British Columbia; Simon Fraser University; Universidade de Lisboa; Hospital Santa Maria; Universidade de Lisboa; Hospital Santa Maria; Portuguese Institute of Oncology; University Children's Hospital Zurich; University Children's Hospital Zurich; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Baylor College of Medicine; Texas Children's Cancer Center; Baylor College of Medicine; Children's Hospitals & Clinics of Minnesota; Utah System of Higher Education; University of Utah; Nemours Alfred I. duPont Hospital for Children; Kitasato University; Tohoku University; University of Cambridge; Stanford University; Stanford University; Stanford University; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; NYU Langone Medical Center; Columbia University; University System of Ohio; Case Western Reserve University; Case Western Reserve University Hospital; University Hospitals of Cleveland; Rainbow Babies & Children's Hospital; University System of Ohio; Case Western Reserve University; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; University of Munich; Masaryk University; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Universite PSL; Institut Curie; Centre National de la Recherche Scientifique (CNRS); BC Children's Hospital; University of British Columbia; Universidade de Sao Paulo; University of Sydney; Kolling Institute of Medical Research; University of Queensland; University of Queensland; Emory University; Emory University; Emory University; Emory University; Emory University; Seoul National University (SNU); Seoul National University Hospital; University of Bonn; University of Duisburg Essen; University of Ulsan; Asan Medical Center; Newcastle University - UK; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Vanderbilt University; Children's National Health System; Fondazione IRCCS Istituto Nazionale Tumori Milan; University of Genoa; IRCCS Istituto Giannina Gaslini; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Sanford Burnham Prebys Medical Discovery Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Wisconsin System; University of Wisconsin Madison; University of Iowa; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; University of Minnesota System; University of Minnesota Twin Cities; McGill University; University of Toronto; University of Toronto; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; Simon Fraser University; University of Toronto
RP Taylor, MD (corresponding author), Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 0A4, Canada.
EM mmarra@bcgsc.ca; mdtaylor@sickkids.ca
FU Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group Ontario; Funds from 'The Family of Kathleen Lorette'; Clark H. Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; Hospital for Sick Children; Sonia and Arthur Labatt Brain Tumour Research Centre; Chief of Research Fund; Cancer Genetics Program; Garron Family Cancer Centre; B.R.A.I.N. Child; BC Childhood Cancer Parents Association; Stand Up To Cancer St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]; Canadian Cancer Society Research Institute; Garron Family Chair in Childhood Cancer Research; Cure Search for Children's Cancer Foundation; National Institutes of Health [R01CA148699, R01CA159859, CA163722, NS096236]; Pediatric Brain Tumour Foundation; Brainchild and The McLaughlin Centre at the University of Toronto; Swifty Foundation; Davis M. Ferguson Memorial Fund at ABTA; V.R; Ontario Institute for Cancer Research through Government of Ontario; CureSearch for Children's Cancer; German Cancer Aid [109252]; German Federal Ministry of Education and Research (BMBF) [01KU1201A, 0315416C, NGFNplus 01GS0883]; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); Hungarian Brain Research Program Grant [KTIA_13_NAP-A-V/3, NAP-A-II/7]; Janos Bolyai scholarship of the Hungarian Academy of Sciences; St. Baldrick's Foundation; Cure Childhood Cancer Foundation; B.R.A.I.N. Child and Megan's Walk; Dr. Mildred Scheel Foundation; Stephen Buttrum Brain Tumour Research Fellowship; CIHR fellowship; Alberta Innovates-Health Solutions Clinical Fellowship; National Cancer Institute [P30CA077598, P30CA030199, R01CA159859] Funding Source: NIH RePORTER; Cancer Research UK [13457] Funding Source: researchfish; Sparks Charity [09NCL02] Funding Source: researchfish; The Brain Tumour Charity [16/193] Funding Source: researchfish
NR 59
TC 265
Z9 307
U1 0
U2 79
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 351
EP +
DI 10.1038/nature16478
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800037
PM 26760213
DA 2026-03-09
ER

PT J
AU Hirose, M
   Cappellaro, P
AF Hirose, Masashi
   Cappellaro, Paola
TI Coherent feedback control of a single qubit in diamond
SO NATURE
LA English
DT Article
ID nuclear-spin; envelope modulation; quantum feedback; spectroscopy; silicon; systems; states
AB Engineering desired operations on qubits subjected to the deleterious effects of their environment is a critical task in quantum information processing, quantum simulation and sensing. The most common approach relies on open-loop quantum control techniques, including optimal-control algorithms based on analytical(1) or numerical(2) solutions, Lyapunov design(3) and Hamiltonian engineering(4). An alternative strategy, inspired by the success of classical control, is feedback control(5). Because of the complications introduced by quantum measurement(6), closed-loop control is less pervasive in the quantum setting and, with exceptions(7,8), its experimental implementations have been mainly limited to quantum optics experiments. Here we implement a feedback-control algorithm using a solid-state spin qubit system associated with the nitrogen vacancy centre in diamond, using coherent feedback(9) to overcome the limitations of measurement-based feedback, and show that it can protect the qubit against intrinsic dephasing noise for milliseconds. In coherent feedback, the quantum system is connected to an auxiliary quantum controller (ancilla) that acquires information about the output state of the system (by an entangling operation) and performs an appropriate feedback action (by a conditional gate). In contrast to open-loop dynamical decoupling techniques(10), feedback control can protect the qubit even against Markovian noise and for an arbitrary period of time (limited only by the coherence time of the ancilla), while allowing gate operations. It is thus more closely related to quantum error-correction schemes(11-14), although these require larger and increasing qubit overheads. Increasing the number of fresh ancillas enables protection beyond their coherence time. We further evaluate the robustness of the feedback protocol, which could be applied to quantum computation and sensing, by exploring a trade-off between information gain and decoherence protection, as measurement of the ancilla-qubit correlation after the feedback algorithm voids the protection, even if the rest of the dynamics is unchanged.
C1 [Hirose, Masashi; Cappellaro, Paola] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Hirose, Masashi; Cappellaro, Paola] MIT, Dept Nucl Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Cappellaro, P (corresponding author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.; Cappellaro, P (corresponding author), MIT, Dept Nucl Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM pcappell@mit.edu
FU US Air Force Office of Scientific Research [FA9550-12-1-0292]; US Office of Naval Research [N00014-14-1-0804]; Direct For Mathematical & Physical Scien; Division Of Physics [1125846, 1205923, 1205635] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1521560] Funding Source: National Science Foundation
NR 37
TC 96
Z9 109
U1 0
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 77
EP +
DI 10.1038/nature17404
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500036
PM 27078567
DA 2026-03-09
ER

PT J
AU Kim, TH
   Puggioni, D
   Yuan, Y
   Xie, L
   Zhou, H
   Campbell, N
   Ryan, PJ
   Choi, Y
   Kim, JW
   Patzner, JR
   Ryu, S
   Podkaminer, JP
   Irwin, J
   Ma, Y
   Fennie, CJ
   Rzchowski, MS
   Pan, XQ
   Gopalan, V
   Rondinelli, JM
   Eom, CB
AF Kim, T. H.
   Puggioni, D.
   Yuan, Y.
   Xie, L.
   Zhou, H.
   Campbell, N.
   Ryan, P. J.
   Choi, Y.
   Kim, J-W
   Patzner, J. R.
   Ryu, S.
   Podkaminer, J. P.
   Irwin, J.
   Ma, Y.
   Fennie, C. J.
   Rzchowski, M. S.
   Pan, X. Q.
   Gopalan, V.
   Rondinelli, J. M.
   Eom, C. B.
TI Polar metals by geometric design
SO NATURE
LA English
DT Article
ID improper ferroelectricity; perovskite; transition; route; films
AB Gauss's law dictates that the net electric field inside a conductor in electrostatic equilibrium is zero by effective charge screening; free carriers within a metal eliminate internal dipoles that may arise owing to asymmetric charge distributions(1). Quantum physics supports this view(2), demonstrating that delocalized electrons make a static macroscopic polarization, an ill-defined quantity in metals(3)-it is exceedingly unusual to find a polar metal that exhibits long-range ordered dipoles owing to cooperative atomic displacements aligned from dipolar interactions as in insulating phases(4). Here we describe the quantum mechanical design and experimental realization of room-temperature polar metals in thin-film ANiO(3) perovskite nickelates using a strategy based on atomic-scale control of inversion-preserving (centric) displacements(5). We predict with ab initio calculations that cooperative polar A cation displacements are geometrically stabilized with a non-equilibrium amplitude and tilt pattern of the corner-connected NiO6 octahedra-the structural signatures of perovskites-owing to geometric constraints imposed by the underlying substrate. Heteroepitaxial thin-films grown on LaAlO3 (111) substrates fulfil the design principles. We achieve both a conducting polar monoclinic oxide that is inaccessible in compositionally identical films grown on (001) substrates, and observe a hidden, previously unreported(6-10), non-equilibrium structure in thin-film geometries. We expect that the geometric stabilization approach will provide novel avenues for realizing new multifunctional materials with unusual coexisting properties.
C1 [Kim, T. H.; Patzner, J. R.; Ryu, S.; Podkaminer, J. P.; Ma, Y.; Eom, C. B.] Univ Wisconsin, Dept Mat Sci & Engn, 1509 Univ Ave, Madison, WI 53706 USA.
   [Puggioni, D.; Rondinelli, J. M.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Yuan, Y.; Gopalan, V.] Penn State Univ, Dept Mat Sci & Engn, University Pk, PA 16802 USA.
   [Yuan, Y.; Gopalan, V.] Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA.
   [Xie, L.; Pan, X. Q.] Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA.
   [Xie, L.; Pan, X. Q.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Xie, L.] Nanjing Univ, Natl Lab Solid State Microstruct, Nanjing 210093, Jiangsu, Peoples R China.
   [Xie, L.] Nanjing Univ, Coll Engn & Appl Sci, Nanjing 210093, Jiangsu, Peoples R China.
   [Zhou, H.; Ryan, P. J.; Choi, Y.; Kim, J-W] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Campbell, N.; Irwin, J.; Rzchowski, M. S.] Univ Wisconsin, Dept Phys, 1150 Univ Ave, Madison, WI 53706 USA.
   [Fennie, C. J.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Northwestern University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California Irvine; University of California System; University of California Irvine; Nanjing University; Nanjing University; United States Department of Energy (DOE); Argonne National Laboratory; University of Wisconsin System; University of Wisconsin Madison; Cornell University
RP Eom, CB (corresponding author), Univ Wisconsin, Dept Mat Sci & Engn, 1509 Univ Ave, Madison, WI 53706 USA.
EM ceom@wisc.edu
FU National Science Foundation (NSF) under Designing Materials to Revolutionize and Engineer our Future grant [DMR-1234096]; US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences (BES) [DE-FG02-06ER46327]; DOE-BES [DE-SC0012375, DE-AC-02-06CH11357]; Army Research Office [W911NF-15-1-0017]; NSF XSEDE [ACI-1053575];  [DMR-1056441]; Division Of Materials Research; Direct For Mathematical & Physical Scien [1056441, 1234096] Funding Source: National Science Foundation
NR 40
TC 295
Z9 343
U1 12
U2 393
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 68
EP +
DI 10.1038/nature17628
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900040
PM 27096369
DA 2026-03-09
ER

PT J
AU Kirkby, J
   Duplissy, J
   Sengupta, K
   Frege, C
   Gordon, H
   Williamson, C
   Heinritzi, M
   Simon, M
   Yan, C
   Almeida, J
   Tröstl, J
   Nieminen, T
   Ortega, IK
   Wagner, R
   Adamov, A
   Amorim, A
   Bernhammer, AK
   Bianchi, F
   Breitenlechner, M
   Brilke, S
   Chen, XM
   Craven, J
   Dias, A
   Ehrhart, S
   Flagan, RC
   Franchin, A
   Fuchs, C
   Guida, R
   Hakala, J
   Hoyle, CR
   Jokinen, T
   Junninen, H
   Kangasluoma, J
   Kim, J
   Krapf, M
   Kürten, A
   Laaksonen, A
   Lehtipalo, K
   Makhmutov, V
   Mathot, S
   Molteni, U
   Onnela, A
   Peräkylä, O
   Piel, F
   Petäjä, T
   Praplan, AP
   Pringle, K
   Rap, A
   Richards, NAD
   Riipinen, I
   Rissanen, MP
   Rondo, L
   Sarnela, N
   Schobesberger, S
   Scott, CE
   Seinfeld, JH
   Sipilä, M
   Steiner, G
   Stozhkov, Y
   Stratmann, F
   Tomé, A
   Virtanen, A
   Vogel, AL
   Wagner, AC
   Wagner, PE
   Weingartner, E
   Wimmer, D
   Winkler, PM
   Ye, PL
   Zhang, X
   Hansel, A
   Dommen, J
   Donahue, NM
   Worsnop, DR
   Baltensperger, U
   Kulmala, M
   Carslaw, KS
   Curtius, J
AF Kirkby, Jasper
   Duplissy, Jonathan
   Sengupta, Kamalika
   Frege, Carla
   Gordon, Hamish
   Williamson, Christina
   Heinritzi, Martin
   Simon, Mario
   Yan, Chao
   Almeida, Joao
   Troestl, Jasmin
   Nieminen, Tuomo
   Ortega, Ismael K.
   Wagner, Robert
   Adamov, Alexey
   Amorim, Antonio
   Bernhammer, Anne-Kathrin
   Bianchi, Federico
   Breitenlechner, Martin
   Brilke, Sophia
   Chen, Xuemeng
   Craven, Jill
   Dias, Antonio
   Ehrhart, Sebastian
   Flagan, Richard C.
   Franchin, Alessandro
   Fuchs, Claudia
   Guida, Roberto
   Hakala, Jani
   Hoyle, Christopher R.
   Jokinen, Tuija
   Junninen, Heikki
   Kangasluoma, Juha
   Kim, Jaeseok
   Krapf, Manuel
   Kuerten, Andreas
   Laaksonen, Ari
   Lehtipalo, Katrianne
   Makhmutov, Vladimir
   Mathot, Serge
   Molteni, Ugo
   Onnela, Antti
   Peraekylae, Otso
   Piel, Felix
   Petaejae, Tuukka
   Praplan, Arnaud P.
   Pringle, Kirsty
   Rap, Alexandru
   Richards, Nigel A. D.
   Riipinen, Ilona
   Rissanen, Matti P.
   Rondo, Linda
   Sarnela, Nina
   Schobesberger, Siegfried
   Scott, Catherine E.
   Seinfeld, John H.
   Sipilae, Mikko
   Steiner, Gerhard
   Stozhkov, Yuri
   Stratmann, Frank
   Tome, Antonio
   Virtanen, Annele
   Vogel, Alexander L.
   Wagner, Andrea C.
   Wagner, Paul E.
   Weingartner, Ernest
   Wimmer, Daniela
   Winkler, Paul M.
   Ye, Penglin
   Zhang, Xuan
   Hansel, Armin
   Dommen, Josef
   Donahue, Neil M.
   Worsnop, Douglas R.
   Baltensperger, Urs
   Kulmala, Markku
   Carslaw, Kenneth S.
   Curtius, Joachim
TI Ion-induced nucleation of pure biogenic particles
SO NATURE
LA English
DT Article
ID atmospheric sulfuric-acid; aerosol formation; mass-spectrometer; molecular-weight; cosmic-rays; size; ozonolysis; products; growth; coagulation
AB Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.
C1 [Kirkby, Jasper; Williamson, Christina; Heinritzi, Martin; Simon, Mario; Almeida, Joao; Brilke, Sophia; Ehrhart, Sebastian; Franchin, Alessandro; Kuerten, Andreas; Piel, Felix; Rondo, Linda; Wagner, Andrea C.; Wimmer, Daniela; Curtius, Joachim] Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.
   [Kirkby, Jasper; Gordon, Hamish; Almeida, Joao; Dias, Antonio; Ehrhart, Sebastian; Franchin, Alessandro; Guida, Roberto; Mathot, Serge; Onnela, Antti; Vogel, Alexander L.] CERN, CH-1211 Geneva, Switzerland.
   [Duplissy, Jonathan; Yan, Chao; Nieminen, Tuomo; Wagner, Robert; Adamov, Alexey; Chen, Xuemeng; Franchin, Alessandro; Hakala, Jani; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Kuerten, Andreas; Lehtipalo, Katrianne; Peraekylae, Otso; Petaejae, Tuukka; Praplan, Arnaud P.; Rap, Alexandru; Rissanen, Matti P.; Sarnela, Nina; Schobesberger, Siegfried; Sipilae, Mikko; Steiner, Gerhard; Vogel, Alexander L.; Wagner, Andrea C.; Wimmer, Daniela; Worsnop, Douglas R.; Kulmala, Markku] Univ Helsinki, Dept Phys, FI-00014 Helsinki, Finland.
   [Duplissy, Jonathan; Nieminen, Tuomo; Sipilae, Mikko; Kulmala, Markku] Univ Helsinki, Helsinki Inst Phys, FI-00014 Helsinki, Finland.
   [Sengupta, Kamalika; Pringle, Kirsty; Rap, Alexandru; Richards, Nigel A. D.; Scott, Catherine E.; Carslaw, Kenneth S.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Frege, Carla; Troestl, Jasmin; Bianchi, Federico; Franchin, Alessandro; Fuchs, Claudia; Hoyle, Christopher R.; Krapf, Manuel; Lehtipalo, Katrianne; Molteni, Ugo; Weingartner, Ernest; Dommen, Josef; Baltensperger, Urs] Paul Scherrer Inst, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
   [Heinritzi, Martin; Bernhammer, Anne-Kathrin; Breitenlechner, Martin; Steiner, Gerhard; Hansel, Armin] Univ Innsbruck, Inst Ion & Appl Phys, A-6020 Innsbruck, Austria.
   [Ortega, Ismael K.] Onera French Aerosp Lab, F-91123 Palaiseau, France.
   [Amorim, Antonio] Univ Lisbon, SIM, P-1849016 Lisbon, Portugal.
   [Bernhammer, Anne-Kathrin; Breitenlechner, Martin; Hansel, Armin] Ionicon Analyt GmbH, A-6020 Innsbruck, Austria.
   [Bianchi, Federico] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Craven, Jill; Flagan, Richard C.; Seinfeld, John H.; Zhang, Xuan] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Hoyle, Christopher R.] WSL Inst Snow & Avalanche Res SLF, CH-7260 Davos, Switzerland.
   [Kim, Jaeseok; Laaksonen, Ari; Virtanen, Annele; Worsnop, Douglas R.] Univ Eastern Finland, FI-70211 Kuopio, Finland.
   [Laaksonen, Ari] Finnish Meteorol Inst, FI-00101 Helsinki, Finland.
   [Makhmutov, Vladimir; Stozhkov, Yuri] Lebedev Phys Inst, Solar & Cosm Ray Res Lab, Moscow 119991, Russia.
   [Richards, Nigel A. D.] Univ Leeds, Natl Ctr Earth Observat Leeds, Leeds LS2 9JT, W Yorkshire, England.
   [Riipinen, Ilona] Univ Stockholm, Dept Appl Environm Sci, SE-10961 Stockholm, Sweden.
   [Steiner, Gerhard; Wagner, Paul E.; Winkler, Paul M.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Stratmann, Frank] Leibniz Inst Tropospher Res, D-04318 Leipzig, Germany.
   [Tome, Antonio] Univ Beira Interior, P-6201001 Covilha, Portugal.
   [Ye, Penglin; Donahue, Neil M.] Carnegie Mellon Univ, Ctr Atmospher Particle Studies, Pittsburgh, PA 15213 USA.
   [Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Williamson, Christina] Univ Colorado, CIRES, Boulder, CO 80309 USA.
   [Kim, Jaeseok] Korea Polar Res Inst, Arct Res Ctr, Inchon 406840, South Korea.
   [Schobesberger, Siegfried] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
C3 Goethe University Frankfurt; European Organization for Nuclear Research (CERN); University of Helsinki; Helsinki Institute of Physics; University of Helsinki; University of Leeds; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Innsbruck; National Office for Aerospace Studies & Research (ONERA); Universite Paris Saclay; Universidade de Lisboa; Swiss Federal Institutes of Technology Domain; ETH Zurich; California Institute of Technology; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Eastern Finland; Finnish Meteorological Institute; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute; University of Leeds; Stockholm University; University of Vienna; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); Universidade da Beira Interior; Carnegie Mellon University; Aerodyne Research; University of Colorado System; University of Colorado Boulder; Korea Polar Research Institute (KOPRI); Korea Institute of Ocean Science & Technology (KIOST); University of Washington; University of Washington Seattle
RP Kirkby, J (corresponding author), Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.; Kirkby, J (corresponding author), CERN, CH-1211 Geneva, Switzerland.
EM jasper.kirkby@cern.ch
FU CERN; EC (Marie Curie Initial Training Network MC-ITN CLOUD-TRAIN) [316662]; EC (EU) [656994]; EC (ERC) [616075, 227463]; German Federal Ministry of Education and Research [01LK1222A]; Swiss National Science Foundation [200020_135307, 200021_140663, 206021_144947/1, 20FI20_149002/1]; Academy of Finland (Center of Excellence) [1118615]; Academy of Finland [135054, 133872, 251427, 139656, 139995, 137749, 141217, 141451]; Finnish Funding Agency for Technology and Innovation; Vaisala Foundation; Nessling Foundation; Austrian Science Fund (FWF) [L593]; Portuguese Foundation for Science and Technology [CERN/FP/116387/2010]; Swedish Research Council, Vetenskapsradet [2011-5120]; Presidium of the Russian Academy of Sciences; Russian Foundation for Basic Research [12-02-91522-CERN]; UK Natural Environment Research Council [NE/K015966/1]; Royal Society; US National Science Foundation [AGS1136479, AGS1447056, CHE1012293]; Caltech ESE Grant (Davidow Foundation); Dreyfus Award [EP-11-117]; French National Research Agency (ANR); Nord-Pas de Calais; European Funds for Regional Economic Development (FEDER, Labex-Cappa) [ANR-11-LABX-0005-01]; Marie Curie Actions (MSCA) [656994] Funding Source: Marie Curie Actions (MSCA); Natural Environment Research Council [NE/K015966/1] Funding Source: researchfish; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1447056] Funding Source: National Science Foundation; Swiss National Science Foundation (SNF) [200021_140663, 20FI20_149002, 206021_144947] Funding Source: Swiss National Science Foundation (SNF); NERC [NE/K015966/1] Funding Source: UKRI
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   Riipinen I, 2011, ATMOS CHEM PHYS, V11, P3865, DOI 10.5194/acp-11-3865-2011
   Rissanen MP, 2015, J PHYS CHEM A, V119, P4633, DOI 10.1021/jp510966g
   Rissanen MP, 2014, J AM CHEM SOC, V136, P15596, DOI 10.1021/ja507146s
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   Sihto SL, 2006, ATMOS CHEM PHYS, V6, P4079, DOI 10.5194/acp-6-4079-2006
   Suni T, 2008, ATMOS CHEM PHYS, V8, P129, DOI 10.5194/acp-8-129-2008
   TAIRA M, 1990, ANAL CHEM, V62, P630, DOI 10.1021/ac00205a018
   Tröstl J, 2016, NATURE, V533, P527, DOI 10.1038/nature18271
   Vanhanen J, 2011, AEROSOL SCI TECH, V45, P533, DOI 10.1080/02786826.2010.547889
   Wimmer D, 2013, ATMOS MEAS TECH, V6, P1793, DOI 10.5194/amt-6-1793-2013
   Zhang K, 2011, ATMOS CHEM PHYS, V11, P7817, DOI 10.5194/acp-11-7817-2011
   Zhang RY, 2004, SCIENCE, V304, P1487, DOI 10.1126/science.1095139
   ZHANG SH, 1995, AEROSOL SCI TECH, V23, P357, DOI 10.1080/02786829508965320
   Zhang X, 2015, P NATL ACAD SCI USA, V112, P14168, DOI 10.1073/pnas.1517742112
   Zhao J, 2013, ATMOS CHEM PHYS, V13, P7631, DOI 10.5194/acp-13-7631-2013
   Zhao Y, 2008, THEOR CHEM ACC, V120, P215, DOI 10.1007/s00214-007-0310-x
NR 74
TC 439
Z9 495
U1 7
U2 532
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 521
EP +
DI 10.1038/nature17953
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100038
PM 27225125
DA 2026-03-09
ER

PT J
AU Li, ZM
   Pradeep, KG
   Deng, Y
   Raabe, D
   Tasan, CC
AF Li, Zhiming
   Pradeep, Konda Gokuldoss
   Deng, Yun
   Raabe, Dierk
   Tasan, Cemal Cem
TI Metastable high-entropy dual-phase alloys overcome the strength-ductility trade-off
SO NATURE
LA English
DT Article
ID stacking-fault; steel; martensite; plasticity; boundary; austenite; design; transformation; stability
AB Metals have been mankind's most essential materials for thousands of years; however, their use is affected by ecological and economical concerns. Alloys with higher strength and ductility could alleviate some of these concerns by reducing weight and improving energy efficiency. However, most metallurgical mechanisms for increasing strength lead to ductility loss, an effect referred to as the strength-ductility trade-off(1,2). Here we present a metastability-engineering strategy in which we design nanostructured, bulk high-entropy alloys with multiple compositionally equivalent high-entropy phases. High-entropy alloys were originally proposed to benefit from phase stabilization through entropy maximization(3-6). Yet here, motivated by recent work that relaxes the strict restrictions on high-entropy alloy compositions by demonstrating the weakness of this connection(7-11), the concept is overturned. We decrease phase stability to achieve two key benefits: interface hardening due to a dual-phase microstructure (resulting from reduced thermal stability of the high-temperature phase(12)); and transformation-induced hardening (resulting from the reduced mechanical stability of the room-temperature phase(13)). This combines the best of two worlds: extensive hardening due to the decreased phase stability known from advanced steels(14,15) and massive solid-solution strengthening of high-entropy alloys(3). In our transformation-induced plasticity-assisted, dual-phase high-entropy alloy (TRIP-DP-HEA), these two contributions lead respectively to enhanced trans-grain and inter-grain slip resistance, and hence, increased strength. Moreover, the increased strain hardening capacity that is enabled by dislocation hardening of the stable phase and transformation-induced hardening of the metastable phase produces increased ductility. This combined increase in strength and ductility distinguishes the TRIP-DP-HEA alloy from other recently developed structural materials(16,17). This metastability-engineering strategy should thus usefully guide design in the near-infinite compositional space of high-entropy alloys.
C1 [Li, Zhiming; Pradeep, Konda Gokuldoss; Deng, Yun; Raabe, Dierk; Tasan, Cemal Cem] Max Planck Inst Eisenforsch GmbH, Max Planck Str 1, D-40237 Dusseldorf, Germany.
   [Tasan, Cemal Cem] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
C3 Max Planck Society; Massachusetts Institute of Technology (MIT)
RP Li, ZM; Raabe, D; Tasan, CC (corresponding author), Max Planck Inst Eisenforsch GmbH, Max Planck Str 1, D-40237 Dusseldorf, Germany.; Tasan, CC (corresponding author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
EM zhiming.li@mpie.de; d.raabe@mpie.de; tasan@mit.edu
FU European Research Council under the EU [290998]; European Research Council (ERC) [290998] Funding Source: European Research Council (ERC)
NR 30
TC 3427
Z9 3539
U1 153
U2 3554
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 227
EP +
DI 10.1038/nature17981
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100036
PM 27279217
DA 2026-03-09
ER

PT J
AU Mallard, C
   Coltice, N
   Seton, M
   Müller, RD
   Tackley, PJ
AF Mallard, Claire
   Coltice, Nicolas
   Seton, Maria
   Muller, R. Dietmar
   Tackley, Paul J.
TI Subduction controls the distribution and fragmentation of Earth's tectonic plates
SO NATURE
LA English
DT Article
ID mantle convection; models; pacific; reconstructions; reorganization; parameters; behavior; basin; flow; ma
AB The theory of plate tectonics describes how the surface of Earth is split into an organized jigsaw of seven large plates(1) of similar sizes and a population of smaller plates whose areas follow a fractal distribution(2,3). The reconstruction of global tectonics during the past 200 million years(4) suggests that this layout is probably a long-term feature of Earth, but the forces governing it are unknown. Previous studies(3,5,6), primarily based on the statistical properties of plate distributions, were unable to resolve how the size of the plates is determined by the properties of the lithosphere and the underlying mantle convection. Here we demonstrate that the plate layout of Earth is produced by a dynamic feedback between mantle convection and the strength of the lithosphere. Using three-dimensional spherical models of mantle convection that self-consistently produce the plate size-frequency distribution observed for Earth, we show that subduction geometry drives the tectonic fragmentation that generates plates. The spacing between the slabs controls the layout of large plates, and the stresses caused by the bending of trenches break plates into smaller fragments. Our results explain why the fast evolution in small back-arc plates(7,8) reflects the marked changes in plate motions during times of major reorganizations. Our study opens the way to using convection simulations with plate-like behaviour to unravel how global tectonics and mantle convection are dynamically connected.
C1 [Mallard, Claire; Coltice, Nicolas] Univ Lyon 1, CNRS, UMR 5276, Lab Geol Lyon,Ecole Normale Super, F-69622 Villeurbanne, France.
   [Coltice, Nicolas] Inst Univ France, 103 Blvd St Michel, F-75005 Paris, France.
   [Seton, Maria; Muller, R. Dietmar] Univ Sydney, Sch Geosci, EarthByte Grp, Madsen Bldg F09, Sydney, NSW 2006, Australia.
   [Tackley, Paul J.] ETH, Dept Earth Sci, Inst Geophys, Sonneggstr 5, CH-8092 Zurich, Switzerland.
C3 Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Ecole Normale Superieure de Lyon (ENS de LYON); Institut Universitaire de France; University of Sydney; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Mallard, C (corresponding author), Univ Lyon 1, CNRS, UMR 5276, Lab Geol Lyon,Ecole Normale Super, F-69622 Villeurbanne, France.
EM claire.mallard@univ-lyon1.fr
FU European Research Council under ERC [617588]; Institut Universitaire de France; ARC [DP130101946, FT130101564]; European Research Council (ERC) [617588] Funding Source: European Research Council (ERC)
NR 37
TC 95
Z9 115
U1 2
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 140
EP +
DI 10.1038/nature17992
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600040
PM 27309815
DA 2026-03-09
ER

PT J
AU Zhou, F
   Li, XL
   Wang, WL
   Zhu, P
   Zhou, J
   He, WY
   Ding, M
   Xiong, FY
   Zheng, XN
   Li, Z
   Ni, YL
   Mu, XH
   Wen, L
   Cheng, T
   Lan, Y
   Yuan, WP
   Tang, FC
   Liu, B
AF Zhou, Fan
   Li, Xianlong
   Wang, Weili
   Zhu, Ping
   Zhou, Jie
   He, Wenyan
   Ding, Meng
   Xiong, Fuyin
   Zheng, Xiaona
   Li, Zhuan
   Ni, Yanli
   Mu, Xiaohuan
   Wen, Lu
   Cheng, Tao
   Lan, Yu
   Yuan, Weiping
   Tang, Fuchou
   Liu, Bing
TI Tracing haematopoietic stem cell formation at single-cell resolution
SO NATURE
LA English
DT Article
ID rna-seq; agm region; definitive hematopoiesis; haemogenic endothelium; transcriptome analysis; embryonic-development; progenitor cells; fetal liver; lineage; differentiation
AB Haematopoietic stem cells (HSCs) are derived early from embryonic precursors, such as haemogenic endothelial cells and pre-haematopoietic stem cells (pre-HSCs), the molecular identity of which still remains elusive. Here we use potent surface markers to capture the nascent pre-HSCs at high purity, as rigorously validated by single-cell-initiated serial transplantation. Then we apply single-cell RNA sequencing to analyse endothelial cells, CD45(-) and CD45(+) pre-HSCs in the aorta-gonad-mesonephros region, and HSCs in fetal liver. Pre-HSCs show unique features in transcriptional machinery, arterial signature, metabolism state, signalling pathway, and transcription factor network. Functionally, activation of mechanistic targets of rapamycin (mTOR) is shown to be indispensable for the emergence of HSCs but not haematopoietic progenitors. Transcriptome data-based functional analysis reveals remarkable heterogeneity in cell-cycle status of pre-HSCs. Finally, the core molecular signature of pre-HSCs is identified. Collectively, our work paves the way for dissection of complex molecular mechanisms regulating stepwise generation of HSCs in vivo, informing future efforts to engineer HSCs for clinical applications.
C1 [Zhou, Fan; Zhou, Jie; He, Wenyan; Ding, Meng; Xiong, Fuyin; Zheng, Xiaona; Li, Zhuan; Ni, Yanli; Liu, Bing] Acad Mil Med Sci, Translat Med Ctr Stem Cells, Ivy Translat Med Ctr 307, Affiliated Hosp,State Key Lab Prote,Lab Oncol, Beijing 100071, Peoples R China.
   [Li, Xianlong; Zhu, Ping; Wen, Lu; Tang, Fuchou] Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.
   [Wang, Weili; Mu, Xiaohuan; Cheng, Tao; Yuan, Weiping; Liu, Bing] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.
   [Wang, Weili; Mu, Xiaohuan; Cheng, Tao; Yuan, Weiping; Liu, Bing] Chinese Acad Med Sci, Blood Dis Hosp, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China.
   [Zhu, Ping; Tang, Fuchou] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
   [Wen, Lu; Tang, Fuchou] Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China.
   [Cheng, Tao] Collaborat Innovat Ctr Canc Med, Natl Inst Biol Sci, Tianjin 300020, Peoples R China.
   [Lan, Yu] Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing 100071, Peoples R China.
   [Tang, Fuchou] CMTM, Beijing 100101, Peoples R China.
   [Liu, Bing] Med Coll Jinan Univ, Inst Hematol, Guangzhou 510632, Guangdong, Peoples R China.
C3 Academy of Military Medical Sciences - China; Peking University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Peking University; Jinan University
RP Liu, B (corresponding author), Acad Mil Med Sci, Translat Med Ctr Stem Cells, Ivy Translat Med Ctr 307, Affiliated Hosp,State Key Lab Prote,Lab Oncol, Beijing 100071, Peoples R China.; Tang, FC (corresponding author), Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.; Yuan, WP; Liu, B (corresponding author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.; Yuan, WP; Liu, B (corresponding author), Chinese Acad Med Sci, Blood Dis Hosp, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China.; Tang, FC (corresponding author), Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.; Tang, FC (corresponding author), Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China.; Tang, FC (corresponding author), CMTM, Beijing 100101, Peoples R China.; Liu, B (corresponding author), Med Coll Jinan Univ, Inst Hematol, Guangzhou 510632, Guangdong, Peoples R China.
EM wpyuan@ihcams.ac.cn; tangfuchou@pku.edu.cn; bingliu17@yahoo.com
FU Chinese National Key Program on Basic Research [2011CB964800, 2012CB966904, 2012CB966704, 2012CB966604]; National Natural Science Foundation of China [31425012, 31371185, 81400076, 31322037, 81561138005, 81421002, 81561138003, 81370596, 91439128]; National Key Program on Stem Cell and Translational Research [SQ2016ZY05002341]; SKLEH-Pilot Research Grant [ZK12-04, ZK13-04]
NR 56
TC 292
Z9 344
U1 3
U2 199
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 487
EP +
DI 10.1038/nature17997
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100031
PM 27225119
DA 2026-03-09
ER

PT J
AU Sassone-Corsi, M
   Nuccio, SP
   Liu, H
   Hernandez, D
   Vu, CT
   Takahashi, AA
   Edwards, RA
   Raffatellu, M
AF Sassone-Corsi, Martina
   Nuccio, Sean-Paul
   Liu, Henry
   Hernandez, Dulcemaria
   Vu, Christine T.
   Takahashi, Amy A.
   Edwards, Robert A.
   Raffatellu, Manuela
TI Microcins mediate competition among Enterobacteriaceae in the inflamed gut
SO NATURE
LA English
DT Article
ID colonization resistance; coli; typhimurium; peptides; growth
AB The Enterobacteriaceae are a family of Gram-negative bacteria that include commensal organisms as well as primary and opportunistic pathogens that are among the leading causes of morbidity and mortality worldwide. Although Enterobacteriaceae often comprise less than 1% of a healthy intestine's microbiota(1), some of these organisms can bloom in the inflamed gut(2-5); expansion of enterobacteria is a hallmark of microbial imbalance known as dysbiosis(6). Microcins are small secreted proteins that possess antimicrobial activity in vitro(7,8), but whose role in vivo has been unclear. Here we demonstrate that microcins enable the probiotic bacterium Escherichia coli Nissle 1917 EcN) to limit the expansion of competing Enterobacteriaceae including pathogens and pathobionts) during intestinal inflammation. Microcin-producing EcN limits the growth of competitors in the inflamed intestine, including commensal E. coli, adherent-invasive E. coli and the related pathogen Salmonella enterica. Moreover, only therapeutic administration of the wild-type, microcin-producing EcN to mice previously infected with S. enterica substantially reduced intestinal colonization by the pathogen. Our work provides the first evidence that microcins mediate inter-and intraspecies competition among the Enterobacteriaceae in the inflamed gut. Moreover, we show that microcins can act as narrow-spectrum therapeutics to inhibit enteric pathogens and reduce enterobacterial blooms.
C1 [Sassone-Corsi, Martina; Nuccio, Sean-Paul; Liu, Henry; Hernandez, Dulcemaria; Vu, Christine T.; Takahashi, Amy A.; Raffatellu, Manuela] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA.
   [Sassone-Corsi, Martina; Nuccio, Sean-Paul; Edwards, Robert A.; Raffatellu, Manuela] Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA.
   [Edwards, Robert A.] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine
RP Raffatellu, M (corresponding author), Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA.; Raffatellu, M (corresponding author), Univ Calif Irvine, Inst Immunol, Irvine, CA 92697 USA.
EM manuelar@uci.edu
FU Public Health Service [AI083663, AI126277, AI101784, AI114625, AI105374, DK058057]; Burroughs Wellcome Fund
NR 28
TC 419
Z9 517
U1 5
U2 213
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 280
EP +
DI 10.1038/nature20557
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700059
PM 27798599
DA 2026-03-09
ER

PT J
AU Hawkins, ED
   Duarte, D
   Akinduro, O
   Khorshed, RA
   Passaro, D
   Nowicka, M
   Straszkowski, L
   Scott, MK
   Rothery, S
   Ruivo, N
   Foster, K
   Waibel, M
   Johnstone, RW
   Harrison, SJ
   Westerman, DA
   Quach, H
   Gribben, J
   Robinson, MD
   Purton, LE
   Bonnet, D
   Lo Celso, C
AF Hawkins, Edwin D.
   Duarte, Delfim
   Akinduro, Olufolake
   Khorshed, Reema A.
   Passaro, Diana
   Nowicka, Malgorzata
   Straszkowski, Lenny
   Scott, Mark K.
   Rothery, Steve
   Ruivo, Nicola
   Foster, Katie
   Waibel, Michaela
   Johnstone, Ricky W.
   Harrison, Simon J.
   Westerman, David A.
   Quach, Hang
   Gribben, John
   Robinson, Mark D.
   Purton, Louise E.
   Bonnet, Dominique
   Lo Celso, Cristina
TI T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; niche; differentiation; inhibition; induction; quiescent; survival; cxcr4; roles; mice
AB It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/ selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function1. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.
C1 [Hawkins, Edwin D.; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A.; Scott, Mark K.; Ruivo, Nicola; Lo Celso, Cristina] Imperial Coll London, Dept Life Sci, Sir Alexander Fleming Bldg, London SW7 2AZ, England.
   [Hawkins, Edwin D.; Scott, Mark K.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Hawkins, Edwin D.] Univ Melbourne, Dept Mol Biol, Parkville, Vic 3010, Australia.
   [Duarte, Delfim; Lo Celso, Cristina] Francis Crick Inst, 1 Midland Rd, London NW1A 1AT, England.
   [Passaro, Diana; Foster, Katie; Bonnet, Dominique] Francis Crick Inst, Haematopoiet Stem Cell Lab, 1 Midland Rd, London NW1A 1AT, England.
   [Nowicka, Malgorzata; Robinson, Mark D.] Univ Zurich, SIB, Winterthurstr 190, CH-8057 Zurich, Switzerland.
   [Nowicka, Malgorzata; Robinson, Mark D.] Univ Zurich, Inst Mol Life Sci, Winterthurstr 190, CH-8057 Zurich, Switzerland.
   [Straszkowski, Lenny; Purton, Louise E.] St Vincents Inst Med Res, Stem Cell Regulat Unit, 41 Victoria Parade, Fitzroy, Vic 3065, Australia.
   [Rothery, Steve] Imperial Coll London, Imperial Coll Facil Imaging Light Microscopy, Sir Alexander Fleming Bldg, London SW7 2AZ, England.
   [Waibel, Michaela; Johnstone, Ricky W.; Harrison, Simon J.; Westerman, David A.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
   [Waibel, Michaela; Johnstone, Ricky W.; Harrison, Simon J.; Westerman, David A.] Peter MacCallum Canc Ctr, Dept Haematol, Melbourne, Vic 3000, Australia.
   [Quach, Hang] St Vincents Hosp, Dept Haematol, Fitzroy, Vic 3065, Australia.
   [Quach, Hang; Purton, Louise E.] Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia.
   [Gribben, John] Queen Mary Univ London, St Bartholomews Hosp, Barts Canc Inst, Ctr Haematooncol,Canc Res UK Clin Ctr, London EC1M 6BQ, England.
C3 Imperial College London; Walter & Eliza Hall Institute; University of Melbourne; Francis Crick Institute; Francis Crick Institute; University of Zurich; Swiss Institute of Bioinformatics; University of Zurich; St. Vincent's Institute of Medical Research; Imperial College London; Peter Maccallum Cancer Center; University of Melbourne; Peter Maccallum Cancer Center; St Vincent's Health; St Vincent's Hospital Melbourne; NSW Health; St Vincents Hospital Sydney; University of Melbourne; University of London; Queen Mary University London; Cancer Research UK
RP Hawkins, ED; Lo Celso, C (corresponding author), Imperial Coll London, Dept Life Sci, Sir Alexander Fleming Bldg, London SW7 2AZ, England.; Hawkins, ED (corresponding author), Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.; Hawkins, ED (corresponding author), Univ Melbourne, Dept Mol Biol, Parkville, Vic 3010, Australia.; Lo Celso, C (corresponding author), Francis Crick Inst, 1 Midland Rd, London NW1A 1AT, England.
EM Hawkins.e@wehi.edu.au; c.lo-celso@imperial.ac.uk
FU European Haematology Association; National Health and Medical Research Council of Australia (NHMRC) as well as a project grant from Bloodwise [12033]; GABBA PhD program (FCT fellowship) [SFRH/BD/52195/2013]; National Health and Medical Research Council of Australia Senior Research Fellowship; Victorian Cancer Agency Early Career Seed Grant; Cancer Research UK (CRUK); Francis Crick Institute; Bloodwise [12033]; Human Frontier Science Program [RGP0051/2011]; CRUK [036195/41183]; Biotechnology and Biological Sciences Research Council [BB/1004033/1]; Kay Kendall Leukaemia Fund [KKL460]; European Research Council [337066]; European Research Council (ERC) [337066] Funding Source: European Research Council (ERC); BBSRC [BB/I004033/1, BB/K021168/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/I004033/1, BB/K021168/1] Funding Source: researchfish; Cancer Research UK [11831, 15692] Funding Source: researchfish; The Francis Crick Institute [10045] Funding Source: researchfish
NR 36
TC 168
Z9 182
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 518
EP +
DI 10.1038/nature19801
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400060
PM 27750279
DA 2026-03-09
ER

PT J
AU Stroud, DA
   Surgenor, EE
   Formosa, LE
   Reljic, B
   Frazier, AE
   Dibley, MG
   Osellame, LD
   Stait, T
   Beilharz, TH
   Thorburn, DR
   Salim, A
   Ryan, MT
AF Stroud, David A.
   Surgenor, Elliot E.
   Formosa, Luke E.
   Reljic, Boris
   Frazier, Ann E.
   Dibley, Marris G.
   Osellame, Laura D.
   Stait, Tegan
   Beilharz, Traude H.
   Thorburn, David R.
   Salim, Agus
   Ryan, Michael T.
TI Accessory subunits are integral for assembly and function of human mitochondrial complex I
SO NATURE
LA English
DT Article
ID respiratory-chain; crystal-structure; gene-expression; protein; mutations; deficiency; identification; reveals; translocase; membrane
AB Complex I (NADH: ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes(1). Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP(2). Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing(3-5). Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear(1,6). The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.
C1 [Stroud, David A.; Surgenor, Elliot E.; Formosa, Luke E.; Dibley, Marris G.; Osellame, Laura D.; Beilharz, Traude H.; Ryan, Michael T.] Monash Univ, Monash Biomedicine Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Formosa, Luke E.; Reljic, Boris] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Bundoora, Vic 3086, Australia.
   [Frazier, Ann E.; Stait, Tegan; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
   [Frazier, Ann E.; Thorburn, David R.] Univ Melbourne, Dept Pediat, Parkville, Vic 3052, Australia.
   [Thorburn, David R.] Royal Childrens Hosp, Victorian Clin Genet Serv, Parkville, Vic 3052, Australia.
   [Salim, Agus] La Trobe Univ, Dept Math & Stat, Bundoora, Vic 3086, Australia.
   [Reljic, Boris] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
C3 Monash University; La Trobe University; Murdoch Children's Research Institute; Royal Children's Hospital Melbourne; University of Melbourne; Murdoch Children's Research Institute; Victorian Clinical Genetics Services; Royal Children's Hospital Melbourne; La Trobe University; Walter & Eliza Hall Institute
RP Stroud, DA (corresponding author), Monash Univ, Monash Biomedicine Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
EM d.stroud@monash.edu; michael.ryan@monash.edu
FU NHMRC [1068056, 1107094, 1070916, 541920, 1022896]; Australian Mitochondrial Disease Foundation; Victorian Government's Operational Infrastructure Support Program; National Health and Medical Research Council of Australia [1107094, 1070916, 1068056] Funding Source: NHMRC; National Health and Medical Research Council (NHMRC) [1068056, 1107094, 1070916, 1022896, 541920] Funding Source: National Health and Medical Research Council (NHMRC)
NR 67
TC 438
Z9 511
U1 6
U2 107
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 123
EP +
DI 10.1038/nature19754
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900047
PM 27626371
DA 2026-03-09
ER

PT J
AU Zhao, WD
   Hamid, E
   Shin, W
   Wen, PJ
   Krystofiak, ES
   Villarreal, SA
   Chiang, HC
   Kachar, B
   Wu, LG
AF Zhao, Wei-Dong
   Hamid, Edaeni
   Shin, Wonchul
   Wen, Peter J.
   Krystofiak, Evan S.
   Villarreal, Seth A.
   Chiang, Hsueh-Cheng
   Kachar, Bechara
   Wu, Ling-Gang
TI Hemi-fused structure mediates and controls fusion and fission in live cells
SO NATURE
LA English
DT Article
ID membrane fission; chromaffin cells; ca2+-triggered exocytosis; snare complex; pores; vesicles; endocytosis; tomography; proteins; intermediate
AB Membrane fusion and fission are vital for eukaryotic life(1-5). For three decades, it has been proposed that fusion is mediated by fusion between the proximal leaflets of two bilayers (hemi-fusion) to produce a hemi-fused structure, followed by fusion between the distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission(1,4,6-10). This hypothesis remained unsupported owing to the lack of observation of hemi-fusion or hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed(2,11-15). Here we report the observation of a hemi-fused Omega-shaped structure in live neuroendocrine chromaffin cells and pancreatic beta-cells, visualized using confocal and super-resolution stimulated emission depletion microscopy. This structure is generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, the transition to full fusion or fission is determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and is notably slow (seconds to tens of seconds) in a substantial fraction of the events. These results provide key missing evidence in support of the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion and fission, as fusion and fission mechanisms compete to determine the transition to fusion or fission.
C1 [Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J.; Villarreal, Seth A.; Chiang, Hsueh-Cheng; Wu, Ling-Gang] NINDS, 35 Convent Dr,Room 2B-1012, Bethesda, MD 20892 USA.
   [Krystofiak, Evan S.; Kachar, Bechara] NIDCD, 35A Convent Dr,Room 3D-824, Bethesda, MD 20892 USA.
   [Chiang, Hsueh-Cheng] Natl Cheng Kung Univ, Dept Pharmacol, Coll Med, 1 Univ Rd, Tainan 701, Taiwan.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD); National Cheng Kung University
RP Wu, LG (corresponding author), NINDS, 35 Convent Dr,Room 2B-1012, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural Research Program [ZIA NS003009-13, ZIA NS003105-08]; National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Research Program [Z01-DC000002]; National Institute on Deafness and Other Communication Disorders (NIDCD) Intramural Research Program (NIDCD Advanced Imaging Core ZIC) [DC000081]; National Institute of Neurological Disorders and Stroke [ZIANS003009, ZIANS003105] Funding Source: NIH RePORTER; National Institute on Deafness and Other Communication Disorders [ZIADC000009, ZIADC000002] Funding Source: NIH RePORTER
NR 34
TC 116
Z9 132
U1 1
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 548
EP +
DI 10.1038/nature18598
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300053
PM 27309816
DA 2026-03-09
ER

PT J
AU Seddon, AWR
   Macias-Fauria, M
   Long, PR
   Benz, D
   Willis, KJ
AF Seddon, Alistair W. R.
   Macias-Fauria, Marc
   Long, Peter R.
   Benz, David
   Willis, Kathy J.
TI Sensitivity of global terrestrial ecosystems to climate variability
SO NATURE
LA English
DT Article
ID carbon dynamics; forest; temperature; resilience
AB The identification of properties that contribute to the persistence and resilience of ecosystems despite climate change constitutes a research priority of global relevance(1). Here we present a novel, empirical approach to assess the relative sensitivity of ecosystems to climate variability, one property of resilience that builds on theoretical modelling work recognizing that systems closer to critical thresholds respond more sensitively to external perturbations2. We develop a new metric, the vegetation sensitivity index, that identifies areas sensitive to climate variability over the past 14 years. The metric uses time series data derived from the moderate-resolution imaging spectroradiometer (MODIS) enhanced vegetation index(3), and three climatic variables that drive vegetation productivity(4) (air temperature, water availability and cloud cover). Underlying the analysis is an autoregressive modelling approach used to identify climate drivers of vegetation productivity on monthly timescales, in addition to regions with memory effects and reduced response rates to external forcing(5). We find ecologically sensitive regions with amplified responses to climate variability in the Arctic tundra, parts of the boreal forest belt, the tropical rainforest, alpine regions worldwide, steppe and prairie regions of central Asia and North and South America, the Caatinga deciduous forest in eastern South America, and eastern areas of Australia. Our study provides a quantitative methodology for assessing the relative response rate of ecosystems-be they natural or with a strong anthropogenic signature-to environmental variability, which is the first step towards addressing why some regions appear to be more sensitive than others, and what impact this has on the resilience of ecosystem service provision and human well-being.
C1 [Seddon, Alistair W. R.; Willis, Kathy J.] Univ Bergen, Dept Biol, Allegaten 41, N-500 Bergen, Norway.
   [Macias-Fauria, Marc] Univ Oxford, Sch Geog & Environm, S Parks Rd, Oxford OX1 3QY, England.
   [Long, Peter R.; Benz, David; Willis, Kathy J.] Univ Oxford, Dept Zool, Oxford Martin Sch, Long Term Ecol Lab,Biodivers Inst, S Parks Rd, Oxford OX1 3PS, England.
   [Willis, Kathy J.] Royal Bot Gardens, Richmond TW9 3AB, Surrey, England.
C3 University of Bergen; University of Oxford; University of Oxford; Royal Botanic Gardens, Kew
RP Seddon, AWR (corresponding author), Univ Bergen, Dept Biol, Allegaten 41, N-500 Bergen, Norway.
EM alistair.seddon@bio.uib.no
FU Statoil ASA, Norway [4501995279]; European Commission [LIFE12 ENV/UK/000473]; Oxford Martin School Fellowship; Natural Environment Research Council Independent Research Fellowship [NE/L011859/1]; Research Council of Norway Postdoctoral Fellowship within a FRIMEDBIO project grant [FRIMEDBIO-214359]; NERC [NE/L011859/1] Funding Source: UKRI; Natural Environment Research Council [NE/L011859/1] Funding Source: researchfish
NR 41
TC 1082
Z9 1258
U1 48
U2 1335
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 229
EP +
DI 10.1038/nature16986
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100040
PM 26886790
DA 2026-03-09
ER

PT J
AU Woolley, SNC
   Tittensor, DP
   Dunstan, PK
   Guillera-Arroita, G
   Lahoz-Monfort, JJ
   Wintle, BA
   Worm, B
   O'Hara, TD
AF Woolley, Skipton N. C.
   Tittensor, Derek P.
   Dunstan, Piers K.
   Guillera-Arroita, Gurutzeta
   Lahoz-Monfort, Jose J.
   Wintle, Brendan A.
   Worm, Boris
   O'Hara, Timothy D.
TI Deep-sea diversity patterns are shaped by energy availability
SO NATURE
LA English
DT Article
ID species-diversity; global patterns; biodiversity; richness; community; predictions; hypothesis; occupancy; gradients; climate
AB The deep ocean is the largest and least-explored ecosystem on Earth, and a uniquely energy-poor environment. The distribution, drivers and origins of deep-sea biodiversity remain unknown at global scales(1-3). Here we analyse a database of more than 165,000 distribution records of Ophiuroidea (brittle stars), a dominant component of sea-floor fauna, and find patterns of biodiversity unlike known terrestrial or coastal marine realms. Both patterns and environmental predictors of deep-sea (2,000-6,500m) species richness fundamentally differ from those found in coastal (0-20 m), continental shelf (20-200 m), and upper-slope (200-2,000 m) waters. Continental shelf to upper-slope richness consistently peaks in tropical Indo-west Pacific and Caribbean (0-30 degrees) latitudes, and is well explained by variations in water temperature. In contrast, deep-sea species show maximum richness at higher latitudes (30-50 degrees), concentrated in areas of high carbon export flux and regions close to continental margins. We reconcile this structuring of oceanic biodiversity using a species-energy framework, with kinetic energy predicting shallow-water richness, while chemical energy (export productivity) and proximity to slope habitats drive deep-sea diversity. Our findings provide a global baseline for conservation efforts across the sea floor, and demonstrate that deep-sea ecosystems show a biodiversity pattern consistent with ecological theory, despite being different from other planetary-scale habitats.
C1 [Woolley, Skipton N. C.; O'Hara, Timothy D.] Museum Victoria, GPO Box 666, Melbourne, Vic 3001, Australia.
   [Woolley, Skipton N. C.; Guillera-Arroita, Gurutzeta; Lahoz-Monfort, Jose J.; Wintle, Brendan A.] Univ Melbourne, Quantitat & Appl Ecol Grp, Sch Biol Sci, BioSci Bldg 2, Melbourne, Vic 3010, Australia.
   [Tittensor, Derek P.; Worm, Boris] Dalhousie Univ, Dept Biol, 1355 Oxford St, Halifax, NS B3H 4J1, Canada.
   [Tittensor, Derek P.] World Conservat Monitoring Ctr, United Nations Environm Programme, 219 Huntingdon Rd, Cambridge CB3 0DL, England.
   [Dunstan, Piers K.] CSIRO, Wealth Oceans Flagship, Hobart, Tas 7000, Australia.
C3 Museum Victoria; University of Melbourne; Dalhousie University; Commonwealth Scientific & Industrial Research Organisation (CSIRO)
RP Woolley, SNC (corresponding author), Museum Victoria, GPO Box 666, Melbourne, Vic 3001, Australia.; Woolley, SNC (corresponding author), Univ Melbourne, Quantitat & Appl Ecol Grp, Sch Biol Sci, BioSci Bldg 2, Melbourne, Vic 3010, Australia.
EM swoolley@museum.vic.gov.au
FU Commonwealth National Environmental Research Program (NERP); Centre of Excellence for Environmental Decisions (CEED)
NR 66
TC 217
Z9 236
U1 5
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 393
EP +
DI 10.1038/nature17937
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300048
PM 27193685
DA 2026-03-09
ER

PT J
AU Kappelman, J
   Ketcham, RA
   Pearce, S
   Todd, L
   Akins, W
   Colbert, MW
   Feseha, M
   Maisano, JA
   Witzel, A
AF Kappelman, John
   Ketcham, Richard A.
   Pearce, Stephen
   Todd, Lawrence
   Akins, Wiley
   Colbert, Matthew W.
   Feseha, Mulugeta
   Maisano, Jessica A.
   Witzel, Adrienne
TI Perimortem fractures in Lucy suggest mortality from fall out of tall tree
SO NATURE
LA English
DT Article
ID australopithecus-afarensis; computed-tomography; hadar formation; climate-change; body size; ethiopia; skeleton; classification; environments; patterns
AB The Pliocene fossil `Lucy' (Australopithecus afarensis) was discovered in the Afar region of Ethiopia in 1974 and is among the oldest and most complete fossil hominin skeletons discovered. Here we propose, on the basis of close study of her skeleton, that her cause of death was a vertical deceleration event or impact following a fall from considerable height that produced compressive and hinge (greenstick) fractures in multiple skeletal elements. Impacts that are so severe as to cause concomitant fractures usually also damage internal organs; together, these injuries are hypothesized to have caused her death. Lucy has been at the centre of a vigorous debate about the role, if any, of arboreal locomotion in early human evolution. It is therefore ironic that her death can be attributed to injuries resulting from a fall, probably out of a tall tree, thus offering unusual evidence for the presence of arborealism in this species.
C1 [Kappelman, John; Todd, Lawrence; Witzel, Adrienne] Univ Texas Austin, Dept Anthropol, Austin, TX 78712 USA.
   [Kappelman, John; Ketcham, Richard A.; Colbert, Matthew W.; Maisano, Jessica A.] Univ Texas Austin, Dept Geol Sci, Austin, TX 78712 USA.
   [Pearce, Stephen] Austin Bone & Joint Clin, Austin, TX 78705 USA.
   [Akins, Wiley] Univ Texas Austin, Dept Radiotelevis Film, Austin, TX 78712 USA.
   [Feseha, Mulugeta] Univ Addis Ababa, Paleoanthropol & Paleoenvironm Program, Addis Ababa, Ethiopia.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Addis Ababa University
RP Kappelman, J (corresponding author), Univ Texas Austin, Dept Anthropol, Austin, TX 78712 USA.; Kappelman, J (corresponding author), Univ Texas Austin, Dept Geol Sci, Austin, TX 78712 USA.
EM jkappelman@austin.utexas.edu
FU Paleoanthropology Laboratory Fund; College of Liberal Arts UT Austin; Houston Museum of Natural Science; US National Science Foundation [EAR-0646848, EAR-0948842, EAR-1258878]; Directorate For Geosciences; Division Of Earth Sciences [1561622] Funding Source: National Science Foundation
NR 34
TC 55
Z9 65
U1 0
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 503
EP +
DI 10.1038/nature19332
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900046
PM 27571283
DA 2026-03-09
ER

PT J
AU Spaun, B
   Changala, PB
   Patterson, D
   Bjork, BJ
   Heckl, OH
   Doyle, JM
   Ye, J
AF Spaun, Ben
   Changala, P. Bryan
   Patterson, David
   Bjork, Bryce J.
   Heckl, Oliver H.
   Doyle, John M.
   Ye, Jun
TI Continuous probing of cold complex molecules with infrared frequency comb spectroscopy
SO NATURE
LA English
DT Article
ID vibrational-spectra; microwave-spectrum; internal-rotation; radical cations; force-field; nitromethane; naphthalene; band; raman; approximation
AB For more than half a century, high-resolution infrared spectroscopy has played a crucial role in probing molecular structure and dynamics. Such studies have so far been largely restricted to relatively small and simple systems, because at room temperature even molecules of modest size already occupy many millions of rotational/vibrational states, yielding highly congested spectra that are difficult to assign. Targeting more complex molecules requires methods that can record broadband infrared spectra (that is, spanning multiple vibrational bands) with both high resolution and high sensitivity. However, infrared spectroscopic techniques have hitherto been limited either by narrow bandwidth and long acquisition time(1), or by low sensitivity and resolution(2). Cavity-enhanced direct frequency comb spectroscopy (CE-DFCS) combines the inherent broad bandwidth and high resolution of an optical frequency comb with the high detection sensitivity provided by a high-finesse enhancement cavity(3,4), but it still suffers from spectral congestion(5). Here we show that this problem can be overcome by using buffer gas cooling(6) to produce continuous, cold samples of molecules that are then subjected to CE-DFCS. This integration allows us to acquire a rotationally resolved direct absorption spectrum in the C-H stretching region of nitromethane, a model system that challenges our understanding of large-amplitude vibrational motion(7-9). We have also used this technique on several large organic molecules that are of fundamental spectroscopic and astrochemical relevance, including naphthalene(10), adamantane(11) and hexamethylenetetramine(12). These findings establish the value of our approach for studying much larger and more complex molecules than have been probed so far, enabling complex molecules and their kinetics to be studied with orders-of-magnitude improvements in efficiency, spectral resolution and specificity.
C1 [Spaun, Ben; Changala, P. Bryan; Bjork, Bryce J.; Heckl, Oliver H.; Ye, Jun] Univ Colorado, Natl Inst Stand & Technol, JILA, Boulder, CO 80309 USA.
   [Spaun, Ben; Changala, P. Bryan; Bjork, Bryce J.; Heckl, Oliver H.; Ye, Jun] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Patterson, David; Doyle, John M.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Harvard University
RP Spaun, B; Ye, J (corresponding author), Univ Colorado, Natl Inst Stand & Technol, JILA, Boulder, CO 80309 USA.; Spaun, B; Ye, J (corresponding author), Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
EM Spaun@jila.colorado.edu; Ye@jila.colorado.edu
FU DARPA SCOUT; AFOSR; NIST; NSF-JILA PFC; NSF; HQOC; NRC; Humboldt Fellowship; NSF GRFP [DGE1144083]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1506868] Funding Source: National Science Foundation
NR 61
TC 116
Z9 132
U1 4
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 517
EP +
DI 10.1038/nature17440
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100037
PM 27144351
DA 2026-03-09
ER

PT J
AU Wilson, MR
   Solà, J
   Carlone, A
   Goldup, SM
   Lebrasseur, N
   Leigh, DA
AF Wilson, Miriam R.
   Sola, Jordi
   Carlone, Armando
   Goldup, Stephen M.
   Lebrasseur, Nathalie
   Leigh, David A.
TI An autonomous chemically fuelled small-molecule motor
SO NATURE
LA English
DT Article
ID rotary motor; driven; motion; contraction; rotation
AB Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process(1). A number of synthetic small-molecule machines have been developed(2), including molecular muscles(3,4), synthesizers(5,6), pumps(7-9), walkers(10), transporters(11) and light-driven(12-16) and electrically(17,18) driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP)(1), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present)(19). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology(2,19,20).
C1 [Wilson, Miriam R.; Sola, Jordi; Carlone, Armando; Goldup, Stephen M.; Lebrasseur, Nathalie; Leigh, David A.] Univ Manchester, Sch Chem, Oxford Rd, Manchester M13 9PL, Lancs, England.
   [Sola, Jordi] Inst Adv Chem Catalonia IQAC CSIC, Jordi Girona 18-26, Barcelona 08034, Spain.
   [Carlone, Armando] Dr Reddys, Chirotech Technol Ctr, Cambridge CB4 0PE, England.
   [Goldup, Stephen M.] Univ Southampton, Dept Chem, Southampton SO17 1BJ, Hants, England.
   [Lebrasseur, Nathalie] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
C3 University of Manchester; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigacion y Desarrollo Pascual Vila (CID-CSIC); CSIC - Instituto de Quimica Avanzada de Cataluna (IQAC); University of Southampton; University of London; Queen Mary University London
RP Leigh, DA (corresponding author), Univ Manchester, Sch Chem, Oxford Rd, Manchester M13 9PL, Lancs, England.
EM david.leigh@manchester.ac.uk
FU European Research Council (ERC)
NR 33
TC 392
Z9 428
U1 9
U2 443
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 235
EP +
DI 10.1038/nature18013
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100038
PM 27279219
DA 2026-03-09
ER

PT J
AU Kay, K
   Sosa, M
   Chung, JE
   Karlsson, MP
   Larkin, MC
   Frank, LM
AF Kay, Kenneth
   Sosa, Marielena
   Chung, Jason E.
   Karlsson, Mattias P.
   Larkin, Margaret C.
   Frank, Loren M.
TI A hippocampal network for spatial coding during immobility and sleep
SO NATURE
LA English
DT Article
ID sharp-wave ripples; pyramidal cells; theta oscillations; entorhinal cortex; path-integration; rat hippocampus; dentate gyrus; behaving rat; ca1 neurons; place cells
AB How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has been unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signalling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.
C1 [Kay, Kenneth; Sosa, Marielena; Chung, Jason E.; Karlsson, Mattias P.; Larkin, Margaret C.; Frank, Loren M.] Univ Calif San Francisco, UCSF Ctr Integrat Neurosci, San Francisco, CA 94158 USA.
   [Kay, Kenneth; Sosa, Marielena; Chung, Jason E.; Karlsson, Mattias P.; Larkin, Margaret C.; Frank, Loren M.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Frank, Loren M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Kay, K; Frank, LM (corresponding author), Univ Calif San Francisco, UCSF Ctr Integrat Neurosci, San Francisco, CA 94158 USA.; Kay, K; Frank, LM (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.; Frank, LM (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
EM kenneth.kay@ucsf.edu; loren@phy.ucsf.edu
FU Howard Hughes Medical Institute; NIH [R01 MH090188]; McKnight Foundation Cognitive and Memory Disorders Award; Ruth L. Kirchstein National Research Service Award Fellowship (NIH/NIMH); UCSF Medical Scientist Training Program
NR 82
TC 148
Z9 193
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 185
EP +
DI 10.1038/nature17144
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100031
PM 26934224
DA 2026-03-09
ER

PT J
AU Sambur, JB
   Chen, TY
   Choudhary, E
   Chen, GQ
   Nissen, EJ
   Thomas, EM
   Zou, NM
   Chen, P
AF Sambur, Justin B.
   Chen, Tai-Yen
   Choudhary, Eric
   Chen, Guanqun
   Nissen, Erin J.
   Thomas, Elayne M.
   Zou, Ningmu
   Chen, Peng
TI Sub-particle reaction and photocurrent mapping to optimize catalyst-modified photoanodes
SO NATURE
LA English
DT Article
ID photoelectrochemical water oxidation; oxygen-evolving catalyst; surface-states; tio2; electrodes; photoelectrolysis; electrocatalysis; photocatalysis; particles; heterogeneity
AB The splitting of water photoelectrochemically into hydrogen and oxygen represents a promising technology for converting solar energy to fuel(1,2). The main challenge is to ensure that photogenerated holes efficiently oxidize water, which generally requires modification of the photoanode with an oxygen evolution catalyst (OEC) to increase the photocurrent and reduce the onset potential(3). However, because excess OEC material can hinder light absorption and decrease photoanode performance(4), its deposition needs to be carefully controlled-yet it is unclear which semiconductor surface sites give optimal improvement if targeted for OEC deposition, and whether sites catalysing water oxidation also contribute to competing charge-carrier recombination with photogenerated electrons(5). Surface heterogeneity(6) exacerbates these uncertainties, especially for nanostructured photoanodes benefiting from small charge-carrier transport distances(1,7,8). Here we use super-resolution imaging(9-13), operated in a charge-carrier-selective manner and with a spatiotemporal resolution of approximately 30 nanometres and 15 milliseconds, to map both the electron-and hole-driven photoelectrocatalytic activities on single titanium oxide nanorods. We then map, with sub-particle resolution (about 390 nanometres), the photocurrent associated with water oxidation, and find that the most active sites for water oxidation are also the most important sites for charge-carrier recombination. Site-selective deposition of an OEC, guided by the activity maps, improves the overall performance of a given nanorod-even though more improvement in photocurrent efficiency correlates with less reduction in onset potential (and vice versa) at the sub-particle level. Moreover, the optimal catalyst deposition sites for photocurrent enhancement are the lower-activity sites, and for onset potential reduction the optimal sites are the sites with more positive onset potential, contrary to what is obtainable under typical deposition conditions. These findings allow us to suggest an activity-based strategy for rationally engineering catalyst-improved photoelectrodes, which should be widely applicable because our measurements can be performed for many different semiconductor and catalyst materials.
C1 [Sambur, Justin B.; Chen, Tai-Yen; Choudhary, Eric; Chen, Guanqun; Zou, Ningmu; Chen, Peng] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Nissen, Erin J.] Colorado Mesa Univ, Dept Chem, Grand Junction, CO 81501 USA.
   [Thomas, Elayne M.] Univ Michigan, Dept Mat Sci & Engn, Ann Arbor, MI 48109 USA.
   [Choudhary, Eric] NIST, Ctr Nanosci & Technol, Gaithersburg, MD 20899 USA.
C3 Cornell University; University of Michigan System; University of Michigan; National Institute of Standards & Technology (NIST) - USA
RP Chen, P (corresponding author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
EM pc252@cornell.edu
FU Department of Energy, Office of Science, Basic Energy Science [DE-FG02-10ER16199]; Army Research Office [63767-CH, 65814-CH]; National Science Foundation [CBET-1263736, CHE-1137217]; REU programme [DMR-1063059]; Petroleum Research Foundation [54289-ND7]; NSF MRSEC programme [DMR-1120296]; NSF National Nanotechnology Infrastructure Network [ECCS-15420819]; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [1263736] Funding Source: National Science Foundation
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NR 70
TC 338
Z9 384
U1 12
U2 882
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 77
EP +
DI 10.1038/nature16534
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500035
PM 26842056
DA 2026-03-09
ER

PT J
AU Albrecht, SM
   Higginbotham, AP
   Madsen, M
   Kuemmeth, F
   Jespersen, TS
   Nygård, J
   Krogstrup, P
   Marcus, CM
AF Albrecht, S. M.
   Higginbotham, A. P.
   Madsen, M.
   Kuemmeth, F.
   Jespersen, T. S.
   Nygard, J.
   Krogstrup, P.
   Marcus, C. M.
TI Exponential protection of zero modes in Majorana islands
SO NATURE
LA English
DT Article
ID semiconductor nanowire; quantum computation; andreev reflection; coulomb-blockade; superconductor; fermions; parity; signature; anyons; states
AB Majorana zero modes are quasiparticle excitations in condensed matter systems that have been proposed as building blocks of fault-tolerant quantum computers(1). They are expected to exhibit non-Abelian particle statistics, in contrast to the usual statistics of fermions and bosons, enabling quantum operations to be performed by braiding isolated modes around one another(1,2). Quantum braiding operations are topologically protected insofar as these modes are pinned near zero energy, with the departure from zero expected to be exponentially small as the modes become spatially separated(3,4). Following theoretical proposals(5,6), several experiments have identified signatures of Majorana modes in nanowires with proximity-induced superconductivity(7-11) and atomic chains(12), with small amounts of mode splitting potentially explained by hybridization of Majorana modes(13-15). Here, we use Coulombblockade spectroscopy in an InAs nanowire segment with epitaxial aluminium, which forms a proximity-induced superconducting Coulomb island (a ;Majorana island') that is isolated from normalmetal leads by tunnel barriers, to measure the splitting of near-zeroenergy Majorana modes. We observe exponential suppression of energy splitting with increasing wire length. For short devices of a few hundred nanometres, sub-gap state energies oscillate as the magnetic field is varied, as is expected for hybridized Majorana modes. Splitting decreases by a factor of about ten for each half a micrometre of increased wire length. For devices longer than about one micrometre, transport in strong magnetic fields occurs through a zero-energy state that is energetically isolated from a continuum, yielding uniformly spaced Coulomb-blockade conductance peaks, consistent with teleportation via Majorana modes(16,17). Our results help to explain the trivial-to-topological transition in finite systems and to quantify the scaling of topological protection with end-mode separation.
C1 [Albrecht, S. M.; Higginbotham, A. P.; Madsen, M.; Kuemmeth, F.; Jespersen, T. S.; Nygard, J.; Krogstrup, P.; Marcus, C. M.] Univ Copenhagen, Ctr Quantum Devices, Copenhagen, Denmark.
   [Albrecht, S. M.; Higginbotham, A. P.; Madsen, M.; Kuemmeth, F.; Jespersen, T. S.; Nygard, J.; Krogstrup, P.; Marcus, C. M.] Univ Copenhagen, Niels Bohr Inst, Stn Copenhagen Q, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
   [Higginbotham, A. P.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 University of Copenhagen; University of Copenhagen; Niels Bohr Institute; Harvard University
RP Marcus, CM (corresponding author), Univ Copenhagen, Ctr Quantum Devices, Copenhagen, Denmark.; Marcus, CM (corresponding author), Univ Copenhagen, Niels Bohr Inst, Stn Copenhagen Q, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
EM marcus@nbi.dk
FU Microsoft Project Q; Danish National Research Foundation; Lundbeck Foundation; Carlsberg Foundation; European Commission; Villum Foundation
NR 30
TC 951
Z9 1047
U1 4
U2 350
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 206
EP +
DI 10.1038/nature17162
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100035
PM 26961654
DA 2026-03-09
ER

PT J
AU Pimentel, D
   Donlea, JM
   Albot, CBT
   Ong, SMS
   Hurston, AJFT
   Miesenböck, G
AF Pimentel, Diogo
   Donlea, Jeffrey M.
   Albot, Clifford B. T.
   Ong, Seoho M. S.
   Hurston, Alexander J. F. T.
   Miesenbock, Gero
TI Operation of a homeostatic sleep switch
SO NATURE
LA English
DT Article
ID targeted gene-expression; potassium channels; drosophila-melanogaster; dopaminergic modulation; remote-control; reduced sleep; voltage-clamp; neurons; memory; behavior
AB Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep(1). In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex(2,3). Artificial activation of these cells induces sleep(2), whereas reductions in excitability cause insomnia(3,4). dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent(3). Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states(3). Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine(4-8) caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab, and the upregulation of voltage-independent leak currents through a two-pore-domain potassium channel that we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus linked to the control of sleep-wake state.
C1 [Pimentel, Diogo; Donlea, Jeffrey M.; Albot, Clifford B. T.; Ong, Seoho M. S.; Hurston, Alexander J. F. T.; Miesenbock, Gero] Univ Oxford, Ctr Neural Circuits & Behav, Tinsley Bldg,Mansfield Rd, Oxford OX1 3SR, England.
C3 University of Oxford
RP Miesenböck, G (corresponding author), Univ Oxford, Ctr Neural Circuits & Behav, Tinsley Bldg,Mansfield Rd, Oxford OX1 3SR, England.
EM gero.miesenboeck@cncb.ox.ac.uk
FU Wellcome Trust; Gatsby Charitable Foundation; Oxford Martin School; National Institutes of Health; Human Frontier Science Program; Wellcome Trust [106988/Z/15/Z] Funding Source: Wellcome Trust; MRC [G0700888] Funding Source: UKRI; Medical Research Council [G0701225, G0700888] Funding Source: researchfish; Wellcome Trust [106988/Z/15/Z, 090309/Z/09/Z] Funding Source: researchfish
NR 42
TC 194
Z9 244
U1 2
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 333
EP +
DI 10.1038/nature19055
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900036
PM 27487216
DA 2026-03-09
ER

PT J
AU Schibich, D
   Gloge, F
   Pöhner, I
   Björkholm, P
   Wade, RC
   von Heijne, G
   Bukau, B
   Kramer, G
AF Schibich, Daniela
   Gloge, Felix
   Poehner, Ina
   Bjorkholm, Patrik
   Wade, Rebecca C.
   von Heijne, Gunnar
   Bukau, Bernd
   Kramer, Guenter
TI Global profiling of SRP interaction with nascent polypeptides
SO NATURE
LA English
DT Article
ID trigger factor; protein translocation; membrane-protein; recognition; localization; pathway; seca
AB Signal recognition particle (SRP) is a universally conserved protein-RNA complex that mediates co-translational protein translocation and membrane insertion by targeting translating ribosomes to membrane translocons(1). The existence of parallel co- and post-translational transport pathways(2), however, raises the question of the cellular substrate pool of SRP and the molecular basis of substrate selection. Here we determine the binding sites of bacterial SRP within the nascent proteome of Escherichia coli at amino acid resolution, by sequencing messenger RNA footprints of ribosome-nascent-chain complexes associated with SRP. SRP, on the basis of its strong preference for hydrophobic transmembrane domains (TMDs), constitutes a compartment-specific targeting factor for nascent inner membrane proteins (IMPs) that efficiently excludes signal-sequence-containing precursors of periplasmic and outer membrane proteins. SRP associates with hydrophobic TMDs enriched in consecutive stretches of hydrophobic and bulky aromatic amino acids immediately on their emergence from the ribosomal exit tunnel. By contrast with current models, N-terminal TMDs are frequently skipped and TMDs internal to the polypeptide sequence are selectively recognized. Furthermore, SRP binds several TMDs in many multi-spanning membrane proteins, suggesting cycles of SRP-mediated membrane targeting. SRP-mediated targeting is not accompanied by a transient slowdown of translation and is not influenced by the ribosome-associated chaperone trigger factor (TF), which has a distinct substrate pool and acts at different stages during translation. Overall, our proteome-wide data set of SRP-binding sites reveals the underlying principles of pathway decisions for nascent chains in bacteria, with SRP acting as the dominant triaging factor, sufficient to separate IMPs from substrates of the SecA-SecB post-translational translocation and TF-assisted cytosolic protein folding pathways.
C1 [Schibich, Daniela; Gloge, Felix; Wade, Rebecca C.; Bukau, Bernd; Kramer, Guenter] Univ Heidelberg ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
   [Schibich, Daniela; Gloge, Felix; Bukau, Bernd; Kramer, Guenter] German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
   [Poehner, Ina; Wade, Rebecca C.] HITS gGmbH, Heidelberg Inst Theoret Studies, Schloss Wolfsbrunnenweg 35, D-69118 Heidelberg, Germany.
   [Bjorkholm, Patrik; von Heijne, Gunnar] Stockholm Univ, Ctr Biomembrane Res, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
   [Bjorkholm, Patrik; von Heijne, Gunnar] Stockholm Univ, Sci Life Lab, S-17121 Solna, Sweden.
   [Bjorkholm, Patrik] Uppsala Univ, Dept Mol Evolut Cell & Mol Biol, S-75236 Uppsala, Sweden.
   [Wade, Rebecca C.] Heidelberg Univ, Interdisciplinary Ctr Sci Comp IWR, Neuenheimer Feld 205, D-69120 Heidelberg, Germany.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Heidelberg Institute for Theoretical Studies; Stockholm University; Stockholm University; Uppsala University; Ruprecht Karls University Heidelberg
RP Bukau, B; Kramer, G (corresponding author), Univ Heidelberg ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.; Bukau, B; Kramer, G (corresponding author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM bukau@zmbh.uni-heidelberg.de; g.kramer@zmbh.uni-heidelberg.de
FU Klaus Tschira Foundation; Deutsche Forschungsgemeinschaft [SFB638, FOR1805]; Human Frontier Science Program grant; Swedish Research Council
NR 35
TC 115
Z9 137
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 219
EP +
DI 10.1038/nature19070
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100038
PM 27487212
DA 2026-03-09
ER

PT J
AU Soldner, F
   Stelzer, Y
   Shivalila, CS
   Abraham, BJ
   Latourelle, JC
   Barrasa, MI
   Goldmann, J
   Myers, RH
   Young, RA
   Jaenisch, R
AF Soldner, Frank
   Stelzer, Yonatan
   Shivalila, Chikdu S.
   Abraham, Brian J.
   Latourelle, Jeanne C.
   Barrasa, M. Inmaculada
   Goldmann, Johanna
   Myers, Richard H.
   Young, Richard A.
   Jaenisch, Rudolf
TI Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
SO NATURE
LA English
DT Article
ID genome-wide association; adult human brain; stem-cells; integrative analysis; genotype imputation; regulatory dna; human-disease; metaanalysis; locus; identification
AB Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis(1). It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types(2-6). Furthermore, single nucleotide polymorphism (SNP)specific changes in transcription factor binding are correlated with heritable alterations in chromatin state and considered a major mediator of sequence-dependent regulation of gene expression(7-10). Here we describe a novel strategy to functionally dissect the cis-acting effect of genetic risk variants in regulatory elements on gene expression by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells. By generating a genetically precisely controlled experimental system, we identify a common Parkinson's disease associated risk variant in a non-coding distal enhancer element that regulates the expression of a-synuclein (SNCA), a key gene implicated in the pathogenesis of Parkinson's disease. Our data suggest that the transcriptional deregulation of SNCA is associated with sequence-dependent binding of the brain-specific transcription factors EMX2 and NKX6-1. This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes.
C1 [Soldner, Frank; Stelzer, Yonatan; Shivalila, Chikdu S.; Abraham, Brian J.; Barrasa, M. Inmaculada; Goldmann, Johanna; Young, Richard A.; Jaenisch, Rudolf] Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
   [Shivalila, Chikdu S.; Young, Richard A.; Jaenisch, Rudolf] MIT, Dept Biol, 31 Ames St, Cambridge, MA 02139 USA.
   [Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Boston University
RP Jaenisch, R (corresponding author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.; Jaenisch, R (corresponding author), MIT, Dept Biol, 31 Ames St, Cambridge, MA 02139 USA.
EM jaenisch@wi.mit.edu
FU NIH [1 R01 NS088538-01, 2R01MH104610-15]; Qatar National Research Fund [NPRP 5-531-1-094]; National Institute of Mental Health [R01MH104610] Funding Source: NIH RePORTER
NR 58
TC 420
Z9 490
U1 1
U2 141
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 95
EP +
DI 10.1038/nature17939
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900046
PM 27096366
DA 2026-03-09
ER

PT J
AU Liu, Y
   Chen, C
   Xu, ZM
   Scuoppo, C
   Rillahan, CD
   Gao, JJ
   Spitzer, B
   Bosbach, B
   Kastenhuber, ER
   Baslan, T
   Ackermann, S
   Cheng, LH
   Wang, QG
   Niu, T
   Schultz, N
   Levine, RL
   Mills, AA
   Lowe, SW
AF Liu, Yu
   Chen, Chong
   Xu, Zhengmin
   Scuoppo, Claudio
   Rillahan, Cory D.
   Gao, Jianjiong
   Spitzer, Barbara
   Bosbach, Benedikt
   Kastenhuber, Edward R.
   Baslan, Timour
   Ackermann, Sarah
   Cheng, Lihua
   Wang, Qingguo
   Niu, Ting
   Schultz, Nikolaus
   Levine, Ross L.
   Mills, Alea A.
   Lowe, Scott W.
TI Deletions linked to TP53 loss drive cancer through p53-independent mechanisms
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; tumor-suppressor gene; mouse models; p53; expression; mutations; survival; mice; induction; reveals
AB Mutations disabling the TP53 tumour suppressor gene represent the most frequent events in human cancer and typically occur through a two-hit mechanism involving a missense mutation in one allele and a 'loss of heterozygosity' deletion encompassing the other. While TP53 missense mutations can also contribute gain-of-function activities that impact tumour progression, it remains unclear whether the deletion event, which frequently includes many genes, impacts tumorigenesis beyond TP53 loss alone. Here we show that somatic heterozygous deletion of mouse chromosome 11B3, a 4-megabase region syntenic to human 17p13.1, produces a greater effect on lymphoma and leukaemia development than Trp53 deletion. Mechanistically, the effect of 11B3 loss on tumorigenesis involves co-deleted genes such as Eif5a and Alox15b (also known as Alox8), the suppression of which cooperates with Trp53 loss to produce more aggressive disease. Our results imply that the selective advantage produced by human chromosome 17p deletion reflects the combined impact of TP53 loss and the reduced dosage of linked tumour suppressor genes.
C1 [Liu, Yu; Chen, Chong; Xu, Zhengmin] Sichuan Univ, West China Hosp, Dept Hematol, Chengdu 610041, Peoples R China.
   [Liu, Yu; Chen, Chong; Xu, Zhengmin] Sichuan Univ, West China Hosp, Dept Liver Surg, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.
   [Liu, Yu; Chen, Chong; Xu, Zhengmin] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China.
   [Liu, Yu; Chen, Chong; Xu, Zhengmin] Natl Collaborat Innovat Ctr, Chengdu 610041, Peoples R China.
   [Liu, Yu; Chen, Chong; Rillahan, Cory D.; Bosbach, Benedikt; Kastenhuber, Edward R.; Baslan, Timour; Ackermann, Sarah; Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10065 USA.
   [Scuoppo, Claudio] Columbia Univ, Inst Canc Genet, Med Ctr, New York, NY 10032 USA.
   [Gao, Jianjiong; Wang, Qingguo; Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Kravis Ctr Mol Oncol, New York, NY 10065 USA.
   [Spitzer, Barbara] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA.
   [Spitzer, Barbara] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Spitzer, Barbara; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA.
   [Cheng, Lihua; Niu, Ting] Sichuan Univ, West China Hosp, Dept Hematol, Chengdu 610041, Peoples R China.
   [Cheng, Lihua; Niu, Ting] Sichuan Univ, West China Hosp, Res Lab Hematol, Chengdu 610041, Peoples R China.
   [Mills, Alea A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Lowe, Scott W.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Sichuan University; Sichuan University; Sichuan University; Memorial Sloan Kettering Cancer Center; Columbia University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Sichuan University; Sichuan University; Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
RP Lowe, SW (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10065 USA.; Lowe, SW (corresponding author), Howard Hughes Med Inst, New York, NY 10065 USA.
EM lowes@mskcc.org
FU National Cancer Institute; Center grant for Cancer Target Discovery and Development; Memorial Sloan Kettering Cancer Center Support Grant; American Association for Cancer Research Millennium Fellowship in Lymphoma Research; Thousand Young Talents Plan; National Natural Science Foundation of China [81522003, 81570150]; National Cancer Institute [P01CA087497, P30CA045508, P30CA008748, P30CA016042] Funding Source: NIH RePORTER
NR 55
TC 211
Z9 241
U1 4
U2 121
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 471
EP +
DI 10.1038/nature17157
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300033
PM 26982726
DA 2026-03-09
ER

PT J
AU Wei, XC
   Song, HW
   Yin, L
   Rizzo, MG
   Sidhu, R
   Covey, DF
   Ory, DS
   Semenkovich, CF
AF Wei, Xiaochao
   Song, Haowei
   Yin, Li
   Rizzo, Michael G., Jr.
   Sidhu, Rohini
   Covey, Douglas F.
   Ory, Daniel S.
   Semenkovich, Clay F.
TI Fatty acid synthesis configures the plasma membrane for inflammation in diabetes
SO NATURE
LA English
DT Article
ID lipid rafts; quantitative proteomics; insulin sensitivity; activation; synthase; cholesterol; macrophages; vesicles; obesity; palmitoylation
AB Dietary fat promotes pathological insulin resistance through chronic inflammation(1-3). The inactivation of inflammatory proteins produced by macrophages improves diet-induced diabetes(4), but how nutrient-dense diets induce diabetes is unknown(5). Membrane lipids affect the innate immune response(6), which requires domains(7) that influence high-fat-diet-induced chronic inflammation(8,9) and alter cell function based on phospholipid composition(10). Endogenous fatty acid synthesis, mediated by fatty acid synthase (FAS)(11), affects membrane composition. Here we show that macrophage FAS is indispensable for diet-induced inflammation. Deleting Fasn in macrophages prevents diet-induced insulin resistance, recruitment of macrophages to adipose tissue and chronic inflammation in mice. We found that FAS deficiency alters membrane order and composition, impairing the retention of plasma membrane cholesterol and disrupting Rho GTPase trafficking-a process required for cell adhesion, migration and activation. Expression of a constitutively active Rho GTPase, however, restored inflammatory signalling. Exogenous palmitate was partitioned to different pools from endogenous lipids and did not rescue inflammatory signalling. However, exogenous cholesterol, as well as other planar sterols, did rescue signalling, with cholesterol restoring FAS-induced perturbations in membrane order. Our results show that the production of endogenous fat in macrophages is necessary for the development of exogenous-fatinduced insulin resistance through the creation of a receptive environment at the plasma membrane for the assembly of cholesterol-dependent signalling networks.
C1 [Wei, Xiaochao; Song, Haowei; Yin, Li; Rizzo, Michael G., Jr.; Semenkovich, Clay F.] Washington Univ, Div Endocrinol Metab & Lipid Res, Sch Med, St Louis, MO 63110 USA.
   [Sidhu, Rohini; Ory, Daniel S.] Washington Univ, Diabet Cardiovasc Dis Ctr, Sch Med, St Louis, MO 63110 USA.
   [Covey, Douglas F.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
   [Semenkovich, Clay F.] Washington Univ, Dept Cell Biol & Physiol, Sch Med, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Semenkovich, CF (corresponding author), Washington Univ, Div Endocrinol Metab & Lipid Res, Sch Med, St Louis, MO 63110 USA.; Semenkovich, CF (corresponding author), Washington Univ, Dept Cell Biol & Physiol, Sch Med, St Louis, MO 63110 USA.
EM csemenko@wustl.edu
FU NIH [DK101392, DK076729, DK088083, DK20579, DK56341, RR00954, HL067773]; Taylor Family Institute for Innovative Psychiatric Research; National Heart Lung and Blood Institute [R01HL067773] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056341, T32DK007120, P30DK020579] Funding Source: NIH RePORTER
NR 41
TC 257
Z9 291
U1 2
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 294
EP +
DI 10.1038/nature20117
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500046
PM 27806377
DA 2026-03-09
ER

PT J
AU Hirano, Y
   Takeda, K
   Miki, K
AF Hirano, Yu
   Takeda, Kazuki
   Miki, Kunio
TI Charge-density analysis of an iron-sulfur protein at an ultra-high resolution of 0.48 Å
SO NATURE
LA English
DT Article
ID x-ray; thermochromatium-tepidum; electronic-structure; diffraction data; small-molecule; crystallography; parameters; clusters; bond; refinement
AB The fine structures of proteins, such as the positions of hydrogen atoms, distributions of valence electrons and orientations of bound waters, are critical factors for determining the dynamic and chemical properties of proteins. Such information cannot be obtained by conventional protein X-ray analyses at 3.0-1.5 angstrom resolution, in which amino acids are fitted into atomically unresolved electron-density maps and refinement calculations are performed under strong restraints(1,2). Therefore, we usually supplement the information on hydrogen atoms and valence electrons in proteins with preexisting common knowledge obtained by chemistry in small molecules. However, even now, computational calculation of such information with quantum chemistry also tends to be difficult, especially for polynuclear metalloproteins(3). Here we report a charge-density analysis of the high-potential iron-sulfur protein from the thermophilic purple bacterium Thermochromatium tepidum using X-ray data at an ultra-high resolution of 0.48 angstrom. Residual electron densities in the conventional refinement are assigned as valence electrons in the multipolar refinement. Iron 3d and sulfur 3p electron densities of the Fe4S4 cluster are visualized around the atoms. Such information provides the most detailed view of the valence electrons of the metal complex in the protein. The asymmetry of the iron-sulfur cluster and the protein environment suggests the structural basis of charge storing on electron transfer. Our charge-density analysis reveals many fine features around the metal complex for the first time, and will enable further theoretical and experimental studies of metalloproteins.
C1 [Hirano, Yu; Takeda, Kazuki; Miki, Kunio] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan.
   [Hirano, Yu] Natl Inst Quantum & Radiol Sci & Technol, Quantum Beam Sci Res Directorate, Tokai, Ibaraki 3191195, Japan.
C3 Kyoto University; National Institutes for Quantum Science & Technology
RP Miki, K (corresponding author), Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan.
EM miki@kuchem.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan; [23657073]; Grants-in-Aid for Scientific Research [15K18494] Funding Source: KAKEN
NR 41
TC 31
Z9 39
U1 0
U2 5
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 281
EP +
DI 10.1038/nature18001
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100048
DA 2026-03-09
ER

PT J
AU Shao, ZH
   Yin, J
   Chapman, K
   Grzemska, M
   Clark, L
   Wang, JM
   Rosenbaum, DM
AF Shao, Zhenhua
   Yin, Jie
   Chapman, Karen
   Grzemska, Magdalena
   Clark, Lindsay
   Wang, Junmei
   Rosenbaum, Daniel M.
TI High-resolution crystal structure of the human CB1 cannabinoid receptor
SO NATURE
LA English
DT Article
ID inverse agonism; ligand-binding; membrane; insights; docking; endocannabinoids; pharmacology; sr141716a; affinity; mk-0364
AB The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) and to the widely consumed plant phytocannabinoid Delta(9)-tetrahydrocannabinol (THC)(1). The cannabinoid receptors have been the targets of intensive drug discovery efforts, because modulation of these receptors has therapeutic potential to control pain(2), epilepsy(3), obesity(4), and other disorders. Although much progress in understanding the biophysical properties of GPCRs has recently been made, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. Here we report the use of GPCR engineering and lipidic cubic phase crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6-angstrom resolution. We found that the extracellular surface of CB1, including the highly conserved membrane-proximal N-terminal region, is distinct from those of other lipid-activated GPCRs, forming a critical part of the ligand-binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function and will aid the design and optimization of therapeutic modulators of the endocannabinoid system.
C1 [Shao, Zhenhua; Yin, Jie; Chapman, Karen; Grzemska, Magdalena; Clark, Lindsay; Rosenbaum, Daniel M.] Univ Texas Southwestern Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
   [Wang, Junmei] Univ Texas Southwestern Med Ctr Dallas, Green Ctr Syst Biol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Rosenbaum, DM (corresponding author), Univ Texas Southwestern Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
EM dan.rosenbaum@utsouthwestern.edu
FU Welch Foundation [I-1770]; Packard Foundation Fellowship; US Department of Energy Office of Science User Facility [DE-AC02-06CH11357]
NR 50
TC 317
Z9 362
U1 6
U2 182
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 602
EP +
DI 10.1038/nature20613
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500056
PM 27851727
DA 2026-03-09
ER

PT J
AU Schine, N
   Ryou, A
   Gromov, A
   Sommer, A
   Simon, J
AF Schine, Nathan
   Ryou, Albert
   Gromov, Andrey
   Sommer, Ariel
   Simon, Jonathan
TI Synthetic Landau levels for photons
SO NATURE
LA English
DT Article
AB Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties(1-5). Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science(6-8). Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip(9). This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock-Darwin Hamiltonian for photons in a magnetic field and harmonic trap(10). Using spatial-and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit(10,11), we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen-Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space(12-15). This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids(16,17) and direct detection of anyons(18,19).
C1 [Schine, Nathan; Ryou, Albert; Sommer, Ariel; Simon, Jonathan] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
   [Schine, Nathan; Ryou, Albert; Sommer, Ariel; Simon, Jonathan] Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
   [Gromov, Andrey] Univ Chicago, Kadanoff Ctr Theoret Phys, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago
RP Simon, J (corresponding author), Univ Chicago, Dept Phys, Chicago, IL 60637 USA.; Simon, J (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM simonjon@uchicago.edu
FU DOE; DARPA; AFOSR; Kadanoff Center for Theoretical Physics; ARO through an NDSEG fellowship
CR Abanov AG, 2014, PHYS REV B, V90, P0, DOI 10.1103/PhysRevB.90.014435
   Baumann K, 2010, NATURE, V464, P1301, DOI 10.1038/nature09009
   Bloch I, 2008, REV MOD PHYS, V80, P885, DOI 10.1103/RevModPhys.80.885
   Can T, 2014, PHYS REV LETT, V113, P0, DOI 10.1103/PhysRevLett.113.046803
   Carusotto I, 2013, REV MOD PHYS, V85, P0, DOI 10.1103/RevModPhys.85.299
   Cooper NR, 2008, ADV PHYS, V57, P539, DOI 10.1080/00018730802564122
   Cooper NR, 2013, PHYS REV LETT, V110, P0, DOI 10.1103/PhysRevLett.110.185301
   Gopalakrishnan S, 2009, NAT PHYS, V5, P845, DOI 10.1038/NPHYS1403
   Hafezi M, 2013, NAT PHOTONICS, V7, P1001, DOI 10.1038/NPHOTON.2013.274
   Hoyos C, 2012, PHYS REV LETT, V108, P0, DOI 10.1103/PhysRevLett.108.066805
   Jia Ningyuan, 2015, PHYS REV X, V5, P0
   Karzig T, 2015, PHYS REV X, V5, P0, DOI 10.1103/PhysRevX.5.031001
   Klaers J, 2010, NATURE, V468, P545, DOI 10.1038/nature09567
   Longhi S, 2015, OPT LETT, V40, P2941, DOI 10.1364/OL.40.002941
   Nayak C, 2008, REV MOD PHYS, V80, P1083, DOI 10.1103/RevModPhys.80.1083
   Otterbach J, 2010, PHYS REV LETT, V104, P0, DOI 10.1103/PhysRevLett.104.033903
   Paredes B, 2001, PHYS REV LETT, V87, P0, DOI 10.1103/PhysRevLett.87.010402
   Peyronel T, 2012, NATURE, V488, P57, DOI 10.1038/nature11361
   Read N, 2009, PHYS REV B, V79, P0, DOI 10.1103/PhysRevB.79.045308
   Rechtsman MC, 2013, NATURE, V496, P196, DOI 10.1038/nature12066
   Rechtsman MC, 2013, NAT PHOTONICS, V7, P153, DOI 10.1038/nphoton.2012.302
   Schweikhard V, 2004, PHYS REV LETT, V92, P0, DOI 10.1103/PhysRevLett.92.040404
   Sommer A, 2015, PREPRINT, V0, P0
   Sommer A, 2016, NEW J PHYS, V18, P0, DOI 10.1088/1367-2630/18/3/035008
   Umucalilar RO, 2014, PHYS REV A, V89, P0, DOI 10.1103/PhysRevA.89.023803
   Umucalilar RO, 2013, PHYS LETT A, V377, P2074, DOI 10.1016/j.physleta.2013.06.011
   Wang Z, 2008, PHYS REV LETT, V100, P0
   Wang Z, 2009, NATURE, V461, P772, DOI 10.1038/nature08293
   WEN XG, 1992, PHYS REV LETT, V69, P953, DOI 10.1103/PhysRevLett.69.953
   Yuan J, 2007, APPL OPTICS, V46, P2980, DOI 10.1364/AO.46.002980
NR 30
TC 178
Z9 210
U1 0
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 671
EP 675
DI 10.1038/nature17943
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000033
PM 27281214
DA 2026-03-09
ER

PT J
AU Masselink, W
   Cole, NJ
   Fenyes, F
   Berger, S
   Sonntag, C
   Wood, A
   Nguyen, PD
   Cohen, N
   Knopf, F
   Weidinger, G
   Hall, TE
   Currie, PD
AF Masselink, Wouter
   Cole, Nicholas J.
   Fenyes, Fruzsina
   Berger, Silke
   Sonntag, Carmen
   Wood, Alasdair
   Nguyen, Phong D.
   Cohen, Naomi
   Knopf, Franziska
   Weidinger, Gilbert
   Hall, Thomas E.
   Currie, Peter D.
TI A somitic contribution to the apical ectodermal ridge is essential for fin formation
SO NATURE
LA English
DT Article
ID fluorescent protein; zebrafish; limb; origin; cells; chick; embryos; muscle; fish; bud
AB The transition from fins to limbs was an important terrestrial adaptation, but how this crucial evolutionary shift arose developmentally is unknown. Current models focus on the distinct roles of the apical ectodermal ridge (AER) and the signalling molecules that it secretes during limb and fin outgrowth. In contrast to the limb AER, the AER of the fin rapidly transitions into the apical fold and in the process shuts off AER-derived signals that stimulate proliferation of the precursors of the appendicular skeleton(1-10). The differing fates of the AER during fish and tetrapod development have led to the speculation that fin-fold formation was one of the evolutionary hurdles to the AER-dependent expansion of the fin mesenchyme required to generate the increased appendicular structure evident within limbs(11). Consequently, a heterochronic shift in the AER-to-apical-fold transition has been postulated to be crucial for limb evolution(11). The ability to test this model has been hampered by a lack of understanding of the mechanisms controlling apical fold induction(11,12). Here we show that invasion by cells of a newly identified somite-derived lineage into the AER in zebrafish regulates apical fold induction. Ablation of these cells inhibits apical fold formation, prolongs AER activity and increases the amount of fin bud mesenchyme, suggesting that these cells could provide the timing mechanism proposed in Thorogood's clock model of the fin-to-limb transition(11). We further demonstrate that apical-fold-inducing cells are progressively lost during gnathostome evolution; the absence of such cells within the tetrapod limb suggests that their loss may have been a necessary prelude to the attainment of limb-like structures in Devonian sarcopterygian fish.
C1 [Masselink, Wouter; Fenyes, Fruzsina; Berger, Silke; Sonntag, Carmen; Wood, Alasdair; Nguyen, Phong D.; Cohen, Naomi; Hall, Thomas E.; Currie, Peter D.] Monash Univ, Australian Regenerat Med Inst, Level 1,15 Innovat Walk,Wellington Rd, Clayton, Vic 3800, Australia.
   [Cole, Nicholas J.] Macquarie Univ, Fac Med & Heath Sci, MND & Neurodegenerat Dis Res Program, N Ryde, NSW 2109, Australia.
   [Knopf, Franziska] Univ Oxford, Kennedy Inst Rheumatol, Roosevelt Dr, Oxford OX3 7FY, England.
   [Weidinger, Gilbert] Univ Ulm, Inst Biochem & Mol Biol, Albert Einstein Allee 11, D-89081 Ulm, Germany.
   [Currie, Peter D.] Monash Univ, EMBL Australia Melbourne Node, Level 1,Bldg 75,Wellington Rd, Clayton, Vic 3800, Australia.
   [Masselink, Wouter; Knopf, Franziska] Tech Univ Dresden, DFG Ctr Regenerat Therapies Dresden, Fetscherstr 105, D-01307 Dresden, Germany.
C3 Australian Regenerative Medicine Institute; Monash University; Macquarie University; University of Oxford; Kennedy Institute for Rheumatology; Ulm University; Monash University; Technische Universitat Dresden; German Research Foundation (DFG)
RP Currie, PD (corresponding author), Monash Univ, Australian Regenerat Med Inst, Level 1,15 Innovat Walk,Wellington Rd, Clayton, Vic 3800, Australia.; Currie, PD (corresponding author), Monash Univ, EMBL Australia Melbourne Node, Level 1,Bldg 75,Wellington Rd, Clayton, Vic 3800, Australia.
EM peter.currie@monash.edu
FU NHMRC; Snow Foundation; BitFury.org; ARC [DP110101482]; State Government of Victoria; Australian Federal Government
NR 43
TC 17
Z9 23
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 542
EP +
DI 10.1038/nature18953
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600027
PM 27437584
DA 2026-03-09
ER

PT J
AU McCoy, VE
   Saupe, EE
   Lamsdell, JC
   Tarhan, LG
   McMahon, S
   Lidgard, S
   Mayer, P
   Whalen, CD
   Soriano, C
   Finney, L
   Vogt, S
   Clark, EG
   Anderson, RP
   Petermann, H
   Locatelli, ER
   Briggs, DEG
AF McCoy, Victoria E.
   Saupe, Erin E.
   Lamsdell, James C.
   Tarhan, Lidya G.
   McMahon, Sean
   Lidgard, Scott
   Mayer, Paul
   Whalen, Christopher D.
   Soriano, Carmen
   Finney, Lydia
   Vogt, Stefan
   Clark, Elizabeth G.
   Anderson, Ross P.
   Petermann, Holger
   Locatelli, Emma R.
   Briggs, Derek E. G.
TI The 'Tully monster' is a vertebrate
SO NATURE
LA English
DT Article
ID fossil; illinois
AB Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica'(1), particularly the 'weird wonders'(2) of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium(3), popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans(4,5), polychaetes(4), gastropods(4), conodonts(6), and the stem arthropod Opabinia(4). Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes(3-6). We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys(7-9), a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.
C1 [McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Whalen, Christopher D.; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E. G.] Yale Univ, Dept Geol & Geophys, 210 Whitney Ave, New Haven, CT 06511 USA.
   [Lamsdell, James C.] Amer Museum Nat Hist, Cent Pk West & 79th St, New York, NY 10024 USA.
   [Lidgard, Scott; Mayer, Paul] Field Museum Nat Hist, 1400 S Lake Shore Dr, Chicago, IL 60605 USA.
   [Soriano, Carmen; Finney, Lydia; Vogt, Stefan] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
   [Briggs, Derek E. G.] Yale Peabody Museum Nat Hist, 170 Whitney Ave, New Haven, CT 06511 USA.
C3 Yale University; American Museum of Natural History (AMNH); Field Museum of Natural History (Chicago); United States Department of Energy (DOE); Argonne National Laboratory; Yale University
RP McCoy, VE (corresponding author), Yale Univ, Dept Geol & Geophys, 210 Whitney Ave, New Haven, CT 06511 USA.
EM victoria.mccoy@yale.edu
FU US Department of Energy Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]; Field Museum visiting scholarship; NASA Astrobiology Institute Foundations of Complex Life, Evolution, Preservation and Detection on Earth and Beyond [NNA13AA90A]
NR 28
TC 39
Z9 49
U1 3
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 496
EP +
DI 10.1038/nature16992
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900046
PM 26982721
DA 2026-03-09
ER

PT J
AU Hassan, MT
   Luu, TT
   Moulet, A
   Raskazovskaya, O
   Zhokhov, P
   Garg, M
   Karpowicz, N
   Zheltikov, AM
   Pervak, V
   Krausz, F
   Goulielmakis, E
AF Hassan, M. Th.
   Luu, T. T.
   Moulet, A.
   Raskazovskaya, O.
   Zhokhov, P.
   Garg, M.
   Karpowicz, N.
   Zheltikov, A. M.
   Pervak, V.
   Krausz, F.
   Goulielmakis, E.
TI Optical attosecond pulses and tracking the nonlinear response of bound electrons
SO NATURE
LA English
DT Article
ID real-time observation; high-harmonic-generation; dynamics; gases; susceptibility; spectroscopy; ionization; solids; delay
AB The time it takes a bound electron to respond to the electromagnetic force of light sets a fundamental speed limit on the dynamic control of matter and electromagnetic signal processing. Time-integrated measurements of the nonlinear refractive index(1) of matter indicate that the nonlinear response of bound electrons to optical fields is not instantaneous; however, a complete spectral characterization of the nonlinear susceptibility tensors(2)-which is essential to deduce the temporal response of a medium to arbitrary driving forces using spectral measurements-has not yet been achieved. With the establishment of attosecond chronoscopy(3-5), the impulsive response of positive-energy electrons to electromagnetic fields has been explored through ionization of atoms(6) and solids(7) by an extreme-ultraviolet attosecond pulse(8) or by strong near-infrared fields(9-11). However, none of the attosecond studies carried out so far have provided direct access to the nonlinear response of bound electrons. Here we demonstrate that intense optical attosecond pulses synthesized in the visible and nearby spectral ranges allow sub-femtosecond control and metrology of bound-electron dynamics. Vacuum ultraviolet spectra emanating from krypton atoms, exposed to intense waveform-controlled optical attosecond pulses, reveal a finite nonlinear response time of bound electrons of up to 115 attoseconds, which is sensitive to and controllable by the super-octave optical field. Our study could enable new spectroscopies of bound electrons in atomic, molecular or lattice potentials of solids(12), as well as light-based electronics operating on sub-femtosecond timescales and at petahertz rates(13-15).
C1 [Hassan, M. Th.; Luu, T. T.; Moulet, A.; Garg, M.; Karpowicz, N.; Krausz, F.; Goulielmakis, E.] Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
   [Raskazovskaya, O.; Pervak, V.; Krausz, F.] Univ Munich, Dept Phys, Coulombwall 1, D-85748 Garching, Germany.
   [Zhokhov, P.; Zheltikov, A. M.] Texas A&M Univ, Dept Phys & Astron, College Stn, TX 77843 USA.
   [Zhokhov, P.; Zheltikov, A. M.] Moscow MV Lomonosov State Univ, Dept Phys, Ctr Int Laser, Moscow 119992, Russia.
C3 Max Planck Society; University of Munich; Texas A&M University System; Texas A&M University College Station; Lomonosov Moscow State University
RP Goulielmakis, E (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM elgo@mpq.mpg.de
FU European Research Council [Attoelectronics-258501]; Deutsche Forschungsgemeinschaft Cluster of Excellence: Munich Centre for Advanced Photonics; Max Planck Society; European Research Training Network ATTOFEL; European Research Training Network MEDEA; Russian Foundation for Basic Research [13-02-01465, 13-02-92115, 13-04-40335]; Welch Foundation [A-1801]; Russian Science Foundation [14-12-00772] Funding Source: Russian Science Foundation
NR 36
TC 410
Z9 444
U1 5
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 66
EP +
DI 10.1038/nature16528
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500033
PM 26842055
DA 2026-03-09
ER

PT J
AU Hsia, Y
   Bale, JB
   Gonen, S
   Shi, D
   Sheffler, W
   Fong, KK
   Nattermann, U
   Xu, CF
   Huang, PS
   Ravichandran, R
   Yi, S
   Davis, TN
   Gonen, T
   King, NP
   Baker, D
AF Hsia, Yang
   Bale, Jacob B.
   Gonen, Shane
   Shi, Dan
   Sheffler, William
   Fong, Kimberly K.
   Nattermann, Una
   Xu, Chunfu
   Huang, Po-Ssu
   Ravichandran, Rashmi
   Yi, Sue
   Davis, Trisha N.
   Gonen, Tamir
   King, Neil P.
   Baker, David
TI Design of a hyperstable 60-subunit protein icosahedron
SO NATURE
LA English
DT Article
ID image; generation; visualization; particles; suite
AB The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport(1,2). There has been considerable interest in repurposing such structures(3-5) for applications ranging from targeted delivery to multivalent immunogen presentation. The ability to design proteins that self-assemble into precisely specified, highly ordered icosahedral structures would open the door to a new generation of protein containers with properties custom-tailored to specific applications. Here we describe the computational design of a 25-nanometre icosahedral nanocage that self-assembles from trimeric protein building blocks. The designed protein was produced in Escherichia coli, and found by electron microscopy to assemble into a homogenous population of icosahedral particles nearly identical to the design model. The particles are stable in 6.7 molar guanidine hydrochloride at up to 80 degrees Celsius, and undergo extremely abrupt, but reversible, disassembly between 2 molar and 2.25 molar guanidinium thiocyanate. The icosahedron is robust to genetic fusions: one or two copies of green fluorescent protein (GFP) can be fused to each of the 60 subunits to create highly fluorescent 'standard candles' for use in light microscopy, and a designed protein pentamer can be placed in the centre of each of the 20 pentameric faces to modulate the size of the entrance/exit channels of the cage. Such robust and customizable nanocages should have considerable utility in targeted drug delivery(6), vaccine design(7) and synthetic biology(8).
C1 [Hsia, Yang; Bale, Jacob B.; Gonen, Shane; Sheffler, William; Fong, Kimberly K.; Nattermann, Una; Xu, Chunfu; Huang, Po-Ssu; Ravichandran, Rashmi; Yi, Sue; Davis, Trisha N.; King, Neil P.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Hsia, Yang; Bale, Jacob B.; Gonen, Shane; Sheffler, William; Nattermann, Una; Xu, Chunfu; Huang, Po-Ssu; Ravichandran, Rashmi; Yi, Sue; King, Neil P.; Baker, David] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
   [Hsia, Yang; Gonen, Shane; Nattermann, Una] Univ Washington, Grad Program Biol Phys Struct & Design, Seattle, WA 98195 USA.
   [Bale, Jacob B.] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA.
   [Gonen, Shane; Shi, Dan; Gonen, Tamir] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
   [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.; Baker, D (corresponding author), Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.; Baker, D (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM dabaker@uw.edu
FU Howard Hughes Medical Institute; JRC; National Science Foundation [CHE-1332907]; UW/Hutch CCSG Pilot Award NCI [5 P30 CA015704-41]; Takeda Pharmaceutical Company; Bill and Melinda Gates Foundation [OPP1120319]; National Institutes of Health (NIH) [P41 GM103533]; Defense Advanced Research Projects Agency [W911NF-14-1-0162]; Air Force Office of Scientific Research (AFOSR) [AFOSR FA950-12-10112]; NIH [T32GM008268]; PHS National Research Service Award from NIGMS [T32GM007270]; NSF Graduate Research Fellowship [DGE-0718124]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1332907] Funding Source: National Science Foundation; National Cancer Institute [P30CA015704] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008268, P41GM103533] Funding Source: NIH RePORTER; Bill and Melinda Gates Foundation [OPP1120319] Funding Source: Bill and Melinda Gates Foundation
NR 43
TC 359
Z9 489
U1 10
U2 252
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 136
EP +
DI 10.1038/nature18010
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600039
PM 27309817
DA 2026-03-09
ER

PT J
AU Ofek, N
   Petrenko, A
   Heeres, R
   Reinhold, P
   Leghtas, Z
   Vlastakis, B
   Liu, YH
   Frunzio, L
   Girvin, SM
   Jiang, L
   Mirrahimi, M
   Devoret, MH
   Schoelkopf, RJ
AF Ofek, Nissim
   Petrenko, Andrei
   Heeres, Reinier
   Reinhold, Philip
   Leghtas, Zaki
   Vlastakis, Brian
   Liu, Yehan
   Frunzio, Luigi
   Girvin, S. M.
   Jiang, L.
   Mirrahimi, Mazyar
   Devoret, M. H.
   Schoelkopf, R. J.
TI Extending the lifetime of a quantum bit with error correction in superconducting circuits
SO NATURE
LA English
DT Article
ID qubit; information; realization; photon; state; code
AB Quantum error correction (QEC) can overcome the errors experienced by qubits1 and is therefore an essential component of a future quantum computer. To implement QEC, a qubit is redundantly encoded in a higher-dimensional space using quantum states with carefully tailored symmetry properties. Projective measurements of these parity-type observables provide error syndrome information, with which errors can be corrected via simple operations(2). The 'break-even' point of QEC-at which the lifetime of a qubit exceeds the lifetime of the constituents of the system-has so far remained out of reach(3). Although previous works have demonstrated elements of QEC(4-16), they primarily illustrate the signatures or scaling properties of QEC codes rather than test the capacity of the system to preserve a qubit over time. Here we demonstrate a QEC system that reaches the break-even point by suppressing the natural errors due to energy loss for a qubit logically encoded in superpositions of Schrodinger-cat states(17) of a superconducting resonator(18-21). We implement a full QEC protocol by using real-time feedback to encode, monitor naturally occurring errors, decode and correct. As measured by full process tomography, without any post-selection, the corrected qubit lifetime is 320 microseconds, which is longer than the lifetime of any of the parts of the system: 20 times longer than the lifetime of the transmon, about 2.2 times longer than the lifetime of an uncorrected logical encoding and about 1.1 longer than the lifetime of the best physical qubit (the vertical bar 0 >(f) and vertical bar 1 >(f) Fock states of the resonator). Our results illustrate the benefit of using hardware-efficient qubit encodings rather than traditional QEC schemes. Furthermore, they advance the field of experimental error correction from confirming basic concepts to exploring the metrics that drive system performance and the challenges in realizing a fault-tolerant system.
C1 [Ofek, Nissim; Petrenko, Andrei; Heeres, Reinier; Reinhold, Philip; Leghtas, Zaki; Vlastakis, Brian; Liu, Yehan; Frunzio, Luigi; Girvin, S. M.; Jiang, L.; Mirrahimi, Mazyar; Devoret, M. H.; Schoelkopf, R. J.] Yale Univ, Dept Phys, New Haven, CT 06510 USA.
   [Ofek, Nissim; Petrenko, Andrei; Heeres, Reinier; Reinhold, Philip; Leghtas, Zaki; Vlastakis, Brian; Liu, Yehan; Frunzio, Luigi; Girvin, S. M.; Jiang, L.; Mirrahimi, Mazyar; Devoret, M. H.; Schoelkopf, R. J.] Yale Univ, Dept Appl Phys, New Haven, CT 06510 USA.
   [Mirrahimi, Mazyar] INRIA Paris, QUANTIC Team, 2 Rue Simone Iff, F-75012 Paris, France.
   [Leghtas, Zaki] PSL Res Univ, Mines ParisTech, Ctr Automat & Syst, 60 Blvd St Michel, F-75006 Paris, France.
C3 Yale University; Yale University; Universite PSL; MINES ParisTech
RP Ofek, N; Petrenko, A; Schoelkopf, RJ (corresponding author), Yale Univ, Dept Phys, New Haven, CT 06510 USA.; Ofek, N; Petrenko, A; Schoelkopf, RJ (corresponding author), Yale Univ, Dept Appl Phys, New Haven, CT 06510 USA.
EM nissim.of@gmail.com; andrei.o.petrenko@gmail.com; robert.schoelkopf@yale.edu
FU US Army Research Office [W911NF-14-1-0011]; National Science Foundation (NSF) [PHY-1309996, DMR-1301798]
NR 30
TC 759
Z9 918
U1 4
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 441
EP 445
DI 10.1038/nature18949
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600038
PM 27437573
DA 2026-03-09
ER

PT J
AU Ribeiro, CMS
   Sarrami-Forooshani, R
   Setiawan, LC
   Zijlstra-Willems, EM
   van Hamme, JL
   Tigchelaar, W
   van der Wel, NN
   Kootstra, NA
   Gringhuis, SI
   Geijtenbeek, TBH
AF Ribeiro, Carla M. S.
   Sarrami-Forooshani, Ramin
   Setiawan, Laurentia C.
   Zijlstra-Willems, Esther M.
   van Hamme, John L.
   Tigchelaar, Wikky
   van der Wel, Nicole N.
   Kootstra, Neeltje A.
   Gringhuis, Sonja I.
   Geijtenbeek, Teunis B. H.
TI Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets
SO NATURE
LA English
DT Article
ID dc-sign; langerhans cells; retrovirus restriction; b30.2(spry) domain; old-world; infection; transmission; proteasome; stability; autophagy
AB The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens(1). Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection(2). Notably, LCs form a protective barrier against HIV-1 infection and transmission(3-5). LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules(5). However, the underlying molecular mechanism of HIV-1 restriction in LCs remains unknown. Here we show that human E3-ubiquitin ligase tri-partite-containing motif 5 alpha (TRIM5 alpha) potently restricts HIV-1 infection of LCs but not of subepithelial DC-SIGN+ DCs. HIV-1 restriction by TRIM5 alpha was thus far considered to be reserved to non-human primate TRIM5 alpha orthologues(6-9), but our data strongly suggest that human TRIM5 alpha is a cell-specific restriction factor dependent on C-type lectin receptor function. Our findings highlight the importance of HIV-1 binding to Langerin for the routeing of HIV-1 into the human TRIM5 alpha-mediated restriction pathway. TRIM5 alpha mediates the assembly of an autophagy-activating scaffold to Langerin, which targets HIV-1 for autophagic degradation and prevents infection of LCs. By contrast, HIV-1 binding to DC-SIGN(+) DCs leads to disassociation of TRIM5 alpha from DC-SIGN, which abrogates TRIM5 alpha restriction. Thus, our data strongly suggest that restriction by human TRIM5 alpha is controlled by C-type-lectin-receptor-dependent uptake of HIV-1, dictating protection or infection of human DC subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans.
C1 [Ribeiro, Carla M. S.; Sarrami-Forooshani, Ramin; Setiawan, Laurentia C.; Zijlstra-Willems, Esther M.; van Hamme, John L.; Kootstra, Neeltje A.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
   [Tigchelaar, Wikky; van der Wel, Nicole N.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
C3 University of Amsterdam; University of Amsterdam
RP Ribeiro, CMS; Geijtenbeek, TBH (corresponding author), Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM c.m.ribeiro@amc.uva.nl; t.b.geijtenbeek@amc.uva.nl
FU Dutch Scientific Organization NWO [VENI 863.13.025, VICI 918.10.619]; Aids Fonds [2010038]; European Research Council [670424]
NR 36
TC 112
Z9 127
U1 1
U2 25
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 448
EP +
DI 10.1038/nature20567
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800045
PM 27919079
DA 2026-03-09
ER

PT J
AU Bentley, MS
   Schmied, R
   Mannel, T
   Torkar, K
   Jeszenszky, H
   Romstedt, J
   Levasseur-Regourd, AC
   Weber, I
   Jessberger, EK
   Ehrenfreund, P
   Koeberl, C
   Havnes, O
AF Bentley, Mark S.
   Schmied, Roland
   Mannel, Thurid
   Torkar, Klaus
   Jeszenszky, Harald
   Romstedt, Jens
   Levasseur-Regourd, Anny-Chantal
   Weber, Iris
   Jessberger, Elmar K.
   Ehrenfreund, Pascale
   Koeberl, Christian
   Havnes, Ove
TI Aggregate dust particles at comet 67P/Churyumov-Gerasimenko
SO NATURE
LA English
DT Article
ID interstellar dust; 81p/wild 2; grains; system; midas; model
AB Comets are thought to preserve almost pristine dust particles, thus providing a unique sample of the properties of the early solar nebula. The microscopic properties of this dust played a key part in particle aggregation during the formation of the Solar System(1,2). Cometary dust was previously considered to comprise irregular, fluffy agglomerates on the basis of interpretations of remote observations in the visible and infrared(3-6) and the study of chondritic porous interplanetary dust particles(7) that were thought, but not proved, to originate in comets. Although the dust returned by an earlier mission(8) has provided detailed mineralogy of particles from comet 81P/Wild, the fine-grained aggregate component was strongly modified during collection. Here we report in situ measurements of dust particles at comet 67P/Churyumov-Gerasimenko. The particles are aggregates of smaller, elongated grains, with structures at distinct sizes indicating hierarchical aggregation. Topographic images of selected dust particles with sizes of one micrometre to a few tens of micrometres show a variety of morphologies, including compact single grains and large porous aggregate particles, similar to chondritic porous interplanetary dust particles. The measured grain elongations are similar to the value inferred for interstellar dust and support the idea that such grains could represent a fraction of the building blocks of comets. In the subsequent growth phase, hierarchical agglomeration could be a dominant process(10) and would produce aggregates that stick more easily at higher masses and velocities than homogeneous dust particles(11). The presence of hierarchical dust aggregates in the near surface of the nucleus of comet 67P also provides a mechanism for lowering the tensile strength of the dust layer and aiding dust release(12).
C1 [Bentley, Mark S.; Schmied, Roland; Mannel, Thurid; Torkar, Klaus; Jeszenszky, Harald] Austrian Acad Sci, Space Res Inst, Schmiedlstr 6, A-8042 Graz, Austria.
   [Mannel, Thurid] Graz Univ, Inst Phys, Univ Pl 5, A-8010 Graz, Austria.
   [Romstedt, Jens] European Space Technol Ctr, Future Missions Off SREF, Noordwijk, Netherlands.
   [Levasseur-Regourd, Anny-Chantal] Univ Paris 06, Sorbonne Univ, BC 102,4 Pl Jussieu, F-75005 Paris, France.
   [Levasseur-Regourd, Anny-Chantal] CNRS, INSU, BC 102,4 Pl Jussieu, F-75005 Paris, France.
   [Levasseur-Regourd, Anny-Chantal] IPSL, LATMOS, BC 102,4 Pl Jussieu, F-75005 Paris, France.
   [Weber, Iris; Jessberger, Elmar K.] Univ Munster, Inst Planetol, Wilhelm Klemm Str 10, D-48149 Munster, Germany.
   [Ehrenfreund, Pascale] Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
   [Ehrenfreund, Pascale] George Washington Univ, Inst Space Policy, Washington, DC 20052 USA.
   [Koeberl, Christian] Univ Vienna, Dept Lithospher Res, Althanstr 14, A-1090 Vienna, Austria.
   [Koeberl, Christian] Nat Hist Museum, Burgring 7, A-1010 Vienna, Austria.
   [Havnes, Ove] UiT, Dept Phys & Technol, N-9037 Tromso, Norway.
C3 Austrian Academy of Sciences; University of Graz; European Space Agency; European Space Research & Technology Centre; Sorbonne Universite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Institut Polytechnique de Paris; Ecole Polytechnique; Universite Paris Saclay; Sorbonne Universite; University of Munster; George Washington University; University of Vienna; UiT The Arctic University of Tromso
RP Bentley, MS (corresponding author), Austrian Acad Sci, Space Res Inst, Schmiedlstr 6, A-8042 Graz, Austria.
EM mark.bentley@oeaw.ac.at
FU European Space Agency's PRODEX programme; Austrian Space Agency; Austrian Academy of Sciences; German funding agency DARA; DLR; French Space Agency, CNES; Austrian Science Fund (FWF) [P 28100-N36]; Steiermarkische Sparkasse; Karl-Franzens Universitat Graz; NASA Astrobiology Institute; Austrian Research Promotion Agency (FFG)
NR 26
TC 159
Z9 164
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 73
EP 75
DI 10.1038/nature19091
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900040
PM 27582221
DA 2026-03-09
ER

PT J
AU Giorgetti, L
   Lajoie, BR
   Carter, AC
   Attia, M
   Zhan, Y
   Xu, J
   Chen, CJ
   Kaplan, N
   Chang, HY
   Heard, E
   Dekker, J
AF Giorgetti, Luca
   Lajoie, Bryan R.
   Carter, Ava C.
   Attia, Mikael
   Zhan, Ye
   Xu, Jin
   Chen, Chong Jian
   Kaplan, Noam
   Chang, Howard Y.
   Heard, Edith
   Dekker, Job
TI Structural organization of the inactive X chromosome in the mouse
SO NATURE
LA English
DT Article
ID gene-expression; xist rna; chromatin; reveals; binding; ctcf; reconstruction; conformation; architecture; territory
AB X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region(1,2), although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts(3). A role for Xist in organizing the inactive X (Xi) chromosome has been proposed(4-6). Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite(7-10). However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions, remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes in different neural progenitor clones are associated with the presence of different TAD-like structures after XCI. These findings suggest a key role for transcription and CTCF in the formation of TADs in the context of the Xi chromosome in neural progenitors.
C1 [Giorgetti, Luca; Attia, Mikael; Chen, Chong Jian; Heard, Edith] PSL Res Univ, Inst Curie, CNRS, UMR3215,INSERM,U934, 26 Rue Ulm, F-75248 Paris 05, France.
   [Lajoie, Bryan R.; Zhan, Ye; Kaplan, Noam; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Syst Biol, 368 Plantat St, Worcester, MA 01605 USA.
   [Carter, Ava C.; Xu, Jin; Chang, Howard Y.] Stanford Univ, Sch Med, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA.
   [Carter, Ava C.; Xu, Jin; Chang, Howard Y.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Heard, Edith] Coll France, 11 Pl Marcelin Berthelot, F-75005 Paris, France.
   [Dekker, Job] Univ Massachusetts, Howard Hughes Med Inst, Sch Med, 368 Plantat St, Worcester, MA 01605 USA.
   [Giorgetti, Luca] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
C3 Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); University of Massachusetts System; University of Massachusetts Worcester; Stanford University; Stanford University; Universite PSL; College de France; University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; Friedrich Miescher Institute for Biomedical Research
RP Heard, E (corresponding author), PSL Res Univ, Inst Curie, CNRS, UMR3215,INSERM,U934, 26 Rue Ulm, F-75248 Paris 05, France.; Dekker, J (corresponding author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Syst Biol, 368 Plantat St, Worcester, MA 01605 USA.; Heard, E (corresponding author), Coll France, 11 Pl Marcelin Berthelot, F-75005 Paris, France.; Dekker, J (corresponding author), Univ Massachusetts, Howard Hughes Med Inst, Sch Med, 368 Plantat St, Worcester, MA 01605 USA.
EM edith.heard@curie.fr; job.dekker@umassmed.edu
FU National Institutes of Health [P50-HG007735]; Scleroderma Research Foundation; National Human Genome Research Institute [R01 HG003143]; National Institutes of Health Common Fund, National Institute of Diabetes and Digestive and Kidney Diseases [U54 DK107980]; Human Frontier Science Program; EMBO Fellowship; ERC [671027]; EU FP7 grant SYBOSS (EU) [242129]; EU FP7 grant MODHEP (EU) [259743]; La Ligue; Fondation de France; Labex DEEP part of the IDEX Idex PSL [ANR-11-LBX-0044, ANR-10-IDEX-0001-02 PSL]; ABS4NGS [ANR-11-BINF-0001]; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER; National Institute on Aging [T32AG047126] Funding Source: NIH RePORTER; European Research Council (ERC) [671027] Funding Source: European Research Council (ERC)
NR 38
TC 308
Z9 385
U1 3
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 575
EP +
DI 10.1038/nature18589
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600034
PM 27437574
DA 2026-03-09
ER

PT J
AU McKinley, GA
   Pilcher, DJ
   Fay, AR
   Lindsay, K
   Long, MC
   Lovenduski, NS
AF McKinley, Galen A.
   Pilcher, Darren J.
   Fay, Amanda R.
   Lindsay, Keith
   Long, Matthew C.
   Lovenduski, Nicole S.
TI Timescales for detection of trends in the ocean carbon sink
SO NATURE
LA English
DT Article
ID earth system model; southern-ocean; anthropogenic co2; natural variability; climate; fluxes; atlantic; learn; cmip5
AB The ocean has absorbed 41 per cent of all anthropogenic carbon emitted as a result of fossil fuel burning and cement manufacture(1,2). The magnitude and the large-scale distribution of the ocean carbon sink is well quantified for recent decades(3,4). In contrast, temporal changes in the oceanic carbon sink remain poorly understood(5-7). It has proved difficult to distinguish between air-to-sea carbon flux trends that are due to anthropogenic climate change and those due to internal climate variability(5,6,8-13). Here we use a modelling approach that allows for this separation(14), revealing how the ocean carbon sink may be expected to change throughout this century in different oceanic regions. Our findings suggest that, owing to large internal climate variability, it is unlikely that changes in the rate of anthropogenic carbon uptake can be directly observed in most oceanic regions at present, but that this may become possible between 2020 and 2050 in some regions.
C1 [McKinley, Galen A.; Pilcher, Darren J.] Univ Wisconsin, Dept Atmospher & Ocean Sci, Madison, WI USA.
   [McKinley, Galen A.] Univ Wisconsin, Ctr Climat Res, Madison, WI USA.
   [McKinley, Galen A.; Fay, Amanda R.] Univ Wisconsin, Space Sci & Engn Ctr, Madison, WI USA.
   [Pilcher, Darren J.] NOAA, Pacific Marine Environm Lab, 7600 Sand Point Way Ne, Seattle, WA 98115 USA.
   [Lindsay, Keith; Long, Matthew C.] Natl Ctr Atmospher Res, POB 3000, Boulder, CO 80307 USA.
   [Lovenduski, Nicole S.] Univ Colorado, Dept Atmospher & Ocean Sci, Boulder, CO 80309 USA.
   [Lovenduski, Nicole S.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; National Oceanic Atmospheric Admin (NOAA) - USA; National Center Atmospheric Research (NCAR) - USA; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder
RP McKinley, GA (corresponding author), Univ Wisconsin, Dept Atmospher & Ocean Sci, Madison, WI USA.; McKinley, GA (corresponding author), Univ Wisconsin, Ctr Climat Res, Madison, WI USA.; McKinley, GA (corresponding author), Univ Wisconsin, Space Sci & Engn Ctr, Madison, WI USA.
EM gamckinley@wisc.edu
FU National Science Foundation; NSF; NCAR's Advanced Study Program; NASA [NNX11AF53G, NNX13AC53G]; NSF [OCE-1155240]; NOAA [NA12OAR4310058]; NASA [146979, NNX13AC53G, 476329, NNX11AF53G] Funding Source: Federal RePORTER; Division Of Ocean Sciences; Directorate For Geosciences [1155240] Funding Source: National Science Foundation
NR 48
TC 115
Z9 133
U1 4
U2 180
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 469
EP 472
DI 10.1038/nature16958
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800033
PM 26911782
DA 2026-03-09
ER

PT J
AU Won, HJ
   de la Torre-Ubieta, L
   Stein, JL
   Parikshak, NN
   Huang, J
   Opland, CK
   Gandal, MJ
   Sutton, GJ
   Hormozdiari, F
   Lu, DN
   Lee, C
   Eskin, E
   Voineagu, I
   Ernst, J
   Geschwind, DH
AF Won, Hyejung
   de la Torre-Ubieta, Luis
   Stein, Jason L.
   Parikshak, Neelroop N.
   Huang, Jerry
   Opland, Carli K.
   Gandal, Michael J.
   Sutton, Gavin J.
   Hormozdiari, Farhad
   Lu, Daning
   Lee, Changhoon
   Eskin, Eleazar
   Voineagu, Irina
   Ernst, Jason
   Geschwind, Daniel H.
TI Chromosome conformation elucidates regulatory relationships in developing human brain
SO NATURE
LA English
DT Article
ID de-novo mutations; human genome; gene-expression; human-cells; hi-c; schizophrenia; landscape; promoter; disease; autism
AB Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner(1-3). However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia(4-6), are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with enhancers gained on the human lineage, many of which are under purifying selection and associated with human cognitive function. We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), highlighting multiple candidate schizophrenia risk genes and pathways, including transcription factors involved in neurogenesis, and cholinergic signalling molecules, several of which are supported by independent expression quantitative trait loci and gene expression analyses. Genome editing in human neural progenitors suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, supporting its potential role as a schizophrenia risk gene. This work provides a framework for understanding the effect of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel mechanisms underlying neuropsychiatric disorders.
C1 [Won, Hyejung; de la Torre-Ubieta, Luis; Stein, Jason L.; Huang, Jerry; Opland, Carli K.; Gandal, Michael J.; Lu, Daning; Lee, Changhoon; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Dept Neurol, Los Angeles, CA 90095 USA.
   [Parikshak, Neelroop N.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Sutton, Gavin J.; Voineagu, Irina] Univ New South Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia.
   [Hormozdiari, Farhad; Eskin, Eleazar; Ernst, Jason] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA.
   [Eskin, Eleazar; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Ernst, Jason] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Stein, Jason L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Stein, Jason L.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of New South Wales Sydney; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill
RP Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Dept Neurol, Los Angeles, CA 90095 USA.; Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA.
EM dhg@mednet.ucla.edu
FU NIH [5R01MH060233, 5R01MH100027, 3U01MH103339, 1R01MH110927, 1R01MH094714, R01MH101782, R01ES022282, T32MH073526, K99MH102357, R01ES024995]; NSF [1254200]; Glenn/AFAR Postdoctoral Fellowship Program [20145357]; Basic Science Research Program through the National Research Foundation of Korea [2013024227]; CIRM-BSCRC [TG2-01169]; NRSA [F30MH099886]; NRSA (UCLA MSTP); NHMRC [APP1062510]; ARC DECRA fellowship [DE140101033]; National Institute of Mental Health [R01MH100027] Funding Source: NIH RePORTER; Direct For Computer & Info Scie & Enginr [1436827] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [1302448] Funding Source: National Science Foundation; Division of Computing and Communication Foundations [1436827] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1254200] Funding Source: National Science Foundation; Australian Research Council [DE140101033] Funding Source: Australian Research Council
NR 46
TC 397
Z9 499
U1 2
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 523
EP +
DI 10.1038/nature19847
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400061
PM 27760116
DA 2026-03-09
ER

PT J
AU Yang, HT
   Hu, MH
   Guo, JL
   Ou, XM
   Cai, TX
   Liu, ZF
AF Yang, Hanting
   Hu, Miaohui
   Guo, Jianli
   Ou, Xiaomin
   Cai, Tanxi
   Liu, Zhenfeng
TI Pore architecture of TRIC channels and insights into their gating mechanism
SO NATURE
LA English
DT Article
ID k+-channel; sarcoplasmic-reticulum; ion-channels; pip2; complex
AB Intracellular Ca2+ signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis(1,2). Release of Ca2+ from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER)(3,4). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca2+ through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen(5,6). Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease(7-12). Despite the pivotal function of TRIC channels in Ca2+ signalling(5,13,14), their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5) P-2, also known as PIP2) lipid molecules. The TRIC-B1/B2 proteins and PIP2 assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP2 in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca2+-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.
C1 [Yang, Hanting; Hu, Miaohui; Guo, Jianli; Ou, Xiaomin; Liu, Zhenfeng] Chinese Acad Sci, Inst Biophys, Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Yang, Hanting; Hu, Miaohui] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Cai, Tanxi] Chinese Acad Sci, Inst Biophys, Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China.
   [Cai, Tanxi] Chinese Acad Sci, Inst Biophys, Lab Prote, Beijing 100101, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Institute of Biophysics, CAS; Chinese Academy of Sciences; Institute of Biophysics, CAS
RP Liu, ZF (corresponding author), Chinese Acad Sci, Inst Biophys, Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
EM liuzf@sun5.ibp.ac.cn
FU National 973 Program from Chinese Ministry of Science and Technology [2014CB910301]; Strategic Priority Research Program [XDB08020302]; Chinese Academy of Sciences (CAS); Office of Global Experts Recruitment in China
NR 41
TC 39
Z9 48
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 537
EP +
DI 10.1038/nature19767
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400064
PM 27698420
DA 2026-03-09
ER

PT J
AU Cho, H
   Du, XL
   Rizzi, JP
   Liberzon, E
   Chakraborty, AA
   Gao, WH
   Carvo, I
   Signoretti, S
   Bruick, RK
   Josey, JA
   Wallace, EM
   Kaelin, WG
AF Cho, Hyejin
   Du, Xinlin
   Rizzi, James P.
   Liberzon, Ella
   Chakraborty, Abhishek A.
   Gao, Wenhua
   Carvo, Ingrid
   Signoretti, Sabina
   Bruick, Richard K.
   Josey, John A.
   Wallace, Eli M.
   Kaelin, William G., Jr.
TI On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models
SO NATURE
LA English
DT Article
ID pas-b domain; transcription factor; cell; inhibition; carcinoma; gene
AB Clear cell renal cell carcinoma, the most common form of kidney cancer, is usually linked to inactivation of the pVHL tumour suppressor protein and consequent accumulation of the HIF-2 alpha transcription factor (also known as EPAS1)(1). Here we show that a small molecule (PT2399) that directly inhibits HIF-2 alpha causes tumour regression in preclinical mouse models of primary and metastatic pVHL-defective clear cell renal cell carcinoma in an ontarget fashion. pVHL-defective clear cell renal cell carcinoma cell lines display unexpectedly variable sensitivity to PT2399, however, suggesting the need for predictive biomarkers to be developed to use this approach optimally in the clinic.
C1 [Cho, Hyejin; Liberzon, Ella; Chakraborty, Abhishek A.; Gao, Wenhua; Carvo, Ingrid; Signoretti, Sabina; Kaelin, William G., Jr.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Cho, Hyejin; Liberzon, Ella; Chakraborty, Abhishek A.; Gao, Wenhua; Carvo, Ingrid; Signoretti, Sabina; Kaelin, William G., Jr.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02215 USA.
   [Du, Xinlin; Rizzi, James P.; Josey, John A.; Wallace, Eli M.] Peloton Therapeut Inc, Dallas, TX 75235 USA.
   [Carvo, Ingrid; Signoretti, Sabina] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Bruick, Richard K.] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75235 USA.
   [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
RP Kaelin, WG (corresponding author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Wallace, EM; Kaelin, WG (corresponding author), Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02215 USA.; Wallace, EM (corresponding author), Peloton Therapeut Inc, Dallas, TX 75235 USA.; Kaelin, WG (corresponding author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM eli.wallace@pelotontx.com; william_kaelin@dfci.harvard.edu
FU NIH; Cancer Prevention and Research Institute of Texas [RP130513]; National Cancer Institute [P50CA101942, R35CA210068] Funding Source: NIH RePORTER
NR 15
TC 374
Z9 429
U1 3
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 107
EP +
DI 10.1038/nature19795
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100039
PM 27595393
DA 2026-03-09
ER

PT J
AU Hayakawa, K
   Esposito, E
   Wang, XH
   Terasaki, Y
   Liu, Y
   Xing, CH
   Ji, XM
   Lo, EH
AF Hayakawa, Kazuhide
   Esposito, Elga
   Wang, Xiaohua
   Terasaki, Yasukazu
   Liu, Yi
   Xing, Changhong
   Ji, Xunming
   Lo, Eng H.
TI Transfer of mitochondria from astrocytes to neurons after stroke
SO NATURE
LA English
DT Article
ID stromal cells; cd38; vulnerability; inhibition; vesicles; protects; recovery
AB Neurons can release damaged mitochondria and transfer them to astrocytes for disposal and recycling(1). This ability to exchange mitochondria may represent a potential mode of cell-to-cell signalling in the central nervous system. Here we show that astrocytes in mice can also release functional mitochondria that enter neurons. Astrocytic release of extracellular mitochondrial particles was mediated by a calcium-dependent mechanism involving CD38 and cyclic ADP ribose signalling. Transient focal cerebral ischaemia in mice induced entry of astrocytic mitochondria into adjacent neurons, and this entry amplified cell survival signals. Suppression of CD38 signalling by short interfering RNA reduced extracellular mitochondria transfer and worsened neurological outcomes. These findings suggest a new mitochondrial mechanism of neuroglial crosstalk that may contribute to endogenous neuroprotective and neurorecovery mechanisms after stroke.
C1 [Hayakawa, Kazuhide; Esposito, Elga; Wang, Xiaohua; Terasaki, Yasukazu; Liu, Yi; Xing, Changhong; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
   [Hayakawa, Kazuhide; Esposito, Elga; Wang, Xiaohua; Terasaki, Yasukazu; Liu, Yi; Xing, Changhong; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
   [Hayakawa, Kazuhide; Esposito, Elga; Wang, Xiaohua; Terasaki, Yasukazu; Liu, Yi; Xing, Changhong; Lo, Eng H.] Harvard Med Sch, Charlestown, MA 02129 USA.
   [Wang, Xiaohua; Liu, Yi; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Res Ctr, Beijing 100053, Peoples R China.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Capital Medical University
RP Hayakawa, K; Lo, EH (corresponding author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.; Hayakawa, K; Lo, EH (corresponding author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.; Hayakawa, K; Lo, EH (corresponding author), Harvard Med Sch, Charlestown, MA 02129 USA.; Ji, XM (corresponding author), Capital Med Univ, Xuanwu Hosp, Cerebrovasc Res Ctr, Beijing 100053, Peoples R China.
EM khayakawa1@mgh.harvard.edu; jixunming@vip.163.com; Lo@helix.mgh.harvard.edu
FU National Institutes of Health (NIH); Rappaport Foundation; China National Natural Science Foundation Award For Distinguished Young Scholars
NR 37
TC 1117
Z9 1273
U1 27
U2 367
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2016
VL 535
IS 7613
BP 551
EP +
DI 10.1038/nature18928
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5XP
UT WOS:000380856600029
PM 27466127
DA 2026-03-09
ER

PT J
AU Koh, MJ
   Nguyen, TT
   Zhang, HM
   Schrock, RR
   Hoveyda, AH
AF Koh, Ming Joo
   Nguyen, Thach T.
   Zhang, Hanmo
   Schrock, Richard R.
   Hoveyda, Amir H.
TI Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis
SO NATURE
LA English
DT Article
ID (e)-beta-aryl vinyl halides; natural-product synthesis; one-pot synthesis; stereoselective-synthesis; olefin metathesis; boronic acids; enantioselective synthesis; terminal alkynes; conversion; oxidation
AB Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site-and stereoselective fluorination of complex organic molecules.
C1 [Koh, Ming Joo; Nguyen, Thach T.; Zhang, Hanmo; Hoveyda, Amir H.] Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA.
   [Schrock, Richard R.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Boston College; Massachusetts Institute of Technology (MIT)
RP Hoveyda, AH (corresponding author), Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU United States National Institutes of Health, Institute of General Medical Sciences [GM-59426, GM-57212]
NR 50
TC 163
Z9 176
U1 2
U2 164
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 459
EP 465
DI 10.1038/nature17396
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300031
PM 27008965
DA 2026-03-09
ER

PT J
AU Cieza, LA
   Casassus, S
   Tobin, J
   Bos, SP
   Williams, JP
   Perez, S
   Zhu, ZH
   Caceres, C
   Canovas, H
   Dunham, MM
   Hales, A
   Prieto, JL
   Principe, DA
   Schreiber, MR
   Ruiz-Rodriguez, D
   Zurlo, A
AF Cieza, Lucas A.
   Casassus, Simon
   Tobin, John
   Bos, Steven P.
   Williams, Jonathan P.
   Perez, Sebastian
   Zhu, Zhaohuan
   Caceres, Claudio
   Canovas, Hector
   Dunham, Michael M.
   Hales, Antonio
   Prieto, Jose L.
   Principe, David A.
   Schreiber, Matthias R.
   Ruiz-Rodriguez, Dary
   Zurlo, Alice
TI Imaging the water snow-line during a protostellar outburst
SO NATURE
LA English
DT Article
ID protoplanetary disks; planet formation; thermal-desorption; alma observations; star-formation; mass stars; tw hya; evolution; co; condensation
AB A snow-line is the region of a protoplanetary disk at which a major volatile, such as water or carbon monoxide, reaches its condensation temperature. Snow-lines play a crucial role in disk evolution by promoting the rapid growth of ice-covered grains(1-6). Signatures of the carbon monoxide snow-line (at temperatures of around 20 kelvin) have recently been imaged in the disks surrounding the pre-main-sequence stars TW Hydra(7-9) and HD163296 (refs 3, 10), at distances of about 30 astronomical units (AU) from the star. But the water snow-line of a protoplanetary disk (at temperatures of more than 100 kelvin) has not hitherto been seen, as it generally lies very close to the star (less than 5 au away for solar-type stars(11)). Water-ice is important because it regulates the efficiency of dust and planetesimal coagulation(5), and the formation of comets, ice giants and the cores of gas giants(12). Here we report images at 0.03-arcsec resolution (12 au) of the protoplanetary disk around V883 Ori, a protostar of 1.3 solar masses that is undergoing an outburst in luminosity arising from a temporary increase in the accretion rate(13). We find an intensity break corresponding to an abrupt change in the optical depth at about 42 au, where the elevated disk temperature approaches the condensation point of water, from which we conclude that the outburst has moved the water snow-line. The spectral behaviour across the snow-line confirms recent model predictions(14): dust fragmentation and the inhibition of grain growth at higher temperatures results in soaring grain number densities and optical depths. As most planetary systems are expected to experience outbursts caused by accretion during their formation(15,16), our results imply that highly dynamical water snow-lines must be considered when developing models of disk evolution and planet formation.
C1 [Cieza, Lucas A.; Principe, David A.; Zurlo, Alice] Univ Diego Portales, Fac Ingn, Nucleo Astron, Av Ejercito 441, Santiago 8370191, Chile.
   [Cieza, Lucas A.; Casassus, Simon; Perez, Sebastian; Caceres, Claudio; Canovas, Hector; Principe, David A.; Schreiber, Matthias R.; Zurlo, Alice] Millenium Nucleus Protoplanetary Disks ALMA Early, Av Ejercito 441, Santiago 8370191, Chile.
   [Casassus, Simon; Perez, Sebastian; Zurlo, Alice] Univ Chile, Dept Astron, Casilla 36-D, Santiago 8330015, Chile.
   [Tobin, John; Bos, Steven P.] Leiden Univ, Leiden Observ, POB 9513, NL-2300 RA Leiden, Netherlands.
   [Williams, Jonathan P.] Univ Hawaii Manoa, Inst Astron, Woodlawn Dr, Honolulu, HI 96822 USA.
   [Zhu, Zhaohuan] Princeton Univ, Dept Astrophys Sci, 4 Ivy Lane,Peyton Hall, Princeton, NJ 08544 USA.
   [Caceres, Claudio; Canovas, Hector; Schreiber, Matthias R.] Univ Valparaiso, Dept Fis & Astron, Av Gran Bretana 111, Valparaiso 2373195, Chile.
   [Dunham, Michael M.] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
   [Hales, Antonio] Joint ALMA Observ, Alonso Cordova 3107, Santiago 7630355, Chile.
   [Prieto, Jose L.] Millennium Inst Astrophys, Av Vicuna Mackenna 4860, Santiago 7820436, Chile.
   [Ruiz-Rodriguez, Dary] Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2611, Australia.
C3 University Diego Portales; Universidad de Chile; Leiden University; Leiden University - Excl LUMC; University of Hawaii System; University of Hawaii Manoa; Princeton University; Universidad de Valparaiso; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Australian National University
RP Cieza, LA (corresponding author), Univ Diego Portales, Fac Ingn, Nucleo Astron, Av Ejercito 441, Santiago 8370191, Chile.; Cieza, LA (corresponding author), Millenium Nucleus Protoplanetary Disks ALMA Early, Av Ejercito 441, Santiago 8370191, Chile.
EM lucas.cieza@mail.udp.cl
FU Millennium Science Initiative (Chilean Ministry of Economy) [RC130007, IC120009]; CONICYT FONDECYT grants [1140109, 3150550, 1151445, 3140592]; Spanish Ministerio de Economia y Competitividad [AYA2014-55840P]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1208911] Funding Source: National Science Foundation
NR 34
TC 179
Z9 199
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 258
EP +
DI 10.1038/nature18612
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600051
PM 27411631
DA 2026-03-09
ER

PT J
AU Breitschwerdt, D
   Feige, J
   Schulreich, MM
   de Avillez, MA
   Dettbarn, C
   Fuchs, B
AF Breitschwerdt, D.
   Feige, J.
   Schulreich, M. M.
   de Avillez, M. A.
   Dettbarn, C.
   Fuchs, B.
TI The locations of recent supernovae near the Sun from modelling 60Fe transport
SO NATURE
LA English
DT Article
ID initial mass function; m-circle-dot; galactic disk; stars; nucleosynthesis; earth; hydrodynamics; associations; explosion; evolution
AB The signature of Fe-60 in deep-sea crusts indicates that one or more supernovae exploded in the solar neighbourhood about 2.2 million years ago(1-4). Recent isotopic analysis is consistent with a core-collapse or electron-capture supernova that occurred 60 to 130 parsecs from the Sun(5). Moreover, peculiarities in the cosmic ray spectrum point to a nearby supernova about two million years ago(6). The Local Bubble of hot, diffuse plasma, in which the Solar System is embedded, originated from 14 to 20 supernovae within a moving group, whose surviving members are now in the Scorpius-Centaurus stellar association(7,8). Here we report calculations of the most probable trajectories and masses of the supernova progenitors, and hence their explosion times and sites. The Fe-60 signal arises from two supernovae at distances between 90 and 100 parsecs. The closest occurred 2.3 million years ago at present-day galactic coordinates l = 327 degrees, b = 11 degrees, and the second-closest exploded about 1.5 million years ago at l = 343 degrees, b = 25 degrees, with masses of 9.2 and 8.8 times the solar mass, respectively. The remaining supernovae, which formed the Local Bubble, contribute to a smaller extent because they happened at larger distances and longer ago (Fe-60 has a half-life of 2.6 million years(9,10)). There are uncertainties relating to the nucleosynthesis yields and the loss of Fe-60 during transport, but they do not influence the relative distribution of Fe-60 in the crust layers, and therefore our model reproduces the measured relative abundances very well.
C1 [Breitschwerdt, D.; Feige, J.; Schulreich, M. M.; de Avillez, M. A.] Berlin Inst Technol, Dept Astron & Astrophys, Hardenbergstr 36, D-10623 Berlin, Germany.
   [de Avillez, M. A.] Univ Evora, Dept Math, Rua Romao Ramalho 59, P-7000 Evora, Portugal.
   [Dettbarn, C.; Fuchs, B.] Heidelberg Univ, Zentrum Astron, Astron Rech Inst, Monchhofstr 12-14, D-69120 Heidelberg, Germany.
C3 Technical University of Berlin; University of Evora; Ruprecht Karls University Heidelberg
RP Breitschwerdt, D (corresponding author), Berlin Inst Technol, Dept Astron & Astrophys, Hardenbergstr 36, D-10623 Berlin, Germany.
EM breitschwerdt@astro.physik.tu-berlin.de
FU DFG [1573]
NR 58
TC 117
Z9 123
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 73
EP +
DI 10.1038/nature17424
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500035
PM 27078566
DA 2026-03-09
ER

PT J
AU De Sanctis, MC
   Raponi, A
   Ammannito, E
   Ciarniello, M
   Toplis, MJ
   McSween, HY
   Castillo-Rogez, JC
   Ehlmann, BL
   Carrozzo, FG
   Marchi, S
   Tosi, F
   Zambon, F
   Capaccioni, F
   Capria, MT
   Fonte, S
   Formisano, M
   Frigeri, A
   Giardino, M
   Longobardo, A
   Magni, G
   Palomba, E
   McFadden, LA
   Pieters, CM
   Jaumann, R
   Schenk, P
   Mugnuolo, R
   Raymond, CA
   Russell, CT
AF De Sanctis, M. C.
   Raponi, A.
   Ammannito, E.
   Ciarniello, M.
   Toplis, M. J.
   McSween, H. Y.
   Castillo-Rogez, J. C.
   Ehlmann, B. L.
   Carrozzo, F. G.
   Marchi, S.
   Tosi, F.
   Zambon, F.
   Capaccioni, F.
   Capria, M. T.
   Fonte, S.
   Formisano, M.
   Frigeri, A.
   Giardino, M.
   Longobardo, A.
   Magni, G.
   Palomba, E.
   McFadden, L. A.
   Pieters, C. M.
   Jaumann, R.
   Schenk, P.
   Mugnuolo, R.
   Raymond, C. A.
   Russell, C. T.
TI Bright carbonate deposits as evidence of aqueous alteration on (1) Ceres
SO NATURE
LA English
DT Article
ID ammonium-bearing minerals; optical-constants; water ice; reflectance spectroscopy; crystalline h2o-ice; surface-composition; mu-m; phyllosilicates; chondrites; relevant
AB The typically dark surface of the dwarf planet Ceres is punctuated by areas of much higher albedo, most prominently in the Occator crater(1). These small bright areas have been tentatively interpreted as containing a large amount of hydrated magnesium sulfate(1), in contrast to the average surface, which is a mixture of lowalbedo materials and magnesium phyllosilicates, ammoniated phyllosilicates and carbonates(2-4). Here we report high spatial and spectral resolution near-infrared observations of the bright areas in the Occator crater on Ceres. Spectra of these bright areas are consistent with a large amount of sodium carbonate, constituting the most concentrated known extraterrestrial occurrence of carbonate on kilometre-wide scales in the Solar System. The carbonates are mixed with a dark component and small amounts of phyllosilicates, as well as ammonium carbonate or ammonium chloride. Some of these compounds have also been detected in the plume of Saturn's sixth-largest moon Enceladus(5). The compounds are endogenous and we propose that they are the solid residue of crystallization of brines and entrained altered solids that reached the surface from below. The heat source may have been transient (triggered by impact heating). Alternatively, internal temperatures may be above the eutectic temperature of subsurface brines, in which case fluids may exist at depth on Ceres today.
C1 [De Sanctis, M. C.; Raponi, A.; Ammannito, E.; Ciarniello, M.; Carrozzo, F. G.; Marchi, S.; Tosi, F.; Zambon, F.; Capaccioni, F.; Capria, M. T.; Fonte, S.; Formisano, M.; Frigeri, A.; Giardino, M.; Longobardo, A.; Magni, G.; Palomba, E.] Ist Nazl Astrofis INAF, Ist Astrofis & Planetol Spaziali, Via Fosso del Cavaliere 100, I-00133 Rome, Italy.
   [Ammannito, E.; Russell, C. T.] Univ Calif Los Angeles, Earth Planetary & Space Sci, Los Angeles, CA USA.
   [Toplis, M. J.] Univ Toulouse 3, Univ Toulouse, CNRS, Inst Rech Astrophys & Planetol, Toulouse, France.
   [McSween, H. Y.] Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA.
   [Castillo-Rogez, J. C.; Ehlmann, B. L.; Raymond, C. A.] CALTECH, Jet Prop Lab, Pasadena, CA USA.
   [Ehlmann, B. L.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Marchi, S.] SRI, Solar Syst Explorat Res Virtual Inst, 1050 Walnut St, Boulder, CO 80302 USA.
   [McFadden, L. A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Pieters, C. M.] Brown Univ, Dept Earth Environm & Planetary Sci, Providence, RI 02912 USA.
   [Jaumann, R.] German Aerosp Ctr DLR, Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany.
   [Schenk, P.] Lunar & Planetary Inst, 3600 Bay Area Blvd, Houston, TX 77058 USA.
   [Mugnuolo, R.] Agenzia Spaziale Italiana, Via Politecn, I-00133 Rome, Italy.
C3 Istituto Nazionale Astrofisica (INAF); University of California System; University of California Los Angeles; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of Tennessee System; University of Tennessee Knoxville; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Brown University; Helmholtz Association; German Aerospace Centre (DLR); Agenzia Spaziale Italiana (ASI)
RP De Sanctis, MC (corresponding author), Ist Nazl Astrofis INAF, Ist Astrofis & Planetol Spaziali, Via Fosso del Cavaliere 100, I-00133 Rome, Italy.
EM mariacristina.desanctis@iaps.inaf.it
FU Italian Space Agency; National Aeronautics and Space Administration (NASA, USA); Deutsches Zentrum fur Luft- und Raumfahrt (DLR, Germany)
NR 38
TC 250
Z9 267
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2016
VL 536
IS 7614
BP 54
EP +
DI 10.1038/nature18290
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200028
PM 27362221
DA 2026-03-09
ER

PT J
AU Katoh, S
   Beyene, Y
   Itaya, T
   Hyodo, H
   Hyodo, M
   Yagi, K
   Gouzu, C
   WoldeGabriel, G
   Hart, WK
   Ambrose, SH
   Nakaya, H
   Bernor, RL
   Boisserie, JR
   Bibi, F
   Saegusa, H
   Sasaki, T
   Sano, K
   Asfaw, B
   Suwa, G
AF Katoh, Shigehiro
   Beyene, Yonas
   Itaya, Tetsumaru
   Hyodo, Hironobu
   Hyodo, Masayuki
   Yagi, Koshi
   Gouzu, Chitaro
   WoldeGabriel, Giday
   Hart, William K.
   Ambrose, Stanley H.
   Nakaya, Hideo
   Bernor, Raymond L.
   Boisserie, Jean-Renaud
   Bibi, Faysal
   Saegusa, Haruo
   Sasaki, Tomohiko
   Sano, Katsuhiro
   Asfaw, Berhane
   Suwa, Gen
TI New geological and palaeontological age constraint for the gorilla-human lineage split
SO NATURE
LA English
DT Article
ID main ethiopian rift; late miocene; great ape; pliopleistocene tephra; history; calibration; evolution; origins; sahara; record
AB The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain similar to 10.5 million year (Myr) old mammalian fossils(1-7). More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade(6), was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between similar to 9 and similar to 7 Ma. The C. abyssinicus fossils are similar to 8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from similar to 8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the similar to 9.8 Myr old Nakalipithecus nakayamai(8) and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by similar to 9 Ma, with decreased faunal interchange thereafter(9-12). The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan-human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of similar to 0.5 x 10(-9) per site per year (refs 13-15).
C1 [Katoh, Shigehiro] Hyogo Museum Nat & Human Act, Div Nat Hist, Sanda 6691546, Japan.
   [Beyene, Yonas] Assoc Conservat Culture Awassa, Addis Ababa, Ethiopia.
   [Beyene, Yonas; Boisserie, Jean-Renaud] French Minist Foreign Affairs, USR CNRS 3137, CFEE, Addis Ababa, Ethiopia.
   [Itaya, Tetsumaru; Hyodo, Hironobu] Okayama Univ Sci, Res Inst Nat Sci, Okayama 7000005, Japan.
   [Hyodo, Masayuki] Kobe Univ, Res Ctr Inland Seas, Kobe, Hyogo 6578501, Japan.
   [Yagi, Koshi; Gouzu, Chitaro] Hiruzen Inst Geol & Chronol, Okayama 7038252, Japan.
   [WoldeGabriel, Giday] Los Alamos Natl Lab, EES 14, MS D462, Los Alamos, NM 87545 USA.
   [Hart, William K.] Miami Univ, Dept Geol & Environm Earth Sci, Oxford, OH 45056 USA.
   [Ambrose, Stanley H.] Univ Illinois, Dept Anthropol, Urbana, IL 61801 USA.
   [Nakaya, Hideo] Kagoshima Univ, Dept Earth & Environm Sci, Kagoshima 8900065, Japan.
   [Bernor, Raymond L.] Howard Univ, Dept Anat, Washington, DC 20059 USA.
   [Boisserie, Jean-Renaud] Univ Poitiers, UMR CNRS 7262, Inst Paleoprimatol Paleontol Humaine Evolut & Pa, F-86022 Poitiers, France.
   [Bibi, Faysal] Leibniz Inst Evolut & Biodivers Sci, Museum Nat Kunde, D-10115 Berlin, Germany.
   [Saegusa, Haruo] Univ Hyogo, Inst Nat & Environm Sci, Sanda 6691546, Japan.
   [Sasaki, Tomohiko; Sano, Katsuhiro; Suwa, Gen] Univ Tokyo, Univ Museum, Bunkyo Ku, Tokyo 1130033, Japan.
   [Asfaw, Berhane] Rift Valley Res Serv, Addis Ababa, Ethiopia.
C3 Okayama University of Science; Kobe University; United States Department of Energy (DOE); Los Alamos National Laboratory; University System of Ohio; Miami University; University of Illinois System; University of Illinois Urbana-Champaign; Kagoshima University; Howard University; Universite de Poitiers; Leibniz Institut fur Evolutions und Biodiversitatsforschung; University of Hyogo; University of Tokyo
RP Suwa, G (corresponding author), Univ Tokyo, Univ Museum, Bunkyo Ku, Tokyo 1130033, Japan.
EM gsuwa@um.u-tokyo.ac.jp
FU Janet and Elliott Banes Professorship; National Science Foundation [EAR-1028789]; Japan Society for the Promotion of Science [21255005, 24000015]; Grants-in-Aid for Scientific Research [24000015, 21255005] Funding Source: KAKEN
NR 49
TC 39
Z9 47
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 215
EP +
DI 10.1038/nature16510
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700038
PM 26863981
DA 2026-03-09
ER

PT J
AU Gu, YH
   Li, HY
   Dong, HH
   Zeng, Y
   Zhang, ZY
   Paterson, NG
   Stansfeld, PJ
   Wang, ZS
   Zhang, YZ
   Wang, WJ
   Dong, CJ
AF Gu, Yinghong
   Li, Huanyu
   Dong, Haohao
   Zeng, Yi
   Zhang, Zhengyu
   Paterson, Neil G.
   Stansfeld, Phillip J.
   Wang, Zhongshan
   Zhang, Yizheng
   Wang, Wenjian
   Dong, Changjiang
TI Structural basis of outer membrane protein insertion by the BAM complex
SO NATURE
LA English
DT Article
ID barrel assembly machinery; escherichia-coli bamb; crystal-structure; evolutionary conservation; essential component; in-vitro; biogenesis; sequence; domain; simulations
AB All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the beta-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB-BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane beta-barrel of BamA to induce movement of the beta-strands of the barrel and promote insertion of the nascent OMP.
C1 [Gu, Yinghong; Li, Huanyu; Dong, Haohao; Zeng, Yi; Zhang, Zhengyu; Wang, Zhongshan; Dong, Changjiang] Univ E Anglia, Norwich Med Sch, Biomed Res Ctr, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England.
   [Paterson, Neil G.] Diamond Light Source, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England.
   [Stansfeld, Phillip J.] Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England.
   [Wang, Zhongshan] Xuzhou Med Coll, Jiangsu Prov Key Lab Anesthesiol, Xuzhou 221004, Peoples R China.
   [Wang, Zhongshan; Zhang, Yizheng] Sichuan Univ, Coll Life Sci, Key Lab Bioresources & Ecoenvironm, Minist Educ,Sichuan Key Lab Mol Biol & Biotechnol, Chengdu 610064, Peoples R China.
   [Wang, Wenjian] Sun Yat Sen Univ, Affiliated Hosp 1, Lab Dept Surg, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China.
C3 University of East Anglia; Diamond Light Source; University of Oxford; Xuzhou Medical University; Sichuan University; Sun Yat Sen University
RP Dong, CJ (corresponding author), Univ E Anglia, Norwich Med Sch, Biomed Res Ctr, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England.; Wang, WJ (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 1, Lab Dept Surg, 58 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China.
EM w166w2000@aliyun.com; c.dong@uea.ac.uk
FU Wellcome Trust [WT106121MA]; Medical research council [G1100110/1]; Science and Technology Program of Guangzhou, China [201510010040]; China National Natural Science Foundation of Guangdong [2015A030313152]; Medical Research Council [G1100110] Funding Source: researchfish; MRC [G1100110] Funding Source: UKRI
NR 65
TC 244
Z9 300
U1 5
U2 214
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 64
EP +
DI 10.1038/nature17199
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900040
PM 26901871
DA 2026-03-09
ER

PT J
AU Beura, LK
   Hamilton, SE
   Bi, K
   Schenkel, JM
   Odumade, OA
   Casey, KA
   Thompson, EA
   Fraser, KA
   Rosato, PC
   Filali-Mouhim, A
   Sekaly, RP
   Jenkins, MK
   Vezys, V
   Haining, WN
   Jameson, SC
   Masopust, D
AF Beura, Lalit K.
   Hamilton, Sara E.
   Bi, Kevin
   Schenkel, Jason M.
   Odumade, Oludare A.
   Casey, Kerry A.
   Thompson, Emily A.
   Fraser, Kathryn A.
   Rosato, Pamela C.
   Filali-Mouhim, Ali
   Sekaly, Rafick P.
   Jenkins, Marc K.
   Vezys, Vaiva
   Haining, W. Nicholas
   Jameson, Stephen C.
   Masopust, David
TI Normalizing the environment recapitulates adult human immune traits in laboratory mice
SO NATURE
LA English
DT Article
ID cd8(+) t-cells; barr-virus infection; memory; mouse; translation; expression; generation; models; lost; gut
AB Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside(1-8). Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice-like newborn, but not adult, humans-lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free- living organisms, including humans.
C1 [Beura, Lalit K.; Schenkel, Jason M.; Casey, Kerry A.; Thompson, Emily A.; Fraser, Kathryn A.; Rosato, Pamela C.; Jenkins, Marc K.; Vezys, Vaiva; Masopust, David] Univ Minnesota, Dept Microbiol & Immunol, Ctr Immunol, Minneapolis, MN 55414 USA.
   [Hamilton, Sara E.; Odumade, Oludare A.; Jameson, Stephen C.] Univ Minnesota, Dept Lab Med & Pathol, Ctr Immunol, Minneapolis, MN 55414 USA.
   [Bi, Kevin; Haining, W. Nicholas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Bi, Kevin; Haining, W. Nicholas] Childrens Hosp, Pediat Hematol & Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
   [Filali-Mouhim, Ali; Sekaly, Rafick P.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
   [Odumade, Oludare A.] Univ Calif San Diego, Rady Childrens Hosp, Dept Pediat, San Diego, CA 92123 USA.
   [Casey, Kerry A.] MedImmune LLC, Dept Resp Inflammat & Autoimmun, Gaithersburg, MD 20878 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University System of Ohio; Case Western Reserve University; University of California System; University of California San Diego; Rady Childrens Hospital San Diego; AstraZeneca; Medimmune
RP Masopust, D (corresponding author), Univ Minnesota, Dept Microbiol & Immunol, Ctr Immunol, Minneapolis, MN 55414 USA.; Jameson, SC (corresponding author), Univ Minnesota, Dept Lab Med & Pathol, Ctr Immunol, Minneapolis, MN 55414 USA.
EM james024@umn.edu; masopust@umn.edu
FU National Institutes of Health [1R01AI111671, R01AI084913, R01AI116678, R01AI075168]; University of Minnesota; National Cancer Institute [P30CA077598] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007313, R01AI084913, P01AI035296] Funding Source: NIH RePORTER
NR 42
TC 833
Z9 992
U1 0
U2 116
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 512
EP +
DI 10.1038/nature17655
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900050
PM 27096360
DA 2026-03-09
ER

PT J
AU Worobey, M
   Watts, TD
   McKay, RA
   Suchard, MA
   Granade, T
   Teuwen, DE
   Koblin, BA
   Heneine, W
   Lemey, P
   Jaffe, HW
AF Worobey, Michael
   Watts, Thomas D.
   McKay, Richard A.
   Suchard, Marc A.
   Granade, Timothy
   Teuwen, Dirk E.
   Koblin, Beryl A.
   Heneine, Walid
   Lemey, Philippe
   Jaffe, Harold W.
TI 1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in North America
SO NATURE
LA English
DT Article
ID new-york-city; homosexual-men; epidemic; cohort; phylogenetics; evolution; spread; aids
AB The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s(1,2) and an even older presence in the Caribbean(2). However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious(3,4) and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome 'snapshot' reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location(3). Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as 'Patient 0' (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.
C1 [Worobey, Michael; Watts, Thomas D.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [McKay, Richard A.] Univ Cambridge, Dept Hist & Philosophy Sci, Cambridge CB2 3RH, England.
   [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Dept Biostat, Los Angeles, CA 90095 USA.
   [Granade, Timothy; Heneine, Walid; Jaffe, Harold W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Teuwen, Dirk E.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
   [Koblin, Beryl A.] UCB, BE-1070 Brussels, Belgium.
   [Lemey, Philippe] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10065 USA.
   KU Leuven Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Minderbroedersstaat 10, B-3000 Leuven, Belgium.
C3 University of Arizona; University of Cambridge; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Centers for Disease Control & Prevention - USA; UCB Pharma SA; New York Blood Center; KU Leuven
RP Worobey, M (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.; McKay, RA (corresponding author), Univ Cambridge, Dept Hist & Philosophy Sci, Cambridge CB2 3RH, England.
EM worobey@email.arizona.edu; ram78@cam.ac.uk
FU NIH/NIAID [R01AI084691]; David and Lucile Packard Foundation (MW); Wellcome Trust [080651]; University of Oxford's Clarendon Fund; Economic and Social Research Council [PTA-026-27-2838]; J. Armand Bombardier Internationalist Fellowship (RAW; the Research Fund KU Leuven (Onderzoeksfonds KU Leuven) [PF/10/018]; 'Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) [G066215N]; NSF DMS [1264153]; NIH [R01 HG006139, R01 A1107034]; Direct For Mathematical & Physical Scien [1264153] Funding Source: National Science Foundation; Division Of Mathematical Sciences [1264153] Funding Source: National Science Foundation; Economic and Social Research Council [ES/I020845/1] Funding Source: researchfish; Wellcome Trust [098705/Z/12/Z] Funding Source: researchfish; ESRC [ES/I020845/1] Funding Source: UKRI; Wellcome Trust [098705/Z/12/Z] Funding Source: Wellcome Trust
NR 34
TC 142
Z9 194
U1 1
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 98
EP +
DI 10.1038/nature19827
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100037
PM 27783600
DA 2026-03-09
ER

PT J
AU Bouton, CE
   Shaikhouni, A
   Annetta, NV
   Bockbrader, MA
   Friedenberg, DA
   Nielson, DM
   Sharma, G
   Sederberg, PB
   Glenn, BC
   Mysiw, WJ
   Morgan, AG
   Deogaonkar, M
   Rezai, AR
AF Bouton, Chad E.
   Shaikhouni, Ammar
   Annetta, Nicholas V.
   Bockbrader, Marcia A.
   Friedenberg, David A.
   Nielson, Dylan M.
   Sharma, Gaurav
   Sederberg, Per B.
   Glenn, Bradley C.
   Mysiw, W. Jerry
   Morgan, Austin G.
   Deogaonkar, Milind
   Rezai, Ali R.
TI Restoring cortical control of functional movement in a human with quadriplegia
SO NATURE
LA English
DT Article
ID motor cortex; tetraplegia; grasp; hand; arm; restoration; neurons; neuroprosthesis; stimulation; performance
AB Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements(1-11). In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles(12,13). Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.
C1 [Bouton, Chad E.; Annetta, Nicholas V.; Sharma, Gaurav; Morgan, Austin G.] Battelle Mem Inst, Med Devices & Neuromodulat, 505 King Ave, Columbus, OH 43201 USA.
   [Shaikhouni, Ammar; Bockbrader, Marcia A.; Nielson, Dylan M.; Sederberg, Per B.; Mysiw, W. Jerry; Deogaonkar, Milind; Rezai, Ali R.] Ohio State Univ, Ctr Neuromodulat, Columbus, OH 43210 USA.
   [Shaikhouni, Ammar; Nielson, Dylan M.; Deogaonkar, Milind; Rezai, Ali R.] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA.
   [Bockbrader, Marcia A.; Mysiw, W. Jerry] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA.
   [Friedenberg, David A.] Battelle Mem Inst, Adv Analyt & Hlth Res, 505 King Ave, Columbus, OH 43201 USA.
   [Sederberg, Per B.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
   [Glenn, Bradley C.] Battelle Mem Inst, Energy Syst, 505 King Ave, Columbus, OH 43201 USA.
   [Bouton, Chad E.] Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA.
C3 Battelle Memorial Institute; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Battelle Memorial Institute; University System of Ohio; Ohio State University; Battelle Memorial Institute; Northwell Health
RP Bouton, CE; Sharma, G (corresponding author), Battelle Mem Inst, Med Devices & Neuromodulat, 505 King Ave, Columbus, OH 43201 USA.; Bouton, CE (corresponding author), Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA.
EM boutonce@gmail.com; sharmag@battelle.org
FU Battelle Memorial Institute; Ohio State University Center for Neuromodulation
NR 30
TC 641
Z9 808
U1 7
U2 381
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 247
EP +
DI 10.1038/nature17435
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200050
PM 27074513
DA 2026-03-09
ER

PT J
AU Iaccarino, HF
   Singer, AC
   Martorell, AJ
   Rudenko, A
   Gao, F
   Gillingham, TZ
   Mathys, H
   Seo, J
   Kritskiy, O
   Abdurrob, F
   Adaikkan, C
   Canter, RG
   Rueda, R
   Brown, EN
   Boyden, ES
   Tsai, LH
AF Iaccarino, Hannah F.
   Singer, Annabelle C.
   Martorell, Anthony J.
   Rudenko, Andrii
   Gao, Fan
   Gillingham, Tyler Z.
   Mathys, Hansruedi
   Seo, Jinsoo
   Kritskiy, Oleg
   Abdurrob, Fatema
   Adaikkan, Chinnakkaruppan
   Canter, Rebecca G.
   Rueda, Richard
   Brown, Emery N.
   Boyden, Edward S.
   Tsai, Li-Huei
TI Gamma frequency entrainment attenuates amyloid load and modifies microglia
SO NATURE
LA English
DT Article
ID hippocampal place cells; alzheimers-disease; neuronal-activity; beta deposition; neural circuits; visual-cortex; awake state; mouse model; oscillations; activation
AB Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-beta (A beta)(1-40) and A beta(1-42) isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with A beta. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced A beta(1-40) and A beta(1-42) levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
C1 [Iaccarino, Hannah F.; Martorell, Anthony J.; Rudenko, Andrii; Gao, Fan; Gillingham, Tyler Z.; Mathys, Hansruedi; Seo, Jinsoo; Kritskiy, Oleg; Abdurrob, Fatema; Adaikkan, Chinnakkaruppan; Canter, Rebecca G.; Rueda, Richard; Brown, Emery N.; Tsai, Li-Huei] MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Singer, Annabelle C.; Boyden, Edward S.] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Iaccarino, Hannah F.; Singer, Annabelle C.; Martorell, Anthony J.; Rudenko, Andrii; Gao, Fan; Gillingham, Tyler Z.; Mathys, Hansruedi; Seo, Jinsoo; Kritskiy, Oleg; Abdurrob, Fatema; Adaikkan, Chinnakkaruppan; Canter, Rebecca G.; Rueda, Richard; Brown, Emery N.; Boyden, Edward S.; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
   [Singer, Annabelle C.; Boyden, Edward S.] MIT, Dept Biol Engn, MIT Media Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Singer, Annabelle C.; Boyden, Edward S.] MIT, Dept Brain & Cognit Sci, MIT Media Lab, E25-618, Cambridge, MA 02139 USA.
   [Brown, Emery N.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Brown, Emery N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Tsai, Li-Huei] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
   [Singer, Annabelle C.] Emory Univ, Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Rudenko, Andrii] CUNY, Dept Biol, New York, NY 10031 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University System of Georgia; Georgia Institute of Technology; Emory University; City University of New York (CUNY) System
RP Tsai, LH (corresponding author), MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Tsai, LH (corresponding author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.; Tsai, LH (corresponding author), Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
EM lhtsai@mit.edu
FU Barbara J. Weedon Fellowship; National Institutes of Health (NIH) [1R01EY023173, 1DP1NS087724]
NR 41
TC 965
Z9 1163
U1 18
U2 335
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 230
EP +
DI 10.1038/nature20587
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700049
PM 27929004
DA 2026-03-09
ER

PT J
AU Anderson, MA
   Burda, JE
   Ren, YL
   Ao, Y
   O'Shea, TM
   Kawaguchi, R
   Coppola, G
   Khakh, BS
   Deming, TJ
   Sofroniew, MV
AF Anderson, Mark A.
   Burda, Joshua E.
   Ren, Yilong
   Ao, Yan
   O'Shea, Timothy M.
   Kawaguchi, Riki
   Coppola, Giovanni
   Khakh, Baljit S.
   Deming, Timothy J.
   Sofroniew, Michael V.
TI Astrocyte scar formation aids central nervous system axon regeneration
SO NATURE
LA English
DT Article
ID chondroitin sulfate proteoglycan; cell-adhesion molecules; spinal-cord; neurite outgrowth; reactive astrocytes; guidance molecule; local-delivery; messenger-rna; sensory axons; tenascin-c
AB Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.
C1 [Anderson, Mark A.; Burda, Joshua E.; Ren, Yilong; Ao, Yan; O'Shea, Timothy M.; Sofroniew, Michael V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
   [Kawaguchi, Riki; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA.
   [Kawaguchi, Riki; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [Khakh, Baljit S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
   [Deming, Timothy J.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
   [Deming, Timothy J.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Anderson, Mark A.] Swiss Fed Inst Technol EPFL, Sch Life Sci, SV BMI UPCourtine, Stn 19, CH-1015 Lausanne, Switzerland.
   [Ren, Yilong] Tongji Univ, Sch Med, Tongji Hosp, Dept Spine Surg, Shanghai 200065, Peoples R China.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Tongji University
RP Sofroniew, MV (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
EM sofroniew@mednet.ucla.edu
FU US National Institutes of Health [NS057624, NS084030, P30 NS062691, NS060677, MH099559A, MH104069]; Dr. Miriam and Sheldon G. Adelson Medical Foundation; Wings for Life; National Institute of Neurological Disorders and Stroke [R01NS084030] Funding Source: NIH RePORTER
NR 103
TC 1445
Z9 1719
U1 11
U2 662
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 195
EP +
DI 10.1038/nature17623
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100031
PM 27027288
DA 2026-03-09
ER

PT J
AU Martinez, EA
   Muschik, CA
   Schindler, P
   Nigg, D
   Erhard, A
   Heyl, M
   Hauke, P
   Dalmonte, M
   Monz, T
   Zoller, P
   Blatt, R
AF Martinez, Esteban A.
   Muschik, Christine A.
   Schindler, Philipp
   Nigg, Daniel
   Erhard, Alexander
   Heyl, Markus
   Hauke, Philipp
   Dalmonte, Marcello
   Monz, Thomas
   Zoller, Peter
   Blatt, Rainer
TI Real-time dynamics of lattice gauge theories with a few-qubit quantum computer
SO NATURE
LA English
DT Article
ID simulation; invariance
AB Gauge theories are fundamental to our understanding of interactions between the elementary constituents of matter as mediated by gauge bosons(1,2). However, computing the real-time dynamics in gauge theories is a notorious challenge for classical computational methods. This has recently stimulated theoretical effort, using Feynman's idea of a quantum simulator(3,4), to devise schemes for simulating such theories on engineered quantum-mechanical devices, with the difficulty that gauge invariance and the associated local conservation laws (Gauss laws) need to be implemented(5-7). Here we report the experimental demonstration of a digital quantum simulation of a lattice gauge theory, by realizing (1 + 1)-dimensional quantum electrodynamics (the Schwinger model(8,9)) on a few-qubit trapped-ion quantum computer. We are interested in the real-time evolution of the Schwinger mechanism(10,11), describing the instability of the bare vacuum due to quantum fluctuations, which manifests itself in the spontaneous creation of electron-positron pairs. To make efficient use of our quantum resources, we map the original problem to a spin model by eliminating the gauge fields(12) in favour of exotic long-range interactions, which can be directly and efficiently implemented on an ion trap architecture(13). We explore the Schwinger mechanism of particle-antiparticle generation by monitoring the mass production and the vacuum persistence amplitude. Moreover, we track the real-time evolution of entanglement in the system, which illustrates how particle creation and entanglement generation are directly related. Our work represents a first step towards quantum simulation of high-energy theories using atomic physics experiments-the long-term intention is to extend this approach to real-time quantum simulations of non-Abelian lattice gauge theories.
C1 [Martinez, Esteban A.; Schindler, Philipp; Nigg, Daniel; Erhard, Alexander; Monz, Thomas; Blatt, Rainer] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Muschik, Christine A.; Heyl, Markus; Hauke, Philipp; Dalmonte, Marcello; Zoller, Peter; Blatt, Rainer] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-6020 Innsbruck, Austria.
   [Muschik, Christine A.; Hauke, Philipp; Dalmonte, Marcello; Zoller, Peter] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
   [Heyl, Markus] Tech Univ Munich, Dept Phys, D-85747 Garching, Germany.
C3 University of Innsbruck; Austrian Academy of Sciences; University of Innsbruck; Technical University of Munich
RP Martinez, EA (corresponding author), Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.; Muschik, CA (corresponding author), Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-6020 Innsbruck, Austria.; Muschik, CA (corresponding author), Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
EM esteban.martinez@uibk.ac.at; christine.muschik@oeaw.ac.at
FU Austrian Science Fund (FWF) through the SFB FoQuS (FWF) [F4002-N16, F4016-N23]; European Commission; ERC synergy grant UQUAM; Deutsche Akademie der Naturforscher Leopoldina [LPDS 2013-07, LPDR 2015-01]; Institut fur Quantenoptik und Quanteninformation GmbH; Austrian Academy of Sciences; Austrian Science Foundation (FWF) Erwin Schrodinger Stipendium [3600-N27]; Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA) through the Army Research Office [W911NF-10-1-0284]; Austrian Science Fund (FWF) [J 3600] Funding Source: researchfish
NR 36
TC 655
Z9 715
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 516
EP +
DI 10.1038/nature18318
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300046
PM 27337339
DA 2026-03-09
ER

PT J
AU Abram, NJ
   McGregor, HV
   Tierney, JE
   Evans, MN
   McKay, NP
   Kaufman, DS
   Kaustubh, T
   Martrat, B
   Goosse, H
   Phipps, SJ
   Steig, EJ
   Kilbourne, KH
   Saenger, CP
   Zinke, J
   Leduc, G
   Addison, JA
   Mortyn, PG
   Seidenkrantz, MS
   Sicre, MA
   Selvaraj, K
   Filipsson, HL
   Neukom, R
   Gergis, J
   Curran, MAJ
   von Gunten, L
AF Abram, Nerilie J.
   McGregor, Helen V.
   Tierney, Jessica E.
   Evans, Michael N.
   McKay, Nicholas P.
   Kaufman, Darrell S.
   Kaustubh, Thirumalai
   Martrat, Belen
   Goosse, Hugues
   Phipps, Steven J.
   Steig, Eric J.
   Kilbourne, K. Halimeda
   Saenger, Casey P.
   Zinke, Jens
   Leduc, Guillaume
   Addison, Jason A.
   Mortyn, P. Graham
   Seidenkrantz, Marit-Solveig
   Sicre, Marie-Alexandrine
   Selvaraj, Kandasamy
   Filipsson, Helena L.
   Neukom, Raphael
   Gergis, Joelle
   Curran, Mark A. J.
   von Gunten, Lucien
TI Early onset of industrial-era warming across the oceans and continents
SO NATURE
LA English
DT Article
ID sea-surface temperature; pacific convergence zone; climate forcing reconstructions; carbon isotopic record; western indian-ocean; tropical pacific; southern-oscillation; stable oxygen; recent intensification; pmip simulations
AB The evolution of industrial-era warming across the continents and oceans provides a context for future climate change and is important for determining climate sensitivity and the processes that control regional warming. Here we use post-AD 1500 palaeoclimate records to show that sustained industrial-era warming of the tropical oceans first developed during the mid-nineteenth century and was nearly synchronous with Northern Hemisphere continental warming. The early onset of sustained, significant warming in palaeoclimate records and model simulations suggests that greenhouse forcing of industrial-era warming commenced as early as the mid-nineteenth century and included an enhanced equatorial ocean response mechanism. The development of Southern Hemisphere warming is delayed in reconstructions, but this apparent delay is not reproduced in climate simulations. Our findings imply that instrumental records are too short to comprehensively assess anthropogenic climate change and that, in some regions, about 180 years of industrial-era warming has already caused surface temperatures to emerge above pre-industrial values, even when taking natural variability into account.
C1 [Abram, Nerilie J.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 2601, Australia.
   [Abram, Nerilie J.] Australian Natl Univ, ARC Ctr Excellence Climate Syst Sci, Canberra, ACT 2601, Australia.
   [McGregor, Helen V.] Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.
   [Tierney, Jessica E.] Univ Arizona, Dept Geosci, Tucson, AZ 85721 USA.
   [Tierney, Jessica E.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [Evans, Michael N.] Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
   [Evans, Michael N.] Univ Maryland, Earth Syst Sci Interdisciplinary Ctr, College Pk, MD 20742 USA.
   [McKay, Nicholas P.; Kaufman, Darrell S.] No Arizona Univ, Sch Earth Sci & Environm Sustainabil, Flagstaff, AZ 86011 USA.
   [Kaustubh, Thirumalai] Univ Texas Austin, Jackson Sch Geosci, Inst Geophys, Austin, TX 78758 USA.
   [Martrat, Belen] CSIC, Inst Environm Assessment & Water Res IDAEA, Dept Environm Chem, ES-08034 Barcelona, Spain.
   [Martrat, Belen] Univ Cambridge, Dept Earth Sci, Downing St, Cambridge CB2 3EQ, England.
   [Goosse, Hugues] Univ Louvain, Earth & Life Inst, Pl Pasteur 3, B-1348 Louvain, Belgium.
   [Phipps, Steven J.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Phipps, Steven J.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Phipps, Steven J.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas 7001, Australia.
   [Steig, Eric J.] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3FE, Midlothian, Scotland.
   [Steig, Eric J.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Kilbourne, K. Halimeda] Univ Maryland, Chesapeake Biol Lab, Ctr Environm Sci, Solomons, MD 20688 USA.
   [Saenger, Casey P.] Univ Washington, Joint Inst Study Atmosphere & Ocean, Seattle, WA USA.
   [Zinke, Jens] Curtin Univ Technol, Dept Environm & Agr, Bentley, WA 6845, Australia.
   [Zinke, Jens] Australian Inst Marine Sci, 39 Fairway, Nedlands, WA 6009, Australia.
   [Zinke, Jens] Free Univ Berlin, Inst Geol Sci, Sect Palaeontol, Malteserstr 74-100, D-12249 Berlin, Germany.
   [Leduc, Guillaume] Aix Marseille Univ, CNRS, IRD, Coll France,CEREGE, F-13545 Aix En Provence, France.
   [Addison, Jason A.] US Geol Survey, 345 Middlefield Rd,MS 910, Menlo Pk, CA 94025 USA.
   [Mortyn, P. Graham] Univ Autonoma Barcelona, Inst Environm Sci & Technol ICTA, Bellaterra 08193, Spain.
   [Mortyn, P. Graham] Univ Autonoma Barcelona, Dept Geog, Bellaterra 08193, Spain.
   [Seidenkrantz, Marit-Solveig] Aarhus Univ, Ctr Past Climate Studies, Hoegh-Guldbergs Gade 2, DK-8000 Aarhus C, Denmark.
   [Seidenkrantz, Marit-Solveig] Aarhus Univ, Arctic Res Ctr, Dept Geosci, Hoegh-Guldbergs Gade 2, DK-8000 Aarhus C, Denmark.
   [Sicre, Marie-Alexandrine] Sorbonne Univ, UPMC, Univ Paris 06, CNRS IRD MNHN,LOCEAN Lab, 4 Pl Jussieu, F-75005 Paris, France.
   [Selvaraj, Kandasamy] Xiamen Univ, State Key Lab Marine Environm Sci, Xiamen 361102, Peoples R China.
   [Selvaraj, Kandasamy] Xiamen Univ, Dept Geol Oceanog, Xiamen 361102, Peoples R China.
   [Filipsson, Helena L.] Lund Univ, Dept Geol, Solvegatan 12, SE-22362 Lund, Sweden.
   [Neukom, Raphael] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Neukom, Raphael] Univ Bern, Inst Geog, CH-3012 Bern, Switzerland.
   [Gergis, Joelle] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
   [Gergis, Joelle] Univ Melbourne, ARC Ctr Excellence Climate Syst Sci, Melbourne, Vic 3010, Australia.
   [Curran, Mark A. J.] Australian Antarctic Div, Hobart, Tas 7000, Australia.
   [Curran, Mark A. J.] Antarctic Climate & Ecosyst Cooperat Res Ctr, Hobart, Tas 7000, Australia.
   [von Gunten, Lucien] PAGES Int Project Off, Falkenpl 16, CH-3012 Bern, Switzerland.
C3 Australian National University; ARC Centre of Excellence for Climate System Science; Australian National University; University of Wollongong; University of Arizona; Woods Hole Oceanographic Institution; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; Northern Arizona University; University of Texas System; University of Texas Austin; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigacion y Desarrollo Pascual Vila (CID-CSIC); CSIC - Instituto de Diagnostico Ambiental y Estudios del Agua (IDAEA); University of Cambridge; ARC Centre of Excellence for Climate System Science; University of New South Wales Sydney; University of New South Wales Sydney; University of Tasmania; University of Edinburgh; University of Washington; University of Washington Seattle; University System of Maryland; University of Maryland Center for Environmental Science; University of Washington; University of Washington Seattle; Curtin University; Australian Institute of Marine Science; Free University of Berlin; Aix-Marseille Universite; Universite PSL; College de France; Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); United States Department of the Interior; United States Geological Survey; Autonomous University of Barcelona; Autonomous University of Barcelona; Aarhus University; Aarhus University; Museum National d'Histoire Naturelle (MNHN); Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; Xiamen University; Xiamen University; Lund University; University of Bern; University of Bern; University of Melbourne; ARC Centre of Excellence for Climate System Science; University of Melbourne; Australian Antarctic Division; Antarctic Climate & Ecosystems Cooperative Research Centre (ACE CRC)
RP Abram, NJ (corresponding author), Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 2601, Australia.; Abram, NJ (corresponding author), Australian Natl Univ, ARC Ctr Excellence Climate Syst Sci, Canberra, ACT 2601, Australia.
EM nerilie.abram@anu.edu.au
FU PAGES - US National Science Foundation (NSF); PAGES - Swiss National Science Foundation (NSF); NOAA; Australian Research Council (ARC) QEII [DP110101161]; ARC Centre of Excellence for Climate System Science; ARC [FT140100286, DP1092945]; CSIC-Ramon y Cajal post-doctoral programme [RYC-2013-14073]; Clare Hall College Cambridge Shackleton Fellowship; ARC DECRA fellowship [DE130100668]; US NSF [OCE1536249]; ARC Special Research Initiative for the Antarctic Gateway Partnership [SR140300001]; Red CONSOLIDER GRACCIE [CTM2014-59111-REDC]; Swiss NSF [PZ00P2_154802]; Danish Council for Independent Research; Natural Science OCEANHEAT [12-126709/FNU]; National Natural Science Foundation of China [(41273083]; Shanghai Fund [2013SH012];  [DP140102059]; Directorate For Geosciences; ICER [1450657] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1440015] Funding Source: National Science Foundation; Australian Research Council [FT140100286] Funding Source: Australian Research Council
NR 131
TC 256
Z9 302
U1 5
U2 275
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 411
EP +
DI 10.1038/nature19082
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600033
PM 27558063
DA 2026-03-09
ER

PT J
AU Nakamura, T
   Okamoto, I
   Sasaki, K
   Yabuta, Y
   Iwatani, C
   Tsuchiya, H
   Seita, Y
   Nakamura, S
   Yamamoto, T
   Saitou, M
AF Nakamura, Tomonori
   Okamoto, Ikuhiro
   Sasaki, Kotaro
   Yabuta, Yukihiro
   Iwatani, Chizuru
   Tsuchiya, Hideaki
   Seita, Yasunari
   Nakamura, Shinichiro
   Yamamoto, Takuya
   Saitou, Mitinori
TI A developmental coordinate of pluripotency among mice, monkeys and humans
SO NATURE
LA English
DT Article
ID embryonic stem-cells; rhesus-monkey; mouse embryo; naive pluripotency; self-organization; human blastocyst; gene-expression; ground-state; mass cells; yolk-sac
AB The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre and post-implantation EPI development in cynomolgus monkeys (Macacafascicularis). We show that after specification in the blastocysts, EPI from cynomolgus monkeys (cyEPI) undergoes major transcriptome changes on implantation. Thereafter, while generating gastrulating cells, cyEPI stably maintains its transcriptome over a week, retains a unique set of pluripotency genes and acquires properties for 'neuron differentiation'. Human and monkey pluripotent stem cells show the highest similarity to post-implantation late cyEPI, which, despite co-existing with gastrulating cells, bears characteristics of pre-gastrulating mouse EPI and epiblast-like cells in vitro. These findings not only reveal the divergence and coherence of EPI development, but also identify a developmental coordinate of the spectrum of pluripotency among key species, providing a basis for better regulation of human pluripotency in vitro.
C1 [Nakamura, Tomonori; Okamoto, Ikuhiro; Sasaki, Kotaro; Yabuta, Yukihiro; Saitou, Mitinori] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
   [Nakamura, Tomonori; Okamoto, Ikuhiro; Sasaki, Kotaro; Yabuta, Yukihiro; Saitou, Mitinori] JST, ERATO, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
   [Iwatani, Chizuru; Tsuchiya, Hideaki; Seita, Yasunari; Nakamura, Shinichiro] Shiga Univ Med Sci, Res Ctr Anim Life Sci, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan.
   [Yamamoto, Takuya; Saitou, Mitinori] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.
   [Yamamoto, Takuya; Saitou, Mitinori] Kyoto Univ, Inst Integrated Cell Material Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan.
   [Yamamoto, Takuya] AMED, CREST, Chiyoda Ku, 1-7-1 Otemachi, Tokyo 1000004, Japan.
C3 Kyoto University; Japan Science & Technology Agency (JST); Shiga University of Medical Science; Kyoto University; Kyoto University; Japan Science & Technology Agency (JST)
RP Saitou, M (corresponding author), Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.; Saitou, M (corresponding author), JST, ERATO, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.; Saitou, M (corresponding author), Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan.; Saitou, M (corresponding author), Kyoto Univ, Inst Integrated Cell Material Sci, Sakyo Ku, Yoshida Ushinomiya Cho, Kyoto 6068501, Japan.
EM saitou@anat2.med.kyoto-u.ac.jp
FU MEXT; JST-ERATO
NR 43
TC 431
Z9 479
U1 0
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 57
EP 62
DI 10.1038/nature19096
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900037
PM 27556940
DA 2026-03-09
ER

PT J
AU Franco, A
   Kitsis, RN
   Fleischer, JA
   Gavathiotis, E
   Kornfeld, OS
   Gong, GH
   Biris, N
   Benz, A
   Qvit, N
   Donnelly, SK
   Chen, Y
   Mennerick, S
   Hodgson, L
   Mochly-Rosen, D
   Dorn, GW
AF Franco, Antonietta
   Kitsis, Richard N.
   Fleischer, Julie A.
   Gavathiotis, Evripidis
   Kornfeld, Opher S.
   Gong, Guohua
   Biris, Nikolaos
   Benz, Ann
   Qvit, Nir
   Donnelly, Sara K.
   Chen, Yun
   Mennerick, Steven
   Hodgson, Louis
   Mochly-Rosen, Daria
   Dorn, Gerald W., II
TI Correcting mitochondrial fusion by manipulating mitofusin conformations
SO NATURE
LA English
DT Article
ID protein-kinase-c; mutations; defects; fission; mfn1; 2a
AB Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is not completely understood. Here we show that mitofusins adopt either a fusion-constrained or a fusion-permissive molecular conformation, directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated in mouse cells by targeting these conformational transitions. On the basis of this model, we engineered a cell-permeant minipeptide to destabilize the fusion-constrained conformation of mitofusin and promote the fusion-permissive conformation, reversing mitochondrial abnormalities in cultured fibroblasts and neurons that harbour CMT2A-associated genetic defects. The relationship between the conformational plasticity of mitofusin 2 and mitochondrial dynamism reveals a central mechanism that regulates mitochondrial fusion, the manipulation of which can correct mitochondrial pathology triggered by defective or imbalanced mitochondrial dynamics.
C1 [Franco, Antonietta; Fleischer, Julie A.; Gong, Guohua; Dorn, Gerald W., II] Washington Univ, Sch Med, Dept Internal Med, Ctr Pharmacogen, St Louis, MO 63110 USA.
   [Kitsis, Richard N.; Chen, Yun] Albert Einstein Coll Med, Dept Med Cardiol, Bronx, NY 10467 USA.
   [Kitsis, Richard N.; Chen, Yun] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA.
   [Kitsis, Richard N.; Chen, Yun] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10467 USA.
   [Gavathiotis, Evripidis; Biris, Nikolaos] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Wilf Family Cardiovasc Res Inst, Dept Biochem, Bronx, NY 10467 USA.
   [Gavathiotis, Evripidis; Biris, Nikolaos] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Wilf Family Cardiovasc Res Inst, Dept Med, Bronx, NY 10467 USA.
   [Kornfeld, Opher S.; Qvit, Nir; Mochly-Rosen, Daria] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Benz, Ann; Mennerick, Steven] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Benz, Ann; Mennerick, Steven] Washington Univ, Sch Med, Taylor Family Inst Innovat Psychiat Res, St Louis, MO USA.
   [Donnelly, Sara K.; Hodgson, Louis] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Dept Anat & Struct Biol, Bronx, NY 10467 USA.
C3 Washington University (WUSTL); Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Stanford University; Washington University (WUSTL); Washington University (WUSTL); Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Dorn, GW (corresponding author), Washington Univ, Sch Med, Dept Internal Med, Ctr Pharmacogen, St Louis, MO 63110 USA.
EM gdorn@wustl.edu
FU National Institutes of Health [HL59888, HL128441, HL128071, CA178394, MH078823, CA205262, HL52141]; American Cancer Society [PF-15-135-01-CSM]; Societa' Italiana Ipertensione Arteriosa (SIIA); National Cancer Institute [R01CA178394, P30CA013330] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [R01HL052141] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [K12GM102779] Funding Source: NIH RePORTER
NR 23
TC 194
Z9 229
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 74
EP +
DI 10.1038/nature20156
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600050
PM 27775718
DA 2026-03-09
ER

PT J
AU Darling, KA
   Rajagopalan, M
   Komarasamy, M
   Bhatia, MA
   Hornbuckle, BC
   Mishra, RS
   Solanki, KN
AF Darling, K. A.
   Rajagopalan, M.
   Komarasamy, M.
   Bhatia, M. A.
   Hornbuckle, B. C.
   Mishra, R. S.
   Solanki, K. N.
TI Extreme creep resistance in a microstructurally stable nanocrystalline alloy
SO NATURE
LA English
DT Article
ID cu-ta alloys; mechanical-property; molecular-dynamics; superalloys; temperature; algorithms; metals; design; system
AB Nanocrystalline metals, with a mean grain size of less than 100 nanometres, have greater room-temperature strength than their coarse-grained equivalents, in part owing to a large reduction in grain size(1). However, this high strength generally comes with substantial losses in other mechanical properties, such as creep resistance, which limits their practical utility; for example, creep rates in nanocrystalline copper are about four orders of magnitude higher than those in typical coarse-grained copper(2,3). The degradation of creep resistance in nanocrystalline materials is in part due to an increase in the volume fraction of grain boundaries, which lack long-range crystalline order and lead to processes such as diffusional creep, sliding and rotation(3). Here we show that nanocrystalline copper-tantalum alloys possess an unprecedented combination of properties: high strength combined with extremely high-temperature creep resistance, while maintaining mechanical and thermal stability. Precursory work on this family of immiscible alloys has previously highlighted their thermo-mechanical stability and strength(4,5), which has motivated their study under more extreme conditions, such as creep. We find a steady-state creep rate of less than 10(-6) per second-six to eight orders of magnitude lower than most nanocrystalline metals-at various temperatures between 0.5 and 0.64 times the melting temperature of the matrix (1,356 kelvin) under an applied stress ranging from 0.85 per cent to 1.2 per cent of the shear modulus. The unusual combination of properties in our nanocrystalline alloy is achieved via a processing route that creates distinct nanoclusters of atoms that pin grain boundaries within the alloy. This pinning improves the kinetic stability of the grains by increasing the energy barrier for grain-boundary sliding and rotation and by inhibiting grain coarsening, under extremely long-term creep conditions. Our processing approach should enable the development of microstructurally stable structural alloys with high strength and creep resistance for various high-temperature applications, including in the aerospace, naval, civilian infrastructure and energy sectors.
C1 [Darling, K. A.; Hornbuckle, B. C.] Army Res Lab, Aberdeen Proving Ground, MD 21005 USA.
   [Rajagopalan, M.; Bhatia, M. A.; Solanki, K. N.] Arizona State Univ, Sch Engn Matter Transport & Energy, Tempe, AZ 85281 USA.
   [Komarasamy, M.; Mishra, R. S.] Univ North Texas, Dept Mat Sci & Engn, Denton, TX 76203 USA.
C3 United States Department of Defense; US Army Research, Development & Engineering Command (RDECOM); US Army Research Laboratory (ARL); United States Army; Arizona State University; Arizona State University-Tempe; University of North Texas System; University of North Texas Denton
RP Solanki, KN (corresponding author), Arizona State Univ, Sch Engn Matter Transport & Energy, Tempe, AZ 85281 USA.
EM kiran.solanki@asu.edu
FU US Army Research Laboratory [W911NF-15-2-0038]
NR 35
TC 241
Z9 280
U1 13
U2 339
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 378
EP +
DI 10.1038/nature19313
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000049
PM 27629642
DA 2026-03-09
ER

PT J
AU Neyer, S
   Kunz, M
   Geiss, C
   Hantsche, M
   Hodirnau, VV
   Seybert, A
   Engel, C
   Scheffer, MP
   Cramer, P
   Frangakis, AS
AF Neyer, Simon
   Kunz, Michael
   Geiss, Christian
   Hantsche, Merle
   Hodirnau, Victor-Valentin
   Seybert, Anja
   Engel, Christoph
   Scheffer, Margot P.
   Cramer, Patrick
   Frangakis, Achilleas S.
TI Structure of RNA polymerase I transcribing ribosomal DNA genes
SO NATURE
LA English
DT Article
ID elongation complex; crystal-structure; transcription; architecture; visualization; validation; resolution; reveals; system
AB RNA polymerase I (Pol I) is a highly processive enzyme that transcribes ribosomal DNA (rDNA) and regulates growth of eukaryotic cells(1-4). Crystal structures of free Pol I from the yeast Saccharomyces cerevisiae have revealed dimers of the enzyme stabilized by a 'connector' element and an expanded cleft containing the active centre in an inactive conformation(5-7). The central bridge helix was unfolded and a Pol-I-specific 'expander' element occupied the DNA-template-binding site. The structure of Pol I in its active transcribing conformation has yet to be determined, whereas structures of Pol II and Pol III have been solved with bound DNA template and RNA transcript(8-10). Here we report structures of active transcribing Pol I from yeast solved by two different cryo-electron microscopy approaches. A single-particle structure at 3.8 angstrom resolution reveals a contracted active centre cleft with bound DNA and RNA, and a narrowed pore beneath the active site that no longer holds the RNA-cleavage-stimulating domain of subunit A12.2. A structure at 29 angstrom resolution that was determined from cryo-electron tomograms of Pol I enzymes transcribing cellular rDNA confirms contraction of the cleft and reveals that incoming and exiting rDNA enclose an angle of around 150 degrees. The structures suggest a model for the regulation of transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively.
C1 [Neyer, Simon; Hantsche, Merle; Engel, Christoph; Cramer, Patrick] Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.
   [Kunz, Michael; Geiss, Christian; Hodirnau, Victor-Valentin; Seybert, Anja; Scheffer, Margot P.; Frangakis, Achilleas S.] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, Max von Laue Str 15, D-60438 Frankfurt, Germany.
   [Kunz, Michael; Geiss, Christian; Hodirnau, Victor-Valentin; Seybert, Anja; Scheffer, Margot P.; Frangakis, Achilleas S.] Goethe Univ Frankfurt, Inst Biophys, Max von Laue Str 15, D-60438 Frankfurt, Germany.
C3 Max Planck Society; Goethe University Frankfurt; Goethe University Frankfurt
RP Cramer, P (corresponding author), Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.; Frangakis, AS (corresponding author), Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, Max von Laue Str 15, D-60438 Frankfurt, Germany.; Frangakis, AS (corresponding author), Goethe Univ Frankfurt, Inst Biophys, Max von Laue Str 15, D-60438 Frankfurt, Germany.
EM patrick.cramer@mpibpc.mpg.de; achilleas.frangakis@biophysik.org
FU Boehringer Ingelheim Fonds; Deutsche Forschungsgemeinschaft [SFB860, SPP1935, SFB 902]; Advanced Grant 'TRANSREGULON' from the European Research Council [693023]; Volkswagen Foundation; Starting Grant 'JTOMO' from the European Research Council; European Research Council (ERC) [693023] Funding Source: European Research Council (ERC)
NR 45
TC 69
Z9 72
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 607
EP +
DI 10.1038/nature20561
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500057
PM 27842382
DA 2026-03-09
ER

PT J
AU Venkatakrishnan, AJ
   Deupi, X
   Lebon, G
   Heydenreich, FM
   Flock, T
   Miljus, T
   Balaji, S
   Bouvier, M
   Veprintsev, DB
   Tate, CG
   Schertler, GFX
   Babu, MM
AF Venkatakrishnan, A. J.
   Deupi, Xavier
   Lebon, Guillaume
   Heydenreich, Franziska M.
   Flock, Tilman
   Miljus, Tamara
   Balaji, Santhanam
   Bouvier, Michel
   Veprintsev, Dmitry B.
   Tate, Christopher G.
   Schertler, Gebhard F. X.
   Babu, M. Madan
TI Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region
SO NATURE
LA English
DT Article
ID receptor activation; beta(2)-adrenergic receptor; structural insights; mechanism
AB Class A G-protein-coupled receptors (GPCRs) are a large family of membrane proteins that mediate a wide variety of physiological functions, including vision, neurotransmission and immune responses(1-4). They are the targets of nearly one-third of all prescribed medicinal drugs(5) such as beta blockers and antipsychotics. GPCR activation is facilitated by extracellular ligands and leads to the recruitment of intracellular G proteins(3,6). Structural rearrangements of residue contacts in the transmembrane domain serve as 'activation pathways' that connect the ligand-binding pocket to the G-protein-coupling region within the receptor. In order to investigate the similarities in activation pathways across class A GPCRs, we analysed 27 GPCRs from diverse subgroups for which structures of active, inactive or both states were available. Here we show that, despite the diversity in activation pathways between receptors, the pathways converge near the G-protein-coupling region. This convergence is mediated by a highly conserved structural rearrangement of residue contacts between transmembrane helices 3, 6 and 7 that releases G-protein-contacting residues. The convergence of activation pathways may explain how the activation steps initiated by diverse ligands enable GPCRs to bind a common repertoire of G proteins.
C1 [Venkatakrishnan, A. J.; Flock, Tilman; Balaji, Santhanam; Tate, Christopher G.; Babu, M. Madan] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
   [Venkatakrishnan, A. J.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
   [Venkatakrishnan, A. J.] Stanford Univ, Dept Comp Sci, 318 Campus Dr, Stanford, CA 94305 USA.
   [Venkatakrishnan, A. J.] Stanford Univ, Inst Computat & Math Engn, 475 Via Ortega, Stanford, CA 94305 USA.
   [Deupi, Xavier; Heydenreich, Franziska M.; Miljus, Tamara; Veprintsev, Dmitry B.; Schertler, Gebhard F. X.] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
   [Lebon, Guillaume] CNRS, UMR 5203, Inst Genom Fonct, 141 Rue Cardonille, F-34094 Montpellier 05, France.
   [Lebon, Guillaume] INSERM, U1191, F-34094 Montpellier, France.
   [Lebon, Guillaume] Univ Montpellier, F-34094 Montpellier, France.
   [Heydenreich, Franziska M.; Miljus, Tamara; Veprintsev, Dmitry B.; Schertler, Gebhard F. X.] ETH, Dept Biol, Wolfgang Pauli Str 27, CH-8093 Zurich, Switzerland.
   [Heydenreich, Franziska M.; Bouvier, Michel] Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada.
   [Heydenreich, Franziska M.; Bouvier, Michel] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
C3 MRC Laboratory Molecular Biology; Stanford University; Stanford University; Stanford University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite de Montreal; Universite de Montreal
RP Venkatakrishnan, AJ; Babu, MM (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.; Venkatakrishnan, AJ (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.; Venkatakrishnan, AJ (corresponding author), Stanford Univ, Dept Comp Sci, 318 Campus Dr, Stanford, CA 94305 USA.; Venkatakrishnan, AJ (corresponding author), Stanford Univ, Inst Computat & Math Engn, 475 Via Ortega, Stanford, CA 94305 USA.
EM ajvenkat@stanford.edu; madanm@mrc-lmb.cam.ac.uk
FU LMB International Scholarship; St. John's College Benefactor Scholarship; MRC Centenary Early Career Award; Medical Research Council [MC_U105185859, MC_U105197215]; Boehringer Ingelheim Fonds; Heptares Therapeutics Ltd; ATIP-Avenir program; Swiss National Science Foundation [310030_153145, 31003A_146520, 31003A_159748, P1EZP3_165219]; Human Frontiers Science Program [RGP0034/2014]; Canadian Institute for Health Research [MOP-10501]; COST Action [CM1207]; Medical Research Council [MC_U105197215, MC_U105185859] Funding Source: researchfish; MRC [MC_U105185859, MC_U105197215] Funding Source: UKRI; Swiss National Science Foundation (SNF) [P1EZP3_165219, 31003A_146520, 310030_153145, 31003A_159748] Funding Source: Swiss National Science Foundation (SNF)
NR 32
TC 244
Z9 296
U1 0
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 484
EP +
DI 10.1038/nature19107
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600047
PM 27525504
DA 2026-03-09
ER

PT J
AU Stappenbeck, TS
   Virgin, HW
AF Stappenbeck, Thaddeus S.
   Virgin, Herbert W.
TI Accounting for reciprocal host-microbiome interactions in experimental science
SO NATURE
LA English
DT Article
ID gut microbiota; intestinal microbiota; bacterial microbiome; enteric virus; mouse model; disease; virome; infection; immunodeficiency; metabolites
AB Mammals are defined by their metagenome, a combination of host and microbiome genes. This knowledge presents opportunities to further basic biology with translation to human diseases. However, the now-documented influence of the metagenome on experimental results and the reproducibility of in vivo mammalian models present new challenges. Here we provide the scientific basis for calling on all investigators, editors and funding agencies to embrace changes that will enhance reproducible and interpretable experiments by accounting for metagenomic effects. Implementation of new reporting and experimental design principles will improve experimental work, speed discovery and translation, and properly use substantial investments in biomedical research.
C1 [Stappenbeck, Thaddeus S.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, Campus Box 8118,660 South Euclid Ave, St Louis, MO 63110 USA.
C3 Washington University (WUSTL)
RP Stappenbeck, TS; Virgin, HW (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, Campus Box 8118,660 South Euclid Ave, St Louis, MO 63110 USA.
EM stappenb@pathology.wustl.edu; virgin@wustl.edu
NR 120
TC 214
Z9 263
U1 2
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 191
EP 199
DI 10.1038/nature18285
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100030
PM 27279212
DA 2026-03-09
ER

PT J
AU Cogliati, S
   Calvo, E
   Loureiro, M
   Guaras, AM
   Nieto-Arellano, R
   Garcia-Poyatos, C
   Ezkurdia, I
   Mercader, N
   Vázquez, J
   Enriquez, JA
AF Cogliati, Sara
   Calvo, Enrique
   Loureiro, Marta
   Guaras, Adela M.
   Nieto-Arellano, Rocio
   Garcia-Poyatos, Carolina
   Ezkurdia, Iakes
   Mercader, Nadia
   Vazquez, Jesus
   Antonio Enriquez, Jose
TI Mechanism of super-assembly of respiratory complexes III and IV
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; supercomplex; chain; organization; architecture; respirasome; cox7a2l
AB Respiratory chain complexes can super-assemble into quaternary structures called supercomplexes that optimize cellular metabolism(1). The interaction between complexes III (CIII) and IV (CIV) is modulated by supercomplex assembly factor 1 (SCAF1, also known as COX7A2L)(2). The discovery of SCAF1 represented strong genetic evidence that supercomplexes exist in vivo(2,3). SCAF1 is present as a long isoform (113 amino acids) or a short isoform (111 amino acids) in different mouse strains(2,4). Only the long isoform can induce the super-assembly of CIII and CIV2-6, but it is not clear whether SCAF1 is required for the formation of the respirasome (a supercomplex of CI, CIII2 and CIV)(1,2,4-6). Here we show, by combining deep proteomics and immunodetection analysis, that SCAF1 is always required for the interaction between CIII and CIV and that the respirasome is absent from most tissues of animals containing the short isoform of SCAF1, with the exception of heart and skeletal muscle. We used directed mutagenesis to characterize SCAF1 regions that interact with CIII and CIV and discovered that this interaction requires the correct orientation of a histidine residue at position 73 that is altered in the short isoform of SCAF1, explaining its inability to interact with CIV. Furthermore, we find that the CIV subunit COX7A2 is replaced by SCAF1 in supercomplexes containing CIII and that dimers seem to be more stable when they include COX6A2 rather than the COX6A1 isoform.
C1 [Cogliati, Sara; Calvo, Enrique; Loureiro, Marta; Guaras, Adela M.; Nieto-Arellano, Rocio; Garcia-Poyatos, Carolina; Ezkurdia, Iakes; Mercader, Nadia; Vazquez, Jesus; Antonio Enriquez, Jose] Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain.
   [Garcia-Poyatos, Carolina; Mercader, Nadia] Univ Bern, Inst Anat, CH-3000 Bern, Switzerland.
   [Antonio Enriquez, Jose] Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50009 Zaragoza, Spain.
C3 Centro Nacional de Investigaciones Cardiovasculares (CNIC); University of Bern; University of Zaragoza
RP Vázquez, J; Enriquez, JA (corresponding author), Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain.
EM jvazquez@cnic.es; jaenriquez@cnic.es
FU MINECO [SAF2015-65633-R, BIO2015-67580-P, PRB2, IPT13/0001-ISCIII-SGEFI/FEDER, RD 12/0042/0054, RD12/0042/0056]; Fundacion La Marato TV3 and ERC-Starting Grant [2013 337703 zebraHeart]; MINECO; Pro-CNIC Foundation; SO-MINECO [SEV-2015-0505]
NR 18
TC 177
Z9 192
U1 2
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 579
EP +
DI 10.1038/nature20157
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600047
PM 27775717
DA 2026-03-09
ER

PT J
AU Wang, L
   Luo, JY
   Li, BC
   Tian, XY
   Chen, LJ
   Huang, YH
   Liu, J
   Deng, D
   Lau, CW
   Wan, S
   Ai, D
   Mak, KLK
   Tong, KK
   Kwan, KM
   Wang, NP
   Chiu, JJ
   Zhu, Y
   Huang, Y
AF Wang, Li
   Luo, Jiang-Yun
   Li, Bochuan
   Tian, Xiao Yu
   Chen, Li-Jing
   Huang, Yuhong
   Liu, Jian
   Deng, Dan
   Lau, Chi Wai
   Wan, Song
   Ai, Ding
   Mak, King-Lun Kingston
   Tong, Ka Kui
   Kwan, Kin Ming
   Wang, Nanping
   Chiu, Jeng-Jiann
   Zhu, Yi
   Huang, Yu
TI Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow
SO NATURE
LA English
DT Article
ID endothelial-cells; hippo pathway; outside-in; stress; yap; activation; expression; subunit; vivo; tead
AB The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli(1). However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis. Atheroprone-disturbed flow increases whereas atheroprotective unidirectional shear stress inhibits YAP/TAZ activity. Unidirectional shear stress activates integrin and promotes integrin-G alpha(13) interaction, leading to RhoA inhibition and YAP phosphorylation and suppression. YAP/TAZ inhibition suppresses JNK signalling and downregulates pro-inflammatory genes expression, thereby reducing monocyte attachment and infiltration. In vivo endothelial-specific YAP overexpression exacerbates, while CRISPR/Cas9-mediated Yap knockdown in endothelium retards, plaque formation in ApoE(-/-) mice. We also show several existing anti-atherosclerotic agents such as statins inhibit YAP/TAZ transactivation. On the other hand, simvastatin fails to suppress constitutively active YAP/TAZ-induced pro-inflammatory gene expression in endothelial cells, indicating that YAP/TAZ inhibition could contribute to the anti-inflammatory effect of simvastatin. Furthermore, activation of integrin by oral administration of MnCl2 reduces plaque formation. Taken together, our results indicate that integrin-G alpha(13)-RhoA-YAP pathway holds promise as a novel drug target against atherosclerosis.
C1 [Wang, Li; Luo, Jiang-Yun; Tian, Xiao Yu; Huang, Yuhong; Liu, Jian; Deng, Dan; Lau, Chi Wai; Huang, Yu] Chinese Univ Hong Kong, Shenzhen Res Inst, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China.
   [Wang, Li; Luo, Jiang-Yun; Tian, Xiao Yu; Huang, Yuhong; Liu, Jian; Deng, Dan; Lau, Chi Wai; Huang, Yu] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.
   [Wang, Li; Luo, Jiang-Yun; Tian, Xiao Yu; Huang, Yuhong; Mak, King-Lun Kingston; Huang, Yu] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
   [Li, Bochuan; Ai, Ding; Zhu, Yi] Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet, Tianjin 300070, Peoples R China.
   [Li, Bochuan; Ai, Ding; Zhu, Yi] Tianjin Med Univ, Dept Physiol & Pathophysiol, Tianjin 300070, Peoples R China.
   [Chen, Li-Jing; Chiu, Jeng-Jiann] Natl Hlth Res Inst, Inst Cellular & Syst Med, Miaoli 35053, Taiwan.
   [Wan, Song] Chinese Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
   [Tong, Ka Kui; Kwan, Kin Ming] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.
   [Wang, Nanping] Dalian Med Univ, Adv Inst Med Sci, Dalian 116044, Peoples R China.
C3 Chinese University of Hong Kong; CUHK Shenzhen Research Institute; Chinese University of Hong Kong; Chinese University of Hong Kong; Tianjin Medical University; Tianjin Medical University; National Health Research Institutes - Taiwan; Chinese University of Hong Kong; Chinese University of Hong Kong; Dalian Medical University
RP Huang, Y (corresponding author), Chinese Univ Hong Kong, Shenzhen Res Inst, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China.; Huang, Y (corresponding author), Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.; Huang, Y (corresponding author), Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.; Zhu, Y (corresponding author), Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet, Tianjin 300070, Peoples R China.; Zhu, Y (corresponding author), Tianjin Med Univ, Dept Physiol & Pathophysiol, Tianjin 300070, Peoples R China.
EM zhuyi@tmu.edu.cn; yu-huang@cuhk.edu.hk
FU Hong Kong Research Grants Council [CUHK2/CRF/12G]; Natural Science Foundation of China [91339117, 81130002, 31430045]; RGC [T12-402/13-N, C7055-14G, CUHK14105814]; Croucher Foundation; CUHK Vice Chancellor's Discretionary Fund; Lui Che Woo Foundation; Ministry of Science and Technology, Taiwan [MOST104-2321-B-400-017, MOST104-2320-B-400-002-MY3]
NR 38
TC 530
Z9 635
U1 17
U2 258
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 579
EP +
DI 10.1038/nature20602
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500051
PM 27926730
DA 2026-03-09
ER

PT J
AU Tomkins, AG
   Bowlt, L
   Genge, M
   Wilson, SA
   Brand, HEA
   Wykes, JL
AF Tomkins, Andrew G.
   Bowlt, Lara
   Genge, Matthew
   Wilson, Siobhan A.
   Brand, Helen E. A.
   Wykes, Jeremy L.
TI Ancient micrometeorites suggestive of an oxygen-rich Archaean upper atmosphere
SO NATURE
LA English
DT Article
ID mass-independent fractionation; sulfur isotopes; pilbara craton; iron; evolution; oxidation; rise
AB It is widely accepted that Earth's early atmosphere contained less than 0.001 per cent of the present-day atmospheric oxygen (O-2) level, until the Great Oxidation Event resulted in a major rise in O-2 concentration about 2.4 billion years ago(1). There are multiple lines of evidence for low O-2 concentrations on early Earth, but all previous observations relate to the composition of the lower atmosphere(2) in the Archaean era; to date no method has been developed to sample the Archaean upper atmosphere. We have extracted fossil micrometeorites from limestone sedimentary rock that had accumulated slowly 2.7 billion years ago before being preserved in Australia's Pilbara region. We propose that these micrometeorites formed when sand-sized particles entered Earth's atmosphere and melted at altitudes of about 75 to 90 kilometres (given an atmospheric density similar to that of today(3)). Here we show that the FeNi metal in the resulting cosmic spherules was oxidized while molten, and quench-crystallized to form spheres of interlocking dendritic crystals primarily of magnetite (Fe3O4), with wstit(FeO)+metal preserved in a few particles. Our model of atmospheric micrometeorite oxidation suggests that Archaean upper-atmosphere oxygen concentrations may have been close to those of the present-day Earth, and that the ratio of oxygen to carbon monoxide was sufficiently high to prevent noticeable inhibition of oxidation by carbon monoxide. The anomalous sulfur isotope (Delta S-33) signature of pyrite (FeS2) in seafloor sediments from this period, which requires an anoxic surface environment(4), implies that there may have been minimal mixing between the upper and lower atmosphere during the Archaean.
C1 [Tomkins, Andrew G.; Bowlt, Lara; Wilson, Siobhan A.; Wykes, Jeremy L.] Monash Univ, Sch Earth Atmosphere & Environm, Melbourne, Vic 3800, Australia.
   [Genge, Matthew] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, Impact & Astromat Res Ctr, Exhibit Rd, London SW7 2AZ, England.
   [Genge, Matthew] Nat Hist Museum, Dept Mineral, Cromwell Rd, London SW7 2BT, England.
   [Brand, Helen E. A.; Wykes, Jeremy L.] Australian Synchrotron, 800 Blackburn Rd, Clayton, Vic 3168, Australia.
   [Wykes, Jeremy L.] Macquarie Univ, Dept Earth & Planetary Sci, N Ryde, NSW 2113, Australia.
C3 Monash University; Imperial College London; Natural History Museum London; Australian Synchrotron; Macquarie University
RP Tomkins, AG (corresponding author), Monash Univ, Sch Earth Atmosphere & Environm, Melbourne, Vic 3800, Australia.
EM andrew.tomkins@monash.edu
FU STFC [ST/J001260/1]; Science and Technology Facilities Council [ST/J001260/1, ST/N000803/1] Funding Source: researchfish; UK Space Agency [ST/M003167/1] Funding Source: researchfish; STFC [ST/J001260/1, ST/N000803/1] Funding Source: UKRI
NR 33
TC 61
Z9 70
U1 0
U2 57
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 235
EP +
DI 10.1038/nature17678
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200047
PM 27172047
DA 2026-03-09
ER

PT J
AU Rodina, A
   Wang, T
   Yan, PR
   Gomes, ED
   Dunphy, MPS
   Pillarsetty, N
   Koren, J
   Gerecitano, JF
   Aldone, TT
   Zong, HL
   Caldas-Lopes, E
   Alpaugh, M
   Corben, A
   Riolo, M
   Beattie, B
   Pressl, C
   Peter, RI
   Xu, C
   Trondl, R
   Patel, HJ
   Shimizu, F
   Bolaender, A
   Yang, CH
   Panchal, P
   Farooq, MF
   Kishinevsky, S
   Modi, S
   Lin, O
   Chu, FX
   Patil, S
   Erdjument-Bromage, H
   Zanzonico, P
   Hudis, C
   Studer, L
   Roboz, GJ
   Cesarman, E
   Cerchietti, L
   Levine, R
   Melnick, A
   Larson, SM
   Lewis, JS
   Guzman, ML
   Chiosis, G
AF Rodina, Anna
   Wang, Tai
   Yan, Pengrong
   Gomes, Erica DaGama
   Dunphy, Mark P. S.
   Pillarsetty, Nagavarakishore
   Koren, John, III
   Gerecitano, John F.
   Aldone, Tony T.
   Zong, Hongliang
   Caldas-Lopes, Eloisi
   Alpaugh, Mary
   Corben, Adriana
   Riolo, Matthew
   Beattie, Brad
   Pressl, Christina
   Peter, Radu I.
   Xu, Chao
   Trondl, Robert
   Patel, Hardik J.
   Shimizu, Fumiko
   Bolaender, Alexander
   Yang, Chenghua
   Panchal, Palak
   Farooq, Mohammad F.
   Kishinevsky, Sarah
   Modi, Shanu
   Lin, Oscar
   Chu, Feixia
   Patil, Sujata
   Erdjument-Bromage, Hediye
   Zanzonico, Pat
   Hudis, Clifford
   Studer, Lorenz
   Roboz, Gail J.
   Cesarman, Ethel
   Cerchietti, Leandro
   Levine, Ross
   Melnick, Ari
   Larson, Steven M.
   Lewis, Jason S.
   Guzman, Monica L.
   Chiosis, Gabriela
TI The epichaperome is an integrated chaperome network that facilitates tumour survival
SO NATURE
LA English
DT Article
ID shock-protein 90; posttranslational modifications; breast-cancer; hsp90; hsp70; inhibitor; affinity; software; reveals; heat-shock-protein-70
AB Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery(1-6). Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy(7-17). As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis. Such limitations have led to a bottleneck in our understanding of chaperome-related disease biology and in the development of chaperome-targeted cancer treatment. Here we examined the chaperome complexes in a large set of tumour specimens. The methods used maintained the endogenous native state of tumours and we exploited this to investigate the molecular characteristics and composition of the chaperome in cancer, the molecular factors that drive chaperome networks to crosstalk in tumours, the distinguishing factors of the chaperome in tumours sensitive to pharmacologic inhibition, and the characteristics of tumours that may benefit from chaperome therapy. We find that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically 'rewired' to form a network of stable, survival-facilitating, high-molecular-weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock cognate protein 70 (HSC70) are nucleating sites for these physically and functionally integrated complexes. The results indicate that these tightly integrated chaperome units, here termed the epichaperome, can function as a network to enhance cellular survival, irrespective of tissue of origin or genetic background. The epichaperome, present in over half of all cancers tested, has implications for diagnostics and also provides potential vulnerability as a target for drug intervention.
C1 [Rodina, Anna; Wang, Tai; Yan, Pengrong; Gomes, Erica DaGama; Koren, John, III; Aldone, Tony T.; Caldas-Lopes, Eloisi; Alpaugh, Mary; Riolo, Matthew; Xu, Chao; Trondl, Robert; Patel, Hardik J.; Shimizu, Fumiko; Bolaender, Alexander; Yang, Chenghua; Panchal, Palak; Kishinevsky, Sarah; Chiosis, Gabriela] Sloan Kettering Inst, Program Chem Biol, New York, NY 10065 USA.
   [Dunphy, Mark P. S.; Pillarsetty, Nagavarakishore; Pressl, Christina; Larson, Steven M.; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
   [Gerecitano, John F.] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10065 USA.
   [Zong, Hongliang; Roboz, Gail J.; Cesarman, Ethel; Cerchietti, Leandro; Melnick, Ari; Guzman, Monica L.] Weill Cornell Med Coll, Dept Med, Haematol & Med Oncol, New York, NY 10065 USA.
   [Corben, Adriana; Lin, Oscar] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Beattie, Brad; Zanzonico, Pat] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA.
   [Peter, Radu I.] Tech Univ Cluj Napoca, Dept Math, Cluj Napoca 400114, Romania.
   [Farooq, Mohammad F.; Chu, Feixia] Univ New Hampshire, Mol Cellular & Biomed Sci, Durham, NH 03824 USA.
   [Modi, Shanu; Hudis, Clifford; Chiosis, Gabriela] Mem Sloan Kettering Canc Ctr, Dept Med, Breast Canc Serv, New York, NY 10065 USA.
   [Patil, Sujata] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY 10065 USA.
   [Erdjument-Bromage, Hediye] Mem Sloan Kettering Canc Ctr, Program Mol Biol, Microchem & Prote Core, New York, NY 10065 USA.
   [Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Levine, Ross] Sloan Kettering Inst, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Alpaugh, Mary] Rowan Univ, Dept Biol, Glassboro, NJ 08028 USA.
   [Alpaugh, Mary] Rowan Univ, Dept Biomed & Translat Sci, Glassboro, NJ 08028 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Technical University of Cluj Napoca; University System Of New Hampshire; University of New Hampshire; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Rowan University; Rowan University
RP Chiosis, G (corresponding author), Sloan Kettering Inst, Program Chem Biol, New York, NY 10065 USA.; Guzman, ML (corresponding author), Weill Cornell Med Coll, Dept Med, Haematol & Med Oncol, New York, NY 10065 USA.; Chiosis, G (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, Breast Canc Serv, New York, NY 10065 USA.
EM mlg2007@med.cornell.edu; chiosisg@mskcc.org
FU NIH [R01 CA172546, R01 CA155226, P01 CA186866, P30 CA08748, P50 CA86438, DP2 OD007399]; Jane H. Gordon Breast Cancer Research Fund; Breast Cancer Research Fund; Susan G. Komen for the Cure; W. H. Goodwin, A. Goodwin and the Commonwealth Foundation for Cancer Research; Experimental Therapeutics Center of MSKCC; Hirshberg Foundation for Pancreatic Cancer; Irma T. Hirschl Foundation; Rubenstein Center for Pancreatic Research; National Center for Advancing Translational Sciences of the NIH [UL1TR000457]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR002384] Funding Source: NIH RePORTER
NR 54
TC 227
Z9 265
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 397
EP +
DI 10.1038/nature19807
PG 28
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100042
PM 27706135
DA 2026-03-09
ER

PT J
AU Jordan, JJ
   Hoffman, M
   Bloom, P
   Rand, DG
AF Jordan, Jillian J.
   Hoffman, Moshe
   Bloom, Paul
   Rand, David G.
TI Third-party punishment as a costly signal of trustworthiness
SO NATURE
LA English
DT Article
ID norm enforcement; cooperation; reciprocity; reputation; evolution; fairness
AB Third-party punishment (TPP)(1-7), in which unaffected observers punish selfishness, promotes cooperation by deterring defection. But why should individuals choose to bear the costs of punishing? We present a game theoretic model of TPP as a costly signal(8-10) of trustworthiness. Our model is based on individual differences in the costs and/ or benefits of being trustworthy. We argue that individuals for whom trustworthiness is payoff-maximizing will find TPP to be less net costly (for example, because mechanisms(11) that incentivize some individuals to be trustworthy also create benefits for deterring selfishness via TPP). We show that because of this relationship, it can be advantageous for individuals to punish selfishness in order to signal that they are not selfish themselves. We then empirically validate our model using economic game experiments. We show that TPP is indeed a signal of trustworthiness: third-party punishers are trusted more, and actually behave in a more trustworthy way, than non-punishers. Furthermore, as predicted by our model, introducing a more informative signal-the opportunity to help directly-attenuates these signalling effects. When potential punishers have the chance to help, they are less likely to punish, and punishment is perceived as, and actually is, a weaker signal of trustworthiness. Costly helping, in contrast, is a strong and highly used signal even when TPP is also possible. Together, our model and experiments provide a formal reputational account of TPP, and demonstrate how the costs of punishing may be recouped by the long-run benefits of signalling one's trustworthiness.
C1 [Jordan, Jillian J.; Bloom, Paul; Rand, David G.] Yale Univ, Dept Psychol, New Haven, CT 06511 USA.
   [Hoffman, Moshe] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Rand, David G.] Yale Univ, Dept Econ, New Haven, CT 06511 USA.
   [Rand, David G.] Yale Univ, Sch Management, New Haven, CT 06511 USA.
C3 Yale University; Harvard University; Yale University; Yale University
RP Jordan, JJ; Rand, DG (corresponding author), Yale Univ, Dept Psychol, New Haven, CT 06511 USA.; Rand, DG (corresponding author), Yale Univ, Dept Econ, New Haven, CT 06511 USA.; Rand, DG (corresponding author), Yale Univ, Sch Management, New Haven, CT 06511 USA.
EM jillian.jordan@yale.edu; david.rand@yale.edu
FU John Templeton Foundation
NR 27
TC 340
Z9 388
U1 14
U2 234
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 473
EP +
DI 10.1038/nature16981
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800034
PM 26911783
DA 2026-03-09
ER

PT J
AU Ruibal, P
   Oestereich, L
   Lüdtke, A
   Becker-Ziaja, B
   Wozniak, DM
   Kerber, R
   Korva, M
   Cabeza-Cabrerizo, M
   Bore, JA
   Koundouno, FR
   Duraffour, S
   Weller, R
   Thorenz, A
   Cimini, E
   Viola, D
   Agrati, C
   Repits, J
   Afrough, B
   Cowley, LA
   Ngabo, D
   Hinzmann, J
   Mertens, M
   Vitoriano, I
   Logue, CH
   Boettcher, JP
   Pallasch, E
   Sachse, A
   Bah, A
   Nitzsche, K
   Kuisma, E
   Michel, J
   Holm, T
   Zekeng, EG
   García-Dorival, I
   Wölfel, R
   Stoecker, K
   Fleischmann, E
   Strecker, T
   Di Caro, A
   Avsic-Zupanc, T
   Kurth, A
   Meschi, S
   Mély, S
   Newman, E
   Bocquin, A
   Kis, Z
   Kelterbaum, A
   Molkenthin, P
   Carletti, F
   Portmann, J
   Wolff, S
   Castilletti, C
   Schudt, G
   Fizet, A
   Ottowell, LJ
   Herker, E
   Jacobs, T
   Kretschmer, B
   Severi, E
   Ouedraogo, N
   Lago, M
   Negredo, A
   Franco, L
   Anda, P
   Schmiedel, S
   Kreuels, B
   Wichmann, D
   Addo, MM
   Lohse, AW
   De Clerck, H
   Nanclares, C
   Jonckheere, S
   Van Herp, M
   Sprecher, A
   Gao, XJ
   Carrington, M
   Miranda, O
   Castro, CM
   Gabriel, M
   Drury, P
   Formenty, P
   Diallo, B
   Koivogui, L
   Magassouba, N
   Carroll, MW
   Günther, S
   Muñoz-Fontela, C
AF Ruibal, Paula
   Oestereich, Lisa
   Luedtke, Anja
   Becker-Ziaja, Beate
   Wozniak, David M.
   Kerber, Romy
   Korva, Misa
   Cabeza-Cabrerizo, Mar
   Bore, Joseph A.
   Koundouno, Fara Raymond
   Duraffour, Sophie
   Weller, Romy
   Thorenz, Anja
   Cimini, Eleonora
   Viola, Domenico
   Agrati, Chiara
   Repits, Johanna
   Afrough, Babak
   Cowley, Lauren A.
   Ngabo, Didier
   Hinzmann, Julia
   Mertens, Marc
   Vitoriano, Ines
   Logue, Christopher H.
   Boettcher, Jan Peter
   Pallasch, Elisa
   Sachse, Andreas
   Bah, Amadou
   Nitzsche, Katja
   Kuisma, Eeva
   Michel, Janine
   Holm, Tobias
   Zekeng, Elsa-Gayle
   Garcia-Dorival, Isabel
   Woelfel, Roman
   Stoecker, Kilian
   Fleischmann, Erna
   Strecker, Thomas
   Di Caro, Antonino
   Avsic-Zupanc, Tatjana
   Kurth, Andreas
   Meschi, Silvia
   Mely, Stephane
   Newman, Edmund
   Bocquin, Anne
   Kis, Zoltan
   Kelterbaum, Anne
   Molkenthin, Peter
   Carletti, Fabrizio
   Portmann, Jasmine
   Wolff, Svenja
   Castilletti, Concetta
   Schudt, Gordian
   Fizet, Alexandra
   Ottowell, Lisa J.
   Herker, Eva
   Jacobs, Thomas
   Kretschmer, Birte
   Severi, Ettore
   Ouedraogo, Nobila
   Lago, Mar
   Negredo, Anabel
   Franco, Leticia
   Anda, Pedro
   Schmiedel, Stefan
   Kreuels, Benno
   Wichmann, Dominic
   Addo, Marylyn M.
   Lohse, Ansgar W.
   De Clerck, Hilde
   Nanclares, Carolina
   Jonckheere, Sylvie
   Van Herp, Michel
   Sprecher, Armand
   Gao Xiaojiang
   Carrington, Mary
   Miranda, Osvaldo
   Castro, Carlos M.
   Gabriel, Martin
   Drury, Patrick
   Formenty, Pierre
   Diallo, Boubacar
   Koivogui, Lamine
   Magassouba, N'Faly
   Carroll, Miles W.
   Guenther, Stephan
   Munoz-Fontela, Cesar
TI Unique human immune signature of Ebola virus disease in Guinea
SO NATURE
LA English
DT Article
ID t-cell response; ctla-4; infection; identification; progression; expression; effector; insights; patient; fever
AB Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus(2,3). Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
C1 [Ruibal, Paula; Luedtke, Anja; Herker, Eva; Munoz-Fontela, Cesar] Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany.
   [Ruibal, Paula; Oestereich, Lisa; Luedtke, Anja; Becker-Ziaja, Beate; Wozniak, David M.; Kerber, Romy; Cabeza-Cabrerizo, Mar; Duraffour, Sophie; Pallasch, Elisa; Holm, Tobias; Jacobs, Thomas; Kreuels, Benno; Gabriel, Martin; Guenther, Stephan; Munoz-Fontela, Cesar] WHO, Bernhard Nocht Inst Trop Med, Collaborating Ctr Arbovirus & Hemorrhag Fever Ref, D-20359 Hamburg, Germany.
   [Ruibal, Paula; Oestereich, Lisa; Luedtke, Anja; Becker-Ziaja, Beate; Wozniak, David M.; Kerber, Romy; Pallasch, Elisa; Nitzsche, Katja; Holm, Tobias; Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Kelterbaum, Anne; Molkenthin, Peter; Wolff, Svenja; Schudt, Gordian; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M.; Lohse, Ansgar W.; Gabriel, Martin; Guenther, Stephan; Munoz-Fontela, Cesar] German Ctr Infect Res DZIF, Partner Sites Hamburg, Munich, Germany.
   [Ruibal, Paula; Oestereich, Lisa; Luedtke, Anja; Becker-Ziaja, Beate; Wozniak, David M.; Kerber, Romy; Korva, Misa; Cabeza-Cabrerizo, Mar; Bore, Joseph A.; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren A.; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Ines; Logue, Christopher H.; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; Garcia-Dorival, Isabel; Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Antonino; Avsic-Zupanc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mely, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudt, Gordian; Fizet, Alexandra; Ottowell, Lisa J.; Negredo, Anabel; Lohse, Ansgar W.; Gabriel, Martin; Carroll, Miles W.; Guenther, Stephan; Munoz-Fontela, Cesar] European Mobile Lab Consortium, Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany.
   [Korva, Misa; Avsic-Zupanc, Tatjana] Univ Ljubljana, Fac Med, Inst Microbiol & Immunol, Ljubljana 1000, Slovenia.
   [Weller, Romy] Twincore, Ctr Expt & Clin Infect Res, Inst Expt Virol, D-30625 Hannover, Germany.
   [Thorenz, Anja] Hannover Med Sch, D-30625 Hannover, Germany.
   [Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Di Caro, Antonino; Meschi, Silvia; Carletti, Fabrizio; Castilletti, Concetta] Natl Inst Infect Dis Lazzaro Spallanzani, I-00149 Rome, Italy.
   [Afrough, Babak; Ngabo, Didier; Vitoriano, Ines; Logue, Christopher H.; Kuisma, Eeva; Newman, Edmund; Ottowell, Lisa J.; Carroll, Miles W.] Publ Hlth England, Porton Down, Salisbury SP4 0JG, Wilts, England.
   [Cowley, Lauren A.] Publ Hlth England, Colindale Ave, London NW9 5EQ, England.
   [Hinzmann, Julia; Boettcher, Jan Peter; Sachse, Andreas; Michel, Janine; Kurth, Andreas; Ouedraogo, Nobila] Robert Koch Inst, D-13353 Berlin, Germany.
   [Mertens, Marc] Friedrich Loeffler Inst, D-17493 Greifswald, Germany.
   [Bah, Amadou] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland.
   [Garcia-Dorival, Isabel] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 7BE, Merseyside, England.
   [Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Molkenthin, Peter] Bundeswehr Inst Microbiol, D-80937 Munich, Germany.
   [Strecker, Thomas; Kelterbaum, Anne; Wolff, Svenja; Schudt, Gordian] Univ Marburg, Inst Virol, D-35043 Marburg, Germany.
   [Mely, Stephane; Bocquin, Anne] INSERM, Lab P4 Jean Merieux, F-69365 Lyon, France.
   [Kis, Zoltan] Hungarian Natl Biosafety Lab, Natl Ctr Epidemiol, H-1097 Budapest, Hungary.
   [Kis, Zoltan; Severi, Ettore] European Ctr Dis Prevent & Control, S-17165 Solna, Sweden.
   [Portmann, Jasmine] Fed Off Civil Protect, CH-3700 Spiez, Switzerland.
   [Fizet, Alexandra] Inst Pasteur, Unite Biol Infect Virales Emergentes, F-69365 Lyon, France.
   [Kretschmer, Birte] European Res & Project Off, Eurice, D-10115 Berlin, Germany.
   [Lago, Mar] Hosp La Paz, Infect Dis Unit, Internal Med Serv, Madrid 28046, Spain.
   [Negredo, Anabel; Franco, Leticia; Anda, Pedro] Inst Hlth Carlos III, Natl Ctr Microbiol, Madrid 28220, Spain.
   [Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M.; Lohse, Ansgar W.] Univ Med Ctr Hamburg Eppendorf, D-20246 Hamburg, Germany.
   [De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand] Med Sans Frontieres, B-1050 Brussels, Belgium.
   [Gao Xiaojiang; Carrington, Mary] Leidos Biomed Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Gao Xiaojiang; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
   [Miranda, Osvaldo; Castro, Carlos M.] Hosp Militar Cent Dr Carlos J Finlay, Havana 11400, Cuba.
   [Drury, Patrick; Formenty, Pierre; Diallo, Boubacar] WHO, CH-1211 Geneva 27, Switzerland.
   [Koivogui, Lamine] Inst Natl Sante Publ, Conakry 2101, Guinea.
   [Magassouba, N'Faly] Univ Gamal Abdel Nasser Conakry, CHU Donka, Conakry 2101, Guinea.
C3 Heinrich Pette Institute; World Health Organization; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; German Center for Infection Research; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; University of Ljubljana; Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; IRCCS Lazzaro Spallanzani; Public Health England; Public Health England; Robert Koch Institute; Friedrich Loeffler Institute; Swiss School of Public Health (SSPH+); University of Basel; Swiss Tropical & Public Health Institute; University of Liverpool; Bundeswehr Institute of Microbiology (IMB); Philipps University Marburg; Institut National de la Sante et de la Recherche Medicale (Inserm); European Centre for Disease Prevention & Control; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Hospital Universitario La Paz; Instituto de Salud Carlos III; Centro Nacional de Microbiologia (CNM); University of Hamburg; University Medical Center Hamburg-Eppendorf; Doctors Without Borders; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Ragon Institute; World Health Organization
RP Muñoz-Fontela, C (corresponding author), Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany.; Günther, S; Muñoz-Fontela, C (corresponding author), WHO, Bernhard Nocht Inst Trop Med, Collaborating Ctr Arbovirus & Hemorrhag Fever Ref, D-20359 Hamburg, Germany.; Günther, S; Muñoz-Fontela, C (corresponding author), German Ctr Infect Res DZIF, Partner Sites Hamburg, Munich, Germany.; Günther, S; Muñoz-Fontela, C (corresponding author), European Mobile Lab Consortium, Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany.
EM guenther@bni.uni-hamburg.de; cesar.munoz-fontela@hpi.uni-hamburg.de
FU European Union [666100]; Directorate-General for International Cooperation and Development [IFS/2011/272-372]; German Research Foundation [GU 883/4-1]; Spanish National Plan for Research and Development ISCIII; FEDER [RD12/0018/006]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research; Leibniz Center of Infection; European Program for Public Health Microbiology Training (EUPHEM); National Cancer Institute [ZIABC010792, ZIABC010791] Funding Source: NIH RePORTER
NR 30
TC 157
Z9 172
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 100
EP +
DI 10.1038/nature17949
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900047
PM 27147028
DA 2026-03-09
ER

PT J
AU Yadav, AK
   Nelson, CT
   Hsu, SL
   Hong, Z
   Clarkson, JD
   Schlepüetz, CM
   Damodaran, AR
   Shafer, P
   Arenholz, E
   Dedon, LR
   Chen, D
   Vishwanath, A
   Minor, AM
   Chen, LQ
   Scott, JF
   Martin, LW
   Ramesh, R
AF Yadav, A. K.
   Nelson, C. T.
   Hsu, S. L.
   Hong, Z.
   Clarkson, J. D.
   Schlepueetz, C. M.
   Damodaran, A. R.
   Shafer, P.
   Arenholz, E.
   Dedon, L. R.
   Chen, D.
   Vishwanath, A.
   Minor, A. M.
   Chen, L. Q.
   Scott, J. F.
   Martin, L. W.
   Ramesh, R.
TI Observation of polar vortices in oxide superlattices
SO NATURE
LA English
DT Article
ID ferroelectric domain-structures; physics; pbtio3
AB The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena(1-5). In recent years, complex spin topologies have emerged as a consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials-(6,7). Here we produce complex topologies of electrical polarization-namely, nanometre-scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies(6)-by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality.
C1 [Yadav, A. K.; Nelson, C. T.; Hsu, S. L.; Clarkson, J. D.; Damodaran, A. R.; Dedon, L. R.; Chen, D.; Minor, A. M.; Martin, L. W.; Ramesh, R.] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
   [Yadav, A. K.; Vishwanath, A.; Minor, A. M.; Martin, L. W.; Ramesh, R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Nelson, C. T.; Hsu, S. L.; Clarkson, J. D.; Chen, D.; Vishwanath, A.; Ramesh, R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Nelson, C. T.; Hsu, S. L.; Minor, A. M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Ctr Electron Microscopy, Mol Foundry, Berkeley, CA 94720 USA.
   [Hong, Z.; Chen, L. Q.] Penn State Univ, Dept Mat Sci & Engn, State Coll, PA 16802 USA.
   [Schlepueetz, C. M.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Shafer, P.; Arenholz, E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Scott, J. F.] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
   [Scott, J. F.] Univ St Andrews, Sch Phys, St Andrews KY16 9ST, Fife, Scotland.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; United States Department of Energy (DOE); Argonne National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of St Andrews; University of St Andrews
RP Ramesh, R (corresponding author), Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
EM rramesh@berkeley.edu
FU Office of Basic Energy Sciences, US Department of Energy [DE-AC02-05CH11231]; National Science Foundation under the MRSEC program [DMR-1420620]; National Science Foundation [DMR-1210588, DMR-1451219]; US Department of Energy, Office of Science, Office of Basic Energy Science [DE-AC02-06CH11357]; Army Research Office [W911NF-14-1-0104]; Office of Science, Office of Basic Energy Sciences, US Department of Energy [DE-AC02-05CH11231]; US Department of Energy, Office of Basic Energy Sciences [DE-SC0012375]; EPSRC [EP/J017825/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/J017825/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Materials Research [1451219] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [1210588] Funding Source: National Science Foundation
NR 45
TC 882
Z9 993
U1 41
U2 1067
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 198
EP +
DI 10.1038/nature16463
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700034
PM 26814971
DA 2026-03-09
ER

PT J
AU Deglincerti, A
   Croft, GF
   Pietila, LN
   Zernicka-Goetz, M
   Siggia, ED
   Brivanlou, AH
AF Deglincerti, Alessia
   Croft, Gist F.
   Pietila, Lauren N.
   Zernicka-Goetz, Magdalena
   Siggia, Eric D.
   Brivanlou, Ali H.
TI Self-organization of the in vitro attached human embryo
SO NATURE
LA English
DT Article
ID human blastocyst; stem-cells; mouse; implantation
AB Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system(1,2) to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.
C1 [Deglincerti, Alessia; Croft, Gist F.; Pietila, Lauren N.; Brivanlou, Ali H.] Rockefeller Univ, Lab Stem Cell Biol & Mol Embryol, New York, NY 10065 USA.
   [Zernicka-Goetz, Magdalena] Univ Cambridge, Dept Physiol Dev & Neurosci, Physiol Bldg,Downing St, Cambridge CB2 3DY, England.
   [Siggia, Eric D.] Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10065 USA.
C3 Rockefeller University; University of Cambridge; Rockefeller University
RP Brivanlou, AH (corresponding author), Rockefeller Univ, Lab Stem Cell Biol & Mol Embryol, New York, NY 10065 USA.
EM brvnlou@rockefeller.edu
FU STARR Foundation [2013-026]; Rockefeller Private funds; Sohn Conference Foundation
NR 15
TC 534
Z9 609
U1 6
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 251
EP +
DI 10.1038/nature17948
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200051
PM 27144363
DA 2026-03-09
ER

PT J
AU Timmermann, A
   Friedrich, T
AF Timmermann, Axel
   Friedrich, Tobias
TI Late Pleistocene climate drivers of early human migration
SO NATURE
LA English
DT Article
ID sea-surface temperatures; central equatorial pacific; south china sea; western pacific; warm pool; california current; north-atlantic; current system; homo-sapiens; mg/ca ratios
AB On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between similar to 50-120 thousand years ago occurred in several orbitally paced migration episodes(1-4). Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect.
C1 [Timmermann, Axel; Friedrich, Tobias] Univ Hawaii Manoa, Int Pacific Res Ctr, Honolulu, HI 96822 USA.
   [Timmermann, Axel] Univ Hawaii Manoa, Dept Oceanog, Honolulu, HI 96822 USA.
C3 University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa
RP Timmermann, A (corresponding author), Univ Hawaii Manoa, Int Pacific Res Ctr, Honolulu, HI 96822 USA.; Timmermann, A (corresponding author), Univ Hawaii Manoa, Dept Oceanog, Honolulu, HI 96822 USA.
EM axel@hawaii.edu
FU US NSF [1341311, 1400914]; Directorate For Geosciences [1400914] Funding Source: National Science Foundation; Division Of Ocean Sciences [1400914] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1341311] Funding Source: National Science Foundation
NR 94
TC 247
Z9 284
U1 7
U2 268
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 92
EP +
DI 10.1038/nature19365
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900040
PM 27654920
DA 2026-03-09
ER

PT J
AU Nik-Zainal, S
   Davies, H
   Staaf, J
   Ramakrishna, M
   Dominik,
   Zou, XQ
   Martincorena, I
   Alexandrov, LB
   Martin, S
   Wedge, DC
   Van Loo, P
   Ju, YS
   Smid, M
   Brinkman, AB
   Morganella, S
   Aure, MR
   Lingjærde, OC
   Langerod, A
   Ringnér, M
   Ahn, SM
   Boyault, S
   Brock, JE
   Broeks, A
   Butler, A
   Desmedt, C
   Dirix, L
   Dronov, S
   Fatima, A
   Foekens, JA
   Gerstung, M
   Hooijer, GKJ
   Jang, SJ
   Jones, DR
   Kim, HY
   King, TA
   Krishnamurthy, S
   Lee, HJ
   Lee, JY
   Li, YL
   McLaren, S
   Menzies, A
   Mustonen, V
   O'Meara, S
   Pauporté, I
   Pivot, X
   Purdie, CA
   Raine, K
   Ramakrishnan, K
   Rodríguez-González, FG
   Romieu, G
   Sieuwerts, AM
   Simpson, PT
   Shepherd, R
   Stebbings, L
   Stefansson, OA
   Teague, J
   Tommasi, S
   Treilleux, I
   Van den Eynden, GG
   Vermeulen, P
   Vincent-Salomon, A
   Yates, L
   Caldas, C
   van't Veer, L
   Tutt, A
   Knappskog, S
   Tan, BKT
   Jonkers, J
   Borg, Å
   Ueno, NT
   Sotiriou, C
   Viari, A
   Futreal, PA
   Campbell, PJ
   Span, PN
   Van Laere, S
   Lakhani, SR
   Eyfjord, JE
   Thompson, AM
   Birney, E
   Stunnenberg, HG
   Van De Vijver, MJ
   Martens, JWM
   Borresen-Dale, AL
   Richardson, AL
   Kong, G
   Thomas, G
   Stratton, MR
AF Nik-Zainal, Serena
   Davies, Helen
   Staaf, Johan
   Ramakrishna, Manasa
   Glodzik, Dominik
   Zou, Xueqing
   Martincorena, Inigo
   Alexandrov, Ludmil B.
   Martin, Sancha
   Wedge, David C.
   Van Loo, Peter
   Ju, Young Seok
   Smid, Marcel
   Brinkman, Arie B.
   Morganella, Sandro
   Aure, Miriam R.
   Lingjaerde, Ole Christian
   Langerod, Anita
   Ringner, Markus
   Ahn, Sung-Min
   Boyault, Sandrine
   Brock, Jane E.
   Broeks, Annegien
   Butler, Adam
   Desmedt, Christine
   Dirix, Luc
   Dronov, Serge
   Fatima, Aquila
   Foekens, John A.
   Gerstung, Moritz
   Hooijer, Gerrit K. J.
   Jang, Se Jin
   Jones, David R.
   Kim, Hyung-Yong
   King, Tari A.
   Krishnamurthy, Savitri
   Lee, Hee Jin
   Lee, Jeong-Yeon
   Li, Yilong
   McLaren, Stuart
   Menzies, Andrew
   Mustonen, Ville
   O'Meara, Sarah
   Pauporte, Iris
   Pivot, Xavier
   Purdie, Colin A.
   Raine, Keiran
   Ramakrishnan, Kamna
   Rodriguez-Gonzalez, F. German
   Romieu, Gilles
   Sieuwerts, Anieta M.
   Simpson, Peter T.
   Shepherd, Rebecca
   Stebbings, Lucy
   Stefansson, Olafur A.
   Teague, Jon
   Tommasi, Stefania
   Treilleux, Isabelle
   Van den Eynden, Gert G.
   Vermeulen, Peter
   Vincent-Salomon, Anne
   Yates, Lucy
   Caldas, Carlos
   van't Veer, Laura
   Tutt, Andrew
   Knappskog, Stian
   Tan, Benita Kiat Tee
   Jonkers, Jos
   Borg, Ake
   Ueno, Naoto T.
   Sotiriou, Christos
   Viari, Alain
   Futreal, P. Andrew
   Campbell, Peter J.
   Span, Paul N.
   Van Laere, Steven
   Lakhani, Sunil R.
   Eyfjord, Jorunn E.
   Thompson, Alastair M.
   Birney, Ewan
   Stunnenberg, Hendrik G.
   van de Vijver, Marc J.
   Martens, John W. M.
   Borresen-Dale, Anne-Lise
   Richardson, Andrea L.
   Kong, Gu
   Thomas, Gilles
   Stratton, Michael R.
TI Landscape of somatic mutations in 560 breast cancer whole-genome sequences
SO NATURE
LA English
DT Article
ID tert promoter mutations; inverted repeats; gene fusions; copy number; dna-repair; signatures; tumors; carcinomas; discovery; heterozygosity
AB We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
C1 [Nik-Zainal, Serena; Davies, Helen; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Butler, Adam; Dronov, Serge; Gerstung, Moritz; Jones, David R.; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O'Meara, Sarah; Raine, Keiran; Ramakrishnan, Kamna; Shepherd, Rebecca; Stebbings, Lucy; Teague, Jon; Yates, Lucy; Futreal, P. Andrew; Campbell, Peter J.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Nik-Zainal, Serena] Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England.
   [Staaf, Johan; Ringner, Markus; Borg, Ake] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.
   [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Theoret Biol & Biophys T6, POB 1663, Los Alamos, NM 87545 USA.
   [Alexandrov, Ludmil B.] Los Alamos Natl Lab, Ctr Nonlinear Studies, POB 1663, Los Alamos, NM 87545 USA.
   [Van Loo, Peter] Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium.
   [Smid, Marcel; Foekens, John A.; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Martens, John W. M.] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CN Rotterdam, Netherlands.
   [Smid, Marcel; Foekens, John A.; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Martens, John W. M.] Erasmus Univ, Med Ctr, Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands.
   [Brinkman, Arie B.; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Fac Sci, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands.
   [Morganella, Sandro; Birney, Ewan] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
   [Aure, Miriam R.; Langerod, Anita; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, N-0310 Oslo, Norway.
   [Aure, Miriam R.; Lingjaerde, Ole Christian; Langerod, Anita; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway.
   [Lingjaerde, Ole Christian] Univ Oslo, Dept Comp Sci, Oslo, Norway.
   [Ahn, Sung-Min] Gachon Univ, Gil Med Ctr, Gachon Inst Genome Med & Sci, Inchon, South Korea.
   [Boyault, Sandrine] Ctr Leon Berard, Translat Res Lab, 28 Rue Laennec, F-69373 Lyon 08, France.
   [Brock, Jane E.; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
   [Broeks, Annegien; van't Veer, Laura; Jonkers, Jos] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Desmedt, Christine; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Bd Waterloo 121, B-1000 Brussels, Belgium.
   [Dirix, Luc; Van den Eynden, Gert G.; Vermeulen, Peter; Van Laere, Steven] Univ Antwerp, Fac Med & Hlth Sci, Oncol Res Ctr, Translat Canc Res Unit, B-2020 Antwerp, Belgium.
   [Fatima, Aquila; Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA.
   [Hooijer, Gerrit K. J.; van de Vijver, Marc J.] Univ Amsterdam, Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
   [Jang, Se Jin; Lee, Hee Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Ulsan 680749, South Korea.
   [Kim, Hyung-Yong; Kong, Gu] Hanyang Univ, Coll Med, Dept Pathol, Seoul 133791, South Korea.
   [King, Tari A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
   [Krishnamurthy, Savitri; Ueno, Naoto T.] Univ Texas MD Anderson Canc Ctr, Morgan Welch Inflammatory Breast Canc Res Program, 1515 Holcombe Boulevard, Houston, TX 77030 USA.
   [Lee, Jeong-Yeon] Hanyang Univ, IBBR, Seoul 133791, South Korea.
   [Pauporte, Iris] Natl Canc Inst, Div Res, Dept Clin Res, 52 Ave Morizet, F-92513 Boulogne, France.
   [Pivot, Xavier] Univ Hosp Minjoz, INSERM UMR 1098, Bd Fleming, F-25000 Besancon, France.
   [Purdie, Colin A.; Thompson, Alastair M.] Ninewells Hosp & Med Sch, Dept Pathol, Dundee DD1 9SY, Scotland.
   [Romieu, Gilles] ICM Inst Reg Canc, Oncol Senol, Montpellier, France.
   [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia.
   [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia.
   [Stefansson, Olafur A.; Eyfjord, Jorunn E.] Univ Iceland, Fac Med, Canc Res Lab, IS-101 Reykjavik, Iceland.
   [Tommasi, Stefania] IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy.
   [Treilleux, Isabelle] Ctr Leon Berard, Dept Pathol, 28 Rue Laennec, F-69373 Lyon 08, France.
   [Van den Eynden, Gert G.; Vermeulen, Peter] GZA Hosp Sint Augustinus, Dept Pathol, Antwerp, Belgium.
   [Vincent-Salomon, Anne] Paris Sci Lettres Univ, Inst Curie, Dept Pathol, 26 Rue Ulm, F-75248 Paris 05, France.
   [Vincent-Salomon, Anne] INSERM U934, 26 Rue Ulm, F-75248 Paris 05, France.
   [Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England.
   [Tutt, Andrew] Kings Coll London, Breast Canc Now Res Unit, London SE1 9RT, England.
   [Tutt, Andrew] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London SW3 6JB, England.
   [Knappskog, Stian] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway.
   [Knappskog, Stian] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway.
   [Tan, Benita Kiat Tee] Natl Canc Ctr Singapore, 11 Hosp Dr, Singapore 169610, Singapore.
   [Tan, Benita Kiat Tee] Singapore Gen Hosp, Outram Rd, Singapore 169608, Singapore.
   [Viari, Alain] INRIA Grenoble Rhone Alpes, Equipe Erable, 655 Ave Europe, F-38330 Montbonnot St Martin, France.
   [Viari, Alain; Thomas, Gilles] Ctr Leon Berard, Synergie Lyon Canc, 28 Rue Laennec, F-69373 Lyon 08, France.
   [Futreal, P. Andrew] UT MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77230 USA.
   [Span, Paul N.] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands.
   [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld 4029, Australia.
   [Thompson, Alastair M.] Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, 1400 Pressler St, Houston, TX 77030 USA.
C3 Wellcome Trust Sanger Institute; University of Cambridge; Lund University; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory; KU Leuven; Erasmus University Rotterdam; Erasmus MC; Erasmus MC Cancer Institute; Erasmus University Rotterdam; Erasmus MC; Radboud University Nijmegen; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Wellcome Trust Sanger Institute; University of Oslo; University of Oslo; University of Oslo; Gachon University; UNICANCER; Centre Leon Berard; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Netherlands Cancer Institute; Universite Libre de Bruxelles; Institut Jules Bordet; University of Antwerp; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Amsterdam; University of Ulsan; Asan Medical Center; Hanyang University; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Hanyang University; Institut National du Cancer (INCA) France; Universite Marie et Louis Pasteur; CHU Besancon; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Dundee; UNICANCER; Universite de Montpellier; Institut Regional du Cancer Montpellier / Val d'Aurelle (ICM); University of Queensland; University of Queensland; University of Iceland; IRCCS Istituto Tumori Bari Giovanni Paolo II; UNICANCER; Centre Leon Berard; UNICANCER; Universite PSL; Institut Curie; Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; University of London; King's College London; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; University of Bergen; University of Bergen; Haukeland University Hospital; National Cancer Centre Singapore (NCCS); Singapore General Hospital; UNICANCER; Centre Leon Berard; University of Texas System; UTMD Anderson Cancer Center; Radboud University Nijmegen; Royal Brisbane & Women's Hospital; University of Texas System; UTMD Anderson Cancer Center
RP Nik-Zainal, S; Stratton, MR (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.; Nik-Zainal, S (corresponding author), Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England.; Kong, G (corresponding author), Hanyang Univ, Coll Med, Dept Pathol, Seoul 133791, South Korea.; Viari, A (corresponding author), INRIA Grenoble Rhone Alpes, Equipe Erable, 655 Ave Europe, F-38330 Montbonnot St Martin, France.; Viari, A (corresponding author), Ctr Leon Berard, Synergie Lyon Canc, 28 Rue Laennec, F-69373 Lyon 08, France.
EM snz@sanger.ac.uk; Alain.Viari@inria.fr; gkong@hanyang.ac.kr; mrs@sanger.ac.uk
FU ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (BASIS), a European research project - European Community's Seventh Framework Programme [242006]; Triple Negative project - Wellcome Trust [077012/Z/05/Z]; HER2+ project - Institut National du Cancer (INCa) in France [226-2009, 02-2011, 41-2012, 144-2008, 06-2012]; Korean Health Technology R& D Project, Ministry of Health and Welfare, Republic of Korea [A111218-SC01]; BASIS; ICGC breast cancer projects; CRUK; University of Dundee; Chief Scientist Office; Breast Cancer Campaign; Wellcome Trust [WT100183MA]; Los Alamos National Laboratory; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer [NIH/NCI 5 P50 CA168504-02]; EU-FP7-SUPPRESSTEM project; Cancer Genomics Netherlands through a grant from the Netherlands Organisation of Scientific research (NWO); EU-FP7-DDR response project; Breast Cancer Research Foundation; EMBL; FNRS (Fonds National de la Recherche Scientifique); Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Republic Korea [NRF 2011-0030105]; National Research Foundation of Korea (NRF) - Korean government [NRF 2015R1A2A1A10052578]; ERC Advanced grant [322737]; US Department of Energy National Nuclear Security Administration [DE-AC52-06NA25396]; National Nuclear Security Administration of the United States Department of Energy; European Research Council (ERC) [322737] Funding Source: European Research Council (ERC); National Cancer Institute [P30CA008748, P50CA168504] Funding Source: NIH RePORTER; Cancer Research UK [16942, 20952] Funding Source: researchfish; National Institute for Health Research [NF-SI-0515-10090, NF-SI-0611-10154] Funding Source: researchfish; The Francis Crick Institute [10202] Funding Source: researchfish
NR 57
TC 1656
Z9 1908
U1 2
U2 295
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 47
EP +
DI 10.1038/nature17676
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300031
PM 27135926
DA 2026-03-09
ER

PT J
AU Chen, DL
   Blom, H
   Sanchez, S
   Tafforeau, P
   Ahlberg, PE
AF Chen, Donglei
   Blom, Henning
   Sanchez, Sophie
   Tafforeau, Paul
   Ahlberg, Per E.
TI The stem osteichthyan Andreolepis and the origin of tooth replacement
SO NATURE
LA English
DT Article
ID dental lamina; evolutionary origins; vertebrates; jaws; teeth; placoderm; scales; gnathostm; mechanisms; anatomy
AB The teeth of gnathostomes (jawed vertebrates) show rigidly patterned, unidirectional replacement that may or may not be associated with a shedding mechanism. These mechanisms, which are critical for the maintenance of the dentition, are incongruently distributed among extant gnathostomes. Although a permanent tooth-generating dental lamina is present in all chondrichthyans, many tetrapods and some teleosts, it is absent in the non-teleost actinopterygians. Tooth-shedding by basal hard tissue resorption occurs in most osteichthyans (including tetrapods) but not in chondrichthyans. Here we report a three-dimensional virtual dissection of the dentition of a 424-million-year-old stem osteichthyan, Andreolepis hedei, using propagation phase-contrast synchrotron microtomography, with a reconstruction of its growth history. Andreolepis, close to the common ancestor of all extant osteichthyans, shed its teeth by basal resorption but probably lacked a permanent dental lamina. This is the earliest documented instance of resorptive tooth shedding and may represent the primitive osteichthyan mode of tooth replacement.
C1 [Chen, Donglei; Blom, Henning] Uppsala Univ, Dept Organismal Biol, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Ahlberg, Per E.] Sci Life Lab, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Ahlberg, Per E.] Uppsala Univ, Dept Organismal Biol, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Tafforeau, Paul] European Synchrotron Radiat Facil, 6 Rue Jules Horowitz, F-38043 Grenoble, France.
C3 Uppsala University; Uppsala University; European Synchrotron Radiation Facility (ESRF)
RP Chen, DL (corresponding author), Uppsala Univ, Dept Organismal Biol, Norbyvagen 18A, SE-75236 Uppsala, Sweden.; Ahlberg, PE (corresponding author), Sci Life Lab, Norbyvagen 18A, SE-75236 Uppsala, Sweden.; Ahlberg, PE (corresponding author), Uppsala Univ, Dept Organismal Biol, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
EM donglei.chen@ebc.uu.se; per.ahlberg@ebc.uu.se
FU ERC [233111]; Knut and Alice Wallenberg Foundation; European Research Council (ERC) [233111] Funding Source: European Research Council (ERC)
NR 50
TC 45
Z9 50
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 237
EP +
DI 10.1038/nature19812
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500034
PM 27750278
DA 2026-03-09
ER

PT J
AU Stello, D
   Cantiello, M
   Fuller, J
   Huber, D
   García, RA
   Bedding, TR
   Bildsten, L
   Aguirre, VS
AF Stello, Dennis
   Cantiello, Matteo
   Fuller, Jim
   Huber, Daniel
   Garcia, Rafael A.
   Bedding, Timothy R.
   Bildsten, Lars
   Aguirre, Victor Silva
TI A prevalence of dynamo-generated magnetic fields in the cores of intermediate-mass stars
SO NATURE
LA English
DT Article
ID red giant stars; k-giants; kepler; modes; asteroseismology; branch
AB Magnetic fields play a part in almost all stages of stellar evolution(1). Most low-mass stars, including the Sun, show surface fields that are generated by dynamo processes in their convective envelopes(2,3). Intermediate-mass stars do not have deep convective envelopes(4), although 10 per cent exhibit strong surface fields that are presumed to be residuals from the star formation process(5). These stars do have convective cores that might produce internal magnetic fields(6), and these fields might survive into later stages of stellar evolution, but information has been limited by our inability to measure the fields below the stellar surface(7). Here we report the strength of dipolar oscillation modes for a sample of 3,600 red giant stars. About 20 per cent of our sample show mode suppression, by strong magnetic fields in the cores(8), but this fraction is a strong function of mass. Strong core fields occur only in red giants heavier than 1.1 solar masses, and the occurrence rate is at least 50 per cent for intermediate-mass stars (1.6-2.0 solar masses), indicating that powerful dynamos were very common in the previously convective cores of these stars.
C1 [Stello, Dennis; Huber, Daniel; Bedding, Timothy R.] Univ Sydney, Sch Phys, Sydney Inst Astron SIfA, Sydney, NSW 2006, Australia.
   [Stello, Dennis; Huber, Daniel; Bedding, Timothy R.; Aguirre, Victor Silva] Aarhus Univ, Dept Phys & Astron, Stellar Astrophys Ctr, DK-8000 Aarhus C, Denmark.
   [Cantiello, Matteo; Fuller, Jim; Bildsten, Lars] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Fuller, Jim] CALTECH, Walter Burke Inst Theoret Phys, TAPIR, Pasadena, CA 91125 USA.
   [Huber, Daniel] SETI Inst, Mountain View, CA 94043 USA.
   [Garcia, Rafael A.] Univ Paris Diderot, IRFU, SAp Ctr Saclay, Lab AIM,CEA,DSM,CNRS, F-91191 Gif Sur Yvette, France.
   [Bildsten, Lars] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
C3 University of Sydney; Aarhus University; University of California System; University of California Santa Barbara; California Institute of Technology; SETI Institute; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of California System; University of California Santa Barbara
RP Stello, D (corresponding author), Univ Sydney, Sch Phys, Sydney Inst Astron SIfA, Sydney, NSW 2006, Australia.
EM stello@physics.usyd.edu.au
FU Australian Research Council Future Fellowship [FT140100147]; NSF [AST-1205732, PHY11-25915, AST11-09174]; Lee DuBridge Fellowship at Caltech; European Community's Seventh Framework Programme [269194]; CNES; IDEE [ANR-12-BS05-0008]; Australian Research Council's Discovery Projects [DE140101364]; National Aeronautics and Space Administration through the Kepler Participating Scientist Program [NNX14AB92G]; NASA under TCAN [NNX14AB53G]; Danish National Research Foundation [DNRF106]; ASTERISK project (ASTERoseismic Investigations with SONG and Kepler) - the European Research Council [267864]; Villum Fonden [00010118] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109174] Funding Source: National Science Foundation; Australian Research Council [FT140100147] Funding Source: Australian Research Council
NR 30
TC 133
Z9 141
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 364
EP +
DI 10.1038/nature16171
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800039
PM 26727160
DA 2026-03-09
ER

PT J
AU Bromham, L
   Dinnage, R
   Hua, X
AF Bromham, Lindell
   Dinnage, Russell
   Hua, Xia
TI Interdisciplinary research has consistently lower funding success
SO NATURE
LA English
DT Article
ID science; impact; diversity; metrics
AB Interdisciplinary research is widely considered a hothouse for innovation, and the only plausible approach to complex problems such as climate change(1,2). One barrier to interdisciplinary research is the widespread perception that interdisciplinary projects are less likely to be funded than those with a narrower focus(3,4). However, this commonly held belief has been difficult to evaluate objectively, partly because of lack of a comparable, quantitative measure of degree of interdisciplinarity that can be applied to funding application data(1). Here we compare the degree to which research proposals span disparate fields by using a biodiversity metric that captures the relative representation of different fields (balance) and their degree of difference (disparity). The Australian Research Council's Discovery Programme provides an ideal test case, because a single annual nationwide competitive grants scheme covers fundamental research in all disciplines, including arts, humanities and sciences. Using data on all 18,476 proposals submitted to the scheme over 5 consecutive years, including successful and unsuccessful applications, we show that the greater the degree of interdisciplinarity, the lower the probability of being funded. The negative impact of interdisciplinarity is significant even when number of collaborators, primary research field and type of institution are taken into account. This is the first broad-scale quantitative assessment of success rates of interdisciplinary research proposals. The interdisciplinary distance metric allows efficient evaluation of trends in research funding, and could be used to identify proposals that require assessment strategies appropriate to interdisciplinary research(5).
C1 [Bromham, Lindell; Dinnage, Russell; Hua, Xia] Australian Natl Univ, Res Sch Biol, 116 Daley Rd, Canberra, ACT 0200, Australia.
C3 Australian National University
RP Bromham, L (corresponding author), Australian Natl Univ, Res Sch Biol, 116 Daley Rd, Canberra, ACT 0200, Australia.
EM lindell.bromham@anu.edu.au
NR 27
TC 400
Z9 483
U1 26
U2 443
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 684
EP +
DI 10.1038/nature18315
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000036
PM 27357795
DA 2026-03-09
ER

PT J
AU Rentas, S
   Holzapfel, NT
   Belew, MS
   Pratt, GA
   Voisin, V
   Wilhelm, BT
   Bader, GD
   Yeo, GW
   Hope, KJ
AF Rentas, Stefan
   Holzapfel, Nicholas T.
   Belew, Muluken S.
   Pratt, Gabriel A.
   Voisin, Veronique
   Wilhelm, Brian T.
   Bader, Gary D.
   Yeo, Gene W.
   Hope, Kristin J.
TI Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells
SO NATURE
LA English
DT Article
ID cord blood; expression profiles; genomic features; chip-seq; rna; populations; regulator; mice; ultrafast; datasets
AB Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers(1). Small molecules that enhance haematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified(2,3), but in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular circuitry that underpins the selfrenewal of human HSCs will facilitate the development of targeted strategies that expand HSCs for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs4,5, the posttranscriptional mechanisms that guide HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we show that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood HSPCs. Our study gives mechanistic insight into RNA networks controlled by RNA-binding proteins that underlie self-renewal and provides evidence that manipulating such networks ex vivo can enhance the regenerative potential of human HSCs.
C1 [Rentas, Stefan; Holzapfel, Nicholas T.; Belew, Muluken S.; Hope, Kristin J.] McMaster Univ, Dept Biochem & Biomed Sci, Stem Cell & Canc Res Inst, Hamilton, ON L8S 4K1, Canada.
   [Pratt, Gabriel A.; Yeo, Gene W.] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.
   [Pratt, Gabriel A.; Yeo, Gene W.] Univ Calif San Diego, Bioinformat Grad Program, La Jolla, CA 92037 USA.
   [Voisin, Veronique; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Wilhelm, Brian T.] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
   [Yeo, Gene W.] Natl Univ Singapore, Dept Physiol, Singapore 138632, Singapore.
   [Yeo, Gene W.] ASTAR, Mol Engn Lab, Singapore 138632, Singapore.
C3 McMaster University; University of California System; University of California San Diego; University of California System; University of California San Diego; University of Toronto; Universite de Montreal; National University of Singapore; Agency for Science Technology & Research (A*STAR)
RP Hope, KJ (corresponding author), McMaster Univ, Dept Biochem & Biomed Sci, Stem Cell & Canc Res Inst, Hamilton, ON L8S 4K1, Canada.; Yeo, GW (corresponding author), Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.; Yeo, GW (corresponding author), Univ Calif San Diego, Bioinformat Grad Program, La Jolla, CA 92037 USA.; Yeo, GW (corresponding author), Natl Univ Singapore, Dept Physiol, Singapore 138632, Singapore.; Yeo, GW (corresponding author), ASTAR, Mol Engn Lab, Singapore 138632, Singapore.
EM geneyeo@ucsd.edu; kristin@mcmaster.ca
FU Ontario Institute for Cancer Research New Investigator Award [IA-033]; Ontario Institute for Cancer Research Cancer Stem Cell Program Team Grant [P.CSC.005]; Canadian Institutes of Health Research [MOP-126030]; CIHR MD/PhD Studentship; NSERC Alexander Graham Bell Doctoral Fellowship; Canadian Blood Services Graduate Fellowship; Health Canada; National Institute of Health [HG004659, NS075449]; California Institute of Regenerative Medicine [RB3-05219]; National Science Graduate Fellowship; National Human Genome Research Institute [R01HG004659] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103504] Funding Source: NIH RePORTER
NR 37
TC 98
Z9 122
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 508
EP +
DI 10.1038/nature17665
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900049
PM 27121842
DA 2026-03-09
ER

PT J
AU Chen, CC
   Fu, LJ
   Maier, J
AF Chen, Chia-Chin
   Fu, Lijun
   Maier, Joachim
TI Synergistic, ultrafast mass storage and removal in artificial mixed conductors
SO NATURE
LA English
DT Article
ID chemical diffusion-coefficient; solid-electrolyte; oxygen nonstoichiometry; transport; temperature; chemistry; graphite; charge; defect; conductivity
AB Mixed conductors-single phases that conduct electronically and ionically-enable stoichiometric variations in a material and, therefore, mass storage and redistribution, for example, in battery electrodes. We have considered how such properties may be achieved synergistically in solid two-phase systems, forming artificial mixed conductors. Previously investigated composites suffered from poor kinetics and did not allow for a clear determination of such stoichiometric variations. Here we show, using electrochemical and chemical methods, that a melt-processed composite of the 'super-ionic' conductor RbAg4I5 and the electronic conductor graphite exhibits both a remarkable silver excess and a silver deficiency, similar to those found in single-phase mixed conductors, even though such behaviour is not possible in the individual phases. Furthermore, the kinetics of silver uptake and release is very fast. Evaluating the upper limit set by interfacial ambipolar diffusion reveals chemical diffusion coefficients that are even higher than those achieved for sodium chloride in bulk liquid water. These results could potentially stimulate systematic research into powerful, even mesoscopic, artificial mixed conductors.
C1 [Chen, Chia-Chin; Fu, Lijun; Maier, Joachim] Max Planck Inst Solid State Res, Heisenbergstr 1, D-70569 Stuttgart, Germany.
C3 Max Planck Society
RP Maier, J (corresponding author), Max Planck Inst Solid State Res, Heisenbergstr 1, D-70569 Stuttgart, Germany.
EM s.weiglein@fkf.mpg.de
NR 52
TC 128
Z9 136
U1 6
U2 297
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 159
EP +
DI 10.1038/nature19078
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100026
PM 27510217
DA 2026-03-09
ER

PT J
AU Tsai, HH
   Nie, WY
   Blancon, JC
   Toumpos, CCS
   Asadpour, R
   Harutyunyan, B
   Neukirch, AJ
   Verduzco, R
   Crochet, JJ
   Tretiak, S
   Pedesseau, L
   Even, J
   Alam, MA
   Gupta, G
   Lou, J
   Ajayan, PM
   Bedzyk, MJ
   Kanatzidis, MG
   Mohite, AD
AF Tsai, Hsinhan
   Nie, Wanyi
   Blancon, Jean-Christophe
   Toumpos, Constantinos C. S.
   Asadpour, Reza
   Harutyunyan, Boris
   Neukirch, Amanda J.
   Verduzco, Rafael
   Crochet, Jared J.
   Tretiak, Sergei
   Pedesseau, Laurent
   Even, Jacky
   Alam, Muhammad A.
   Gupta, Gautam
   Lou, Jun
   Ajayan, Pulickel M.
   Bedzyk, Michael J.
   Kanatzidis, Mercouri G.
   Mohite, Aditya D.
TI High-efficiency two-dimensional Ruddlesden-Popper perovskite solar cells
SO NATURE
LA English
DT Article
ID stability; performance; hysteresis; absorber
AB Three-dimensional organic-inorganic perovskites have emerged as one of the most promising thin-film solar cell materials owing to their remarkable photophysical properties(1-5), which have led to power conversion efficiencies exceeding 20 per cent(6,7), with the prospect of further improvements towards the Shockley-Queisser limit for a single-junction solar cell (33.5 per cent) (8). Besides efficiency, another critical factor for photovoltaics and other optoelectronic applications is environmental stability and photostability under operating conditions(9-15). In contrast to their three-dimensional counterparts, Ruddlesden-Popper phases-layered two-dimensional perovskite films-have shown promising stability, but poor efficiency at only 4.73 per cent(13,16,17). This relatively poor efficiency is attributed to the inhibition of out-of-plane charge transport by the organic cations, which act like insulating spacing layers between the conducting inorganic slabs. Here we overcome this issue in layered perovskites by producing thin films of near-single-crystalline quality, in which the crystallographic planes of the inorganic perovskite component have a strongly preferential out-of-plane alignment with respect to the contacts in planar solar cells to facilitate efficient charge transport. We report a photovoltaic efficiency of 12.52 per cent with no hysteresis, and the devices exhibit greatly improved stability in comparison to their three-dimensional counterparts when subjected to light, humidity and heat stress tests. Unencapsulated two-dimensional perovskite devices retain over 60 per cent of their efficiency for over 2,250 hours under constant, standard (AM1.5G) illumination, and exhibit greater tolerance to 65 per cent relative humidity than do three-dimensional equivalents. When the devices are encapsulated, the layered devices do not show any degradation under constant AM1.5G illumination or humidity. We anticipate that these results will lead to the growth of single-crystalline, solution-processed, layered, hybrid, perovskite thin films, which are essential for high-performance opto-electronic devices with technologically relevant long-term stability.
C1 [Tsai, Hsinhan; Nie, Wanyi; Blancon, Jean-Christophe; Neukirch, Amanda J.; Crochet, Jared J.; Tretiak, Sergei; Gupta, Gautam; Mohite, Aditya D.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Tsai, Hsinhan; Verduzco, Rafael; Lou, Jun; Ajayan, Pulickel M.] Rice Univ, Dept Mat Sci & Nanoengn, Houston, TX 77005 USA.
   [Toumpos, Constantinos C. S.; Kanatzidis, Mercouri G.] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
   [Toumpos, Constantinos C. S.; Harutyunyan, Boris; Bedzyk, Michael J.; Kanatzidis, Mercouri G.] Northwestern Univ, Dept Mat Sci, Evanston, IL 60208 USA.
   [Toumpos, Constantinos C. S.; Harutyunyan, Boris; Bedzyk, Michael J.; Kanatzidis, Mercouri G.] Northwestern Univ, Engn & Argonne Northwestern Solar Energy Res ANSE, Evanston, IL 60208 USA.
   [Asadpour, Reza; Alam, Muhammad A.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
   [Verduzco, Rafael] Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77005 USA.
   [Pedesseau, Laurent; Even, Jacky] INSA Rennes, CNRS, UMR 6082, Fonct Opt Technol Informat,FOTON, F-35708 Rennes, France.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; Rice University; Northwestern University; Northwestern University; Northwestern University; Purdue University System; Purdue University; Rice University; Universite de Rennes; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Institut National des Sciences Appliquees de Rennes
RP Mohite, AD (corresponding author), Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
EM amohite@lanl.gov
FU ANSER Center, an Energy Frontier Research Center - US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-SC0001059]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; French national centres (GENCI/CINES/IDRIS grant) [2015-c2012096724]; Cellule Energie du CNRS (SOLHYBTRANS Project); University of Rennes 1 (Action Incitative, Defis Scientifique Emergents); Fondation d'entreprises banque Populaire de l'Ouest; Bay Area PV Consortium (a Department of Energy project with Prime Award) [DE-EE0004946]; NSF [DMR-1352099]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1352099] Funding Source: National Science Foundation
NR 36
TC 3032
Z9 3320
U1 44
U2 3078
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 312
EP +
DI 10.1038/nature18306
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900031
PM 27383783
DA 2026-03-09
ER

PT J
AU Sutikna, T
   Tocheri, MW
   Morwood, MJ
   Saptomo, EW
   Jatmiko
   Awe, RD
   Wasisto, S
   Westaway, KE
   Aubert, M
   Li, B
   Zhao, JX
   Storey, M
   Alloway, BV
   Morley, MW
   Meijer, HJM
   van den Bergh, GD
   Grün, R
   Dosseto, A
   Brumm, A
   Jungers, WL
   Roberts, RG
AF Sutikna, Thomas
   Tocheri, Matthew W.
   Morwood, Michael J.
   Saptomo, E. Wahyu
   Jatmiko
   Awe, Rokus Due
   Wasisto, Sri
   Westaway, Kira E.
   Aubert, Maxime
   Li, Bo
   Zhao, Jian-xin
   Storey, Michael
   Alloway, Brent V.
   Morley, Mike W.
   Meijer, Hanneke J. M.
   van den Bergh, Gerrit D.
   Gruen, Rainer
   Dosseto, Anthony
   Brumm, Adam
   Jungers, William L.
   Roberts, Richard G.
TI Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia
SO NATURE
LA English
DT Article
ID late pleistocene; human occupation; northern australia; southeast-asia; hominin; luminescence; feldspar; age; archaeology; site
C1 [Sutikna, Thomas; Morwood, Michael J.; Saptomo, E. Wahyu; Jatmiko; Awe, Rokus Due; Li, Bo; Alloway, Brent V.; Morley, Mike W.; van den Bergh, Gerrit D.; Roberts, Richard G.] Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [Sutikna, Thomas; Saptomo, E. Wahyu; Jatmiko; Awe, Rokus Due; Wasisto, Sri] Pusat Penelitian Arkeol Nas, Jakarta 12510, Indonesia.
   [Tocheri, Matthew W.] Lakehead Univ, Dept Anthropol, Thunder Bay, ON P7B 5E1, Canada.
   [Tocheri, Matthew W.; Meijer, Hanneke J. M.] Smithsonian Inst, Dept Anthropol, Human Origins Program, Natl Museum Nat Hist, Washington, DC 20013 USA.
   [Westaway, Kira E.] Macquarie Univ, Dept Environm Sci, Traps MQ Luminescence Dating Facil, Sydney, NSW 2109, Australia.
   [Aubert, Maxime] Griffith Univ, Pl Evolut & Rock Art Heritage Unit, Res Ctr Human Evolut, Gold Coast, Qld 4222, Australia.
   [Aubert, Maxime; Brumm, Adam] Univ Wollongong, Sch Earth & Environm Sci, Wollongong, NSW 2522, Australia.
   [Zhao, Jian-xin] Univ Queensland, Sch Earth Sci, Brisbane, Qld 4072, Australia.
   [Storey, Michael] Nat Hist Museum Denmark, Sect Earth & Planetary Syst Sci, QUADLAB, DK-1350 Copenhagen, Denmark.
   [Alloway, Brent V.] Victoria Univ Wellington, Sch Geog Environm & Earth Sci, Wellington 6012, New Zealand.
   [Meijer, Hanneke J. M.] Univ Bergen, Univ Museum Bergen, Dept Nat Hist, N-5007 Bergen, Norway.
   [Gruen, Rainer; Brumm, Adam] Griffith Univ, Environm Futures Res Inst, Res Ctr Human Evolut, Brisbane, Qld 4111, Australia.
   [Gruen, Rainer] Australian Natl Univ, Res Sch Earth Sci, GPO Box 4, Canberra, ACT 0200, Australia.
   [Dosseto, Anthony] Univ Wollongong, Sch Earth & Environm Sci, GeoQuEST Res Ctr, Wollongong, NSW 2522, Australia.
   [Jungers, William L.] SUNY Stony Brook, Med Ctr, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Jungers, William L.] Assoc Vahatra, BP 3972, Antananarivo 101, Madagascar.
C3 University of Wollongong; Lakehead University; Smithsonian Institution; Smithsonian National Museum of Natural History; Macquarie University; Griffith University; University of Wollongong; University of Queensland; Victoria University Wellington; University of Bergen; Griffith University; Australian National University; University of Wollongong; State University of New York (SUNY) System; Stony Brook University
RP Sutikna, T; Roberts, RG (corresponding author), Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.; Sutikna, T (corresponding author), Pusat Penelitian Arkeol Nas, Jakarta 12510, Indonesia.; Tocheri, MW (corresponding author), Lakehead Univ, Dept Anthropol, Thunder Bay, ON P7B 5E1, Canada.; Tocheri, MW (corresponding author), Smithsonian Inst, Dept Anthropol, Human Origins Program, Natl Museum Nat Hist, Washington, DC 20013 USA.
EM thomasutikna@gmail.com; tocherim@gmail.com; rgrob@uow.edu.au
FU Australian Research Council (ARC) [DP0770234]; Waitt Foundation/National Geographic Society [2121-2]; Smithsonian Scholarly Studies Program; Peter Buck Fund for Human Origins Research; Smithsonian's Human Origins Program; University of Wollongong (UOW); ARC [DP1093049, DE140100254, DE130101560, FT14010038]; UOW postgraduate scholarship; Canada Research Chair; ARC Australian Laureate Fellowship [FL130100116]; Victoria University of Wellington Science Faculty Research Grant [201255]; Villum Foundation; Australian Research Council [DE130101560, DP0770234, DE140100254] Funding Source: Australian Research Council; Villum Fonden [00007408] Funding Source: researchfish
NR 63
TC 198
Z9 231
U1 2
U2 167
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 366
EP +
DI 10.1038/nature17179
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700031
PM 27027286
DA 2026-03-09
ER

PT J
AU Dilley, RL
   Verma, P
   Cho, NW
   Winters, HD
   Wondisford, AR
   Greenberg, RA
AF Dilley, Robert L.
   Verma, Priyanka
   Cho, Nam Woo
   Winters, Harrison D.
   Wondisford, Anne R.
   Greenberg, Roger A.
TI Break-induced telomere synthesis underlies alternative telomere maintenance
SO NATURE
LA English
DT Article
ID dna-polymerase-delta; induced replication; human-cells; accessory subunits; repair; yeast; recombination; pathway; absence; pcna
AB Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance. DNA double-strand breaks enact nascent telomere synthesis by long-tract unidirectional replication. Proliferating cell nuclear antigen (PCNA) loading by replication factor C (RFC) acts as the initial sensor of telomere damage to establish predominance of DNA polymerase delta (Pol delta) through its POLD3 subunit. Break-induced telomere synthesis requires the RFC-PCNA-Pol delta axis, but is independent of other canonical replisome components, ATM and ATR, or the homologous recombination protein Rad51. Thus, the inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomere maintenance.
C1 [Dilley, Robert L.; Verma, Priyanka; Cho, Nam Woo; Winters, Harrison D.; Wondisford, Anne R.; Greenberg, Roger A.] Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Canc Biol, 421 Curie Blvd, Philadelphia, PA 19104 USA.
   [Greenberg, Roger A.] Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Pathol, 421 Curie Blvd, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania
RP Greenberg, RA (corresponding author), Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Canc Biol, 421 Curie Blvd, Philadelphia, PA 19104 USA.; Greenberg, RA (corresponding author), Univ Penn, Perelman Sch Med, Basser Res Ctr BRCA, Abramson Family Canc Res Inst,Dept Pathol, 421 Curie Blvd, Philadelphia, PA 19104 USA.
EM rogergr@mail.med.upenn.edu
FU NIH [GM101149, CA138835, CA17494, T32GM007170, T32GM008216]; Abramson Family Cancer Research Institute; Basser Research Center for BRCA; National Cancer Institute [R01CA138835, R01CA174904] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008216, T32GM007170, R01GM101149] Funding Source: NIH RePORTER
NR 36
TC 342
Z9 402
U1 2
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 54
EP +
DI 10.1038/nature20099
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100027
PM 27760120
DA 2026-03-09
ER

PT J
AU Alsbaiee, A
   Smith, BJ
   Xiao, LL
   Ling, YH
   Helbling, DE
   Dichtel, WR
AF Alsbaiee, Alaaeddin
   Smith, Brian J.
   Xiao, Leilei
   Ling, Yuhan
   Helbling, Damian E.
   Dichtel, William R.
TI Rapid removal of organic micropollutants from water by a porous β-cyclodextrin polymer
SO NATURE
LA English
DT Article
ID personal care products; waste-water; bisphenol-a; emerging contaminants; adsorption; pharmaceuticals; pesticides; exposure; chitosan; surface
AB The global occurrence in water resources of organic micropollutants, such as pesticides and pharmaceuticals, has raised concerns about potential negative effects on aquatic ecosystems and human health(1-5). Activated carbons are the most widespread adsorbent materials used to remove organic pollutants from water but they have several deficiencies, including slow pollutant uptake (of the order of hours)(6,7) and poor removal of many relatively hydrophilic micropollutants(8). Furthermore, regenerating spent activated carbon is energy intensive (requiring heating to 500-900 degrees Celsius) and does not fully restore performance(9,10). Insoluble polymers of beta-cyclodextrin, an inexpensive, sustainably produced macrocycle of glucose, are likewise of interest for removing micropollutants from water by means of adsorption(11). beta-cyclodextrin is known to encapsulate pollutants to form well-defined host-guest complexes, but until now cross-linked beta-cyclodextrin polymers have had low surface areas and poor removal performance compared to conventional activated carbons(11-13). Here we crosslink beta-cyclodextrin with rigid aromatic groups, providing a high-surface-area, mesoporous polymer of beta-cyclodextrin. It rapidly sequesters a variety of organic micropollutants with adsorption rate constants 15 to 200 times greater than those of activated carbons and non-porous beta-cyclodextrin adsorbent materials(7,8,11-13). In addition, the polymer can be regenerated several times using a mild washing procedure with no loss in performance. Finally, the polymer outperformed a leading activated carbon for the rapid removal of a complex mixture of organic micropollutants at environmentally relevant concentrations. These findings demonstrate the promise of porous cyclodextrin-based polymers for rapid, flow-through water treatment.
C1 [Alsbaiee, Alaaeddin; Smith, Brian J.; Xiao, Leilei; Dichtel, William R.] Cornell Univ, Dept Chem & Chem Biol, Baker Lab, Ithaca, NY 14853 USA.
   [Ling, Yuhan; Helbling, Damian E.] Cornell Univ, Sch Civil & Environm Engn, Ithaca, NY 14853 USA.
C3 Cornell University; Cornell University
RP Dichtel, WR (corresponding author), Cornell Univ, Dept Chem & Chem Biol, Baker Lab, Ithaca, NY 14853 USA.
EM damian.helbling@cornell.edu; wdichtel@cornell.edu
FU National Science Foundation (NSF) through Center for Sustainable Polymers [CHE-1413862]; NSF [DMR-1120296]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1413862] Funding Source: National Science Foundation
NR 35
TC 1564
Z9 1736
U1 79
U2 3654
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 190
EP U146
DI 10.1038/nature16185
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700032
PM 26689365
DA 2026-03-09
ER

PT J
AU Sousa, CM
   Biancur, DE
   Wang, XX
   Halbrook, CJ
   Sherman, MH
   Zhang, L
   Kremer, D
   Hwang, RF
   Witkiewicz, AK
   Ying, HQ
   Asara, JM
   Evans, RM
   Cantley, LC
   Lyssiotis, CA
   Kimmelman, AC
AF Sousa, Cristovao M.
   Biancur, Douglas E.
   Wang, Xiaoxu
   Halbrook, Christopher J.
   Sherman, Mara H.
   Zhang, Li
   Kremer, Daniel
   Hwang, Rosa F.
   Witkiewicz, Agnes K.
   Ying, Haoqiang
   Asara, John M.
   Evans, Ronald M.
   Cantley, Lewis C.
   Lyssiotis, Costas A.
   Kimmelman, Alec C.
TI Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion
SO NATURE
LA English
DT Article
ID cancer; fibroblasts; growth; progression; protein
AB Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism(1-4). The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context(5-10). The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment(4,11,12). As such, these tumours must alter how they capture and use nutrients to support their metabolic needs(11,13). Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour's dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment(4,11). Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.
C1 [Sousa, Cristovao M.; Biancur, Douglas E.; Wang, Xiaoxu; Kimmelman, Alec C.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA.
   [Halbrook, Christopher J.; Zhang, Li; Kremer, Daniel; Lyssiotis, Costas A.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
   [Sherman, Mara H.; Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA.
   [Hwang, Rosa F.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA.
   [Witkiewicz, Agnes K.] UT Southwestern, Dept Pathol, Dallas, TX 75390 USA.
   [Witkiewicz, Agnes K.] UT Southwestern, Simmons Canc Ctr, Dallas, TX 75390 USA.
   [Ying, Haoqiang] UT MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Asara, John M.] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02115 USA.
   [Asara, John M.] Harvard Med Sch, Boston, MA 02115 USA.
   [Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, Meyer Canc Ctr, New York, NY 10065 USA.
   [Lyssiotis, Costas A.] Univ Michigan, Sch Med, Div Gastroenterol, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Kimmelman, Alec C.] NYU, Langone Med Ctr, Perlmutter Canc Ctr, Dept Radiat Oncol, New York, NY 10016 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; University of Michigan System; University of Michigan; Salk Institute; Howard Hughes Medical Institute; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Cornell University; Weill Cornell Medicine; University of Michigan System; University of Michigan; New York University; NYU Langone Medical Center
RP Kimmelman, AC (corresponding author), Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA.; Lyssiotis, CA (corresponding author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.; Lyssiotis, CA (corresponding author), Univ Michigan, Sch Med, Div Gastroenterol, Dept Internal Med, Ann Arbor, MI 48109 USA.; Kimmelman, AC (corresponding author), NYU, Langone Med Ctr, Perlmutter Canc Ctr, Dept Radiat Oncol, New York, NY 10016 USA.
EM clyssiot@med.umich.edu; alec.kimmelman@nyumc.org
FU NIH [5P30CA06516, GM095567, DK097153]; NCI [R01CA157490, R01CA188048]; ACS [RSG-13-298-01-TBG]; Lustgarten Foundation; PanCAN-AACRPathway to Leadership award; Dale F. Frey award from Damon Runyon Cancer Research Foundation [DFS-09-14]; PanCAN-AACR; Stand Up to Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation [SU2C-AACR-DT0509];  [P01CA117969];  [P30CA006516];  [P01CA120964]; National Cancer Institute [P01CA120964, P30CA046592, P30CA014195, P30CA006516, P01CA117969, T32CA009370] Funding Source: NIH RePORTER
NR 29
TC 888
Z9 1025
U1 2
U2 266
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 479
EP +
DI 10.1038/nature19084
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600046
PM 27509858
DA 2026-03-09
ER

PT J
AU Poorter, L
   Bongers, F
   Aide, TM
   Almeyda Zambrano, AM
   Balvanera, P
   Becknell, JM
   Boukili, V
   Brancalion, PHS
   Broadbent, EN
   Chazdon, RL
   Craven, D
   de Almeida-Cortez, JS
   Cabral, GAL
   de Jong, BHJ
   Denslow, JS
   Dent, DH
   DeWalt, SJ
   Dupuy, JM
   Durán, SM
   Espírito-Santo, MM
   Fandino, MC
   César, RG
   Hall, JS
   Hernandez-Stefanoni, JL
   Jakovac, CC
   Junqueira, AB
   Kennard, D
   Letcher, SG
   Licona, JC
   Lohbeck, M
   Marin-Spiotta, E
   Martínez-Ramos, M
   Massoca, P
   Meave, JA
   Mesquita, R
   Mora, F
   Muñoz, R
   Muscarella, R
   Nunes, YRF
   Ochoa-Gaona, S
   de Oliveira, AA
   Orihuela-Belmonte, E
   Peña-Claros, M
   Pérez-García, EA
   Piotto, D
   Powers, JS
   Rodríguez-Velázquez, J
   Romero-Pérez, IE
   Ruíz, J
   Saldarriaga, JG
   Sanchez-Azofeifa, A
   Schwartz, NB
   Steininger, MK
   Swenson, NG
   Toledo, M
   Uriarte, M
   van Breugel, M
   van der Wal, H
   Veloso, MDM
   Vester, HFM
   Vicentini, A
   Vieira, ICG
   Bentos, TV
   Williamson, GB
   Rozendaal, DMA
AF Poorter, Lourens
   Bongers, Frans
   Aide, T. Mitchell
   Almeyda Zambrano, Angelica M.
   Balvanera, Patricia
   Becknell, Justin M.
   Boukili, Vanessa
   Brancalion, Pedro H. S.
   Broadbent, Eben N.
   Chazdon, Robin L.
   Craven, Dylan
   de Almeida-Cortez, Jarcilene S.
   Cabral, George A. L.
   de Jong, Ben H. J.
   Denslow, Julie S.
   Dent, Daisy H.
   DeWalt, Saara J.
   Dupuy, Juan M.
   Duran, Sandra M.
   Espirito-Santo, Mario M.
   Fandino, Maria C.
   Cesar, Ricardo G.
   Hall, Jefferson S.
   Hernandez-Stefanoni, Jose Luis
   Jakovac, Catarina C.
   Junqueira, Andre B.
   Kennard, Deborah
   Letcher, Susan G.
   Licona, Juan-Carlos
   Lohbeck, Madelon
   Marin-Spiotta, Erika
   Martinez-Ramos, Miguel
   Massoca, Paulo
   Meave, Jorge A.
   Mesquita, Rita
   Mora, Francisco
   Munoz, Rodrigo
   Muscarella, Robert
   Nunes, Yule R. F.
   Ochoa-Gaona, Susana
   de Oliveira, Alexandre A. .
   Orihuela-Belmonte, Edith
   Pena-Claros, Marielos
   Perez-Garcia, Eduardo A. .
   Piotto, Daniel
   Powers, Jennifer S.
   Rodriguez-Velazquez, Jorge
   Romero-Perez, I. Eunice
   Ruiz, Jorge
   Saldarriaga, Juan G.
   Sanchez-Azofeifa, Arturo
   Schwartz, Naomi B.
   Steininger, Marc K.
   Swenson, Nathan G.
   Toledo, Marisol
   Uriarte, Maria
   van Breugel, Michiel
   van der Wal, Hans
   Veloso, Maria D. M.
   Vester, Hans F. M.
   Vicentini, Alberto
   Vieira, Ima C. G.
   Bentos, Tony Vizcarra
   Williamson, G. Bruce
   Rozendaal, Danae M. A.
TI Biomass resilience of Neotropical secondary forests
SO NATURE
LA English
DT Article
ID tropical dry forest; aboveground biomass; carbon stocks; species composition; stand age; land-use; tree; chronosequence; succession; patterns
AB Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle(1). However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use(2-4). Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold ( from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.
C1 [Poorter, Lourens; Bongers, Frans; Jakovac, Catarina C.; Lohbeck, Madelon; Pena-Claros, Marielos] Wageningen Univ, Forest Ecol & Forest Management Grp, POB 47, NL-6700 AA Wageningen, Netherlands.
   [Aide, T. Mitchell] Univ Puerto Rico, Dept Biol, San Juan, PR 00931 USA.
   [Almeyda Zambrano, Angelica M.; Broadbent, Eben N.] Univ Alabama, Dept Geog, Spatial Ecol & Conservat Lab, Tuscaloosa, AL 35487 USA.
   [Balvanera, Patricia; Martinez-Ramos, Miguel; Mora, Francisco; Rodriguez-Velazquez, Jorge] Univ Nacl Autonoma Mexico, Inst Invest Ecosistemas & Sustentabilidad, Morelia, Michoacan, Mexico.
   [Becknell, Justin M.] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02912 USA.
   [Boukili, Vanessa; Chazdon, Robin L.] Univ Connecticut, Dept Ecol & Evolutionary Biol, Storrs, CT 06269 USA.
   [Brancalion, Pedro H. S.; Cesar, Ricardo G.] Univ Sao Paulo, Luiz Queiroz Coll Agr, Dept Forest Sci, BR-13418900 Piracicaba, SP, Brazil.
   [Craven, Dylan; Hall, Jefferson S.; van Breugel, Michiel] Smithsonian Trop Res Inst, SI ForestGEO, Balboa, Panama.
   [Craven, Dylan] German Ctr Integrat Biodiversity Res iDiv Halle J, D-04103 Leipzig, Germany.
   [Craven, Dylan] Univ Leipzig, Inst Biol, D-04103 Leipzig, Germany.
   [de Almeida-Cortez, Jarcilene S.; Cabral, George A. L.] Univ Fed Pernambuco, Dept Bot, BR-50670901 Recife, PE, Brazil.
   [de Jong, Ben H. J.; Ochoa-Gaona, Susana; Orihuela-Belmonte, Edith] El Colegio Frontera Sur, Unidad Campeche, Dept Sustainabil Sci, Campeche, Mexico.
   [Denslow, Julie S.] Tulane Univ, Dept Ecol & Evolutionary Biol, New Orleans, LA 70130 USA.
   [Dent, Daisy H.] Smithsonian Trop Res Inst, Balboa, Panama.
   [Dent, Daisy H.] Univ Stirling, Biol & Environm Sci, Stirling FK9 4LA, Scotland.
   [DeWalt, Saara J.; Rozendaal, Danae M. A.] Clemson Univ, Dept Sci Biol, Clemson, SC 29634 USA.
   [Dupuy, Juan M.; Hernandez-Stefanoni, Jose Luis] Ctr Invest Cient Yucatan, Unidad Recursos Nat, Merida, Yucatan, Mexico.
   [Duran, Sandra M.; Sanchez-Azofeifa, Arturo] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Espirito-Santo, Mario M.; Nunes, Yule R. F.; Veloso, Maria D. M.] Univ Estadual Montes Claros, Dept Biol Geral, BR-39401089 Montes Claros, MG, Brazil.
   [Fandino, Maria C.] Fondo Patrimonio Nat Biodiversidad & Areas Proteg, Bogota, Colombia.
   [Jakovac, Catarina C.; Massoca, Paulo; Mesquita, Rita; Vicentini, Alberto; Bentos, Tony Vizcarra; Williamson, G. Bruce] Inst Nacl de Pesquisas da Amazonia, Environm Dynam Res Coordinat, Biol Dynam Forest Fragments Project, BR-69067375 Manaus, Amazonas, Brazil.
   [Junqueira, Andre B.] Wageningen Univ, Ctr Crop Syst Anal, NL-6700 AK Wageningen, Netherlands.
   [Junqueira, Andre B.] Wageningen Univ, Knowledge Technol & Innovat Grp, NL-6700 EW Wageningen, Netherlands.
   [Junqueira, Andre B.] Inst Nacl de Pesquisas da Amazonia, Coordenacao Tecnol & Inovacao, BR-69060001 Manaus, Amazonas, Brazil.
   [Kennard, Deborah] Colorado Mesa Univ, Dept Physiol & Environm Sci, Grand Junction, CO 81501 USA.
   [Letcher, Susan G.] SUNY Coll Purchase, Dept Environm Studies, Purchase, NY 10577 USA.
   [Licona, Juan-Carlos; Toledo, Marisol] FCA UAGRM, IBIF, Santa Cruz, Bolivia.
   [Lohbeck, Madelon] World Agroforestry Ctr ICRAF, Nairobi 00100, Kenya.
   [Marin-Spiotta, Erika] Univ Wisconsin, Dept Geog, Madison, WI 53706 USA.
   [Meave, Jorge A.; Mora, Francisco; Munoz, Rodrigo; Perez-Garcia, Eduardo A. .; Romero-Perez, I. Eunice] Univ Nacl Autonoma Mexico, Fac Ciencias, Dept Ecol & Recursos Nat, Mexico City 04510, DF, Mexico.
   [Muscarella, Robert; Schwartz, Naomi B.; Uriarte, Maria] Columbia Univ, Dept Ecol Evolut & Environm Biol, New York, NY 10027 USA.
   [Muscarella, Robert] Aarhus Univ, Dept Biosci, Sect Ecoinformat & Biodivers, DK-8000 Aarhus, Denmark.
   [de Oliveira, Alexandre A. .] Univ Sao Paulo, Inst Biociencias, Dept Ecol, BR-05508090 Sao Paulo, Brazil.
   [Piotto, Daniel] Univ Fed Sul Bahia, Ctr Formacao Ciencias Agroflorestais, BR-45613204 Itabuna, BA, Brazil.
   [Powers, Jennifer S.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Powers, Jennifer S.] Univ Minnesota, Dept Plant Biol, St Paul, MN 55108 USA.
   [Ruiz, Jorge] UPTC, Sch Social Sci, Geog Area, Tunja, Colombia.
   [Ruiz, Jorge] Univ Calif Santa Barbara, Dept Geog, Santa Barbara, CA 93106 USA.
   [Saldarriaga, Juan G.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Steininger, Marc K.] Yale NUS Coll, Singapore 138610, Singapore.
   [Swenson, Nathan G.] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore.
   [van Breugel, Michiel] El Colegio Frontera Unidad Villahermosa, Dept Agr Sociedad & Ambiente, Centro 86280, Tabasco, Mexico.
   [van Breugel, Michiel] Univ Amsterdam, IBED, NL-1090 GE Amsterdam, Netherlands.
   [van der Wal, Hans] Bonhoeffer Coll, NL-7545 AX Enschede, Netherlands.
   [Vester, Hans F. M.] Museu Paraense Emilio Goeldi, BR-66040170 Belem, Para, Brazil.
   [Vester, Hans F. M.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Vieira, Ima C. G.] Univ Regina, Dept Biol, Regina, SK S4S 0A2, Canada.
C3 Wageningen University & Research; University of Puerto Rico; University of Puerto Rico Medical Sciences Campus; University of Alabama System; University of Alabama Tuscaloosa; Universidad Nacional Autonoma de Mexico; Brown University; University of Connecticut; Universidade de Sao Paulo; Smithsonian Institution; Smithsonian Tropical Research Institute; Leipzig University; Universidade Federal de Pernambuco; El Colegio de la Frontera Sur (ECOSUR); Tulane University; Smithsonian Institution; Smithsonian Tropical Research Institute; University of Stirling; Clemson University; Centro de Investigacion Cientifica de Yucatan; University of Alberta; Universidade Estadual de Montes Claros; Institute Nacional de Pesquisas da Amazonia; Wageningen University & Research; Wageningen University & Research; Institute Nacional de Pesquisas da Amazonia; State University of New York (SUNY) System; CGIAR; World Agroforestry (ICRAF); University of Wisconsin System; University of Wisconsin Madison; Universidad Nacional Autonoma de Mexico; Columbia University; Aarhus University; Universidade de Sao Paulo; Universidade Federal do Sul da Bahia; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Universidad Pedagogica y Tecnologica de Colombia (UPTC); University of California System; University of California Santa Barbara; University System of Maryland; University of Maryland College Park; Yale NUS College; National University of Singapore; University of Amsterdam; Museu Paraense Emilio Goeldi; Louisiana State University System; Louisiana State University; University of Regina
RP Poorter, L (corresponding author), Wageningen Univ, Forest Ecol & Forest Management Grp, POB 47, NL-6700 AA Wageningen, Netherlands.
EM lourens.poorter@wur.nl
FU Australian Department of Foreign Affairs and Trade-DFAT; CGIAR-FTA; CIFOR; Colciencias grant [243-13-16640]; Consejo Nacional de Ciencia y Tecnologia [SEP-CONACYT 2009-129740, CONACYT 33851-B]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [563304/2010-3, 562955/2010-0, 574008/2008-0, PQ 307422/2012-7]; FOMIX-Yucatan [YUC-2008-C06-108863]; ForestGEO; Fundacao de Amparo a Pesquisa de Minas Gerais (FAPEMIG CRA) [APQ-00001-11]; Fundacion Ecologica de Cuixmala, Heising-Simons Foundation; HSBC; ICETEX; Instituto Internacional de Educacao do Brasil-IEB; Instituto Nacional de Servicos Ambientais da Amazonia-Servamb-INPA; Inter-American Institute for Global Change (Tropi-Dr Network) via a grant from the US National Science Foundation [CRN3-025, GEO-1128040]; Motta Family Foundation; NASA; National Science Foundation (NSF-CNH-RCN) [1313788]; NSF [DEB-0129104, BCS-1349952, DEB-1053237, DEB 1050957, 0639393, 1147429, 0639114, 1147434]; NUFFIC; USAID (BOLFOR); Science without Borders Program (CAPES/CNPq) [88881.064976/2014-01]; Sao Paulo Research Foundation (FAPESP) [2011/06782-5, 2014/14503-7]; Silicon Valley Foundation; Stichting Het Kronendak; Tropenbos Foundation; University of Connecticut Research Foundation; Wageningen University; European Union [283093]; Swedish Research Council [2011-06782] Funding Source: Swedish Research Council; Direct For Biological Sciences; Division Of Environmental Biology [1147434, 1147429, 0639393] Funding Source: National Science Foundation; Direct For Biological Sciences; Division Of Environmental Biology [1053237, 0639114, 1546686] Funding Source: National Science Foundation; Direct For Biological Sciences; Emerging Frontiers [1137364, 1318164] Funding Source: National Science Foundation; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1349952] Funding Source: National Science Foundation; ICER; Directorate For Geosciences [1128040] Funding Source: National Science Foundation; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/06782-5] Funding Source: FAPESP
NR 69
TC 891
Z9 1011
U1 30
U2 863
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 211
EP +
DI 10.1038/nature16512
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700037
PM 26840632
DA 2026-03-09
ER

PT J
AU Banerjee, A
   Dick, GR
   Yoshino, T
   Kanan, MW
AF Banerjee, Aanindeeta
   Dick, Graham R.
   Yoshino, Tatsuhiko
   Kanan, Matthew W.
TI Carbon dioxide utilization via carbonate-promoted C-H carboxylation
SO NATURE
LA English
DT Article
ID acid; chemicals; biomass; transformation; platform
AB Using carbon dioxide (CO2) as a feedstock for commodity synthesis is an attractive means of reducing greenhouse gas emissions and a possible stepping-stone towards renewable synthetic fuels(1,2). A major impediment to synthesizing compounds from CO2 is the difficulty of forming carbon-carbon (C-C) bonds efficiently: although CO2 reacts readily with carbon-centred nucleophiles, generating these intermediates requires high-energy reagents (such as highly reducing metals or strong organic bases), carbon-heteroatom bonds or relatively acidic carbon-hydrogen (C-H) bonds(3-5). These requirements negate the environmental benefit of using CO2 as a substrate and limit the chemistry to low-volume targets. Here we show that intermediate-temperature (200 to 350 degrees Celsius) molten salts containing caesium or potassium cations enable carbonate ions (CO32-) to deprotonate very weakly acidic C-H bonds (pK(a) > 40), generating carbon-centred nucleophiles that react with CO2 to form carboxylates. To illustrate a potential application, we use C-H carboxylation followed by protonation to convert 2-furoic acid into furan-2,5-dicarboxylic acid (FDCA)-a highly desirable bio-based feedstock(6) with numerous applications, including the synthesis of polyethylene furandicarboxylate (PEF), which is a potential large-scale substitute for petroleum-derived polyethylene terephthalate (PET)(7,8). Since 2-furoic acid can readily be made from lignocellulose9, CO32--promoted C-H carboxylation thus reveals a way to transform inedible biomass and CO2 into a valuable feedstock chemical. Our results provide a new strategy for using CO2 in the synthesis of multi-carbon compounds.
C1 [Banerjee, Aanindeeta; Dick, Graham R.; Yoshino, Tatsuhiko; Kanan, Matthew W.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Yoshino, Tatsuhiko] Hokkaido Univ, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan.
C3 Stanford University; Hokkaido University
RP Kanan, MW (corresponding author), Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
EM mkanan@stanford.edu
FU Stanford University; Henry and Camille Dreyfus Foundation; Stanford Center for Molecular Analysis and Design; Japan Society for the Promotion of Science
NR 30
TC 380
Z9 422
U1 20
U2 882
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 215
EP +
DI 10.1038/nature17185
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100037
PM 26961655
DA 2026-03-09
ER

PT J
AU Guérin, T
   Levernier, N
   Bénichou, O
   Voituriez, R
AF Guerin, T.
   Levernier, N.
   Benichou, O.
   Voituriez, R.
TI Mean first-passage times of non-Markovian random walkers in confinement
SO NATURE
LA English
DT Article
ID geometry-controlled kinetics; brownian-motion; diffusion; persistence; polymers; colloids
AB The first-passage time, defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes(1). Its importance comes from its crucial role in quantifying the efficiency of processes as varied as diffusion-limited reactions(2,3), target search processes(4) or the spread of diseases(5). Most methods of determining the properties of first-passage time in confined domains have been limited to Markovian (memoryless) processes(3,6,7). However, as soon as the random walker interacts with its environment, memory effects cannot be neglected: that is, the future motion of the random walker does not depend only on its current position, but also on its past trajectory. Examples of non-Markovian dynamics include single-file diffusion in narrow channels(8), or the motion of a tracer particle either attached to a polymeric chain(9) or diffusing in simple(10) or complex fluids such as nematics(11), dense soft colloids(12) or viscoelastic solutions(13,14). Here we introduce an analytical approach to calculate, in the limit of a large confining volume, the mean first-passage time of a Gaussian non-Markovian random walker to a target. The non-Markovian features of the dynamics are encompassed by determining the statistical properties of the fictitious trajectory that the random walker would follow after the first-passage event takes place, which are shown to govern the first-passage time kinetics. This analysis is applicable to a broad range of stochastic processes, which may be correlated at long times. Our theoretical predictions are confirmed by numerical simulations for several examples of non-Markovian processes, including the case of fractional Brownian motion in one and higher dimensions. These results reveal, on the basis of Gaussian processes, the importance of memory effects in first-passage statistics of non-Markovian random walkers in confinement.
C1 [Guerin, T.] Univ Bordeaux, Lab Ondes & Mat Aquitaine, Unite Mixte Rech 5798, CNRS, F-33400 Talence, France.
   [Levernier, N.; Benichou, O.; Voituriez, R.] Univ Paris 06, CNRS, Lab Phys Theor Mat Condensee, 4 Pl Jussieu, F-75005 Paris, France.
   [Voituriez, R.] Univ Paris 06, CNRS, Lab Jean Perrin, 4 Pl Jussieu, F-75005 Paris, France.
C3 Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Bénichou, O; Voituriez, R (corresponding author), Univ Paris 06, CNRS, Lab Phys Theor Mat Condensee, 4 Pl Jussieu, F-75005 Paris, France.; Voituriez, R (corresponding author), Univ Paris 06, CNRS, Lab Jean Perrin, 4 Pl Jussieu, F-75005 Paris, France.
EM benichou@lptmc.jussieu.fr; voiturie@lptmc.jussieu.fr
FU ERC [FPTOpt-277998]
NR 30
TC 129
Z9 137
U1 3
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 356
EP 359
DI 10.1038/nature18272
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800029
PM 27306185
DA 2026-03-09
ER

PT J
AU Li, H
   O'Donoghue, AJ
   van der Linden, WA
   Xie, SC
   Yoo, E
   Foe, IT
   Tilley, L
   Craik, CS
   da Fonseca, PCA
   Bogyo, M
AF Li, Hao
   O'Donoghue, Anthony J.
   van der Linden, Wouter A.
   Xie, Stanley C.
   Yoo, Euna
   Foe, Ian T.
   Tilley, Leann
   Craik, Charles S.
   da Fonseca, Paula C. A.
   Bogyo, Matthew
TI Structure- and function-based design of Plasmodium-selective proteasome inhibitors
SO NATURE
LA English
DT Article
ID human 20s proteasome; artemisinin resistance; electron-microscopy; falciparum malaria; identification; visualization; mechanism; parasite; specificity; validation
AB The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation(1). Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle(2-5). Most compounds that have been tested against the parasite also inhibit the mammalian proteasome, resulting in toxicity that precludes their use as therapeutic agents(2,6). Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, here we use a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We design inhibitors based on amino-acid preferences specific to the parasite proteasome, and find that they preferentially inhibit the beta 2-subunit. We determine the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryoelectron microscopy and single-particle analysis, to a resolution of 3.6 angstrom. These data reveal the unusually open P. falciparum beta 2 active site and provide valuable information about active-site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin family anti-malarials(7,8), we observe growth inhibition synergism with low doses of this beta 2-selective inhibitor in artemisinin-sensitive and -resistant parasites. Finally, we demonstrate that a parasite-selective inhibitor could be used to attenuate parasite growth in vivo without appreciable toxicity to the host. Thus, the Plasmodium proteasome is a chemically tractable target that could be exploited by nextgeneration anti-malarial agents.
C1 [Li, Hao; van der Linden, Wouter A.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Li, Hao; Yoo, Euna; Foe, Ian T.; Bogyo, Matthew] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [O'Donoghue, Anthony J.; Craik, Charles S.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Xie, Stanley C.; Tilley, Leann] Univ Melbourne, Dept Biochem & Mol Biol, Inst Bio21, Melbourne, Vic 3010, Australia.
   [da Fonseca, Paula C. A.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Li, Hao] Agcy Sci Technol & Res, Inst Biomed Sci, Mol Engn Lab, Singapore 138673, Singapore.
   [O'Donoghue, Anthony J.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 Stanford University; Stanford University; University of California System; University of California San Francisco; University of Melbourne; MRC Laboratory Molecular Biology; Agency for Science Technology & Research (A*STAR); University of California System; University of California San Diego
RP Bogyo, M (corresponding author), MRC Lab Mol Biol, Francis Crick Ave,Cambridge Biomed Campus, Cambridge CB2 0QH, England.
EM pauladf@mrc-lmb.cam.ac.uk; mbogyo@stanford.edu
FU National Institutes of Health [R01AI078947, R01EB05011]; Medical Research Council [MC-UP-1201/5]; Agency for Science, Technology and Research (A*STAR) Singapore; Netherlands Organization for Scientific Research (NWO); Program for Breakthrough Biomedical Research (PBBR); Sandler Foundation; American Heart Association [14POST20280004]; Australian Research Council; Australian National Health and Medical Research Council; American Heart Association (AHA) [14POST20280004] Funding Source: American Heart Association (AHA); National Institute of Allergy and Infectious Diseases [T32AI007328, R01AI105106] Funding Source: NIH RePORTER; Medical Research Council [MC_UP_1201/5] Funding Source: researchfish; MRC [MC_UP_1201/5] Funding Source: UKRI
NR 41
TC 195
Z9 229
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 233
EP +
DI 10.1038/nature16936
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700042
PM 26863983
DA 2026-03-09
ER

PT J
AU Li, BG
   Gasser, T
   Ciais, P
   Piao, SL
   Tao, S
   Balkanski, Y
   Hauglustaine, D
   Boisier, JP
   Chen, Z
   Huang, MT
   Li, LZ
   Li, Y
   Liu, HY
   Liu, JF
   Peng, SS
   Shen, ZH
   Sun, ZZ
   Wang, R
   Wang, T
   Yin, GD
   Yin, Y
   Zeng, H
   Zeng, ZZ
   Zhou, F
AF Li, Bengang
   Gasser, Thomas
   Ciais, Philippe
   Piao, Shilong
   Tao, Shu
   Balkanski, Yves
   Hauglustaine, Didier
   Boisier, Juan-Pablo
   Chen, Zhuo
   Huang, Mengtian
   Li, Laurent Zhaoxin
   Li, Yue
   Liu, Hongyan
   Liu, Junfeng
   Peng, Shushi
   Shen, Zehao
   Sun, Zhenzhong
   Wang, Rong
   Wang, Tao
   Yin, Guodong
   Yin, Yi
   Zeng, Hui
   Zeng, Zhenzhong
   Zhou, Feng
TI The contribution of China's emissions to global climate forcing
SO NATURE
LA English
DT Article
ID land-use change; co2 emissions; carbon; uncertainty
AB Knowledge of the contribution that individual countries have made to global radiative forcing is important to the implementation of the agreement on "common but differentiated responsibilities" reached by the United Nations Framework Convention on Climate Change. Over the past three decades, China has experienced rapid economic development(1), accompanied by increased emission of greenhouse gases, ozone precursors and aerosols(2,3), but the magnitude of the associated radiative forcing has remained unclear. Here we use a global coupled biogeochemistry-climate model(4,5) and a chemistry and transport model(6) to quantify China's present-day contribution to global radiative forcing due to well-mixed greenhouse gases, short-lived atmospheric climate forcers and land-use-induced regional surface albedo changes. We find that China contributes 10% +/- 4% of the current global radiative forcing. China's relative contribution to the positive (warming) component of global radiative forcing, mainly induced by well-mixed greenhouse gases and black carbon aerosols, is 12% +/- 2%. Its relative contribution to the negative (cooling) component is 15% +/- 6%, dominated by the effect of sulfate and nitrate aerosols. China's strongest contributions are 0.16 +/- 0.02 watts per square metre for CO2 from fossil fuel burning, 0.13 +/- 0.05 watts per square metre for CH4, -0.11 +/- 0.05 watts per square metre for sulfate aerosols, and 0.09 +/- 0.06 watts per square metre for black carbon aerosols. China's eventual goal of improving air quality will result in changes in radiative forcing in the coming years: a reduction of sulfur dioxide emissions would drive a faster future warming, unless offset by larger reductions of radiative forcing from well-mixed greenhouse gases and black carbon.
C1 [Li, Bengang; Piao, Shilong; Tao, Shu; Chen, Zhuo; Huang, Mengtian; Li, Yue; Liu, Hongyan; Liu, Junfeng; Peng, Shushi; Shen, Zehao; Sun, Zhenzhong; Yin, Guodong; Zeng, Hui; Zeng, Zhenzhong; Zhou, Feng] Peking Univ, Coll Urban & Environm Sci, Lab Earth Surface Proc, Sinofrench Inst Earth Syst Sci, Beijing 100871, Peoples R China.
   [Li, Bengang] Jiangsu Ctr Collaborat Innovat Geog Informat Reso, Nanjing 210023, Jiangsu, Peoples R China.
   [Gasser, Thomas; Ciais, Philippe; Balkanski, Yves; Hauglustaine, Didier; Boisier, Juan-Pablo; Wang, Rong; Wang, Tao; Yin, Yi] UVSQ, CNRS, CEA, Lab Sci Climat & Environm, F-91191 Gif Sur Yvette, France.
   [Gasser, Thomas] CIRAD, AgroParisTech, EHESS, Ctr Int Rech Environm & Dev,CNRS,PontsParisTech, F-94736 Nogent Sur Marne, France.
   [Piao, Shilong] Chinese Acad Sci, Ctr Excellence Tibetan Earth Sci, Inst Tibetan Plateau Res, Key Lab Alpine Ecol & Biodivers, Beijing 100085, Peoples R China.
   [Li, Laurent Zhaoxin] Univ Paris 06, CNRS, Lab Meteorol Dynam, F-75252 Paris, France.
C3 Peking University; Nanjing Normal University; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CIRAD; AgroParisTech; Chinese Academy of Sciences; Institute of Tibetan Plateau Research, CAS; Institut Polytechnique de Paris; Ecole Polytechnique; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Li, BG (corresponding author), Peking Univ, Coll Urban & Environm Sci, Lab Earth Surface Proc, Sinofrench Inst Earth Syst Sci, Beijing 100871, Peoples R China.; Li, BG (corresponding author), Jiangsu Ctr Collaborat Innovat Geog Informat Reso, Nanjing 210023, Jiangsu, Peoples R China.
EM lbg@urban.pku.edu.cn
FU National Natural Science Foundation of China [41371443, 41390240]; 111 project [B14001]; GIS Climat-Environnement-Societe; European Research Council Synergy grant [ERC-2013-SyG-610028]
NR 30
TC 242
Z9 278
U1 22
U2 1024
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 357
EP +
DI 10.1038/nature17165
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300050
PM 26983540
DA 2026-03-09
ER

PT J
AU Pinto, C
   Middleton, MJ
   Fabian, AC
AF Pinto, Ciro
   Middleton, Matthew J.
   Fabian, Andrew C.
TI Resolved atomic lines reveal outflows in two ultraluminous X-ray sources
SO NATURE
LA English
DT Article
ID reflection grating spectrometer; photon imaging camera; black-hole winds; xmm-newton; accretion disk; spectroscopy; evolution; emission; galaxy; feedback
AB Ultraluminous X-ray sources are extragalactic, off-nucleus, point sources in galaxies, and have X-ray luminosities in excess of 3 x 10(39) ergs per second. They are thought to be powered by accretion onto a compact object. Possible explanations include accretion onto neutron stars with strong magnetic fields(1), onto stellar-mass black holes (of up to 20 solar masses) at or in excess of the classical Eddington limit(2-4), or onto intermediate-mass black holes (10(3)-10(5) solar masses)(5). The lack of sufficient energy resolution in previous analyses has prevented an unambiguous identification of any emission or absorption lines in the X-ray band, thereby precluding a detailed analysis of the accretion flow(6-8). Here we report the presence of X-ray emission lines arising from highly ionized iron, oxygen and neon with a cumulative significance in excess of five standard deviations, together with blueshifted (about 0.2 times light velocity) absorption lines of similar significance, in the high-resolution X-ray spectra of the ultraluminous X-ray sources NGC 1313 X-1 and NGC 5408 X-1. The blueshifted absorption lines must occur in a fast-outflowing gas, whereas the emission lines originate in slow-moving gas around the source. We conclude that the compact object in each source is surrounded by powerful winds with an outflow velocity of about 0.2 times that of light, as predicted by models of accreting supermassive black holes and hyper-accreting stellar-mass black holes(9,10).
C1 [Pinto, Ciro; Middleton, Matthew J.; Fabian, Andrew C.] Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
C3 University of Cambridge
RP Pinto, C (corresponding author), Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
EM cpinto@ast.cam.ac.uk
FU European Research Council [340492]; STFC; ESA Member States; NASA; Science and Technology Facilities Council [ST/N000927/1] Funding Source: researchfish; STFC [ST/M005283/1, ST/M005283/2] Funding Source: UKRI
NR 32
TC 216
Z9 220
U1 0
U2 13
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 64
EP +
DI 10.1038/nature17417
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900039
PM 27120159
DA 2026-03-09
ER

PT J
AU Sorensen, JJWH
   Pedersen, MK
   Munch, M
   Haikka, P
   Jensen, JH
   Planke, T
   Andreasen, MG
   Gajdacz, M
   Molmer, K
   Lieberoth, A
   Sherson, JF
AF Sorensen, Jens Jakob W. H.
   Pedersen, Mads Kock
   Munch, Michael
   Haikka, Pinja
   Jensen, Jesper Halkjaer
   Planke, Tilo
   Andreasen, Morten Ginnerup
   Gajdacz, Miroslav
   Molmer, Klaus
   Lieberoth, Andreas
   Sherson, Jacob F.
TI RETRACTED: Retracted: Exploring the quantum speed limit with computer games (Publication with Expression of Concern. See vol. 581, 2020) (Publication with Expression of Concern. See vol. 581, 2020) (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID neutral atoms; transition
AB Humans routinely solve problems of immense computational complexity by intuitively forming simple, low-dimensional heuristic strategies(1,2). Citizen science (or crowd sourcing) is a way of exploiting this ability by presenting scientific research problems to non-experts. 'Gamification'-the application of game elements in a non-game context-is an effective tool with which to enable citizen scientists to provide solutions to research problems. The citizen science games Foldit(3), EteRNA(4) and EyeWire(5) have been used successfully to study protein and RNA folding and neuron mapping, but so far gamification has not been applied to problems in quantum physics. Here we report on Quantum Moves, an online platform gamifying optimization problems in quantum physics. We show that human players are able to find solutions to difficult problems associated with the task of quantum computing(6). Players succeed where purely numerical optimization fails, and analyses of their solutions provide insights into the problem of optimization of a more profound and general nature. Using player strategies, we have thus developed a few-parameter heuristic optimization method that efficiently outperforms the most prominent established numerical methods. The numerical complexity associated with time-optimal solutions increases for shorter process durations. To understand this better, we produced a low-dimensional rendering of the optimization landscape. This rendering reveals why traditional optimization methods fail near the quantum speed limit (that is, the shortest process duration with perfect fidelity)(7-9). Combined analyses of optimization landscapes and heuristic solution strategies may benefit wider classes of optimization problems in quantum physics and beyond.
C1 [Sorensen, Jens Jakob W. H.; Pedersen, Mads Kock; Munch, Michael; Haikka, Pinja; Jensen, Jesper Halkjaer; Planke, Tilo; Andreasen, Morten Ginnerup; Gajdacz, Miroslav; Molmer, Klaus; Lieberoth, Andreas; Sherson, Jacob F.] Aarhus Univ, Dept Phys & Astron, Aarhus, Denmark.
C3 Aarhus University
RP Sherson, JF (corresponding author), Aarhus Univ, Dept Phys & Astron, Aarhus, Denmark.
EM sherson@phys.au.dk
FU European Research Council; Lundbeck Foundation; Aarhus University Research Foundation; Templeton Foundation; Danish Council for Independent Research; Villum Foundation; Carlsberg Foundation; Villum Fonden [00007335] Funding Source: researchfish
NR 35
TC 89
Z9 104
U1 0
U2 123
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 210
EP +
DI 10.1038/nature17620
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100034
PM 27075097
DA 2026-03-09
ER

PT J
AU Mertins, P
   Mani, DR
   Ruggles, KV
   Gillette, MA
   Clauser, KR
   Wang, P
   Wang, XL
   Qiao, JW
   Cao, S
   Petralia, F
   Kawaler, E
   Mundt, F
   Krug, K
   Tu, ZD
   Lei, JT
   Gatza, ML
   Wilkerson, M
   Perou, CM
   Yellapantula, V
   Huang, KL
   Lin, CW
   McLellan, MD
   Yan, P
   Davies, SR
   Townsend, RR
   Skates, SJ
   Wang, J
   Zhang, B
   Kinsinger, CR
   Mesri, M
   Rodriguez, H
   Ding, L
   Paulovich, AG
   Fenyö, D
   Ellis, MJ
   Carr, SA
AF Mertins, Philipp
   Mani, D. R.
   Ruggles, Kelly V.
   Gillette, Michael A.
   Clauser, Karl R.
   Wang, Pei
   Wang, Xianlong
   Qiao, Jana W.
   Cao, Song
   Petralia, Francesca
   Kawaler, Emily
   Mundt, Filip
   Krug, Karsten
   Tu, Zhidong
   Lei, Jonathan T.
   Gatza, Michael L.
   Wilkerson, Matthew
   Perou, Charles M.
   Yellapantula, Venkata
   Huang, Kuan-lin
   Lin, Chenwei
   McLellan, Michael D.
   Yan, Ping
   Davies, Sherri R.
   Townsend, R. Reid
   Skates, Steven J.
   Wang, Jing
   Zhang, Bing
   Kinsinger, Christopher R.
   Mesri, Mehdi
   Rodriguez, Henry
   Ding, Li
   Paulovich, Amanda G.
   Fenyo, David
   Ellis, Matthew J.
   Carr, Steven A.
TI Proteogenomics connects somatic mutations to signalling in breast cancer
SO NATURE
LA English
DT Article
ID pik3ca mutations; expression; receptor; pathways; genes; phosphorylation; heterogeneity; signature; reveals; biology
AB Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.
C1 [Mertins, Philipp; Mani, D. R.; Gillette, Michael A.; Clauser, Karl R.; Qiao, Jana W.; Mundt, Filip; Krug, Karsten; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Ruggles, Kelly V.; Kawaler, Emily; Fenyo, David] NYU, Langone Med Ctr, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [Gillette, Michael A.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
   [Wang, Pei; Petralia, Francesca; Tu, Zhidong] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Wang, Xianlong; Lin, Chenwei; Yan, Ping; Paulovich, Amanda G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Cao, Song; Yellapantula, Venkata; Huang, Kuan-lin; McLellan, Michael D.; Ding, Li] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Med,McDonnell Genome Inst, St Louis, MO 63108 USA.
   [Mundt, Filip] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
   [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
   [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   [Lei, Jonathan T.; Ellis, Matthew J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Gatza, Michael L.; Wilkerson, Matthew; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
   [Davies, Sherri R.; Townsend, R. Reid] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Canc, Biostat Ctr, Boston, MA 02114 USA.
   [Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA.
   [Wang, Jing; Zhang, Bing] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA.
   [Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; New York University; NYU Langone Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; Fred Hutchinson Cancer Center; Siteman Cancer Center; Washington University (WUSTL); Karolinska Institutet; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; University of North Carolina; University of North Carolina Chapel Hill; Washington University (WUSTL); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Vanderbilt University; Vanderbilt University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Mertins, P; Carr, SA (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Ellis, MJ (corresponding author), Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.; Ellis, MJ (corresponding author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA.; Ellis, MJ (corresponding author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
EM pmertins@broadinstitute.org; Matthew.Ellis@bcm.edu; scarr@broad.mit.edu
FU National Cancer Institute (NCI) [U24CA160034, U24CA160036, U24CA160019, U24CA159988, U24CA160035]; CPRIT grant [RR140033]; Leidos contract [13XS068]; National Cancer Institute (NCI) CPTAC award [U24CA160035]; NCI Cancer Center Support Grant [P30 CA91842]; NIH/NCRR Washington University-ICTS [UL1 RR024992]; Susan G. Komen for the Cure [KG 090422]; Swedish Research Council [Dnr 2014-323];  [SUB-R01GM108711]; National Cancer Institute [P30CA016087, P30CA091842] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM108711] Funding Source: NIH RePORTER
NR 41
TC 1283
Z9 1481
U1 8
U2 366
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 55
EP +
DI 10.1038/nature18003
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300032
PM 27251275
DA 2026-03-09
ER

PT J
AU Langer, F
   Hohenleutner, M
   Schmid, CP
   Poellmann, C
   Nagler, P
   Korn, T
   Schüller, C
   Sherwin, MS
   Huttner, U
   Steiner, JT
   Koch, SW
   Kira, M
   Huber, R
AF Langer, F.
   Hohenleutner, M.
   Schmid, C. P.
   Poellmann, C.
   Nagler, P.
   Korn, T.
   Schueller, C.
   Sherwin, M. S.
   Huttner, U.
   Steiner, J. T.
   Koch, S. W.
   Kira, M.
   Huber, R.
TI Lightwave-driven quasiparticle collisions on a subcycle timescale
SO NATURE
LA English
DT Article
ID high-harmonic generation; side-band generation; many-body; monolayer; electrons; dynamics; excitons; pulses; wse2
AB Ever since Ernest Rutherford scattered alpha-particles from gold foils(1), collision experiments have revealed insights into atoms, nuclei and elementary particles(2). In solids, many-body correlations lead to characteristic resonances(3)-called quasiparticles-such as excitons, dropletons(4), polarons and Cooper pairs. The structure and dynamics of quasiparticles are important because they define macroscopic phenomena such as Mott insulating states, spontaneous spin-and charge-order, and high-temperature superconductivity(5). However, the extremely short lifetimes of these entities(6) make practical implementations of a suitable collider challenging. Here we exploit lightwave-driven charge transport(7-24), the foundation of attosecond science(9-13), to explore ultrafast quasiparticle collisions directly in the time domain: a femtosecond optical pulse creates excitonic electron-hole pairs in the layered dichalcogenide tungsten diselenide while a strong terahertz field accelerates and collides the electrons with the holes. The underlying dynamics of the wave packets, including collision, pair annihilation, quantum interference and dephasing, are detected as light emission in high-order spectral sidebands(17-19) of the optical excitation. A full quantum theory explains our observations microscopically. This approach enables collision experiments with various complex quasiparticles and suggests a promising new way of generating sub-femtosecond pulses.
C1 [Langer, F.; Hohenleutner, M.; Schmid, C. P.; Poellmann, C.; Nagler, P.; Korn, T.; Schueller, C.; Huber, R.] Univ Regensburg, Dept Phys, D-93040 Regensburg, Germany.
   [Sherwin, M. S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Sherwin, M. S.] Univ Calif Santa Barbara, Inst Terahertz Sci & Technol, Santa Barbara, CA 93106 USA.
   [Huttner, U.; Steiner, J. T.; Koch, S. W.; Kira, M.] Univ Marburg, Dept Phys, D-35032 Marburg, Germany.
C3 University of Regensburg; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Philipps University Marburg
RP Huber, R (corresponding author), Univ Regensburg, Dept Phys, D-93040 Regensburg, Germany.; Kira, M (corresponding author), Univ Marburg, Dept Phys, D-35032 Marburg, Germany.
EM mackillo.kira@physik.uni-marburg.de; rupert.huber@physik.uni-regensburg.de
FU European Research Council [305003]; Deutsche Forschungsgemeinschaft [HU 1598/2-1, GRK 1570, SFB 1083, SPP 1840, KI 917/2-2, KI 917/3-1]; National Science Foundation [DMR 1405964]; Direct For Mathematical & Physical Scien [1405964] Funding Source: National Science Foundation; Division Of Materials Research [1405964] Funding Source: National Science Foundation
NR 47
TC 248
Z9 270
U1 0
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 225
EP +
DI 10.1038/nature17958
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200045
PM 27172045
DA 2026-03-09
ER

PT J
AU Kang, JS
   Hu, JX
   Karra, R
   Dickson, AL
   Tornini, VA
   Nachtrab, G
   Gemberling, M
   Goldman, JA
   Black, BL
   Poss, KD
AF Kang, Junsu
   Hu, Jianxin
   Karra, Ravi
   Dickson, Amy L.
   Tornini, Valerie A.
   Nachtrab, Gregory
   Gemberling, Matthew
   Goldman, Joseph A.
   Black, Brian L.
   Poss, Kenneth D.
TI Modulation of tissue repair by regeneration enhancer elements
SO NATURE
LA English
DT Article
ID gene-expression; heart regeneration; limb regeneration; zebrafish; cell; growth; mechanisms; evolution; capacity
AB How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro-or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.
C1 [Kang, Junsu; Dickson, Amy L.; Tornini, Valerie A.; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A.; Poss, Kenneth D.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   [Hu, Jianxin; Black, Brian L.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   [Karra, Ravi] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
C3 Duke University; University of California System; University of California San Francisco; Duke University
RP Poss, KD (corresponding author), Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
EM kenneth.poss@duke.edu
FU AHA [12POST11920060]; NIH Clinical Investigator Award [K08 HL116485]; NSF Graduate Research Fellowship [1106401]; NIH [F32 HL120494, R01 HL089707, R01 HL064658, R01 GM074057, R01 HL081674]; HHMI; Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD040372] Funding Source: NIH RePORTER; American Heart Association (AHA) [12POST11920060] Funding Source: American Heart Association (AHA)
NR 53
TC 245
Z9 298
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 201
EP +
DI 10.1038/nature17644
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100032
PM 27049946
DA 2026-03-09
ER

PT J
AU Ponce-Salvatierra, A
   Wawrzyniak-Turek, K
   Steuerwald, U
   Höbartner, C
   Pena, V
AF Ponce-Salvatierra, Almudena
   Wawrzyniak-Turek, Katarzyna
   Steuerwald, Ulrich
   Hoebartner, Claudia
   Pena, Vladimir
TI Crystal structure of a DNA catalyst
SO NATURE
LA English
DT Article
ID phosphorothioate oligonucleotides; efficient synthesis; rna; ribozyme; complex; deoxyribozyme
AB Catalysis in biology is restricted to RNA (ribozymes) and protein enzymes, but synthetic biomolecular catalysts can also be made of DNA (deoxyribozymes)(1) or synthetic genetic polymers(2). In vitro selection from synthetic random DNA libraries identified DNA catalysts for various chemical reactions beyond RNA backbone cleavage(3). DNA-catalysed reactions include RNA and DNA ligation in various topologies(4,5), hydrolytic cleavage(6,7) and photorepair of DNA(8), as well as reactions of peptides(9,10) and small molecules(11,12). In spite of comprehensive biochemical studies of DNA catalysts for two decades, fundamental mechanistic understanding of their function is lacking in the absence of three-dimensional models at atomic resolution. Early attempts to solve the crystal structure of an RNA-cleaving deoxyribozyme resulted in a catalytically irrelevant nucleic acid fold(13). Here we report the crystal structure of the RNA-ligating deoxyribozyme 9DB1 (ref. 14) at 2.8 angstrom resolution. The structure captures the ligation reaction in the post-catalytic state, revealing a compact folding unit stabilized by numerous tertiary interactions, and an unanticipated organization of the catalytic centre. Structure-guided mutagenesis provided insights into the basis for regioselectivity of the ligation reaction and allowed remarkable manipulation of substrate recognition and reaction rate. Moreover, the structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst, in support of its intricate three-dimensional organization. The structural principles underlying the catalytic ability of DNA elucidate differences and similarities in DNA versus RNA catalysts, which is relevant for comprehending the privileged position of folded RNA in the prebiotic world and in current organisms.
C1 [Ponce-Salvatierra, Almudena; Wawrzyniak-Turek, Katarzyna; Hoebartner, Claudia] Max Planck Inst Biophys Chem, Max Planck Res Grp Nucle Acid Chem, D-37077 Gottingen, Germany.
   [Ponce-Salvatierra, Almudena; Steuerwald, Ulrich; Pena, Vladimir] Max Planck Inst Biophys Chem, Res Grp Macromol Crystallog, D-37077 Gottingen, Germany.
   [Wawrzyniak-Turek, Katarzyna; Hoebartner, Claudia] Univ Gottingen, Inst Organ & Biomol Chem, D-37077 Gottingen, Germany.
C3 Max Planck Society; Max Planck Society; University of Gottingen
RP Pena, V (corresponding author), Max Planck Inst Biophys Chem, Res Grp Macromol Crystallog, Fassberg 11, D-37077 Gottingen, Germany.
EM choebar1@gwdg.de; vpena@gwdg.de
FU Max Planck Society
NR 46
TC 124
Z9 146
U1 3
U2 192
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 231
EP U272
DI 10.1038/nature16471
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700041
PM 26735012
DA 2026-03-09
ER

PT J
AU Planer, JD
   Peng, YQ
   Kau, AL
   Blanton, LV
   Ndao, IM
   Tarr, PI
   Warner, BB
   Gordon, JI
AF Planer, Joseph D.
   Peng, Yangqing
   Kau, Andrew L.
   Blanton, Laura V.
   Ndao, I. Malick
   Tarr, Phillip I.
   Warner, Barbara B.
   Gordon, Jeffrey I.
TI Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice
SO NATURE
LA English
DT Article
ID secretory iga; bacteria; patterns
AB Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function(1-3). The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways(4,5), plus glycans present on the antibody's secretory component(6). Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice(7,8). A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA(9-11). How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.
C1 [Planer, Joseph D.; Peng, Yangqing; Kau, Andrew L.; Blanton, Laura V.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.
   [Planer, Joseph D.; Peng, Yangqing; Kau, Andrew L.; Blanton, Laura V.; Gordon, Jeffrey I.] Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA.
   [Ndao, I. Malick; Tarr, Phillip I.; Warner, Barbara B.] Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.; Gordon, JI (corresponding author), Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA.
EM jgordon@wustl.edu
FU National Institutes of Health [DK30292, DK052574]; Children's Discovery Institute; Bill & Melinda Gates Foundation; Crohn's and Colitis Foundation of America; Washington University Medical Scientist Training Program (National Institutes of Health) [GM007200]; Crohn&apos;s & Colitis Foundation; Action Medical Research [2158] Funding Source: researchfish; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK030292, P30DK052574] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007200] Funding Source: NIH RePORTER
NR 30
TC 245
Z9 296
U1 1
U2 147
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2016
VL 534
IS 7606
BP 263
EP +
DI 10.1038/nature17940
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO0NH
UT WOS:000377475100044
PM 27279225
DA 2026-03-09
ER

PT J
AU Metzger, MJ
   Villalba, A
   Carballal, MJ
   Iglesias, D
   Sherry, J
   Reinisch, C
   Muttray, AF
   Baldwin, SA
   Goff, SP
AF Metzger, Michael J.
   Villalba, Antonio
   Carballal, Maria J.
   Iglesias, David
   Sherry, James
   Reinisch, Carol
   Muttray, Annette F.
   Baldwin, Susan A.
   Goff, Stephen P.
TI Widespread transmission of independent cancer lineages within multiple bivalve species
SO NATURE
LA English
DT Article
ID hemic neoplasia; cerastoderma-edule; mytilus-trossulus; evolution; populations; veneridae; sequence; diseases; mussels; cells
AB Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils(1) and dogs(2,3)), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria)(4) suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers are found spreading within the species of origin, cross-species transmission of cancer cells can occur.
C1 [Metzger, Michael J.; Goff, Stephen P.] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
   [Metzger, Michael J.; Goff, Stephen P.] Howard Hughes Med Inst, New York, NY 10032 USA.
   [Villalba, Antonio; Carballal, Maria J.; Iglesias, David] Conselleria Mar, Ctr Invest Marinas, Xunta De Galicia 36620, Vilanova De Aro, Spain.
   [Villalba, Antonio] Univ Alcala de Henares, Dept Life Sci, E-28871 Alcala De Henares, Spain.
   [Sherry, James; Reinisch, Carol] Environm Canada, Water Sci & Technol Directorate, Burlington, ON L7R 4A6, Canada.
   [Muttray, Annette F.; Baldwin, Susan A.] Univ British Columbia, Chem & Biol Engn, Vancouver, BC V6T 1Z3, Canada.
   [Muttray, Annette F.] SLR Consulting Canada Ltd, Vancouver, BC V6J 1V4, Canada.
   [Goff, Stephen P.] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
C3 Columbia University; Howard Hughes Medical Institute; Universidad de Alcala; Environment & Climate Change Canada; University of British Columbia; Columbia University
RP Goff, SP (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.; Goff, SP (corresponding author), Howard Hughes Med Inst, New York, NY 10032 USA.; Goff, SP (corresponding author), Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
EM spg1@cumc.columbia.edu
FU Howard Hughes Medical Institute and Training Grant [T32 CA009503]; Conselleria do Mar da Xunta de Galicia, through the project PGIDIT-CIMA [13/03]
NR 36
TC 154
Z9 173
U1 0
U2 136
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 705
EP +
DI 10.1038/nature18599
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000041
PM 27338791
DA 2026-03-09
ER

PT J
AU Snyder, CW
AF Snyder, Carolyn W.
TI Evolution of global temperature over the past two million years
SO NATURE
LA English
DT Article
ID sea-surface-temperature; last glacial maximum; south china sea; eastern equatorial pacific; carbon-dioxide; north-atlantic; ocean temperature; scale features; climate-change; mg/ca ratios
AB Reconstructions of Earth's past climate strongly influence our understanding of the dynamics and sensitivity of the climate system. Yet global temperature has been reconstructed for only a few isolated windows of time(1,2), and continuous reconstructions across glacial cycles remain elusive. Here I present a spatially weighted proxy reconstruction of global temperature over the past 2 million years estimated from a multi-proxy database of over 20,000 sea surface temperature point reconstructions. Global temperature gradually cooled until roughly 1.2 million years ago and cooling then stalled until the present. The cooling trend probably stalled before the beginning of the mid-Pleistocene transition(3), and predated the increase in the maximum size of ice sheets around 0.9 million years ago(4-6). Thus, global cooling may have been a precondition for, but probably is not the sole causal mechanism of, the shift to quasi-100,000-year glacial cycles at the mid-Pleistocene transition. Over the past 800,000 years, polar amplification (the amplification of temperature change at the poles relative to global temperature change) has been stable over time, and global temperature and atmospheric greenhouse gas concentrations have been closely coupled across glacial cycles. A comparison of the new temperature reconstruction with radiative forcing from greenhouse gases estimates an Earth system sensitivity of 9 degrees Celsius (range 7 to 13 degrees Celsius, 95 per cent credible interval) change in global average surface temperature per doubling of atmospheric carbon dioxide over millennium timescales. This result suggests that stabilization at today's greenhouse gas levels may already commit Earth to an eventual total warming of 5 degrees Celsius (range 3 to 7 degrees Celsius, 95 per cent credible interval) over the next few millennia as ice sheets, vegetation and atmospheric dust continue to respond to global warming.
C1 [Snyder, Carolyn W.] Stanford Univ, Interdisciplinary Program Environm & Resources, Stanford, CA 94305 USA.
C3 Stanford University
RP Snyder, CW (corresponding author), Stanford Univ, Interdisciplinary Program Environm & Resources, Stanford, CA 94305 USA.
EM carolyn.snyder@gmail.com
FU National Science Foundation Graduate Research Fellowship
NR 99
TC 233
Z9 266
U1 11
U2 334
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 226
EP +
DI 10.1038/nature19798
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000041
PM 27669024
DA 2026-03-09
ER

PT J
AU Gao, JX
   Barzel, B
   Barabási, AL
AF Gao, Jianxi
   Barzel, Baruch
   Barabasi, Albert-Laszlo
TI Universal resilience patterns in complex networks
SO NATURE
LA English
DT Article
ID dynamics; internet
AB Resilience, a system's ability to adjust its activity to retain its basic functionality when errors, failures and environmental changes occur, is a defining property of many complex systems(1). Despite widespread consequences for human health(2), the economy(3) and the environment(4), events leading to loss of resilience-from cascading failures in technological systems(5) to mass extinctions in ecological networks(6)-are rarely predictable and are often irreversible. These limitations are rooted in a theoretical gap: the current analytical framework of resilience is designed to treat low-dimensional models with a few interacting components(7), and is unsuitable for multi-dimensional systems consisting of a large number of components that interact through a complex network. Here we bridge this theoretical gap by developing a set of analytical tools with which to identify the natural control and state parameters of a multi-dimensional complex system, helping us derive effective one-dimensional dynamics that accurately predict the system's resilience. The proposed analytical framework allows us systematically to separate the roles of the system's dynamics and topology, collapsing the behaviour of different networks onto a single universal resilience function. The analytical results unveil the network characteristics that can enhance or diminish resilience, offering ways to prevent the collapse of ecological, biological or economic systems, and guiding the design of technological systems resilient to both internal failures and environmental changes.
C1 [Gao, Jianxi; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Barzel, Baruch] Bar Ilan Univ, Dept Math, IL-52900 Ramat Gan, Israel.
   [Barabasi, Albert-Laszlo] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
   [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary.
C3 Northeastern University; Bar Ilan University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Central European University
RP Barabási, AL (corresponding author), Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.; Barabási, AL (corresponding author), Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.; Barabási, AL (corresponding author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.; Barabási, AL (corresponding author), Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary.
EM alb@neu.edu
NR 29
TC 883
Z9 1018
U1 48
U2 1092
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 307
EP 312
DI 10.1038/nature16948
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100031
PM 26887493
DA 2026-03-09
ER

PT J
AU Theillet, FX
   Binolfi, A
   Bekei, B
   Martorana, A
   Rose, HM
   Stuiver, M
   Verzini, S
   Lorenz, D
   van Rossum, M
   Goldfarb, D
   Selenko, P
AF Theillet, Francois-Xavier
   Binolfi, Andres
   Bekei, Beata
   Martorana, Andrea
   Rose, Honor May
   Stuiver, Marchel
   Verzini, Silvia
   Lorenz, Dorothea
   van Rossum, Marleen
   Goldfarb, Daniella
   Selenko, Philipp
TI Structural disorder of monomeric α-synuclein persists in mammalian cells
SO NATURE
LA English
DT Article
ID n-terminal acetylation; protein; aggregation; nmr; reveals; forms; dynamics
AB Intracellular aggregation of the human amyloid protein alpha-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of alpha-synuclein in different mammalian cell types. We show that the disordered nature of monomeric alpha-synuclein is stably preserved in non-neuronal and neuronal cells. Under physiological cell conditions, alpha-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-beta component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote alpha-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells.
C1 [Theillet, Francois-Xavier; Binolfi, Andres; Bekei, Beata; Rose, Honor May; Stuiver, Marchel; Verzini, Silvia; van Rossum, Marleen; Selenko, Philipp] Leibniz Inst Mol Pharmacol FMP Berlin, Dept NMR Supported Struct Biol, In Cell NMR Lab, Robert Rossle Str 10, D-13125 Berlin, Germany.
   [Martorana, Andrea; Goldfarb, Daniella] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
   [Lorenz, Dorothea] Leibniz Inst Mol Pharmacol FMP Berlin, Dept Mol Physiol & Cell Biol, Robert Rossle Str 10, D-13125 Berlin, Germany.
   [Theillet, Francois-Xavier] CEA Saclay, Dept Biochem Biophys & Struct Biol, Inst Integrat Biol Cell I2BC, CNRS,UMR 198, Bat 144, F-91191 Gif Sur Yvette, France.
   [Binolfi, Andres] Max Planck Lab Struct Biol Chem & Mol Biophys Ros, 27 Febrero 210 Bis,S2002LRK, Rosario, Santa Fe, Argentina.
   [Binolfi, Andres] Inst Invest Descubrimiento Farmacos Rosario IIDEF, 27 Febrero 210 Bis,S2002LRK, Rosario, Santa Fe, Argentina.
C3 Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Weizmann Institute of Science; Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CEA
RP Selenko, P (corresponding author), Leibniz Inst Mol Pharmacol FMP Berlin, Dept NMR Supported Struct Biol, In Cell NMR Lab, Robert Rossle Str 10, D-13125 Berlin, Germany.
EM selenko@fmp-berlin.de
FU Association pour la Recherche sur le Cancer (ARC); Israel Science Foundation (ISF) [1114/12]; Deutsche Forschungsgemeinschaft (DFG) [SE1794/1-1]; European Research Council (ERC) [647474]; European Research Council (ERC) [647474] Funding Source: European Research Council (ERC)
NR 36
TC 730
Z9 818
U1 8
U2 382
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 45
EP +
DI 10.1038/nature16531
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500029
PM 26808899
DA 2026-03-09
ER

PT J
AU Engreitz, JM
   Haines, JE
   Perez, EM
   Munson, G
   Chen, J
   Kane, M
   McDonel, PE
   Guttman, M
   Lander, ES
AF Engreitz, Jesse M.
   Haines, Jenna E.
   Perez, Elizabeth M.
   Munson, Glen
   Chen, Jenny
   Kane, Michael
   McDonel, Patrick E.
   Guttman, Mitchell
   Lander, Eric S.
TI Local regulation of gene expression by lncRNA promoters, transcription and splicing
SO NATURE
LA English
DT Article
ID long noncoding rnas; chromatin; reveals; mammals; annotation; evolution
AB Mammalian genomes are pervasively transcribed(1,2) to produce thousands of long non-coding RNAs (lncRNAs)(3,4). A few of these lncRNAs have been shown to recruit regulatory complexes through RNA-protein interactions to influence the expression of nearby genes(5-7), and it has been suggested that many other lncRNAs can also act as local regulators(8,9). Such local functions could explain the observation that lncRNA expression is often correlated with the expression of nearby genes(2,10,11). However, these correlations have been challenging to dissect(12) and could alternatively result from processes that are not mediated by the lncRNA transcripts themselves. For example, some gene promoters have been proposed to have dual functions as enhancers(13-16), and the process of transcription itself may contribute to gene regulation by recruiting activating factors or remodelling nucleosomes(10,17,18). Here we use genetic manipulation in mouse cell lines to dissect 12 genomic loci that produce lncRNAs and find that 5 of these loci influence the expression of a neighbouring gene in cis. Notably, none of these effects requires the specific lncRNA transcripts themselves and instead involves general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Furthermore, such effects are not limited to lncRNA loci: we find that four out of six protein-coding loci also influence the expression of a neighbour. These results demonstrate that cross-talk among neighbouring genes is a prevalent phenomenon that can involve multiple mechanisms and cis-regulatory signals, including a role for RNA splice sites. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs and broadly contribute to the regulation of both coding and non-coding genes.
C1 [Engreitz, Jesse M.; Haines, Jenna E.; Perez, Elizabeth M.; Munson, Glen; Chen, Jenny; Kane, Michael; McDonel, Patrick E.; Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Engreitz, Jesse M.; Chen, Jenny] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Guttman, Mitchell] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
   [Lander, Eric S.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Lander, Eric S.] Harvard Med Sch, Dept Syst Biol, Boston, MA 02114 USA.
   [Haines, Jenna E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [McDonel, Patrick E.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); California Institute of Technology; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; University of California System; University of California Berkeley; University of Massachusetts System; University of Massachusetts Worcester
RP Lander, ES (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Lander, ES (corresponding author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Lander, ES (corresponding author), Harvard Med Sch, Dept Syst Biol, Boston, MA 02114 USA.
EM eric@broadinstitute.org
FU Fannie and John Hertz Foundation; National Defense Science and Engineering Graduate Fellowship; NIH [DP5OD012190]; Edward Mallinckrodt Foundation; Sontag Foundation; Searle Scholars Program; Broad Institute
NR 28
TC 976
Z9 1122
U1 4
U2 255
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 452
EP 455
DI 10.1038/nature20149
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700059
PM 27783602
DA 2026-03-09
ER

PT J
AU Thomas, J
   Ma, CP
   McConnell, NJ
   Greene, JE
   Blakeslee, JP
   Janish, R
AF Thomas, Jens
   Ma, Chung-Pei
   McConnell, Nicholas J.
   Greene, Jenny E.
   Blakeslee, John P.
   Janish, Ryan
TI A 17-billion-solar-mass black hole in a group galaxy with a diffuse core
SO NATURE
LA English
DT Article
ID initial mass function; to-light ratio; sight velocity distributions; elliptic galaxy; fundamental plane; space-telescope; survey. i.; dark halo; cluster; centers
AB Quasars are associated with and powered by the accretion of material onto massive black holes; the detection of highly luminous quasars with redshifts greater than z = 6 suggests that black holes of up to ten billion solar masses already existed 13 billion years ago(1). Two possible present-day 'dormant' descendants of this population of 'active' black holes have been found(2) in the galaxies NGC 3842 and NGC 4889 at the centres of the Leo and Coma galaxy clusters, which together form the central region of the Great Wall(3)-the largest local structure of galaxies. The most luminous quasars, however, are not confined to such high-density regions of the early Universe(4,5); yet dormant black holes of this high mass have not yet been found outside of modern-day rich clusters. Here we report observations of the stellar velocity distribution in the galaxy NGC 1600-a relatively isolated elliptical galaxy near the centre of a galaxy group at a distance of 64 megaparsecs from Earth. We use orbit superposition models to determine that the black hole at the centre of NGC 1600 has a mass of 17 billion solar masses. The spatial distribution of stars near the centre of NGC 1600 is rather diffuse. We find that the region of depleted stellar density in the cores of massive elliptical galaxies extends over the same radius as the gravitational sphere of influence of the central black holes, and interpret this as the dynamical imprint of the black holes.
C1 [Thomas, Jens] Max Planck Inst Extraterr Phys, Giessenbachstr 1, D-85741 Garching, Germany.
   [Thomas, Jens] Univ Sternwarte Munchen, Scheinerstr 1, D-81679 Munich, Germany.
   [Ma, Chung-Pei] Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
   [McConnell, Nicholas J.; Blakeslee, John P.] NRC Herzberg Inst Astrophys, Domin Astrophys Observ, Victoria, BC V9E 2E7, Canada.
   [Greene, Jenny E.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Janish, Ryan] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
C3 Max Planck Society; University of Munich; University of California System; University of California Berkeley; National Research Council Canada; Princeton University; University of California System; University of California Berkeley
RP Thomas, J (corresponding author), Max Planck Inst Extraterr Phys, Giessenbachstr 1, D-85741 Garching, Germany.; Thomas, J (corresponding author), Univ Sternwarte Munchen, Scheinerstr 1, D-81679 Munich, Germany.; Ma, CP (corresponding author), Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
EM jthomas@mpe.mpg.de; cpma@berkeley.edu
FU National Science Foundation (NSF); Miller Institute for Basic Research in Science, University of California, Berkeley; Beatrice Watson Parrent Fellowship; Plaskett Fellowship; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1411642] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1411945] Funding Source: National Science Foundation
NR 64
TC 129
Z9 138
U1 0
U2 1
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 340
EP +
DI 10.1038/nature17197
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700027
PM 27049949
DA 2026-03-09
ER

PT J
AU Yokota, Y
   Ishikawa, T
   Watanabe, S
   Tashiro, T
   Asada, A
AF Yokota, Yusuke
   Ishikawa, Tadashi
   Watanabe, Shun-ichi
   Tashiro, Toshiharu
   Asada, Akira
TI Seafloor geodetic constraints on interplate coupling of the Nankai Trough megathrust zone
SO NATURE
LA English
DT Article
ID tohoku-oki earthquake; subduction zone; crustal deformation; southwest japan; slip; gps; geometry; rupture; locking; kyushu
AB Interplate megathrust earthquakes have inflicted catastrophic damage on human society. Such an earthquake is predicted to occur in the near future along the Nankai Trough off southwestern Japan-an economically active and densely populated area in which megathrust earthquakes have already occurred(1-5). Megathrust earthquakes are the result of a plate-subduction mechanism and occur at slip-deficit regions (also known as 'coupling' regions)(6,7), where friction prevents plates from slipping against each other and the accumulated energy is eventually released forcefully. Many studies have attempted to capture distributions of slip-deficit rates (SDRs) in order to predict earthquakes(8-10). However, these studies could not obtain a complete view of the earthquake source region, because they had no seafloor geodetic data. The Hydrographic and Oceanographic Department of the Japan Coast Guard (JHOD) has been developing a precise and sustainable seafloor geodetic observation network(11) in this subduction zone to obtain information related to offshore SDRs. Here, we present seafloor geodetic observation data and an offshore interplate SDR-distribution model. Our data suggest that most offshore regions in this subduction zone have positive SDRs. Specifically, our observations indicate previously unknown regions of high SDR that will be important for tsunami disaster mitigation, and regions of low SDR that are consistent with distributions of shallow slow earthquakes and subducting seamounts. This is the first direct evidence that coupling conditions might be related to these seismological and geological phenomena. Our findings provide information for inferring megathrust earthquake scenarios and interpreting research on the Nankai Trough subduction zone.
C1 [Yokota, Yusuke; Ishikawa, Tadashi; Watanabe, Shun-ichi; Tashiro, Toshiharu] Japan Coast Guard, Hydrog & Oceanog Dept, Chiyoda Ku, 3-1-1 Kasumigaseki, Tokyo 1008932, Japan.
   [Asada, Akira] Univ Tokyo, Inst Ind Sci, Meguro Ku, 4-6-1 Komaba, Tokyo 1538505, Japan.
C3 University of Tokyo
RP Yokota, Y (corresponding author), Japan Coast Guard, Hydrog & Oceanog Dept, Chiyoda Ku, 3-1-1 Kasumigaseki, Tokyo 1008932, Japan.
EM eisei@jodc.go.jp
NR 45
TC 246
Z9 273
U1 1
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 374
EP +
DI 10.1038/nature17632
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800033
PM 27281197
DA 2026-03-09
ER

PT J
AU Shi, SL
   Wong, ZL
   Buchwald, SL
AF Shi, Shi-Liang
   Wong, Zackary L.
   Buchwald, Stephen L.
TI Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols
SO NATURE
LA English
DT Article
ID asymmetric hydroamination; diastereoselectivity; aldehydes; alkenes; olefins; ketones
AB The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation(1,2). Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge(3). Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.
C1 [Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Buchwald, SL (corresponding author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM sbuchwal@mit.edu
FU National Institutes of Health [GM-58160]; National Science Foundation [CHE-0946721]
NR 30
TC 234
Z9 256
U1 1
U2 237
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 353
EP 356
DI 10.1038/nature17191
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700029
PM 27018656
DA 2026-03-09
ER

PT J
AU Sánchez-Danés, A
   Hannezo, E
   Larsimont, JC
   Liagre, M
   Youssef, KK
   Simons, BD
   Blanpain, C
AF Sanchez-Danes, Adriana
   Hannezo, Edouard
   Larsimont, Jean-Christophe
   Liagre, Melanie
   Youssef, Khalil Kass
   Simons, Benjamin D.
   Blanpain, Cedric
TI Defining the clonal dynamics leading to mouse skin tumour initiation
SO NATURE
LA English
DT Article
ID intestinal stem-cells; lineage; origin; progression; model
AB The changes in cell dynamics after oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the effect of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, initiated tumour formation upon oncogenic hedgehog signalling. This difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase in symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is dependent not only on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.
C1 [Sanchez-Danes, Adriana; Larsimont, Jean-Christophe; Liagre, Melanie; Youssef, Khalil Kass; Blanpain, Cedric] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
   [Hannezo, Edouard; Simons, Benjamin D.] Dept Phys, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Hannezo, Edouard; Simons, Benjamin D.] Univ Cambridge, Canc Res UK Gurdon Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QN, England.
   [Hannezo, Edouard; Simons, Benjamin D.] Univ Cambridge, Stem Cell Inst, MRC, Wellcome Trust, Cambridge CB2 1QR, England.
   [Blanpain, Cedric] Univ Libre Bruxelles, WELBIO, B-1070 Brussels, Belgium.
C3 Universite Libre de Bruxelles; University of Cambridge; Wellcome Trust Sanger Institute; University of Cambridge; Wellcome Trust; Cancer Research UK; Wellcome Trust; Wellcome Trust Sanger Institute; University of Cambridge; WELBIO; Universite Libre de Bruxelles
RP Blanpain, C (corresponding author), Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.; Simons, BD (corresponding author), Dept Phys, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.; Simons, BD (corresponding author), Univ Cambridge, Canc Res UK Gurdon Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QN, England.; Simons, BD (corresponding author), Univ Cambridge, Stem Cell Inst, MRC, Wellcome Trust, Cambridge CB2 1QR, England.; Blanpain, C (corresponding author), Univ Libre Bruxelles, WELBIO, B-1070 Brussels, Belgium.
EM bds10@cam.ac.uk; Cedric.Blanpain@ulb.ac.be
FU FNRS; FRIA; Wellcome Trust [098357/Z/12/Z, 110326/Z/15/Z]; Trinity College, Cambridge; IUAP program; Fondation contre le Cancer; ULB fondation; foundation Bettencourt Schueller; foundation Baillet Latour; European Research Council; Engineering and Physical Sciences Research Council [EP/F032773/1] Funding Source: researchfish; Medical Research Council [MC_PC_12009] Funding Source: researchfish; Wellcome Trust [098357/Z/12/Z] Funding Source: researchfish; Wellcome Trust [110326/Z/15/Z] Funding Source: Wellcome Trust; EPSRC [EP/F032773/1] Funding Source: UKRI
NR 27
TC 97
Z9 113
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 298
EP +
DI 10.1038/nature19069
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900028
PM 27459053
DA 2026-03-09
ER

PT J
AU Ng, SWK
   Mitchell, A
   Kennedy, JA
   Chen, WC
   McLeod, J
   Ibrahimova, N
   Arruda, A
   Popescu, A
   Gupta, V
   Schimmer, AD
   Schuh, AC
   Yee, KW
   Bullinger, L
   Herold, T
   Görlich, D
   Büchner, T
   Hiddemann, W
   Berdel, WE
   Wörmann, B
   Cheok, M
   Preudhomme, C
   Dombret, H
   Metzeler, K
   Buske, C
   Löwenberg, B
   Valk, PJM
   Zandstra, PW
   Minden, MD
   Dick, JE
   Wang, JCY
AF Ng, Stanley W. K.
   Mitchell, Amanda
   Kennedy, James A.
   Chen, Weihsu C.
   McLeod, Jessica
   Ibrahimova, Narmin
   Arruda, Andrea
   Popescu, Andreea
   Gupta, Vikas
   Schimmer, Aaron D.
   Schuh, Andre C.
   Yee, Karen W.
   Bullinger, Lars
   Herold, Tobias
   Goerlich, Dennis
   Buechner, Thomas
   Hiddemann, Wolfgang
   Berdel, Wolfgang E.
   Woermann, Bernhard
   Cheok, Meyling
   Preudhomme, Claude
   Dombret, Herve
   Metzeler, Klaus
   Buske, Christian
   Lowenberg, Bob
   Valk, Peter J. M.
   Zandstra, Peter W.
   Minden, Mark D. .
   Dick, John E.
   Wang, Jean C. Y.
TI A 17-gene stemness score for rapid determination of risk in acute leukaemia
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; proportional hazards model; gene-expression signature; gemtuzumab ozogamicin; regularization paths; adult patients; aml; recommendations; resistance; survival
AB Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML)(1). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories(2,3). However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors(4). There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials(5). The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance(6-10). Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC+ and 89 LSC- cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.
C1 [Ng, Stanley W. K.; Zandstra, Peter W.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5G 1A1, Canada.
   [Mitchell, Amanda; Kennedy, James A.; Chen, Weihsu C.; McLeod, Jessica; Ibrahimova, Narmin; Arruda, Andrea; Popescu, Andreea; Gupta, Vikas; Schimmer, Aaron D.; Schuh, Andre C.; Yee, Karen W.; Minden, Mark D. .; Dick, John E.; Wang, Jean C. Y.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [Kennedy, James A.; Gupta, Vikas; Schimmer, Aaron D.; Schuh, Andre C.; Yee, Karen W.; Minden, Mark D. .; Wang, Jean C. Y.] Univ Hlth Network, Div Med Oncol & Hematol, Dept Med, Toronto, ON M5G 2M9, Canada.
   [Kennedy, James A.; Gupta, Vikas; Schimmer, Aaron D.; Schuh, Andre C.; Yee, Karen W.; Minden, Mark D. .; Wang, Jean C. Y.] Univ Toronto, Dept Med, Toronto, ON M5G 1A1, Canada.
   [Schimmer, Aaron D.; Minden, Mark D. .] Univ Toronto, Dept Med Biophys, Toronto, ON M5G IA1, Canada.
   [Bullinger, Lars] Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany.
   [Herold, Tobias; Hiddemann, Wolfgang; Metzeler, Klaus] Univ Munich, Dept Internal Med 3, D-81377 Munich, Germany.
   [Herold, Tobias; Hiddemann, Wolfgang; Metzeler, Klaus] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
   [Goerlich, Dennis] Univ Munster, Inst Biostat & Clin Res, D-48149 Munster, Germany.
   [Buechner, Thomas; Berdel, Wolfgang E.] Univ Munster, Dept Med Hematol & Oncol, D-48149 Munster, Germany.
   [Woermann, Bernhard] Charite, Dept Hematol Oncol & Tumor Immunol, Campus Virchow, D-10117 Berlin, Germany.
   [Cheok, Meyling] Jean Pierre AUBERT Res Ctr, Inst Canc Res Lille, UMR S 1172, F-59045 Lille, France.
   [Preudhomme, Claude] Univ Hosp Lille, Ctr Pathol, Hematol Lab, F-59037 Lille, France.
   [Dombret, Herve] Univ Paris Diderot, Dept Hematol, St Louis Hosp, F-75010 Paris, France.
   [Buske, Christian] Univ Hosp Ulm, Inst Expt Canc Res, Comprehens Canc Ctr Ulm, D-89081 Ulm, Germany.
   [Lowenberg, Bob; Valk, Peter J. M.] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 CE Rotterdam, Netherlands.
   [Dick, John E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1A1, Canada.
C3 University of Toronto; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University Health Network Toronto; University of Toronto; University of Toronto; Ulm University; University of Munich; Helmholtz Association; German Cancer Research Center (DKFZ); University of Munster; University of Munster; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Lille; Universite de Lille; CHU Lille; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Ulm University; Erasmus University Rotterdam; Erasmus MC; University of Toronto
RP Wang, JCY (corresponding author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.; Wang, JCY (corresponding author), Univ Hlth Network, Div Med Oncol & Hematol, Dept Med, Toronto, ON M5G 2M9, Canada.; Wang, JCY (corresponding author), Univ Toronto, Dept Med, Toronto, ON M5G 1A1, Canada.
EM jwang@uhnresearch.ca
FU Ontario Institute for Cancer Research; province of Ontario; Cancer Stem Cell Consortium; Government of Canada through Genome Canada; Ontario Genomics Institute [OGI-047]; Canadian Institutes of Health Research [CSC-105367]; Canadian Cancer Society; Terry Fox Foundation; Canada Research Chair; Philip S. Orsino Chair in Leukemia Research; Collaborative Translational Cancer Research Grant from the Princess Margaret Cancer Centre (formerly Ontario Cancer Institute); Leukemia & Lymphoma Society of Canada [493946]; Stem Cell Network [492019]; Ontario Graduate Scholarships; Ontario Ministry of Health and Long Term Care (OMOHLTC); Deutsche Forschungsgemeinschaft (Heisenberg-Professur) [BU 1339/8-1]; Wilhelm-Sander-Stiftung [2013.086.1]; Deutsche Forschungsgemeinschaft [DFG SFB 1243]; European Hematology Association [TRTH1, RG11] Funding Source: researchfish
NR 53
TC 682
Z9 764
U1 2
U2 83
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 433
EP +
DI 10.1038/nature20598
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800042
PM 27926740
DA 2026-03-09
ER

PT J
AU Grace, JB
   Anderson, TM
   Seabloom, EW
   Borer, ET
   Adler, PB
   Harpole, WS
   Hautier, Y
   Hillebrand, H
   Lind, EM
   Pärtel, M
   Bakker, JD
   Buckley, YM
   Crawley, MJ
   Damschen, EI
   Davies, KF
   Fay, PA
   Firn, J
   Gruner, DS
   Hector, A
   Knops, JMH
   MacDougall, AS
   Melbourne, BA
   Morgan, JW
   Orrock, JL
   Prober, SM
   Smith, MD
AF Grace, James B.
   Anderson, T. Michael
   Seabloom, Eric W.
   Borer, Elizabeth T.
   Adler, Peter B.
   Harpole, W. Stanley
   Hautier, Yann
   Hillebrand, Helmut
   Lind, Eric M.
   Paertel, Meelis
   Bakker, Jonathan D.
   Buckley, Yvonne M.
   Crawley, Michael J.
   Damschen, Ellen I.
   Davies, Kendi F.
   Fay, Philip A.
   Firn, Jennifer
   Gruner, Daniel S.
   Hector, Andy
   Knops, Johannes M. H.
   MacDougall, Andrew S.
   Melbourne, Brett A.
   Morgan, John W.
   Orrock, John L.
   Prober, Suzanne M.
   Smith, Melinda D.
TI Integrative modelling reveals mechanisms linking productivity and plant species richness
SO NATURE
LA English
DT Article
ID structural equation models; net primary production; ecosystem function; biodiversity; diversity; ecology; scale; hypothesis
AB How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology(1). Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns(2,3). Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models(4-7). These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis(8), is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.
C1 [Grace, James B.] US Geol Survey, Wetland & Aquat Res Ctr, Lafayette, LA 70506 USA.
   [Anderson, T. Michael] Wake Forest Univ, Dept Biol, Winston Salem, NC 27109 USA.
   [Seabloom, Eric W.; Borer, Elizabeth T.; Lind, Eric M.] Univ Minnesota, Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Adler, Peter B.] Utah State Univ, Dept Wildland Resources, Logan, UT 84322 USA.
   [Adler, Peter B.] Utah State Univ, Ctr Ecol, Logan, UT 84322 USA.
   [Harpole, W. Stanley] UFZ Helmholtz Ctr Environm Res, Dept Physiol Divers, D-04318 Leipzig, Germany.
   [Harpole, W. Stanley] German Ctr Integrat Biodivers Res iDiv, D-04103 Leipzig, Germany.
   [Harpole, W. Stanley] Univ Halle Wittenberg, D-06108 Halle, Saale, Germany.
   [Hautier, Yann] Univ Utrecht, Dept Biol, Ecol & Biodivers Grp, NL-3584 CH Utrecht, Netherlands.
   [Hillebrand, Helmut] Carl von Ossietzky Univ Oldenburg, Inst Chem & Biol, Marine Environm, D-26381 Wilhelmshaven, Germany.
   [Paertel, Meelis] Univ Tartu, Inst Ecol & Earth Sci, EE-51005 Tartu, Estonia.
   [Bakker, Jonathan D.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Buckley, Yvonne M.] Univ Dublin Trinity Coll, Sch Nat Sci, Zool, Dublin 2, Ireland.
   [Crawley, Michael J.] Univ London Imperial Coll Sci Technol & Med, Dept Biol Sci, Ascot SL5 7PY, Berks, England.
   [Damschen, Ellen I.; Orrock, John L.] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
   [Davies, Kendi F.; Melbourne, Brett A.] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
   [Fay, Philip A.] ARS, Grassland Soil & Water Res Lab, USDA, Temple, TX 76502 USA.
   [Firn, Jennifer] Queensland Univ Technol, Sch Earth Environm & Biol Sci, Brisbane, Qld 4001, Australia.
   [Gruner, Daniel S.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Hector, Andy] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
   [Knops, Johannes M. H.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
   [MacDougall, Andrew S.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Morgan, John W.] La Trobe Univ, Dept Ecol Environm & Evolut, Bundoora, Vic 3083, Australia.
   [Prober, Suzanne M.] CSIRO Land & Water, Wembley, WA 6913, Australia.
   [Smith, Melinda D.] Colorado State Univ, Dept Biol, Ft Collins, CO 80526 USA.
C3 United States Department of the Interior; United States Geological Survey; Wake Forest University; University of Minnesota System; University of Minnesota Twin Cities; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); Martin Luther University Halle Wittenberg; Utrecht University; Carl von Ossietzky Universitat Oldenburg; University of Tartu; Tartu University Institute of Ecology & Earth Sciences; University of Washington; University of Washington Seattle; Trinity College Dublin; Imperial College London; University of Wisconsin System; University of Wisconsin Madison; University of Colorado System; University of Colorado Boulder; United States Department of Agriculture (USDA); Queensland University of Technology (QUT); University System of Maryland; University of Maryland College Park; University of Oxford; University of Nebraska System; University of Nebraska Lincoln; University of Guelph; La Trobe University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Land & Water; Colorado State University System; Colorado State University Fort Collins
RP Grace, JB (corresponding author), US Geol Survey, Wetland & Aquat Res Ctr, 700 Cajundome Blvd, Lafayette, LA 70506 USA.
EM gracej@usgs.gov
FU US Geological Survey; Nutrient Network; National Science Foundation (NSF) Research Coordination Network [NSF-DEB-1042132]; National Science Foundation (NSF) Long Term Ecological Research program [NSF-DEB-1234162]; UMN Institute on the Environment [DG-0001-13]; Division Of Environmental Biology; Direct For Biological Sciences [1440484, 1234162] Funding Source: National Science Foundation
NR 45
TC 676
Z9 781
U1 45
U2 1074
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2016
VL 529
IS 7586
BP 390
EP +
DI 10.1038/nature16524
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB2QT
UT WOS:000368354800045
PM 26760203
DA 2026-03-09
ER

PT J
AU Gómez, JM
   Verdú, M
   Gonzalez-Megías, A
   Méndez, M
AF Maria Gomez, Jose
   Verdu, Miguel
   Gonzalez-Megias, Adela
   Mendez, Marcos
TI The phylogenetic roots of human lethal violence
SO NATURE
LA English
DT Article
ID evolution; aggression; neanderthals; infanticide; mammalia; warfare; traits; signal; state; war
AB The psychological, sociological and evolutionary roots of conspecific violence in humans are still debated, despite attracting the attention of intellectuals for over two millennia(1-11). Here we propose a conceptual approach towards understanding these roots based on the assumption that aggression in mammals, including humans, has a significant phylogenetic component. By compiling sources of mortality from a comprehensive sample of mammals, we assessed the percentage of deaths due to conspecifics and, using phylogenetic comparative tools, predicted this value for humans. The proportion of human deaths phylogenetically predicted to be caused by interpersonal violence stood at 2%. This value was similar to the one phylogenetically inferred for the evolutionary ancestor of primates and apes, indicating that a certain level of lethal violence arises owing to our position within the phylogeny of mammals. It was also similar to the percentage seen in prehistoric bands and tribes, indicating that we were as lethally violent then as common mammalian evolutionary history would predict. However, the level of lethal violence has changed through human history and can be associated with changes in the socio-political organization of human populations. Our study provides a detailed phylogenetic and historical context against which to compare levels of lethal violence observed throughout our history.
C1 [Maria Gomez, Jose] EEZA CSIC, E-04120 Almeria, Spain.
   [Maria Gomez, Jose] Univ Granada, Dept Ecol, E-18071 Granada, Spain.
   [Verdu, Miguel] Ctr Invest Desertificac CSIC UV GV, E-46113 Valencia, Spain.
   [Gonzalez-Megias, Adela] Univ Granada, Dept Zool, E-18071 Granada, Spain.
   [Mendez, Marcos] Univ Rey Juan Carlos, Area Biodiversidad & Conservac, E-28933 Madrid, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Experimental de Zonas Aridas (EEZA); University of Granada; Consejo Superior de Investigaciones Cientificas (CSIC); University of Valencia; CSIC-GV-UV - Centro de Investigaciones sobre Desertificacion (CIDE); University of Granada; Universidad Rey Juan Carlos
RP Gómez, JM (corresponding author), EEZA CSIC, E-04120 Almeria, Spain.; Gómez, JM (corresponding author), Univ Granada, Dept Ecol, E-18071 Granada, Spain.
EM jmgreyes@eeza.csic.es
NR 51
TC 126
Z9 159
U1 2
U2 158
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 233
EP +
DI 10.1038/nature19758
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000043
PM 27680701
DA 2026-03-09
ER

PT J
AU Zhang, Y
   Luo, Y
   Zhang, Y
   Yu, YJ
   Kuang, YM
   Zhang, L
   Meng, QS
   Luo, Y
   Yang, JL
   Dong, ZC
   Hou, JG
AF Zhang, Yang
   Luo, Yang
   Zhang, Yao
   Yu, Yun-Jie
   Kuang, Yan-Min
   Zhang, Li
   Meng, Qiu-Shi
   Luo, Yi
   Yang, Jin-Long
   Dong, Zhen-Chao
   Hou, J. G.
TI Visualizing coherent intermolecular dipole-dipole coupling in real space
SO NATURE
LA English
DT Article
ID energy-transfer; free-base; resolution; photon; fluorescence; spectroscopy; absorption; emission
AB Many important energy-transfer and optical processes, in both biological and artificial systems, depend crucially on excitonic coupling that spans several chromophores(1-9). Such coupling can in principle be described in a straightforward manner by considering the coherent intermolecular dipole-dipole interactions involved(10,11). However, in practice, it is challenging to directly observe in real space the coherent dipole coupling and the related exciton delocalizations, owing to the diffraction limit in conventional optics. Here we demonstrate that the highly localized excitations that are produced by electrons tunnelling from the tip of a scanning tunnelling microscope, in conjunction with imaging of the resultant luminescence, can be used to map the spatial distribution of the excitonic coupling in well-defined arrangements of a few zinc-phthalocyanine molecules. The luminescence patterns obtained for excitons in a dimer, which are recorded for different energy states and found to resemble sigma and pi molecular orbitals, reveal the local optical response of the system and the dependence of the local optical response on the relative orientation and phase of the transition dipoles of the individual molecules in the dimer. We generate an in-line arrangement up to four zinc-phthalocyanine molecules, with a larger total transition dipole, and show that this results in enhanced 'single-molecule' superradiance from the oligomer upon site-selective excitation. These findings demonstrate that our experimental approach provides detailed spatial information about coherent dipole-dipole coupling in molecular systems, which should enable a greater understanding and rational engineering of light-harvesting structures and quantum light sources.
C1 [Zhang, Yang; Luo, Yang; Zhang, Yao; Yu, Yun-Jie; Kuang, Yan-Min; Zhang, Li; Meng, Qiu-Shi; Luo, Yi; Yang, Jin-Long; Dong, Zhen-Chao; Hou, J. G.] Univ Sci & Technol China, Hefei Natl Lab Phys Sci, Microscale & Synerget Innovat Ctr Quantum Informa, Hefei 230026, Anhui, Peoples R China.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Dong, ZC; Hou, JG (corresponding author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci, Microscale & Synerget Innovat Ctr Quantum Informa, Hefei 230026, Anhui, Peoples R China.
EM zcdong@ustc.edu.cn; jghou@ustc.edu.cn
FU National Basic Research Program of China; Strategic Priority Research Program of the Chinese Academy of Sciences; Natural Science Foundation of China; Fundamental Research Funds for the Central Universities; Hefei Science Center of the Chinese Academy of Sciences
NR 45
TC 331
Z9 365
U1 9
U2 612
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 623
EP +
DI 10.1038/nature17428
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400035
PM 27029277
DA 2026-03-09
ER

PT J
AU Seifert, L
   Werba, G
   Tiwari, S
   Ly, NNG
   Alothman, S
   Alqunaibit, D
   Avanzi, A
   Barilla, R
   Daley, D
   Greco, SH
   Torres-Hernandez, A
   Pergamo, M
   Ochi, A
   Zambirinis, CP
   Pansari, M
   Rendon, M
   Tippens, D
   Hundeyin, M
   Mani, VR
   Hajdu, C
   Engle, D
   Miller, G
AF Seifert, Lena
   Werba, Gregor
   Tiwari, Shaun
   Nancy Ngoc Giao Ly
   Alothman, Sara
   Alqunaibit, Dalia
   Avanzi, Antonina
   Barilla, Rocky
   Daley, Donnele
   Greco, Stephanie H.
   Torres-Hernandez, Alejandro
   Pergamo, Matthew
   Ochi, Atsuo
   Zambirinis, Constantinos P.
   Pansari, Mridul
   Rendon, Mauricio
   Tippens, Daniel
   Hundeyin, Mautin
   Mani, Vishnu R.
   Hajdu, Cristina
   Engle, Dannielle
   Miller, George
TI The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression
SO NATURE
LA English
DT Article
ID cells; cancer; apoptosis; mice; receptor; tumor; carcinogenesis; chemotherapy; neoplasia
AB Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis(1). Conversely, cancer cells often disrupt apoptosis to survive(2,3). Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs(4,5). Here we report that the principal components of the necrosome, receptor-interacting protein (RIP) 1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle-its cognate receptor-was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.
C1 [Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Nancy Ngoc Giao Ly; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H.; Torres-Hernandez, Alejandro; Ochi, Atsuo; Zambirinis, Constantinos P.; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R.; Miller, George] NYU, Sch Med, Dept Surg, S Arthur Localio Lab, 550 First Ave, New York, NY 10016 USA.
   [Pergamo, Matthew; Miller, George] NYU, Sch Med, Dept Cell Biol, 550 First Ave, New York, NY 10016 USA.
   [Hajdu, Cristina] NYU, Sch Med, Dept Pathol, 550 First Ave, New York, NY 10016 USA.
   [Engle, Dannielle] Cold Spring Harbor Labs, Cold Spring Harbor, NY 11724 USA.
C3 New York University; New York University; New York University; Cold Spring Harbor Laboratory
RP Miller, G (corresponding author), NYU, Sch Med, Dept Surg, S Arthur Localio Lab, 550 First Ave, New York, NY 10016 USA.; Miller, G (corresponding author), NYU, Sch Med, Dept Cell Biol, 550 First Ave, New York, NY 10016 USA.
EM george.miller@nyumc.org
FU German Research Foundation; National Pancreas Foundation; Pancreatic Cancer Action Network; Lustgarten Foundation; National Institute of Health [CA155649, CA168611, CA193111]; Cancer Center Support Grant [P30CA016087]; National Center for the Advancement of Translational Science (NCATS) [UL1 TR000038]; National Cancer Institute [T32CA193111, P30CA016087] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001445] Funding Source: NIH RePORTER
NR 26
TC 520
Z9 565
U1 5
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 245
EP +
DI 10.1038/nature17403
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100042
PM 27049944
DA 2026-03-09
ER

PT J
AU Navon, N
   Gaunt, AL
   Smith, RP
   Hadzibabic, Z
AF Navon, Nir
   Gaunt, Alexander L.
   Smith, Robert P.
   Hadzibabic, Zoran
TI Emergence of a turbulent cascade in a quantum gas
SO NATURE
LA English
DT Article
ID superfluid turbulence; surface
AB A central concept in the modern understanding of turbulence is the existence of cascades of excitations from large to small length scales, or vice versa. This concept was introduced in 1941 by Kolmogorov and Obukhov(1,2), and such cascades have since been observed in various systems, including interplanetary plasmas(3), supernovae(4), ocean waves(5) and financial markets(6). Despite much progress, a quantitative understanding of turbulence remains a challenge, owing to the interplay between many length scales that makes theoretical simulations of realistic experimental conditions difficult. Here we observe the emergence of a turbulent cascade in a weakly interacting homogeneous Bose gas-a quantum fluid that can be theoretically described on all relevant length scales. We prepare a Bose-Einstein condensate in an optical box(7), drive it out of equilibrium with an oscillating force that pumps energy into the system at the largest length scale, study its nonlinear response to the periodic drive, and observe a gradual development of a cascade characterized by an isotropic power-law distribution in momentum space. We numerically model our experiments using the Gross-Pitaevskii equation and find excellent agreement with the measurements. Our experiments establish the uniform Bose gas as a promising new medium for investigating many aspects of turbulence, including the interplay between vortex and wave turbulence, and the relative importance of quantum and classical effects.
C1 [Navon, Nir; Gaunt, Alexander L.; Smith, Robert P.; Hadzibabic, Zoran] Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
C3 University of Cambridge
RP Navon, N (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM nn270@cam.ac.uk
FU AFOSR; ARO; DARPA OLE; EPSRC [EP/N011759/1]; ERC (QBox); Trinity College, Cambridge; Royal Society; Engineering and Physical Sciences Research Council [1104880, EP/N011759/1] Funding Source: researchfish; EPSRC [EP/N011759/1] Funding Source: UKRI
NR 30
TC 204
Z9 228
U1 1
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 72
EP +
DI 10.1038/nature20114
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100031
PM 27808196
DA 2026-03-09
ER

PT J
AU García-Prat, L
   Martínez-Vicente, M
   Perdiguero, E
   Ortet, L
   Rodríguez-Ubreva, J
   Rebollo, E
   Ruiz-Bonilla, V
   Gutarra, S
   Ballestar, E
   Serrano, AL
   Sandri, M
   Muñoz-Cánoves, P
AF Garcia-Prat, Laura
   Martinez-Vicente, Marta
   Perdiguero, Eusebio
   Ortet, Laura
   Rodriguez-Ubreva, Javier
   Rebollo, Elena
   Ruiz-Bonilla, Vanessa
   Gutarra, Susana
   Ballestar, Esteban
   Serrano, Antonio L.
   Sandri, Marco
   Munoz-Canoves, Pura
TI Autophagy maintains stemness by preventing senescence
SO NATURE
LA English
DT Article
ID skeletal-muscle; muscular-dystrophy; satellite cells; life-span; p38 mapk; quiescent; pathways; supports; niche; ros
AB During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.
C1 [Garcia-Prat, Laura; Perdiguero, Eusebio; Ortet, Laura; Ruiz-Bonilla, Vanessa; Gutarra, Susana; Serrano, Antonio L.; Munoz-Canoves, Pura] Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain.
   [Martinez-Vicente, Marta] Vall dHebron Res Inst, Neurodegenerat Dis Res Grp, CIBERNED, E-08035 Barcelona, Spain.
   [Rodriguez-Ubreva, Javier; Ballestar, Esteban] Bellvitge Biomed Res Inst IDIBELL, Chromatin & Dis Grp, Canc Epigenet & Biol Programme PEBC, E-08907 Lhospitalet De Llobregat, Spain.
   [Rebollo, Elena] CSIC, Adv Fluorescence Microscopy Unit, Mol Biol Inst Barcelona IBMB, E-08028 Barcelona, Spain.
   [Sandri, Marco] Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy.
   [Sandri, Marco] Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy.
   [Munoz-Canoves, Pura] ICREA, E-08908 Barcelona, Spain.
C3 Pompeu Fabra University; CIBERNED; CIBERNED; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Biologia Molecular de Barcelona (IBMB); University of Padua; Fondazione Telethon; Telethon Institute of Genetics & Medicine (TIGEM); ICREA
RP Muñoz-Cánoves, P (corresponding author), Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain.; Muñoz-Cánoves, P (corresponding author), ICREA, E-08908 Barcelona, Spain.
EM pura.munoz@upf.edu
FU MINECO, Spain [SAF2012-38547, SAF2015-67369-R, PLE2009-0124, SAF2009-08374]; "Maria de Maeztu" Programme for Units of Excellence in RD [MDM-2014-0370]; AFM; E-Rare/ERANET; Fundacio Marato TV3; MDA; EU-FP7 (Myoage); EU-FP7 (Optistem); EU-FP7 (Endostem); DuchennePP-NL; ISCIII, Spain [FIS-PS09/01267, FIS-PI13/02512, CP09/00184, PI14/01529]; CIBERNED; European Union ERC [282310-MyoPHAGY]; Foundation Leducq; Programa de Formacion de Personal Investigador (Spain); ICREA Funding Source: Custom
NR 54
TC 1109
Z9 1278
U1 18
U2 435
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 37
EP +
DI 10.1038/nature16187
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900022
PM 26738589
DA 2026-03-09
ER

PT J
AU Sallam, T
   Jones, MC
   Gilliland, T
   Zhang, L
   Wu, XH
   Eskin, A
   Sandhu, J
   Casero, D
   Vallim, TQD
   Hong, C
   Katz, M
   Lee, R
   Whitelegge, J
   Tontonoz, P
AF Sallam, Tamer
   Jones, Marius C.
   Gilliland, Thomas
   Zhang, Li
   Wu, Xiaohui
   Eskin, Ascia
   Sandhu, Jaspreet
   Casero, David
   Vallim, Thomas Q. de Aguiar
   Hong, Cynthia
   Katz, Melanie
   Lee, Richard
   Whitelegge, Julian
   Tontonoz, Peter
TI Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis
SO NATURE
LA English
DT Article
ID lxr-alpha; mice; protein; liver; gene; receptor; atherosclerosis; transcripts; activation; expression
AB Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux(1), facilitates cholesterol esterification by promoting fatty acid synthesis(2), and inhibits cholesterol uptake by the low-density lipoprotein receptor(3). The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.
C1 [Sallam, Tamer; Jones, Marius C.; Gilliland, Thomas; Zhang, Li; Wu, Xiaohui; Sandhu, Jaspreet; Casero, David; Hong, Cynthia; Tontonoz, Peter] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   [Sallam, Tamer; Wu, Xiaohui; Vallim, Thomas Q. de Aguiar] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA.
   [Eskin, Ascia] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Katz, Melanie; Lee, Richard] Ionis Pharmaceut, Carlsbad, CA 92008 USA.
   [Whitelegge, Julian] Univ Calif Los Angeles, NPI Semel Inst, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Ionis Pharmaceuticals, Inc.; University of California System; University of California Los Angeles
RP Tontonoz, P (corresponding author), Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
EM ptontonoz@mednet.ucla.edu
FU NIH [HL030568, HL066088, DK063491, HL128822, DK102559, HL69766]; American Heart Association [13POST17080115]; American College of Cardiology Presidential CDA; UCLA Cardiovascular Discovery Fund; American Heart Association (AHA) [13POST17080115] Funding Source: American Heart Association (AHA); National Heart Lung and Blood Institute [T32HL069766, T32HL007895] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK063491] Funding Source: NIH RePORTER
NR 38
TC 176
Z9 198
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 124
EP +
DI 10.1038/nature17674
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300047
PM 27251289
DA 2026-03-09
ER

PT J
AU Jordan, NV
   Bardia, A
   Wittner, BS
   Benes, C
   Ligorio, M
   Zheng, Y
   Yu, M
   Sundaresan, TK
   Licausi, JA
   Desai, R
   O'Keefe, RM
   Ebright, RY
   Boukhali, M
   Sil, S
   Onozato, ML
   Iafrate, AJ
   Kapur, R
   Sgroi, D
   Ting, DT
   Toner, M
   Ramaswamy, S
   Haas, W
   Maheswaran, S
   Haber, DA
AF Jordan, Nicole Vincent
   Bardia, Aditya
   Wittner, Ben S.
   Benes, Cyril
   Ligorio, Matteo
   Zheng, Yu
   Yu, Min
   Sundaresan, Tilak K.
   Licausi, Joseph A.
   Desai, Rushil
   O'Keefe, Ryan M.
   Ebright, Richard Y.
   Boukhali, Myriam
   Sil, Srinjoy
   Onozato, Maristela L.
   Iafrate, Anthony J.
   Kapur, Ravi
   Sgroi, Dennis
   Ting, David T.
   Toner, Mehmet
   Ramaswamy, Sridhar
   Haas, Wilhelm
   Maheswaran, Shyamala
   Haber, Daniel A.
TI HER2 expression identifies dynamic functional states within circulating breast cancer cells
SO NATURE
LA English
DT Article
ID tumor-cells; stem-cells; signaling pathways; hedgehog pathway; notch; inhibitor; tumorigenesis; trastuzumab; recurrence; axis
AB Circulating tumour cells in women with advanced oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy(1,2). In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2(-) primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2(+) and HER2(-) subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2(-), consistent with activation of multiple signalling pathways; HER2(-) circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2(+) and HER2(-) circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2(+) and HER2(-) circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2(+) state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2(-) phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance.
C1 [Jordan, Nicole Vincent; Bardia, Aditya; Wittner, Ben S.; Benes, Cyril; Ligorio, Matteo; Zheng, Yu; Yu, Min; Sundaresan, Tilak K.; Licausi, Joseph A.; Desai, Rushil; O'Keefe, Ryan M.; Ebright, Richard Y.; Boukhali, Myriam; Sil, Srinjoy; Onozato, Maristela L.; Iafrate, Anthony J.; Sgroi, Dennis; Ting, David T.; Ramaswamy, Sridhar; Haas, Wilhelm; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
   [Bardia, Aditya; Wittner, Ben S.; Benes, Cyril; Sundaresan, Tilak K.; Ting, David T.; Ramaswamy, Sridhar; Haas, Wilhelm; Haber, Daniel A.] Harvard Med Sch, Dept Med, Boston, MA 02114 USA.
   [Ligorio, Matteo; Toner, Mehmet; Maheswaran, Shyamala] Harvard Med Sch, Dept Surg, Boston, MA 02114 USA.
   [Onozato, Maristela L.; Iafrate, Anthony J.; Sgroi, Dennis] Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA.
   [Kapur, Ravi; Toner, Mehmet] Harvard Med Sch, Ctr Bioengn Med, Boston, MA 02114 USA.
   [Kapur, Ravi; Toner, Mehmet] Harvard Med Sch, Shriners Hosp, Boston, MA 02114 USA.
   [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Yu, Min] Univ Southern Calif, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90033 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; University of Southern California
RP Jordan, NV (corresponding author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
FU National Institutes of Health (NIH) [2RO1CA129933]; Howard Hughes Medical Institute; Breast Cancer Research Foundation; National Foundation for Cancer Research; Wellcome Trust [102696]; NIH [2U01EB012493, T32 CA009361]; Susan G. Komen Foundation [PDF16376429, K12 5K12CA087723]; National Cancer Institute [K12CA087723, R01CA129933] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 25
TC 328
Z9 376
U1 5
U2 245
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 102
EP 106
DI 10.1038/nature19328
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900047
PM 27556950
DA 2026-03-09
ER

PT J
AU Cavadini, S
   Fischer, ES
   Bunker, RD
   Potenza, A
   Lingaraju, GM
   Goldie, KN
   Mohamed, WI
   Faty, M
   Petzold, G
   Beckwith, REJ
   Tichkule, RB
   Hassiepen, U
   Abdulrahman, W
   Pantelic, RS
   Matsumoto, S
   Sugasawa, K
   Stahlberg, H
   Thomä, NH
AF Cavadini, Simone
   Fischer, Eric S.
   Bunker, Richard D.
   Potenza, Alessandro
   Lingaraju, Gondichatnahalli M.
   Goldie, Kenneth N.
   Mohamed, Weaam I.
   Faty, Mahamadou
   Petzold, Georg
   Beckwith, Rohan E. J.
   Tichkule, Ritesh B.
   Hassiepen, Ulrich
   Abdulrahman, Wassim
   Pantelic, Radosav S.
   Matsumoto, Syota
   Sugasawa, Kaoru
   Stahlberg, Henning
   Thomae, Nicolas H.
TI Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome
SO NATURE
LA English
DT Article
ID pigmentosum group-e; growth-factor receptor; dna-binding protein; damaged dna; c-cbl; structural basis; complex; scf; lenalidomide; architecture
AB The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 angstrom resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.
C1 [Cavadini, Simone; Fischer, Eric S.; Bunker, Richard D.; Potenza, Alessandro; Lingaraju, Gondichatnahalli M.; Mohamed, Weaam I.; Faty, Mahamadou; Petzold, Georg; Abdulrahman, Wassim; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
   [Cavadini, Simone; Fischer, Eric S.; Bunker, Richard D.; Potenza, Alessandro; Lingaraju, Gondichatnahalli M.; Mohamed, Weaam I.; Faty, Mahamadou; Petzold, Georg; Abdulrahman, Wassim; Thomae, Nicolas H.] Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland.
   [Fischer, Eric S.] Dana Farber Canc Inst, Dept Canc Biol, LC-4312,360 Longwood Ave, Boston, MA 02215 USA.
   [Fischer, Eric S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA.
   [Goldie, Kenneth N.; Pantelic, Radosav S.; Stahlberg, Henning] Univ Basel, Ctr Cellular Imaging & NanoAnalyt, Biozentrum, CH-4058 Basel, Switzerland.
   [Beckwith, Rohan E. J.; Tichkule, Ritesh B.] Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Hassiepen, Ulrich] Novartis Pharma AG, Inst Biomed Res, Novartis Campus, CH-4056 Basel, Switzerland.
   [Pantelic, Radosav S.] Gatan R&D, 5974 W Las Positas Blvd, Pleasanton, CA 94588 USA.
   [Matsumoto, Syota; Sugasawa, Kaoru] Kobe Univ, Org Adv Sci & Technol, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan.
   [Matsumoto, Syota; Sugasawa, Kaoru] Kobe Univ, Grad Sch Sci, Kobe, Hyogo 6578501, Japan.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; University of Basel; Novartis; Novartis USA; Universita della Svizzera Italiana; Novartis; Kobe University; Kobe University
RP Thomä, NH (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.; Thomä, NH (corresponding author), Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland.
EM nicolas.thoma@fmi.ch
FU Novartis Research Foundation; European Research Council [ERC-2014-ADG 666068 CSNCRL]; Swiss initiative for Systems Biology (SystemsX.ch grant 'C-CINA'); European Molecular Biology Organization (EMBO) [ALTF-1350-2013]; Human Frontier Science Program (HFSP) [LT000210/2014]; Boehringer Ingelheim Fonds
NR 47
TC 177
Z9 201
U1 1
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 598
EP +
DI 10.1038/nature17416
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400030
PM 27029275
DA 2026-03-09
ER

PT J
AU Dai, HQ
   Wang, BA
   Yang, L
   Chen, JJ
   Zhu, GC
   Sun, ML
   Ge, H
   Wang, R
   Hapman, DLC
   Tang, FC
   Sun, X
   Xu, GL
AF Dai, Hai-Qiang
   Wang, Bang-An
   Yang, Lu
   Chen, Jia-Jia
   Zhu, Guo-Chun
   Sun, Mei-Ling
   Ge, Hao
   Wang, Rui
   Hapman, Deborah L. C.
   Tang, Fuchou
   Sun, Xin
   Xu, Guo-Liang
TI TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling
SO NATURE
LA English
DT Article
ID one-step generation; methyltransferases dnmt3a; cre recombinase; methylation; 5-methylcytosine; transcriptome; expression; proteins; roles; tdg
AB Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation(1-3). Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined(4-9). Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling(10). Introduction of a single mutant allele of Nodal in the Tet mutant background partially restored patterning, suggesting that hyperactive Nodal signalling contributes to the gastrulation failure of Tet mutants. Increased Nodal signalling is probably due to diminished expression of the Lefty1 and Lefty2 genes, which encode inhibitors of Nodal signalling. Moreover, reduction in Lefty gene expression is linked to elevated DNA methylation, as both Lefty-Nodal signalling and normal morphogenesis are largely restored in Tet-deficient embryos when the Dnmt3a and Dnmt3b genes are disrupted. Additionally, a point mutation in Tet that specifically abolishes the dioxygenase activity causes similar morphological and molecular abnormalities as the null mutation. Taken together, our results show that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B. These findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation.
C1 [Dai, Hai-Qiang; Wang, Bang-An; Chen, Jia-Jia; Zhu, Guo-Chun; Xu, Guo-Liang] Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
   [Dai, Hai-Qiang; Wang, Bang-An; Chen, Jia-Jia; Zhu, Guo-Chun; Xu, Guo-Liang] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Dai, Hai-Qiang; Wang, Bang-An; Chen, Jia-Jia; Zhu, Guo-Chun; Xu, Guo-Liang] Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl, Shanghai 200031, Peoples R China.
   [Yang, Lu; Ge, Hao; Wang, Rui; Tang, Fuchou] Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.
   [Yang, Lu; Wang, Rui; Tang, Fuchou] Peking Univ, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China.
   [Sun, Mei-Ling; Xu, Guo-Liang] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China.
   [Hapman, Deborah L. C.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
   [Sun, Xin] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
   [Sun, Xin] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Peking University; Peking University; ShanghaiTech University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Wisconsin System; University of Wisconsin Madison; University of California System; University of California San Diego
RP Xu, GL (corresponding author), Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,State Key Lab Mol Biol, Shanghai 200031, Peoples R China.; Xu, GL (corresponding author), Univ Chinese Acad Sci, Beijing 100049, Peoples R China.; Xu, GL (corresponding author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl, Shanghai 200031, Peoples R China.; Xu, GL (corresponding author), ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China.; Sun, X (corresponding author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.; Sun, X (corresponding author), Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA.
EM xsun@wisc.edu; glxu@sibcb.ac.cn
FU National Science Foundation of China [31230039, 31521061, 31429003]; Ministry of Sciences and Technology of China [2012CB966903, 2014CB965200]; 'Key New Drug Creation and Manufacturing Program' of China [2014ZX09507002-005]
NR 51
TC 163
Z9 195
U1 5
U2 130
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 528
EP +
DI 10.1038/nature20095
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400062
PM 27760115
DA 2026-03-09
ER

PT J
AU Caracausi, A
   Avice, G
   Burnard, PG
   Füri, E
   Marty, B
AF Caracausi, Antonio
   Avice, Guillaume
   Burnard, Peter G.
   Furi, Evelyn
   Marty, Bernard
TI Chondritic xenon in the Earth's mantle
SO NATURE
LA English
DT Article
ID noble-gases; differentiation; atmosphere; reservoirs; accretion; volcanism; isotopes; plume; neon; evolution
AB Noble gas isotopes are powerful tracers of the origins of planetary volatiles, and the accretion and evolution of the Earth. The compositions of magmatic gases provide insights into the evolution of the Earth's mantle and atmosphere(1-7). Despite recent analytical progress in the study of planetary materials(8,9) and mantle-derived gases(2-7), the possible dual origin(1,10) of the planetary gases in the mantle and the atmosphere remains unconstrained. Evidence relating to the relationship between the volatiles within our planet and the potential cosmochemical end-members is scarce(5). Here we show, using high-precision analysis of magmatic gas from the Eifel volcanic area (in Germany), that the light xenon isotopes identify a chondritic primordial component that differs from the precursor of atmospheric xenon. This is consistent with an asteroidal origin for the volatiles in the Earth's mantle, and indicates that the volatiles in the atmosphere and mantle originated from distinct cosmochemical sources. Furthermore, our data are consistent with the origin of Eifel magmatism being a deep mantle plume. The corresponding mantle source has been isolated from the convective mantle since about 4.45 billion years ago, in agreement with models that predict the early isolation of mantle domains(11). Xenon isotope systematics support a clear distinction between mid-ocean-ridge and continental or oceanic plume sources(6), with chemical heterogeneities dating back to the Earth's accretion(1,7). The deep reservoir now sampled by the Eifel gas had a lower volatile/refractory (iodine/plutonium) composition than the shallower mantle sampled by mid-ocean-ridge volcanism, highlighting the increasing contribution of volatile-rich material during the first tens of millions of years of terrestrial accretion.
C1 [Caracausi, Antonio] Inst Nazl Geofis & Vulcanol, Sez Palermo, I-90146 Palermo, Italy.
   [Caracausi, Antonio; Avice, Guillaume; Burnard, Peter G.; Furi, Evelyn; Marty, Bernard] Univ Lorraine, CNRS, UMR 7358, Ctr Rech Petrograph & Geochim, F-54501 Vandoeuvre Les Nancy, France.
C3 Istituto Nazionale Geofisica e Vulcanologia (INGV); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Lorraine
RP Caracausi, A (corresponding author), Inst Nazl Geofis & Vulcanol, Sez Palermo, I-90146 Palermo, Italy.; Caracausi, A (corresponding author), Univ Lorraine, CNRS, UMR 7358, Ctr Rech Petrograph & Geochim, F-54501 Vandoeuvre Les Nancy, France.
EM antonio.caracausi@ingv.it
FU Instituto Nazionale di Geofisica e Vulcanologia; European Research Council under European Community [267255]; Deep Carbon Observatory
NR 30
TC 72
Z9 77
U1 2
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 82
EP +
DI 10.1038/nature17434
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900043
PM 27111512
DA 2026-03-09
ER

PT J
AU Zimmerman, CA
   Lin, YC
   Leib, DE
   Guo, L
   Huey, EL
   Daly, GE
   Chen, YM
   Knight, ZA
AF Zimmerman, Christopher A.
   Lin, Yen-Chu
   Leib, David E.
   Guo, Ling
   Huey, Erica L.
   Daly, Gwendolyn E.
   Chen, Yiming
   Knight, Zachary A.
TI Thirst neurons anticipate the homeostatic consequences of eating and drinking
SO NATURE
LA English
DT Article
ID subfornical organ; water-intake; vasopressin secretion; angiotensin-ii; body-fluid; rats; food; consciousness; populations; mechanisms
AB Thirst motivates animals to drink in order to maintain fluid balance. Thirst has conventionally been viewed as a homeostatic response to changes in blood volume or tonicity(1-3). However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise(4-11). How this is achieved remains unknown. Here we reveal an unexpected role for the subfornical organ (SFO) in the anticipatory regulation of thirst in mice. By monitoring deep-brain calcium dynamics, we show that thirst-promoting SFO neurons respond to inputs from the oral cavity during eating and drinking and then integrate these inputs with information about the composition of the blood. This integration allows SFO neurons to predict how ongoing food and water consumption will alter fluid balance in the future and then to adjust behaviour pre-emptively. Complementary optogenetic manipulations show that this anticipatory modulation is necessary for drinking in several contexts. These findings provide a neural mechanism to explain longstanding behavioural observations, including the prevalence of drinking during meals(10,11), the rapid satiation of thirst(7-9), and the fact that oral cooling is thirst-quenching(12-14).
C1 [Zimmerman, Christopher A.; Lin, Yen-Chu; Leib, David E.; Guo, Ling; Huey, Erica L.; Daly, Gwendolyn E.; Chen, Yiming; Knight, Zachary A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Zimmerman, Christopher A.; Lin, Yen-Chu; Leib, David E.; Guo, Ling; Huey, Erica L.; Daly, Gwendolyn E.; Chen, Yiming; Knight, Zachary A.] Univ Calif San Francisco, Kavli Inst Fundamental Neurosci, San Francisco, CA 94158 USA.
   [Zimmerman, Christopher A.; Leib, David E.; Guo, Ling; Chen, Yiming; Knight, Zachary A.] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Knight, ZA (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.; Knight, ZA (corresponding author), Univ Calif San Francisco, Kavli Inst Fundamental Neurosci, San Francisco, CA 94158 USA.; Knight, ZA (corresponding author), Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA.
EM zachary.knight@ucsf.edu
FU NSF Graduate Research Fellowship [1144247]; UCSF Discovery Fellowship; New York Stem Cell Foundation; American Diabetes Association; Rita Allen Foundation; McKnight Foundation; Sloan Foundation; Brain and Behavior Research Foundation; Klingenstein Foundation; Program for Breakthrough Biological Research Foundation; NIH [DP2-DK109533, R01-DK106399, R01-NS094781]; UCSF Diabetes and Obesity Centers [U01 DK089541]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK098722, R01DK106399] Funding Source: NIH RePORTER
NR 33
TC 220
Z9 262
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 680
EP +
DI 10.1038/nature18950
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700050
PM 27487211
DA 2026-03-09
ER

PT J
AU Demory, BO
   Gillon, M
   de Wit, J
   Madhusudhan, N
   Bolmont, E
   Heng, K
   Kataria, T
   Lewis, N
   Hu, RY
   Krick, J
   Stamenkovic, V
   Benneke, B
   Kane, S
   Queloz, D
AF Demory, Brice-Olivier
   Gillon, Michael
   de Wit, Julien
   Madhusudhan, Nikku
   Bolmont, Emeline
   Heng, Kevin
   Kataria, Tiffany
   Lewis, Nikole
   Hu, Renyu
   Krick, Jessica
   Stamenkovic, Vlada
   Benneke, Bjorn
   Kane, Stephen
   Queloz, Didier
TI A map of the large day-night temperature gradient of a super-Earth exoplanet
SO NATURE
LA English
DT Article
ID 55 cancri; planet; transit; eclipses; spitzer; variability; atmospheres; inference; radius
AB Over the past decade, observations of giant exoplanets (Jupiter-size) have provided key insights into their atmospheres(1,2), but the properties of lower-mass exoplanets (sub-Neptune) remain largely unconstrained because of the challenges of observing small planets. Numerous efforts to observe the spectra of super-Earths-exoplanets with masses of one to ten times that of Earth-have so far revealed only featureless spectra(3). Here we report a longitudinal thermal brightness map of the nearby transiting super-Earth 55 Cancri e (refs 4, 5) revealing highly asymmetric dayside thermal emission and a strong day-night temperature contrast. Dedicated space-based monitoring of the planet in the infrared revealed a modulation of the thermal flux as 55 Cancri e revolves around its star in a tidally locked configuration. These observations reveal a hot spot that is located 41 +/- 12 degrees east of the substellar point (the point at which incident light from the star is perpendicular to the surface of the planet). From the orbital phase curve, we also constrain the nightside brightness temperature of the planet to 1,380 +/- 400 kelvin and the temperature of the warmest hemisphere (centred on the hot spot) to be about 1,300 kelvin hotter (2,700 +/- 270 kelvin) at a wavelength of 4.5 micrometres, which indicates inefficient heat redistribution from the dayside to the nightside. Our observations are consistent with either an optically thick atmosphere with heat recirculation confined to the planetary dayside, or a planet devoid of atmosphere with low-viscosity magma flows at the surface(6).
C1 [Demory, Brice-Olivier; Queloz, Didier] Univ Cambridge, Cavendish Lab, Astrophys Grp, JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Gillon, Michael] Univ Liege, Inst Astrophys & Geophys, Allee 6 Aout 17, B-4000 Liege, Belgium.
   [de Wit, Julien] MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Madhusudhan, Nikku] Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
   [Bolmont, Emeline] Univ Namur, Dept Math, NaXys, 8 Rempart Vierge, B-5000 Namur, Belgium.
   [Heng, Kevin] Univ Bern, Ctr Space & Habitabil, Sidlerstr 5, CH-3012 Bern, Switzerland.
   [Kataria, Tiffany] Univ Exeter, Sch Phys, Astrophys Grp, Stocker Rd, Exeter EX4 4QL, Devon, England.
   [Lewis, Nikole] Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
   [Hu, Renyu; Stamenkovic, Vlada] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
   [Hu, Renyu; Stamenkovic, Vlada; Benneke, Bjorn] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Krick, Jessica] CALTECH, Jet Prop Lab, Spitzer Sci Ctr, MS 220-6, Pasadena, CA 91125 USA.
   [Kane, Stephen] San Francisco State Univ, Dept Phys & Astron, 1600 Holloway Ave, San Francisco, CA 94132 USA.
C3 University of Cambridge; University of Liege; Massachusetts Institute of Technology (MIT); University of Cambridge; University of Namur; University of Bern; University of Exeter; Space Telescope Science Institute; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; California State University System; San Francisco State University
RP Demory, BO (corresponding author), Univ Cambridge, Cavendish Lab, Astrophys Grp, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM bod21@cam.ac.uk
FU NASA; Simons Foundation [338555]; Science and Technology Facilities Council [ST/N000927/1] Funding Source: researchfish
NR 46
TC 224
Z9 254
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 207
EP +
DI 10.1038/nature17169
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100033
PM 27027283
DA 2026-03-09
ER

PT J
AU Choi, GJ
   Zhu, QL
   Miller, DC
   Gu, CJ
   Knowles, RR
AF Choi, Gilbert J.
   Zhu, Qilei
   Miller, David C.
   Gu, Carol J.
   Knowles, Robert R.
TI Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer
SO NATURE
LA English
DT Article
ID centered radicals; atom-transfer; functionalization; hydroamination; carboxamides; abstraction; cyclization; generation; oxidation; energy
AB Despite advances in hydrogen atom transfer (HAT) catalysis(1-5), there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination(6-11) and directed carbon-hydrogen (C-H) bond functionalization(12-16). In the latter process-a subset of the classical Hofmann-Loffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds(17-21). Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Loffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.
C1 [Choi, Gilbert J.; Zhu, Qilei; Miller, David C.; Gu, Carol J.; Knowles, Robert R.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University
RP Knowles, RR (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
EM rknowles@princeton.edu
FU NIH [R01 GM113105]; Sloan Foundation Research Fellow; Amgen Young Investigator Award
NR 30
TC 646
Z9 758
U1 29
U2 713
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 268
EP 271
DI 10.1038/nature19811
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500040
PM 27732585
DA 2026-03-09
ER

PT J
AU Streich, FC
   Lima, CD
AF Streich, Frederick C., Jr.
   Lima, Christopher D.
TI Capturing a substrate in an activated RING E3/E2-SUMO complex
SO NATURE
LA English
DT Article
ID e3 ligase; structural basis; crystal-structure; sumo modification; ubiquitin; pcna; ubc9; mechanism; conjugation; insights
AB Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins such as small ubiquitinlike modifier (SUMO) regulates processes including protein homeostasis, the DNA damage response, and the cell cycle. Proliferating cell nuclear antigen (PCNA) is modified by Ub or poly-Ub at lysine (Lys) 164 after DNA damage to recruit repair factors. Yeast PCNA is modified by SUMO on Lys164 and Lys127 during S-phase to recruit the anti-recombinogenic helicase Srs2. Lys164 modification requires specialized E2/E3 enzyme pairs for SUMO or Ub conjugation. For SUMO, Lys164 modification is strictly dependent on the E3 ligase Siz1, suggesting the E3 alters E2 specificity to promote Lys164 modification. The structural basis for substrate interactions in activated E3/E2-Ub/Ubl complexes remains unclear. Here we report an engineered E2 protein and cross-linking strategies that trap an E3/E2-Ubl/substrate complex for structure determination, illustrating how an E3 can bypass E2 specificity to force-feed a substrate lysine into the E2 active site.
C1 [Streich, Frederick C., Jr.; Lima, Christopher D.] Sloan Kettering Inst, Struct Biol Program, 1275 York Ave, New York, NY 10065 USA.
   [Lima, Christopher D.] Howard Hughes Med Inst, 1275 York Ave, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute
RP Lima, CD (corresponding author), Sloan Kettering Inst, Struct Biol Program, 1275 York Ave, New York, NY 10065 USA.; Lima, CD (corresponding author), Howard Hughes Med Inst, 1275 York Ave, New York, NY 10065 USA.
EM limac@mskcc.org
FU National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) [P41 GM103403]; NIH-ORIP (Office of Research Infrastructure Programs) High-End Shared Instrument grant) at the Advanced Photon Source [S10 RR029205]; DOE Office of Science [DE-AC02-06CH11357]; NIH/NIGMS [GM065872, GM118080]; NIH/National Cancer Institute [P30CA008748]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R35GM118080] Funding Source: NIH RePORTER
NR 53
TC 90
Z9 104
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 304
EP +
DI 10.1038/nature19071
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900029
PM 27509863
DA 2026-03-09
ER

PT J
AU Gillon, M
   Jehin, E
   Lederer, SM
   Delrez, L
   de Wit, J
   Burdanov, A
   Van Grootel, V
   Burgasser, AJ
   Triaud, AHMJ
   Opitom, C
   Demory, BO
   Sahu, DK
   Gagliuffi, DB
   Magain, P
   Queloz, D
AF Gillon, Michael
   Jehin, Emmanuel
   Lederer, Susan M.
   Delrez, Laetitia
   de Wit, Julien
   Burdanov, Artem
   Van Grootel, Valerie
   Burgasser, Adam J.
   Triaud, Amaury H. M. J.
   Opitom, Cyrielle
   Demory, Brice-Olivier
   Sahu, Devendra K.
   Gagliuffi, Daniella Bardalez
   Magain, Pierre
   Queloz, Didier
TI Temperate Earth-sized planets transiting a nearby ultracool dwarf star
SO NATURE
LA English
DT Article
ID adaptive optics survey; volume-limited sample; solar neighborhood; main-sequence; habitable zones; super-earths; mass; ii.; multiplicity; stellar
AB Star-like objects with effective temperatures of less than 2,700 kelvin are referred to as 'ultracool dwarfs'(1). This heterogeneous group includes stars of extremely low mass as well as brown dwarfs (substellar objects not massive enough to sustain hydrogen fusion), and represents about 15 per cent of the population of astronomical objects near the Sun(2). Core-accretion theory predicts that, given the small masses of these ultracool dwarfs, and the small sizes of their protoplanetary disks(3,4), there should be a large but hitherto undetected population of terrestrial planets orbiting them(5)-ranging from metal-rich Mercury-sized planets(6) to more hospitable volatile-rich Earth-sized planets(7). Here we report observations of three short-period Earth-sized planets transiting an ultracool dwarf star only 12 parsecs away. The inner two planets receive four times and two times the irradiation of Earth, respectively, placing them close to the inner edge of the habitable zone of the star(8). Our data suggest that 11 orbits remain possible for the third planet, the most likely resulting in irradiation significantly less than that received by Earth. The infrared brightness of the host star, combined with its Jupiter-like size, offers the possibility of thoroughly characterizing the components of this nearby planetary system.
C1 [Gillon, Michael; Jehin, Emmanuel; Delrez, Laetitia; Burdanov, Artem; Van Grootel, Valerie; Opitom, Cyrielle; Magain, Pierre] Univ Liege, Inst Astrophys & Geophys, Allee 6 Aout 19C, B-4000 Liege, Belgium.
   [Lederer, Susan M.] NASA Johnson Space Ctr, 2101 NASA Pkwy, Houston, TX 77058 USA.
   [de Wit, Julien] MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Burgasser, Adam J.; Gagliuffi, Daniella Bardalez] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
   [Triaud, Amaury H. M. J.] Univ Cambridge, Inst Astron, Madingley Rd, Cambridge CB3 0HA, England.
   [Demory, Brice-Olivier; Queloz, Didier] Univ Cambridge, Cavendish Lab, Astrophys Grp, 19 JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Sahu, Devendra K.] Indian Inst Astrophys, Bangalore 560034, Karnataka, India.
C3 University of Liege; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; University of Cambridge; University of Cambridge; Department of Science & Technology (India); Indian Institute of Astrophysics (IIA)
RP Gillon, M (corresponding author), Univ Liege, Inst Astrophys & Geophys, Allee 6 Aout 19C, B-4000 Liege, Belgium.
EM michael.gillon@ulg.ac.be
FU Belgian Fund for Scientific Research (FRS-FNRS) [FRFC 2.5.594.09.F]; Swiss Fund for Scientific Research; European Research Council (ERC) [336480]; Action de Recherche Concertee (ARC) grant - Wallonia-Brussels Federation; NASA [NNX15AI75G]; NASA [NNX15AI75G, 807250] Funding Source: Federal RePORTER; European Research Council (ERC) [336480] Funding Source: European Research Council (ERC)
NR 78
TC 507
Z9 592
U1 1
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 221
EP +
DI 10.1038/nature17448
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200044
PM 27135924
DA 2026-03-09
ER

PT J
AU Borducchi, EN
   Cabral, C
   Stephenson, KE
   Liu, JY
   Abbink, P
   Ng'ang'a, D
   Nkolola, JP
   Brinkman, AL
   Peter, L
   Lee, BC
   Jimenez, J
   Jetton, D
   Mondesir, J
   Mojta, S
   Chandrashekar, A
   Molloy, K
   Alter, G
   Gerold, JM
   Hill, AL
   Lewis, MG
   Pau, MG
   Schuitemaker, H
   Hesselgesser, J
   Geleziunas, R
   Kim, JH
   Robb, ML
   Michael, NL
   Barouch, DH
AF Borducchi, Erica N.
   Cabral, Crystal
   Stephenson, Kathryn E.
   Liu, Jinyan
   Abbink, Peter
   Ng'ang'a, David
   Nkolola, Joseph P.
   Brinkman, Amanda L.
   Peter, Lauren
   Lee, Benjamin C.
   Jimenez, Jessica
   Jetton, David
   Mondesir, Jade
   Mojta, Shanell
   Chandrashekar, Abishek
   Molloy, Katherine
   Alter, Galit
   Gerold, Jeffrey M.
   Hill, Alison L.
   Lewis, Mark G.
   Pau, Maria G.
   Schuitemaker, Hanneke
   Hesselgesser, Joseph
   Geleziunas, Romas
   Kim, Jerome H.
   Robb, Merlin L.
   Michael, Nelson L.
   Barouch, Dan H.
TI Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys
SO NATURE
LA English
DT Article
ID latent reservoir; viral reservoir; hiv-1 remission; t-cells; viremia; persistence; challenges; aids
AB The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research(1,2). However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost)(3,4) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.
C1 [Borducchi, Erica N.; Cabral, Crystal; Stephenson, Kathryn E.; Liu, Jinyan; Abbink, Peter; Ng'ang'a, David; Nkolola, Joseph P.; Brinkman, Amanda L.; Peter, Lauren; Lee, Benjamin C.; Jimenez, Jessica; Jetton, David; Mondesir, Jade; Mojta, Shanell; Chandrashekar, Abishek; Molloy, Katherine; Barouch, Dan H.] Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Alter, Galit; Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
   [Gerold, Jeffrey M.; Hill, Alison L.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Lewis, Mark G.] Bioqual, Rockville, MD 20852 USA.
   [Pau, Maria G.; Schuitemaker, Hanneke] Janssen Infect Dis & Vaccines, NL-2301 Leiden, Netherlands.
   [Hesselgesser, Joseph; Geleziunas, Romas] Gilead Sci, Foster City, CA 94404 USA.
   [Kim, Jerome H.; Robb, Merlin L.; Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
   [Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; BIOQUAL Inc.; Gilead Sciences; United States Department of Defense; United States Army; Walter Reed Army Institute of Research (WRAIR); International Vaccine Institute
RP Barouch, DH (corresponding author), Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.; Barouch, DH (corresponding author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
EM dbarouch@bidmc.harvard.edu
FU US Army Medical Research and Materiel Command; HIV Research Program, Walter Reed Army Institute of Research; Henry M. Jackson Foundation [W81XWH-11-2-0174]; National Institutes of Health [AI096040, AI124377, AI126603, OD019851]; Ragon Institute of MGH, MIT, and Harvard
NR 35
TC 240
Z9 279
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 284
EP +
DI 10.1038/nature20583
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700060
PM 27841870
DA 2026-03-09
ER

PT J
AU Trowbridge, AJ
   Melosh, HJ
   Steckloff, JK
   Freed, AM
AF Trowbridge, A. J.
   Melosh, H. J.
   Steckloff, J. K.
   Freed, A. M.
TI Vigorous convection as the explanation for Pluto's polygonal terrain
SO NATURE
LA English
DT Article
ID phase-transitions; origin; viscosity
AB Pluto's surface is surprisingly young and geologically active(1). One of its youngest terrains is the near-equatorial region informally named Sputnik Planum, which is a topographic basin filled by nitrogen (N-2) ice mixed with minor amounts of CH4 and CO ices(1). Nearly the entire surface of the region is divided into irregular polygons about 20-30 kilometres in diameter, whose centres rise tens of metres above their sides. The edges of this region exhibit bulk flow features without polygons(1). Both thermal contraction and convection have been proposed to explain this terrain(1), but polygons formed from thermal contraction (analogous to ice-wedges or mud-crack networks)(2,3) of N-2 are inconsistent with the observations on Pluto of non-brittle deformation within the N-2-ice sheet. Here we report a parameterized convection model to compute the Rayleigh number of the N-2 ice and show that it is vigorously convecting, making Rayleigh-Benard convection the most likely explanation for these polygons. The diameter of Sputnik Planum's polygons and the dimensions of the 'floating mountains' (the hills of of water ice along the edges of the polygons) suggest that its N-2 ice is about ten kilometres thick. The estimated convection velocity of 1.5 centimetres a year indicates a surface age of only around a million years.
C1 [Trowbridge, A. J.; Melosh, H. J.; Freed, A. M.] Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
   [Melosh, H. J.; Steckloff, J. K.] Purdue Univ, Dept Phys & Astron, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Purdue University System; Purdue University
RP Trowbridge, AJ (corresponding author), Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
EM atrowbr@purdue.edu
FU Fredrick N. Andrews Fellowship
NR 26
TC 59
Z9 70
U1 3
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 79
EP +
DI 10.1038/nature18016
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300036
PM 27251278
DA 2026-03-09
ER

PT J
AU Plaschka, C
   Hantsche, M
   Dienemann, C
   Burzinski, C
   Plitzko, J
   Cramer, P
AF Plaschka, C.
   Hantsche, M.
   Dienemann, C.
   Burzinski, C.
   Plitzko, J.
   Cramer, P.
TI Transcription initiation complex structures elucidate DNA opening
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; crystal-structure; preinitiation complex; immediately upstream; promoter dna; factor tfiif; architecture; domains; visualization; mechanism
AB Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 angstrom and 3.6 angstrom, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.
C1 [Plaschka, C.; Hantsche, M.; Dienemann, C.; Burzinski, C.; Cramer, P.] Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.
   [Plitzko, J.] Max Planck Inst Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
C3 Max Planck Society; Max Planck Society
RP Cramer, P (corresponding author), Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany.
EM patrick.cramer@mpibpc.mpg.de
FU Deutsche Forschungsgemeinschaft; European Research Council; Volkswagen Foundation
NR 79
TC 168
Z9 194
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 353
EP +
DI 10.1038/nature17990
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300040
PM 27193681
DA 2026-03-09
ER

PT J
AU Lin, J
   Kumari, S
   Kim, C
   Van, TM
   Wachsmuth, L
   Polykratis, A
   Pasparakis, M
AF Lin, Juan
   Kumari, Snehlata
   Kim, Chun
   Van, Trieu-My
   Wachsmuth, Laurens
   Polykratis, Apostolos
   Pasparakis, Manolis
TI RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation
SO NATURE
LA English
DT Article
ID cell-death; programmed necrosis; innate; homeostasis; activation; caspase-8; mice
AB Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions(1-7). RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis(8-13). In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers(14-18). The mechanism by which RIPK1 counteracts RIPK3-MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3-MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1(mRHIM)) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1(mRHIM) in keratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1(mRHIM), suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases.
C1 [Lin, Juan; Kumari, Snehlata; Kim, Chun; Van, Trieu-My; Wachsmuth, Laurens; Polykratis, Apostolos; Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50931 Cologne, Germany.
   [Lin, Juan; Kumari, Snehlata; Kim, Chun; Van, Trieu-My; Wachsmuth, Laurens; Polykratis, Apostolos; Pasparakis, Manolis] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
C3 University of Cologne; University of Cologne
RP Pasparakis, M (corresponding author), Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50931 Cologne, Germany.; Pasparakis, M (corresponding author), Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
EM pasparakis@uni-koeln.de
FU ERC [323040]; DFG [SFB829, SFB670]; Humboldt research fellowship; EMBO; European Research Council (ERC) [323040] Funding Source: European Research Council (ERC)
NR 32
TC 345
Z9 390
U1 11
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 124
EP +
DI 10.1038/nature20558
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600061
PM 27819681
DA 2026-03-09
ER

PT J
AU He, R
   Hou, SY
   Liu, C
   Zhang, AL
   Bai, Q
   Han, M
   Yang, Y
   Wei, G
   Shen, T
   Yang, XX
   Xu, LF
   Chen, XY
   Hao, YX
   Wang, PC
   Zhu, CH
   Ou, JJ
   Liang, HJ
   Ni, T
   Zhang, XY
   Zhou, XY
   Deng, K
   Chen, YK
   Luo, YD
   Xu, JQ
   Qi, H
   Wu, YZ
   Ye, LL
AF He, Ran
   Hou, Shiyue
   Liu, Cheng
   Zhang, Anli
   Bai, Qiang
   Han, Miao
   Yang, Yu
   Wei, Gang
   Shen, Ting
   Yang, Xinxin
   Xu, Lifan
   Chen, Xiangyu
   Hao, Yaxing
   Wang, Pengcheng
   Zhu, Chuhong
   Ou, Juanjuan
   Liang, Houjie
   Ni, Ting
   Zhang, Xiaoyan
   Zhou, Xinyuan
   Deng, Kai
   Chen, Yaokai
   Luo, Yadong
   Xu, Jianqing
   Qi, Hai
   Wu, Yuzhang
   Ye, Lilin
TI Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection
SO NATURE
LA English
DT Article
ID in-vivo; differentiation; transcription; exhaustion; hiv-1; replication; tolerance; roles; fh
AB During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential(1-4). However, exhausted CD8(+) T cells can still contain viral replication in chronic infections(5-9), although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T cells were able to migrate into B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(+) subset. Furthermore, we identified the Id2-E2A signalling axis as an important regulator of the generation of this subset. In patients with HIV, we also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number was inversely correlated with viral load. The CXCR5(+) subset showed greater therapeutic potential than the CXCR5(+) subset when adoptively transferred to chronically infected mice, and exhibited synergistic reduction of viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8(+) T cells that has a pivotal role in the control of viral replication during chronic viral infection.
C1 [He, Ran; Liu, Cheng; Bai, Qiang; Yang, Xinxin; Xu, Lifan; Chen, Xiangyu; Hao, Yaxing; Wang, Pengcheng; Zhou, Xinyuan; Wu, Yuzhang; Ye, Lilin] Third Mil Med Univ, Inst Immunol, Chongqing 400038, Peoples R China.
   [Hou, Shiyue; Qi, Hai] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Lab Dynam Immunobiol, Beijing 100084, Peoples R China.
   [Zhang, Anli; Yang, Yu; Zhang, Xiaoyan; Xu, Jianqing] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China.
   [Zhang, Anli; Yang, Yu; Zhang, Xiaoyan; Xu, Jianqing] Fudan Univ, Inst Biomed Sci, Shanghai 201508, Peoples R China.
   [Han, Miao; Wei, Gang; Shen, Ting; Ni, Ting] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Shanghai 200438, Peoples R China.
   [Han, Miao; Wei, Gang; Shen, Ting; Ni, Ting] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, MOE Key Lab Contemporary Anthropol, Shanghai 200438, Peoples R China.
   [Zhu, Chuhong] Third Mil Med Univ, Sch Basic Med, Dept Anat, Chongqing 400038, Peoples R China.
   [Ou, Juanjuan; Liang, Houjie] Third Mil Med Univ, Southwestern Hosp, Dept Oncol, Chongqing 400038, Peoples R China.
   [Deng, Kai] Sun Yat Sen Univ, Inst Human Virol, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China.
   [Chen, Yaokai; Luo, Yadong] Chongqing Publ Hlth Med Ctr, Chongqing 400000, Peoples R China.
C3 Army Medical University; Tsinghua University; Fudan University; Fudan University; Fudan University; Fudan University; Army Medical University; Army Medical University; Sun Yat Sen University
RP Wu, YZ; Ye, LL (corresponding author), Third Mil Med Univ, Inst Immunol, Chongqing 400038, Peoples R China.; Qi, H (corresponding author), Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Lab Dynam Immunobiol, Beijing 100084, Peoples R China.
EM qihai@mail.tsinghua.edu.cn; wuyuzhang@tmmu.edu.cn; yelilinlcmv@tmmu.edu.cn
FU National Basic Research Program of China (973 program) [2013CB531500, 2014CB542501]; National Natural Science Foundation of China [81220108024, 81471624, U1202228, 81425011, 81330070, 31500733]
NR 37
TC 556
Z9 657
U1 6
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 412
EP +
DI 10.1038/nature19317
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000056
PM 27501245
DA 2026-03-09
ER

PT J
AU Shin, HJR
   Kim, H
   Oh, S
   Lee, JG
   Kee, M
   Ko, HJ
   Kweon, MN
   Won, KJ
   Baek, SH
AF Shin, Hi-Jai R.
   Kim, Hyunkyung
   Oh, Sungryong
   Lee, Jun-Gi
   Kee, Minjung
   Ko, Hyun-Jeong
   Kweon, Mi-Na
   Won, Kyoung-Jae
   Baek, Sung Hee
TI AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy
SO NATURE
LA English
DT Article
ID activated protein-kinase; ampk; coactivator; degradation; homeostasis; expression; inhibitor; complexes; tfeb
AB Autophagy is a highly conserved self-digestion process, which is essential for maintaining homeostasis and viability in response to nutrient starvation(1-4). Although the components of autophagy in the cytoplasm have been well studied(5,6), the molecular basis for the transcriptional and epigenetic regulation of autophagy is poorly understood. Here we identify co-activator-associated arginine methyltransferase 1 (CARM1) as a crucial component of autophagy in mammals. Notably, CARM1 stability is regulated by the SKP2-containing SCF (SKP1-cullin1-F-box protein) E3 ubiquitin ligase in the nucleus, but not in the cytoplasm, under nutrient-rich conditions. Furthermore, we show that nutrient starvation results in AMP-activated protein kinase (AMPK)-dependent phosphorylation of FOXO3a in the nucleus, which in turn transcriptionally represses SKP2. This repression leads to increased levels of CARM1 protein and subsequent increases in histone H3 Arg17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional co-activator function on autophagy-related and lysosomal genes through transcription factor EB (TFEB). Our findings demonstrate that CARM1-dependent histone arginine methylation is a crucial nuclear event in autophagy, and identify a new signalling axis of AMPK-SKP2-CARM1 in the regulation of autophagy induction after nutrient starvation.
C1 [Shin, Hi-Jai R.; Kim, Hyunkyung; Oh, Sungryong; Lee, Jun-Gi; Kee, Minjung; Baek, Sung Hee] Seoul Natl Univ, Sch Biol Sci, Creat Res Initiat Ctr Chromatin Dynam, Seoul, South Korea.
   [Ko, Hyun-Jeong] Kangwon Natl Univ, Coll Pharm, Lab Microbiol & Immunol, Chunchon, South Korea.
   [Kweon, Mi-Na] Univ Ulsan, Coll Med, Asan Med Ctr, Mucosal Immunol Lab,Dept Convergence Med, Seoul, South Korea.
   [Won, Kyoung-Jae] Univ Penn, Perelman Sch Med, Dept Genet, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
C3 Seoul National University (SNU); Kangwon National University; University of Ulsan; Asan Medical Center; University of Pennsylvania
RP Baek, SH (corresponding author), Seoul Natl Univ, Sch Biol Sci, Creat Res Initiat Ctr Chromatin Dynam, Seoul, South Korea.
EM sbaek@snu.ac.kr
FU Creative Research Initiatives Program (Research Center for Chromatin Dynamics) [2009-0081563]; National Junior Research Fellowship [NRF-2011-A01496-0001806]; National Research Foundation (NRF) - South Korean government (MSIP) [NRF-2014R1A6A3A0405 7910]; NIH [R01DK106027]
NR 32
TC 384
Z9 414
U1 0
U2 131
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 553
EP +
DI 10.1038/nature18014
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300054
PM 27309807
DA 2026-03-09
ER

PT J
AU Laatiaoui, M
   Lauth, W
   Backe, H
   Block, M
   Ackermann, D
   Cheal, B
   Chhetri, P
   Düllmann, CE
   Van Duppen, P
   Even, J
   Ferrer, R
   Giacoppo, F
   Götz, S
   Hessberger, FP
   Huyse, M
   Kaleja, O
   Khuyagbaatar, J
   Kunz, P
   Lautenschläger, F
   Mistry, AK
   Raeder, S
   Ramirez, EM
   Walther, T
   Wraith, C
   Yakushev, A
AF Laatiaoui, Mustapha
   Lauth, Werner
   Backe, Hartmut
   Block, Michael
   Ackermann, Dieter
   Cheal, Bradley
   Chhetri, Premaditya
   Duellmann, Christoph Emanuel
   Van Duppen, Piet
   Even, Julia
   Ferrer, Rafael
   Giacoppo, Francesca
   Goetz, Stefan
   Hessberger, Fritz Peter
   Huyse, Mark
   Kaleja, Oliver
   Khuyagbaatar, Jadambaa
   Kunz, Peter
   Lautenschlaeger, Felix
   Mistry, Andrew Kishor
   Raeder, Sebastian
   Minaya Ramirez, Enrique
   Walther, Thomas
   Wraith, Calvin
   Yakushev, Alexander
TI Atom-at-a-time laser resonance ionization spectroscopy of nobelium
SO NATURE
LA English
DT Article
ID buffer gas cell; equal-to 104; superheavy elements; heavy; ship
AB Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements(1) and theoretical modelling can be performed to high precision(2,3), taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown. These radioactive elements are produced in nuclear fusion reactions at rates of only a few atoms per second at most and must be studied immediately following their production(4), which has so far precluded their optical spectroscopy. Here we report laser resonance ionization spectroscopy of nobelium (No; atomic number 102) in single-atom-at-a-time quantities, in which we identify the ground-state transition S-1(0) -> P-1(1). By combining this result with data from an observed Rydberg series, we obtain an upper limit for the ionization potential of nobelium. These accurate results from direct laser excitations of outer-shell electrons cannot be achieved using state-of-the-art relativistic many-body calculations(5-8) that include quantum electrodynamic effects, owing to large uncertainties in the modelled transition energies of the complex systems under consideration. Our work opens the door to high-precision measurements of various atomic and nuclear properties of elements heavier than nobelium, and motivates future theoretical work.
C1 [Laatiaoui, Mustapha; Block, Michael; Duellmann, Christoph Emanuel; Even, Julia; Giacoppo, Francesca; Goetz, Stefan; Hessberger, Fritz Peter; Khuyagbaatar, Jadambaa; Mistry, Andrew Kishor; Raeder, Sebastian; Minaya Ramirez, Enrique; Yakushev, Alexander] Helmholtz Inst Mainz, Staudingerweg 18, D-55128 Mainz, Germany.
   [Laatiaoui, Mustapha; Block, Michael; Ackermann, Dieter; Duellmann, Christoph Emanuel; Giacoppo, Francesca; Goetz, Stefan; Hessberger, Fritz Peter; Kaleja, Oliver; Khuyagbaatar, Jadambaa; Mistry, Andrew Kishor; Raeder, Sebastian; Yakushev, Alexander] GSI Helmholtzzentrum Schwerionenforsch GmbH, Planckstr 1, D-64291 Darmstadt, Germany.
   [Lauth, Werner; Backe, Hartmut] Johannes Gutenberg Univ Mainz, Inst Kernphys, Johann Joachim Becher Weg 45, D-55128 Mainz, Germany.
   [Block, Michael; Duellmann, Christoph Emanuel; Goetz, Stefan] Johannes Gutenberg Univ Mainz, Inst Kernchem, Fritz Strassmann Weg 2, D-55128 Mainz, Germany.
   [Cheal, Bradley; Wraith, Calvin] Univ Liverpool, Dept Phys, Oxford St, Liverpool L69 7ZE, Merseyside, England.
   [Chhetri, Premaditya; Lautenschlaeger, Felix; Walther, Thomas] Tech Univ Darmstadt, Inst Angew Phys, Schlossgartenstr 7, D-64289 Darmstadt, Germany.
   [Van Duppen, Piet; Ferrer, Rafael; Huyse, Mark; Raeder, Sebastian] Katholieke Univ Leuven, Inst Kern Stralingsfys, Celestijnenlaan 200D, B-3001 Louvain, Belgium.
   [Kaleja, Oliver] Tech Univ Darmstadt, Inst Kernphys, Schlossgartenstr 9, D-64289 Darmstadt, Germany.
   [Kunz, Peter] TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3, Canada.
   [Ackermann, Dieter] Grand Accelerateur Natl Ions Lourds, Bd Henri Becquerel,BP 55027, F-14076 Caen 05, France.
   [Even, Julia] Univ Groningen, Adv Radiat Technol Ctr, Zernikelaan 25, NL-9747 AA Groningen, Netherlands.
   [Minaya Ramirez, Enrique] Inst Phys Nucl Orsay, 15 Rue Georges Clemenceau, F-91406 Orsay, France.
C3 Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; University of Liverpool; Technical University of Darmstadt; KU Leuven; Technical University of Darmstadt; University of British Columbia; University of Groningen; Universite Paris Saclay
RP Laatiaoui, M (corresponding author), Helmholtz Inst Mainz, Staudingerweg 18, D-55128 Mainz, Germany.; Laatiaoui, M (corresponding author), GSI Helmholtzzentrum Schwerionenforsch GmbH, Planckstr 1, D-64291 Darmstadt, Germany.
EM M.Laatiaoui@gsi.de
FU German Federal Ministry of Education and Research [06MZ169I, 06LM236I]; FAIR NuSTAR [05P09RDFN4, 05P12RDFN8, 05P15RDFN1]; GSI; Helmholtz-Institut Mainz; Science and Technology Facilities Council [ST/L005670/1, ST/I004726/2, 1511460] Funding Source: researchfish; STFC [ST/L005670/1, ST/I004726/2] Funding Source: UKRI
CR Backe H, 2007, EUR PHYS J D, V45, P99, DOI 10.1140/epjd/e2007-00198-1
   Backe H, 2005, HYPERFINE INTERACT, V162, P3, DOI 10.1007/s10751-005-9209-x
   Backe H, 2015, NUCL PHYS A, V944, P492, DOI 10.1016/j.nuclphysa.2015.07.002
   Backe H, 2001, NUCL PHYS A, V690, P215C, DOI 10.1016/S0375-9474(01)00944-7
   Backe H, 1998, PHYS REV LETT, V80, P920, DOI 10.1103/PhysRevLett.80.920
   Borschevsky A, 2007, PHYS REV A, V75, P0, DOI 10.1103/PhysRevA.75.042514
   Campbell P, 2016, PROG PART NUCL PHYS, V86, P127, DOI 10.1016/j.ppnp.2015.09.003
   Dzuba VA, 2014, PHYS REV A, V90, P0, DOI 10.1103/PhysRevA.90.012504
   Eliav E, 2015, NUCL PHYS A, V944, P518, DOI 10.1016/j.nuclphysa.2015.06.017
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   Kindler B, 2006, NUCL INSTRUM METH A, V561, P107, DOI 10.1016/j.nima.2005.12.232
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   Lautenschläger F, 2016, NUCL INSTRUM METH B, V383, P115, DOI 10.1016/j.nimb.2016.06.001
   LAUTH W, 1992, PHYS REV LETT, V68, P1675, DOI 10.1103/PhysRevLett.68.1675
   Letokhov VS, 1987, LASER PHOTOIONIZATION SPECTROSCOPY, V0, P0
   Liu Y, 2007, PHYS REV A, V76, P0, DOI 10.1103/PhysRevA.76.062503
   Martin WC, 1980, J OPT SOC AM, V70, P784
   Nagame Y, 2015, NUCL PHYS A, V944, P614, DOI 10.1016/j.nuclphysa.2015.07.013
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   Sato TK, 2015, NATURE, V520, P209, DOI 10.1038/nature14342
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   Sewtz M, 2003, SPECTROCHIM ACTA B, V58, P1077, DOI 10.1016/S0584-8547(03)00065-X
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   Worden EF, 2008, CHEM ACTINIDE TRANS, V3, P0
NR 33
TC 100
Z9 117
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2016
VL 538
IS 7626
BP 495
EP +
DI 10.1038/nature19345
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5IY
UT WOS:000386654400054
PM 27680707
DA 2026-03-09
ER

PT J
AU Bierman, PR
   Shakun, JD
   Corbett, LB
   Zimmerman, SR
   Rood, DH
AF Bierman, Paul R.
   Shakun, Jeremy D.
   Corbett, Lee B.
   Zimmerman, Susan R.
   Rood, Dylan H.
TI A persistent and dynamic East Greenland Ice Sheet over the past 7.5 million years
SO NATURE
LA English
DT Article
ID nuclide production-rates; late pliocene greenland; situ cosmogenic be-10; deep-sea-temperature; half-life; southern greenland; rafted detritus; heat-flux; glaciation; climate
AB Climate models show that ice-sheet melt will dominate sea-level rise over the coming centuries, but our understanding of ice-sheet variations before the last interglacial 125,000 years ago remains fragmentary. This is because terrestrial deposits of ancient glacial and interglacial periods(1-3) are overrun and eroded by more recent glacial advances, and are therefore usually rare, isolated and poorly dated(4). In contrast, material shed almost continuously from continents is preserved as marine sediment that can be analysed to infer the time-varying state of major ice sheets. Here we show that the East Greenland Ice Sheet existed over the past 7.5 million years, as indicated by beryllium and aluminium isotopes (Be-10 and Al-26) in quartz sand removed by deep, ongoing glacial erosion on land and deposited offshore in the marine sedimentary record(5,6.) During the early Pleistocene epoch, ice cover in East Greenland was dynamic; in contrast, East Greenland was mostly ice-covered during the mid-to-late Pleistocene. The isotope record we present is consistent with distinct signatures of changes in ice sheet behaviour coincident with major climate transitions. Although our data are continuous, they are from low-deposition-rate sites and sourced only from East Greenland. Consequently, the signal of extensive deglaciation during short, intense interglacials could be missed or blurred, and we cannot distinguish between a remnant ice sheet in the East Greenland highlands and a diminished continent-wide ice sheet. A clearer constraint on the behaviour of the ice sheet during past and, ultimately, future interglacial warmth could be produced by Be-10 and Al-26 records from a coring site with a higher deposition rate. Nonetheless, our analysis challenges the possibility of complete and extended deglaciation over the past several million years.
C1 [Bierman, Paul R.; Corbett, Lee B.] Univ Vermont, Dept Geol, Burlington, VT 05405 USA.
   [Bierman, Paul R.; Corbett, Lee B.] Univ Vermont, Rubenstein Sch Environm & Nat Resources, Burlington, VT 05405 USA.
   [Shakun, Jeremy D.] Boston Coll, Dept Earth & Environm Sci, Chestnut Hill, MA 02467 USA.
   [Zimmerman, Susan R.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94550 USA.
   [Rood, Dylan H.] Imperial Coll London, Dept Earth Sci & Engn, South Kensington Campus, London SW7 2AZ, England.
   [Rood, Dylan H.] Scottish Univ Environm Res Ctr, E Kilbride G75 0QF, Lanark, Scotland.
C3 University of Vermont; University of Vermont; Boston College; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Imperial College London; Scottish Universities Research & Reactor Center
RP Bierman, PR (corresponding author), Univ Vermont, Dept Geol, Burlington, VT 05405 USA.; Bierman, PR (corresponding author), Univ Vermont, Rubenstein Sch Environm & Nat Resources, Burlington, VT 05405 USA.
EM pbierman@uvm.edu
FU NSF [ARC-1023191]; Directorate For Geosciences; Office of Polar Programs (OPP) [1023191] Funding Source: National Science Foundation
NR 87
TC 88
Z9 105
U1 5
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 256
EP +
DI 10.1038/nature20147
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700054
PM 27929005
DA 2026-03-09
ER

PT J
AU Yang, W
   Bai, YB
   Xiong, Y
   Zhang, J
   Chen, SK
   Zheng, XJ
   Meng, XB
   Li, LY
   Wang, J
   Xu, CG
   Yan, CS
   Wang, LJ
   Chang, CCY
   Chang, TY
   Zhang, T
   Zhou, PH
   Song, BL
   Liu, WL
   Sun, SC
   Liu, XL
   Li, BL
   Xu, CQ
AF Yang, Wei
   Bai, Yibing
   Xiong, Ying
   Zhang, Jin
   Chen, Shuokai
   Zheng, Xiaojun
   Meng, Xiangbo
   Li, Lunyi
   Wang, Jing
   Xu, Chenguang
   Yan, Chengsong
   Wang, Lijuan
   Chang, Catharine C. Y.
   Chang, Ta-Yuan
   Zhang, Ti
   Zhou, Penghui
   Song, Bao-Liang
   Liu, Wanli
   Sun, Shao-Cong
   Liu, Xiaolong
   Li, Bo-liang
   Xu, Chenqi
TI Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
SO NATURE
LA English
DT Article
ID thymocyte positive selection; cancer-immunotherapy; acyl-coenzyme; immunological synapse; immune modulation; membrane-binding; acat inhibitors; receptor; activation; domain
AB CD8(+) T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment(1-4). Reactivating the cytotoxicity of CD8(+) T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8(+) T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme(5), led to potentiated effector function and enhanced proliferation of CD8(+) but not CD4(+) T cells. This is due to the increase in the plasma membrane cholesterol level of CD8(+) T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8(+) T cells were better than wildtype CD8(+) T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile(6,7), to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.
C1 [Yang, Wei; Bai, Yibing; Zhang, Jin; Chen, Shuokai; Meng, Xiangbo; Li, Lunyi; Yan, Chengsong; Xu, Chenqi] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai Sci Res Ctr,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
   [Xiong, Ying; Wang, Lijuan; Li, Bo-liang] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
   [Zheng, Xiaojun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
   [Wang, Jing; Xu, Chenguang; Liu, Wanli] Tsinghua Univ, Collaborat Innovat Ctr Infect Dis, Sch Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Chang, Catharine C. Y.; Chang, Ta-Yuan] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USA.
   [Zhang, Ti] Second Mil Med Univ, ChangZheng Hosp, Rheumatol & Immunol Dept, Shanghai 200433, Peoples R China.
   [Zhou, Penghui] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China.
   [Song, Bao-Liang] Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei Province, Peoples R China.
   [Sun, Shao-Cong] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA.
   [Liu, Xiaolong] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.
   [Xu, Chenqi] ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Tsinghua University; Dartmouth College; Naval Medical University; Sun Yat Sen University; State Key Lab Oncology South China; Wuhan University; University of Texas System; UTMD Anderson Cancer Center; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; ShanghaiTech University
RP Xu, CQ (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai Sci Res Ctr,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.; Li, BL (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.; Xu, CQ (corresponding author), ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China.
EM blli@sibcb.ac.cn; cqxu@sibcb.ac.cn
FU NSFC [31370860, 31425009, 31530022, 31271377, 31400745]; CAS [XDB08020100, KSCX2-EW-J-11]; China Postdoctoral Science Foundation [2014M561533, 2014T70440]; NIH [HL 60306]; MOST [2011CB910901, 2012CB910804]
NR 38
TC 654
Z9 700
U1 6
U2 448
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 651
EP +
DI 10.1038/nature17412
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400041
PM 26982734
DA 2026-03-09
ER

PT J
AU Brito, IL
   Yilmaz, S
   Huang, K
   Xu, L
   Jupiter, SD
   Jenkins, AP
   Naisilisili, W
   Tamminen, M
   Smillie, CS
   Wortman, JR
   Birren, BW
   Xavier, RJ
   Blainey, PC
   Singh, AK
   Gevers, D
   Alm, EJ
AF Brito, I. L.
   Yilmaz, S.
   Huang, K.
   Xu, L.
   Jupiter, S. D.
   Jenkins, A. P.
   Naisilisili, W.
   Tamminen, M.
   Smillie, C. S.
   Wortman, J. R.
   Birren, B. W.
   Xavier, R. J.
   Blainey, P. C.
   Singh, A. K.
   Gevers, D.
   Alm, E. J.
TI Mobile genes in the human microbiome are structured from global to individual scales
SO NATURE
LA English
DT Article
ID level mupirocin resistance; staphylococcus-aureus; gut microbiome; bacteria; plasmid; sequences; community; accurate; impact; faster
AB Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals(1-5). However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
C1 [Brito, I. L.; Smillie, C. S.; Alm, E. J.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Brito, I. L.; Huang, K.; Xu, L.; Wortman, J. R.; Birren, B. W.; Xavier, R. J.; Blainey, P. C.; Gevers, D.; Alm, E. J.] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.
   [Yilmaz, S.; Singh, A. K.] Sandia Natl Labs, Livermore, CA 94608 USA.
   [Jupiter, S. D.; Naisilisili, W.] Wildlife Conservat Soc, Suva, Fiji.
   [Jenkins, A. P.] Edith Cowan Univ, Joondalup, WA 6027, Australia.
   [Tamminen, M.] Eawag, Dept Aquat Ecol, CH-8600 Dubendorf, Switzerland.
   [Tamminen, M.] ETH, Dept Environm Syst Sci, CH-8092 Zurich, Switzerland.
   [Xavier, R. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Xavier, R. J.; Alm, E. J.] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; United States Department of Energy (DOE); Sandia National Laboratories; Edith Cowan University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Swiss Federal Institutes of Technology Domain; ETH Zurich; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT)
RP Alm, EJ (corresponding author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Alm, EJ (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.; Alm, EJ (corresponding author), MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ejalm@mit.edu
FU National Human Genome Research Institute [U54HG003067]; Center for Environmental Health Sciences at MIT; Center for Microbiome Informatics and Therapeutics at MIT; Fijian Ministry of Health; Columbia University Earth Institute Fellowship; Broad Institute Lawrence Summers Fellowship; Burroughs Wellcome Fund Career Award at the Scientific Interface; NIDCR [R01 DE020891]; ENIGMA; US Department of Energy, Office of Science, Office of Biological and Environmental Research; United States Department of Energy [DE-AC04-94AL85000]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM087237] Funding Source: NIH RePORTER
NR 62
TC 191
Z9 243
U1 3
U2 106
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 435
EP +
DI 10.1038/nature18927
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200043
PM 27409808
DA 2026-03-09
ER

PT J
AU Zubko, P
   Wojdel, JC
   Hadjimichael, M
   Fernandez-Pena, S
   Sené, A
   Luk'yanchuk, I
   Triscone, JM
   Iñiguez, J
AF Zubko, Pavlo
   Wojdel, Jacek C.
   Hadjimichael, Marios
   Fernandez-Pena, Stephanie
   Sene, Anais
   Luk'yanchuk, Igor
   Triscone, Jean-Marc
   Iniguez, Jorge
TI Negative capacitance in multidomain ferroelectric superlattices
SO NATURE
LA English
DT Article
ID thin-films; room-temperature; domains; oxide; interfaces; batio3
AB The stability of spontaneous electrical polarization in ferroelectrics is fundamental to many of their current applications, which range from the simple electric cigarette lighter to non-volatile random access memories(1). Research on nanoscale ferroelectrics reveals that their behaviour is profoundly different from that in bulk ferroelectrics, which could lead to new phenomena with potential for future devices(2-4). As ferroelectrics become thinner, maintaining a stable polarization becomes increasingly challenging. On the other hand, intentionally destabilizing this polarization can cause the effective electric permittivity of a ferroelectric to become negative(5), enabling it to behave as a negative capacitance when integrated in a heterostructure. Negative capacitance has been proposed as a way of overcoming fundamental limitations on the power consumption of field-effect transistors(6). However, experimental demonstrations of this phenomenon remain contentious(7). The prevalent interpretations based on homogeneous polarization models are difficult to reconcile with the expected strong tendency for domain formation(8,9), but the effect of domains on negative capacitance has received little attention(5,10-12). Here we report negative capacitance in a model system of multidomain ferroelectric-dielectric superlattices across a wide range of temperatures, in both the ferroelectric and paraelectric phases. Using a phenomenological model, we show that domain-wall motion not only gives rise to negative permittivity, but can also enhance, rather than limit, its temperature range. Our first-principles-based atomistic simulations provide detailed microscopic insight into the origin of this phenomenon, identifying the dominant contribution of near-interface layers and paving the way for its future exploitation.
C1 [Zubko, Pavlo; Hadjimichael, Marios] UCL, London Ctr Nanotechnol, 17-19 Gordon St, London WC1H 0HA, England.
   [Zubko, Pavlo; Hadjimichael, Marios] UCL, Dept Phys & Astron, 17-19 Gordon St, London WC1H 0HA, England.
   [Wojdel, Jacek C.; Iniguez, Jorge] Inst Ciencia Mat Barcelona ICMAB CSIC, Campus UAB, Bellaterra 08193, Spain.
   [Fernandez-Pena, Stephanie; Triscone, Jean-Marc] Univ Geneva, Dept Quantum Matter Phys, CH-1211 Geneva, Switzerland.
   [Sene, Anais; Luk'yanchuk, Igor] Univ Picardie, Lab Condensed Matter Phys, F-80000 Amiens, France.
   [Luk'yanchuk, Igor] LD Landau Theoret Phys Inst, Moscow, Russia.
   [Iniguez, Jorge] LIST, Mat Res & Technol Dept, 5 Ave Hauts Fourneaux, L-4362 Esch Sur Alzette, Luxembourg.
C3 University of London; University College London; University of London; University College London; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB); University of Geneva; Universite de Picardie Jules Verne (UPJV); Russian Academy of Sciences; Landau Institute for Theoretical Physics; Luxembourg Institute of Science & Technology
RP Zubko, P (corresponding author), UCL, London Ctr Nanotechnol, 17-19 Gordon St, London WC1H 0HA, England.; Zubko, P (corresponding author), UCL, Dept Phys & Astron, 17-19 Gordon St, London WC1H 0HA, England.; Iñiguez, J (corresponding author), Inst Ciencia Mat Barcelona ICMAB CSIC, Campus UAB, Bellaterra 08193, Spain.; Iñiguez, J (corresponding author), LIST, Mat Res & Technol Dept, 5 Ave Hauts Fourneaux, L-4362 Esch Sur Alzette, Luxembourg.
EM p.zubko@ucl.ac.uk; jorge.iniguez@list.lu
FU EPSRC [EP/M007073/1]; A. G. Leventis Foundation; FNR Luxembourg [FNR/P12/4853155/Kreisel]; MINECO-Spain [MAT2013-40581-P]; Swiss National Science Foundation Division II; European Research Council under the European Union [319286]; EU; Engineering and Physical Sciences Research Council [EP/M007073/1] Funding Source: researchfish; EPSRC [EP/M007073/1] Funding Source: UKRI
NR 47
TC 349
Z9 382
U1 9
U2 534
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 524
EP +
DI 10.1038/nature17659
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300048
PM 27296225
DA 2026-03-09
ER

PT J
AU Snyder, BER
   Vanelderen, P
   Bols, ML
   Hallaert, SD
   Böttger, LH
   Ungur, L
   Pierloot, K
   Schoonheydt, RA
   Sels, BF
   Solomon, EI
AF Snyder, Benjamin E. R.
   Vanelderen, Pieter
   Bols, Max L.
   Hallaert, Simon D.
   Bottger, Lars H.
   Ungur, Liviu
   Pierloot, Kristine
   Schoonheydt, Robert A.
   Sels, Bert F.
   Solomon, Edward I.
TI The active site of low-temperature methane hydroxylation in iron-containing zeolites
SO NATURE
LA English
DT Article
ID circular-dichroism spectroscopy; electronic-structure; perturbation-theory; fe-bea; oxidation; benzene; state; activation; complexes; spectra
AB An efficient catalytic process for converting methane into methanol could have far-reaching economic implications. Iron-containing zeolites (microporous aluminosilicate minerals) are noteworthy in this regard, having an outstanding ability to hydroxylate methane rapidly at room temperature to form methanol(1-3). Reactivity occurs at an extra-lattice active site called alpha-Fe(ii), which is activated by nitrous oxide to form the reactive intermediate alpha-O-4,O-5; however, despite nearly three decades of research(5), the nature of the active site and the factors determining its exceptional reactivity are unclear. The main difficulty is that the reactive species-alpha-Fe(ii) and alpha-O-are challenging to probe spectroscopically: data from bulk techniques such as X-ray absorption spectroscopy and magnetic susceptibility are complicated by contributions from inactive 'spectator' iron. Here we show that a site-selective spectroscopic method regularly used in bioinorganic chemistry can overcome this problem. Magnetic circular dichroism reveals alpha-Fe(ii) to be a mononuclear, high-spin, square planar Fe(ii) site, while the reactive intermediate, alpha-O, is a mononuclear, high-spin Fe(IV)=O species, whose exceptional reactivity derives from a constrained coordination geometry enforced by the zeolite lattice. These findings illustrate the value of our approach to exploring active sites in heterogeneous systems. The results also suggest that using matrix constraints to activate metal sites for function-producing what is known in the context of metalloenzymes as an 'entatic' state(6)-might be a useful way to tune the activity of heterogeneous catalysts.
C1 [Snyder, Benjamin E. R.; Vanelderen, Pieter; Bottger, Lars H.; Solomon, Edward I.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Vanelderen, Pieter; Bols, Max L.; Schoonheydt, Robert A.; Sels, Bert F.] Univ Leuven, KU Leuven, Ctr Surface Chem & Catalysis, Dept Microbial & Mol Syst, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
   [Hallaert, Simon D.; Ungur, Liviu; Pierloot, Kristine] Katholieke Univ Leuven, Dept Chem, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
   [Solomon, Edward I.] SLAC Natl Accelerator Lab, Photon Sci, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA.
   [Ungur, Liviu] Lund Univ, Div Theoret Chem, POB 124, S-22100 Lund, Sweden.
C3 Stanford University; KU Leuven; KU Leuven; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Lund University
RP Solomon, EI (corresponding author), Stanford Univ, Dept Chem, Stanford, CA 94305 USA.; Schoonheydt, RA; Sels, BF (corresponding author), Univ Leuven, KU Leuven, Ctr Surface Chem & Catalysis, Dept Microbial & Mol Syst, Celestijnenlaan 200F, B-3001 Leuven, Belgium.; Solomon, EI (corresponding author), SLAC Natl Accelerator Lab, Photon Sci, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA.
EM robert.schoonheydt@biw.kuleuven.be; bert.sels@biw.kuleuven.be; edward.solomon@stanford.edu
FU National Science Foundation [DGE-11474, CHE-1360046]; Munger; Pollock; Reynolds; Robinson, Smith & Yoedicke Stanford Graduate Fellowship; Research Foundation-Flanders (FWO) [12L0715N]; KU Leuven; FWO [G0A2216N, G.0865.13]; Hercules Foundation; Flemish Government department EWI; Direct For Mathematical & Physical Scien; Division Of Chemistry [1360046] Funding Source: National Science Foundation
NR 43
TC 384
Z9 434
U1 19
U2 714
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 317
EP +
DI 10.1038/nature19059
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900032
PM 27535535
DA 2026-03-09
ER

PT J
AU Falkner, S
   Grade, S
   Dimou, L
   Conzelmann, KK
   Bonhoeffer, T
   Götz, M
   Hübener, M
AF Falkner, Susanne
   Grade, Sofia
   Dimou, Leda
   Conzelmann, Karl-Klaus
   Bonhoeffer, Tobias
   Goetz, Magdalena
   Huebener, Mark
TI Transplanted embryonic neurons integrate into adult neocortical circuits
SO NATURE
LA English
DT Article
ID mouse visual-cortex; cortical-neurons; stem-cells; pyramidal neurons; receptive-fields; in-vivo; experience; brain; reconstruction; degeneration
AB The ability of the adult mammalian brain to compensate for neuronal loss caused by injury or disease is very limited. Transplantation aims to replace lost neurons, but the extent to which new neurons can integrate into existing circuits is unknown. Here, using chronic in vivo two-photon imaging, we show that embryonic neurons transplanted into the visual cortex of adult mice mature into bona fide pyramidal cells with selective pruning of basal dendrites, achieving adult-like densities of dendritic spines and axonal boutons within 4-8 weeks. Monosynaptic tracing experiments reveal that grafted neurons receive area-specific, afferent inputs matching those of pyramidal neurons in the normal visual cortex, including topographically organized geniculo-cortical connections. Furthermore, stimulus-selective responses refine over the course of many weeks and finally become indistinguishable from those of host neurons. Thus, grafted neurons can integrate with great specificity into neocortical circuits that normally never incorporate new neurons in the adult brain.
C1 [Falkner, Susanne; Bonhoeffer, Tobias; Huebener, Mark] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
   [Grade, Sofia; Dimou, Leda; Goetz, Magdalena] Ludwig Maximilians Univ Munchen, Biomed Ctr, Physiol Genom, D-82152 Planegg, Germany.
   [Grade, Sofia; Dimou, Leda; Goetz, Magdalena] Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
   [Dimou, Leda; Goetz, Magdalena] Luclwig Maximilians Univ Munich, Biomed Ctr, SYNERGY, Excellence Cluster Syst Neurol, D-82152 Planegg, Germany.
   [Conzelmann, Karl-Klaus] Ludwig Maximilians Univ Munchen, Max von Pettenkofer Inst, D-81377 Munich, Germany.
   [Conzelmann, Karl-Klaus] Ludwig Maximilians Univ Munchen, Gene Ctr, D-81377 Munich, Germany.
C3 Max Planck Society; University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; University of Munich; University of Munich
RP Hübener, M (corresponding author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.; Götz, M (corresponding author), Ludwig Maximilians Univ Munchen, Biomed Ctr, Physiol Genom, D-82152 Planegg, Germany.; Götz, M (corresponding author), Helmholtz Ctr Munich, German Res Ctr Environm Hlth, Inst Stem Cell Res, D-85764 Neuherberg, Germany.; Götz, M (corresponding author), Luclwig Maximilians Univ Munich, Biomed Ctr, SYNERGY, Excellence Cluster Syst Neurol, D-82152 Planegg, Germany.
EM magdalena.goetz@helmholtz-muenchen.de; mark@neuro.mpg.de
FU German Research Foundation [SFB 870, SPP 1757]; Advanced ERC grant ChroNeuroRepair; Helmholtz Alliance Icemed; Boehringer Ingelheim Fonds; Max Planck Society
NR 41
TC 136
Z9 166
U1 1
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 248
EP +
DI 10.1038/nature20113
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500036
PM 27783592
DA 2026-03-09
ER

PT J
AU Egan, PJ
   Mullin, M
AF Egan, Patrick J.
   Mullin, Megan
TI Recent improvement and projected worsening of weather in the United States
SO NATURE
LA English
DT Article
ID climate variability; temperature; trends; belief; cmip5; frequency; humidity
AB As climate change unfolds, weather systems in the United States have been shifting in patterns that vary across regions and seasons(1-7). Climate science research typically assesses these changes by examining individual weather indicators, such as temperature or precipitation, in isolation, and averaging their values across the spatial surface. As a result, little is known about population exposure to changes in weather and how people experience and evaluate these changes considered together. Here we show that in the United States from 1974 to 2013, the weather conditions experienced by the vast majority of the population improved. Using previous research on how weather affects local population growth(8-14) to develop an index of people's weather preferences, we find that 80% of Americans live in counties that are experiencing more pleasant weather than they did four decades ago. Virtually all Americans are now experiencing the much milder winters that they typically prefer, and these mild winters have not been offset by markedly more uncomfortable summers or other negative changes. Climate change models predict that this trend is temporary, however, because US summers will eventually warm more than winters. Under a scenario in which greenhouse gas emissions proceed at an unabated rate (Representative Concentration Pathway 8.5), we estimate that 88% of the US public will experience weather at the end of the century that is less preferable than weather in the recent past. Our results have implications for the public's understanding of the climate change problem, which is shaped in part by experiences with local weather(15-20). Whereas weather patterns in recent decades have served as a poor source of motivation for Americans to demand a policy response to climate change, public concern may rise once people's everyday experiences of climate change effects start to become less pleasant.
C1 [Egan, Patrick J.] NYU, Wilf Family Dept Polit, 550 1St Ave, New York, NY 10012 USA.
   [Mullin, Megan] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
C3 New York University; Duke University
RP Egan, PJ (corresponding author), NYU, Wilf Family Dept Polit, 550 1St Ave, New York, NY 10012 USA.
EM patrick.egan@nyu.edu
NR 43
TC 33
Z9 47
U1 1
U2 54
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 357
EP +
DI 10.1038/nature17441
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700030
PM 27127821
DA 2026-03-09
ER

PT J
AU Keane, JT
   Matsuyama, I
   Kamata, S
   Steckloff, JK
AF Keane, James T.
   Matsuyama, Isamu
   Kamata, Shunichi
   Steckloff, Jordan K.
TI Reorientation and faulting of Pluto due to volatile loading within Sputnik Planitia
SO NATURE
LA English
DT Article
ID true polar wander; eccentricity; convection; rotation; moon
AB Pluto is an astoundingly diverse, geologically dynamic world. The dominant feature is Sputnik Planitia-a tear-drop-shaped topographic depression approximately 1,000 kilometres in diameter possibly representing an ancient impact basin(1,2). The interior of Sputnik Planitia is characterized by a smooth, craterless plain three to four kilometres beneath the surrounding rugged uplands, and represents the surface of a massive unit of actively convecting volatile ices (N-2, CH4 and CO) several kilometres thick(1-5). This large feature is very near the Pluto-Charon tidal axis. Here we report that the location of Sputnik Planitia is the natural consequence of the sequestration of volatile ices within the basin and the resulting reorientation (true polar wander) of Pluto. Loading of volatile ices within a basin the size of Sputnik Planitia can substantially alter Pluto's inertia tensor, resulting in a reorientation of the dwarf planet of around 60 degrees with respect to the rotational and tidal axes. The combination of this reorientation, loading and global expansion due to the freezing of a possible subsurface ocean generates stresses within the planet's lithosphere, resulting in a global network of extensional faults that closely replicate the observed fault networks on Pluto. Sputnik Planitia probably formed northwest of its present location, and was loaded with volatiles over million-year timescales as a result of volatile transport cycles on Pluto(6,7). Pluto's past, present and future orientation is controlled by feedbacks between volatile sublimation and condensation, changing insolation conditions and Pluto's interior structure.
C1 [Keane, James T.; Matsuyama, Isamu] Univ Arizona, Dept Planetary Sci, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Kamata, Shunichi] Hokkaido Univ, Creat Res Inst, Sapporo, Hokkaido, Japan.
   [Steckloff, Jordan K.] Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
   [Steckloff, Jordan K.] Planetary Sci Inst, Tucson, AZ 85719 USA.
C3 University of Arizona; Hokkaido University; Purdue University System; Purdue University
RP Keane, JT (corresponding author), Univ Arizona, Dept Planetary Sci, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
EM jkeane@lpl.arizona.edu
FU University of Arizona Theoretical Astrophysics Program; NASA Solar System Workings
NR 41
TC 60
Z9 73
U1 3
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 90
EP +
DI 10.1038/nature20120
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600053
PM 27851731
DA 2026-03-09
ER

PT J
AU Schwietzke, S
   Sherwood, OA
   Ruhwiler, LMPB
   Miller, JB
   Etiope, G
   Dlugokencky, EJ
   Michel, SE
   Arling, VA
   Vaughn, BH
   White, JWC
   Tans, PP
AF Schwietzke, Stefan
   Sherwood, Owen A.
   Ruhwiler, Lori M. P. B.
   Miller, John B.
   Etiope, Giuseppe
   Dlugokencky, Edward J.
   Michel, Sylvia Englund
   Arling, Victoria A.
   Vaughn, Bruce H.
   White, James W. C.
   Tans, Pieter P.
TI Upward revision of global fossil fuel methane emissions based on isotope database
SO NATURE
LA English
DT Article
ID atmospheric methane; natural-gas; fraction
AB Methane has the second-largest global radiative forcing impact of anthropogenic greenhouse gases after carbon dioxide, but our understanding of the global atmospheric methane budget is incomplete. The global fossil fuel industry (production and usage of natural gas, oil and coal) is thought to contribute 15 to 22 per cent of methane emissions(1-10) to the total atmospheric methane budget(11). However, questions remain regarding methane emission trends as a result of fossil fuel industrial activity and the contribution to total methane emissions of sources from the fossil fuel industry and from natural geological seepage(12,13), which are often co-located. Here we re-evaluate the global methane budget and the contribution of the fossil fuel industry to methane emissions based on long-term global methane and methane carbon isotope records. We compile the largest isotopic methane source signature database so far, including fossil fuel, microbial and biomass-burning methane emission sources. We find that total fossil fuel methane emissions (fossil fuel industry plus natural geological seepage) are not increasing over time, but are 60 to 110 per cent greater than current estimates(1-10) owing to large revisions in isotope source signatures. We show that this is consistent with the observed global latitudinal methane gradient. After accounting for natural geological methane seepage(12,13), we find that methane emissions from natural gas, oil and coal production and their usage are 20 to 60 per cent greater than inventories(1,2). Our findings imply a greater potential for the fossil fuel industry to mitigate anthropogenic climate forcing, but we also find that methane emissions from natural gas as a fraction of production have declined from approximately 8 per cent to approximately 2 per cent over the past three decades.
C1 [Schwietzke, Stefan; Miller, John B.; Arling, Victoria A.] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Schwietzke, Stefan; Ruhwiler, Lori M. P. B.; Miller, John B.; Dlugokencky, Edward J.; Arling, Victoria A.; Tans, Pieter P.] NOAA, Earth Syst Res Lab, Global Monitoring Div, Boulder, CO 80305 USA.
   [Sherwood, Owen A.; Michel, Sylvia Englund; Vaughn, Bruce H.; White, James W. C.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
   [Etiope, Giuseppe] Ist Nazl Geofis & Vulcanol, Sez Roma 2, Rome, Italy.
   [Etiope, Giuseppe] Univ Babes Bolyai, Fac Environm Sci & Engn, Cluj Napoca, Romania.
C3 University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA; University of Colorado System; University of Colorado Boulder; Istituto Nazionale Geofisica e Vulcanologia (INGV); Babes Bolyai University from Cluj
RP Schwietzke, S (corresponding author), Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.; Schwietzke, S (corresponding author), NOAA, Earth Syst Res Lab, Global Monitoring Div, Boulder, CO 80305 USA.
EM stefan.schwietzke@noaa.gov
FU National Research Council RAP fellowship; CIRES IRP grant; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [1240584] Funding Source: National Science Foundation
NR 29
TC 419
Z9 492
U1 10
U2 445
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 88
EP 91
DI 10.1038/nature19797
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900039
PM 27708291
DA 2026-03-09
ER

PT J
AU Pagani, L
   Lawson, DJ
   Jagoda, E
   Mörseburg, A
   Eriksson, A
   Mitt, M
   Clemente, F
   Hudjashov, G
   DeGiorgio, M
   Saag, L
   Wall, JD
   Cardona, A
   Mägi, R
   Sayres, MAW
   Kaewert, S
   Inchley, C
   Scheib, CL
   Järve, M
   Karmin, M
   Jacobs, GS
   Antao, T
   Iliescu, FM
   Kushniarevich, A
   Ayub, Q
   Tyler-Smith, C
   Xue, YL
   Yunusbayev, B
   Tambets, K
   Mallick, CB
   Saag, L
   Pocheshkhova, E
   Andriadze, G
   Muller, C
   Westaway, MC
   Lambert, DM
   Zoraqi, G
   Turdikulova, S
   Dalimova, D
   Sabitov, Z
   Sultana, GNN
   Lachance, J
   Tishkoff, S
   Momynaliev, K
   Isakova, J
   Damba, LD
   Gubina, M
   Nymadawa, P
   Evseeva, I
   Atramentova, L
   Utevska, O
   Ricaut, FX
   Brucato, N
   Sudoyo, H
   Letellier, T
   Cox, MP
   Barashkov, NA
   Skaro, V
   Mulahasanovic, L
   Primorac, D
   Sahakyan, H
   Mormina, M
   Eichstaedt, CA
   Lichman, DV
   Abdullah, S
   Chaubey, G
   Wee, JTS
   Mihailov, E
   Karunas, A
   Litvinov, S
   Khusainova, R
   Ekomasova, N
   Akhmetova, V
   Khidiyatova, I
   Marjanovi, D
   Yepiskoposyan, L
   Behar, DM
   Balanovska, E
   Metspalu, A
   Derenko, M
   Malyarchuk, B
   Voevoda, M
   Fedorova, SA
   Osipova, LP
   Mirazón, M
   Gerbault, P
   Leavesley, M
   Migliano, AB
   Petraglia, M
   Balanovsky, O
   Khusnutdinova, EK
   Metspalu, E
   Thomas, MG
   Manica, A
   Nielsen, R
   Villems, R
   Willerslev, E
   Kivisild, T
   Metspalu, M
AF Pagani, Luca
   Lawson, Daniel John
   Jagoda, Evelyn
   Moerseburg, Alexander
   Eriksson, Anders
   Mitt, Mario
   Clemente, Florian
   Hudjashov, Georgi
   DeGiorgio, Michael
   Saag, Lauri
   Wall, Jeffrey D.
   Cardona, Alexia
   Maegi, Reedik
   Sayres, Melissa A. Wilson
   Kaewert, Sarah
   Inchley, Charlotte
   Scheib, Christiana L.
   Jaerve, Mari
   Karmin, Monika
   Jacobs, Guy S.
   Antao, Tiago
   Iliescu, Florin Mircea
   Kushniarevich, Alena
   Ayub, Qasim
   Tyler-Smith, Chris
   Xue, Yali
   Yunusbayev, Bayazit
   Tambets, Kristiina
   Mallick, Chandana Basu
   Saag, Lehti
   Pocheshkhova, Elvira
   Andriadze, George
   Muller, Craig
   Westaway, Michael C.
   Lambert, David M.
   Zoraqi, Grigor
   Turdikulova, Shahlo
   Dalimova, Dilbar
   Sabitov, Zhaxylyk
   Sultana, Gazi Nurun Nahar
   Lachance, Joseph
   Tishkoff, Sarah
   Momynaliev, Kuvat
   Isakova, Jainagul
   Damba, Larisa D.
   Gubina, Marina
   Nymadawa, Pagbajabyn
   Evseeva, Irina
   Atramentova, Lubov
   Utevska, Olga
   Ricaut, Francois-Xavier
   Brucato, Nicolas
   Sudoyo, Herawati
   Letellier, Thierry
   Cox, Murray P.
   Barashkov, Nikolay A.
   Skaro, Vedrana
   Mulahasanovic, Lejla
   Primorac, Dragan
   Sahakyan, Hovhannes
   Mormina, Maru
   Eichstaedt, Christina A.
   Lichman, Daria V.
   Abdullah, Syafiq
   Chaubey, Gyaneshwer
   Wee, Joseph T. S.
   Mihailov, Evelin
   Karunas, Alexandra
   Litvinov, Sergei
   Khusainova, Rita
   Ekomasova, Natalya
   Akhmetova, Vita
   Khidiyatova, Irina
   Marjanovi, Damir
   Yepiskoposyan, Levon
   Behar, Doron M.
   Balanovska, Elena
   Metspalu, Andres
   Derenko, Miroslava
   Malyarchuk, Boris
   Voevoda, Mikhail
   Fedorova, Sardana A.
   Osipova, Ludmila P.
   Mirazon, Marta
   Gerbault, Pascale
   Leavesley, Matthew
   Migliano, Andrea Bamberg
   Petraglia, Michael
   Balanovsky, Oleg
   Khusnutdinova, Elza K.
   Metspalu, Ene
   Thomas, Mark G.
   Manica, Andrea
   Nielsen, Rasmus
   Villems, Richard
   Willerslev, Eske
   Kivisild, Toomas
   Metspalu, Mait
TI Genomic analyses inform on migration events during the peopling of Eurasia
SO NATURE
LA English
DT Article
ID modern human dispersals; modern humans; history; admixture; sequence; evolution; africa; route; atlas
AB High-coverage whole-genome sequence studies have so far focused on a limited number(1) of geographically restricted populations(2-5), or been targeted at specific diseases, such as cancer(6). Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history(7-9) and refuelled the debate on the mutation rate in humans(10). Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long-and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record(11), and admixture between AMHs and Neanderthals predating the main Eurasian expansion(12), our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.
C1 [Pagani, Luca; Hudjashov, Georgi; Saag, Lauri; Jaerve, Mari; Karmin, Monika; Yunusbayev, Bayazit; Tambets, Kristiina; Mallick, Chandana Basu; Litvinov, Sergei; Behar, Doron M.; Metspalu, Ene; Villems, Richard; Kivisild, Toomas; Metspalu, Mait] Estonian Bioctr, EE-51010 Tartu, Estonia.
   [Pagani, Luca; Jagoda, Evelyn; Moerseburg, Alexander; Clemente, Florian; Cardona, Alexia; Kaewert, Sarah; Inchley, Charlotte; Scheib, Christiana L.; Iliescu, Florin Mircea; Kivisild, Toomas] Univ Cambridge, Dept Archaeol & Anthropol, Cambridge CB2 1QH, England.
   [Pagani, Luca] Univ Bologna, Dept Biol Geol & Environm Sci, Via Salmi 3, I-40126 Bologna, Italy.
   [Lawson, Daniel John] Univ Bristol, Sch Social & Community Med, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
   [Jagoda, Evelyn] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Eriksson, Anders] King Abdullah Univ Sci & Technol, Div Biol & Environm Sci & Engn, Integrat Syst Biol Lab, Thuwal 239556900, Saudi Arabia.
   [Manica, Andrea] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Mitt, Mario; Maegi, Reedik; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
   [Mitt, Mario; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-51010 Tartu, Estonia.
   [Clemente, Florian] Univ Montpellier 2, Inst Biol Computat, F-34095 Montpellier, France.
   [Hudjashov, Georgi; Karmin, Monika] Univ Auckland, Dept Psychol, Auckland 1142, New Zealand.
   [Hudjashov, Georgi; Cox, Murray P.; Kivisild, Toomas] Massey Univ, Inst Fundamental Sci, Stat & Bioinformat Grp, Palmerston North 4442, New Zealand.
   [DeGiorgio, Michael] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [Wall, Jeffrey D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Cardona, Alexia] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Box 285,Hills Rd, Cambridge CB2 0QQ, England.
   [Sayres, Melissa A. Wilson] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
   [Sayres, Melissa A. Wilson] Biodesign Inst, Ctr Evolut & Med, Tempe, AZ 85287 USA.
   [Karmin, Monika; Saag, Lehti; Metspalu, Ene; Villems, Richard] Univ Tartu, Inst Mol & Cell Biol, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Jacobs, Guy S.] Univ Southampton, Math Sci, Southampton SO17 1BJ, Hants, England.
   [Jacobs, Guy S.] Univ Southampton, Inst Complex Syst Simulat, Southampton SO17 1BJ, Hants, England.
   [Antao, Tiago] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Kushniarevich, Alena] Natl Acad Sci, Inst Cytol & Genet, BY-220072 Minsk, BELARUS.
   [Ayub, Qasim; Tyler-Smith, Chris; Xue, Yali] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Yunusbayev, Bayazit; Karunas, Alexandra; Litvinov, Sergei; Khusainova, Rita; Akhmetova, Vita; Khidiyatova, Irina; Khusnutdinova, Elza K.] RAS, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450054, Russia.
   [Pocheshkhova, Elvira] Kuban State Med Univ, Krasnodar 350040, Russia.
   [Andriadze, George] St Andrews Georgian Univ, Ctr Sci Res, Caucasian Ethn Groups, Tbilisi 0162, Georgia.
   [Muller, Craig; Nielsen, Rasmus; Willerslev, Eske] Univ Copenhagen, Ctr GeoGenet, DK-1350 Copenhagen, Denmark.
   [Westaway, Michael C.; Lambert, David M.] Griffith Univ, Environm Futures Res Inst, Res Ctr Human Evolut, Nathan, Qld 4111, Australia.
   [Zoraqi, Grigor] Univ Hosp Obstet & Gynecol, Ctr Mol Diag & Genet Res, Tirana 1000, Albania.
   [Turdikulova, Shahlo] Acad Sci, Ctr High Technol, Tashkent 100047, Uzbekistan.
   [Dalimova, Dilbar] Acad Sci, Inst Bioorgan Chem, Tashkent 100047, Uzbekistan.
   [Sultana, Gazi Nurun Nahar] LN Gumilyov Eurasian Natl Univ, Astana 010008, Kazakhstan.
   [Sultana, Gazi Nurun Nahar] Univ Dhaka, Ctr Adv Res Sci CARS, DNA Sequencing Res Lab, Dhaka 1000, Bangladesh.
   [Lachance, Joseph] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Lachance, Joseph] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA.
   [Tishkoff, Sarah] Univ Penn, Dept Genet & Biol, Philadelphia, PA 19104 USA.
   [Momynaliev, Kuvat] DNcode Labs, Moscow 117623, Russia.
   [Isakova, Jainagul] Inst Mol Biol & Med, Bishkek 720040, Kyrgyzstan.
   [Damba, Larisa D.; Gubina, Marina; Lichman, Daria V.; Voevoda, Mikhail; Osipova, Ludmila P.] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia.
   [Nymadawa, Pagbajabyn] Mongolian Acad Med Sci, Ulaanbaatar 210620, Mongolia.
   [Evseeva, Irina] Northern State Med Univ, Arkhangelsk 163000, Russia.
   [Evseeva, Irina] Royal Free Hosp, Anthony Nolan, Pond St, London NW3 2QG, England.
   [Atramentova, Lubov; Utevska, Olga] Kharkov Natl Univ, UA-61022 Kharkov, Ukraine.
   [Ricaut, Francois-Xavier; Brucato, Nicolas; Letellier, Thierry] Univ Toulouse 3, CNRS, Lab Anthropol Mol & Imagerie Synth, UMR 5288,Evolutionary Med Grp, F-31073 Toulouse, France.
   [Sudoyo, Herawati] Eijkman Inst Mol Biol, Genome Divers & Dis Lab, Jakarta 10430, Indonesia.
   [Barashkov, Nikolay A.; Fedorova, Sardana A.] Yakut Sci Ctr Complex Med Problems, Dept Mol Genet, Yakutsk 677027, Russia.
   [Barashkov, Nikolay A.; Fedorova, Sardana A.] MK Ammosov North Eastern Fed Univ, Inst Nat Sci, Lab Mol Biol, Yakutsk 677027, Russia.
   [Skaro, Vedrana] Genos DNA Lab, Zagreb 10000, Croatia.
   [Skaro, Vedrana; Primorac, Dragan] Univ Osijek, Sch Med, Osijek 31000, Croatia.
   [Mulahasanovic, Lejla] CeGaT GmbH, Ctr Genom & Transcript, D-72076 Tubingen, Germany.
   [Primorac, Dragan] St Catherine Specialty Hosp, Zabok 49210, Croatia.
   [Primorac, Dragan] St Catherine Specialty Hosp, Zagreb 10000, Croatia.
   [Primorac, Dragan] Penn State Univ, Eberly Coll Sci, University Pk, PA 16802 USA.
   [Primorac, Dragan] Univ Split, Sch Med, Split 21000, Croatia.
   [Sahakyan, Hovhannes; Yepiskoposyan, Levon] Natl Acad Sci Republ Armenia, Inst Mol Biol, Lab Ethnogen, 7 Hasratyan St, Yerevan 0014, Armenia.
   [Mormina, Maru] Univ Winchester, Dept Appl Social Sci, Sparkford Rd, Winchester S022 4NR, Hants, England.
   [Eichstaedt, Christina A.] Thoraxklin Heidelberg Univ Hosp Heidelberg, D-69120 Heidelberg, Germany.
   [Kushniarevich, Alena; Lichman, Daria V.; Voevoda, Mikhail; Osipova, Ludmila P.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
   [Abdullah, Syafiq] RIPAS Hosp, BE-1518 Bandar Seri Begawan, Brunei.
   [Wee, Joseph T. S.] Natl Canc Ctr Singapore, Singapore 169610, Singapore.
   [Karunas, Alexandra; Litvinov, Sergei; Khusainova, Rita; Ekomasova, Natalya; Khidiyatova, Irina; Khusnutdinova, Elza K.] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450000, Russia.
   [Marjanovi, Damir] Int Burch Univ, Fac Engn & Informat Technol, Dept Genet & Bioengn, Sarajevo 71000, Bosnia & Herceg.
   [Marjanovi, Damir] Inst Anthropol Res, Zagreb 10000, Croatia.
   [Balanovska, Elena; Balanovsky, Oleg] Russian Acad Sci, Res Ctr Med Genet, Moscow 115473, Russia.
   [Derenko, Miroslava; Malyarchuk, Boris] Russian Acad Sci, Inst Biol Problems North, Genet Lab, Magadan 685000, Russia.
   [Voevoda, Mikhail] Russian Acad Med Sci, Inst Internal Med, Siberian Branch, Novosibirsk 630009, Russia.
   [Mirazon, Marta] Univ Cambridge, Dept Archaeol & Anthropol, Leverhulme Ctr Human Evolutionary Studies, Cambridge CB2 1QH, England.
   [Gerbault, Pascale; Thomas, Mark G.] UCL, Res Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Leavesley, Matthew] Univ Papua New Guinea, Dept Archaeol, Univ POB 320, Ncd 134, Papua N Guinea.
   [Leavesley, Matthew] James Cook Univ, Coll Arts Soc & Educ, POB 6811, Cairns, Qld 4870, Australia.
   [Migliano, Andrea Bamberg] UCL, Dept Anthropol, London WC1H 0BW, England.
   [Petraglia, Michael] Max Planck Inst Sci Human Hist, Kahla Str 10, D-07743 Jena, Germany.
   [Balanovsky, Oleg] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119333, Russia.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Villems, Richard] Estonian Acad Sci, 6 Kohtu St, EE-10130 Tallinn, Estonia.
C3 Estonian Biocentre; University of Cambridge; University of Bologna; University of Bristol; Harvard University; King Abdullah University of Science & Technology; University of Cambridge; University of Tartu; University of Tartu; Universite de Montpellier; University of Auckland; Massey University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California San Francisco; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; Arizona State University; Arizona State University-Tempe; University of Tartu; University of Southampton; University of Southampton; University of Montana System; University of Montana; National Academy of Sciences of Belarus (NASB); Institute of Genetics & Cytology of the National Academy of Sciences of Belarus; Wellcome Trust Sanger Institute; Russian Academy of Sciences; Institute of Biochemistry & Genetics of Ufa Science Centre of the RAS; Kuban State Medical University; University of Copenhagen; Griffith University; Ministry of Innovative Development of the Republic of Uzbekistan; Center for Advanced Technologies, Ministry of Innovative Development of the Republic of Uzbekistan; Academy of Sciences of Uzbekistan; Sadykov Institute of Bioorganic Chemistry; L.N. Gumilyov Eurasian National University; University of Dhaka; University of Pennsylvania; University System of Georgia; Georgia Institute of Technology; University of Pennsylvania; Ministry of Health - Kyrgyzstan; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; Mongolian Academy of Sciences; Northern State Medical University; University of London; University College London; Royal Free London NHS Foundation Trust; UCL Medical School; Ministry of Education & Science of Ukraine; VN Karazin Kharkiv National University; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Eijkman Institute; Yakut Science Centre of Complex Medical Problems; North-Eastern Federal University in Yakutsk; University of JJ Strossmayer Osijek; CeGaT; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Split; National Academy of Sciences of Armenia; Institute of Molecular Biology - NAS RA; Novosibirsk State University; National Cancer Centre Singapore (NCCS); Ufa University of Science & Technology; Institute for Anthropological Research Zagreb; Russian Academy of Sciences; Research Centre for Medical Genetics; Institute of Biological Problems of the North; Russian Academy of Sciences; Russian Academy of Medical Sciences; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; University of Cambridge; University of London; University College London; University of Papua New Guinea; James Cook University; University of London; University College London; Russian Academy of Sciences; Vavilov Institute of General Genetics; University of California System; University of California Berkeley; Estonian Academy of Sciences
RP Pagani, L; Kivisild, T; Metspalu, M (corresponding author), Estonian Bioctr, EE-51010 Tartu, Estonia.; Pagani, L; Kivisild, T (corresponding author), Univ Cambridge, Dept Archaeol & Anthropol, Cambridge CB2 1QH, England.; Pagani, L (corresponding author), Univ Bologna, Dept Biol Geol & Environm Sci, Via Salmi 3, I-40126 Bologna, Italy.
EM lp.lucapagani@gmail.com; tk331@cam.ac.uk; mait@ebc.ee
FU Estonian Research Infrastructure Roadmap grant [3.2.0304.11-0312]; Australian Research Council [DP110102635, DP140101405]; Danish National Research Foundation; Lundbeck Foundation; ERC [FP7 - 261213]; Estonian Research Council [PUT766]; EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre; Centre of Excellence for Genomics and Translational Medicine Project [2014-2020.4.01.15-0012]; Estonian Institutional Research grant [IUT24-1]; French Ministry of Foreign and European Affairs; French ANR grant [ANR-14-CE31-0013-01]; Gates Cambridge Trust; ICG SB RAS [VI.58.1.1]; Leverhulme Programme grant [RP2011-R-045]; Ministry of Education and Science of Russia [6.656.2014/K]; NEFREX grant - European Union (People Marie Curie Actions; International Research Staff Exchange Scheme) [318979]; NIH [5DP1ES022577 05, 1R01DK104339-01, 1R01GM113657-01]; Russian Foundation for Basic Research [N 14-06-00180a, 16-04-00890, 14-04-00725-a, 16-06-00303]; Russian Science Foundation [14-14-00827]; Russian Humanitarian Scientific Foundation [13-11-02014]; Program of the Basic Research of the RAS Presidium "Biological diversity"; Wellcome Trust; Royal Society [WT104125AIA]; Bristol Advanced Computing Research Centre; Wellcome Trust [098051, 100719/Z/12/Z]; Young Explorers Grant from the National Geographic Society [8900-11]; ERC Consolidator Grant [647787]; RAS Presidium "Basic research for the development of the Russian Arctic"; Rutherford Fellowship from the Royal Society of New Zealand [RDF-10-MAU-001];  [KU2016]; BBSRC [BB/H005854/1] Funding Source: UKRI; MRC [MC_UU_12013/1] Funding Source: UKRI; Russian Science Foundation [14-14-00827] Funding Source: Russian Science Foundation; Academy of Finland (AKA) [318979] Funding Source: Academy of Finland (AKA); Biotechnology and Biological Sciences Research Council [BB/H005854/1] Funding Source: researchfish; Lundbeck Foundation [R70-2010-6286, R155-2013-16338, R109-2012-9995, R38-2008-3048, R24-2008-2527] Funding Source: researchfish; Medical Research Council [MC_UU_12013/1] Funding Source: researchfish; Wellcome Trust [100719/Z/12/Z] Funding Source: researchfish
NR 34
TC 294
Z9 344
U1 1
U2 229
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 238
EP +
DI 10.1038/nature19792
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000044
PM 27654910
DA 2026-03-09
ER

PT J
AU Mertens, SFL
   Hemmi, A
   Muff, S
   Gröning, O
   De Feyter, S
   Osterwalder, J
   Greber, T
AF Mertens, Stijn F. L.
   Hemmi, Adrian
   Muff, Stefan
   Groning, Oliver
   De Feyter, Steven
   Osterwalder, Jurg
   Greber, Thomas
TI Switching stiction and adhesion of a liquid on a solid
SO NATURE
LA English
DT Article
ID hexagonal boron-nitride; underpotential deposition; contact-angle; hydrogen; rhodium; adsorption; dependence; nanomesh; kinetics; proton
AB When a gecko moves on a ceiling it makes use of adhesion and stiction. Stiction-static friction-is experienced on microscopic and macroscopic scales and is related to adhesion and sliding friction(1). Although important for most locomotive processes, the concepts of adhesion, stiction and sliding friction are often only empirically correlated. A more detailed understanding of these concepts will, for example, help to improve the design of increasingly smaller devices such as micro-and nanoelectromechanical switches(2). Here we show how stiction and adhesion are related for a liquid drop on a hexagonal boron nitride monolayer on rhodium(3), by measuring dynamic contact angles in two distinct states of the solid-liquid interface: a corrugated state in the absence of hydrogen intercalation and an intercalation-induced flat state. Stiction and adhesion can be reversibly switched by applying different electrochemical potentials to the sample, causing atomic hydrogen to be intercalated or not. We ascribe the change in adhesion to a change in lateral electric field of in-plane two-nanometre dipole rings(4), because it cannot be explained by the change in surface roughness known from the Wenzel model(5). Although the change in adhesion can be calculated for the system we study(6), it is not yet possible to determine the stiction at such a solid-liquid interface using ab initio methods. The inorganic hybrid of hexagonal boron nitride and rhodium is very stable and represents a new class of switchable surfaces with the potential for application in the study of adhesion, friction and lubrication.
C1 [Mertens, Stijn F. L.; De Feyter, Steven] Katholieke Univ Leuven, Dept Chem, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
   [Mertens, Stijn F. L.] Vienna Univ Technol, Inst Angew Phys, Wiedner Hauptstr 8-10-E134, A-1040 Vienna, Austria.
   [Hemmi, Adrian; Muff, Stefan; Osterwalder, Jurg; Greber, Thomas] Univ Zurich, Phys Inst, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
   [Groning, Oliver] Empa, Swiss Fed Labs Mat Sci & Technol, Uberlandstr 129, CH-8600 Dubendorf, Switzerland.
C3 KU Leuven; Technische Universitat Wien; University of Zurich; Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA)
RP Mertens, SFL (corresponding author), Katholieke Univ Leuven, Dept Chem, Celestijnenlaan 200F, B-3001 Leuven, Belgium.; Mertens, SFL (corresponding author), Vienna Univ Technol, Inst Angew Phys, Wiedner Hauptstr 8-10-E134, A-1040 Vienna, Austria.; Greber, T (corresponding author), Univ Zurich, Phys Inst, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM stmerten@gmail.com; greber@physik.uzh.ch
FU Swiss National Science Foundation; FP7 Marie Curie European reintegration grant, ERC grant OxideSurfaces; FWO-Vlaanderen
NR 40
TC 77
Z9 86
U1 5
U2 312
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 676
EP +
DI 10.1038/nature18275
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000034
PM 27357755
DA 2026-03-09
ER

PT J
AU Yao, RF
   Ming, ZH
   Yan, LM
   Li, SH
   Wang, F
   Ma, S
   Yu, CT
   Yang, M
   Chen, L
   Chen, LH
   Li, YW
   Yan, C
   Miao, D
   Sun, ZY
   Yan, JB
   Sun, YN
   Wang, L
   Chu, JF
   Fan, SL
   He, W
   Deng, HT
   Nan, FJ
   Li, JY
   Rao, ZH
   Lou, ZY
   Xie, DX
AF Yao, Ruifeng
   Ming, Zhenhua
   Yan, Liming
   Li, Suhua
   Wang, Fei
   Ma, Sui
   Yu, Caiting
   Yang, Mai
   Chen, Li
   Chen, Linhai
   Li, Yuwen
   Yan, Chun
   Miao, Di
   Sun, Zhongyuan
   Yan, Jianbin
   Sun, Yuna
   Wang, Lei
   Chu, Jinfang
   Fan, Shilong
   He, Wei
   Deng, Haiteng
   Nan, Fajun
   Li, Jiayang
   Rao, Zihe
   Lou, Zhiyong
   Xie, Daoxin
TI DWARF14 is a non-canonical hormone receptor for strigolactone
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; structural basis; perception; rice; degradation; inhibition; karrikin; recognition; mechanism; repressor
AB Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection(1-3). However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At) D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
C1 [Yao, Ruifeng; Li, Suhua; Wang, Fei; Ma, Sui; Yu, Caiting; Yang, Mai; Chen, Li; Li, Yuwen; Yan, Chun; Miao, Di; Sun, Zhongyuan; Yan, Jianbin; Fan, Shilong; Deng, Haiteng; Xie, Daoxin] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
   [Yao, Ruifeng; Li, Suhua; Wang, Fei; Ma, Sui; Yu, Caiting; Yang, Mai; Chen, Li; Li, Yuwen; Yan, Chun; Miao, Di; Sun, Zhongyuan; Yan, Jianbin; Fan, Shilong; Deng, Haiteng; Xie, Daoxin] Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China.
   [Ming, Zhenhua; Yan, Liming; Rao, Zihe; Lou, Zhiyong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Ming, Zhenhua; Yan, Liming; Rao, Zihe; Lou, Zhiyong] Tsinghua Univ, Collaborat Innovat Ctr Biotherapy, Beijing 100084, Peoples R China.
   [Chen, Linhai; Nan, Fajun] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China.
   [Sun, Yuna; Rao, Zihe] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
   [Wang, Lei; Chu, Jinfang; Li, Jiayang] Chinese Acad Sci, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
   [Wang, Lei; Chu, Jinfang; Li, Jiayang] Chinese Acad Sci, Inst Genet & Dev Biol, Natl Ctr Plant Gene Res Beijing, Beijing 100101, Peoples R China.
   [He, Wei] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; Institute of Biophysics, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Tsinghua University
RP Xie, DX (corresponding author), Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.; Xie, DX (corresponding author), Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China.; Rao, ZH; Lou, ZY (corresponding author), Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.; Rao, ZH; Lou, ZY (corresponding author), Tsinghua Univ, Collaborat Innovat Ctr Biotherapy, Beijing 100084, Peoples R China.; Rao, ZH (corresponding author), Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
EM raozh@mail.tsinghua.edu.cn; louzy@mail.tsinghua.edu.cn; daoxinlab@mail.tsinghua.edu.cn
FU National Natural Science Foundation of China [91417302, 81322023, 31421001, 91335204]; Ministry of Science and Technology [2013CB911100, 2016YFA0500500]; Ministry of Agriculture [2014ZX08011006]
NR 30
TC 427
Z9 485
U1 22
U2 524
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 469
EP +
DI 10.1038/nature19073
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600044
PM 27479325
DA 2026-03-09
ER

PT J
AU Tan, YJ
   Tolstoy, M
   Waldhauser, F
   Wilcock, WSD
AF Tan, Yen Joe
   Tolstoy, Maya
   Waldhauser, Felix
   Wilcock, William S. D.
TI Dynamics of a seafloor-spreading episode at the East Pacific Rise
SO NATURE
LA English
DT Article
ID midocean ridge; volcanic-eruptions; emplacement; event; constraints; seismicity; beneath; system; ocean; axis
AB Seafloor spreading is largely unobserved because 98 per cent of the global mid-ocean-ridge system is below the ocean surface. Our understanding of the dynamic processes that control seafloor spreading is thus inferred largely from geophysical observations of spreading events on land at Afar in East Africa and Iceland(1). However, these are slow-spreading centres(1) influenced by mantle plumes(2,3). The roles of magma pressure and tectonic stress in the development of seafloor spreading are still unclear. Here we use seismic observations to show that the most recent eruption at the fast-spreading East Pacific Rise just North of the Equator initiated at a melt-rich segment about 5 kilometres long(4). The change in static stress then promoted almost-concurrent rupturing along at least 35 kilometres of the ridge axis, where tectonic stress had built up to a critical level, triggering magma movement. The location of impulsive seismic events indicative of lava reaching the seafloor(5) suggests that lava subsequently erupted from multiple isolated(6,7) magma lenses (reservoir chambers) with variable magma ascent rates, mostly within 48 hours. Therefore, even at magmatically robust fast-spreading ridges, a substantial portion of the spreading may be due to tectonic stress building up to a critical level rather than magma overpressure in the underlying magma lenses.
C1 [Tan, Yen Joe; Tolstoy, Maya; Waldhauser, Felix] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Wilcock, William S. D.] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
C3 Columbia University; University of Washington; University of Washington Seattle
RP Tan, YJ (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM yjt@ldeo.columbia.edu
FU NSF [OCE-0961594]; Division Of Ocean Sciences; Directorate For Geosciences [1536219, 1536320] Funding Source: National Science Foundation
NR 42
TC 45
Z9 57
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 261
EP +
DI 10.1038/nature20116
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700055
PM 27842380
DA 2026-03-09
ER

PT J
AU de Dieuleveult, M
   Yen, KY
   Hmitou, I
   Depaux, A
   Oussouar, FB
   Dargham, DB
   Jounier, S
   Humbertclaude, H
   Ibierre, FR
   Baulard, C
   Farrell, NP
   Park, B
   Keime, C
   Carrière, L
   Erlivet, SB
   Gut, M
   Gut, I
   Werner, M
   Deleuze, JF
   Olaso, R
   Aude, JC
   Chantalat, S
   Pugh, BFR
   Gérard, M
AF de Dieuleveult, Maud
   Yen, Kuangyu
   Hmitou, Isabelle
   Depaux, Arnaud
   Oussouar, Faycal B.
   Dargham, Daria Bou
   Jounier, Sylvie
   Humbertclaude, Helene
   Ibierre, Florence R.
   Baulard, Celine
   Farrell, Nina P.
   Park, Bongsoo
   Keime, Celine
   Carriere, Lucie
   Erlivet, Soizick B.
   Gut, Marta
   Gut, Ivo
   Werner, Michel
   Deleuze, Jean-Francois
   Olaso, Robert
   Aude, Jean-Christophe
   Chantalat, Sophie
   Pugh, B. F. Ranklin
   Gerard, Matthieu
TI Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells
SO NATURE
LA English
DT Article
ID embryonic stem-cells; transcription elongation; cpg islands; pluripotency; binding; esbaf
AB ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers(1-3) target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.
C1 [de Dieuleveult, Maud; Hmitou, Isabelle; Depaux, Arnaud; Oussouar, Faycal B.; Dargham, Daria Bou; Jounier, Sylvie; Humbertclaude, Helene; Carriere, Lucie; Erlivet, Soizick B.; Werner, Michel; Aude, Jean-Christophe; Gerard, Matthieu] Univ Paris Saclay, Univ Paris Sud, I2BC, IBITECS,CEA,CNRS, F-91198 Gif Sur Yvette, France.
   [Yen, Kuangyu] Southern Med Univ, Key Lab Zebrafish Modeling & Drug Screening Human, Dept Dev Biol, Sch Basic Med Sci, Guangzhou 510515, Guangdong, Peoples R China.
   [Yen, Kuangyu; Farrell, Nina P.; Park, Bongsoo; Pugh, B. F. Ranklin] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
   [Ibierre, Florence R.; Baulard, Celine; Deleuze, Jean-Francois; Olaso, Robert; Chantalat, Sophie] CEA, Ctr Natl Genotypage, Inst Genom, F-91057 Evry, France.
   [Keime, Celine] Univ Strasbourg, IGBMC, CNRS, UMR7104,INSERM,U964, F-67404 Illkirch Graffenstaden, France.
   [Gut, Marta; Gut, Ivo] Ctr Nacl Anal Genom, Barcelona 08028, Spain.
   [Oussouar, Faycal B.] Univ Grenoble Alpes, INSERM, U823, Inst Albert Bonniot Grenoble, F-38700 Grenoble, France.
C3 Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CEA; Southern Medical University - China; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; CEA; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP de Dieuleveult, M (corresponding author), Univ Paris Saclay, Univ Paris Sud, I2BC, IBITECS,CEA,CNRS, F-91198 Gif Sur Yvette, France.; Yen, KY (corresponding author), Southern Med Univ, Key Lab Zebrafish Modeling & Drug Screening Human, Dept Dev Biol, Sch Basic Med Sci, Guangzhou 510515, Guangdong, Peoples R China.; Yen, KY (corresponding author), Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
EM matthieu.gerard@cea.fr; kuangyuyen@smu.edu.cn; bfp2@psu.edu
FU CEA; Association pour la Recherche sur le Cancer [3164]; Agence Nationale de la Recherche [ANR-05-BLAN-0396]; Fondation pour la Recherche Medicale (FRM); National Institutes of Health [HG004160]; Southern Medical University [B1000465]; Agence Nationale de la Recherche (ANR) [ANR-05-BLAN-0396] Funding Source: Agence Nationale de la Recherche (ANR); National Human Genome Research Institute [R01HG004160] Funding Source: NIH RePORTER
NR 37
TC 158
Z9 193
U1 2
U2 116
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 113
EP +
DI 10.1038/nature16505
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500043
PM 26814966
DA 2026-03-09
ER

PT J
AU Wolf, F
   Wan, Y
   Heip, JC
   Gebert, F
   Shi, CY
   Schmidt, PO
AF Wolf, Fabian
   Wan, Yong
   Heip, Jan C.
   Gebert, Florian
   Shi, Chunyan
   Schmidt, Piet O.
TI Non-destructive state detection for quantum logic spectroscopy of molecular ions
SO NATURE
LA English
DT Article
AB Precision laser spectroscopy(1) of cold and trapped molecular ions is a powerful tool in fundamental physics-used, for example, in determining fundamental constants(2), testing for their possible variation in the laboratory(3,4), and searching for a possible electric dipole moment of the electron(5). However, the absence of cycling transitions in molecules poses a challenge for direct laser cooling of the ions(6), and for controlling(7-11) and detecting their quantum states. Previously used state-detection techniques based on photodissociation(12) or chemical reactions(13) are destructive and therefore inefficient, restricting the achievable resolution in laser spectroscopy. Here, we experimentally demonstrate non-destructive detection of the quantum state of a single trapped molecular ion through its strong Coulomb coupling to a well controlled, co-trapped atomic ion. An algorithm based on a state-dependent optical dipole force(14) changes the internal state of the atom according to the internal state of the molecule. We show that individual quantum states in the molecular ion can be distinguished by the strength of their coupling to the optical dipole force. We also observe quantum jumps (induced by black-body radiation) between rotational states of a single molecular ion. Using the detuning dependence of the state-detection signal, we implement a variant of quantum logic spectroscopy(15,16) of a molecular resonance. Our state-detection technique is relevant to a wide range of molecular ions, and could be applied to state-controlled quantum chemistry(17) and to spectroscopic investigations of molecules that serve as probes for interstellar clouds(18,19).
C1 [Wolf, Fabian; Wan, Yong; Heip, Jan C.; Gebert, Florian; Shi, Chunyan; Schmidt, Piet O.] Phys Tech Bundesanstalt, D-38116 Braunschweig, Germany.
   [Schmidt, Piet O.] Leibniz Univ Hannover, Inst Quantenopt, D-30167 Hannover, Germany.
   [Wan, Yong] Natl Inst Stand & Technol, 325 Broadway, Boulder, CO 80305 USA.
C3 Physikalisch-Technische Bundesanstalt (PTB); Leibniz University Hannover; National Institute of Standards & Technology (NIST) - USA
RP Schmidt, PO (corresponding author), Phys Tech Bundesanstalt, D-38116 Braunschweig, Germany.; Schmidt, PO (corresponding author), Leibniz Univ Hannover, Inst Quantenopt, D-30167 Hannover, Germany.
EM piet.schmidt@quantummetrology.de
FU Deutsche Forschungsgemeinschaft through QUEST; State of Lower-Saxony, Hannover, Germany; Braunschweig International Graduate School of Metrology;  [SCHM2678/3-1]
NR 38
TC 147
Z9 172
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 457
EP +
DI 10.1038/nature16513
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800030
PM 26855427
DA 2026-03-09
ER

PT J
AU Okumura, R
   Kurakawa, T
   Nakano, T
   Kayama, H
   Kinoshita, M
   Motooka, D
   Gotoh, K
   Kimura, T
   Kamiyama, N
   Kusu, T
   Ueda, Y
   Wu, H
   Iijima, H
   Barman, S
   Osawa, H
   Matsuno, H
   Nishimura, J
   Ohba, Y
   Nakamura, S
   Iida, T
   Yamamoto, M
   Umemoto, E
   Sano, K
   Takeda, K
AF Okumura, Ryu
   Kurakawa, Takashi
   Nakano, Takashi
   Kayama, Hisako
   Kinoshita, Makoto
   Motooka, Daisuke
   Gotoh, Kazuyoshi
   Kimura, Taishi
   Kamiyama, Naganori
   Kusu, Takashi
   Ueda, Yoshiyasu
   Wu, Hong
   Iijima, Hideki
   Barman, Soumik
   Osawa, Hideki
   Matsuno, Hiroshi
   Nishimura, Junichi
   Ohba, Yusuke
   Nakamura, Shota
   Iida, Tetsuya
   Yamamoto, Masahiro
   Umemoto, Eiji
   Sano, Koichi
   Takeda, Kiyoshi
TI Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia
SO NATURE
LA English
DT Article
ID mucus layers; paneth cells; gut; bacteria; mucin; host; homeostasis; molecules; intestine; lectin
AB Colonic epithelial cells are covered by thick inner and outer mucus layers(1,2). The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis(3-6). In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified(7-11). Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.
C1 [Okumura, Ryu; Kurakawa, Takashi; Kayama, Hisako; Kinoshita, Makoto; Kimura, Taishi; Kamiyama, Naganori; Kusu, Takashi; Ueda, Yoshiyasu; Barman, Soumik; Umemoto, Eiji; Takeda, Kiyoshi] Osaka Univ, WPI Immunol Frontier Res Ctr, Grad Sch Med, Lab Immune Regulat,Dept Microbiol & Immunol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Okumura, Ryu; Kayama, Hisako; Kinoshita, Makoto; Barman, Soumik; Umemoto, Eiji; Takeda, Kiyoshi] Japan Agcy Med Res & Dev, Core Res Evolut Sci & Technol, Tokyo 1000004, Japan.
   [Nakano, Takashi; Wu, Hong; Sano, Koichi] Osaka Med Coll, Dept Microbiol & Infect Control, Takatsuki, Osaka 5698686, Japan.
   [Motooka, Daisuke; Gotoh, Kazuyoshi; Nakamura, Shota; Iida, Tetsuya] Osaka Univ, Microbial Dis Res Inst, Genome Informat Res Ctr, Dept Infect Metagenom, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Gotoh, Kazuyoshi] Okayama Univ, Grad Sch Med, Dept Bacteriol, Okayama 7008558, Japan.
   [Iijima, Hideki] Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Suita, Osaka 5650871, Japan.
   [Osawa, Hideki; Matsuno, Hiroshi; Nishimura, Junichi] Osaka Univ, Grad Sch Med, Dept Gastroenterol Surg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Ohba, Yusuke] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido 0608638, Japan.
   [Iida, Tetsuya] Osaka Univ, Dept Bacterial Infect, Microbial Dis Res Inst, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
   [Yamamoto, Masahiro] Osaka Univ, WPI Immunol Frontier Res Ctr, Microbial Dis Res Inst, Lab Immunoparasitol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
C3 University of Osaka; Japan Science & Technology Agency (JST); Osaka Medical & Pharmaceutical University; University of Osaka; Okayama University; University of Osaka; University of Osaka; Hokkaido University; University of Osaka; University of Osaka
RP Takeda, K (corresponding author), Osaka Univ, WPI Immunol Frontier Res Ctr, Grad Sch Med, Lab Immune Regulat,Dept Microbiol & Immunol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.; Takeda, K (corresponding author), Japan Agcy Med Res & Dev, Core Res Evolut Sci & Technol, Tokyo 1000004, Japan.
EM ktakeda@ongene.med.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology; Japan Agency for Medical Research and Development; Grants-in-Aid for Scientific Research [26460969, 15KK0290, 15K15023, 15H02511, 15H01248, 15K15152, 24111005, 26115701, 26293041] Funding Source: KAKEN
NR 21
TC 164
Z9 199
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 117
EP +
DI 10.1038/nature17406
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500045
PM 27027293
DA 2026-03-09
ER

PT J
AU Harpole, WS
   Sullivan, LL
   Lind, EM
   Firn, J
   Adler, PB
   Borer, ET
   Chase, J
   Fay, PA
   Hautier, Y
   Hillebrand, H
   MacDougallm, AS
   Seabloom, EW
   Williams, R
   Bakker, JD
   Cadotte, MW
   Chaneton, EJ
   Chu, CJ
   Cleland, EE
   D'Antonio, C
   Davies, KF
   Gruner, DS
   Hagenah, N
   Kirkman, K
   Knops, JMH
   La Pierre, KJ
   McCulley, RL
   Moore, JL
   Morgan, JW
   Prober, SM
   Risch, AC
   Schuetz, M
   Stevens, CJ
   Wragg, PD
AF Harpole, W. Stanley
   Sullivan, Lauren L.
   Lind, Eric M.
   Firn, Jennifer
   Adler, Peter B.
   Borer, Elizabeth T.
   Chase, Jonathan
   Fay, Philip A.
   Hautier, Yann
   Hillebrand, Helmut
   MacDougallm, Andrew S.
   Seabloom, Eric W.
   Williams, Ryan
   Bakker, Jonathan D.
   Cadotte, Marc W.
   Chaneton, Enrique J.
   Chu, Chengjin
   Cleland, Elsa E.
   D'Antonio, Carla
   Davies, Kendi F.
   Gruner, Daniel S.
   Hagenah, Nicole
   Kirkman, Kevin
   Knops, Johannes M. H.
   La Pierre, Kimberly J.
   McCulley, Rebecca L.
   Moore, Joslin L.
   Morgan, John W.
   Prober, Suzanne M.
   Risch, Anita C.
   Schuetz, Martin
   Stevens, Carly J.
   Wragg, Peter D.
TI Addition of multiple limiting resources reduces grassland diversity
SO NATURE
LA English
DT Article
ID nutrient enrichment; biodiversity loss; species richness; plant diversity; nitrogen; limitation; herbivores; ecology
AB Niche dimensionality provides a general theoretical explanation for biodiversity-more niches, defined by more limiting factors, allow for more ways that species can coexist(1). Because plant species compete for the same set of limiting resources, theory predicts that addition of a limiting resource eliminates potential trade-offs, reducing the number of species that can coexist(2). Multiple nutrient limitation of plant production is common and therefore fertilization may reduce diversity by reducing the number or dimensionality of belowground limiting factors. At the same time, nutrient addition, by increasing biomass, should ultimately shift competition from belowground nutrients towards a one-dimensional competitive trade-off for light(3). Here we show that plant species diversity decreased when a greater number of limiting nutrients were added across 45 grassland sites from a multi-continent experimental network(4). The number of added nutrients predicted diversity loss, even after controlling for effects of plant biomass, and even where biomass production was not nutrient-limited. We found that elevated resource supply reduced niche dimensionality and diversity and increased both productivity(5) and compositional turnover. Our results point to the importance of understanding dimensionality in ecological systems that are undergoing diversity loss in response to multiple global change factors.
C1 [Harpole, W. Stanley] UFZ Helmholtz Ctr Environm Res, Dept Physiol Divers, Permoserstr 15, D-04318 Leipzig, Germany.
   [Harpole, W. Stanley; Chase, Jonathan] German Ctr Integrat Biodivers Res iDiv, Deutsch Pl 5E, D-04103 Leipzig, Germany.
   [Harpole, W. Stanley; Chase, Jonathan] Univ Halle Wittenberg, Inst Biol, Kirchtor 1, D-06108 Halle, Saale, Germany.
   [Sullivan, Lauren L.; Lind, Eric M.; Borer, Elizabeth T.; Seabloom, Eric W.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Firn, Jennifer] Queensland Univ Technol, Sch Earth Environm & Biol Sci, Brisbane, Qld 4001, Australia.
   [Adler, Peter B.] Utah State Univ, Dept Wildland Resources, Logan, UT 84322 USA.
   [Adler, Peter B.] Utah State Univ, Ctr Ecol, Logan, UT 84322 USA.
   [Fay, Philip A.] ARS, USDA, Grassland Soil & Water Res Lab, Temple, TX 76502 USA.
   [Hautier, Yann] Univ Utrecht, Dept Biol, Ecol & Biodivers Grp, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
   [Hillebrand, Helmut] Carl von Ossietzky Univ Oldenburg, Inst Chem & Biol Marine Environm, Schleusenstr 1, D-026381 Wilhelmshaven, Germany.
   [MacDougallm, Andrew S.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Williams, Ryan] Iowa State Univ, Agr & Biosyst Engn, Ames, IA 50011 USA.
   [Bakker, Jonathan D.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Cadotte, Marc W.] Univ Toronto Scarborough, Dept Biol Sci, 1265 Mil Trail, Toronto, ON M1C 1A4, Canada.
   [Chaneton, Enrique J.] Univ Buenos Aires, IFEVA CONICET, Dept Recursos Nat & Ambiente, Fac Agron, Av San Martin 4453 C1417DSE, Buenos Aires, DF, Argentina.
   [Chu, Chengjin] Sun Yat Sen Univ, SYSU Alberta Joint Lab Biodivers Conservat, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China.
   [Chu, Chengjin] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China.
   [Cleland, Elsa E.] Univ Calif La Jolla, Ecol Behav & Evolut Sect, San Diego, CA 92093 USA.
   [D'Antonio, Carla] Univ Calif, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Davies, Kendi F.] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
   [Gruner, Daniel S.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Hagenah, Nicole; Kirkman, Kevin] Univ KwaZutu Natal, Sch Life Sci, ZA-3209 Pietermaritzburg, South Africa.
   [Knops, Johannes M. H.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
   [La Pierre, Kimberly J.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [McCulley, Rebecca L.] Univ Kentucky, Dept Plant & Soil Sci, Lexington, KY 40546 USA.
   [Moore, Joslin L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [Morgan, John W.] La Trobe Univ, Dept Ecol Environm & Evolut, Bundoora, Vic 3086, Australia.
   [Prober, Suzanne M.] CSIRO Land & Water, Private Bag 5, Wembley, WA 6913, Australia.
   [Risch, Anita C.; Schuetz, Martin] Swiss Fed Inst Forest Snow & Landscape Res, Community Ecol, CH-8903 Birmensdorf, Switzerland.
   [Stevens, Carly J.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Wragg, Peter D.] Yale Univ, Dept Ecol & Evolutionary Biol, 165 Prospect St, New Haven, CT 06511 USA.
C3 Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv); Martin Luther University Halle Wittenberg; University of Minnesota System; University of Minnesota Twin Cities; Queensland University of Technology (QUT); Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; United States Department of Agriculture (USDA); Utrecht University; Carl von Ossietzky Universitat Oldenburg; University of Guelph; Iowa State University; University of Washington; University of Washington Seattle; University of Toronto; University Toronto Scarborough; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; Sun Yat Sen University; Sun Yat Sen University; University of California System; University of California San Diego; University of California System; University of California Santa Barbara; University of Colorado System; University of Colorado Boulder; University System of Maryland; University of Maryland College Park; University of Nebraska System; University of Nebraska Lincoln; University of California System; University of California Berkeley; University of Kentucky; Monash University; La Trobe University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Land & Water; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Lancaster University; Yale University
RP Harpole, WS (corresponding author), UFZ Helmholtz Ctr Environm Res, Dept Physiol Divers, Permoserstr 15, D-04318 Leipzig, Germany.
EM stan.harpole@idiv.de
FU National Science Foundation Research Coordination Network [NSF-DEB-1042132]; Long Term Ecological Research program [NSF-DEB-1234162]; Institute on the Environment [DG-0001-13]; Konza Prairie LTER; Yale Institute for Biospheric Studies Pilot Grant; Division Of Environmental Biology; Direct For Biological Sciences [1440484, 1234162] Funding Source: National Science Foundation; ARS [ARS-0429095, 911909] Funding Source: Federal RePORTER
NR 26
TC 466
Z9 556
U1 40
U2 1024
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 93
EP 96
DI 10.1038/nature19324
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900045
PM 27556951
DA 2026-03-09
ER

PT J
AU Fung, R
   Hanna, AM
   Vendrell, O
   Ramakrishna, S
   Seideman, T
   Santra, R
   Ourmazd, A
AF Fung, R.
   Hanna, A. M.
   Vendrell, O.
   Ramakrishna, S.
   Seideman, T.
   Santra, R.
   Ourmazd, A.
TI Dynamics from noisy data with extreme timing uncertainty
SO NATURE
LA English
DT Article
ID time; molecules; emission; nitrogen; ions
AB Imperfect knowledge of the times at which ' snapshots' of a system are recorded degrades our ability to recover dynamical information, and can scramble the sequence of events. In X-ray free-electron lasers, for example, the uncertainty-the so-called timing jitter-between the arrival of an optical trigger ('pump') pulse and a probing X-ray pulse can exceed the length of the X-ray pulse by up to two orders of magnitude(1), marring the otherwise precise time-resolution capabilities of this class of instruments. The widespread notion that little dynamical information is available on timescales shorter than the timing uncertainty has led to various hardware schemes to reduce timing uncertainty(2-4). These schemes are expensive, tend to be specific to one experimental approach and cannot be used when the record was created under ill-defined or uncontrolled conditions such as during geological events. Here we present a data-analytical approach, based on singular-value decomposition and nonlinear Laplacian spectral analysis(5-7), that can recover the history and dynamics of a system from a dense collection of noisy snapshots spanning a sufficiently large multiple of the timing uncertainty. The power of the algorithm is demonstrated by extracting the underlying dynamics on the few-femtosecond timescale from noisy experimental X-ray free-electron laser data recorded with 300-femtosecond timing uncertainty(1). Using a noisy dataset from a pump-probe experiment on the Coulomb explosion of nitrogen molecules, our analysis reveals vibrational wave-packets consisting of components with periods as short as 15 femtoseconds, as well as more rapid changes, which have yet to be fully explored. Our approach can potentially be applied whenever dynamical or historical information is tainted by timing uncertainty.
C1 [Fung, R.; Ourmazd, A.] Univ Wisconsin, Dept Phys, 3135 North Maryland Ave, Milwaukee, WI 53211 USA.
   [Hanna, A. M.; Vendrell, O.; Santra, R.] DESY, Ctr Free Electron Laser Sci, Notkestr 85, D-22607 Hamburg, Germany.
   [Hanna, A. M.; Vendrell, O.; Santra, R.] Hamburg Ctr Ultrafast Imaging, Luruper Chausee 149, D-22761 Hamburg, Germany.
   [Hanna, A. M.; Santra, R.] Univ Hamburg, Dept Chem, Grindelallee 117, D-20146 Hamburg, Germany.
   [Ramakrishna, S.; Seideman, T.] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
   [Santra, R.] Univ Hamburg, Dept Phys, Jungiusstr 9, D-20355 Hamburg, Germany.
C3 University of Wisconsin System; University of Wisconsin Milwaukee; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Hamburg; University of Hamburg; Northwestern University; University of Hamburg
RP Ourmazd, A (corresponding author), Univ Wisconsin, Dept Phys, 3135 North Maryland Ave, Milwaukee, WI 53211 USA.
EM Ourmazd@uwm.edu
FU US Department of Energy, Office of Science, Basic Energy Sciences [DE-SC0002164, DE-FG02-04ER15612]; US National Science Foundation [STC 1231306, 1551489]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1465201] Funding Source: National Science Foundation; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [1551489] Funding Source: National Science Foundation
NR 29
TC 40
Z9 44
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 471
EP 475
DI 10.1038/nature17627
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900040
PM 27121840
DA 2026-03-09
ER

PT J
AU Olivares-Chauvet, P
   Mukamel, Z
   Lifshitz, A
   Schwartzman, O
   Elkayam, NO
   Lubling, Y
   Deikus, G
   Sebra, RP
   Tanay, A
AF Olivares-Chauvet, Pedro
   Mukamel, Zohar
   Lifshitz, Aviezer
   Schwartzman, Omer
   Elkayam, Noa Oded
   Lubling, Yaniv
   Deikus, Gintaras
   Sebra, Robert P.
   Tanay, Amos
TI Capturing pairwise and multi-way chromosomal conformations using chromosomal walks
SO NATURE
LA English
DT Article
ID chromatin architecture; organization; genome; domains; principles; cohesin
AB Chromosomes are folded into highly compacted structures to accommodate physical constraints within nuclei and to regulate access to genomic information(1,2). Recently, global mapping of pairwise contacts showed that loops anchoring topological domains (TADs) are highly conserved between cell types and species(3-8). Whether pairwise loops(9-14) synergize to form higher-order structures is still unclear. Here we develop a conformation capture assay to study higher-order organization using chromosomal walks (C-walks) that link multiple genomic loci together into proximity chains in human and mouse cells. This approach captures chromosomal structure at varying scales. Inter-chromosomal contacts constitute only 7-10% of the pairs and are restricted by interfacing TADs. About half of the C-walks stay within one chromosome, and almost half of those are restricted to intra-TAD spaces. C-walks that couple 2-4 TADs indicate stochastic associations between transcriptionally active, early replicating loci. Targeted analysis of thousands of 3-walks anchored at highly expressed genes support pairwise, rather than hub-like, chromosomal topology at active loci. Polycomb-repressed Hox domains are shown by the same approach to enrich for synergistic hubs. Together, the data indicate that chromosomal territories, TADs, and intra-TAD loops are primarily driven by nested, possibly dynamic, pairwise contacts.
C1 [Olivares-Chauvet, Pedro; Mukamel, Zohar; Lifshitz, Aviezer; Schwartzman, Omer; Elkayam, Noa Oded; Lubling, Yaniv; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Olivares-Chauvet, Pedro; Mukamel, Zohar; Lifshitz, Aviezer; Schwartzman, Omer; Elkayam, Noa Oded; Lubling, Yaniv; Tanay, Amos] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Deikus, Gintaras; Sebra, Robert P.] Icahn Sch Med Mt Sinai, Icahn Inst, New York, NY 10029 USA.
   [Deikus, Gintaras; Sebra, Robert P.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Tanay, A (corresponding author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.; Tanay, A (corresponding author), Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
EM amos.tanay@weizmann.ac.il
FU European Research Council (EVOEPIC); Flight Attendant Medical Research Institute (FAMRI); Israel Science Foundation (ISF)
NR 33
TC 107
Z9 122
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2016
VL 540
IS 7632
BP 296
EP +
DI 10.1038/nature20158
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE4CF
UT WOS:000389548700063
PM 27919068
DA 2026-03-09
ER

PT J
AU Sagi, I
   Chia, G
   Golan-Lev, T
   Peretz, M
   Weissbein, U
   Sui, L
   Sauer, MV
   Yanuka, O
   Egli, D
   Benvenisty, N
AF Sagi, Ido
   Chia, Gloryn
   Golan-Lev, Tamar
   Peretz, Mordecai
   Weissbein, Uri
   Sui, Lina
   Sauer, Mark V.
   Yanuka, Ofra
   Egli, Dieter
   Benvenisty, Nissim
TI Derivation and differentiation of haploid human embryonic stem cells
SO NATURE
LA English
DT Article
ID in-vitro; nuclear transfer; somatic-cells; mouse embryos; generation; lines; inactivation; piggybac; genome; gene
AB Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to ensure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species(1-6), but haploid human ES cells have yet to be reported. Here we generated and analysed a collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics, such as self-renewal capacity and a pluripotency-specific molecular signature. Moreover, we demonstrated the utility of these cells as a platform for loss-of-function genetic screening. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and of genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Surprisingly, we found that a haploid human genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers both in vitro and in vivo, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics and development.
C1 [Sagi, Ido; Golan-Lev, Tamar; Peretz, Mordecai; Weissbein, Uri; Yanuka, Ofra; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Azrieli Ctr Stem Cells & Genet Res, Dept Genet, IL-91904 Jerusalem, Israel.
   [Chia, Gloryn; Sui, Lina; Egli, Dieter] Columbia Univ, Dept Pediat, New York, NY 10032 USA.
   [Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Ctr Womens Reprod Care, New York, NY 10019 USA.
   [Egli, Dieter] New York Stem Cell Fdn Res Inst, New York, NY 10032 USA.
C3 Hebrew University of Jerusalem; Columbia University; Columbia University
RP Benvenisty, N (corresponding author), Hebrew Univ Jerusalem, Silberman Inst Life Sci, Azrieli Ctr Stem Cells & Genet Res, Dept Genet, IL-91904 Jerusalem, Israel.; Egli, D (corresponding author), Columbia Univ, Dept Pediat, New York, NY 10032 USA.; Egli, D (corresponding author), New York Stem Cell Fdn Res Inst, New York, NY 10032 USA.
EM de2220@cumc.columbia.edu; nissimb@cc.huji.ac.il
FU Adams Fellowships Program; A*STAR International Fellowship; Rosetrees Trust; Azrieli Foundation; Russell Berrie Foundation Program in Cellular Therapies of Diabetes; New York State Stem Cell Science (NYSTEM) IIRP Award [C026184]; New York Stem Cell Foundation; Rosetrees [M108-F1] Funding Source: researchfish
NR 41
TC 129
Z9 156
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 107
EP +
DI 10.1038/nature17408
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500043
PM 26982723
DA 2026-03-09
ER

PT J
AU Tran, MT
   Zsengeller, ZK
   Berg, AH
   Khankin, EV
   Bhasin, MK
   Kim, W
   Clish, CB
   Stillman, IE
   Karumanchi, SA
   Rhee, EP
   Parikh, SM
AF Tran, Mei T.
   Zsengeller, Zsuzsanna K.
   Berg, Anders H.
   Khankin, Eliyahu V.
   Bhasin, Manoj K.
   Kim, Wondong
   Clish, Clary B.
   Stillman, Isaac E.
   Karumanchi, S. Ananth
   Rhee, Eugene P.
   Parikh, Samir M.
TI PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection
SO NATURE
LA English
DT Article
ID acute kidney injury; nicotinamide phosphoribosyltransferase; mitochondrial injury; coactivator; promotes; inflammation; inhibition; failure; pathway; enzyme
AB The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischaemia. Acute kidney injury (AKI) affects 3% of all hospitalized patients(1,2). Here we show that the mitochondrial biogenesis regulator, PGC1 alpha(3,4), is a pivotal determinant of renal recovery from injury by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis. Following renal ischaemia, PGC1 alpha(-/-) (also known as Ppargc1a(-/-)) mice develop local deficiency of the NAD precursor niacinamide (NAM, also known as nicotinamide), marked fat accumulation, and failure to reestablish normal function. Notably, exogenous NAM improves local NAD levels, fat accumulation, and renal function in post-ischaemic PGC1 alpha(-/-) mice. Inducible tubular transgenic mice (iNephPGC1 alpha) recapitulate the effects of NAM supplementation, including more local NAD and less fat accumulation with better renal function after ischaemia. PGC1 alpha coordinately upregulates the enzymes that synthesize NAD de novo from amino acids whereas PGC1 alpha deficiency or AKI attenuates the de novo pathway. NAM enhances NAD via the enzyme NAMPT and augments production of the fat breakdown product beta-hydroxybutyrate, leading to increased production of prostaglandin PGE(2) (ref. 5), a secreted autacoid that maintains renal function. NAM treatment reverses established ischaemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of beta-hydroxybutyrate signalling or prostaglandin production similarly abolishes PGC1 alpha-dependent renoprotection. Given the importance of mitochondrial health in ageing and the function of metabolically active organs, the results implicate NAM and NAD as key effectors for achieving PGC1 alpha-dependent stress resistance.
C1 [Tran, Mei T.; Zsengeller, Zsuzsanna K.; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA.
   [Tran, Mei T.; Zsengeller, Zsuzsanna K.; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Tran, Mei T.; Zsengeller, Zsuzsanna K.; Berg, Anders H.; Khankin, Eliyahu V.; Bhasin, Manoj K.; Stillman, Isaac E.; Karumanchi, S. Ananth; Parikh, Samir M.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Tran, Mei T.; Zsengeller, Zsuzsanna K.; Khankin, Eliyahu V.; Bhasin, Manoj K.; Karumanchi, S. Ananth; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA.
   [Zsengeller, Zsuzsanna K.; Berg, Anders H.] Beth Israel Deaconess Med Ctr, Div Clin Chem, Boston, MA 02215 USA.
   [Berg, Anders H.; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
   [Bhasin, Manoj K.] Beth Israel Deaconess Med Ctr, Bioinformat & Syst Biol Core, Boston, MA 02215 USA.
   [Kim, Wondong; Rhee, Eugene P.] Massachusetts Gen Hosp, Nephrol Div, Boston, MA 02114 USA.
   [Kim, Wondong; Rhee, Eugene P.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA.
   [Kim, Wondong; Rhee, Eugene P.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Clish, Clary B.; Rhee, Eugene P.] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.
   [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Howard Hughes Medical Institute
RP Parikh, SM (corresponding author), Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA.; Parikh, SM (corresponding author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.; Parikh, SM (corresponding author), Harvard Univ, Sch Med, Boston, MA 02215 USA.; Parikh, SM (corresponding author), Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA.
EM sparikh1@bidmc.harvard.edu
FU Satellite Healthcare;  [R01-DK095072];  [K08-DK090142];  [K08-DK101560]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK079337, R01DK095072] Funding Source: NIH RePORTER
NR 41
TC 452
Z9 510
U1 4
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 528
EP +
DI 10.1038/nature17184
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300046
PM 26982719
DA 2026-03-09
ER

PT J
AU Rakoff-Nahoum, S
   Foster, KR
   Comstock, LE
AF Rakoff-Nahoum, Seth
   Foster, Kevin R.
   Comstock, Laurie E.
TI The evolution of cooperation within the gut microbiota
SO NATURE
LA English
DT Article
ID public-goods dilemma; polysaccharide utilization; bacteroides-fragilis; general-model; community; prevalence; bacteria; yeast
AB Cooperative phenotypes are considered central to the functioning of microbial communities in many contexts, including communication via quorum sensing, biofilm formation, antibiotic resistance, and pathogenesis(1-5). The human intestine houses a dense and diverse microbial community critical to health(1,2,4-9), yet we know little about cooperation within this important ecosystem. Here we test experimentally for evolved cooperation within the Bacteroidales, the dominant Gram-negative bacteria of the human intestine. We show that during growth on certain dietary polysaccharides, the model member Bacteroides thetaiotaomicron exhibits only limited cooperation. Although this organism digests these polysaccharides extracellularly, mutants lacking this ability are outcompeted. In contrast, we discovered a dedicated cross-feeding enzyme system in the prominent gut symbiont Bacteroides ovatus, which digests polysaccharide at a cost to itself but at a benefit to another species. Using in vitro systems and gnotobiotic mouse colonization models, we find that extracellular digestion of inulin increases the fitness of B. ovatus owing to reciprocal benefits when it feeds other gut species such as Bacteroides vulgatus. This is a rare example of naturally-evolved cooperation between microbial species. Our study reveals both the complexity and importance of cooperative phenotypes within the mammalian intestinal microbiota.
C1 [Rakoff-Nahoum, Seth] Boston Childrens Hosp, Dept Med, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA.
   [Rakoff-Nahoum, Seth] Harvard Univ, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA.
   [Rakoff-Nahoum, Seth; Comstock, Laurie E.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, 181 Longwood Ave, Boston, MA 02115 USA.
   [Rakoff-Nahoum, Seth; Comstock, Laurie E.] Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA.
   [Foster, Kevin R.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Foster, Kevin R.] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3PS, England.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Oxford; University of Oxford
RP Rakoff-Nahoum, S (corresponding author), Boston Childrens Hosp, Dept Med, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA.; Rakoff-Nahoum, S (corresponding author), Harvard Univ, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA.; Rakoff-Nahoum, S (corresponding author), Brigham & Womens Hosp, Dept Med, Div Infect Dis, 181 Longwood Ave, Boston, MA 02115 USA.; Rakoff-Nahoum, S (corresponding author), Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM seth.rakoff-nahoum@childrens.harvard.edu
FU HDDC, NIH Grant [P30 DK34845]; PIDS-St Jude Research Hospital Fellowship Program in Basic Research; K12 Child Health Research Center grant through Boston Children's Hospital; Pilot Feasibility Award - HDDC [P30 DK034854]; European Research Council [242670]; Public Health Service grant from the NIH/NIAID [R01AI081843]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD052896] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854] Funding Source: NIH RePORTER
CR Cameron EA, 2014, MBIO, V5, P0, DOI 10.1128/mBio.01441-14
   Costello EK, 2012, SCIENCE, V336, P1255, DOI 10.1126/science.1224203
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   Estrela S, 2015, TRENDS MICROBIOL, V23, P134, DOI 10.1016/j.tim.2014.11.005
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   STEVENS AM, 1990, J BACTERIOL, V172, P4271, DOI 10.1128/jb.172.8.4271-4279.1990
   Subramanian S, 2015, CELL, V161, P36, DOI 10.1016/j.cell.2015.03.013
   Waldor MK, 2015, PLOS BIOL, V13, P0, DOI 10.1371/journal.pbio.1002050
   West SA, 2006, NAT REV MICROBIOL, V4, P597, DOI 10.1038/nrmicro1461
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NR 33
TC 456
Z9 545
U1 12
U2 569
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2016
VL 533
IS 7602
BP 255
EP +
DI 10.1038/nature17626
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0BJ
UT WOS:000376007200052
PM 27111508
DA 2026-03-09
ER

PT J
AU Hayashi, R
   Schnabl, J
   Handler, D
   Mohn, F
   Arneres, SL
   Brenneeke, J
AF Hayashi, Rippei
   Schnabl, Jakob
   Handler, Dominik
   Mohn, Fabio
   Ameres, Stefan L.
   Brenneeke, Julius
TI Genetic and mechanistic diversity of piRNA 3′-end formation
SO NATURE
LA English
DT Article
ID piwi-interacting rnas; 3' ends; drosophila; biogenesis; micrornas; nibbler; germline; genome; ago3; identification
AB Small regulatory RNAs guide Argonaute (Ago) proteins in a sequence-specific manner to their targets and therefore have important roles in eukaryotic gene silencing(1). Of the three small RNA classes, microRNAs and short interfering RNAs are processed from double-stranded precursors into defined 21- to 23-mers by Dicer, an endoribonuclease with intrinsic ruler function. PIWI-interacting RNAs (piRNAs)-the 22-30-nt-long guides for PIWI-clade Ago proteins that silence transposons in animal gonads-are generated independently of Dicer from single-stranded precursors(2,3). piRNA 5' ends are defined either by Zucchini, the Drosophila homologue of mitoPLD-a mitochondria-anchored endonuclease(4,5), or by piRNA-guided target cleavage(6,7). Formation of piRNA 3' ends is poorly understood. Here we report that two genetically and mechanistically distinct pathways generate piRNA 3' ends in Drosophila. The initiating nucleases are either Zucchini or the PIWI-clade proteins Aubergine (Aub) or Ago3. While Zucchini-mediated cleavages directly define mature piRNA 3' ends(8,9), Aub/Ago3-mediated cleavages liberate pre-piRNAs that require extensive resection by the 3'-to-5' exoribonuclease Nibbler (Drosophila homologue of Mut-7)(10-13). The relative activity of these two pathways dictates the extent to which piRNAs are directed to cytoplasmic or nuclear PIWI-clade proteins and thereby sets the balance between post-transcriptional and transcriptional silencing. Notably, loss of both Zucchini and Nibbler reveals a minimal, Argonaute-driven small RNA biogenesis pathway in which piRNA 5' and 3' ends are directly produced by closely spaced Aub/Ago3-mediated cleavage events. Our data reveal a coherent model for piRNA biogenesis, and should aid the mechanistic dissection of the processes that govern piRNA 3'-end formation.
C1 [Hayashi, Rippei; Schnabl, Jakob; Handler, Dominik; Ameres, Stefan L.; Brenneeke, Julius] Austrian Acad Sci, Vienna Bioctr VBC, Inst Mol Biotechnol IMBA, Dr Bohrgasse 3, A-1030 Vienna, Austria.
   [Mohn, Fabio] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Friedrich Miescher Institute for Biomedical Research
RP Arneres, SL; Brenneeke, J (corresponding author), Austrian Acad Sci, Vienna Bioctr VBC, Inst Mol Biotechnol IMBA, Dr Bohrgasse 3, A-1030 Vienna, Austria.
EM stefan.ameres@imba.oeaw.ac.at; julius.brennecke@imba.oeaw.ac.at
FU Austrian Academy of Sciences; European Community [ERC-StG-260711, ERC-StG-338252]; Austrian Science Fund [Y510-B12, F4303-B09, W12-7-B09, Y733-B22]; HFSP postdoctoral fellowship; Austrian Science Fund (FWF) [W1207, Y733] Funding Source: Austrian Science Fund (FWF)
NR 39
TC 110
Z9 128
U1 1
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 588
EP +
DI 10.1038/nature20162
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600049
PM 27851737
DA 2026-03-09
ER

PT J
AU O'Herron, P
   Chhatbar, PY
   Levy, M
   Shen, ZM
   Schramm, AE
   Lu, ZY
   Kara, P
AF O'Herron, Philip
   Chhatbar, Pratik Y.
   Levy, Manuel
   Shen, Zhiming
   Schramm, Adrien E.
   Lu, Zhongyang
   Kara, Prakash
TI Neural correlates of single-vessel haemodynamic responses in vivo
SO NATURE
LA English
DT Article
ID primary visual-cortex; blood-flow; neuronal-activity; capillary pericytes; fmri; stimulation; signals; brain; microarchitecture; oxygenation
AB Neural activation increases blood flow locally. This vascular signal is used by functional imaging techniques to infer the location and strength of neural activity(1,2). However, the precise spatial scale over which neural and vascular signals are correlated is unknown. Furthermore, the relative role of synaptic and spiking activity in driving haemodynamic signals is controversial(3-9). Previous studies recorded local field potentials as a measure of synaptic activity together with spiking activity and low-resolution haemodynamic imaging. Here we used two-photon microscopy to measure sensory-evoked responses of individual blood vessels (dilation, blood velocity) while imaging synaptic and spiking activity in the surrounding tissue using fluorescent glutamate and calcium sensors. In cat primary visual cortex, where neurons are clustered by their preference for stimulus orientation, we discovered new maps for excitatory synaptic activity, which were organized similarly to those for spiking activity but were less selective for stimulus orientation and direction. We generated tuning curves for individual vessel responses for the first time and found that parenchymal vessels in cortical layer 2/3 were orientation selective. Neighbouring penetrating arterioles had different orientation preferences. Pial surface arteries in cats, as well as surface arteries and penetrating arterioles in rat visual cortex (where orientation maps do not exist(10)), responded to visual stimuli but had no orientation selectivity. We integrated synaptic or spiking responses around individual parenchymal vessels in cats and established that the vascular and neural responses had the same orientation preference. However, synaptic and spiking responses were more selective than vascular responses-vessels frequently responded robustly to stimuli that evoked little to no neural activity in the surrounding tissue. Thus, local neural and haemodynamic signals were partly decoupled. Together, these results indicate that intrinsic cortical properties, such as propagation of vascular dilation between neighbouring columns, need to be accounted for when decoding haemodynamic signals.
C1 [O'Herron, Philip; Chhatbar, Pratik Y.; Levy, Manuel; Shen, Zhiming; Schramm, Adrien E.; Lu, Zhongyang; Kara, Prakash] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
C3 Medical University of South Carolina
RP Kara, P (corresponding author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
EM kara@musc.edu
FU National Institutes of Health [NS088827]; National Science Foundation [1539034]; Whitehall and Dana Foundations; Office of Integrative Activities; Office Of The Director [1539034] Funding Source: National Science Foundation
NR 37
TC 159
Z9 187
U1 0
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 378
EP +
DI 10.1038/nature17965
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800034
PM 27281215
DA 2026-03-09
ER

PT J
AU Katz, LN
   Ates, JLY
   Pillow, JW
   Huk, AC
AF Katz, Leor N.
   Ates, Jacob L. Y.
   Pillow, Jonathan W.
   Huk, Alexander C.
TI Dissociated functional significance of decision-related activity in the primate dorsal stream
SO NATURE
LA English
DT Article
ID lateral intraparietal area; parietal cortex; perceptual decision; visual-cortex; motion signals; macaque monkey; neural basis; neurons; mt; inactivation
AB During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions(1-6). However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making(7-9). Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making(2,10), with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding(1). The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions.
C1 [Katz, Leor N.; Ates, Jacob L. Y.; Huk, Alexander C.] Univ Texas Austin, Dept Neurosci, Ctr Perceptual Syst, Austin, TX 78712 USA.
   [Katz, Leor N.; Ates, Jacob L. Y.; Huk, Alexander C.] Univ Texas Austin, Dept Psychol, Ctr Perceptual Syst, Austin, TX 78712 USA.
   [Pillow, Jonathan W.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08540 USA.
   [Pillow, Jonathan W.] Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Princeton University; Princeton University
RP Katz, LN (corresponding author), Univ Texas Austin, Dept Neurosci, Ctr Perceptual Syst, Austin, TX 78712 USA.; Katz, LN (corresponding author), Univ Texas Austin, Dept Psychol, Ctr Perceptual Syst, Austin, TX 78712 USA.
EM leor.katz@utexas.edu
FU Howard Hughes Medical Institute International Student Research Fellowship; McKnight Foundation; National Eye Institute [R01-EY017366]; National Institutes of Health from the National Institute on Drug Abuse [T32DA018926]; National Institutes of Health from the National Eye Institute [T32EY021462]; National Eye Institute [T32EY021462] Funding Source: NIH RePORTER; National Institute on Drug Abuse [T32DA018926] Funding Source: NIH RePORTER
NR 51
TC 191
Z9 231
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 285
EP +
DI 10.1038/nature18617
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600057
PM 27376476
DA 2026-03-09
ER

PT J
AU Zhang, WF
   Cao, GX
   Li, XL
   Zhang, HY
   Wang, C
   Liu, QQ
   Chen, XP
   Cui, ZL
   Shen, JB
   Jiang, RF
   Mi, GH
   Miao, YX
   Zhang, FS
   Dou, ZX
AF Zhang, Weifeng
   Cao, Guoxin
   Li, Xiaolin
   Zhang, Hongyan
   Wang, Chong
   Liu, Quanqing
   Chen, Xinping
   Cui, Zhenling
   Shen, Jianbo
   Jiang, Rongfeng
   Mi, Guohua
   Miao, Yuxin
   Zhang, Fusuo
   Dou, Zhengxia
TI Closing yield gaps in China by empowering smallholder farmers
SO NATURE
LA English
DT Article
ID global food security; management; intensification; fertilizer; systems; growth; wheat
AB Sustainably feeding the world's growing population is a challenge(1-3), and closing yield gaps (that is, differences between farmers' yields and what are attainable for a given region)(4-6) is a vital strategy to address this challenge(3,4,7). The magnitude of yield gaps is particularly large in developing countries where smallholder farming dominates the agricultural landscape(4,7). Many factors and constraints interact to limit yields(3-6,8-10), and progress in problem-solving to bring about changes at the ground level is rare. Here we present an innovative approach for enabling smallholders to achieve yield and economic gains sustainably via the Science and Technology Backyard (STB) platform. STB involves agricultural scientists living in villages among farmers, advancing participatory innovation and technology transfer, and garnering public and private support. We identified multifaceted yield-limiting factors involving agronomic, infrastructural, and socioeconomic conditions. When these limitations and farmers' concerns were addressed, the farmers adopted recommended management practices, thereby improving production outcomes. In one region in China, the five-year average yield increased from 67.9% of the attainable level to 97.0% among 71 leading farmers, and from 62.8% to 79.6% countywide (93,074 households); this was accompanied by resource and economic benefits.
C1 [Zhang, Weifeng; Cao, Guoxin; Li, Xiaolin; Zhang, Hongyan; Wang, Chong; Chen, Xinping; Cui, Zhenling; Shen, Jianbo; Jiang, Rongfeng; Mi, Guohua; Miao, Yuxin; Zhang, Fusuo] China Agr Univ, Minist Educ, Key Lab Plant Soil Interact, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
   [Liu, Quanqing] Hebei Acad Agr & Forestry Sci, Inst Resources & Environm Sci, Shijiazhuang 050051, Peoples R China.
   [Dou, Zhengxia] Univ Penn, Sch Vet Med, Ctr Anim Hlth & Prod, Kennett Sq, PA 19348 USA.
C3 China Agricultural University; Hebei Academy of Agricultural & Forestry Sciences; University of Pennsylvania
RP Zhang, FS (corresponding author), China Agr Univ, Minist Educ, Key Lab Plant Soil Interact, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
EM zhangfs@cau.edu.cn
FU China 973 Program [2015CB150405]; Innovative Group Grant of the Natural Science Foundation of China [31421092]; Special Fund for Agro Scientific Research in the Public Interest [201203079]; Program for New Century Excellent Talents in University [2016QC125]
NR 34
TC 514
Z9 613
U1 48
U2 1069
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 671
EP +
DI 10.1038/nature19368
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700048
PM 27602513
DA 2026-03-09
ER

PT J
AU Bassett, D
   Sandwell, DT
   Fialko, Y
   Watts, AB
AF Bassett, Dan
   Sandwell, David T.
   Fialko, Yuri
   Watts, Anthony B.
TI Upper-plate controls on co-seismic slip in the 2011 magnitude 9.0 Tohoku-oki earthquake
SO NATURE
LA English
DT Article
ID median tectonic line; fore-arc region; structural characteristics; east shikoku; fault; rupture; inversion; gravity; zone; reflection
AB The March 2011 Tohoku-oki earthquake was only the second giant (moment magnitude M-w >= 9.0) earthquake to occur in the last 50 years and is the most recent to be recorded using modern geophysical techniques. Available data place high-resolution constraints on the kinematics of earthquake rupture(1), which have challenged prior knowledge about how much a fault can slip in a single earthquake and the seismic potential of a partially coupled megathrust interface(2). But it is not clear what physical or structural characteristics controlled either the rupture extent or the amplitude of slip in this earthquake. Here we use residual topography and gravity anomalies to constrain the geological structure of the overthrusting (upper) plate offshore northeast Japan. These data reveal an abrupt southwest-northeast-striking boundary in upperplate structure, across which gravity modelling indicates a south-tonorth increase in the density of rocks overlying the megathrust of 150-200 kilograms per cubic metre. We suggest that this boundary represents the offshore continuation of the Median Tectonic Line, which onshore juxtaposes geological terranes composed of granite batholiths (in the north) and accretionary complexes (in the south) 3. The megathrust north of the Median Tectonic Line is interseismically locked(2), has a history of large earthquakes (18 with M-w >= 7 since 1896) and produced peak slip exceeding 40 metres in the Tohoku-oki earthquake(1). In contrast, the megathrust south of this boundary has higher rates of interseismic creep(2), has not generated an earthquake with M-J > 7 (local magnitude estimated by the Japan Meteorological Agency) since 1923, and experienced relatively minor (if any) co-seismic slip in 2011(1). We propose that the structure and frictional properties of the overthrusting plate control megathrust coupling and seismogenic behaviour in northeast Japan.
C1 [Bassett, Dan; Sandwell, David T.; Fialko, Yuri] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Watts, Anthony B.] Univ Oxford, Dept Earth Sci, S Parks Rd, Oxford OX1 3PR, England.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Oxford
RP Bassett, D (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
EM dbassett@ucsd.edu
FU University of Oxford; Green Foundation; National Geospatial Agency [HM01771310008]; Scripps Seafloor Electromagnetics Consortium; NERC [NE/F005318/1] Funding Source: UKRI; Directorate For Geosciences; Division Of Ocean Sciences [1128801] Funding Source: National Science Foundation; Natural Environment Research Council [NE/F005318/1] Funding Source: researchfish
NR 66
TC 87
Z9 99
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 92
EP +
DI 10.1038/nature16945
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900046
PM 26935698
DA 2026-03-09
ER

PT J
AU Jiang, L
   Shestov, AA
   Swain, P
   Yang, CD
   Parker, SJ
   Wang, QA
   Terada, LS
   Adams, ND
   McCabe, MT
   Pietrak, B
   Schmidt, S
   Metallo, CM
   Dranka, BP
   Schwartz, B
   DeBerardinis, RJ
AF Jiang, Lei
   Shestov, Alexander A.
   Swain, Pamela
   Yang, Chendong
   Parker, Seth J.
   Wang, Qiong A.
   Terada, Lance S.
   Adams, Nicholas D.
   McCabe, Michael T.
   Pietrak, Beth
   Schmidt, Stan
   Metallo, Christian M.
   Dranka, Brian P.
   Schwartz, Benjamin
   DeBerardinis, Ralph J.
TI Reductive carboxylation supports redox homeostasis during anchorage-independent growth
SO NATURE
LA English
DT Article
ID cell-survival; flux analysis; tumor-cells; mitochondria; stress; cancer; antioxidant; contributes; metabolism; maintains
AB Cells receive growth and survival stimuli through their attachment to an extracellular matrix (ECM)(1). Overcoming the addiction to ECM-induced signals is required for anchorage-independent growth, a property of most malignant cells(2). Detachment from ECM is associated with enhanced production of reactive oxygen species (ROS) owing to altered glucose metabolism(2). Here we identify an unconventional pathway that supports redox homeostasis and growth during adaptation to anchorage independence. We observed that detachment from monolayer culture and growth as anchorage-independent tumour spheroids was accompanied by changes in both glucose and glutamine metabolism. Specifically, oxidation of both nutrients was suppressed in spheroids, whereas reductive formation of citrate from glutamine was enhanced. Reductive glutamine metabolism was highly dependent on cytosolic isocitrate dehydrogenase-1 (IDH1), because the activity was suppressed in cells homozygous null for IDH1 or treated with an IDH1 inhibitor. This activity occurred in absence of hypoxia, a well-known inducer of reductive metabolism. Rather, IDH1 mitigated mitochondrial ROS in spheroids, and suppressing IDH1 reduced spheroid growth through a mechanism requiring mitochondrial ROS. Isotope tracing revealed that in spheroids, isocitrate/citrate produced reductively in the cytosol could enter the mitochondria and participate in oxidative metabolism, including oxidation by IDH2. This generates NADPH in the mitochondria, enabling cells to mitigate mitochondrial ROS and maximize growth. Neither IDH1 nor IDH2 was necessary for monolayer growth, but deleting either one enhanced mitochondrial ROS and reduced spheroid size, as did deletion of the mitochondrial citrate transporter protein. Together, the data indicate that adaptation to anchorage independence requires a fundamental change in citrate metabolism, initiated by IDH1-dependent reductive carboxylation and culminating in suppression of mitochondrial ROS.
C1 [Jiang, Lei; Yang, Chendong; DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA.
   [Shestov, Alexander A.] Univ Penn, Sch Med, Dept Radiol, 3620 Hamilton Walk, Philadelphia, PA 19104 USA.
   [Swain, Pamela; Dranka, Brian P.] Seahorse Biosci, 16 Esquire Rd, North Billerica, MA 01862 USA.
   [Parker, Seth J.; Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Wang, Qiong A.] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA.
   [Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Adams, Nicholas D.; McCabe, Michael T.; Pietrak, Beth; Schmidt, Stan; Schwartz, Benjamin] GlaxoSmithKline, 1250 South Collegeville Rd, Collegeville, PA 19426 USA.
   [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Pennsylvania; University of California System; University of California San Diego; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; GlaxoSmithKline; Glaxosmithkline USA; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP DeBerardinis, RJ (corresponding author), Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA.; DeBerardinis, RJ (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.; DeBerardinis, RJ (corresponding author), Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
EM Ralph.Deberardinis@UTSouthwestern.edu
FU N.I.H [R01CA157996]; Cancer Prevention and Research Institute of Texas [RP130272]; Robert A. Welch Foundation [I1733]; N.I.H. [R01CA188652]
NR 30
TC 470
Z9 553
U1 4
U2 260
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 255
EP +
DI 10.1038/nature17393
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100044
PM 27049945
DA 2026-03-09
ER

PT J
AU Xia, Y
   Lu, G
   Liu, P
   Dong, GB
AF Xia, Ying
   Lu, Gang
   Liu, Peng
   Dong, Guangbin
TI Catalytic activation of carbon-carbon bonds in cyclopentanones
SO NATURE
LA English
DT Article
ID c-c bond; enantioselective synthesis; (+)-erogorgiaene; migration; breaking
AB In the chemical industry, molecules of interest are based primarily on carbon skeletons. When synthesizing such molecules, the activation of carbon-carbon single bonds (C-C bonds) in simple substrates is strategically important: it offers a way of disconnecting such inert bonds, forming more active linkages (for example, between carbon and a transition metal) and eventually producing more versatile scaffolds(1-13). The challenge in achieving such activation is the kinetic inertness of C-C bonds and the relative weakness of newly formed carbon-metal bonds(6,14). The most common tactic starts with a three-or four-membered carbon-ring system(9-13), in which strain release provides a crucial thermodynamic driving force. However, broadly useful methods that are based on catalytic activation of unstrained C-C bonds have proven elusive, because the cleavage process is much less energetically favourable. Here we report a general approach to the catalytic activation of C-C bonds in simple cyclopentanones and some cyclohexanones. The key to our success is the combination of a rhodium pre-catalyst, an N-heterocyclic carbene ligand and an amino-pyridine co-catalyst. When an aryl group is present in the C3 position of cyclopentanone, the less strained C-C bond can be activated; this is followed by activation of a carbon-hydrogen bond in the aryl group, leading to efficient synthesis of functionalized alpha-tetralones-alpha common structural motif and versatile building block in organic synthesis. Furthermore, this method can substantially enhance the efficiency of the enantioselective synthesis of some natural products of terpenoids. Density functional theory calculations reveal a mechanism involving an intriguing rhodiumbridged bicyclic intermediate.
C1 [Xia, Ying; Dong, Guangbin] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
   [Xia, Ying; Dong, Guangbin] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Lu, Gang; Liu, Peng] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
C3 University of Texas System; University of Texas Austin; University of Chicago; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Dong, GB (corresponding author), Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.; Liu, P; Dong, GB (corresponding author), Univ Chicago, Dept Chem, Chicago, IL 60637 USA.; Liu, P (corresponding author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
EM pengliu@pitt.edu; gbdong@uchicago.edu
FU Cancer Prevention Research Institute of Texas [R1118]; National Institute of General Medical Science [R01GM109054]; Welch Foundation [F1781]; Office of China Postdoctoral Council (OCPC) [38]; National Science Foundation; National Institute of General Medical Sciences [R01GM109054] Funding Source: NIH RePORTER
NR 30
TC 221
Z9 238
U1 7
U2 265
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 546
EP 550
DI 10.1038/nature19849
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600040
PM 27806379
DA 2026-03-09
ER

PT J
AU Faure, LM
   Fiche, JB
   Espinosa, L
   Ducret, A
   Anantharaman, V
   Luciano, J
   Lhospice, S
   Islam, ST
   Tréguier, J
   Sotes, M
   Kuru, E
   Van Nieuwenhze, MS
   Brun, YV
   Théodoly, O
   Aravind, L
   Nollmann, M
   Mignot, T
AF Faure, Laura M.
   Fiche, Jean-Bernard
   Espinosa, Leon
   Ducret, Adrien
   Anantharaman, Vivek
   Luciano, Jennifer
   Lhospice, Sebastien
   Islam, Salim T.
   Treguier, Julie
   Sotes, Melanie
   Kuru, Erkin
   Van Nieuwenhze, Michael S.
   Brun, Yves V.
   Theodoly, Olivier
   Aravind, L.
   Nollmann, Marcelo
   Mignot, Tam
TI The mechanism of force transmission at bacterial focal adhesion complexes
SO NATURE
LA English
DT Article
ID hidden markov model; myxococcus-xanthus; gliding motility; actin cytoskeleton; signal; topology; accurate
AB Various rod-shaped bacteria mysteriously glide on surfaces in the absence of appendages such as flagella or pili. In the deltaproteobacterium Myxococcus xanthus, a putative gliding motility machinery (the Agl-Glt complex) localizes to so-called focal adhesion sites (FASs) that form stationary contact points with the underlying surface. Here we show that the Agl-Glt machinery contains an inner-membrane motor complex that moves intracellularly along a right-handed helical path; when the machinery becomes stationary at FASs, the motor complex powers a left-handed rotation of the cell around its long axis. At FASs, force transmission requires cyclic interactions between the molecular motor and the adhesion proteins of the outer membrane via a periplasmic interaction platform, which presumably involves contractile activity of motor components and possible interactions with peptidoglycan. Our results provide a molecular model of bacterial gliding motility.
C1 [Faure, Laura M.; Espinosa, Leon; Ducret, Adrien; Luciano, Jennifer; Lhospice, Sebastien; Islam, Salim T.; Treguier, Julie; Sotes, Melanie; Mignot, Tam] Aix Marseille Univ, CNRS, Inst Microbiol Mediterranee, Lab Chim Bacterienne,UMR7283, F-13009 Marseille, France.
   [Fiche, Jean-Bernard; Nollmann, Marcelo] Univ Montpellier, INSERM, CNRS, Ctr Biochim Struct,UMR5048,U1054, 29 Rue Navacelles, F-34090 Montpellier, France.
   [Ducret, Adrien; Brun, Yves V.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Anantharaman, Vivek] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
   [Kuru, Erkin] Indiana Univ, Interdisciplinary Biochem Program, Bloomington, IN 47405 USA.
   [Van Nieuwenhze, Michael S.] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.
   [Theodoly, Olivier] Aix Marseille Univ, INSERM, Adhes & Inflammat Lab, U1067,UMR7333, F-13288 Marseille, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Indiana University System; Indiana University Bloomington; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Mignot, T (corresponding author), Aix Marseille Univ, CNRS, Inst Microbiol Mediterranee, Lab Chim Bacterienne,UMR7283, F-13009 Marseille, France.; Nollmann, M (corresponding author), Univ Montpellier, INSERM, CNRS, Ctr Biochim Struct,UMR5048,U1054, 29 Rue Navacelles, F-34090 Montpellier, France.
EM marcelo.nollmann@cbs.cnrs.fr; tmignot@imm.cnrs.fr
FU Fondation ARC; Fondation pour la Recherche Medicale; Canadian Institutes of Health Research; AMIDEX program of Aix-Marseille Universite; IRP funds of the NIH; NIH [GM113172, GM51986]; European Research Council [DOME-261105, 260787]; Bettencourt-Schueller "Coup d'elan pour la recherche Francaise; ANR grant IBM [ANR-14-CE09-0025-01]; ANR grant HiResBacs [ANR-15-CE11-0023]; France-BioImaging ("Investments for the future") [ANR-10-INBS-04]; Imagine Optic; European Research Council (ERC) [260787] Funding Source: European Research Council (ERC); Agence Nationale de la Recherche (ANR) [ANR-15-CE11-0023, ANR-14-CE09-0025] Funding Source: Agence Nationale de la Recherche (ANR)
NR 38
TC 97
Z9 113
U1 1
U2 71
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 530
EP +
DI 10.1038/nature20121
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600037
PM 27749817
DA 2026-03-09
ER

PT J
AU Jaccard, SL
   Galbraith, ED
   Martínez-García, A
   Anderson, RF
AF Jaccard, Samuel L.
   Galbraith, Eric D.
   Martinez-Garcia, Alfredo
   Anderson, Robert F.
TI Covariation of deep Southern Ocean oxygenation and atmospheric CO2 through the last ice age
SO NATURE
LA English
DT Article
ID glacial-interglacial changes; authigenic uranium; late-quaternary; scale changes; sea sediment; 2 modes; productivity; variability; sector; th-230
AB No single mechanism can account for the full amplitude of past atmospheric carbon dioxide (CO2) concentration variability over glacial-interglacial cycles(1). A build-up of carbon in the deep ocean has been shown to have occurred during the Last Glacial Maximum(2,3). However, the mechanisms responsible for the release of the deeply sequestered carbon to the atmosphere at deglaciation, and the relative importance of deep ocean sequestration in regulating millennial-timescale variations in atmospheric CO2 concentration before the Last Glacial Maximum, have remained unclear. Here we present sedimentary redox-sensitive trace-metal records from the Antarctic Zone of the Southern Ocean that provide a reconstruction of transient changes in deep ocean oxygenation and, by inference, respired carbon storage throughout the last glacial cycle. Our data suggest that respired carbon was removed from the abyssal Southern Ocean during the Northern Hemisphere cold phases of the deglaciation, when atmospheric CO2 concentration increased rapidly, reflecting-at least in part-a combination of dwindling iron fertilization by dust and enhanced deep ocean ventilation. Furthermore, our records show that the observed covariation between atmospheric CO2 concentration and abyssal Southern Ocean oxygenation was maintained throughout most of the past 80,000 years. This suggests that on millennial timescales deep ocean circulation and iron fertilization in the Southern Ocean played a consistent role in modifying atmospheric CO2 concentration.
C1 [Jaccard, Samuel L.] Univ Bern, Inst Geol Sci, Bern, Switzerland.
   [Jaccard, Samuel L.] Univ Bern, Oeschger Ctr Climate Change Res, Bern, Switzerland.
   [Galbraith, Eric D.] McGill Univ, Dept Earth & Planetary Sci, Montreal, PQ, Canada.
   [Galbraith, Eric D.] ICREA, Barcelona, Spain.
   [Galbraith, Eric D.] Univ Autonoma Barcelona, Inst Ciencia & Tecnol Ambientals, E-08193 Barcelona, Spain.
   [Galbraith, Eric D.] Univ Autonoma Barcelona, Dept Math, E-08193 Barcelona, Spain.
   [Martinez-Garcia, Alfredo] Swiss Fed Inst Technol, Inst Geol, Zurich, Switzerland.
   [Martinez-Garcia, Alfredo] Max Planck Inst Chem, Climate Geochem Dept, Mainz, Germany.
   [Anderson, Robert F.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY USA.
C3 University of Bern; University of Bern; McGill University; ICREA; Autonomous University of Barcelona; Autonomous University of Barcelona; Swiss Federal Institutes of Technology Domain; ETH Zurich; Max Planck Society; Columbia University
RP Jaccard, SL (corresponding author), Univ Bern, Inst Geol Sci, Bern, Switzerland.
EM samuel.jaccard@geo.unibe.ch
FU Swiss National Science Foundation [PP00P2-144811, PZ00P2_142424]; NSERC; US NSF; Swiss National Science Foundation (SNF) [PZ00P2_142424] Funding Source: Swiss National Science Foundation (SNF); ICREA Funding Source: Custom
NR 56
TC 202
Z9 226
U1 4
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 207
EP +
DI 10.1038/nature16514
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700036
PM 26840491
DA 2026-03-09
ER

PT J
AU Charbonneau, MR
   Blanton, LV
   DiGiulio, DB
   Relman, DA
   Lebrilla, CB
   Mills, DA
   Gordon, JI
AF Charbonneau, Mark R.
   Blanton, Laura V.
   DiGiulio, Daniel B.
   Relman, David A.
   Lebrilla, Carlito B.
   Mills, David A.
   Gordon, Jeffrey I.
TI A microbial perspective of human developmental biology
SO NATURE
LA English
DT Article
ID human-milk oligosaccharides; low-birth-weight; vaginal microbiome; amniotic-fluid; gut microbiota; preterm labor; sialic-acid; oral microbiome; pregnant-women; infection
AB When most people think of human development, they tend to consider only human cells and organs. Yet there is another facet that involves human-associated microbial communities. A microbial perspective of human development provides opportunities to refine our definitions of healthy prenatal and postnatal growth and to develop innovative strategies for disease prevention and treatment. Given the dramatic changes in lifestyles and disease patterns that are occurring with globalization, we issue a call for the establishment of 'human microbial observatories' designed to examine microbial community development in birth cohorts representing populations with diverse anthropological characteristics, including those undergoing rapid change.
C1 [Charbonneau, Mark R.; Blanton, Laura V.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.
   [Charbonneau, Mark R.; Blanton, Laura V.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Gut Microbiome & Nutr Res, St Louis, MO 63110 USA.
   [DiGiulio, Daniel B.; Relman, David A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
   [DiGiulio, Daniel B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
   [Relman, David A.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Lebrilla, Carlito B.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA.
   [Lebrilla, Carlito B.; Mills, David A.] Univ Calif Davis, Foods Hlth Inst, Davis, CA 95616 USA.
   [Mills, David A.] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA.
   [Mills, David A.] Univ Calif Davis, Dept Viticulture & Enol, Davis, CA 95616 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Stanford University; University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA.; Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Gut Microbiome & Nutr Res, St Louis, MO 63110 USA.
EM jgordon@wustl.edu
FU US National Institutes of Health [DK30292, HD061923, AT007079, AT008759]; Bill & Melinda Gates Foundation; March of Dimes Foundation; Thomas C. and Joan M. Merigan Endowment at Stanford University; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK030292] Funding Source: NIH RePORTER
NR 100
TC 179
Z9 208
U1 2
U2 178
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 48
EP 55
DI 10.1038/nature18845
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600027
PM 27383979
DA 2026-03-09
ER

PT J
AU Mei, Y
   Monteiro, P
   Zhou, Y
   Kim, JA
   Gao, X
   Fu, ZY
   Feng, GP
AF Mei, Yuan
   Monteiro, Patricia
   Zhou, Yang
   Kim, Jin-Ah
   Gao, Xian
   Fu, Zhanyan
   Feng, Guoping
TI Adult restoration of Shank3 expression rescues selective autistic-like phenotypes
SO NATURE
LA English
DT Article
ID spectrum disorder; rett-syndrome; mutant mice; behaviors; mutations; proteins; family; dysfunction; defects; mouse
AB Because autism spectrum disorders are neurodevelopmental disorders and patients typically display symptoms before the age of three(1), one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigate the developmental requirement of Shank(3) in mice, a prominent monogenic autism gene that is estimated to contribute to approximately 1% of all autism spectrum disorder cases(2-6). SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density macromolecular signalling complex(7-9). Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviours including anxiety, social interaction deficits, and repetitive behaviour(10-13). We generated a novel Shank3 conditional knock-in mouse model, and show that re-expression of the Shank3 gene in adult mice led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provide behavioural evidence that certain behavioural abnormalities including social interaction deficit and repetitive grooming behaviour could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain.
C1 [Mei, Yuan; Monteiro, Patricia; Zhou, Yang; Kim, Jin-Ah; Gao, Xian; Fu, Zhanyan; Feng, Guoping] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA.
   [Monteiro, Patricia] Univ Coimbra, Ctr Neurosci & Cell Biol, PhD Programme Expt Biol & Biomed PDBEB, P-3004517 Coimbra, Portugal.
   [Monteiro, Patricia; Fu, Zhanyan; Feng, Guoping] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Gao, Xian] E China Normal Univ, Sch Psychol & Cognitve Sci, Key Lab Brain Funct Genom,Inst Cognit Neurosci, Minist Educ & Sci & Technol,Commiss Shanghai Muni, Shanghai 200062, Peoples R China.
C3 Massachusetts Institute of Technology (MIT); Universidade de Coimbra; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; East China Normal University
RP Feng, GP (corresponding author), MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA.; Feng, GP (corresponding author), Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
EM fengg@mit.edu
FU 'Programa Doutoral em Biologia Experimental e Biomedicina' (CNC, Coimbra, Portugal); National Science Foundation Graduate Fellowship; Integrative Neuronal Systems; Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard; Portuguese Foundation for Science and Technology [SFRH/BD/33894/2009]; Simons Center for the Social Brain at MIT; Nancy Lurie Marks Family Foundation; Shenzhen Overseas Innovation Team Project [KQTD20140630180249366]; China Scholarship Council; Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard; NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation; Poitras Center for Affective Disorders Research at MIT; National Institute of Health [NIMH R01MH097104]; Simons Foundation Autism Research Initiative (SFARI); Fundação para a Ciência e a Tecnologia [SFRH/BD/33894/2009] Funding Source: FCT
NR 29
TC 304
Z9 390
U1 2
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 481
EP +
DI 10.1038/nature16971
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800036
PM 26886798
DA 2026-03-09
ER

PT J
AU Lee, JY
   Kinch, LN
   Borek, DM
   Wang, J
   Wang, JM
   Urbatsch, IL
   Xie, XS
   Grishin, NV
   Cohen, JC
   Otwinowski, Z
   Hobbs, HH
   Rosenbaum, DM
AF Lee, Jyh-Yeuan
   Kinch, Lisa N.
   Borek, Dominika M.
   Wang, Jin
   Wang, Junmei
   Urbatsch, Ina L.
   Xie, Xiao-Song
   Grishin, Nikolai V.
   Cohen, Jonathan C.
   Otwinowski, Zbyszek
   Hobbs, Helen H.
   Rosenbaum, Daniel M.
TI Crystal structure of the human sterol transporter ABCG5/ABCG8
SO NATURE
LA English
DT Article
ID protein-sequence alignment; abc transporter; drosophila-melanogaster; diffraction intensity; density modification; dietary-cholesterol; maltose transporter; membrane-proteins; binding-protein; force-field
AB ATP binding cassette (ABC) transporters play critical roles in maintaining sterol balance in higher eukaryotes. The ABCG5/ABCG8 heterodimer (G5G8) mediates excretion of neutral sterols in liver and intestines(1-5). Mutations disrupting G5G8 cause sitosterolaemia, a disorder characterized by sterol accumulation and premature atherosclerosis. Here we use crystallization in lipid bilayers to determine the X-ray structure of human G5G8 in a nucleotide-free state at 3.9 angstrom resolution, generating the first atomic model of an ABC sterol transporter. The structure reveals a new transmembrane fold that is present in a large and functionally diverse superfamily of ABC transporters. The transmembrane domains are coupled to the nucleotide-binding sites by networks of interactions that differ between the active and inactive ATPases, reflecting the catalytic asymmetry of the transporter. The G5G8 structure provides a mechanistic framework for understanding sterol transport and the disruptive effects of mutations causing sitosterolaemia.
C1 [Lee, Jyh-Yeuan; Wang, Jin; Xie, Xiao-Song; Cohen, Jonathan C.; Hobbs, Helen H.] Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
   [Kinch, Lisa N.; Borek, Dominika M.; Grishin, Nikolai V.; Otwinowski, Zbyszek; Rosenbaum, Daniel M.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
   [Kinch, Lisa N.; Borek, Dominika M.; Grishin, Nikolai V.; Otwinowski, Zbyszek; Rosenbaum, Daniel M.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Kinch, Lisa N.; Grishin, Nikolai V.; Hobbs, Helen H.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Wang, Junmei] Univ Texas SW Med Ctr Dallas, Cecil & Ida Green Ctr Mol Computat & Syst Biol, Dallas, TX 75390 USA.
   [Urbatsch, Ina L.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Texas Tech University System; Texas Tech University Health Sciences Center Lubbock
RP Hobbs, HH (corresponding author), Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.; Rosenbaum, DM (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.; Rosenbaum, DM (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.; Hobbs, HH (corresponding author), Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
EM Helen.Hobbs@UTSouthwestern.edu; Dan.Rosenbaum@UTSouthwestern.edu
FU American Heart Association South Central Affiliate- [0825285F]; American Heart Association Texas Affiliate [0463130Y]; Welch Foundation [I-1770]; Packard Foundation; Howard Hughes Medical Institute; National Institutes of Health [HL72304, P01-HL20948, GM094575, GM053163, GM117080, GM113050]; National Heart Lung and Blood Institute [P01HL020948, R01HL072304] Funding Source: NIH RePORTER; American Heart Association (AHA) [0825285F] Funding Source: American Heart Association (AHA)
NR 73
TC 227
Z9 255
U1 0
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 561
EP +
DI 10.1038/nature17666
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100047
PM 27144356
DA 2026-03-09
ER

PT J
AU Tao, G
   Kahr, PC
   Morikawa, Y
   Zhang, M
   Rahmani, M
   Heallen, TR
   Li, LL
   Sun, Z
   Olson, EN
   Amendt, BA
   Martin, JF
AF Tao, Ge
   Kahr, Peter C.
   Morikawa, Yuka
   Zhang, Min
   Rahmani, Mahdis
   Heallen, Todd R.
   Li, Lele
   Sun, Zhao
   Olson, Eric N.
   Amendt, Brad A.
   Martin, James F.
TI Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury
SO NATURE
LA English
DT Article
ID cardiomyocyte proliferation; oxidative stress; rieger-syndrome; regeneration; genome; growth; enhancers; elements; family; gene
AB Myocardial infarction results in compromised myocardial function and heart failure owing to insufficient cardiomyocyte self-renewal(1). Unlike many vertebrates, mammalian hearts have only a transient neonatal renewal capacity(2). Reactivating primitive reparative ability in the mature mammalian heart requires knowledge of the mechanisms that promote early heart repair. By testing an established Hippo-deficient heart regeneration mouse model for factors that promote renewal, here we show that the expression of Pitx2 is induced in injured, Hippo-deficient ventricles. Pitx2-deficient neonatal mouse hearts failed to repair after apex resection, whereas adult mouse cardiomyocytes with Pitx2 gain-of-function efficiently regenerated after myocardial infarction. Genomic analyses indicated that Pitx2 activated genes encoding electron transport chain components and reactive oxygen species scavengers. A subset of Pitx2 target genes was cooperatively regulated with the Hippo pathway effector Yap. Furthermore, Nrf2, a regulator of the antioxidant response(3), directly regulated the expression and subcellular localization of Pitx2. Pitx2 mutant myocardium had increased levels of reactive oxygen species, while antioxidant supplementation suppressed the Pitx2 loss-of-function phenotype. These findings reveal a genetic pathway activated by tissue damage that is essential for cardiac repair.
C1 [Tao, Ge; Kahr, Peter C.; Zhang, Min; Li, Lele; Martin, James F.] Baylor Coll Med, Dept Mol Physiol & Biophys, One Baylor Plaza, Houston, TX 77030 USA.
   [Morikawa, Yuka; Rahmani, Mahdis; Heallen, Todd R.; Martin, James F.] Texas Heart Inst, Houston, TX 77030 USA.
   [Sun, Zhao; Amendt, Brad A.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
   [Sun, Zhao; Amendt, Brad A.] Univ Iowa, Craniofacial Anomalies Res Ctr, Iowa City, IA 52242 USA.
   [Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA.
   [Martin, James F.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
   [Martin, James F.] Baylor Coll Med, Cardiovasc Res Inst, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Texas Heart Institute; University of Iowa; University of Iowa; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Baylor College of Medicine; Baylor College of Medicine
RP Martin, JF (corresponding author), Baylor Coll Med, Dept Mol Physiol & Biophys, One Baylor Plaza, Houston, TX 77030 USA.; Martin, JF (corresponding author), Texas Heart Inst, Houston, TX 77030 USA.; Martin, JF (corresponding author), Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.; Martin, JF (corresponding author), Baylor Coll Med, Cardiovasc Res Inst, Houston, TX 77030 USA.
EM jfmartin@bcm.edu
FU IDDRC from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [1U54 HD083092]; Mouse Phenotyping Core at Baylor College of Medicine; National Institutes of Health (NIH) [U54 HG006348]; NIH [DE 023177, HL 118761, DE 13941, HL-077439, HL-111665, HL-093039, DK-099653, U01-HL-100401]; Vivian L. Smith Foundation; Transatlantic Network of Excellence Award LeDucq Foundation Transatlantic Networks of Excellence in Cardiovascular Research [14CVD01]; Fondation Leducq Networks of Excellence; Cancer Prevention and Research Institute of Texas; Robert A. Welch Foundation [1-0025]; American Heart Association (AHA) [13POST17040027]; German Research Foundation (DFG) [KA4018/1-1]; American Heart Association (AHA) [13POST17040027] Funding Source: American Heart Association (AHA); National Heart Lung and Blood Institute [R01HL127717, R01HL118761] Funding Source: NIH RePORTER
NR 32
TC 244
Z9 283
U1 1
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 119
EP +
DI 10.1038/nature17959
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300046
PM 27251288
DA 2026-03-09
ER

PT J
AU Marceau, CD
   Puschnik, AS
   Majzoub, K
   Ooi, YS
   Brewer, SM
   Fuchs, G
   Swaminathan, K
   Mata, MA
   Elias, JE
   Sarnow, P
   Carette, JE
AF Marceau, Caleb D.
   Puschnik, Andreas S.
   Majzoub, Karim
   Ooi, Yaw Shin
   Brewer, Susan M.
   Fuchs, Gabriele
   Swaminathan, Kavya
   Mata, Miguel A.
   Elias, Joshua E.
   Sarnow, Peter
   Carette, Jan E.
TI Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens
SO NATURE
LA English
DT Article
ID hepatitis-c virus; human-cells; n-glycosylation; dengue virus; replication; infection; protein; hur; oligosaccharyltransferase; membrane
AB The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide(1). No approved antivirals are available to date, and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates(2). Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available(3). Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies(4). A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy(5,6) to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER)-associated multi-protein complexes involved in signal sequence recognition, N-linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for infection by other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects(7). By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host-dependency factors between DENV and HCV, and illuminates new host targets for antiviral therapy.
C1 [Marceau, Caleb D.; Puschnik, Andreas S.; Majzoub, Karim; Ooi, Yaw Shin; Brewer, Susan M.; Fuchs, Gabriele; Mata, Miguel A.; Sarnow, Peter; Carette, Jan E.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Swaminathan, Kavya; Elias, Joshua E.] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Carette, JE (corresponding author), Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
EM carette@stanford.edu
FU National Institutes of Health (NIH) [DP2 AI104557]; NIH [AI109662]; David and Lucile Packard Foundation; Stanford Graduate Fellowship; Boehringer Ingelheim Fonds; NSF-GFRP; National Institute of Allergy and Infectious Diseases [T32AI007328] Funding Source: NIH RePORTER
NR 42
TC 349
Z9 419
U1 2
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 159
EP +
DI 10.1038/nature18631
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600044
PM 27383987
DA 2026-03-09
ER

PT J
AU Kuhlwilm, M
   Gronau, I
   Hubisz, MJ
   de Filippo, C
   Prado-Martinez, J
   Kircher, M
   Fu, QM
   Burbano, HA
   Lalueza-Fox, C
   de la Rasilla, M
   Rosas, A
   Rudan, P
   Brajkovic, D
   Kucan, Z
   Gusic, I
   Marques-Bonet, T
   Andrés, AM
   Viola, B
   Pääbo, S
   Meyer, M
   Siepel, A
   Castellano, S
AF Kuhlwilm, Martin
   Gronau, Ilan
   Hubisz, Melissa J.
   de Filippo, Cesare
   Prado-Martinez, Javier
   Kircher, Martin
   Fu, Qiaomei
   Burbano, Hernan A.
   Lalueza-Fox, Carles
   de la Rasilla, Marco
   Rosas, Antonio
   Rudan, Pavao
   Brajkovic, Dejana
   Kucan, Zeljko
   Gusic, Ivan
   Marques-Bonet, Tomas
   Andres, Aida M.
   Viola, Bence
   Paeaebo, Svante
   Meyer, Matthias
   Siepel, Adam
   Castellano, Sergi
TI Ancient gene flow from early modern humans into Eastern Neanderthals
SO NATURE
LA English
DT Article
ID genome sequence; transcription factor; selection; southern; inference; ancestry; patterns; history; cave
AB It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.
C1 [Kuhlwilm, Martin; de Filippo, Cesare; Kircher, Martin; Fu, Qiaomei; Burbano, Hernan A.; Andres, Aida M.; Paeaebo, Svante; Meyer, Matthias; Castellano, Sergi] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Gronau, Ilan] Herzliya Interdisciplinary Ctr IDC, Efi Arazi Sch Comp Sci, IL-46150 Herzliyya, Israel.
   [Hubisz, Melissa J.; Siepel, Adam] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14850 USA.
   [Prado-Martinez, Javier; Lalueza-Fox, Carles; Marques-Bonet, Tomas] Inst Evolutionary Biol UPF CSIC, Barcelona 08003, Spain.
   [Kircher, Martin] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Fu, Qiaomei] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Fu, Qiaomei] Chinese Acad Sci, Key Lab Vertebrate Evolut & Human Origins Chinese, IVPP, Beijing 100044, Peoples R China.
   [Burbano, Hernan A.] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany.
   [de la Rasilla, Marco] Univ Oviedo, Dept Hist, Area Prehist, Oviedo 33011, Spain.
   [Rosas, Antonio] CSIC, Museo Nacl Ciencias Nat, Dept Paleobiol, Plaza Murillo 2, E-28006 Madrid, Spain.
   [Rudan, Pavao; Kucan, Zeljko; Gusic, Ivan] Croatian Acad Sci & Arts, Anthropol Ctr, Zagreb 10000, Croatia.
   [Brajkovic, Dejana] Croatian Acad Sci & Arts, Inst Quaternary Paleontol & Geol, Zagreb 10000, Croatia.
   [Marques-Bonet, Tomas] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain.
   [Marques-Bonet, Tomas] Ctr Nacl Anal Genom CRG CNAG, Barcelona 08028, Spain.
   [Viola, Bence] Univ Toronto, Dept Anthropol, Toronto, ON M5S 2S2, Canada.
   [Viola, Bence] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Siepel, Adam] Cold Spring Harbor Lab, Simons Ctr Quantitat Biol, Cold Spring Harbor, NY 11724 USA.
C3 Max Planck Society; Reichman University; Cornell University; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); University of Washington; University of Washington Seattle; Harvard University; Harvard Medical School; Chinese Academy of Sciences; Max Planck Society; University of Oviedo; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Museo Nacional de Ciencias Naturales (MNCN); Croatian Academy of Sciences & Arts; Croatian Academy of Sciences & Arts; ICREA; University of Toronto; Max Planck Society; Cold Spring Harbor Laboratory
RP Castellano, S (corresponding author), Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.; Siepel, A (corresponding author), Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14850 USA.; Siepel, A (corresponding author), Cold Spring Harbor Lab, Simons Ctr Quantitat Biol, Cold Spring Harbor, NY 11724 USA.
EM asiepel@cshl.edu; sergi.castellano@eva.mpg.de
FU National Science Foundation [DGE-1144153]; Special Foundation of the President of the Chinese Academy of Sciences; ICREA; EMBO YIP; Fundacio Barcelona Zoo; Max Planck Society; Krekeler Foundation; MINECO [BFU2014-55090-P FEDER, BFU2015-7116-ERC, BFU2015-6215-ERC, BFU2012-34157 FEDER]; US National Institutes of Health [GM102192, U01 MH106874]; ICREA Funding Source: Custom
NR 44
TC 314
Z9 374
U1 0
U2 303
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2016
VL 530
IS 7591
BP 429
EP +
DI 10.1038/nature16544
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE5RW
UT WOS:000370690800025
PM 26886800
DA 2026-03-09
ER

PT J
AU Jackman, SL
   Turecek, J
   Belinsky, JE
   Regehr, WG
AF Jackman, Skyler L.
   Turecek, Josef
   Belinsky, Justine E.
   Regehr, Wade G.
TI The calcium sensor synaptotagmin 7 is required for synaptic facilitation
SO NATURE
LA English
DT Article
ID paired-pulse facilitation; transmitter release; ca2+ sensor; buffer saturation; granule cell; transmission; synapses; channels; vii; potentiation
AB It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner(1). At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release(2). Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses(3), but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release(2,4), and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed(5,6). Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation.
C1 [Jackman, Skyler L.; Turecek, Josef; Belinsky, Justine E.; Regehr, Wade G.] Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Regehr, WG (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM wade_regehr@hms.harvard.edu
FU National Institutes of Health (NIH) [NS032405]; Nancy Lurie Marks Foundation; Vision Core; NINDS P30 Core Center grant [NS072030]; Nancy Lurie Marks Fellowship
NR 46
TC 238
Z9 272
U1 1
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 88
EP +
DI 10.1038/nature16507
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900032
PM 26738595
DA 2026-03-09
ER

PT J
AU Zheng, Y
   Miller, GW
   Tobias, WA
   Cates, GD
AF Zheng, Yuan
   Miller, G. Wilson
   Tobias, William A.
   Cates, Gordon D.
TI A method for imaging and spectroscopy using γ-rays and magnetic resonance
SO NATURE
LA English
DT Article
ID laser-polarized xe-129; nuclear-medicine; spin-exchange; nmr; xenon; field; mri; radionuclide; relaxation; anisotropy
AB Magnetic resonance imaging (MRI) provides fine spatial resolution, spectral sensitivity and a rich variety of contrast mechanisms for diagnostic medical applications(1,2). Nuclear imaging using gamma-ray cameras offers the benefits of using small quantities of radioactive tracers that seek specific targets of interest within the body(3). Here we describe an imaging and spectroscopic modality that combines favourable aspects of both approaches. Spatial information is encoded into the spin orientations of tiny amounts of a polarized radioactive tracer using pulses of both radio-frequency electromagnetic radiation and magnetic-field gradients, as in MRI. However, rather than detecting weak radio-frequency signals, imaging information is obtained through the detection of gamma-rays. A single gamma-ray detector can be used to acquire an image; no gamma-ray camera is needed. We demonstrate the feasibility of our technique by producing images and spectra from a glass cell containing only about 4 x 10(13) atoms (about 1 millicurie) of the metastable isomer Xe-131m that were polarized using the laser technique of spin-exchange optical pumping(4). If the cell had instead been filled with water and imaged using conventional MRI, then it would have contained more than 10(24) water molecules. The high sensitivity of our modality expands the breadth of applications of magnetic resonance, and could lead to a new class of radioactive tracers.
C1 [Zheng, Yuan; Tobias, William A.; Cates, Gordon D.] Univ Virginia, Dept Phys, Charlottesville, VA 22904 USA.
   [Miller, G. Wilson; Cates, Gordon D.] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA 22908 USA.
   [Zheng, Yuan] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
C3 University of Virginia; University of Virginia; Stanford University
RP Cates, GD (corresponding author), Univ Virginia, Dept Phys, Charlottesville, VA 22904 USA.; Cates, GD (corresponding author), Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA 22908 USA.
EM cates@virginia.edu
FU Ivy Biomedical Innovation Fund at the University of Virginia; Ivy Foundation; US Department of Energy. Office of Science, Office of Nuclear Physics [DE-FG02-01ER41163]
NR 39
TC 21
Z9 28
U1 4
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 652
EP +
DI 10.1038/nature19775
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700044
PM 27680938
DA 2026-03-09
ER

PT J
AU Proffitt, T
   Luncz, LV
   Falótico, T
   Ottoni, EB
   de la Torre, I
   Haslam, M
AF Proffitt, Tomos
   Luncz, Lydia V.
   Falotico, Tiago
   Ottoni, Eduardo B.
   de la Torre, Ignacio
   Haslam, Michael
TI Wild monkeys flake stone tools
SO NATURE
LA English
DT Article
ID capuchin monkeys; west turkana; ethiopia; oldowan; artifacts; skills; brazil; kenya; gona
AB Our understanding of the emergence of technology shapes how we view the origins of humanity(1,2). Sharp-edged stone flakes, struck from larger cores, are the primary evidence for the earliest stone technology(3). Here we show that wild bearded capuchin monkeys (Sapajus libidinosus) in Brazil deliberately break stones, unintentionally producing recurrent, conchoidally fractured, sharp-edged flakes and cores that have the characteristics and morphology of intentionally produced hominin tools. The production of archaeologically visible cores and flakes is therefore no longer unique to the human lineage, providing a comparative perspective on the emergence of lithic technology. This discovery adds an additional dimension to interpretations of the human Palaeolithic record, the possible function of early stone tools, and the cognitive requirements for the emergence of stone flaking.
C1 [Proffitt, Tomos; Luncz, Lydia V.; Haslam, Michael] Univ Oxford, Sch Archaeol, Primate Archaeol Res Grp, Dyson Perrins Bldg,South Parks Rd, Oxford OX1 3QY, England.
   [Falotico, Tiago; Ottoni, Eduardo B.] Univ Sao Paulo, Inst Psychol, BR-05508030 Sao Paulo, SP, Brazil.
   [de la Torre, Ignacio] UCL, Inst Archaeol, 31-34 Gordon Sq, London WC1H 0PY, England.
C3 University of Oxford; Universidade de Sao Paulo; University of London; University College London
RP Proffitt, T; Haslam, M (corresponding author), Univ Oxford, Sch Archaeol, Primate Archaeol Res Grp, Dyson Perrins Bldg,South Parks Rd, Oxford OX1 3QY, England.
EM tomos.proffitt@arch.ox.ac.uk; michael.haslam@arch.ox.ac.uk
FU European Research Council Starting Investigator Grant [283959]; Sao Paulo Research Foundation (FAPESP) [2013/05219-0, 2014/04818-0]; University College London (ERC) [283366]; Vinnova [2013-05219] Funding Source: Vinnova; Swedish Research Council [2013-05219] Funding Source: Swedish Research Council; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/05219-0] Funding Source: FAPESP
NR 34
TC 127
Z9 144
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 85
EP +
DI 10.1038/nature20112
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100034
PM 27760117
DA 2026-03-09
ER

PT J
AU Cao, LYL
   Riascos-Bernal, DF
   Chinnasamy, P
   Dunaway, CM
   Hou, R
   Pujato, MA
   O'Rourke, BP
   Miskolci, V
   Gou, L
   Hodgson, L
   Fiser, A
   Sibinga, NES
AF Cao, Longyue L.
   Riascos-Bernal, Dario F.
   Chinnasamy, Prameladevi
   Dunaway, Charlene M.
   Hou, Rong
   Pujato, Mario A.
   O'Rourke, Brian P.
   Miskolci, Veronika
   Gou, Liang
   Hodgson, Louis
   Fiser, Andras
   Sibinga, Nicholas E. S.
TI Control of mitochondrial function and cell growth by the atypical cadherin Fat1
SO NATURE
LA English
DT Article
ID stomatin-like protein-2; complex i; human interactome; living cells; cancer-cells; gene; identification; biogenesis; expression; matrix
AB Mitochondrial products such as ATP, reactive oxygen species, and aspartate are key regulators of cellular metabolism and growth. Abnormal mitochondrial function compromises integrated growth-related processes such as development and tissue repair(1,2), as well as homeostatic mechanisms that counteract ageing and neurodegeneration(3), cardiovascular disease(4,5), and cancer(6,7). Physiologic mechanisms that control mitochondrial activity in such settings remain incompletely understood. Here we show that the atypical Fat1 cadherin acts as a molecular 'brake' on mitochondrial respiration that regulates vascular smooth muscle cell (SMC) proliferation after arterial injury. Fragments of Fat1 accumulate in SMC mitochondria, and the Fat1 intracellular domain interacts with multiple mitochondrial proteins, including critical factors associated with the inner mitochondrial membrane. SMCs lacking Fat1 (Fat1(KO)) grow faster, consume more oxygen for ATP production, and contain more aspartate. Notably, expression in Fat1(KO) cells of a modified Fat1 intracellular domain that localizes exclusively to mitochondria largely normalizes oxygen consumption, and the growth advantage of these cells can be suppressed by inhibition of mitochondrial respiration, which suggest that a Fat1-mediated growth control mechanism is intrinsic to mitochondria. Consistent with this idea, Fat1 species associate with multiple respiratory complexes, and Fat1 deletion both increases the activity of complexes I and II and promotes the formation of complex-I-containing supercomplexes. In vivo, Fat1 is expressed in injured human and mouse arteries, and inactivation of SMC Fat1 in mice potentiates the response to vascular damage, with markedly increased medial hyperplasia and neointimal growth, and evidence of higher SMC mitochondrial respiration. These studies suggest that Fat1 controls mitochondrial activity to restrain cell growth during the reparative, proliferative state induced by vascular injury. Given recent reports linking Fat1 to cancer, abnormal kidney and muscle development, and neuropsychiatric disease(8-13), this Fat1 function may have importance in other settings of altered cell growth and metabolism.
C1 [Cao, Longyue L.; Riascos-Bernal, Dario F.; Chinnasamy, Prameladevi; Dunaway, Charlene M.; Hou, Rong; Sibinga, Nicholas E. S.] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Dept Med Cardiol, Bronx, NY 10461 USA.
   [Cao, Longyue L.; Riascos-Bernal, Dario F.; Chinnasamy, Prameladevi; Dunaway, Charlene M.; Hou, Rong; Sibinga, Nicholas E. S.] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
   [Pujato, Mario A.; Fiser, Andras] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
   [O'Rourke, Brian P.] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA.
   [Miskolci, Veronika; Hodgson, Louis] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
   [Gou, Liang] CVPath Inst, Gaithersburg, MD 20878 USA.
   [Hodgson, Louis] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10461 USA.
   [Pujato, Mario A.] St Louis Univ Hosp, Dept Internal Med, Div Infect Dis Allergy & Immunol, St Louis, MO 63104 USA.
   [Pujato, Mario A.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
C3 Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; CVPath Institute; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Saint Louis University; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center
RP Sibinga, NES (corresponding author), Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Dept Med Cardiol, Bronx, NY 10461 USA.; Sibinga, NES (corresponding author), Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
EM nicholas.sibinga@einstein.yu.edu
FU Diabetes Training and Research Center of Albert Einstein College of Medicine (NIH) [P60DK20541]; Medical Scientist Training Program (NIH) [T32-GM007288]; Cellular, Molecular Biology, and, Genetics Training Grant (NIH) [T32-GM007491]; American Medical Association Seed Grant; American Heart Association [11PRE5450002, 13GRNT16950064]; NIH [CA205262, HL088104, HL104518]; National Cancer Institute [P30CA013330] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK026687] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007491, T32GM007288] Funding Source: NIH RePORTER; American Heart Association (AHA) [11PRE5450002, 13GRNT16950064] Funding Source: American Heart Association (AHA)
NR 66
TC 59
Z9 65
U1 2
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 575
EP +
DI 10.1038/nature20170
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600046
PM 27828948
DA 2026-03-09
ER

PT J
AU Aitken, ARA
   Roberts, JL
   van Ommen, TD
   Young, DA
   Golledge, NR
   Greenbaum, JS
   Blankenship, DD
   Siegert, MJ
AF Aitken, A. R. A.
   Roberts, J. L.
   van Ommen, T. D.
   Young, D. A.
   Golledge, N. R.
   Greenbaum, J. S.
   Blankenship, D. D.
   Siegert, M. J.
TI Repeated large-scale retreat and advance of Totten Glacier indicated by inland bed erosion
SO NATURE
LA English
DT Article
ID antarctic ice-sheet; east antarctica; sea-level; temperature variability; pliocene; stability; greenland; surface; model; ocean
AB Climate variations cause ice sheets to retreat and advance, raising or lowering sea level by metres to decametres. The basic relationship is unambiguous, but the timing, magnitude and sources of sea-level change remain unclear; in particular, the contribution of the East Antarctic Ice Sheet (EAIS) is ill defined, restricting our appreciation of potential future change. Several lines of evidence suggest possible collapse of the Totten Glacier into interior basins during past warm periods, most notably the Pliocene epoch(1-4), causing several metres of sea-level rise. However, the structure and long-term evolution of the ice sheet in this region have been understood insufficiently to constrain past ice-sheet extents. Here we show that deep ice-sheet erosion-enough to expose basement rocks-has occurred in two regions: the head of the Totten Glacier, within 150 kilometres of today's grounding line; and deep within the Sabrina Subglacial Basin, 350-550 kilometres from this grounding line. Our results, based on ICECAP aerogeophysical data, demarcate the marginal zones of two distinct quasi-stable EAIS configurations, corresponding to the 'modern-scale' ice sheet (with a marginal zone near the present ice-sheet margin) and the retreated ice sheet (with the marginal zone located far inland). The transitional region of 200-250 kilometres in width is less eroded, suggesting shorter-lived exposure to eroding conditions during repeated retreat-advance events, which are probably driven by ocean-forced instabilities. Representative ice-sheet models indicate that the global sea-level increase resulting from retreat in this sector can be up to 0.9 metres in the modern-scale configuration, and exceeds 2 metres in the retreated configuration.
C1 [Aitken, A. R. A.] Univ Western Australia, Sch Earth & Environm, Perth, WA 6008, Australia.
   [Roberts, J. L.; van Ommen, T. D.] Australian Antarctic Div, Channel Highway, Kingston, Tas 7050, Australia.
   [Roberts, J. L.; van Ommen, T. D.] Univ Tasmania, Antarctic Climate & Ecosyst Cooperat Res Ctr, Hobart, Tas 7005, Australia.
   [Young, D. A.; Greenbaum, J. S.; Blankenship, D. D.] Univ Texas Austin, Inst Geophys, Austin, TX 78758 USA.
   [Golledge, N. R.] Victoria Univ Wellington, Antarctic Res Ctr, Wellington 6140, New Zealand.
   [Golledge, N. R.] GNS Sci, Lower Hutt 5011, New Zealand.
   [Siegert, M. J.] Univ London Imperial Coll Sci Technol & Med, Grantham Inst, London SW7 2AZ, England.
   [Siegert, M. J.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
C3 University of Western Australia; Australian Antarctic Division; University of Tasmania; Antarctic Climate & Ecosystems Cooperative Research Centre (ACE CRC); University of Texas System; University of Texas Austin; Victoria University Wellington; Earth Sciences New Zealand; GNS Science - New Zealand; Imperial College London; Imperial College London
RP Aitken, ARA (corresponding author), Univ Western Australia, Sch Earth & Environm, Perth, WA 6008, Australia.
EM alan.aitken@uwa.edu.au
FU National Science Foundation [PLR-0733025]; National Aeronautics and Space Administration [NNX09AR52G, NNG10HPO6C, NNX11AD33G]; Australian Antarctic Division [3013, 4077]; National Environment and Research Council [NE/D003733/1]; Jackson School of Geosciences; G. Unger Vetlesen Foundation; Australian Government's Cooperative Research Centres Programme through the Antarctic Climate & Ecosystems Cooperative Research Centre (ACE CRC); Royal Society of New Zealand's Marsden Fund [VUW1203]; Natural Environment Research Council [NE/F016646/1, NE/F016646/2] Funding Source: researchfish; NERC [NE/F016646/1, NE/F016646/2] Funding Source: UKRI
NR 45
TC 90
Z9 99
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 385
EP +
DI 10.1038/nature17447
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300046
PM 27193684
DA 2026-03-09
ER

PT J
AU East-Seletsky, A
   O'Connell, MR
   Knight, SC
   Burstein, D
   Cate, JHD
   Tjian, R
   Doudna, JA
AF East-Seletsky, Alexandra
   O'Connell, Mitchell R.
   Knight, Spencer C.
   Burstein, David
   Cate, Jamie H. D.
   Tjian, Robert
   Doudna, Jennifer A.
TI Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection
SO NATURE
LA English
DT Article
ID cas systems; dual-rna; dna; endoribonuclease; protein; cleavage; immunity; defense; complex; endonuclease
AB Bacterial adaptive immune systems use CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage(1,2). Although most prokaryotic adaptive immune systems generally target DNA substrates(3-5), type III and VI CRISPR systems direct interference complexes against single-stranded RNA substrates(6-9). In type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease (RNase)(9,10). How this enzyme acquires mature CRISPR RNAs (crRNAs) that are essential for immune surveillance and how it carries out crRNA-mediated RNA cleavage remain unclear. Here we show that bacterial C2c2 possesses a unique RNase activity responsible for CRISPR RNA maturation that is distinct from its RNA-activated single-stranded RNA degradation activity. These dual RNase functions are chemically and mechanistically different from each other and from the crRNA-processing behaviour of the evolutionarily unrelated CRISPR enzyme Cpf1 (ref. 11). The two RNase activities of C2c2 enable multiplexed processing and loading of guide RNAs that in turn allow sensitive detection of cellular transcripts.
C1 [East-Seletsky, Alexandra; O'Connell, Mitchell R.; Cate, Jamie H. D.; Tjian, Robert; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Knight, Spencer C.; Cate, Jamie H. D.; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Burstein, David] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Cate, Jamie H. D.; Doudna, Jennifer A.] Lawrence Berkeley Natl Lab, MBIB Div, Berkeley, CA 94720 USA.
   [Tjian, Robert] Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
   [Tjian, Robert; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Tjian, Robert] Univ Calif Berkeley, Li Ka Shing Biomed & Hlth Sci Ctr, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Howard Hughes Medical Institute; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Stanford University; Li Ka Shing Center; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Doudna, JA (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.; Doudna, JA (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Doudna, JA (corresponding author), Lawrence Berkeley Natl Lab, MBIB Div, Berkeley, CA 94720 USA.; Doudna, JA (corresponding author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.; Doudna, JA (corresponding author), Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA.
EM doudna@berkeley.edu
FU National Science Foundation Graduate Research Fellowship Program; C. J. Martin Overseas Early Career Fellowship from the National Health and Medical Research Council of Australia; Frontiers Science award from the Paul Allen Institute; National Science Foundation [MCB-1244557]; California Institute for Regenerative Medicine (CIRM) [RB4-06016]; National Institutes of Health [P50-GM102706]
NR 34
TC 947
Z9 1258
U1 15
U2 632
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 270
EP +
DI 10.1038/nature19802
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000050
PM 27669025
DA 2026-03-09
ER

PT J
AU Rogelj, J
   den Elzen, M
   Höhne, N
   Fransen, T
   Fekete, H
   Winkler, H
   Chaeffer, RS
   Ha, F
   Riahi, K
   Meinshausen, M
AF Rogelj, Joeri
   den Elzen, Michel
   Hoehne, Niklas
   Fransen, Taryn
   Fekete, Hanna
   Winkler, Harald
   Chaeffer, Roberto S.
   Ha, Fus
   Riahi, Keywan
   Meinshausen, Malte
TI Paris Agreement climate proposals need a boost to keep warming well below 2 °C
SO NATURE
LA English
DT Article
ID greenhouse-gas emissions; co2 emissions; targets; technology; scenarios
AB The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to "pursue efforts" to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess the effect of current INDCs on reducing aggregate greenhouse gas emissions, its implications for achieving the temperature objective of the Paris climate agreement, and potential options for overachievement. The INDCs collectively lower greenhouse gas emissions compared to where current policies stand, but still imply a median warming of 2.6-3.1 degrees Celsius by 2100. More can be achieved, because the agreement stipulates that targets for reducing greenhouse gas emissions are strengthened over time, both in ambition and scope. Substantial enhancement or over-delivery on current INDCs by additional national, sub-national and non-state actions is required to maintain a reasonable chance of meeting the target of keeping warming well below 2 degrees Celsius.
C1 [Rogelj, Joeri; Riahi, Keywan] Int Inst Appl Syst Anal, ENE Program, A-2361 Laxenburg, Austria.
   [Rogelj, Joeri] Swiss Fed Inst Technol, Inst Atmospher & Climate Sci, Zurich, Switzerland.
   [den Elzen, Michel] PBL Netherlands Environm Assessment Agcy, Bilthoven, Netherlands.
   [Hoehne, Niklas; Fekete, Hanna] NewClimate Inst, Cologne, Germany.
   [Hoehne, Niklas] Wageningen Univ, Environm Syst Anal Grp, NL-6700 AP Wageningen, Netherlands.
   [Fransen, Taryn] World Resources Inst, Washington, DC 20006 USA.
   [Winkler, Harald] Univ Cape Town, Energy Res Ctr, ZA-7925 Cape Town, South Africa.
   [Chaeffer, Roberto S.] Univ Fed Rio de Janeiro COPPE UFRJ, Rio De Janeiro, Brazil.
   [Ha, Fus] Natl Ctr Climate Change Strategy & Int Cooperat, Beijing, Peoples R China.
   [Riahi, Keywan] Graz Univ Technol, A-8010 Graz, Austria.
   [Meinshausen, Malte] Univ Melbourne, Australian German Climate & Energy Coll, Sch Earth Sci, Melbourne, Vic, Australia.
   [Meinshausen, Malte] Potsdam Inst Climate Impact Res PIK, PRIMAP Grp, Potsdam, Germany.
C3 International Institute for Applied Systems Analysis (IIASA); Swiss Federal Institutes of Technology Domain; ETH Zurich; Wageningen University & Research; University of Cape Town; Graz University of Technology; University of Melbourne; Potsdam Institut fur Klimafolgenforschung
RP den Elzen, M (corresponding author), PBL Netherlands Environm Assessment Agcy, Bilthoven, Netherlands.; Höhne, N (corresponding author), NewClimate Inst, Cologne, Germany.; Höhne, N (corresponding author), Wageningen Univ, Environm Syst Anal Grp, NL-6700 AP Wageningen, Netherlands.
EM Michel.denElzen@pbl.nl; n.hoehne@newclimate.org
FU European Union [642147]; Australian Research Council (ARC) [FT130100809]; Australian Research Council [FT130100809] Funding Source: Australian Research Council
NR 77
TC 2564
Z9 3006
U1 59
U2 1763
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2016
VL 534
IS 7609
BP 631
EP 639
DI 10.1038/nature18307
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7JV
UT WOS:000378676000026
PM 27357792
DA 2026-03-09
ER

PT J
AU Haumann, FA
   Gruber, N
   Münnich, M
   Frenger, I
   Kern, S
AF Haumann, F. Alexander
   Gruber, Nicolas
   Munnich, Matthias
   Frenger, Ivy
   Kern, Stefan
TI Sea-ice transport driving Southern Ocean salinity and its recent trends
SO NATURE
LA English
DT Article
ID data assimilation; climate-change; circulation; pacific; carbon
AB Recent salinity changes in the Southern Ocean(1-7) are among the most prominent signals of climate change in the global ocean, yet their underlying causes have not been firmly established(1,3,4,6). Here we propose that trends in the northward transport of Antarctic sea ice are a major contributor to these changes. Using satellite observations supplemented by sea-ice reconstructions, we estimate that wind-driven(8,9) northward freshwater transport by sea ice increased by 20 +/- 10 per cent between 1982 and 2008. The strongest and most robust increase occurred in the Pacific sector, coinciding with the largest observed salinity changes(4,5). We estimate that the additional freshwater for the entire northern sea-ice edge entails a freshening rate of -0.02 +/- 0.01 grams per kilogram per decade in the surface and intermediate waters of the open ocean, similar to the observed freshening(1-5). The enhanced rejection of salt near the coast of Antarctica associated with stronger sea-ice export counteracts the freshening of both continental shelf(2,10,11) and newly formed bottom waters(6) due to increases in glacial meltwater(12). Although the data sources underlying our results have substantial uncertainties, regional analyses(13) and independent data from an atmospheric reanalysis support our conclusions. Our finding that northward sea-ice freshwater transport is also a key determinant of the mean salinity distribution in the Southern Ocean further underpins the importance of the sea-ice-induced freshwater flux. Through its influence on the density structure of the ocean, this process has critical consequences for the global climate by affecting the exchange of heat, carbon and nutrients between the deep ocean and surface waters(14-17).
C1 [Haumann, F. Alexander; Gruber, Nicolas; Munnich, Matthias; Frenger, Ivy] Swiss Fed Inst Technol, Inst Biogeochem & Pollutant Dynam, Environm Phys, Univ Str 16, CH-8092 Zurich, Switzerland.
   [Haumann, F. Alexander; Gruber, Nicolas] Swiss Fed Inst Technol, Ctr Climate Syst Modeling, Univ Str 16, CH-8092 Zurich, Switzerland.
   [Frenger, Ivy] GEOMAR Helmholtz Ctr Ocean Res Kiel, Biogeochem Modelling, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
   [Kern, Stefan] Univ Hamburg, ICDC, Ctr Earth Syst Res & Sustainabil, Hamburg, Germany.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Hamburg
RP Haumann, FA (corresponding author), Swiss Fed Inst Technol, Inst Biogeochem & Pollutant Dynam, Environm Phys, Univ Str 16, CH-8092 Zurich, Switzerland.; Haumann, FA (corresponding author), Swiss Fed Inst Technol, Ctr Climate Syst Modeling, Univ Str 16, CH-8092 Zurich, Switzerland.
EM alexander.haumann@usys.ethz.ch
FU ETH [CH2-01 11-1]; European Union (EU) [264879]; C2SM at ETH Zurich; Swiss National Science Foundation [P2EZP2-152133]; Center of Excellence for Climate System Analysis and Prediction (CliSAP), University of Hamburg, Germany; International Space Science Institute (ISSI), Bern, Switzerland [245]; Swiss National Science Foundation (SNF) [P2EZP2_152133] Funding Source: Swiss National Science Foundation (SNF)
NR 30
TC 238
Z9 261
U1 0
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 89
EP 92
DI 10.1038/nature19101
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900044
PM 27582222
DA 2026-03-09
ER

PT J
AU Jia, Y
   Yun, CH
   Park, E
   Rcan, DE
   Manuia, M
   Juarez, J
   Xu, CX
   Rhee, K
   Chen, T
   Zhang, HK
   Palakurthi, S
   Jang, JB
   Lelais, G
   DiDonato, M
   Bursulaya, B
   Michellys, PY
   Epple, R
   Marsilje, TH
   McNeill, M
   Lu, WS
   Harris, J
   Bender, S
   Wong, KK
   Jänne, PA
   Eck, MJ
AF Jia, Yong
   Yun, Cai-Hong
   Park, Eunyoung
   Rcan, Dalia E.
   Manuia, Mari
   Juarez, Jose
   Xu, Chunxiao
   Rhee, Kevin
   Chen, Ting
   Zhang, Haikuo
   Palakurthi, Sangeetha
   Jang, Jaebong
   Lelais, Gerald
   DiDonato, Michael
   Bursulaya, Badry
   Michellys, Pierre-Yves
   Epple, Robert
   Marsilje, Thomas H.
   McNeill, Matthew
   Lu, Wenshuo
   Harris, Jennifer
   Bender, Steven
   Wong, Kwok-Kin
   Janne, Pasi A.
   Eck, Michael J.
TI Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors
SO NATURE
LA English
DT Article
ID growth-factor receptor; cell lung-cancer; egfr kinase; targeted therapy; mutations; gefitinib; azd9291; activation; mechanism
AB The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase(1,2), but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor(3,4). Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant(5,6), but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond(7). All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state(8). We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization(9,10), rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors.
C1 [Jia, Yong; Manuia, Mari; Juarez, Jose; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H.; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
   [Yun, Cai-Hong; Park, Eunyoung; Jang, Jaebong; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Yun, Cai-Hong; Park, Eunyoung; Jang, Jaebong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Rcan, Dalia E.; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
   [Palakurthi, Sangeetha; Wong, Kwok-Kin; Janne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02215 USA.
   [Yun, Cai-Hong] Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China.
   [Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China.
C3 Novartis; Novartis USA; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Peking University; Peking University
RP Eck, MJ (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Eck, MJ (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM eck@crystal.harvard.edu
FU NIH [CA116020, CA154303, CA120964, CA135257]; Gross-Loh Family Fund for Lung Cancer Research; National Cancer Institute [R01CA201049, P01CA120964, R01CA116020, P01CA154303, R01CA166480] Funding Source: NIH RePORTER
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NR 32
TC 743
Z9 888
U1 5
U2 392
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 129
EP +
DI 10.1038/nature17960
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300048
PM 27251290
DA 2026-03-09
ER

PT J
AU Hayashi, R
   Ishikawa, Y
   Sasamoto, Y
   Katori, R
   Nomura, N
   Ichikawa, T
   Araki, S
   Soma, T
   Kawasaki, S
   Sekiguchi, K
   Quantock, AJ
   Tsujikawa, M
   Nishida, K
AF Hayashi, Ryuhei
   Ishikawa, Yuki
   Sasamoto, Yuzuru
   Katori, Ryosuke
   Nomura, Naoki
   Ichikawa, Tatsuya
   Araki, Saori
   Soma, Takeshi
   Kawasaki, Satoshi
   Sekiguchi, Kiyotoshi
   Quantock, Andrew J.
   Tsujikawa, Motokazu
   Nishida, Kohji
TI Co-ordinated ocular development from human iPS cells and recovery of corneal function
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; neural retina; stem/progenitor cells; human fibroblasts; epithelial-cells; differentiation; generation; keratinocyte; expression; culture
AB The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells(1-5). Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells(6-9). These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.
C1 [Hayashi, Ryuhei] Osaka Univ, Grad Sch Med, Dept Stem Cells & Appl Med, Suita, Osaka 5650871, Japan.
   [Hayashi, Ryuhei; Ishikawa, Yuki; Sasamoto, Yuzuru; Katori, Ryosuke; Nomura, Naoki; Ichikawa, Tatsuya; Araki, Saori; Soma, Takeshi; Kawasaki, Satoshi; Tsujikawa, Motokazu; Nishida, Kohji] Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan.
   [Sekiguchi, Kiyotoshi] Osaka Univ, Inst Prot Res, Lab Extracellular Matrix Biochem, Suita, Osaka 5650871, Japan.
   [Quantock, Andrew J.] Cardiff Univ, Coll Biomed & Life Sci, Sch Optometry & Vis Sci, Struct Biophys Grp, Cardiff CF24 4HQ, S Glam, Wales.
C3 University of Osaka; University of Osaka; University of Osaka; Cardiff University
RP Nishida, K (corresponding author), Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan.
EM knishida@ophthal.med.osaka-u.ac.jp
FU Japan Agency for Medical Research and Development (AMED); Japan Science and Technology Agency (JST); Ministry of Health, Labour, and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; BBSRC [BB/M025349/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/M025349/1] Funding Source: researchfish; Grants-in-Aid for Scientific Research [24592675, 25670731, 26462685] Funding Source: KAKEN
NR 28
TC 203
Z9 242
U1 2
U2 131
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 376
EP +
DI 10.1038/nature17000
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300054
PM 26958835
DA 2026-03-09
ER

PT J
AU Thaiss, CA
   Tav, SI
   Rothschild, D
   Eijer, MTM
   Levy, M
   Moresi, C
   Dohnalová, L
   Braverman, S
   Rozin, S
   Malitsky, S
   Dori-Bachash, M
   Kuperman, Y
   Biton, I
   Gertler, A
   Harmelin, A
   Shapiro, H
   Halpern, Z
   Aharoni, A
   Segal, E
   Elinav, E
AF Thaiss, Christoph A.
   Tav, Shlomik I.
   Rothschild, Daphna
   Eijer, Mariska T. M.
   Levy, Maayan
   Moresi, Claudia
   Dohnalova, Lenka
   Braverman, Sofia
   Rozin, Shachar
   Malitsky, Sergey
   Dori-Bachash, Mally
   Kuperman, Yael
   Biton, Inbal
   Gertler, Arieh
   Harmelin, Alon
   Shapiro, Hagit
   Halpern, Zamir
   Aharoni, Asaph
   Segal, Eran
   Elinav, Eran
TI Persistent microbiome alterations modulate the rate of post-dieting weight regain
SO NATURE
LA English
DT Article
ID gut microbiota; obesity; apigenin; fat; flavonoids; quercetin; health; genes; risk
AB In tackling the obesity pandemic, considerable efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here we identify an intestinal microbiome signature that persists after successful dieting of obese mice and contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions. Faecal transfer experiments show that the accelerated weight regain phenotype can be transmitted to germ-free mice. We develop a machine-learning algorithm that enables personalized microbiome-based prediction of the extent of post-dieting weight regain. Additionally, we find that the microbiome contributes to diminished post-dieting flavonoid levels and reduced energy expenditure, and demonstrate that flavonoid-based 'post-biotic' intervention ameliorates excessive secondary weight gain. Together, our data highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.
C1 [Thaiss, Christoph A.; Tav, Shlomik I.; Eijer, Mariska T. M.; Levy, Maayan; Moresi, Claudia; Dohnalova, Lenka; Braverman, Sofia; Rozin, Shachar; Dori-Bachash, Mally; Shapiro, Hagit; Elinav, Eran] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Rothschild, Daphna; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Rothschild, Daphna; Segal, Eran] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Malitsky, Sergey; Aharoni, Asaph] Weizmann Inst Sci, Dept Plant & Environm Sci, IL-76100 Rehovot, Israel.
   [Kuperman, Yael; Biton, Inbal; Harmelin, Alon] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel.
   [Gertler, Arieh] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, Israel.
   [Halpern, Zamir] Tel Aviv Univ, Res Ctr Digest Tract & Liver Dis, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
   [Halpern, Zamir] Tel Aviv Sourasky Med Ctr, Digest Ctr, IL-64239 Tel Aviv, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Hebrew University of Jerusalem; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center
RP Elinav, E (corresponding author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.; Segal, E (corresponding author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.; Segal, E (corresponding author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM eran.segal@weizmann.ac.il; eran.elinav@weizmann.ac.il
FU Boehringer Ingelheim Fonds PhD Fellowship; Levi Eshkol PhD Scholarship for Personalized Medicine by the Israeli Ministry of Science; Crown Human Genome Center; Else Kroener Fresenius Foundation; European Research Council; National Institute of Health; Israel Science Foundation; Frenkel Foundation for the Promotion of Life Sciences; Gurwin Family Fund for Scientific Research; Leona M. and Harry B. Helmsley Charitable Trust; Crown Endowment Fund for Immunological Research; Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; French National Center for Scientific Research (CNRS); Marie Curie Integration grant; German-Israeli Foundation for Scientific Research and Development; Minerva Foundation; Rising Tide Foundation; Helmholtz Foundation; European Foundation for the Study of Diabetes
NR 34
TC 376
Z9 425
U1 4
U2 248
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 544
EP +
DI 10.1038/nature20796
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500044
PM 27906159
DA 2026-03-09
ER

PT J
AU Nacu, E
   Gromberg, E
   Oliveira, CR
   Drechsel, D
   Tanaka, EM
AF Nacu, Eugeniu
   Gromberg, Elena
   Oliveira, Catarina R.
   Drechsel, David
   Tanaka, Elly M.
TI FGF8 and SHH substitute for anterior-posterior tissue interactions to induce limb regeneration
SO NATURE
LA English
DT Article
ID sonic hedgehog; feedback loop; notophthalmus-viridescens; supernumerary limbs; vertebrate limb; double-half; axolotl; cells; bud; blastema
AB In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs(1-4). This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders(5-10). However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements.
C1 [Nacu, Eugeniu; Gromberg, Elena; Oliveira, Catarina R.; Tanaka, Elly M.] Tech Univ Dresden, DFG Res Ctr Regenerat Therapies, D-01307 Dresden, Germany.
   [Nacu, Eugeniu; Gromberg, Elena; Drechsel, David; Tanaka, Elly M.] Max Planck Inst Mol Zellbiol & Genet, D-01307 Dresden, Germany.
   [Oliveira, Catarina R.] Univ Porto, Abel Salazar Biomed Sci Inst, Grad Program Areas Basic & Appl Biol, P-4099003 Oporto, Portugal.
C3 Technische Universitat Dresden; Max Planck Society; Universidade do Porto
RP Nacu, E; Tanaka, EM (corresponding author), Tech Univ Dresden, DFG Res Ctr Regenerat Therapies, D-01307 Dresden, Germany.; Nacu, E; Tanaka, EM (corresponding author), Max Planck Inst Mol Zellbiol & Genet, D-01307 Dresden, Germany.
EM eugeniu_nacu@harvard.edu; elly.tanaka@crt-dresden.de
FU CRTD; MPI-CBG; ERC Advanced Investigator grant; Portuguese Foundation for Science and Technology (FCT)
NR 33
TC 134
Z9 153
U1 1
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 407
EP +
DI 10.1038/nature17972
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300051
PM 27120163
DA 2026-03-09
ER

PT J
AU Zalocusky, KA
   Ramakrishnan, C
   Lerner, TN
   Davidson, TJ
   Knutson, B
   Deisseroth, K
AF Zalocusky, Kelly A.
   Ramakrishnan, Charu
   Lerner, Talia N.
   Davidson, Thomas J.
   Knutson, Brian
   Deisseroth, Karl
TI Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making
SO NATURE
LA English
DT Article
ID orbitofrontal cortex; prefrontal cortex; dopamine; reinforcement; distinct; preferences; uncertainty; activation; selection; behavior
AB A marked bias towards risk aversion has been observed in nearly every species tested(1-4). A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives(2,5). It is not known how neural activity underlies such important shifts in decision-making-either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.
C1 [Zalocusky, Kelly A.; Ramakrishnan, Charu; Lerner, Talia N.; Davidson, Thomas J.; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Zalocusky, Kelly A.] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Zalocusky, Kelly A.; Ramakrishnan, Charu; Lerner, Talia N.; Davidson, Thomas J.; Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
   [Knutson, Brian] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.; Deisseroth, K (corresponding author), Stanford Univ, CNC Program, Stanford, CA 94305 USA.; Deisseroth, K (corresponding author), Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU Deisseroth laboratory; Stanford University Neurosciences Program; NSF Graduate Research Fellowship Program; Stanford Neurosciences Program NIH Training Grant; NRSA Predoctoral Fellowship from NIDA [1F31MH105151-01]; Stanford Dean's Postdoctoral Fellowship; NRSA Postdoctoral Fellowship [1F32MH105053-01]; Stanford Neuroscience Institute Big Ideas Grant; NIMH; NIDA; NSF; Wiegers Family Fund; Nancy and James Grosfeld Foundation; H.L. Snyder Medical Foundation; Samuel and Betsy Reeves Fund; US Army Research Laboratory; Defense Advanced Research Projects Agency [W911NF-14-2-0013]
NR 35
TC 170
Z9 207
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 642
EP +
DI 10.1038/nature17400
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400039
PM 27007845
DA 2026-03-09
ER

PT J
AU Iijima, N
   Iwasaki, A
AF Iijima, Norifumi
   Iwasaki, Akiko
TI Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
SO NATURE
LA English
DT Article
ID herpes-simplex-virus; blood-brain-barrier; sensory ganglia; viral-infection; nerve barrier; b-cells; receptor; type-2; mice; recruitment
AB Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier(1) and blood-nerve barrier(2), respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-gamma and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.
C1 [Iijima, Norifumi; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA.
C3 Yale University; Howard Hughes Medical Institute
RP Iwasaki, A (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA.
EM akiko.iwasaki@yale.edu
FU National Institutes of Health [AI054359, AI062428, AI064705]; National Cancer Institute [P30CA016359] Funding Source: NIH RePORTER
NR 30
TC 69
Z9 80
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 552
EP +
DI 10.1038/nature17979
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100045
PM 27225131
DA 2026-03-09
ER

PT J
AU Paez-Espino, D
   Eloe-Fadrosh, EA
   Pavlopoulos, GA
   Thomas, AD
   Huntemann, M
   Mikhailova, N
   Rubin, E
   Ivanova, NN
   Kyrpides, NC
AF Paez-Espino, David
   Eloe-Fadrosh, Emiley A.
   Pavlopoulos, Georgios A.
   Thomas, Alex D.
   Huntemann, Marcel
   Mikhailova, Natalia
   Rubin, Edward
   Ivanova, Natalia N.
   Kyrpides, Nikos C.
TI Uncovering Earth's virome
SO NATURE
LA English
DT Article
ID marine virus; phage; bacteriophage; protein; sequences; gene; environment; resistance; algorithm; database
AB Viruses are the most abundant biological entities on Earth, but challenges in detecting, isolating, and classifying unknown viruses have prevented exhaustive surveys of the global virome. Here we analysed over 5 Tb of metagenomic sequence data from 3,042 geographically diverse samples to assess the global distribution, phylogenetic diversity, and host specificity of viruses. We discovered over 125,000 partial DNA viral genomes, including the largest phage yet identified, and increased the number of known viral genes by 16-fold. Half of the predicted partial viral genomes were clustered into genetically distinct groups, most of which included genes unrelated to those in known viruses. Using CRISPR spacers and transfer RNA matches to link viral groups to microbial host(s), we doubled the number of microbial phyla known to be infected by viruses, and identified viruses that can infect organisms from different phyla. Analysis of viral distribution across diverse ecosystems revealed strong habitat-type specificity for the vast majority of viruses, but also identified some cosmopolitan groups. Our results highlight an extensive global viral diversity and provide detailed insight into viral habitat distribution and host-virus interactions.
C1 [Paez-Espino, David; Eloe-Fadrosh, Emiley A.; Pavlopoulos, Georgios A.; Thomas, Alex D.; Huntemann, Marcel; Mikhailova, Natalia; Rubin, Edward; Ivanova, Natalia N.; Kyrpides, Nikos C.] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
   [Rubin, Edward] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Rubin, Edward] Metabiota Inc, San Francisco, CA 94104 USA.
C3 United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Kyrpides, NC (corresponding author), Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
EM nckyrpides@lbl.gov
FU US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility [DE-AC02-05CH11231]; Office of Science of US Department of Energy
NR 65
TC 804
Z9 944
U1 17
U2 446
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2016
VL 536
IS 7617
BP 425
EP +
DI 10.1038/nature19094
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV0YL
UT WOS:000382646600035
PM 27533034
DA 2026-03-09
ER

PT J
AU Aydin, H
   Sultana, A
   Li, S
   Thavalingam, A
   Lee, JE
AF Aydin, Halil
   Sultana, Azmiri
   Li, Sheng
   Thavalingam, Annoj
   Lee, Jeffrey E.
TI Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex
SO NATURE
LA English
DT Article
ID structure refinement; structural basis; fusion; mass; glycoprotein; resolution; crystals; exchange; adhesion; insights
AB Fertilization is an essential biological process in sexual reproduction and comprises a series of molecular interactions between the sperm and egg(1,2). The fusion of the haploid spermatozoon and oocyte is the culminating event in mammalian fertilization, enabling the creation of a new, genetically distinct diploid organism(3,4). The merger of two gametes is achieved through a two-step mechanism in which the sperm protein IZUMO1 on the equatorial segment of the acrosome-reacted sperm recognizes its receptor, JUNO, on the egg surface(4-6). This recognition is followed by the fusion of the two plasma membranes. IZUMO1 and JUNO proteins are indispensable for fertilization, as constitutive knockdown of either protein results in mice that are healthy but infertile(5,6). Despite their central importance in reproductive medicine, the molecular architectures of these proteins and the details of their functional roles in fertilization are not known. Here we present the crystal structures of human IZUMO1 and JUNO in unbound and bound conformations. The human IZUMO1 structure exhibits a distinct boomerang shape and provides structural insights into the IZUMO family of proteins(7). Human IZUMO1 forms a high-affinity complex with JUNO and undergoes a major conformational change within its N-terminal domain upon binding to the egg-surface receptor. Our results provide insights into the molecular basis of sperm-egg recognition, cross-species fertilization, and the barrier to polyspermy, thereby promising benefits for the rational development of non-hormonal contraceptives and fertility treatments for humans and other mammals.
C1 [Aydin, Halil; Sultana, Azmiri; Thavalingam, Annoj; Lee, Jeffrey E.] Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada.
   [Li, Sheng] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
C3 University of Toronto; University of California System; University of California San Diego
RP Lee, JE (corresponding author), Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada.
EM jeff.lee@utoronto.ca
FU CIHR [MOP-115066]; NSERC [RGPIN 435607-13]; Ontario Early Researcher Award [ER-13-09-116]; Canada Research Chair; NIH [1U19AI117905, R01 GM020501, R01 AI101436]; University of Toronto; Ontario Graduate Scholarships; NSERC USRA; NSERC; National Research Council of Canada; CIHR; Province of Saskatchewan; Western Economic Diversification Canada; University of Saskatchewan; US Department of Energy (Office of Basic Energy Sciences) through the Integrated Diffraction Analysis Technologies program [DE-AC02-05CH11231]; DOE Office of Biological and Environmental Research; NIH project MINOS [R01GM105404]
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NR 54
TC 122
Z9 143
U1 2
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 562
EP +
DI 10.1038/nature18595
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300056
PM 27309818
DA 2026-03-09
ER

PT J
AU Perera, D
   Poulos, RC
   Shah, A
   Beck, D
   Pimanda, JE
   Wong, JWH
AF Perera, Dilmi
   Poulos, Rebecca C.
   Shah, Anushi
   Beck, Dominik
   Pimanda, John E.
   Wong, Jason W. H.
TI Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes
SO NATURE
LA English
DT Article
ID somatic mutations; chromatin organization; regulatory mutations; excision-repair; wide analysis; damage; identification; signatures; landscape; enhancers
AB Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development(1-4). As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER5 shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.
C1 [Perera, Dilmi; Poulos, Rebecca C.; Shah, Anushi; Beck, Dominik; Pimanda, John E.; Wong, Jason W. H.] UNSW Australia, Prince Wales Clin Sch, Sydney, NSW 2052, Australia.
   [Perera, Dilmi; Poulos, Rebecca C.; Shah, Anushi; Beck, Dominik; Pimanda, John E.; Wong, Jason W. H.] UNSW Australia, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia.
   [Pimanda, John E.] Prince Wales Hosp, Dept Haematol, Sydney, NSW 2031, Australia.
C3 University of New South Wales Sydney; University of New South Wales Sydney; University of New South Wales Sydney; Prince of Wales Hospital (POWH)
RP Wong, JWH (corresponding author), UNSW Australia, Prince Wales Clin Sch, Sydney, NSW 2052, Australia.; Wong, JWH (corresponding author), UNSW Australia, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia.
EM jason.wong@unsw.edu.au
FU Cancer Institute NSW [13/DATA/1-02]; Cure Cancer Foundation Australia; Cancer Australia, through the Priority-driven Collaborative Cancer Research Scheme [APP1057921]; UNSW Australia; Australian Postgraduate Award; National Health and Medical Research Council [APP1073768]; National Health and Medical Research Council (Australia); Australian Research Council [FT130100096]; Australian Research Council [FT130100096] Funding Source: Australian Research Council
NR 45
TC 157
Z9 188
U1 0
U2 79
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 259
EP +
DI 10.1038/nature17437
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100045
PM 27075100
DA 2026-03-09
ER

PT J
AU Gao, S
   Lin, Y
   Jiao, XC
   Sun, YF
   Luo, QQ
   Zhang, WH
   Li, DQ
   Yang, JL
   Xie, Y
AF Gao, Shan
   Lin, Yue
   Jiao, Xingchen
   Sun, Yongfu
   Luo, Qiquan
   Zhang, Wenhua
   Li, Dianqi
   Yang, Jinlong
   Xie, Yi
TI Partially oxidized atomic cobalt layers for carbon dioxide electroreduction to liquid fuel
SO NATURE
LA English
DT Article
ID co2 reduction; electrochemical reduction; formate; oxide; electrodes; catalysts; co3o4; nanoparticles; hydrocarbons; conversion
AB Electroreduction of CO2 into useful fuels, especially if driven by renewable energy, represents a potentially 'clean' strategy for replacing fossil feedstocks and dealing with increasing CO2 emissions and their adverse effects on climate(1-4). The critical bottleneck lies in activating CO2 into the CO2-radical anion or other intermediates that can be converted further, as the activation usually requires impractically high overpotentials. Recently, electrocatalysts based on oxide-derived metal nanostructures have been shown(5-8) to enable CO2 reduction at low overpotentials. However, it remains unclear how the electrocatalytic activity of these metals is influenced by their native oxides, mainly because microstructural features such as interfaces and defects(9) influence CO2 reduction activity yet are difficult to control. To evaluate the role of the two different catalytic sites, here we fabricate two kinds of four-atom-thick layers: pure cobalt metal, and co-existing domains of cobalt metal and cobalt oxide. Cobalt mainly produces formate (HCOO-) during CO2 electroreduction; we find that surface cobalt atoms of the atomically thin layers have higher intrinsic activity and selectivity towards formate production, at lower overpotentials, than do surface cobalt atoms on bulk samples. Partial oxidation of the atomic layers further increases their intrinsic activity, allowing us to realize stable current densities of about 10 milliamperes per square centimetre over 40 hours, with approximately 90 per cent formate selectivity at an overpotential of only 0.24 volts, which outperforms previously reported metal or metal oxide electrodes evaluated under comparable conditions(1,2,6,7,10). The correct morphology and oxidation state can thus transform a material from one considered nearly non-catalytic for the CO2 electroreduction reaction into an active catalyst. These findings point to new opportunities for manipulating and improving the CO2 electroreduction properties of metal systems, especially once the influence of both the atomic-scale structure and the presence of oxide are mechanistically better understood.
C1 [Gao, Shan; Lin, Yue; Jiao, Xingchen; Sun, Yongfu; Luo, Qiquan; Zhang, Wenhua; Li, Dianqi; Yang, Jinlong; Xie, Yi] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Collaborat Innovat Ctr Chem Energy Mat, Hefei 230026, Anhui, Peoples R China.
   [Sun, Yongfu; Xie, Yi] Chinese Acad Sci, Hefei Sci Ctr, Hefei 230061, Anhui, Peoples R China.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences
RP Sun, YF; Xie, Y (corresponding author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Collaborat Innovat Ctr Chem Energy Mat, Hefei 230026, Anhui, Peoples R China.; Sun, YF; Xie, Y (corresponding author), Chinese Acad Sci, Hefei Sci Ctr, Hefei 230061, Anhui, Peoples R China.
EM yfsun@ustc.edu.cn; yxie@ustc.edu.cn
FU National Basic Research Program of China [2015CB932302]; National Nature Science Foundation [21422107, 21331005, 91422303, 21201157, 11321503]; Program for New Century Excellent Talents in University [NCET-13-0546]; Youth Innovation Promotion Association of CAS [CX2340000100]; Chinese Academy of Science [XDB01020300]; Fundamental Research Funds for the Central Universities [WK2340000063]; Scientific Research Grant of the Hefei Science Center of CAS [2015HSC-UE006, 2015HSC-UP015]
NR 25
TC 1682
Z9 1786
U1 42
U2 2898
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 68
EP +
DI 10.1038/nature16455
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900027
PM 26738592
DA 2026-03-09
ER

PT J
AU McDonald, MJ
   Rice, DP
   Desai, MM
AF McDonald, Michael J.
   Rice, Daniel P.
   Desai, Michael M.
TI Sex speeds adaptation by altering the dynamics of molecular evolution
SO NATURE
LA English
DT Article
ID experimental yeast populations; beneficial mutations; saccharomyces-cerevisiae; asexual populations; clonal interference; deleterious mutations; natural-selection; recombination; advantage; hitchhiking
AB Sex and recombination are pervasive throughout nature despite their substantial costs(1). Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology(2,3). One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation(4). Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect)(5,6) or by separating them from deleterious load (the ruby in the rubbish effect)(7,8). Previous experiments confirm that sex can increase the rate of adaptation(9-17), but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.
C1 [McDonald, Michael J.; Rice, Daniel P.; Desai, Michael M.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [McDonald, Michael J.; Rice, Daniel P.; Desai, Michael M.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Desai, Michael M.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University
RP Desai, MM (corresponding author), Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.; Desai, MM (corresponding author), Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.; Desai, MM (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM mmdesai@fas.harvard.edu
FU NSF; James S. McDonnell Foundation; Alfred P. Sloan Foundation; Harvard Milton Fund; Simons Foundation [376196]; National Science Foundation [PHY 1313638]; National Institutes of Health [GM104239]; National Institute of General Medical Sciences [R01GM104239] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Physics [1313638] Funding Source: National Science Foundation
NR 43
TC 240
Z9 307
U1 1
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 233
EP +
DI 10.1038/nature17143
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100041
PM 26909573
DA 2026-03-09
ER

PT J
AU Staus, DP
   Strachan, RT
   Manglik, A
   Pani, B
   Kahsai, AW
   Kim, TH
   Wingler, LM
   Ahn, S
   Chatterjee, A
   Masoudi, A
   Kruse, AC
   Pardon, E
   Steyaert, J
   Weis, WI
   Prosser, RS
   Kobilka, BK
   Costa, T
   Lefkowitz, RJ
AF Staus, Dean P.
   Strachan, Ryan T.
   Manglik, Aashish
   Pani, Biswaranjan
   Kahsai, Alem W.
   Kim, Tae Hun
   Wingler, Laura M.
   Ahn, Seungkirl
   Chatterjee, Arnab
   Masoudi, Ali
   Kruse, Andrew C.
   Pardon, Els
   Steyaert, Jan
   Weis, William I.
   Prosser, R. Scott
   Kobilka, Brian K.
   Costa, Tommaso
   Lefkowitz, Robert J.
TI Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation
SO NATURE
LA English
DT Article
ID ternary complex model; beta(2)-adrenergic receptor; conformations; efficacy; binding; state
AB G-protein-coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signalling effectors such as G proteins and beta-arrestins. It is well known that different agonists can share the same binding pocket but evoke unique receptor conformations leading to a wide range of downstream responses ('efficacy')(1). Furthermore, increasing biophysical evidence, primarily using the beta(2)-adrenergic receptor (beta(2)AR) as a model system, supports the existence of multiple active and inactive conformational states(2-5). However, how agonists with varying efficacy modulate these receptor states to initiate cellular responses is not well understood. Here we report stabilization of two distinct beta(2)AR conformations using single domain camelid antibodies (nanobodies)-a previously described positive allosteric nanobody (Nb80)(6,7) and a newly identified negative allosteric nanobody (Nb60). We show that Nb60 stabilizes a previously unappreciated low-affinity receptor state which corresponds to one of two inactive receptor conformations as delineated by X-ray crystallography and NMR spectroscopy. We find that the agonist isoprenaline has a 15,000-fold higher affinity for beta(2)AR in the presence of Nb80 compared to the affinity of isoprenaline for beta(2)AR in the presence of Nb60, highlighting the full allosteric range of a GPCR. Assessing the binding of 17 ligands of varying efficacy to the beta(2)AR in the absence and presence of Nb60 or Nb80 reveals large ligand-specific effects that can only be explained using an allosteric model which assumes equilibrium amongst at least three receptor states. Agonists generally exert efficacy by stabilizing the active Nb80-stabilized receptor state (R-80). In contrast, for a number of partial agonists, both stabilization of R-80 and destabilization of the inactive, Nb60-bound state (R-60) contribute to their ability to modulate receptor activation. These data demonstrate that ligands can initiate a wide range of cellular responses by differentially stabilizing multiple receptor states.
C1 [Staus, Dean P.; Pani, Biswaranjan; Kahsai, Alem W.; Wingler, Laura M.; Ahn, Seungkirl; Chatterjee, Arnab; Masoudi, Ali; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Strachan, Ryan T.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Manglik, Aashish; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Kim, Tae Hun; Prosser, R. Scott] Univ Toronto, Dept Chem, 3359 Mississauga Rd North, Mississauga, ON L5L 1C6, Canada.
   [Kruse, Andrew C.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Pardon, Els; Steyaert, Jan] Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium.
   [Pardon, Els; Steyaert, Jan] VIB, Struct Biol Res Ctr, Pl Laan 2, B-1050 Brussels, Belgium.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA.
   [Costa, Tommaso] Ist Super Sanita, Dept Pharmacol, I-00161 Rome, Italy.
   [Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
   [Lefkowitz, Robert J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Duke University; University of North Carolina; University of North Carolina Chapel Hill; Stanford University; University of Toronto; University Toronto Mississauga; Harvard University; Harvard Medical School; Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); Stanford University; Istituto Superiore di Sanita (ISS); Duke University; Howard Hughes Medical Institute
RP Lefkowitz, RJ (corresponding author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.; Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.; Costa, T (corresponding author), Ist Super Sanita, Dept Pharmacol, I-00161 Rome, Italy.; Lefkowitz, RJ (corresponding author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.; Lefkowitz, RJ (corresponding author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM kobilka@stanford.edu; tommaso.costa@iss.it; lefko001@receptor-biol.duke.edu
FU National Institute of Health [NS028471, T32HL007101, HL16037, HL70631]; Stanford Medical Scientist Training Program; American Heart Association; Italian Ministry of Health [RF-2011-02351158]; Mathers Foundation; National Heart Lung and Blood Institute [R01HL016037] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007731] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
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NR 36
TC 257
Z9 307
U1 1
U2 196
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 448
EP +
DI 10.1038/nature18636
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200046
PM 27409812
DA 2026-03-09
ER

PT J
AU Secchi, E
   Marbach, S
   Niguès, A
   Stein, D
   Siria, A
   Bocquet, L
AF Secchi, Eleonora
   Marbach, Sophie
   Nigues, Antoine
   Stein, Derek
   Siria, Alessandro
   Bocquet, Lyderic
TI Massive radius-dependent flow slippage in carbon nanotubes
SO NATURE
LA English
DT Article
ID fast water transport; boron-nitride; fluid-flow; membranes; graphene; translocation; friction; channel
AB Measurements and simulations have found that water moves through carbon nanotubes at exceptionally high rates owing to nearly frictionless interfaces(1-4). These observations have stimulated interest in nanotube-based membranes for applications including desalination, nano-filtration and energy harvesting(5-10), yet the exact mechanisms of water transport inside the nanotubes and at the water-carbon interface continue to be debated(11,12) because existing theories do not provide a satisfactory explanation for the limited number of experimental results available so far(13). This lack of experimental results arises because, even though controlled and systematic studies have explored transport through individual nanotubes(7-9,14-17), none has met the considerable technical challenge of unambiguously measuring the permeability of a single nanotube(11). Here we show that the pressure-driven flow rate through individual nanotubes can be determined with unprecedented sensitivity and without dyes from the hydrodynamics of water jets as they emerge from single nanotubes into a surrounding fluid. Our measurements reveal unexpectedly large and radius-dependent surface slippage in carbon nanotubes, and no slippage in boron nitride nanotubes that are crystallographically similar to carbon nanotubes, but electronically different. This pronounced contrast between the two systems must originate from subtle differences in the atomic-scale details of their solid-liquid interfaces, illustrating that nanofluidics is the frontier at which the continuum picture of fluid mechanics meets the atomic nature of matter.
C1 [Secchi, Eleonora; Marbach, Sophie; Nigues, Antoine; Stein, Derek; Siria, Alessandro; Bocquet, Lyderic] PSL Res Univ, Ecole Normale Super, Lab Phys Stat, F-75005 Paris 05, France.
   [Stein, Derek] Brown Univ, Dept Phys, Providence, RI 02912 USA.
C3 Universite PSL; Brown University
RP Siria, A; Bocquet, L (corresponding author), PSL Res Univ, Ecole Normale Super, Lab Phys Stat, F-75005 Paris 05, France.
EM alessandro.siria@lps.ens.fr; lyderic.bocquet@lps.ens.fr
FU European Union/ERC [637748 - NanoSOFT]; European Union/ERC; J.-P. Aguilar grant; PSL chair of excellence; ANR project BlueEnergy
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NR 29
TC 664
Z9 721
U1 28
U2 757
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2016
VL 537
IS 7619
BP 210
EP 213
DI 10.1038/nature19315
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU9LQ
UT WOS:000382539100043
PM 27604947
DA 2026-03-09
ER

PT J
AU Kimura, M
   Isogai, K
   Kato, T
   Ueda, Y
   Nakahira, S
   Shidatsu, M
   Enoto, T
   Hori, T
   Nogami, D
   Littlefield, C
   Ishioka, R
   Chen, YT
   King, SK
   Wen, CY
   Wang, SY
   Lehner, MJ
   Schwamb, ME
   Wang, JH
   Zhang, ZW
   Alcock, C
   Axelrod, T
   Bianco, FB
   Byun, YI
   Chen, WP
   Cook, KH
   Kim, DW
   Lee, T
   Marshall, SL
   Pavlenko, EP
   Antonyuk, OI
   Antonyuk, KA
   Pit, NV
   Sosnovskij, AA
   Babina, JV
   Baklanov, AV
   Pozanenko, AS
   Mazaeva, ED
   Schmalz, SE
   Reva, IV
   Belan, SP
   Inasaridze, RY
   Tungalag, N
   Volnova, AA
   Molotov, IE
   de Miguel, E
   Kasai, K
   Stein, WL
   Dubovsky, PA
   Kiyota, S
   Miller, I
   Richmond, M
   Goff, W
   Andreev, MV
   Takahashi, H
   Kojiguchi, N
   Sugiura, Y
   Takeda, N
   Yamada, E
   Matsumoto, K
   James, N
   Pickard, RD
   Tordai, T
   Maeda, Y
   Ruiz, J
   Miyashita, A
   Cook, LM
   Imada, A
   Uemura, M
AF Kimura, Mariko
   Isogai, Keisuke
   Kato, Taichi
   Ueda, Yoshihiro
   Nakahira, Satoshi
   Shidatsu, Megumi
   Enoto, Teruaki
   Hori, Takafumi
   Nogami, Daisaku
   Littlefield, Colin
   Ishioka, Ryoko
   Chen, Ying-Tung
   King, Sun-Kun
   Wen, Chih-Yi
   Wang, Shiang-Yu
   Lehner, Matthew J.
   Schwamb, Megan E.
   Wang, Jen-Hung
   Zhang, Zhi-Wei
   Alcock, Charles
   Axelrod, Tim
   Bianco, Federica B.
   Byun, Yong-Ik
   Chen, Wen-Ping
   Cook, Kem H.
   Kim, Dae-Won
   Lee, Typhoon
   Marshall, Stuart L.
   Pavlenko, Elena P.
   Antonyuk, Oksana I.
   Antonyuk, Kirill A.
   Pit, Nikolai V.
   Sosnovskij, Aleksei A.
   Babina, Julia V.
   Baklanov, Aleksei V.
   Pozanenko, Alexei S.
   Mazaeva, Elena D.
   Schmalz, Sergei E.
   Reva, Inna V.
   Belan, Sergei P.
   Inasaridze, Raguli Ya.
   Tungalag, Namkhai
   Volnova, Alina A.
   Molotov, Igor E.
   de Miguel, Enrique
   Kasai, Kiyoshi
   Stein, William L.
   Dubovsky, Pavol A.
   Kiyota, Seiichiro
   Miller, Ian
   Richmond, Michael
   Goff, William
   Andreev, Maksim V.
   Takahashi, Hiromitsu
   Kojiguchi, Naoto
   Sugiura, Yuki
   Takeda, Nao
   Yamada, Eiji
   Matsumoto, Katsura
   James, Nick
   Pickard, Roger D.
   Tordai, Tamas
   Maeda, Yutaka
   Ruiz, Javier
   Miyashita, Atsushi
   Cook, Lewis M.
   Imada, Akira
   Uemura, Makoto
TI Repetitive patterns in rapid optical variations in the nearby black-hole binary V404 Cygni
SO NATURE
LA English
DT Article
ID x-ray binary; transient gs 2023+338; light curves; parallax distance; relativistic jets; v4641 sagittarii; igr j17091-3624; grs 1915+105; compact jet; outburst
AB How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours(1). In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source(6) containing a black hole of nine solar masses(7) (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought(1). This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion-not the actual rate-would then be the critical factor causing large-amplitude oscillations in long-period systems.
C1 [Kimura, Mariko; Isogai, Keisuke; Kato, Taichi; Ueda, Yoshihiro; Enoto, Teruaki; Hori, Takafumi; Nogami, Daisaku] Kyoto Univ, Grad Sch Sci, Dept Astron, Sakyo Ku, Kyoto 6068502, Japan.
   [Nakahira, Satoshi] Japan Aerosp Explorat Agcy, Human Spaceflight Technol Directorate, JEM Mission Operat & Integrat Ctr, 2-1-1 Sengen, Tsukuba, Ibaraki 3058505, Japan.
   [Shidatsu, Megumi] RIKEN, MAXI Team, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
   [Enoto, Teruaki] Kyoto Univ, Hakubi Ctr Adv Res, Kyoto 6068302, Japan.
   [Littlefield, Colin] Wesleyan Univ, Dept Astron, Middletown, CT 06459 USA.
   [Ishioka, Ryoko; Chen, Ying-Tung; King, Sun-Kun; Wen, Chih-Yi; Wang, Shiang-Yu; Lehner, Matthew J.; Schwamb, Megan E.; Wang, Jen-Hung; Zhang, Zhi-Wei; Cook, Kem H.; Lee, Typhoon] Acad Sinica, Inst Astron & Astrophys, 11F Astron Math Bldg,AS NTU 1,Sect 4,Roosevelt Rd, Taipei 10617, Taiwan.
   [Lehner, Matthew J.] Univ Penn, Dept Phys & Astron, 209 South 33rd St, Philadelphia, PA 19125 USA.
   [Lehner, Matthew J.; Alcock, Charles] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
   [Axelrod, Tim] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Bianco, Federica B.] NYU, Ctr Cosmol & Particle Phys, 4 Washington Pl, New York, NY 10003 USA.
   [Byun, Yong-Ik] Yonsei Univ, Dept Astron, Seoul 120749, South Korea.
   [Byun, Yong-Ik] Yonsei Univ, Univ Observ, Seoul 120749, South Korea.
   [Chen, Wen-Ping] Natl Cent Univ, Inst Astron, Chungli 32054, Taiwan.
   [Chen, Wen-Ping] Natl Cent Univ, Dept Phys, Chungli 32054, Taiwan.
   [Kim, Dae-Won] Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
   [Marshall, Stuart L.] Stanford Univ, KIPAC, 452 Lomita Mall, Stanford, CA 94309 USA.
   [Pavlenko, Elena P.; Antonyuk, Oksana I.; Antonyuk, Kirill A.; Pit, Nikolai V.; Sosnovskij, Aleksei A.; Babina, Julia V.; Baklanov, Aleksei V.; Belan, Sergei P.] Crimean Astrophys Observ, Nauchnyi, Crimea, Ukraine.
   [Pozanenko, Alexei S.; Mazaeva, Elena D.; Volnova, Alina A.] Russian Acad Sci, Space Res Inst, Moscow 117997, Russia.
   [Pozanenko, Alexei S.] Natl Res Nucl Univ, MEPhI Moscow Engn Phys Inst, Moscow, Russia.
   [Schmalz, Sergei E.] Leibniz Inst Astrophys, Potsdam, Germany.
   [Reva, Inna V.] Fesenkov Astrophys Inst, Alma Ata, Kazakhstan.
   [Inasaridze, Raguli Ya.] Ilia State Univ, Kharadze Abastumani Astrophys Observ, Tbilisi, Georgia.
   [Tungalag, Namkhai] Mongolian Acad Sci, Inst Astron & Geophys, Ulaanbaatar 13343, Mongolia.
   [Molotov, Igor E.] Russian Acad Sci, Keldysh Inst Appl Math, Moscow, Russia.
   [de Miguel, Enrique] Univ Huelva, Fac Ciencias Expt, Dept Fis Aplicada, Huelva 21071, Spain.
   [de Miguel, Enrique] Observ CIECEM, Ctr Backyard Astrophys, Parque Dunar, Almonte 21760, Huelva, Spain.
   [Kasai, Kiyoshi] Baselstr 133D, CH-4132 Muttenz, Switzerland.
   [Stein, William L.] 6025 Calle Paraiso, Las Cruces, NM 88012 USA.
   [Dubovsky, Pavol A.] Vihorlat Observ, Mierova 4, Humenne, Slovakia.
   [Kiyota, Seiichiro] VSOLJ, 7-1 Kitahatsutomi, Chiba 2730126, Japan.
   [Miller, Ian] Furzehill House, Swansea SA2 7LE, W Glam, Wales.
   [Richmond, Michael] Rochester Inst Technol, Dept Phys, Rochester, NY 14623 USA.
   [Goff, William] AAVSO, 13508 Monitor Lane, Sutter Creek, CA 95685 USA.
   [Andreev, Maksim V.] Russian Acad Sci, Inst Astron, Peak Terskol 361605, Kabardino Balka, Russia.
   [Andreev, Maksim V.] Natl Acad Sci Ukraine, Int Ctr Astron Med & Ecol Res, 27 Akad Zabolotnoho St, UA-03680 Kiev, Ukraine.
   [Takahashi, Hiromitsu] Hiroshima Univ, Sch Sci, Dept Phys Sci, 1-3-1 Kagamiyama, Hiroshima 7398526, Japan.
   [Kojiguchi, Naoto; Sugiura, Yuki; Takeda, Nao; Yamada, Eiji; Matsumoto, Katsura] Osaka Kyoiku Univ, 4-698-1 Asahigaoka, Osaka 5828582, Japan.
   [James, Nick] 1 Tavistock Rd, Chelmsford CM1 6JL, Essex, England.
   [Pickard, Roger D.] BAA VSS, Burlington House, London W1J 0DU, England.
   [Pickard, Roger D.] 3 Birches, Leominster HR6 9NG, Hereford, England.
   [Tordai, Tamas] Hungarian Astron Assoc, Polaris Observ, Laborc Utca 2-C, H-1037 Budapest, Hungary.
   [Maeda, Yutaka] 112-14 Kaminishiyama Machi, Nagasaki, Nagasaki 8500006, Japan.
   [Ruiz, Javier] Observ Cantabria, Carretera Rocamundo Sin Numero, Valderredible, Cantabria, Spain.
   [Ruiz, Javier] CSIC UC, Inst Fis Cantabria, Ave Los Castros Sin Numero, E-39005 Santander, Cantabria, Spain.
   [Ruiz, Javier] Agrupac Astron Cantabra, Apartado 573, Santander 39080, Spain.
   [Miyashita, Atsushi] Seikei High Sch, Seikei Meteorol Observ, Kichijoji Kitamachi 3-10-13, Tokyo 1808633, Japan.
   [Cook, Lewis M.] Ctr Backyard Astrophys Concord, 1730 Helix Court, Concord, CA 94518 USA.
   [Imada, Akira] Kyoto Univ, Kwasan Observ, Yamashina Ku, Kitakazan Ohmine Cho, Kyoto 6078471, Japan.
   [Imada, Akira] Kyoto Univ, Hida Observ, Yamashina Ku, Kitakazan Ohmine Cho, Kyoto 6078471, Japan.
   [Uemura, Makoto] Hiroshima Univ, Hiroshima Astrophys Sci Ctr, Kagamiyama 1-3-1, Hiroshima 7398526, Japan.
C3 Kyoto University; Japan Aerospace Exploration Agency (JAXA); RIKEN; Kyoto University; Wesleyan University; Academia Sinica - Taiwan; University of Pennsylvania; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; University of Arizona; New York University; Yonsei University; Yonsei University; National Central University; National Central University; Max Planck Society; Stanford University; Crimean Astrophysical Observatory; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Leibniz Association; Leibniz Institut fur Astrophysik Potsdam (AIP); Fesenkov Astrophysical Institute; Ilia State University; Mongolian Academy of Sciences; Russian Academy of Sciences; Keldysh Institute of Applied Mathematics; Universidad de Huelva; Rochester Institute of Technology; Institute of Astronomy of the Russian Academy of Sciences; Russian Academy of Sciences; National Academy of Sciences Ukraine; International Center for Astronomical & Medico-Ecological Research NASU; Hiroshima University; Osaka University of Education; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad de Cantabria; CSIC - Instituto de Fisica de Cantabria (IFCA); Kyoto University; Kyoto University; Hiroshima University
RP Kimura, M (corresponding author), Kyoto Univ, Grad Sch Sci, Dept Astron, Sakyo Ku, Kyoto 6068502, Japan.
EM mkimura@kusastro.kyoto-u.ac.jp
FU thematic research program [AS-88-TP-A02]; Russian Science Foundation [15-12-30016]; grant RUSTAVELI [FR/379/6-300/14]; Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [25120007, 26400228]; Grants-in-Aid for Scientific Research [26400228] Funding Source: KAKEN
NR 91
TC 74
Z9 79
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 54
EP +
DI 10.1038/nature16452
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900024
PM 26738590
DA 2026-03-09
ER

PT J
AU Richardson, TT
   Harran, O
   Murray, H
AF Richardson, Tomas T.
   Harran, Omar
   Murray, Heath
TI The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding
SO NATURE
LA English
DT Article
ID bacillus-subtilis chromosome; escherichia-coli; structural basis; open complex; protein; recognition; region; mechanism
AB DNA replication is tightly controlled to ensure accurate inheritance of genetic information. In all organisms, initiator proteins possessing AAA+ (ATPases associated with various cellular activities) domains bind replication origins to license new rounds of DNA synthesis(1). In bacteria the master initiator protein, DnaA, is highly conserved and has two crucial DNA binding activities(2). DnaA monomers recognize the replication origin (oriC) by binding double-stranded DNA sequences (DnaA-boxes); subsequently, DnaA filaments assemble and promote duplex unwinding by engaging and stretching a single DNA strand(3-5). While the specificity for duplex DnaA-boxes by DnaA has been appreciated for over 30 years, the sequence specificity for single-strand DNA binding has remained unknown. Here we identify a new indispensable bacterial replication origin element composed of a repeating trinucleotide motif that we term the DnaA-trio. We show that the function of the DnaA-trio is to stabilize DnaA filaments on a single DNA strand, thus providing essential precision to this binding mechanism. Bioinformatic analysis detects Dna-Atrios in replication origins throughout the bacterial kingdom, indicating that this element is part of the core oriC structure. The discovery and characterization of the novel DnaA-trio extends our fundamental understanding of bacterial DNA replication initiation, and because of the conserved structure of AAA+ initiator proteins these findings raise the possibility of specific recognition motifs within replication origins of higher organisms.
C1 [Richardson, Tomas T.; Harran, Omar; Murray, Heath] Newcastle Univ, Ctr Bacterial Cell Biol, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
C3 Newcastle University - UK
RP Murray, H (corresponding author), Newcastle Univ, Ctr Bacterial Cell Biol, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
EM heath.murray@newcastle.ac.uk
FU Royal Society University Research Fellowship; Biotechnology and Biological Sciences Research Council Research Grant [BB/K017527/1]; Iraqi Ministry of Higher Education and Scientific Research Studentship; Biotechnology and Biological Sciences Research Council [BB/K017527/1] Funding Source: researchfish; Medical Research Council [MC_PC_13071] Funding Source: researchfish; BBSRC [BB/K017527/1] Funding Source: UKRI; MRC [MC_PC_13071] Funding Source: UKRI
NR 37
TC 57
Z9 65
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 412
EP +
DI 10.1038/nature17962
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800041
PM 27281207
DA 2026-03-09
ER

PT J
AU Trentini, DB
   Suskiewicz, MJ
   Heuck, A
   Kurzbauer, R
   Deszcz, L
   Mechtler, K
   Clausen, T
AF Trentini, Debora Broch
   Suskiewicz, Marcin Jozef
   Heuck, Alexander
   Kurzbauer, Robert
   Deszcz, Luiza
   Mechtler, Karl
   Clausen, Tim
TI Arginine phosphorylation marks proteins for degradation by a Clp protease
SO NATURE
LA English
DT Article
ID bacillus-subtilis; adapter protein; peptide identification; tyrosine kinase; ubiquitin; ctsr; regulator; expression; bacterial; stress
AB Protein turnover is a tightly controlled process that is crucial for the removal of aberrant polypeptides and for cellular signalling. Whereas ubiquitin marks eukaryotic proteins for proteasomal degradation, a general tagging system for the equivalent bacterial Clp proteases is not known. Here we describe the targeting mechanism of the ClpC-ClpP proteolytic complex from Bacillus subtilis. Quantitative affinity proteomics using a ClpP-trapping mutant show that proteins phosphorylated on arginine residues are selectively targeted to ClpC-ClpP. In vitro reconstitution experiments demonstrate that arginine phosphorylation by the McsB kinase is required and sufficient for the degradation of substrate proteins. The docking site for phosphoarginine is located in the amino-terminal domain of the ClpC ATPase, as resolved at high resolution in a co-crystal structure. Together, our data demonstrate that phosphoarginine functions as a bona fide degradation tag for the ClpC-ClpP protease. This system, which is widely distributed across Gram-positive bacteria, is functionally analogous to the eukaryotic ubiquitin-proteasome system.
C1 [Trentini, Debora Broch; Suskiewicz, Marcin Jozef; Heuck, Alexander; Kurzbauer, Robert; Deszcz, Luiza; Mechtler, Karl; Clausen, Tim] Res Inst Mol Pathol IMP, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
   [Mechtler, Karl] Austrian Acad Sci IMBA, Inst Mol Biotechnol, Dr Bohr Gasse 3, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Austrian Academy of Sciences
RP Clausen, T (corresponding author), Res Inst Mol Pathol IMP, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM clausen@imp.univie.ac.at
FU Austrian Research Promotion Agency (FFG); Boehringer Ingelheim
NR 60
TC 182
Z9 221
U1 4
U2 119
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 48
EP +
DI 10.1038/nature20122
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100026
PM 27749819
DA 2026-03-09
ER

PT J
AU Zhu, JP
   Vinothkumar, KR
   Hirst, J
AF Zhu, Jiapeng
   Vinothkumar, Kutti R.
   Hirst, Judy
TI Structure of mammalian respiratory complex I
SO NATURE
LA English
DT Article
ID nadh-ubiquinone oxidoreductase; acyl carrier protein; crystal-structure; binding-site; subunit; features; domain; nd1; kda
AB Complex I (NADH: ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits(1,2). Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-angstrom resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia(3,4). Our structures therefore provide a foundation for understanding complex I assembly(5) and the effects of mutations that cause clinically relevant complex I dysfunctions(6), give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis.
C1 [Zhu, Jiapeng; Hirst, Judy] MRC Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.
   [Vinothkumar, Kutti R.] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
   [Zhu, Jiapeng] Nanjing Univ Chinese Med, Nanjing 210023, Jiangsu, Peoples R China.
C3 MRC Laboratory Molecular Biology; Nanjing University of Chinese Medicine
RP Hirst, J (corresponding author), MRC Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.; Vinothkumar, KR (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM vkumar@mrc-lmb.cam.ac.uk; jh@mrc-mbu.cam.ac.uk
FU Medical Research Council [U105184322, U105663141]; Medical Research Council [MC_U105663141] Funding Source: researchfish; MRC [MC_U105663141] Funding Source: UKRI
NR 44
TC 454
Z9 510
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2016
VL 536
IS 7616
BP 354
EP +
DI 10.1038/nature19095
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT9GN
UT WOS:000381804900040
PM 27509854
DA 2026-03-09
ER

PT J
AU Barlow, J
   Lennox, GD
   Ferreira, J
   Berenguer, E
   Lees, AC
   Mac Nally, R
   Thomson, JR
   Ferraz, SFD
   Louzada, J
   Oliveira, VHF
   Parry, L
   Solar, RRD
   Vieira, ICG
   Aragao, LEOC
   Begotti, RA
   Braga, RF
   Cardoso, TM
   de Oliveira, RC
   Souza, CM
   Moura, NG
   Nunes, SS
   Siqueira, JV
   Pardini, R
   Silveira, JM
   Vaz-de-Mello, FZ
   Veiga, RCS
   Venturieri, A
   Gardner, TA
AF Barlow, Jos
   Lennox, Gareth D.
   Ferreira, Joice
   Berenguer, Erika
   Lees, Alexander C.
   Mac Nally, Ralph
   Thomson, James R.
   de Barros Ferraz, Silvio Frosini
   Louzada, Julio
   Fonseca Oliveira, Victor Hugo
   Parry, Luke
   de Castro Solar, Ricardo Ribeiro
   Vieira, Ima C. G.
   Aragao, Luiz E. O. C.
   Begotti, Rodrigo Anzolin
   Braga, Rodrigo F.
   Cardoso, Thiago Moreira
   de Oliveira, Raimundo Cosme, Jr.
   Souza, Carlos M., Jr.
   Moura, Nargila G.
   Nunes, Samia Serra
   Siqueira, Joao Victor
   Pardini, Renata
   Silveira, Juliana M.
   Vaz-de-Mello, Fernando Z.
   Stulpen Veiga, Ruan Carlo
   Venturieri, Adriano
   Gardner, Toby A.
TI Anthropogenic disturbance in tropical forests can double biodiversity loss from deforestation
SO NATURE
LA English
DT Article
ID conservation; degradation; extinction; responses; risk; fire
AB Concerted political attention has focused on reducing deforestation(1-3), and this remains the cornerstone of most biodiversity conservation strategies(4-6). However, maintaining forest cover may not reduce anthropogenic forest disturbances, which are rarely considered in conservation programmes(6). These disturbances occur both within forests, including selective logging and wildfires(7,8), and at the landscape level, through edge, area and isolation effects(9). Until now, the combined effect of anthropogenic disturbance on the conservation value of remnant primary forests has remained unknown, making it impossible to assess the relative importance of forest disturbance and forest loss. Here we address these knowledge gaps using a large data set of plants, birds and dung beetles (1,538, 460 and 156 species, respectively) sampled in 36 catchments in the Brazilian state of Para. Catchments retaining more than 69-80% forest cover lost more conservation value from disturbance than from forest loss. For example, a 20% loss of primary forest, the maximum level of deforestation allowed on Amazonian properties under Brazil's Forest Code(5), resulted in a 39-54% loss of conservation value: 96-171% more than expected without considering disturbance effects. We extrapolated the disturbance-mediated loss of conservation value throughout Para, which covers 25% of the Brazilian Amazon. Although disturbed forests retained considerable conservation value compared with deforested areas, the toll of disturbance outside Para's strictly protected areas is equivalent to the loss of 92,000-139,000 km(2) of primary forest. Even this lowest estimate is greater than the area deforested across the entire Brazilian Amazon between 2006 and 2015 (ref. 10). Species distribution models showed that both landscape and within-forest disturbances contributed to biodiversity loss, with the greatest negative effects on species of high conservation and functional value. These results demonstrate an urgent need for policy interventions that go beyond the maintenance of forest cover to safeguard the hyper-diversity of tropical forest ecosystems.
C1 [Barlow, Jos; Lennox, Gareth D.; Berenguer, Erika; Louzada, Julio; Fonseca Oliveira, Victor Hugo; Parry, Luke; Silveira, Juliana M.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Barlow, Jos; Lees, Alexander C.; Vieira, Ima C. G.; Moura, Nargila G.] MCTI Museu Paraense Emilio Goeldi, CP 399, BR-66040170 Belem, Para, Brazil.
   [Barlow, Jos; Louzada, Julio; Fonseca Oliveira, Victor Hugo; Braga, Rodrigo F.; Silveira, Juliana M.] Univ Fed Lavras, Setor Ecologia Conservacao, BR-37200000 Lavras, MG, Brazil.
   [Ferreira, Joice; Cardoso, Thiago Moreira; de Oliveira, Raimundo Cosme, Jr.; Venturieri, Adriano] EMBRAPA Amazonia Oriental, BR-66095100 Belem, Para, Brazil.
   [Lees, Alexander C.; Moura, Nargila G.] Cornell Univ, Cornell Lab Ornithol, Ithaca, NY 14850 USA.
   [Mac Nally, Ralph; Thomson, James R.] Univ Canberra, Inst Appl Ecol, Bruce, ACT 2617, Australia.
   [Thomson, James R.] Arthur Rylah Inst Environm Res, Dept Environm Land Water & Planning, 123 Brown St, Heidelberg, Vic 3084, Australia.
   [de Barros Ferraz, Silvio Frosini; Begotti, Rodrigo Anzolin] Univ Sao Paulo, Escola Super Agr Luiz de Queiroz, Esalq USP, Ave Padua Dias 11, BR-13418900 Piracicaba, SP, Brazil.
   [Parry, Luke] Univ Fed Para UFPA, NAEA, Av Perimetral 1, BR-66075750 Belem, Para, Brazil.
   [de Castro Solar, Ricardo Ribeiro] Univ Fed Vicosa, Dept Biol Geral, Av PH Rolfs S-N, BR-36570900 Vicosa, MG, Brazil.
   [Aragao, Luiz E. O. C.] Natl Inst Space Res INPE, Remote Sensing Div, Trop Ecosyst & Environm Sci Grp TREES, Ave Astronautas,1-758 Jd Granja, BR-12227010 Sao Jose Dos Campos, SP, Brazil.
   [Aragao, Luiz E. O. C.] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4RJ, Devon, England.
   [Souza, Carlos M., Jr.; Nunes, Samia Serra; Siqueira, Joao Victor] IMAZON, Rua Dom Romualdo Seixas 1698, BR-66055200 Belem, Para, Brazil.
   [Pardini, Renata] Univ Sao Paulo, Inst Biociencias, Rua Matao,Travessa 14,101, BR-05508090 Sao Paulo, Brazil.
   [Vaz-de-Mello, Fernando Z.] Univ Fed Mato Grosso, Inst Biociencias, Dept Biol & Zool, Av Fernando Correa da Costa 2367, BR-78060900 Cuiaba, MT, Brazil.
   [Stulpen Veiga, Ruan Carlo] ISASM, Estrada Ribeirao das Voltas S-N, BR-28616010 Lumiar, Nova Friburgo, Brazil.
   [Gardner, Toby A.] Stockholm Environm Inst, Linnegatan 87D,Box 24218, S-10451 Stockholm, Sweden.
   [Gardner, Toby A.] Int Inst Sustainabil, Estrada Dona Castorina 124, BR-22460320 Rio De Janeiro, Brazil.
C3 Lancaster University; Museu Paraense Emilio Goeldi; Universidade Federal de Lavras; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); EMBRAPA Amazonia Oriental; Cornell University; University of Canberra; Arthur Rylah Institute for Environmental Research (ARI); Universidade de Sao Paulo; Universidade Federal do Para; Universidade Federal de Vicosa; University of Exeter; Universidade de Sao Paulo; Universidade Federal de Mato Grosso do Sul; Universidade Federal de Mato Grosso; Stockholm Environment Institute
RP Barlow, J (corresponding author), Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.; Barlow, J (corresponding author), MCTI Museu Paraense Emilio Goeldi, CP 399, BR-66040170 Belem, Para, Brazil.; Barlow, J (corresponding author), Univ Fed Lavras, Setor Ecologia Conservacao, BR-37200000 Lavras, MG, Brazil.
EM josbarlow@gmail.com
FU Brazil (CNPq) [574008/2008-0, 458022/2013-6, 400640/2012-0]; Brazil (Embrapa) [SEG:02.08.06.005.00]; Brazil (Nature Conservancy - Brasil); Brazil (CAPES); UK (Darwin Initiative) [17-023, NE/F01614X/1, NE/G000816/1, NE/F015356/2, NE/l018123/1, NE/K016431/1]; Formas [2013-1571]; Australian Research Council [DP120100797]; NERC [NE/G000816/1, NE/K016385/1, NE/K016431/1, NE/F015356/2] Funding Source: UKRI; Natural Environment Research Council [NE/G000816/1, NE/K016385/1, NE/F015356/2, NE/K016431/1] Funding Source: researchfish
NR 37
TC 815
Z9 933
U1 27
U2 926
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 144
EP +
DI 10.1038/nature18326
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600041
PM 27362236
DA 2026-03-09
ER

PT J
AU Young, ID
   Ibrahim, M
   Chatterjee, R
   Gul, S
   Fuller, FD
   Koroidov, S
   Brewster, AS
   Tran, R
   Alonso-Mori, R
   Kroll, T
   Michels-Clark, T
   Laksmono, H
   Sierra, RG
   Stan, CA
   Hussein, R
   Zhang, M
   Douthit, L
   Kubin, M
   de Lichtenberg, C
   Pham, LV
   Nilsson, H
   Cheah, MH
   Shevela, D
   Saracini, C
   Bean, MA
   Seuffert, I
   Sokaras, D
   Weng, TC
   Pastor, E
   Weninger, C
   Fransson, T
   Lassalle, L
   Bräuer, P
   Aller, P
   Docker, PT
   Andi, B
   Orville, AM
   Glownia, JM
   Nelson, S
   Sikorski, M
   Zhu, DL
   Hunter, MS
   Lane, TJ
   Aquila, A
   Koglin, JE
   Robinson, J
   Liang, MN
   Boutet, S
   Lyubimov, AY
   Uervirojnangkoorn, M
   Moriarty, NW
   Liebschner, D
   Afonine, PV
   Waterman, DG
   Evans, G
   Wernet, P
   Dobbek, H
   Weis, WI
   Brunger, AT
   Zwart, PH
   Adams, PD
   Zouni, A
   Messinger, J
   Bergmann, U
   Sauter, NK
   Kern, J
   Yachandra, VK
   Yano, J
AF Young, Iris D.
   Ibrahim, Mohamed
   Chatterjee, Ruchira
   Gul, Sheraz
   Fuller, Franklin D.
   Koroidov, Sergey
   Brewster, Aaron S.
   Tran, Rosalie
   Alonso-Mori, Roberto
   Kroll, Thomas
   Michels-Clark, Tara
   Laksmono, Hartawan
   Sierra, Raymond G.
   Stan, Claudiu A.
   Hussein, Rana
   Zhang, Miao
   Douthit, Lacey
   Kubin, Markus
   de Lichtenberg, Casper
   Long Vo Pham
   Nilsson, Hakan
   Cheah, Mun Hon
   Shevela, Dmitriy
   Saracini, Claudio
   Bean, Mackenzie A.
   Seuffert, Ina
   Sokaras, Dimosthenis
   Weng, Tsu-Chien
   Pastor, Ernest
   Weninger, Clemens
   Fransson, Thomas
   Lassalle, Louise
   Braeuer, Philipp
   Aller, Pierre
   Docker, Peter T.
   Andi, Babak
   Orville, Allen M.
   Glownia, James M.
   Nelson, Silke
   Sikorski, Marcin
   Zhu, Diling
   Hunter, Mark S.
   Lane, Thomas J.
   Aquila, Andy
   Koglin, Jason E.
   Robinson, Joseph
   Liang, Mengning
   Boutet, Sebastien
   Lyubimov, Artem Y.
   Uervirojnangkoorn, Monarin
   Moriarty, Nigel W.
   Liebschner, Dorothee
   Afonine, Pavel V.
   Waterman, David G.
   Evans, Gwyndaf
   Wernet, Philippe
   Dobbek, Holger
   Weis, William I.
   Brunger, Axel T.
   Zwart, Petrus H.
   Adams, Paul D.
   Zouni, Athina
   Messinger, Johannes
   Bergmann, Uwe
   Sauter, Nicholas K.
   Kern, Jan
   Yachandra, Vittal K.
   Yano, Junko
TI Structure of photosystem II and substrate binding at room temperature
SO NATURE
LA English
DT Article
ID oxygen-evolving complex; photosynthetic water oxidation; ammonia binds; o-2-evolving complex; s-2 state; diffraction; manganese; evolution; cluster; instrument
AB Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S-0 to S-4)(1), in which S-1 is the dark-stable state and S-3 is the last semi-stable state before O-O bond formation and O-2 evolution(2,3). A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site(4-6). Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S-1), two-flash illuminated (2F; S-3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S-3-enriched) PS II. Although the recent 1.95 angstrom resolution structure of PS II at cryogenic temperature using an XFEL7 provided a damage-free view of the S-1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions(8,9), and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S-2 and S-3 states(10). Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site(10-13). This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.
C1 [Young, Iris D.; Chatterjee, Ruchira; Gul, Sheraz; Fuller, Franklin D.; Brewster, Aaron S.; Tran, Rosalie; Michels-Clark, Tara; Douthit, Lacey; Saracini, Claudio; Bean, Mackenzie A.; Pastor, Ernest; Lassalle, Louise; Moriarty, Nigel W.; Liebschner, Dorothee; Afonine, Pavel V.; Zwart, Petrus H.; Sauter, Nicholas K.; Yachandra, Vittal K.; Yano, Junko] Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA.
   [Ibrahim, Mohamed; Hussein, Rana; Zhang, Miao; Seuffert, Ina; Dobbek, Holger; Zouni, Athina] Humboldt Univ, Inst Biol, D-10099 Berlin, Germany.
   [Koroidov, Sergey; de Lichtenberg, Casper; Long Vo Pham; Nilsson, Hakan; Cheah, Mun Hon; Shevela, Dmitriy; Messinger, Johannes] Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden.
   [Alonso-Mori, Roberto; Sierra, Raymond G.; Glownia, James M.; Nelson, Silke; Sikorski, Marcin; Zhu, Diling; Hunter, Mark S.; Lane, Thomas J.; Aquila, Andy; Koglin, Jason E.; Robinson, Joseph; Liang, Mengning; Boutet, Sebastien; Kern, Jan] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Kroll, Thomas; Laksmono, Hartawan; Sierra, Raymond G.; Stan, Claudiu A.; Weninger, Clemens; Fransson, Thomas; Bergmann, Uwe] SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA.
   [Kroll, Thomas; Sokaras, Dimosthenis; Weng, Tsu-Chien] SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA.
   [Kubin, Markus; Wernet, Philippe] Helmholtz Zentrum, Inst Methods & Instrumentat Synchrotron Radiat Re, D-14109 Berlin, Germany.
   [Braeuer, Philipp] Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England.
   [Braeuer, Philipp; Aller, Pierre; Docker, Peter T.; Orville, Allen M.; Evans, Gwyndaf] Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England.
   [Andi, Babak] Brookhaven Natl Lab, Natl Synchrotron Light Source 2, Upton, NY 11973 USA.
   [Lyubimov, Artem Y.; Uervirojnangkoorn, Monarin; Weis, William I.; Brunger, Axel T.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Lyubimov, Artem Y.; Uervirojnangkoorn, Monarin; Brunger, Axel T.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Waterman, David G.] STFC Rutherford Appleton Lab, Didcot OX11 0QX, Oxon, England.
   [Waterman, David G.] Rutherford Appleton Lab, CCP4,Res Complex Harwell, Didcot OX11 0FA, Oxon, England.
   [Weis, William I.; Brunger, Axel T.] Stanford Univ, Dept Photon Sci, Stanford, CA 94305 USA.
   [Weis, William I.; Brunger, Axel T.] Stanford Univ, Dept Struct Biol, Stanford, CA 94305 USA.
   [Adams, Paul D.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
   [Messinger, Johannes] Uppsala Univ, Mol Biomimet, Dept Chem, Angstrom, SE-75237 Uppsala, Sweden.
   [Weng, Tsu-Chien] Ctr High Pressure Sci & Technol Adv Res, Shanghai 201203, Peoples R China.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Humboldt University of Berlin; Umea University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); University of Oxford; Diamond Light Source; United States Department of Energy (DOE); Brookhaven National Laboratory; Stanford University; Stanford University; Howard Hughes Medical Institute; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Stanford University; Stanford University; University of California System; University of California Berkeley; Uppsala University
RP Yachandra, VK; Yano, J (corresponding author), Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA.; Zouni, A (corresponding author), Humboldt Univ, Inst Biol, D-10099 Berlin, Germany.; Messinger, J (corresponding author), Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden.; Messinger, J (corresponding author), Uppsala Univ, Mol Biomimet, Dept Chem, Angstrom, SE-75237 Uppsala, Sweden.
EM athina.zouni@hu-berlin.de; johannes.messinger@umu.se; johannes.messinger@umu.se; vkyachandra@lbl.gov; jyano@lbl.gov
FU National Institutes of Health (NIH) [GM055302, GM110501, GM102520, GM117126]; Ruth L. Kirschstein National Research Service Award [GM116423-02]; Human Frontiers Science Project [RGP0063/2013 310]; DFG-Cluster of Excellence "UniCat"; Humboldt Universitat Berlin [Sfb1078]; Solar Fuels Strong Research Environment (Umea University); Artificial Leaf Project (K&A Wallenberg Foundation) [2011.0055]; Energimyndigheten [36648-1]; US DOE, OBES, CSGB Division; HHMI; Office of Science, DOE [DE-AC02-5CH11231]; BNL/US DOE, LDRD [11-008]; NIH/NCRR [2-P41-RR012408]; NIH/NIGMS [8P41GM103473-16, P41GM111244]; US DOE, OBER [FWP BO-70]; Diamond Light Source; Wellcome Trust; Biotechnology and Biological Sciences Research Council [102593]; DOE OBES [DE-AC02-05CH11231, DE-AC02-76SF00515]; DOE OBER; NIH [P41GM103393]; US DOE, Office of Science, OBES [DE-AC02-76SF00515];  [TP A5]; National Institute of General Medical Sciences [P01GM063210, R01GM117126, R01GM055302, R01GM110501] Funding Source: NIH RePORTER
NR 68
TC 313
Z9 356
U1 4
U2 405
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 453
EP +
DI 10.1038/nature20161
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800046
PM 27871088
DA 2026-03-09
ER

PT J
AU Bouley, S
   Baratoux, D
   Matsuyama, I
   Forget, F
   Séjourné, A
   Turbet, M
   Costard, F
AF Bouley, Sylvain
   Baratoux, David
   Matsuyama, Isamu
   Forget, Francois
   Sejourne, Antoine
   Turbet, Martin
   Costard, Francois
TI Late Tharsis formation and implications for early Mars
SO NATURE
LA English
DT Article
ID planets; history; climate; retreat; time
AB The Tharsis region is the largest volcanic complex on Mars and in the Solar System. Young lava flows cover its surface (from the Amazonian period, less than 3 billion years ago) but its growth started during the Noachian era (more than 3.7 billion years ago). Its position has induced a reorientation of the planet with respect to its spin axis (true polar wander, TPW), which is responsible for the present equatorial position of the volcanic province. It has been suggested that the Tharsis load on the lithosphere influenced the orientation of the Noachian/Early Hesperian (more than 3.5 billion years ago) valley networks(1) and therefore that most of the topography of Tharsis was completed before fluvial incision. Here we calculate the rotational figure of Mars (that is, its equilibrium shape) and its surface topography before Tharsis formed, when the spin axis of the planet was controlled by the difference in elevation between the northern and southern hemispheres (hemispheric dichotomy). We show that the observed directions of valley networks are also consistent with topographic gradients in this configuration and thus do not require the presence of the Tharsis load. Furthermore, the distribution of the valleys along a small circle tilted with respect to the equator is found to correspond to a southern-hemisphere latitudinal band in the pre-TPW geographical frame. Preferential accumulation of ice or water in a south tropical band is predicted by climate model simulations of early Mars applied to the pre-TPW topography. A late growth of Tharsis, contemporaneous with valley incision, has several implications for the early geological history of Mars, including the existence of glacial environments near the locations of the pre-TPW poles of rotation, and a possible link between volcanic outgassing from Tharsis and the stability of liquid water at the surface of Mars.
C1 [Bouley, Sylvain; Sejourne, Antoine; Costard, Francois] Univ Paris Saclay, Univ Paris Sud, CNRS, GEOPS Geosci Paris Sud, Rue Belvedere,Batiment 504-509, F-91405 Orsay, France.
   [Bouley, Sylvain] Inst Mecan Celeste & Calcul Ephemerides, UMR8028, 77 Ave Denfert Rochereau, F-75014 Paris, France.
   [Baratoux, David] Univ Toulouse 3, Geosci Environm Toulouse, UMR 5563, 14 Ave Edouard Belin, F-31400 Toulouse, France.
   [Baratoux, David] Inst Rech Dev, Dakar, Senegal.
   [Baratoux, David] Inst Fondamental Afrique Noire, Dakar, Senegal.
   [Matsuyama, Isamu] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Forget, Francois; Turbet, Martin] Univ Paris 06, CNRS, Inst Pierre Simon Laplace, Lab Meteorol Dynam, Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National d'Etudes Spatiales (CNES); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Institut de Recherche pour le Developpement (IRD); University of Arizona; Universite Paris Saclay; Institut Polytechnique de Paris; Ecole Polytechnique; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Bouley, S (corresponding author), Univ Paris Saclay, Univ Paris Sud, CNRS, GEOPS Geosci Paris Sud, Rue Belvedere,Batiment 504-509, F-91405 Orsay, France.; Bouley, S (corresponding author), Inst Mecan Celeste & Calcul Ephemerides, UMR8028, 77 Ave Denfert Rochereau, F-75014 Paris, France.
EM sylvain.bouley@u-psud.fr
FU GEOPS laboratory; Programme National de Planetologie of INSU-CNRS; Centre National d'Etude Spatiale (CNES)
NR 41
TC 88
Z9 98
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 344
EP +
DI 10.1038/nature17171
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300047
PM 26934230
DA 2026-03-09
ER

PT J
AU Liu, BH
   Huberman, AD
   Scanziani, M
AF Liu, Bao-hua
   Huberman, Andrew D.
   Scanziani, Massimo
TI Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour
SO NATURE
LA English
DT Article
ID dorsal terminal nucleus; optic tract; unilateral labyrinthectomy; quantitative-analysis; optokinetic response; eye-movements; gain-control; projections; neurons; channelrhodopsin-2
AB The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections(1). Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood(1-4). A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system(3,5,6), that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision(5). The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life(7-11). Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei(10-13), cortical lesions have suggested that the visual cortex might also be involved(9,14,15). Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment(11,16-18), is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function(19), to plastically adapt the execution of innate motor behaviours.
C1 [Liu, Bao-hua; Scanziani, Massimo] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Liu, Bao-hua; Scanziani, Massimo] Univ Calif San Diego, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
   [Liu, Bao-hua; Scanziani, Massimo] Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Liu, Bao-hua; Scanziani, Massimo] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Huberman, Andrew D.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
   [Scanziani, Massimo] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Stanford University; University of California System; University of California San Francisco
RP Liu, BH; Scanziani, M (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.; Liu, BH; Scanziani, M (corresponding author), Univ Calif San Diego, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.; Liu, BH; Scanziani, M (corresponding author), Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA.; Liu, BH; Scanziani, M (corresponding author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.; Scanziani, M (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
EM lbaohua@ucsd.edu; massimo@ucsf.edu
FU Gatsby Charitable Foundation; US National Institutes of Health [R01 EY025668]; National Eye Institute [P30EY002162] Funding Source: NIH RePORTER
NR 45
TC 63
Z9 77
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 383
EP +
DI 10.1038/nature19818
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100039
PM 27732573
DA 2026-03-09
ER

PT J
AU Buss, JA
   Agapie, T
AF Buss, Joshua A.
   Agapie, Theodor
TI Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site
SO NATURE
LA English
DT Article
ID electrochemical reduction; crystal-structure; uranium complex; methylidyne; co; hydrogenation; homologation; cleavage; tungsten; copper
AB Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained(1). Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide(2), further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging(3). Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources(4). Electrocatalytic reduction of carbon monoxide on copper catalysts(5) also uses a combination of electrons and protons, while the industrial Fischer-Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures(6). However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively(6-23) to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon-oxygen bonds and generate carbon-carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl-diphosphine ligand, that activates and cleaves the strong carbon-oxygen bond of carbon monoxide, enacts carbon-carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl-diphosphine ligand(24,25), which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site.
C1 [Buss, Joshua A.; Agapie, Theodor] CALTECH, Div Chem & Chem Engn, 1200 East Calif Blvd,MC 127-72, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Agapie, T (corresponding author), CALTECH, Div Chem & Chem Engn, 1200 East Calif Blvd,MC 127-72, Pasadena, CA 91125 USA.
EM agapie@caltech.edu
FU Caltech; National Science Foundation [CHE-1151918]; GRFP; Direct For Mathematical & Physical Scien; Division Of Chemistry [1151918] Funding Source: National Science Foundation
NR 30
TC 97
Z9 114
U1 5
U2 341
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 72
EP 75
DI 10.1038/nature16154
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900028
PM 26689364
DA 2026-03-09
ER

PT J
AU Chikkaraddy, R
   de Nijs, B
   Benz, F
   Barrow, SJ
   Scherman, OA
   Rosta, E
   Demetriadou, A
   Fox, P
   Hess, O
   Baumberg, JJ
AF Chikkaraddy, Rohit
   de Nijs, Bart
   Benz, Felix
   Barrow, Steven J.
   Scherman, Oren A.
   Rosta, Edina
   Demetriadou, Angela
   Fox, Peter
   Hess, Ortwin
   Baumberg, Jeremy J.
TI Single-molecule strong coupling at room temperature in plasmonic nanocavities
SO NATURE
LA English
DT Article
ID light; enhancement
AB Photon emitters placed in an optical cavity experience an environment that changes how they are coupled to the surrounding light field. In the weak-coupling regime, the extraction of light from the emitter is enhanced. But more profound effects emerge when single-emitter strong coupling occurs: mixed states are produced that are part light, part matter(1,2), forming building blocks for quantum information systems and for ultralow-power switches and lasers(3-6). Such cavity quantum electrodynamics has until now been the preserve of low temperatures and complicated fabrication methods, compromising its use(5,7,8). Here, by scaling the cavity volume to less than 40 cubic nanometres and using host-guest chemistry to align one to ten protectively isolated methylene-blue molecules, we reach the strong-coupling regime at room temperature and in ambient conditions. Dispersion curves from more than 50 such plasmonic nanocavities display characteristic light-matter mixing, with Rabi frequencies of 300 millielectronvolts for ten methylene-blue molecules, decreasing to 90 millielectronvolts for single molecules-matching quantitative models. Statistical analysis of vibrational spectroscopy time series and dark-field scattering spectra provides evidence of single-molecule strong coupling. This dressing of molecules with light can modify photochemistry, opening up the exploration of complex natural processes such as photosynthesis(9) and the possibility of manipulating chemical bonds(10).
C1 [Chikkaraddy, Rohit; de Nijs, Bart; Benz, Felix; Baumberg, Jeremy J.] Univ Cambridge, Cavendish Lab, NanoPhoton Ctr, Cambridge CB3 0HE, England.
   [Barrow, Steven J.; Scherman, Oren A.] Univ Cambridge, Dept Chem, Melville Lab Polymer Synth, Lensfield Rd, Cambridge CB2 1EW, England.
   [Rosta, Edina] Kings Coll London, Dept Chem, London SE1 1DB, England.
   [Demetriadou, Angela; Fox, Peter; Hess, Ortwin] Univ London Imperial Coll Sci Technol & Med, Dept Phys, Blackett Lab, Prince Consort Rd, London SW7 2AZ, England.
C3 University of Cambridge; University of Cambridge; University of London; King's College London; Imperial College London
RP Baumberg, JJ (corresponding author), Univ Cambridge, Cavendish Lab, NanoPhoton Ctr, Cambridge CB3 0HE, England.
EM jjb12@cam.ac.uk
FU UK's Engineering and Physical Sciences Research Council [EP/G060649/1, EP/N020669/1, EP/L027151/1, EP/I012060/1]; European Research Council [LINASS 320503]; Air Force Office of Scientific Research (AFOSR); European Office of Aerospace Research and Development (EOARD); Dr. Manmohan Singh scholarship from St John's College, University of Cambridge; Winton Programme for the Physics of Sustainability; European Commission (NANOSPHERE) [658360]; EPSRC [EP/L000253/1, EP/L027151/1, EP/I012060/1, EP/M022609/1, EP/G060649/1, EP/N020669/1, EP/K028510/1, EP/H007024/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/I012060/1, EP/L027151/1, EP/N020669/1, EP/M022609/1, 1366370, EP/K028510/1, EP/G060649/1, 1352498, EP/L000253/1, EP/H007024/1] Funding Source: researchfish; Marie Curie Actions (MSCA) [658360] Funding Source: Marie Curie Actions (MSCA)
NR 30
TC 1680
Z9 1831
U1 45
U2 1621
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 127
EP 130
DI 10.1038/nature17974
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600037
PM 27296227
DA 2026-03-09
ER

PT J
AU Fattahi, F
   Steinbeck, JA
   Kriks, S
   Tchieu, J
   Zimmer, B
   Kishinevsky, S
   Zeltner, N
   Mica, Y
   El-Nachef, W
   Zhao, HY
   de Stanchina, E
   Gershon, MD
   Grikscheit, TC
   Chen, SB
   Studer, L
AF Fattahi, Faranak
   Steinbeck, Julius A.
   Kriks, Sonja
   Tchieu, Jason
   Zimmer, Bastian
   Kishinevsky, Sarah
   Zeltner, Nadja
   Mica, Yvonne
   El-Nachef, Wael
   Zhao, Huiyong
   de Stanchina, Elisa
   Gershon, Michael D.
   Grikscheit, Tracy C.
   Chen, Shuibing
   Studer, Lorenz
TI Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease
SO NATURE
LA English
DT Article
ID embryonic stem-cells; neural crest; migration; gut; differentiation; megacolon; motility; neurons; gene
AB The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord(1). The ENS has been called the ` second brain'(1) given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon(2). Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell-and drug-based strategies for the treatment of HSCR.
C1 [Fattahi, Faranak; Steinbeck, Julius A.; Kriks, Sonja; Tchieu, Jason; Zimmer, Bastian; Kishinevsky, Sarah; Zeltner, Nadja; Mica, Yvonne; Studer, Lorenz] Ctr Stem Cell Biol, New York, NY 10065 USA.
   [Fattahi, Faranak; Steinbeck, Julius A.; Kriks, Sonja; Tchieu, Jason; Zimmer, Bastian; Kishinevsky, Sarah; Zeltner, Nadja; Mica, Yvonne; Studer, Lorenz] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA.
   [Fattahi, Faranak; Kishinevsky, Sarah] Cornell Univ, Weill Grad Sch Med Sci, New York, NY 10065 USA.
   [El-Nachef, Wael; Zhao, Huiyong; de Stanchina, Elisa] Mol Pharmacol Program, New York, NY 10065 USA.
   [Gershon, Michael D.] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Grikscheit, Tracy C.] Childrens Hosp Los Angeles, Pediat Surg, Los Angeles, CA 90027 USA.
   [Chen, Shuibing] Cornell Univ, Dept Surg, Weill Med Coll, New York, NY 10065 USA.
   [Mica, Yvonne] Thermo Fisher Sci, Waltham, MA 02451 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Columbia University; Children's Hospital Los Angeles; Cornell University; Weill Cornell Medicine; Thermo Fisher Scientific
RP Studer, L (corresponding author), Ctr Stem Cell Biol, New York, NY 10065 USA.; Studer, L (corresponding author), Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA.
EM studerl@mskcc.org
FU Starr Foundation; NYSTEM [C026446]; NINDS [NS15547]; California Institute for Regenerative Medicine (CIRM) [RN200946-1, RN3-06425]; New York Stem Cell Foundation [R-103]; NIDDK [DP2 DK098093-01]; DFG;  [P30 CA008748];  [TRI-SCI 2014-030]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS015547] Funding Source: NIH RePORTER
NR 31
TC 232
Z9 307
U1 4
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 105
EP +
DI 10.1038/nature16951
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900049
PM 26863197
DA 2026-03-09
ER

PT J
AU Laso-Pérez, R
   Wegener, G
   Knittel, K
   Widdel, F
   Harding, KJ
   Krukenberg, V
   Meier, DV
   Richter, M
   Tegetmeyer, HE
   Riedel, D
   Richnow, HH
   Adrian, L
   Reemtsma, T
   Lechtenfeld, OJ
   Musat, F
AF Laso-Perez, Rafael
   Wegener, Gunter
   Knittel, Katrin
   Widdel, Friedrich
   Harding, Katie J.
   Krukenberg, Viola
   Meier, Dimitri V.
   Richter, Michael
   Tegetmeyer, Halina E.
   Riedel, Dietmar
   Richnow, Hans-Hermann
   Adrian, Lorenz
   Reemtsma, Thorsten
   Lechtenfeld, Oliver J.
   Musat, Florin
TI Thermophilic archaea activate butane via alkyl-coenzyme M formation
SO NATURE
LA English
DT Article
ID sulfate-reducing bacterium; anaerobic oxidation; methanotrophic archaea; electron-transfer; alkane degraders; single-cell; methane; degradation; metabolism; reductase
AB The anaerobic formation and oxidation of methane involve unique enzymatic mechanisms and cofactors, all of which are believed to be specific for C-1-compounds. Here we show that an anaerobic thermophilic enrichment culture composed of dense consortia of archaea and bacteria apparently uses partly similar pathways to oxidize the C-4 hydrocarbon butane. The archaea, proposed genus Candidatus Syntrophoarchaeum', show the characteristic autofluorescence of methanogens, and contain highly expressed genes encoding enzymes similar to methyl-coenzyme M reductase. We detect butyl-coenzyme M, indicating archaeal butane activation analogous to the first step in anaerobic methane oxidation. In addition, Ca. Syntrophoarchaeum expresses the genes encoding beta-oxidation enzymes, carbon monoxide dehydrogenase and reversible C-1 methanogenesis enzymes. This allows for the complete oxidation of butane. Reducing equivalents are seemingly channelled to HotSeep-1, a thermophilic sulfate-reducing partner bacterium known from the anaerobic oxidation of methane. Genes encoding 16S rRNA and methyl-coenzyme M reductase similar to those identifying Ca. Syntrophoarchaeum were repeatedly retrieved from marine subsurface sediments, suggesting that the presented activation mechanism is naturally widespread in the anaerobic oxidation of short-chain hydrocarbons.
C1 [Laso-Perez, Rafael; Wegener, Gunter; Knittel, Katrin; Widdel, Friedrich; Harding, Katie J.; Krukenberg, Viola; Meier, Dimitri V.; Richter, Michael; Musat, Florin] Max Planck Inst Marine Mikrobiol, D-28359 Bremen, Germany.
   [Laso-Perez, Rafael; Wegener, Gunter; Krukenberg, Viola; Tegetmeyer, Halina E.] Alfred Wegener Inst, Helmholtz Ctr Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Wegener, Gunter] Univ Bremen, Ctr Marine Environm Sci, MARUM, D-28359 Bremen, Germany.
   [Tegetmeyer, Halina E.] Univ Bielefeld, Ctr Biotechnol, D-33615 Bielefeld, Germany.
   [Riedel, Dietmar] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany.
   [Richnow, Hans-Hermann; Adrian, Lorenz; Reemtsma, Thorsten; Lechtenfeld, Oliver J.; Musat, Florin] UFZ Helmholtz Ctr Environm Res, D-04318 Leipzig, Germany.
   [Harding, Katie J.] Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
C3 Max Planck Society; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Bremen; University of Bielefeld; Max Planck Society; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); University of California System; University of California Santa Cruz
RP Wegener, G; Musat, F (corresponding author), Max Planck Inst Marine Mikrobiol, D-28359 Bremen, Germany.; Wegener, G (corresponding author), Alfred Wegener Inst, Helmholtz Ctr Polar & Marine Res, D-27570 Bremerhaven, Germany.; Wegener, G (corresponding author), Univ Bremen, Ctr Marine Environm Sci, MARUM, D-28359 Bremen, Germany.; Musat, F (corresponding author), UFZ Helmholtz Ctr Environm Res, D-04318 Leipzig, Germany.
EM gwegener@mpi-bremen.de; florin.musat@ufz.de
FU Deutsche Forschungsgemeinschaft (DFG); DFG Research Center; Cluster of Excellence MARUM; Deep Carbon Observatory (Deep Life grant) [11121/6152-2121-2329-9973-CC]; Max Planck Society; Helmholtz Society; NSF [OCE-0647633]
NR 48
TC 207
Z9 235
U1 5
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 396
EP 401
DI 10.1038/nature20152
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700047
PM 27749816
DA 2026-03-09
ER

PT J
AU Ortmayer, M
   Lafite, P
   Menon, BRK
   Tralau, T
   Fisher, K
   Denkhaus, L
   Scrutton, NS
   Rigby, SEJ
   Munro, AW
   Hay, S
   Leys, D
AF Ortmayer, Mary
   Lafite, Pierre
   Menon, Binuraj R. K.
   Tralau, Tewes
   Fisher, Karl
   Denkhaus, Lukas
   Scrutton, Nigel S.
   Rigby, Stephen E. J.
   Munro, Andrew W.
   Hay, Sam
   Leys, David
TI An oxidative N-demethylase reveals PAS transition from ubiquitous sensor to enzyme
SO NATURE
LA English
DT Article
ID electron-paramagnetic-resonance; secondary amine monooxygenase; heme; trimethylamine; biocatalysts; oxygenases; mechanism; myoglobin; catalysis; reductase
AB The universal Per-ARNT-Sim (PAS) domain functions as a signal transduction module involved in sensing diverse stimuli such as small molecules, light, redox state and gases(1,2). The highly evolvable PAS scaffold can bind a broad range of ligands, including haem, flavins and metal ions. However, although these ligands can support catalytic activity, to our knowledge no enzymatic PAS domain has been found. Here we report characterization of the first PAS enzyme: a haem-dependent oxidative N-demethylase. Unrelated to other amine oxidases, this enzyme contains haem, flavin mononucleotide, 2Fe-2S and tetrahydrofolic acid cofactors, and specifically catalyses the NADPH-dependent oxidation of dimethylamine. The structure of the a subunit reveals that it is a haem-binding PAS domain, similar in structure to PAS gas sensors(3). The dimethylamine substrate forms part of a highly polarized oxygen-binding site, and directly assists oxygen activation by acting as both an electron and proton donor. Our data reveal that the ubiquitous PAS domain can make the transition from sensor to enzyme, suggesting that the PAS scaffold can support the development of artificial enzymes.
C1 [Ortmayer, Mary; Lafite, Pierre; Menon, Binuraj R. K.; Tralau, Tewes; Fisher, Karl; Denkhaus, Lukas; Scrutton, Nigel S.; Rigby, Stephen E. J.; Munro, Andrew W.; Hay, Sam; Leys, David] Univ Manchester, Manchester Inst Biotechnol, Sch Chem, 131 Princess St, Manchester M1 7DN, Lancs, England.
   [Lafite, Pierre] Univ Orleans, CNRS, ICOA, UMR 7311, F-45067 Orleans, France.
   [Tralau, Tewes] German Fed Inst Risk Assessment BfR, Dept Chem & Product Safety, Max Dohrn Str 8-10, D-10589 Berlin, Germany.
C3 University of Manchester; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); CEA; Universite de Orleans; Federal Institute for Risk Assessment
RP Leys, D (corresponding author), Univ Manchester, Manchester Inst Biotechnol, Sch Chem, 131 Princess St, Manchester M1 7DN, Lancs, England.
EM david.leys@manchester.ac.uk
FU BBSRC grant [BBE0170101]; BBSRC/EPSRC SYNBIOCHEM Centre [BB/M017702/1]; Royal Society; BBSRC [BB/M017702/1, BB/E013007/1, BB/E017010/1] Funding Source: UKRI; EPSRC [EP/J020192/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E013007/1, BB/E017010/1, BB/M017702/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/J020192/1] Funding Source: researchfish
NR 38
TC 19
Z9 24
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2016
VL 539
IS 7630
BP 593
EP +
DI 10.1038/nature20159
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED0GI
UT WOS:000388520600050
PM 27851736
DA 2026-03-09
ER

PT J
AU Evan, AT
   Flamant, C
   Gaetani, M
   Guichard, F
AF Evan, Amato T.
   Flamant, Cyrille
   Gaetani, Marco
   Guichard, Franoise
TI The past, present and future of African dust
SO NATURE
LA English
DT Article
ID soil-moisture; mineral dust; reanalysis; variability; emission; climate; impact; atmosphere; evolution; transport
AB African dust emission and transport exhibits variability on diurnal(1) to decadal(2) timescales and is known to influence processes such as Amazon productivity(3), Atlantic climate modes(4), regional atmospheric composition and radiative balance(5) and precipitation in the Sahel(6). To elucidate the role of African dust in the climate system, it is necessary to understand the factors governing its emission and transport. However, African dust is correlated with seemingly disparate atmospheric phenomena, including the El Nino/Southern Oscillation(7,8), the North Atlantic Oscillation(9), the meridional position of the intertropical convergence zone(10,11), Sahelian rainfall(8) and surface temperatures over the Sahara Desert(12), all of which obfuscate the connection between dust and climate. Here we show that the surface wind field responsible for most of the variability in North African dust emission reflects the topography of the Sahara, owing to orographic acceleration of the surface flow. As such, the correlations between dust and various climate phenomena probably arise from the projection of the winds associated with these phenomena onto an orographically controlled pattern of wind variability. A 161-year time series of dust from 1851 to 2011, created by projecting this wind field pattern onto surface winds from a historical reanalysis(13), suggests that the highest concentrations of dust occurred from the 1910s to the 1940s and the 1970s to the 1980s, and that there have been three periods of persistent anomalously low dust concentrations-in the 1860s, 1950s and 2000s. Projections of the wind pattern onto climate models give a statistically significant downward trend in African dust emission and transport as greenhouse gas concentrations increase over the twenty-first century, potentially associated with a slow-down of the tropical circulation. Such a dust feedback, which is not represented in climate models, may be of benefit to human and ecosystem health in West Africa via improved air quality(14) and increased rainfall(6). This feedback may also enhance warming of the tropical North Atlantic(15), which would make the basin more suitable for hurricane formation and growth(16).
C1 [Evan, Amato T.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Evan, Amato T.; Flamant, Cyrille; Gaetani, Marco] Sorbonne Univ, Univ Paris 06, Observat Spatiales LATMOS IPSL, Lab Atmospheres,Milieux,UVSQ,CNRS, Paris, France.
   [Guichard, Franoise] CNRS, UMR 3589, CNRM GAME, Toulouse, France.
   [Guichard, Franoise] Meteo France, Toulouse, France.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Universite Paris Saclay; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Evan, AT (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.; Evan, AT (corresponding author), Sorbonne Univ, Univ Paris 06, Observat Spatiales LATMOS IPSL, Lab Atmospheres,Milieux,UVSQ,CNRS, Paris, France.
EM aevan@ucsd.edu
FU Agence Nationale de la Recherche (ANR) of the national Programme Investissements d'Avenir by the Laboratoire d'excellence Institut Pierre Simon Laplace (L-IPSL) [ANR-10-LABX-18-01]
NR 44
TC 197
Z9 221
U1 2
U2 179
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2016
VL 531
IS 7595
BP 493
EP +
DI 10.1038/nature17149
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH3QK
UT WOS:000372701300038
PM 27008968
DA 2026-03-09
ER

PT J
AU Hamilton, NB
   Kolodziejczyk, K
   Kougioumtzidou, E
   Attwell, D
AF Hamilton, Nicola B.
   Kolodziejczyk, Karolina
   Kougioumtzidou, Eleni
   Attwell, David
TI Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia
SO NATURE
LA English
DT Article
ID white-matter; nmda receptors; neuronal death; glial-cells; glutamate; injury; calcium; hypoxia; oligodendrocytes; depolarization
AB The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca2+-dependent manner, abolishing action potential propagation(1,2). This has been attributed to glutamate release activating Ca2+-permeable N-methyl-d-aspartate (NMDA) receptors(2-4). Surprisingly, we now show that NMDA does not raise the intracellular Ca2+ concentration ([Ca2+](i)) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current(4), this is generated by a rise of extracellular [K+] and decrease of membrane K+ conductance. Nevertheless, ischaemia raises oligodendrocyte [Ca2+](i), [Mg2+](i) and [H+](i), and buffering intracellular pH reduces the [Ca2+](i) and [Mg2+](i) increases, showing that these are evoked by the rise of [H+](i). The H+-gated [Ca2+](i) elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.
C1 [Hamilton, Nicola B.; Kolodziejczyk, Karolina; Kougioumtzidou, Eleni; Attwell, David] UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England.
   [Kolodziejczyk, Karolina] Univ British Columbia, Dept Psychiat, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
C3 University of London; University College London; University of British Columbia
RP Hamilton, NB; Attwell, D (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England.
EM nicola.hamilton-whitaker@ucl.ac.uk; d.attwell@ucl.ac.uk
FU Wellcome Trust; ERC Advanced Investigator Award; EU (Leukotreat); Wellcome Trust [099222/Z/12/Z] Funding Source: Wellcome Trust; Wellcome Trust [099222/Z/12/Z] Funding Source: researchfish
NR 33
TC 135
Z9 157
U1 0
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2016
VL 529
IS 7587
BP 523
EP +
DI 10.1038/nature16519
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DB7DD
UT WOS:000368673800036
PM 26760212
DA 2026-03-09
ER

PT J
AU Pittis, AA
   Gabaldón, T
AF Pittis, Alexandros A.
   Gabaldon, Toni
TI Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry
SO NATURE
LA English
DT Article
ID multiple sequence alignment; eukaryotic evolution; common ancestor; origin; orthology; genome; genes; tool
AB The origin of eukaryotes stands as a major conundrum in biology(1). Current evidence indicates that the last eukaryotic common ancestor already possessed many eukaryotic hallmarks, including a complex subcellular organization(1-3). In addition, the lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Mitochondria are ubiquitous organelles derived from an alphaproteobacterial endosymbiont(4). Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis(5). Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote(1,3,6,7). Most competing scenarios can be roughly grouped into either mito-early, which consider the driving force of eukaryogenesis to be mitochondrial endosymbiosis into a simple host, or mito-late, which postulate that a significant complexity predated mitochondrial endosymbiosis(3). Here we provide evidence for late mitochondrial endosymbiosis. We use phylogenomics to directly test whether proto-mitochondrial proteins were acquired earlier or later than other proteins of the last eukaryotic common ancestor. We find that last eukaryotic common ancestor protein families of alphaproteobacterial ancestry and of mitochondrial localization show the shortest phylogenetic distances to their closest prokaryotic relatives, compared with proteins of different prokaryotic origin or cellular localization. Altogether, our results shed new light on a long-standing question and provide compelling support for the late acquisition of mitochondria into a host that already had a proteome of chimaeric phylogenetic origin. We argue that mitochondrial endosymbiosis was one of the ultimate steps in eukaryogenesis and that it provided the definitive selective advantage to mitochondria-bearing eukaryotes over less complex forms.
C1 [Pittis, Alexandros A.; Gabaldon, Toni] Ctr Genom Regulat CRG, Bioinformat & Genom Programme, Carrer Dr Aiguader 88, Barcelona 08003, Spain.
   [Pittis, Alexandros A.; Gabaldon, Toni] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain.
   [Gabaldon, Toni] ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; ICREA
RP Gabaldón, T (corresponding author), Ctr Genom Regulat CRG, Bioinformat & Genom Programme, Carrer Dr Aiguader 88, Barcelona 08003, Spain.; Gabaldón, T (corresponding author), Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain.; Gabaldón, T (corresponding author), ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain.
EM tgabaldon@crg.es
FU Spanish Ministry of Economy and Competitiveness [BIO2012-37161]; European Union [FP7 FP7-PEOPLE-2013-ITN-606786]; European Research Council under the European Union [ERC-2012-StG-310325]; ICREA Funding Source: Custom
NR 30
TC 174
Z9 196
U1 1
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2016
VL 531
IS 7592
BP 101
EP +
DI 10.1038/nature16941
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF2YW
UT WOS:000371211900048
PM 26840490
DA 2026-03-09
ER

PT J
AU Wang, DL
   Garcia, H
   Huang, W
   Tran, DD
   Jain, AD
   Yi, DH
   Gong, Z
   Jech, JM
   Godo, OR
   Makris, NC
   Ratilal, P
AF Wang, Delin
   Garcia, Heriberto
   Huang, Wei
   Tran, Duong D.
   Jain, Ankita D.
   Yi, Dong Hoon
   Gong, Zheng
   Jech, J. Michael
   Godo, Olav Rune
   Makris, Nicholas C.
   Ratilal, Purnima
TI Vast assembly of vocal marine mammals from diverse species on fish spawning ground
SO NATURE
LA English
DT Article
ID passive source localization; herring clupea-harengus; humpback whale songs; fin whales; transmission scintillation; eubalaena-glacialis; foraging behavior; long-distance; orcinus-orca; ocean
AB Observing marine mammal (MM) populations continuously in time and space over the immense ocean areas they inhabit is challenging but essential for gathering an unambiguous record of their distribution, as well as understanding their behaviour and interaction with prey species(1-6). Here we use passive ocean acoustic waveguide remote sensing (POAWRS)(7,8) in an important North Atlantic feeding ground(9,10) to instantaneously detect, localize and classify MM vocalizations from diverse species over an approximately 100,000 km(2) region. More than eight species of vocal MMs are found to spatially converge on fish spawning areas containing massive densely populated herring shoals at night-time(11-16) and diffuse herring distributions during daytime. We find the vocal MMs divide the enormous fish prey field into species-specific foraging areas with varying degrees of spatial overlap, maintained for at least two weeks of the herring spawning period. The recorded vocalization rates are diel (24 h)-dependent for all MM species, with some significantly more vocal at night and others more vocal during the day. The four key baleen whale species of the region: fin, humpback, blue and minke have vocalization rate trends that are highly correlated to trends in fish shoaling density and to each other over the diel cycle. These results reveal the temporospatial dynamics of combined multi-species MM foraging activities in the vicinity of an extensive fish prey field that forms a massive ecological hotspot, and would be unattainable with conventional methodologies. Understanding MM behaviour and distributions is essential for management of marine ecosystems and for accessing anthropogenic impacts on these protected marine species(1-5,17,18).
C1 [Wang, Delin; Garcia, Heriberto; Huang, Wei; Tran, Duong D.; Gong, Zheng; Ratilal, Purnima] Northeastern Univ, Lab Ocean Acoust & Ecosyst Sensing, 360 Huntington Ave, Boston, MA 02115 USA.
   [Jain, Ankita D.; Yi, Dong Hoon; Gong, Zheng; Makris, Nicholas C.] MIT, Lab Undersea Remote Sensing, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
   [Jech, J. Michael] Northeast Fisheries Sci Ctr, 166 Water St, Woods Hole, MA 02543 USA.
   [Godo, Olav Rune] Inst Marine Res, POB 1870, N-5817 Bergen, Norway.
C3 Northeastern University; Massachusetts Institute of Technology (MIT); Institute of Marine Research - Norway
RP Ratilal, P (corresponding author), Northeastern Univ, Lab Ocean Acoust & Ecosyst Sensing, 360 Huntington Ave, Boston, MA 02115 USA.
EM purnima@ece.neu.edu
FU National Oceanographic Partnership Program [321RF/096/06]; US National Science Foundation; US Office of Naval Research (Ocean Acoustics Program); National Oceanographic Partnership Program; US Presidential Early Career Award for Scientists and Engineers; Alfred P. Sloan Foundation; Census of Marine Life; Northeastern University; Division Of Ocean Sciences; Directorate For Geosciences [1550294] Funding Source: National Science Foundation
NR 100
TC 49
Z9 60
U1 4
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2016
VL 531
IS 7594
BP 366
EP +
DI 10.1038/nature16960
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DG4TA
UT WOS:000372064300052
PM 26934221
DA 2026-03-09
ER

PT J
AU Tang, AH
   Chen, HW
   Li, TP
   Metzbower, SR
   MacGillavry, HD
   Blanpied, TA
AF Tang, Ai-Hui
   Chen, Haiwen
   Li, Tuo P.
   Metzbower, Sarah R.
   MacGillavry, Harold D.
   Blanpied, Thomas A.
TI A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
SO NATURE
LA English
DT Article
ID ca2+ channels; imaging reveals; ampa receptors; active zone; microscopy; synapses; probability; hippocampus; endocytosis; depression
AB Synaptic transmission is maintained by a delicate, sub-synaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorders(1,2). Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, while it has long been recognized that this spatial relationship modulates synaptic strength(3), it has not been precisely described, owing in part to the limited resolution of light microscopy. Using localization microscopy, here we show that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometre-scale subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses in cultured rat hippocampal neurons, we find that action-potential-evoked fusion is guided by this protein gradient and occurs preferentially in confined areas with higher local density of Rab3-interacting molecule (RIM) within the active zones. These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins(4-6), suggesting the existence of a trans-synaptic molecular 'nanocolumn'. Thus, we propose that the nanoarchitecture of the active zone directs action-potential-evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor-scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by trans-synaptic nanoscale realignment. This architecture suggests a simple organizational principle of central nervous system synapses to maintain and modulate synaptic efficiency.
C1 [Tang, Ai-Hui; Chen, Haiwen; Li, Tuo P.; Metzbower, Sarah R.; Blanpied, Thomas A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
   [Tang, Ai-Hui; Chen, Haiwen; Li, Tuo P.; Metzbower, Sarah R.; Blanpied, Thomas A.] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
   [Chen, Haiwen; Li, Tuo P.] Univ Maryland, Sch Med, Med Scientist Training Program, Baltimore, MD 21201 USA.
   [MacGillavry, Harold D.] Univ Utrecht, Fac Sci, Dept Biol, Cell Biol, NL-3584 CH Utrecht, Netherlands.
C3 University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; Utrecht University
RP Tang, AH; Blanpied, TA (corresponding author), Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.; Tang, AH; Blanpied, TA (corresponding author), Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
EM tangaihui@gmail.com; tblanpied@som.umaryland.edu
FU [F30-MH105111];  [F30-MH102891];  [F31-MH105105];  [T32-GM008181];  [R01-MH080046];  [NS090644]; National Institute of General Medical Sciences [T32GM008181] Funding Source: NIH RePORTER
NR 50
TC 481
Z9 543
U1 1
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2016
VL 536
IS 7615
BP 210
EP +
DI 10.1038/nature19058
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT4SV
UT WOS:000381472100036
PM 27462810
DA 2026-03-09
ER

PT J
AU Lin, ZH
   Luo, XL
   Yu, HT
AF Lin, Zhonghui
   Luo, Xuelian
   Yu, Hongtao
TI Structural basis of cohesin cleavage by separase
SO NATURE
LA English
DT Article
ID sister-chromatid separation; protein phosphatase 2a; inhibition; anaphase; securin; phosphorylation; localization; activation; substrate; binding
AB Accurate chromosome segregation requires timely dissolution of chromosome cohesion after chromosomes are properly attached to the mitotic spindle. Separase is absolutely essential for cohesion dissolution in organisms from yeast to man(1,2). It cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation. Cohesin cleavage is spatiotemporally controlled by separase-associated regulatory proteins, including the inhibitory chaperone securin(3-6), and by phosphorylation of both the enzyme and substrates(7-12). Dysregulation of this process causes chromosome missegregation and aneuploidy, contributing to cancer and birth defects. Despite its essential functions, atomic structures of separase have not been determined. Here we report crystal structures of the separase protease domain from the thermophilic fungus Chaetomium thermophilum, alone or covalently bound to unphosphorylated and phosphorylated inhibitory peptides derived from a cohesin cleavage site. These structures reveal how separase recognizes cohesin and how cohesin phosphorylation by polo-like kinase 1 ( Plk1) enhances cleavage. Consistent with a previous cellular study(13), mutating two securin residues in a conserved motif that partly matches the separase cleavage consensus converts securin from a separase inhibitor to a substrate. Our study establishes atomic mechanisms of substrate cleavage by separase and suggests competitive inhibition by securin.
C1 [Lin, Zhonghui; Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
   [Lin, Zhonghui; Luo, Xuelian; Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
   [Luo, Xuelian] Univ Texas SW Med Ctr Dallas, Dept Biophys, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
C3 Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Yu, HT (corresponding author), Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, 6001 Forest Pk Rd, Dallas, TX 75390 USA.; Yu, HT (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pharmacol, 6001 Forest Pk Rd, Dallas, TX 75390 USA.
EM hongtao.yu@utsouthwestern.edu
FU Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; Cancer Prevention and Research Institute of Texas [RP110465-P3]; National Institutes of Health [GM107415]; Welch Foundation [I-1441]
NR 36
TC 62
Z9 68
U1 2
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2016
VL 532
IS 7597
BP 131
EP +
DI 10.1038/nature17402
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI5RE
UT WOS:000373555500048
PM 27027290
DA 2026-03-09
ER

PT J
AU Weiss, Y
   Class, C
   Goldstein, SL
   Hanyu, T
AF Weiss, Yaakov
   Class, Cornelia
   Goldstein, Steven L.
   Hanyu, Takeshi
TI Key new pieces of the HIMU puzzle from olivines and diamond inclusions
SO NATURE
LA English
DT Article
ID oceanic island basalts; mantle; pb; isotopes; sr; nd; carbonatite; kimberlites; lavas; crust
AB Mantle melting, which leads to the formation of oceanic and continental crust, together with crust recycling through plate tectonics, are the primary processes that drive the chemical differentiation of the silicate Earth. The present-day mantle, as sampled by oceanic basalts, shows large chemical and isotopic variability bounded by a few end-member compositions(1). Among these, the HIMU end-member (having a high U/Pb ratio, mu) has been generally considered to represent subducted/recycled basaltic oceanic crust(2-5). However, this concept has been challenged by recent studies of the mantle source of HIMU magmas. For example, analyses of olivine phenocrysts in HIMU lavas indicate derivation from the partial melting of peridotite, rather than from the pyroxenitic remnants of recycled oceanic basalt(6). Here we report data that elucidate the source of these lavas: high-precision trace-element analyses of olivine phenocrysts point to peridotite that has been metasomatized by carbonatite fluids. Moreover, similarities in the trace-element patterns of carbonatitic melt inclusions in diamonds(7) and HIMU lavas indicate that the metasomatism occurred in the subcontinental lithospheric mantle, fused to the base of the continental crust and isolated from mantle convection. Taking into account evidence from sulfur isotope data(8) for Archean to early Proterozoic surface material in the deep HIMU mantle source, a multi-stage evolution is revealed for the HIMU end-member, spanning more than half of Earth's history. Before entrainment in the convecting mantle, storage in a boundary layer, upwelling as a mantle plume and partial melting to become ocean island basalt, the HIMU source formed as Archean-early Proterozoic subduction-related carbonatite-metasomatized subcontinental lithospheric mantle.
C1 [Weiss, Yaakov; Class, Cornelia; Goldstein, Steven L.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Goldstein, Steven L.] Columbia Univ, Dept Earth & Environm Sci, Palisades, NY 10964 USA.
   [Hanyu, Takeshi] Japan Agcy Marine Earth Sci & Technol, Dept Solid Earth Geochem, Yokosuka, Kanagawa 2370061, Japan.
C3 Columbia University; Columbia University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Weiss, Y; Class, C; Goldstein, SL (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.; Goldstein, SL (corresponding author), Columbia Univ, Dept Earth & Environm Sci, Palisades, NY 10964 USA.; Hanyu, T (corresponding author), Japan Agcy Marine Earth Sci & Technol, Dept Solid Earth Geochem, Yokosuka, Kanagawa 2370061, Japan.
EM yweiss@ldeo.columbia.edu; class@ldeo.columbia.edu; steveg@ldeo.columbia.edu; hanyut@jamstec.go.jp
FU LDEO Postdoctoral Fellowship; NSF [EAR13-48045]; Storke Endowment of the Columbia University Department of Earth and Environmental Sciences; Grants-in-Aid for Scientific Research [26302010, 26400527] Funding Source: KAKEN; Division Of Earth Sciences; Directorate For Geosciences [1348045] Funding Source: National Science Foundation
NR 44
TC 152
Z9 171
U1 2
U2 131
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2016
VL 537
IS 7622
BP 666
EP +
DI 10.1038/nature19113
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX4DR
UT WOS:000384331700047
PM 27595333
DA 2026-03-09
ER

PT J
AU Lee, JE
   Westrate, LM
   Wu, HX
   Page, C
   Voeltz, GK
AF Lee, Jason E.
   Westrate, Laura M.
   Wu, Haoxi
   Page, Cynthia
   Voeltz, Gia K.
TI Multiple dynamin family members collaborate to drive mitochondrial division
SO NATURE
LA English
DT Article
ID fission; drp1; recruitment; gtpase; cell; endocytosis; tomography; morphology; efficient; dnm1p
AB Mitochondria cannot be generated de novo; they must grow, replicate their genome, and divide in order to be inherited by each daughter cell during mitosis. Mitochondrial division is a structural challenge that requires the substantial remodelling of membrane morphology(1-3). Although division factors differ across organisms, the need for multiple constriction steps and a dynamin-related protein (Drp1, Dnm1 in yeast) has been conserved(4-6). In mammalian cells, mitochondrial division has been shown to proceed with at least two sequential constriction steps: the endoplasmic reticulum and actin must first collaborate to generate constrictions suitable for Drp1 assembly on the mitochondrial outer membrane; Drp1 then further constricts membranes until mitochondrial fission occurs(2,7-9). In vitro experiments, however, indicate that Drp1 does not have the dynamic range to complete membrane fission(7). In contrast to Drp1, the neuron-specific classical dynamin dynamin-1 (Dyn1) has been shown to assemble on narrower lipid profiles and facilitate spontaneous membrane fission upon GTP hydrolysis(10,11). Here we report that the ubiquitously expressed classical dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in three different mammalian cell lines reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events that build up to division. Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.
C1 [Lee, Jason E.; Westrate, Laura M.; Wu, Haoxi; Page, Cynthia; Voeltz, Gia K.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
C3 University of Colorado System; University of Colorado Boulder
RP Voeltz, GK (corresponding author), Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
EM gia.voeltz@colorado.edu
FU National Institutes of Health [GM083977, F32CA174158, F32GM116371, T32GM08759]
NR 36
TC 414
Z9 502
U1 2
U2 95
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 139
EP +
DI 10.1038/nature20555
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600064
PM 27798601
DA 2026-03-09
ER

PT J
AU Fray, N
   Bardyn, A
   Cottin, H
   Altwegg, K
   Baklouti, D
   Briois, C
   Colangeli, L
   Engrand, C
   Fischer, H
   Glasmachers, A
   Grün, E
   Haerendel, G
   Henkel, H
   Höfner, H
   Hornung, K
   Jessberger, EK
   Koch, A
   Krüger, H
   Langevin, Y
   Lehto, H
   Lehto, K
   Le Roy, L
   Merouane, S
   Modica, P
   Orthous-Daunay, FR
   Paquette, J
   Raulin, F
   Rynö, J
   Schulz, R
   Silén, J
   Siljeström, S
   Steiger, W
   Stenzel, O
   Stephan, T
   Thirkell, L
   Thomas, R
   Torkar, K
   Varmuza, K
   Wanczek, KP
   Zaprudin, B
   Kissel, J
   Hilchenbach, M
AF Fray, Nicolas
   Bardyn, Anais
   Cottin, Herve
   Altwegg, Kathrin
   Baklouti, Donia
   Briois, Christelle
   Colangeli, Luigi
   Engrand, Cecile
   Fischer, Henning
   Glasmachers, Albrecht
   Gruen, Eberhard
   Haerendel, Gerhard
   Henkel, Hartmut
   Hoefner, Herwig
   Hornung, Klaus
   Jessberger, Elmar K.
   Koch, Andreas
   Kruger, Harald
   Langevin, Yves
   Lehto, Harry
   Lehto, Kirsi
   Le Roy, Lena
   Merouane, Sihane
   Modica, Paola
   Orthous-Daunay, Francois-Regis
   Paquette, John
   Raulin, Francois
   Ryno, Jouni
   Schulz, Rita
   Silen, Johan
   Siljestrom, Sandra
   Steiger, Wolfgang
   Stenzel, Oliver
   Stephan, Thomas
   Thirkell, Laurent
   Thomas, Roger
   Torkar, Klaus
   Varmuza, Kurt
   Wanczek, Karl-Peter
   Zaprudin, Boris
   Kissel, Jochen
   Hilchenbach, Martin
TI High-molecular-weight organic matter in the particles of comet 67P/Churyumov-Gerasimenko
SO NATURE
LA English
DT Article
ID halley dust particles; mass-spectrometer; solar-system; origin; cosima; chondrites
AB The presence of solid carbonaceous matter in cometary dust was established by the detection of elements such as carbon, hydrogen, oxygen and nitrogen in particles from comet 1P/Halley(1,2). Such matter is generally thought to have originated in the interstellar medium(3), but it might have formed in the solar nebula-the cloud of gas and dust that was left over after the Sun formed(4). This solid carbonaceous material cannot be observed from Earth, so it has eluded unambiguous characterization(5). Many gaseous organic molecules, however, have been observed(6-9); they come mostly from the sublimation of ices at the surface or in the subsurface of cometary nuclei(8). These ices could have been formed from material inherited from the interstellar medium that suffered little processing in the solar nebula(10). Here we report the in situ detection of solid organic matter in the dust particles emitted by comet 67P/Churyumov-Gerasimenko; the carbon in this organic material is bound in very large macromolecular compounds, analogous to the insoluble organic matter found in the carbonaceous chondrite meteorites(11,12). The organic matter in meteorites might have formed in the interstellar medium and/or the solar nebula, but was almost certainly modified in the meteorites' parent bodies(11). We conclude that the observed cometary carbonaceous solid matter could have the same origin as the meteoritic insoluble organic matter, but suffered less modification before and/or after being incorporated into the comet.
C1 [Fray, Nicolas; Bardyn, Anais; Cottin, Herve; Modica, Paola; Raulin, Francois] Univ Paris Est Creteil, UMR CNRS 7583, LISA, F-94000 Creteil, France.
   [Fray, Nicolas; Bardyn, Anais; Cottin, Herve; Modica, Paola; Raulin, Francois] Univ Paris Diderot, Inst Pierre Simon Laplace, F-94000 Creteil, France.
   [Bardyn, Anais; Briois, Christelle; Modica, Paola; Thirkell, Laurent; Thomas, Roger] Univ Orleans, CNRS, LPC2E, F-45071 Orleans, France.
   [Altwegg, Kathrin; Le Roy, Lena] Univ Bern, CSH, Sidlerstr 5, CH-3012 Bern, Switzerland.
   [Baklouti, Donia; Langevin, Yves] Univ Paris Sud, CNRS, Inst Astrophys Spatiale, Batiment 121, F-91405 Orsay, France.
   [Colangeli, Luigi] European Space Agcy, European Space Res & Technol Ctr, Keplerlaan 1,Postbus 299, NL-2200 AG Noordwijk, Netherlands.
   [Engrand, Cecile] Univ Paris Saclay, Univ Paris Sud, CNRS IN2P3, Ctr Sci Nucl & Sci Mat,UMR 8609, F-91405 Orsay, France.
   [Fischer, Henning; Kruger, Harald; Merouane, Sihane; Paquette, John; Stenzel, Oliver; Kissel, Jochen; Hilchenbach, Martin] Max Planck Inst Sonnensyst Forsch, Justus von Liebig Weg 3, D-37077 Gottingen, Germany.
   [Glasmachers, Albrecht] Univ Wuppertal, FB, Lehrstuhl Messtech, Rainer Gruenter Str 21, D-42119 Wuppertal, Germany.
   [Gruen, Eberhard] Max Planck Inst Kernphys, Saupfercheckweg 1, D-69115 Heidelberg, Germany.
   [Haerendel, Gerhard; Hoefner, Herwig] Max Planck Inst Extraterr Phys, Giessenbachstr, D-85748 Garching, Germany.
   [Henkel, Hartmut; Koch, Andreas] von Hoerner & Sulger GmbH, Schlosspl 8, D-68723 Schwetzingen, Germany.
   [Hornung, Klaus] Univ Bundeswehr LRT 7, Werner Heisenberg Weg 39, D-85577 Neubiberg, Germany.
   [Jessberger, Elmar K.] Univ Munster, Inst Planetol, Berghalde 31f, D-69126 Heidelberg, Germany.
   [Lehto, Harry; Zaprudin, Boris] Univ Turku, Dept Phys & Astron, Tuorla Observ, Vaisalantie 20, Piikkio 21500, Finland.
   [Lehto, Kirsi] Univ Turku, Dept Biochem, Lab Mol Plant Biol, PharmaCity, Itainen Pitkakatu 4B 6 Krs, FIN-20520 Turku, Finland.
   [Orthous-Daunay, Francois-Regis] Univ Grenoble Alpes, CNRS, UMR 5274, Inst Planetol & Astrophys Grenoble, F-38000 Grenoble, France.
   [Ryno, Jouni; Silen, Johan] Finnish Meteorol Inst, Observat Serv, Erik Palmenin Aukio 1, Helsinki 00560, Finland.
   [Schulz, Rita] European Space Agcy, Sci Support Off, Keplerlaan 1,Postbus 299, NL-2200 AG Noordwijk, Netherlands.
   [Siljestrom, Sandra] SP Tech Res Inst Sweden, Dept Chem Mat & Surfaces, Box 857, S-50115 Boras, Sweden.
   [Steiger, Wolfgang] RC Seibersdorf Res GmbH Business Field Aerosp Tec, A-2444 Seibersdorf, Austria.
   [Stephan, Thomas] Univ Chicago, Dept Geophys Sci, 5734 South Ellis Ave, Chicago, IL 60637 USA.
   [Torkar, Klaus] Austrian Acad Sci, Space Res Inst, Schmiedlstr 6, A-8042 Graz, Austria.
   [Varmuza, Kurt] Vienna Univ Technol, Inst Stat & Math Methods Econ, Wiedner Hauptstr 7 105-6, A-1040 Vienna, Austria.
   [Wanczek, Karl-Peter] Univ Bremen, Inst Anorgan & Phys Chem, FB 2,NW 2, D-28334 Bremen, Germany.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Universite Paris Cite; Universite Paris Saclay; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Universite de Orleans; University of Bern; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; European Space Agency; European Space Research & Technology Centre; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Max Planck Society; University of Wuppertal; Max Planck Society; Max Planck Society; Bundeswehr University Munich; University of Munster; University of Turku; Finland National Institute for Health & Welfare; University of Turku; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Finnish Meteorological Institute; SP Technical Research Institute of Sweden; University of Chicago; Austrian Academy of Sciences; Technische Universitat Wien; University of Bremen
RP Fray, N (corresponding author), Univ Paris Est Creteil, UMR CNRS 7583, LISA, F-94000 Creteil, France.; Fray, N (corresponding author), Univ Paris Diderot, Inst Pierre Simon Laplace, F-94000 Creteil, France.
EM nicolas.fray@lisa.u-pec.fr
FU Deutsches Zentrum fur Luft- und Raumfahrt (DLR) [50 QP 1302]; Centre National d'Etude Spatiales (CNES); European Space Agency (ESA) Technical Directorate; CNES; Labex Exploration Spatiale des Environnements Planetaires (ESEP) [2011-LABX-030]; Idex Paris Sciences et Lettres (PSL) [ANR-10-IDEX-0001-02]; Swedish National Space Board [121/11, 198/15]; Academy of Finland [277375]; Swedish National Space Agency (SNSA) [198/15, 198/15, 121/11] Funding Source: Swedish National Space Agency (SNSA); Austrian Science Fund (FWF) [P26871] Funding Source: Austrian Science Fund (FWF)
NR 34
TC 139
Z9 144
U1 1
U2 82
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 72
EP +
DI 10.1038/nature19320
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900035
PM 27602514
DA 2026-03-09
ER

PT J
AU Blokzijl, F
   de Ligt, J
   Jager, M
   Sasselli, V
   Roerink, S
   Sasaki, N
   Huch, M
   Boymans, S
   Kuijk, E
   Prins, P
   Nijman, IJ
   Martincorena, I
   Mokry, M
   Wiegerinck, CL
   Middendorp, S
   Sato, T
   Schwank, G
   Nieuwenhuis, EES
   Verstegen, MMA
   van der Laan, LJW
   de Jonge, J
   IJzermans, JNM
   Vries, RG
   van de Wetering, M
   Stratton, MR
   Clevers, H
   Cuppen, E
   van Boxtel, R
AF Blokzijl, Francis
   de Ligt, Joep
   Jager, Myrthe
   Sasselli, Valentina
   Roerink, Sophie
   Sasaki, Nobuo
   Huch, Meritxell
   Boymans, Sander
   Kuijk, Ewart
   Prins, Pjotr
   Nijman, Isaac J.
   Martincorena, Inigo
   Mokry, Michal
   Wiegerinck, Caroline L.
   Middendorp, Sabine
   Sato, Toshiro
   Schwank, Gerald
   Nieuwenhuis, Edward E. S.
   Verstegen, Monique M. A.
   van der Laan, Luc J. W.
   de Jonge, Jeroen
   IJzermans, Jan N. M.
   Vries, Robert G.
   van de Wetering, Marc
   Stratton, Michael R.
   Clevers, Hans
   Cuppen, Edwin
   van Boxtel, Ruben
TI Tissue-specific mutation accumulation in human adult stem cells during life
SO NATURE
LA English
DT Article
ID somatic mutations; clonal hematopoiesis; cancer-risk; age; database; population; signatures; discovery; expansion; alignment
AB The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer(1,2). Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication(1). However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells(3-5). Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues(1). Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.
C1 [Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Boymans, Sander; Kuijk, Ewart; Cuppen, Edwin; van Boxtel, Ruben] Univ Med Ctr Utrecht, Ctr Mol Med, Canc Genom Netherlands, Dept Genet, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
   [Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Sato, Toshiro; Schwank, Gerald; van de Wetering, Marc; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben] KNAW, Hubrecht Inst Dev Biol & Stem Cell Res, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
   [Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Martincorena, Inigo; Sato, Toshiro; Schwank, Gerald; van de Wetering, Marc; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben] Univ Med Ctr Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
   [Roerink, Sophie; Martincorena, Inigo; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.
   [Mokry, Michal; Wiegerinck, Caroline L.; Middendorp, Sabine; Nieuwenhuis, Edward E. S.] Univ Med Ctr Utrecht, Dept Pediat, Lundlaan 6, NL-3584 EA Utrecht, Netherlands.
   [Verstegen, Monique M. A.; van der Laan, Luc J. W.; de Jonge, Jeroen; IJzermans, Jan N. M.] Erasmus MC Univ Med Ctr, Dept Surg, Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
   [Vries, Robert G.] Fdn Hubrecht Organoid Technol HUB, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
C3 Utrecht University; Utrecht University Medical Center; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Wellcome Trust Sanger Institute; Utrecht University; Utrecht University Medical Center; Erasmus University Rotterdam; Erasmus MC
RP Cuppen, E (corresponding author), Univ Med Ctr Utrecht, Ctr Mol Med, Canc Genom Netherlands, Dept Genet, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.; Cuppen, E (corresponding author), KNAW, Hubrecht Inst Dev Biol & Stem Cell Res, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.; Cuppen, E (corresponding author), Univ Med Ctr Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM ecuppen@umcutrecht.nl
FU Zenith grant of the Netherlands Genomics Initiative [935.12.003]; NWO Zwaartekracht program Cancer Genomics.nl; Worldwide Cancer Research (WCR) [16-0193]; Grants-in-Aid for Scientific Research [26293177, 15K15297, 15K08974, 26115007, 16H07176] Funding Source: KAKEN; Versus Arthritis; Cancer Research UK [21777] Funding Source: researchfish
NR 42
TC 716
Z9 811
U1 6
U2 149
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 260
EP +
DI 10.1038/nature19768
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000048
PM 27698416
DA 2026-03-09
ER

PT J
AU Drake, EJ
   Miller, BR
   Shi, C
   Tarrasch, JT
   Sundlov, JA
   Allen, CL
   Skiniotis, G
   Aldrich, CC
   Gulick, AM
AF Drake, Eric J.
   Miller, Bradley R.
   Shi, Ce
   Tarrasch, Jeffrey T.
   Sundlov, Jesse A.
   Allen, C. Leigh
   Skiniotis, Georgios
   Aldrich, Courtney C.
   Gulick, Andrew M.
TI Structures of two distinct conformations of holo-non-ribosomal peptide synthetases
SO NATURE
LA English
DT Article
ID carrier protein; condensation domain; adenylation; crystal; enzyme; mechanism; module; genes
AB Many important natural products are produced by multidomain non-ribosomal peptide synthetases (NRPSs)(1-4). During synthesis, intermediates are covalently bound to integrated carrier domains and transported to neighbouring catalytic domains in an assembly line fashion(5). Understanding the structural basis for catalysis with non-ribosomal peptide synthetases will facilitate bioengineering to create novel products. Here we describe the structures of two different holo-non-ribosomal peptide synthetase modules, each revealing a distinct step in the catalytic cycle. One structure depicts the carrier domain cofactor bound to the peptide bond-forming condensation domain, whereas a second structure captures the installation of the amino acid onto the cofactor within the adenylation domain. These structures demonstrate that a conformational change within the adenylation domain guides transfer of intermediates between domains. Furthermore, one structure shows that the condensation and adenylation domains simultaneously adopt their catalytic conformations, increasing the overall efficiency in a revised structural cycle. These structures and the single-particle electron microscopy analysis demonstrate a highly dynamic domain architecture and provide the foundation for understanding the structural mechanisms that could enable engineering of novel non-ribosomal peptide synthetases.
C1 [Drake, Eric J.; Miller, Bradley R.; Sundlov, Jesse A.; Allen, C. Leigh; Gulick, Andrew M.] Hauptman Woodward Med Res Inst, Buffalo, NY 14203 USA.
   [Drake, Eric J.; Miller, Bradley R.; Sundlov, Jesse A.; Gulick, Andrew M.] SUNY Buffalo, Dept Biol Struct, Buffalo, NY 14203 USA.
   [Shi, Ce; Aldrich, Courtney C.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA.
   [Shi, Ce; Aldrich, Courtney C.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
   [Tarrasch, Jeffrey T.; Skiniotis, Georgios] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA.
   [Tarrasch, Jeffrey T.; Skiniotis, Georgios] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
C3 Hauptman Woodward Medical Research Institute; State University of New York (SUNY) System; University at Buffalo, SUNY; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Gulick, AM (corresponding author), Hauptman Woodward Med Res Inst, 700 Ellicott St, Buffalo, NY 14203 USA.
EM gulick@hwi.buffalo.edu
FU National Institutes of Health [GM-068440, GM-115601]; Telemedicine and Advanced Technology Research Center of the US Army Medical Research and Materiel Command [W81XWH-11-2-0218]; National Cancer Institute [ACB-12002]; National Institute of General Medical Sciences under Department of Energy [AGM-12006, DE-AC02-06CH11357]; Hauptman-Woodward Institute
NR 46
TC 195
Z9 255
U1 1
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 235
EP U289
DI 10.1038/nature16163
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700042
PM 26762461
DA 2026-03-09
ER

PT J
AU Dahl, JA
   Jung, I
   Aanes, H
   Greggains, GD
   Manaf, A
   Lerdrup, M
   Li, GQ
   Kuan, S
   Li, B
   Lee, AY
   Preissl, S
   Jermstad, I
   Haugen, MH
   Suganthan, R
   Bjorås, M
   Hansen, K
   Dalen, KT
   Fedorcsak, P
   Ren, B
   Klungland, A
AF Dahl, John Arne
   Jung, Inkyung
   Aanes, Havard
   Greggains, Gareth D.
   Manaf, Adeel
   Lerdrup, Mads
   Li, Guoqiang
   Kuan, Samantha
   Li, Bin
   Lee, Ah Young
   Preissl, Sebastian
   Jermstad, Ingunn
   Haugen, Mads Haugland
   Suganthan, Rajikala
   Bjoras, Magnar
   Hansen, Klaus
   Dalen, Knut Tomas
   Fedorcsak, Peter
   Ren, Bing
   Klungland, Arne
TI Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition
SO NATURE
LA English
DT Article
ID dna methylation; chip-seq; chromatin; demethylation; replication; expression; landscape; sequences; lysine-4; dynamics
AB Maternal-to-zygotic transition (MZT) is essential for the formation of a new individual, but is still poorly understood despite recent progress in analysis of gene expression and DNA methylation in early embryogenesis(1-9). Dynamic histone modifications may have important roles in MZT(10-13), but direct measurements of chromatin states have been hindered by technical difficulties in profiling histone modifications from small quantities of cells. Recent improvements allow for 500 cell-equivalents of chromatin per reaction, but require 10,000 cells for initial steps(14) or require a highly specialized microfluidics device that is not readily available(15). We developed a micro-scale chromatin immunoprecipitation and sequencing (mu ChIP-seq) method, which we used to profile genome-wide histone H3 lysine methylation (H3K4me3) and acetylation (H3K27ac) in mouse immature and metaphase II oocytes and in 2-cell and 8-cell embryos. Notably, we show that similar to 22% of the oocyte genome is associated with broad H3K4me3 domains that are anti-correlated with DNA methylation. The H3K4me3 signal becomes confined to transcriptional-start-site regions in 2-cell embryos, concomitant with the onset of major zygotic genome activation. Active removal of broad H3K4me3 domains by the lysine demethylases KDM5A and KDM5B is required for normal zygotic genome activation and is essential for early embryo development. Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT.
C1 [Dahl, John Arne; Aanes, Havard; Manaf, Adeel; Suganthan, Rajikala; Bjoras, Magnar; Klungland, Arne] Natl Hosp Norway, Oslo Univ Hosp, Dept Microbiol, NO-0027 Oslo, Norway.
   [Jung, Inkyung; Li, Guoqiang; Kuan, Samantha; Li, Bin; Lee, Ah Young; Preissl, Sebastian; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Greggains, Gareth D.; Fedorcsak, Peter] Natl Hosp Norway, Oslo Univ Hosp, Sect Reprod Med, Dept Gynecol, NO-0027 Oslo, Norway.
   [Lerdrup, Mads; Hansen, Klaus] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark.
   [Lerdrup, Mads; Hansen, Klaus] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark.
   [Jermstad, Ingunn; Dalen, Knut Tomas] Univ Oslo, Inst Basic Med Sci, Norwegian Transgen Ctr, NO-0317 Oslo, Norway.
   [Haugen, Mads Haugland] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Tumor Biol, NO-0424 Oslo, Norway.
   [Haugen, Mads Haugland] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Canc Genet, Inst Canc Res, NO-0424 Oslo, Norway.
   [Bjoras, Magnar] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, NO-7491 Trondheim, Norway.
   [Dalen, Knut Tomas] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Fac Med, NO-0027 Oslo, Norway.
   [Ren, Bing] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Ren, Bing] Univ Calif San Diego, UCSD Moores Canc Ctr, La Jolla, CA 92093 USA.
   [Klungland, Arne] Univ Oslo, Inst Basic Med Sci, Dept Mol Med, NO-0317 Oslo, Norway.
C3 University of Oslo; National Hospital Norway; Ludwig Institute for Cancer Research; University of Oslo; National Hospital Norway; University of Copenhagen; University of Copenhagen; University of Oslo; University of Oslo; University of Oslo; Norwegian University of Science & Technology (NTNU); University of Oslo; University of California System; University of California San Diego; University of California System; University of California San Diego; University of Oslo
RP Dahl, JA; Klungland, A (corresponding author), Natl Hosp Norway, Oslo Univ Hosp, Dept Microbiol, NO-0027 Oslo, Norway.; Ren, B (corresponding author), Ludwig Inst Canc Res, La Jolla, CA 92093 USA.; Ren, B (corresponding author), Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.; Ren, B (corresponding author), Univ Calif San Diego, UCSD Moores Canc Ctr, La Jolla, CA 92093 USA.; Klungland, A (corresponding author), Univ Oslo, Inst Basic Med Sci, Dept Mol Med, NO-0317 Oslo, Norway.
EM j.a.dahl@medisin.uio.no; biren@ucsd.edu; arne.klungland@medisin.uio.no
FU Ludwig Institute for Cancer Research [U54HG006997]; American Heart Association; Oslo University Hospital; Norwegian Cancer Society; Anders Jahre Foundation; Norwegian Research council
NR 41
TC 495
Z9 571
U1 5
U2 175
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2016
VL 537
IS 7621
BP 548
EP +
DI 10.1038/nature19360
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DW3MO
UT WOS:000383545900056
PM 27626377
DA 2026-03-09
ER

PT J
AU Key, HM
   Dydio, P
   Clark, DS
   Hartwig, JF
AF Key, Hanna M.
   Dydio, Pawel
   Clark, Douglas S.
   Hartwig, John F.
TI Abiological catalysis by artificial haem proteins containing noble metals in place of iron
SO NATURE
LA English
DT Article
ID enantioselective catalysis; olefin cyclopropanation; directed evolution; metalloenzymes; complexes; hydroxylation; myoglobin; cytochrome-p450; insertion
AB Enzymes that contain metal ions-that is, metalloenzymes-possess the reactivity of a transition metal centre and the potential of molecular evolution to modulate the reactivity and substrate-selectivity of the system(1). By exploiting substrate promiscuity and protein engineering, the scope of reactions catalysed by native metalloenzymes has been expanded recently to include abiological transformations(2,3). However, this strategy is limited by the inherent reactivity of metal centres in native metalloenzymes. To overcome this limitation, artificial metalloproteins have been created by incorporating complete, noble-metal complexes within proteins lacking native metal sites(1,4,5). The interactions of the substrate with the protein in these systems are, however, distinct from those with the native protein because the metal complex occupies the substrate binding site. At the intersection of these approaches lies a third strategy, in which the native metal of a metalloenzyme is replaced with an abiological metal with reactivity different from that of the metal in a native protein(6-8). This strategy could create artificial enzymes for abiological catalysis within the natural substrate binding site of an enzyme that can be subjected to directed evolution. Here we report the formal replacement of iron in Fe-porphyrin IX (Fe-PIX) proteins with abiological, noble metals to create enzymes that catalyse reactions not catalysed by native Fe-enzymes or other metalloenzymes(9,10). In particular, we prepared modified myoglobins containing an Ir(Me) site that catalyse the functionalization of C-H bonds to form C-C bonds by carbene insertion and add carbenes to both beta-substituted vinylarenes and unactivated aliphatic alpha-olefins. We conducted directed evolution of the Ir(Me)-myoglobin and generated mutants that form either enantiomer of the products of C-H insertion and catalyse the enantio-and diastereoselective cyclopropanation of unactivated olefins. The presented method of preparing artificial haem proteins containing abiological metal porphyrins sets the stage for the generation of artificial enzymes from innumerable combinations of PIX-protein scaffolds and unnatural metal cofactors to catalyse a wide range of abiological transformations.
C1 [Key, Hanna M.; Dydio, Pawel; Hartwig, John F.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Key, Hanna M.; Dydio, Pawel; Hartwig, John F.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, 1 Cyclotron Rd, Berkeley, CA 94720 USA.
   [Clark, Douglas S.] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA.
   [Clark, Douglas S.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, 1 Cyclotron Rd, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Hartwig, JF (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Hartwig, JF (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, 1 Cyclotron Rd, Berkeley, CA 94720 USA.
EM jhartwig@berkeley.edu
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; NSF; NWO Netherlands Organization for Scientific Research [680-50-1306]; NIH [1S10RR022393-01]
NR 30
TC 343
Z9 405
U1 9
U2 520
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 534
EP 537
DI 10.1038/nature17968
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300050
PM 27296224
DA 2026-03-09
ER

PT J
AU Martinez, J
   Cunha, LD
   Park, S
   Yang, M
   Lu, Q
   Orchard, R
   Li, QZ
   Yan, M
   Janke, L
   Guy, C
   Linkermann, A
   Virgin, HW
   Green, DR
AF Martinez, Jennifer
   Cunha, Larissa D.
   Park, Sunmin
   Yang, Mao
   Lu, Qun
   Orchard, Robert
   Li, Quan-Zhen
   Yan, Mei
   Janke, Laura
   Guy, Cliff
   Linkermann, Andreas
   Virgin, Herbert W.
   Green, Douglas R.
TI RETRACTED: Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID autoimmune-disease; erythematosus; phagocytosis; clearance; il-10; mice; susceptibility; association; macrophages; proteins
AB Defects in clearance of dying cells have been proposed to underlie the pathogenesis of systemic lupus erythematosus (SLE)(1). Mice lacking molecules associated with dying cell clearance develop SLE-like disease(2), and phagocytes from patients with SLE often display defective clearance and increased inflammatory cytokine production when exposed to dying cells in vitro. Previously, we(3-6) and others(7) described a form of noncanonical autophagy known as LC3-associated phagocytosis (LAP), in which phagosomes containing engulfed particles, including dying cells(3,4,7), recruit elements of the autophagy pathway to facilitate maturation of phagosomes and digestion of their contents. Genome-wide association studies have identified polymorphisms in the Atg5 (ref. 8) and possibly Atg7 (ref. 9) genes, involved in both canonical autophagy and LAP(3-7), as markers of a predisposition for SLE. Here we describe the consequences of defective LAP in vivo. Mice lacking any of several components of the LAP pathway show increased serum levels of inflammatory cytokines and autoantibodies, glomerular immune complex deposition, and evidence of kidney damage. When dying cells are injected into LAP-deficient mice, they are engulfed but not efficiently degraded and trigger acute elevation of pro-inflammatory cytokines but not anti-inflammatory interleukin (IL)-10. Repeated injection of dying cells into LAP-deficient, but not LAP-sufficient, mice accelerated the development of SLE-like disease, including increased serum levels of autoantibodies. By contrast, mice deficient in genes required for canonical autophagy but not LAP do not display defective dying cell clearance, inflammatory cytokine production, or SLE-like disease, and, like wild-type mice, produce IL-10 in response to dying cells. Therefore, defects in LAP, rather than canonical autophagy, can cause SLE-like phenomena, and may contribute to the pathogenesis of SLE.
C1 [Martinez, Jennifer; Cunha, Larissa D.; Yang, Mao; Janke, Laura; Guy, Cliff; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
   [Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
   [Park, Sunmin; Lu, Qun; Orchard, Robert; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Li, Quan-Zhen; Yan, Mei] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Linkermann, Andreas] Univ Kiel, Div Nephrol & Hypertens, D-24105 Kiel, Germany.
C3 St Jude Children's Research Hospital; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; University of Kiel
RP Martinez, J; Green, DR (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.; Martinez, J (corresponding author), NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jennifer.martinez3@nih.gov; douglas.green@stjude.org
FU Intramural Research Program of the National Institutes of Health, NIEHS [1ZIAES10328601]; US National Institutes of Health [RO1 AI40646, U19 AI109725]; Lupus Research Institute; German Research Foundation [EXC306]; ALSAC; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007163, R01AI040646] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [ZIAES103286, ZICES102445] Funding Source: NIH RePORTER
NR 29
TC 314
Z9 355
U1 2
U2 92
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2016
VL 533
IS 7601
BP 115
EP +
DI 10.1038/nature17950
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DL2OE
UT WOS:000375473900050
PM 27096368
DA 2026-03-09
ER

PT J
AU Browne, HP
   Forster, SC
   Anonye, BO
   Kumar, N
   Neville, BA
   Stares, MD
   Goulding, D
   Lawley, TD
AF Browne, Hilary P.
   Forster, Samuel C.
   Anonye, Blessing O.
   Kumar, Nitin
   Neville, B. Anne
   Stares, Mark D.
   Goulding, David
   Lawley, Trevor D.
TI Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation
SO NATURE
LA English
DT Article
ID clostridium-difficile; gen. nov.; identification; alignment; catalog; genm; trees
AB Our intestinal microbiota harbours a diverse bacterial community required for our health, sustenance and wellbeing(1,2). Intestinal colonization begins at birth and climaxes with the acquisition of two dominant groups of strict anaerobic bacteria belonging to the Firmicutes and Bacteroidetes phyla(2). Culture-independent, genomic approaches have transformed our understanding of the role of the human microbiome in health and many diseases(1). However, owing to the prevailing perception that our indigenous bacteria are largely recalcitrant to culture, many of their functions and phenotypes remain unknown(3). Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale whole-genome sequencing, phylogenetic analysis and computational modelling that demonstrates that a substantial proportion of the intestinal bacteria are culturable. Applying this approach to healthy individuals, we isolated 137 bacterial species from characterized and candidate novel families, genera and species that were archived as pure cultures. Whole-genome and metagenomic sequencing, combined with computational and phenotypic analysis, suggests that at least 50-60% of the bacterial genera from the intestinal microbiota of a healthy individual produce resilient spores, specialized for host-to-host transmission. Our approach unlocks the human intestinal microbiota for phenotypic analysis and reveals how a marked proportion of oxygen-sensitive intestinal bacteria can be transmitted between individuals, affecting microbiota heritability.
C1 [Browne, Hilary P.; Forster, Samuel C.; Anonye, Blessing O.; Kumar, Nitin; Neville, B. Anne; Stares, Mark D.; Lawley, Trevor D.] Wellcome Trust Sanger Inst, Host Microbiota Interact Lab, Hinxton CB10 1SA, England.
   [Forster, Samuel C.] Hudson Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic 3168, Australia.
   [Forster, Samuel C.] Monash Univ, Dept Mol & Translat Sci, Clayton, Vic 3800, Australia.
   [Goulding, David] Wellcome Trust Sanger Inst, Microbial Pathogenesis Lab, Hinxton CB10 1SA, England.
C3 Wellcome Trust Sanger Institute; Hudson Institute of Medical Research; Monash University; Wellcome Trust Sanger Institute
RP Lawley, TD (corresponding author), Wellcome Trust Sanger Inst, Host Microbiota Interact Lab, Hinxton CB10 1SA, England.
EM tl2@sanger.ac.uk
FU Wellcome Trust [098051]; United Kingdom Medical Research Council [PF451]; Australian National Health and Medical Research Council [1091097]; Victorian Government; Wellcome Trust Sanger Institute Technology Translation team; Medical Research Council [MR/K000551/1, G1000214] Funding Source: researchfish; MRC [MR/K000551/1, G1000214] Funding Source: UKRI
NR 40
TC 870
Z9 1096
U1 6
U2 280
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 543
EP +
DI 10.1038/nature17645
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100043
PM 27144353
DA 2026-03-09
ER

PT J
AU Hudry, B
   Khadayate, S
   Miguel-Aliaga, I
AF Hudry, Bruno
   Khadayate, Sanjay
   Miguel-Aliaga, Irene
TI The sexual identity of adult intestinal stem cells controls organ size and plasticity
SO NATURE
LA English
DT Article
ID drosophila-melanogaster; genetic feminization; cytogenetic analysis; nervous-system; doublesex gene; male courtship; fruitless; behavior; protein; midgut
AB Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles(1,2). Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cellspecific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex-and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized.
C1 [Hudry, Bruno; Khadayate, Sanjay; Miguel-Aliaga, Irene] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
C3 Imperial College London
RP Hudry, B; Miguel-Aliaga, I (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Hammersmith Campus,Du Cane Rd, London W12 0NN, England.
EM bruno.hudry@imperial.ac.uk; i.miguel-aliaga@imperial.ac.uk
FU European Research Council [310411] Funding Source: Medline; Medical Research Council [MC_UP_1102/3] Funding Source: Medline; BBSRC [BB/N000528/1] Funding Source: UKRI; MRC [MC_UP_1102/3] Funding Source: UKRI; European Research Council (ERC) [310411] Funding Source: European Research Council (ERC); Biotechnology and Biological Sciences Research Council [BB/N000528/1] Funding Source: researchfish; Medical Research Council [MC_UP_1102/3] Funding Source: researchfish
NR 94
TC 144
Z9 161
U1 0
U2 41
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2016
VL 530
IS 7590
BP 344
EP +
DI 10.1038/nature16953
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DE0PP
UT WOS:000370327100039
PM 26887495
DA 2026-03-09
ER

PT J
AU Worrall, LJ
   Hong, C
   Vuckovic, M
   Deng, W
   Bergeron, JRC
   Majewski, DD
   Huang, RK
   Spreter, T
   Finlay, BB
   Yu, Z
   Strynadka, NCJ
AF Worrall, L. J.
   Hong, C.
   Vuckovic, M.
   Deng, W.
   Bergeron, J. R. C.
   Majewski, D. D.
   Huang, R. K.
   Spreter, T.
   Finlay, B. B.
   Yu, Z.
   Strynadka, N. C. J.
TI Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body
SO NATURE
LA English
DT Article
ID iii secretion system; structural-characterization; membrane insertion; needle complex; protein; model; identification; visualization; validation; platform
AB The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular assembly spans both bacterial membranes and that of the infected host cell. The internal channel formed by the injectisome allows for the direct delivery of partially unfolded virulence effectors into the host cytoplasm(1). The structural foundation of the injectisome is the basal body, a molecular lock-nut structure composed predominantly of three proteins that form highly oligomerized concentric rings spanning the inner and outer membranes(2-5). Here we present the structure of the prototypical Salmonella enterica serovar Typhimurium pathogenicity island 1 basal body, determined using single-particle cryo-electron microscopy, with the inner-membrane-ring and outer-membranering oligomers defined at 4.3 angstrom and 3.6 angstrom resolution, respectively. This work presents the first, to our knowledge, high-resolution structural characterization of the major components of the basal body in the assembled state, including that of the widespread class of outer-membrane portals known as secretins.
C1 [Worrall, L. J.; Vuckovic, M.; Bergeron, J. R. C.; Majewski, D. D.; Spreter, T.; Strynadka, N. C. J.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
   [Worrall, L. J.; Vuckovic, M.; Bergeron, J. R. C.; Majewski, D. D.; Spreter, T.; Strynadka, N. C. J.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada.
   [Hong, C.; Huang, R. K.; Yu, Z.] Howard Hughes Med Inst, CryoEM Shared Resources, Janelia Res Campus, Ashburn, VA 20147 USA.
   [Deng, W.; Finlay, B. B.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada.
   [Bergeron, J. R. C.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Spreter, T.] Zymeworks, Vancouver, BC V6H 3V9, Canada.
C3 University of British Columbia; University of British Columbia; Howard Hughes Medical Institute; University of British Columbia; University of Washington; University of Washington Seattle
RP Strynadka, NCJ (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.; Strynadka, NCJ (corresponding author), Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada.; Yu, Z (corresponding author), Howard Hughes Med Inst, CryoEM Shared Resources, Janelia Res Campus, Ashburn, VA 20147 USA.
EM yuz@janelia.hhmi.org; ncjs@mail.ubc.ca
FU Canadian Institutes of Health Research (CIHR); Michael Smith Foundation of Health Research; CIHR; Howard Hughes International Senior Scholar program; Canada Research Chair in Antibiotic Discovery
NR 59
TC 105
Z9 118
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2016
VL 540
IS 7634
BP 597
EP +
DI 10.1038/nature20576
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EG6XV
UT WOS:000391190500055
PM 27974800
DA 2026-03-09
ER

PT J
AU Larsen, IJ
   Lamb, MP
AF Larsen, Isaac J.
   Lamb, Michael P.
TI Progressive incision of the Channeled Scablands by outburst floods
SO NATURE
LA English
DT Article
ID canyon; bed; erosion; gorge; water; transport; insights; gravel; model; earth
AB The surfaces of Earth and Mars contain large bedrock canyons that were carved by catastrophic outburst floods(1,2). Reconstructing the magnitude of these canyon-forming floods is essential for understanding the ways in which floods modify planetary surfaces(1,2), the hydrology of early Mars(3) and abrupt changes in climate(4). Flood discharges are often estimated by assuming that the floods filled the canyons to their brims with water; however, an alternative hypothesis is that canyon morphology adjusts during incision such that bed shear stresses exceed the threshold for erosion by a small amount(5). Here we show that accounting for erosion thresholds during canyon incision results in near-constant discharges that are five-to ten-fold smaller than full-to-the-brim estimates for Moses Coulee, a canyon in the Channeled Scablands, which was carved during the Pleistocene by the catastrophic Missoula floods in eastern Washington, USA. The predicted discharges are consistent with flow-depth indicators from gravel bars within the canyon. In contrast, under the assumption that floods filled canyons to their brims, a large and monotonic increase in flood discharge is predicted as the canyon was progressively incised, which is at odds with the discharges expected for floods originating from glacial lake outbursts. These findings suggest that flood-carved landscapes in fractured rock might evolve to a threshold state for bedrock erosion, thus implying much lower flood discharges than previously thought.
C1 [Larsen, Isaac J.] Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.
   [Larsen, Isaac J.; Lamb, Michael P.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
C3 University of Massachusetts System; University of Massachusetts Amherst; California Institute of Technology
RP Larsen, IJ (corresponding author), Univ Massachusetts, Dept Geosci, Amherst, MA 01003 USA.; Larsen, IJ (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM ilarsen@umass.edu
FU Caltech Texaco Prize Postdoctoral Fellowship; NSF [1529528, 1529110]; NASA [NNX13AM83G]; NASA [469234, NNX13AM83G] Funding Source: Federal RePORTER; Directorate For Geosciences; Division Of Earth Sciences [1529528, 1529110] Funding Source: National Science Foundation
NR 41
TC 101
Z9 120
U1 8
U2 79
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2016
VL 538
IS 7624
BP 229
EP +
DI 10.1038/nature19817
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OS
UT WOS:000386671000042
PM 27734850
DA 2026-03-09
ER

PT J
AU Wei, XP
   Su, XD
   Cao, P
   Liu, XY
   Chang, WR
   Li, M
   Zhang, XZ
   Liu, ZF
AF Wei, Xuepeng
   Su, Xiaodong
   Cao, Peng
   Liu, Xiuying
   Chang, Wenrui
   Li, Mei
   Zhang, Xinzheng
   Liu, Zhenfeng
TI Structure of spinach photosystem II-LHCII supercomplex at 3.2 Å resolution
SO NATURE
LA English
DT Article
ID light-harvesting complex; excitation-energy transfer; higher-plants; crystal-structure; spectroscopic characterization; supramolecular organization; functional architecture; 3-dimensional structure; binding-protein; cross-linking
AB During photosynthesis, the plant photosystem II core complex receives excitation energy from the peripheral light-harvesting complex II (LHCII). The pathways along which excitation energy is transferred between them, and their assembly mechanisms, remain to be deciphered through high-resolution structural studies. Here we report the structure of a 1.1-megadalton spinach photosystem II-LHCII supercomplex solved at 3.2 angstrom resolution through single-particle cryo-electron microscopy. The structure reveals a homodimeric supramolecular system in which each monomer contains 25 protein subunits, 105 chlorophylls, 28 carotenoids and other cofactors. Three extrinsic subunits (PsbO, PsbP and PsbQ), which are essential for optimal oxygen-evolving activity of photosystem II, form a triangular crown that shields the Mn4CaO5-binding domains of CP43 and D1. One major trimeric and two minor monomeric LHCIIs associate with each core-complex monomer, and the antenna-core interactions are reinforced by three small intrinsic subunits (PsbW, PsbH and PsbZ). By analysing the closely connected interfacial chlorophylls, we have obtained detailed insights into the energy-transfer pathways between the antenna and core complexes.
C1 [Wei, Xuepeng; Su, Xiaodong; Cao, Peng; Liu, Xiuying; Chang, Wenrui; Li, Mei; Zhang, Xinzheng; Liu, Zhenfeng] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Wei, Xuepeng; Liu, Xiuying] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
RP Li, M; Zhang, XZ (corresponding author), Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
EM meili@moon.ibp.ac.cn; xzzhang@ibp.ac.cn
FU National 973 project [2011CBA00900]; Strategic Priority Research Program of CAS [XDB08020302]; National Natural Science Foundation of China [31570724, 31270793, 31170703]; 'National Thousand (Young) Talents Program' from the Office of Global Experts Recruitment in China
NR 66
TC 486
Z9 551
U1 8
U2 439
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 69
EP +
DI 10.1038/nature18020
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300034
PM 27251276
DA 2026-03-09
ER

PT J
AU Dejean, C
   Courtin, J
   Karalis, N
   Chaudun, F
   Wurtz, H
   Bienvenu, TCM
   Herry, C
AF Dejean, Cyril
   Courtin, Julien
   Karalis, Nikolaos
   Chaudun, Fabrice
   Wurtz, Helene
   Bienvenu, Thomas C. M.
   Herry, Cyril
TI Prefrontal neuronal assemblies temporally control fear behaviour
SO NATURE
LA English
DT Article
ID cell assembly; cortex; hippocampus; expression; amygdala; oscillations; interneuron; circuits; patterns; rat
AB Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing(1-6). In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity(7,8). Whereas this form of coding has been described for sensory processing and spatial learning(9-12), its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression(13-16). In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli(14,17-19). However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses.
C1 [Dejean, Cyril; Courtin, Julien; Karalis, Nikolaos; Chaudun, Fabrice; Wurtz, Helene; Bienvenu, Thomas C. M.; Herry, Cyril] Neuroctr Magendie, INSERM, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.
   [Dejean, Cyril; Courtin, Julien; Karalis, Nikolaos; Chaudun, Fabrice; Wurtz, Helene; Bienvenu, Thomas C. M.; Herry, Cyril] Univ Bordeaux, Neuroctr Magendie, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.
   [Courtin, Julien] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
   [Karalis, Nikolaos] Univ Munich, Fac Med, D-82152 Planegg Martinsried, Germany.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm); Friedrich Miescher Institute for Biomedical Research; University of Munich
RP Dejean, C; Herry, C (corresponding author), Neuroctr Magendie, INSERM, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.; Dejean, C; Herry, C (corresponding author), Univ Bordeaux, Neuroctr Magendie, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.
EM cyril.dejean@scilight.eu; cyril.herry@inserm.fr
FU French National Research Agency [ANR-10-EQPX-08 OPTOPATH]; French National Research Agency (LABEX BRAIN) [ANR 10-LABX-43]; French National Research Agency (LABEX TRAIL) [ANR 10-LABX-57]; European Research Council (ERC) under European Union/ERC [281168]; Conseil Regional d'Aquitaine; European Research Council (ERC) [281168] Funding Source: European Research Council (ERC)
NR 37
TC 159
Z9 179
U1 0
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 420
EP +
DI 10.1038/nature18630
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200040
PM 27409809
DA 2026-03-09
ER

PT J
AU Perry, M
   Kinoshita, M
   Saldi, G
   Huo, L
   Arikawa, K
   Desplan, C
AF Perry, Michael
   Kinoshita, Michiyo
   Saldi, Giuseppe
   Huo, Lucy
   Arikawa, Kentaro
   Desplan, Claude
TI Molecular logic behind the three-way stochastic choices that expand butterfly colour vision
SO NATURE
LA English
DT Article
ID 2 visual pigments; histological localization; photoreceptor cells; expression; drosophila; eye; receptor; retina; opsins; gene
AB Butterflies rely extensively on colour vision to adapt to the natural world. Most species express a broad range of colour-sensitive Rhodopsin proteins in three types of ommatidia (unit eyes), which are distributed stochastically across the retina(1-3). The retinas of Drosophila melanogaster use just two main types, in which fate is controlled by the binary stochastic decision to express the transcription factor Spineless in R7 photoreceptors(4). We investigated how butterflies instead generate three stochastically distributed ommatidial types, resulting in a more diverse retinal mosaic that provides the basis for additional colour comparisons and an expanded range of colour vision. We show that the Japanese yellow swallowtail (Papilio xuthus, Papilionidae) and the painted lady (Vanessa cardui, Nymphalidae) butterflies have a second R7-like photoreceptor in each ommatidium. Independent stochastic expression of Spineless in each R7-like cell results in expression of a blue-sensitive (SpinelessON) or an ultraviolet (UV)-sensitive (Spineless(OFF)) Rhodopsin. In P. xuthus these choices of blue/blue, blue/UV or UV/UV sensitivity in the two R7 cells are coordinated with expression of additional Rhodopsin proteins in the remaining photoreceptors, and together define the three types of ommatidia. Knocking out spineless using CRISPR/Cas9 (refs 5, 6) leads to the loss of the blue-sensitive fate in R7-like cells and transforms retinas into homogeneous fields of UV/UV-type ommatidia, with corresponding changes in other coordinated features of ommatidial type. Hence, the three possible outcomes of Spineless expression define the three ommatidial types in butterflies. This developmental strategy allowed the deployment of an additional red-sensitive Rhodopsin in P. xuthus, allowing for the evolution of expanded colour vision with a greater variety of receptors(7,8). This surprisingly simple mechanism that makes use of two binary stochastic decisions coupled with local coordination may prove to be a general means of generating an increased diversity of developmental outcomes.
C1 [Perry, Michael; Huo, Lucy; Desplan, Claude] NYU, Dept Biol, New York, NY 10003 USA.
   [Kinoshita, Michiyo; Arikawa, Kentaro] Grad Univ Adv Studies, Dept Evolutionary Studies Biosyst, Lab Neuroethol, SOKENDAI, Hayama, Kanagawa 2400115, Japan.
   [Saldi, Giuseppe; Desplan, Claude] New York Univ Abu Dhabi, Abu Dhabi, U Arab Emirates.
C3 New York University; Graduate University for Advanced Studies - Japan; New York University; New York University Abu Dhabi
RP Desplan, C (corresponding author), NYU, Dept Biol, New York, NY 10003 USA.; Desplan, C (corresponding author), New York Univ Abu Dhabi, Abu Dhabi, U Arab Emirates.
EM cd38@nyu.edu
FU NIH [EY13010]; Center for Genomics and Systems Biology of NYU Abu Dhabi; JSPS [26251036, 20167232]; NIH Ruth L. Kirschstein NRSA; JSPS Short Term Fellowship award; Revson Biomedical Research Foundation Postdoctoral Fellowship; National Eye Institute [P30EY013079, R01EY013010] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [26650117, 26251036] Funding Source: KAKEN
NR 36
TC 98
Z9 117
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 280
EP +
DI 10.1038/nature18616
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600056
PM 27383790
DA 2026-03-09
ER

PT J
AU Murphy, BP
   Johnson, JPL
   Gasparini, NM
   Sklar, LS
AF Murphy, Brendan P.
   Johnson, Joel P. L.
   Gasparini, Nicole M.
   Sklar, Leonard S.
TI Chemical weathering as a mechanism for the climatic control of bedrock river incision
SO NATURE
LA English
DT Article
ID profile evolution; kohala volcano; schmidt hammer; big island; erosion; precipitation; landscape; rates; erodibility; gradients
AB Feedbacks between climate, erosion and tectonics influence the rates of chemical weathering reactions(1,2), which can consume atmospheric CO2 and modulate global climate(3,4). However, quantitative predictions for the coupling of these feedbacks are limited because the specific mechanisms by which climate controls erosion are poorly understood. Here we show that climate-dependent chemical weathering controls the erodibility of bedrock-floored rivers across a rainfall gradient on the Big Island of Hawai'i. Field data demonstrate that the physical strength of bedrock in streambeds varies with the degree of chemical weathering, which increases systematically with local rainfall rate. We find that incorporating the quantified relationships between local rainfall and erodibility into a commonly used river incision model is necessary to predict the rates and patterns of downcutting of these rivers. In contrast to using only precipitation-dependent river discharge to explain the climatic control of bedrock river incision(5,6), the mechanism of chemical weathering can explain strong coupling between local climate and river incision.
C1 [Murphy, Brendan P.; Johnson, Joel P. L.] Univ Texas Austin, Dept Geol Sci, Austin, TX 78712 USA.
   [Gasparini, Nicole M.] Tulane Univ, Dept Earth & Environm Sci, New Orleans, LA 70118 USA.
   [Sklar, Leonard S.] San Francisco State Univ, Dept Earth & Climate Sci, San Francisco, CA 94132 USA.
C3 University of Texas System; University of Texas Austin; Tulane University; California State University System; San Francisco State University
RP Murphy, BP (corresponding author), Univ Texas Austin, Dept Geol Sci, Austin, TX 78712 USA.
EM bpmurphy@utexas.edu
FU NSF [EAR-1024982, EAR-1025055]; Tulane Research Enhancement grant; NSF; NCALM; Division Of Earth Sciences; Directorate For Geosciences [1339015] Funding Source: National Science Foundation
NR 46
TC 105
Z9 130
U1 7
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2016
VL 532
IS 7598
BP 223
EP +
DI 10.1038/nature17449
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7TJ
UT WOS:000374415100037
PM 27075099
DA 2026-03-09
ER

PT J
AU Sommer, A
   Bothschafter, EM
   Sato, SA
   Jakubeit, C
   Latka, T
   Razskazovskaya, O
   Fattahi, H
   Jobst, M
   Schweinberger, W
   Shirvanyan, V
   Yakovlev, VS
   Kienberger, R
   Yabana, K
   Karpowicz, N
   Schultze, M
   Krausz, F
AF Sommer, A.
   Bothschafter, E. M.
   Sato, S. A.
   Jakubeit, C.
   Latka, T.
   Razskazovskaya, O.
   Fattahi, H.
   Jobst, M.
   Schweinberger, W.
   Shirvanyan, V.
   Yakovlev, V. S.
   Kienberger, R.
   Yabana, K.
   Karpowicz, N.
   Schultze, M.
   Krausz, F.
TI Attosecond nonlinear polarization and light-matter energy transfer in solids
SO NATURE
LA English
DT Article
ID refractive-index; field; generation
AB Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization(1,2) produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques(3-8) have provided experimental access to this important observable up to frequencies of several terahertz(9-13). Here we demonstrate that attosecond metrology(14) extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per angstrom) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light-matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible-infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per angstrom) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device.
C1 [Sommer, A.; Bothschafter, E. M.; Jakubeit, C.; Latka, T.; Razskazovskaya, O.; Fattahi, H.; Jobst, M.; Schweinberger, W.; Shirvanyan, V.; Yakovlev, V. S.; Karpowicz, N.; Schultze, M.; Krausz, F.] Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
   [Bothschafter, E. M.; Schweinberger, W.; Schultze, M.; Krausz, F.] Univ Munich, Fak Phys, Coulombwall 1, D-85748 Garching, Germany.
   [Sato, S. A.; Yabana, K.] Univ Tsukuba, Grad Sch Pure & Appl Sci, Tsukuba, Ibaraki 3058571, Japan.
   [Yakovlev, V. S.] Georgia State Univ, Ctr Nanoopt, Atlanta, GA 30303 USA.
   [Yakovlev, V. S.] Georgia State Univ, Dept Phys & Astron, Atlanta, GA 30303 USA.
   [Kienberger, R.] Tech Univ Munich, Dept Phys, James Franck Str 1, D-85748 Garching, Germany.
   [Yabana, K.] Univ Tsukuba, Ctr Computat Sci, Tsukuba, Ibaraki 3058577, Japan.
   [Bothschafter, E. M.] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
C3 Max Planck Society; University of Munich; University of Tsukuba; University System of Georgia; Georgia State University; University System of Georgia; Georgia State University; Technical University of Munich; University of Tsukuba; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute
RP Schultze, M; Krausz, F (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.; Schultze, M; Krausz, F (corresponding author), Univ Munich, Fak Phys, Coulombwall 1, D-85748 Garching, Germany.
EM martin.schultze@mpq.mpg.de; ferenc.krausz@mpq.mpg.de
FU Max Planck Society; Deutsche Forschungsgemeinschaft Cluster of Excellence: Munich Centre for Advanced Photonics; Marie Curie International Outgoing Fellowship [FP7-PEOPLE-2011-IOF]; European Community's Seventh Framework Programme [290605]; Swiss National Science Foundation through NCCR MUST; US Air Force Office of Scientific Research [FA9550-16-1-0073]; RIKEN Advanced Institute for Computational Science through the HPCI System Research project [hp140103]; Grants-in-Aid for Scientific Research [14J01511, 15H03674] Funding Source: KAKEN
NR 30
TC 209
Z9 226
U1 2
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2016
VL 534
IS 7605
BP 86
EP 90
DI 10.1038/nature17650
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DN3LB
UT WOS:000376962300038
PM 27251280
DA 2026-03-09
ER

PT J
AU Schmitt, M
   Wenzel, M
   Böttcher, F
   Ferrier-Barbut, I
   Pfau, T
AF Schmitt, Matthias
   Wenzel, Matthias
   Boettcher, Fabian
   Ferrier-Barbut, Igor
   Pfau, Tilman
TI Self-bound droplets of a dilute magnetic quantum liquid
SO NATURE
LA English
DT Article
ID helium nanodroplets
AB Self-bound many-body systems are formed through a balance of attractive and repulsive forces and occur in many physical scenarios. Liquid droplets are an example of a self-bound system, formed by a balance of the mutual attractive and repulsive forces that derive from different components of the inter-particle potential. It has been suggested(1,2) that self-bound ensembles of ultracold atoms should exist for atom number densities that are 10(8) times lower than in a helium droplet, which is formed from a dense quantum liquid. However, such ensembles have been elusive up to now because they require forces other than the usual zero-range contact interaction, which is either attractive or repulsive but never both. On the basis of the recent finding that an unstable bosonic dipolar gas can be stabilized by a repulsive many-body term(3), it was predicted that three-dimensional self-bound quantum droplets of magnetic atoms should exist(4,5). Here we report the observation of such droplets in a trap-free levitation field. We find that this dilute magnetic quantum liquid requires a minimum, critical number of atoms, below which the liquid evaporates into an expanding gas as a result of the quantum pressure of the individual constituents. Consequently, around this critical atom number we observe an interaction-driven phase transition between a gas and a self-bound liquid in the quantum degenerate regime with ultracold atoms. These droplets are the dilute counterpart of strongly correlated self-bound systems such as atomic nuclei(6) and helium droplets(7).
C1 [Schmitt, Matthias; Wenzel, Matthias; Boettcher, Fabian; Ferrier-Barbut, Igor; Pfau, Tilman] Univ Stuttgart, Phys Inst 5, Pfaffenwaldring 57, D-70550 Stuttgart, Germany.
   [Schmitt, Matthias; Wenzel, Matthias; Boettcher, Fabian; Ferrier-Barbut, Igor; Pfau, Tilman] Univ Stuttgart, Ctr Integrated Quantum Sci & Technol, Pfaffenwaldring 57, D-70550 Stuttgart, Germany.
C3 University of Stuttgart; University of Stuttgart
RP Schmitt, M; Pfau, T (corresponding author), Univ Stuttgart, Phys Inst 5, Pfaffenwaldring 57, D-70550 Stuttgart, Germany.; Schmitt, M; Pfau, T (corresponding author), Univ Stuttgart, Ctr Integrated Quantum Sci & Technol, Pfaffenwaldring 57, D-70550 Stuttgart, Germany.
EM m.schmitt@physik.uni-stuttgart.de; t.pfau@physik.uni-stuttgart.de
FU German Research Foundation (DFG) [SFB/TRR21]; FOR [2247]; EU within Horizon2020 Marie Sklodowska Curie IF [703419]; Marie Curie Actions (MSCA) [703419] Funding Source: Marie Curie Actions (MSCA)
NR 22
TC 484
Z9 523
U1 2
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2016
VL 539
IS 7628
BP 259
EP +
DI 10.1038/nature20126
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EB4CZ
UT WOS:000387318500038
PM 27830811
DA 2026-03-09
ER

PT J
AU Izotov, YI
   Orlitová, I
   Schaerer, D
   Thuan, TX
   Verhamme, A
   Guseva, NG
   Worseck, G
AF Izotov, Y. I.
   Orlitova, I.
   Schaerer, D.
   Thuan, T. X.
   Verhamme, A.
   Guseva, N. G.
   Worseck, G.
TI Eight per cent leakage of Lyman continuum photons from a compact, star-forming dwarf galaxy
SO NATURE
LA English
DT Article
ID emission-line galaxy; starburst galaxy; ly-alpha; sky; ultraviolet; dust; reionization; metallicity; extinction; radiation
AB One of the key questions in observational cosmology is the identification of the sources responsible for ionization of the Universe after the cosmic 'Dark Ages', when the baryonic matter was neutral. The currently identified distant galaxies are insufficient to fully reionize the Universe by redshift z approximate to 6 (refs 1-3), but low-mass, star-forming galaxies are thought to be responsible for the bulk of the ionizing radiation(4-6). As direct observations at high redshift are difficult for a variety of reasons, one solution is to identify local proxies of this galaxy population. Starburst galaxies at low redshifts, however, generally are opaque to Lyman continuum photons(7-9). Small escape fractions of about 1 to 3 per cent, insufficient to ionize much surrounding gas, have been detected only in three low-redshift galaxies(10,11). Here we report far-ultraviolet observations of the nearby low-mass star-forming galaxy J0925+ 1403. The galaxy is leaking ionizing radiation with an escape fraction of about 8 per cent. The total number of photons emitted during the starburst phase is sufficient to ionize intergalactic medium material that is about 40 times as massive as the stellar mass of the galaxy.
C1 [Izotov, Y. I.; Guseva, N. G.] Natl Acad Sci Ukraine, Main Astron Observ, 27 Zabolotnoho St, UA-03680 Kiev, Ukraine.
   [Orlitova, I.] Acad Sci Czech Republ, Inst Astron, Prague 14100, Czech Republic.
   [Schaerer, D.; Verhamme, A.] Univ Geneva, Observ Geneve, CH-1290 Versoix, Switzerland.
   [Schaerer, D.] CNRS, IRAP, F-31400 Toulouse, France.
   [Thuan, T. X.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Worseck, G.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 National Academy of Sciences Ukraine; Main Astronomical Observatory of NASU; Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; University of Geneva; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of Virginia; Max Planck Society
RP Izotov, YI (corresponding author), Natl Acad Sci Ukraine, Main Astron Observ, 27 Zabolotnoho St, UA-03680 Kiev, Ukraine.
EM izotov@mao.kiev.ua
FU NASA [NAS 5-26555]; NASA from STScI [HST-GO-13744.001-A]; Czech Science Foundation [GACR 14-20666P]; NASA
NR 53
TC 249
Z9 286
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2016
VL 529
IS 7585
BP 178
EP 180
DI 10.1038/nature16456
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA7WK
UT WOS:000368015700029
PM 26762455
DA 2026-03-09
ER

PT J
AU Borsanyi, S
   Fodor, Z
   Guenther, J
   Kampert, KH
   Katz, SD
   Kawanai, T
   Kovacs, TG
   Mages, SW
   Pasztor, A
   Pittler, F
   Redondo, J
   Ringwald, A
   Szabo, KK
AF Borsanyi, S.
   Fodor, Z.
   Guenther, J.
   Kampert, K. -H.
   Katz, S. D.
   Kawanai, T.
   Kovacs, T. G.
   Mages, S. W.
   Pasztor, A.
   Pittler, F.
   Redondo, J.
   Ringwald, A.
   Szabo, K. K.
TI Calculation of the axion mass based on high-temperature lattice quantum chromodynamics
SO NATURE
LA English
DT Article
ID qcd
AB Unlike the electroweak sector of the standard model of particle physics, quantum chromodynamics (QCD) is surprisingly symmetric under time reversal. As there is no obvious reason for QCD being so symmetric, this phenomenon poses a theoretical problem, often referred to as the strong CP problem. The most attractive solution for this(1) requires the existence of a new particle, the axion(2,3)-a promising dark-matter candidate. Here we determine the axion mass using lattice QCD, assuming that these particles are the dominant component of dark matter. The key quantities of the calculation are the equation of state of the Universe and the temperature dependence of the topological susceptibility of QCD, a quantity that is notoriously difficult to calculate4-8, especially in the most relevant high-temperature region (up to several gigaelectronvolts). But by splitting the vacuum into different sectors and re-defining the fermionic determinants, its controlled calculation becomes feasible. Thus, our twofold prediction helps most cosmological calculations(9) to describe the evolution of the early Universe by using the equation of state, and may be decisive for guiding experiments looking for dark-matter axions. In the next couple of years, it should be possible to confirm or rule out post-inflation axions experimentally, depending on whether the axion mass is found to be as predicted here. Alternatively, in a pre-inflation scenario, our calculation determines the universal axionic angle that corresponds to the initial condition of our Universe.
C1 [Borsanyi, S.; Fodor, Z.; Guenther, J.; Kampert, K. -H.; Pasztor, A.; Szabo, K. K.] Univ Wuppertal, Dept Phys, D-42119 Wuppertal, Germany.
   [Fodor, Z.; Kawanai, T.; Mages, S. W.; Szabo, K. K.] Forschungszentrum Julich, Julich Supercomp Ctr, D-52428 Julich, Germany.
   [Fodor, Z.; Katz, S. D.; Pittler, F.] Eotvos Lorand Univ, Inst Theoret Phys, H-1117 Budapest, Hungary.
   [Katz, S. D.; Pittler, F.] MTA ELTE Lendulet Lattice Gauge Theory Res Grp, H-1117 Budapest, Hungary.
   [Kovacs, T. G.] Hungarian Acad Sci, Inst Nucl Res, H-4026 Debrecen, Hungary.
   [Redondo, J.] Univ Zaragoza, E-50009 Zaragoza, Spain.
   [Redondo, J.] Max Planck Inst Phys & Astrophys, D-80803 Munich, Germany.
   [Ringwald, A.] DESY, D-22607 Hamburg, Germany.
C3 University of Wuppertal; Helmholtz Association; Julich Research Centre; Eotvos Lorand University; HUN-REN; HUN-REN Institute for Nuclear Research; Hungarian Academy of Sciences; University of Zaragoza; Max Planck Society; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY)
RP Fodor, Z (corresponding author), Univ Wuppertal, Dept Phys, D-42119 Wuppertal, Germany.; Fodor, Z (corresponding author), Forschungszentrum Julich, Julich Supercomp Ctr, D-52428 Julich, Germany.; Fodor, Z (corresponding author), Eotvos Lorand Univ, Inst Theoret Phys, H-1117 Budapest, Hungary.
EM fodor@bodri.elte.hu
FU DFG [SFB/TR55]; OTKA [OTKA-K-113034]; Hungarian Academy of Sciences under 'Lendulet' [LP 2011-011]; Ramon y Cajal Fellowship; MINECO/FEDER [FPA2015-65745-P]
NR 34
TC 598
Z9 647
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2016
VL 539
IS 7627
BP 69
EP +
DI 10.1038/nature20115
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5OJ
UT WOS:000386670100030
PM 27808190
DA 2026-03-09
ER

PT J
AU Badalyan, A
   Stahl, SS
AF Badalyan, Artavazd
   Stahl, Shannon S.
TI Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators
SO NATURE
LA English
DT Article
ID mechanism; electrooxidation; catalysis; aldehydes; amines; cells
AB The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis(1-7). Small-molecule electrocatalysts for processes of this type are promising targets for further development(8), as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen(9-11). Complexes with tethered amines that resemble the active site of hydrogenases(12) have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes(11,13) and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance(14). Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however(15). Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation(5-7,16-19). These catalysts exhibit good activity (1-2 turnovers per second) with a wide range of alcohols(18) and have great promise for electro-organic synthesis(7). Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2'-bipyridine) Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2'-bipyridine) Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how electron-proton-transfer mediators, such as TEMPO, may be used in combination with first-row transition metals, such as copper, to achieve efficient two-electron electrochemical processes, thereby introducing a new concept for the development of non-precious-metal electrocatalysts.
C1 [Badalyan, Artavazd; Stahl, Shannon S.] Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Stahl, SS (corresponding author), Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA.
EM stahl@chem.wisc.edu
FU Great Lakes Bioenergy Research Center (Department of Energy Biological and Environmental Research Office of Science) [DE-FC02-07ER64494]
NR 30
TC 444
Z9 495
U1 45
U2 1118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2016
VL 535
IS 7612
BP 406
EP 410
DI 10.1038/nature18008
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS1GQ
UT WOS:000380344200037
PM 27350245
DA 2026-03-09
ER

PT J
AU Ding, HY
   Smith, RG
   Poleg-Polsky, A
   Diamond, JS
   Briggman, KL
AF Ding, Huayu
   Smith, Robert G.
   Poleg-Polsky, Alon
   Diamond, Jeffrey S.
   Briggman, Kevin L.
TI Species-specific wiring for direction selectivity in the mammalian retina
SO NATURE
LA English
DT Article
ID starburst amacrine cells; rabbit retina; mouse retina; ganglion-cells; neural computation; synaptic input; axial length; dendrites; circuit; motion
AB Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC-SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli.
C1 [Ding, Huayu; Poleg-Polsky, Alon; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, Bethesda, MD 20892 USA.
   [Smith, Robert G.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA.
   [Briggman, Kevin L.] Max Planck Inst Med Res, Dept Biomed Opt, Jahnstr 29, D-69120 Heidelberg, Germany.
   [Briggman, Kevin L.] NINDS, Circuit Dynam & Connect Unit, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); University of Pennsylvania; Max Planck Society; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RP Briggman, KL (corresponding author), Max Planck Inst Med Res, Dept Biomed Opt, Jahnstr 29, D-69120 Heidelberg, Germany.; Briggman, KL (corresponding author), NINDS, Circuit Dynam & Connect Unit, Bethesda, MD 20892 USA.
EM kevin.briggman@nih.gov
FU NIH [EY016607, EY022070]; NINDS [NS003145, NS003133]; Max-Planck Society; Pew Charitable Trusts; National Institute of Neurological Disorders and Stroke [ZIANS003145] Funding Source: NIH RePORTER
NR 47
TC 149
Z9 185
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 105
EP +
DI 10.1038/nature18609
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600033
PM 27350241
DA 2026-03-09
ER

PT J
AU Sugiura, T
   Wang, H
   Barsacchi, R
   Simon, A
   Tanaka, EM
AF Sugiura, Takuji
   Wang, Heng
   Barsacchi, Rico
   Simon, Andras
   Tanaka, Elly M.
TI MARCKS-like protein is an initiating molecule in axolotl appendage regeneration
SO NATURE
LA English
DT Article
ID limb regeneration; ambystoma-mexicanum; cdna library; cells; expression; family; brain
AB Identifying key molecules that launch regeneration has been a long-sought goal. Multiple regenerative animals show an initial wound-associated proliferative response that transits into sustained proliferation if a considerable portion of the body part has been removed(1-3). In the axolotl, appendage amputation initiates a round of wound-associated cell cycle induction followed by continued proliferation that is dependent on nerve-derived signals(4,5). A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Here, using an expression cloning strategy followed by in vivo gain-and loss-of-function assays, we identified axolotl MARCKS-like protein (MLP) as an extracellularly released factor that induces the initial cell cycle response during axolotl appendage regeneration. The identification of a regeneration-initiating molecule opens the possibility of understanding how to elicit regeneration in other animals.
C1 [Sugiura, Takuji; Tanaka, Elly M.] Tech Univ Dresden, DFG Res Ctr Regenerat Therapies CRTD, Fetscherstr 105, D-01307 Dresden, Germany.
   [Sugiura, Takuji; Barsacchi, Rico; Tanaka, Elly M.] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
   [Wang, Heng; Simon, Andras] Karolinska Inst, Dept Cell & Mol Biol, Ctr Dev Biol Regenerat Med, SE-17177 Stockholm, Sweden.
   [Sugiura, Takuji; Tanaka, Elly M.] Tech Univ Dresden, DFG Res Ctr Regenerat Therapies, Fetscherstr 105, D-01307 Dresden, Germany.
C3 Technische Universitat Dresden; Max Planck Society; Karolinska Institutet; Technische Universitat Dresden
RP Sugiura, T; Tanaka, EM (corresponding author), Tech Univ Dresden, DFG Res Ctr Regenerat Therapies CRTD, Fetscherstr 105, D-01307 Dresden, Germany.; Sugiura, T; Tanaka, EM (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.; Sugiura, T; Tanaka, EM (corresponding author), Tech Univ Dresden, DFG Res Ctr Regenerat Therapies, Fetscherstr 105, D-01307 Dresden, Germany.
EM takuji.sugiura@crt-dresden.de; elly.tanaka@crt-dresden.de
FU German Federal Ministry of Education and Research (BMBF) Biofutures grant; German Research Foundation (DFG) [TA274/5-1]; European Research Council; Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG); DFG Research Center for Regenerative Therapies Dresden (CRTD); Swedish Research Council; Cancerfonden
NR 27
TC 106
Z9 114
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2016
VL 531
IS 7593
BP 237
EP +
DI 10.1038/nature16974
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DF9EZ
UT WOS:000371665100042
PM 26934225
DA 2026-03-09
ER

PT J
AU Doppler, J
   Mailybaev, AA
   Böhm, J
   Kuhl, U
   Girschik, A
   Libisch, F
   Milburn, TJ
   Rabl, P
   Moiseyev, N
   Rotter, S
AF Doppler, Jorg
   Mailybaev, Alexei A.
   Bohm, Julian
   Kuhl, Ulrich
   Girschik, Adrian
   Libisch, Florian
   Milburn, Thomas J.
   Rabl, Peter
   Moiseyev, Nimrod
   Rotter, Stefan
TI Dynamically encircling an exceptional point for asymmetric mode switching
SO NATURE
LA English
DT Article
ID laser; degeneracy
AB Physical systems with loss or gain have resonant modes that decay or grow exponentially with time. Whenever two such modes coalesce both in their resonant frequency and their rate of decay or growth, an 'exceptional point' occurs, giving rise to fascinating phenomena that defy our physical intuition(1-6). Particularly intriguing behaviour is predicted to appear when an exceptional point is encircled sufficiently slowly(7,8), such as a state-flip or the accumulation of a geometric phase(9,10). The topological structure of exceptional points has been experimentally explored(11-13), but a full dynamical encircling of such a point and the associated breakdown of adiabaticity(14-21) have remained out of reach of measurement. Here we demonstrate that a dynamical encircling of an exceptional point is analogous to the scattering through a two-mode waveguide with suitably designed boundaries and losses. We present experimental results from a corresponding waveguide structure that steers incoming waves around an exceptional point during the transmission process. In this way, mode transitions are induced that transform this device into a robust and asymmetric switch between different waveguide modes. This work will enable the exploration of exceptional point physics in system control and state transfer schemes at the crossroads between fundamental research and practical applications.
C1 [Doppler, Jorg; Girschik, Adrian; Libisch, Florian; Rotter, Stefan] Vienna Univ Technol TU Wien, Inst Theoret Phys, A-1040 Vienna, Austria.
   [Mailybaev, Alexei A.] Inst Nacl Matemat Pura & Aplicada IMPA, BR-22460320 Rio De Janeiro, Brazil.
   [Bohm, Julian; Kuhl, Ulrich] Univ Nice Sophia Antipolis, Lab Phys Mat Condensee, CNRS, UMR 7336, F-06108 Nice, France.
   [Milburn, Thomas J.; Rabl, Peter] Vienna Univ Technol TU Wien, Atominst, Vienna Ctr Quantum Sci & Technol, A-1020 Vienna, Austria.
   [Moiseyev, Nimrod] Technion Israel Inst Technol, Schulich Fac Chem, IL-32000 Haifa, Israel.
   [Moiseyev, Nimrod] Technion Israel Inst Technol, Fac Phys, IL-32000 Haifa, Israel.
C3 Technische Universitat Wien; Instituto Nacional de Matematica Pura e Aplicada (IMPA); Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Technische Universitat Wien; Technion Israel Institute of Technology; Technion Israel Institute of Technology
RP Rotter, S (corresponding author), Vienna Univ Technol TU Wien, Inst Theoret Phys, A-1040 Vienna, Austria.; Mailybaev, AA (corresponding author), Inst Nacl Matemat Pura & Aplicada IMPA, BR-22460320 Rio De Janeiro, Brazil.; Kuhl, U (corresponding author), Univ Nice Sophia Antipolis, Lab Phys Mat Condensee, CNRS, UMR 7336, F-06108 Nice, France.
EM alexei@impa.br; ulrich.kuhl@unice.fr; stefan.rotter@tuwien.ac.at
FU Austrian Science Fund (FWF) [SFB IR-ON F25-14, SFB-NextLite F49-P10, 11142- N27]; National Council for Scientific and Technological Development (CNPq) [302351/2015-9]; FAPERJ [E-26/210.874/2014]; ANR [11142-N27]; FWF [SFB-F41, DK CoQuS W 1210, SFB FOQUS F40]; START [Y 591-N16]; OPSOQI of the WWTF [316607]; I-Core (the Israeli Excellence Center 'Circle of Light'); Israel Science Foundation [298/11, 1530/15]; Austrian Science Fund (FWF) [I 1142] Funding Source: researchfish; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 31
TC 895
Z9 1000
U1 21
U2 317
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2016
VL 537
IS 7618
BP 76
EP 79
DI 10.1038/nature18605
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DU7XC
UT WOS:000382426900041
PM 27454554
DA 2026-03-09
ER

PT J
AU Lee, MH
   Appleton, KM
   Strungs, EG
   Kwon, JY
   Morinelli, TA
   Peterson, YK
   Laporte, SA
   Luttrell, LM
AF Lee, Mi-Hye
   Appleton, Kathryn M.
   Strungs, Erik G.
   Kwon, Joshua Y.
   Morinelli, Thomas A.
   Peterson, Yuri K.
   Laporte, Stephane A.
   Luttrell, Louis M.
TI The conformational signature of β-arrestin2 predicts its trafficking and signalling functions
SO NATURE
LA English
DT Article
ID protein-coupled receptors; beta-arrestin; crystal-structure; clathrin adapter; biased agonism; endocytosis; activation; mechanism; phosphorylation; desensitization
AB Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling(1,2). Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits(3,4). Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'(5,6). Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters(7) to monitor conformational changes in beta-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of a-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in beta-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average a-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands(8,9) and in identifying factors that dictate arrestin conformation and function.
C1 [Lee, Mi-Hye; Appleton, Kathryn M.; Strungs, Erik G.; Kwon, Joshua Y.; Morinelli, Thomas A.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
   [Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
   [Laporte, Stephane A.] McGill Univ, Res Inst, Ctr Hlth, Dept Med, Quebec City, PQ H4A 3J1, Canada.
   [Laporte, Stephane A.] McGill Univ, Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada.
   [Laporte, Stephane A.] McGill Univ, Anat & Cell Biol, Quebec City, PQ H3A 0C7, Canada.
   [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA.
C3 Medical University of South Carolina; Medical University of South Carolina; McGill University; McGill University; McGill University; US Department of Veterans Affairs; Veterans Health Administration (VHA); Ralph H Johnson VA Medical Center
RP Luttrell, LM (corresponding author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.; Luttrell, LM (corresponding author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA.
EM luttrell@musc.edu
FU National Institutes of Health [DK055524, GM095497, RR027777]; Dialysis Clinics, Inc.; Research Service of the Charleston, SC Veterans Affairs Medical Center; Canadian Institutes of Health [MOP-74603]; National Institute of General Medical Sciences [T32GM008716] Funding Source: NIH RePORTER
NR 34
TC 177
Z9 209
U1 2
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 665
EP +
DI 10.1038/nature17154
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400044
PM 27007854
DA 2026-03-09
ER

PT J
AU Chen, JY
   Miyanishi, M
   Wang, SK
   Yamazaki, S
   Sinha, R
   Kao, KS
   Seita, J
   Sahoo, D
   Nakauchi, H
   Weissman, IL
AF Chen, James Y.
   Miyanishi, Masanori
   Wang, Sean K.
   Yamazaki, Satoshi
   Sinha, Rahul
   Kao, Kevin S.
   Seita, Jun
   Sahoo, Debashis
   Nakauchi, Hiromitsu
   Weissman, Irving L.
TI Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche
SO NATURE
LA English
DT Article
ID bone-marrow; in-vivo; differentiation; reconstitution; progenitors; expression
AB Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation(1), complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal(2-4), differentiation, ageing, niche(5), and diversity(6-8). Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs.
C1 [Chen, James Y.; Miyanishi, Masanori; Wang, Sean K.; Sinha, Rahul; Kao, Kevin S.; Seita, Jun; Sahoo, Debashis; Nakauchi, Hiromitsu; Weissman, Irving L.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA.
   [Chen, James Y.; Miyanishi, Masanori; Wang, Sean K.; Sinha, Rahul; Kao, Kevin S.; Sahoo, Debashis; Weissman, Irving L.] Stanford Univ, Ludwig Ctr Canc Stem Cell Res & Med, Sch Med, Stanford, CA 94305 USA.
   [Yamazaki, Satoshi; Nakauchi, Hiromitsu] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Stem Cell Therapy, Tokyo 1088639, Japan.
   [Sahoo, Debashis] Univ Calif San Diego, Dept Pediat, San Diego, CA 92123 USA.
   [Sahoo, Debashis] Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92123 USA.
C3 Stanford University; Stanford University; University of Tokyo; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Weissman, IL (corresponding author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA.
EM supamasa@stanford.edu; irv@stanford.edu
FU NCI; NHLBI of the NIH [R01 CA086065, U01 HL099999, R01 HL058770]; Virginia and D. K. Ludwig Fund for Cancer Research; Stanford University Medical Scientist Training Program [T32 GM007365]; NHLBI Ruth L. Kirschstein National Research Service Award [F30-HL122096]; Human Frontier Science Program Long-Term Fellowships; Uehara Memorial Foundation Research Fellowship; Toyobo Biotechnology Foundation Research Fellowship; Kanzawa Medical Research Foundation Overseas study grants; Grants-in-Aid for Scientific Research [16H02661, 25640044] Funding Source: KAKEN; National Institute of General Medical Sciences [T32GM007365] Funding Source: NIH RePORTER
NR 34
TC 259
Z9 319
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 223
EP +
DI 10.1038/nature16943
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700040
PM 26863982
DA 2026-03-09
ER

PT J
AU Tan, J
   Pieper, K
   Piccoli, L
   Abdi, A
   Foglierini, M
   Geiger, R
   Tully, CM
   Jarrossay, D
   Ndungu, FM
   Wambua, J
   Bejon, P
   Fregni, CS
   Fernandez-Rodriguez, B
   Barbieri, S
   Bianchi, S
   Marsh, K
   Thathy, V
   Corti, D
   Sallusto, F
   Bull, P
   Lanzavecchia, A
AF Tan, Joshua
   Pieper, Kathrin
   Piccoli, Luca
   Abdi, Abdirahman
   Foglierini, Mathilde
   Geiger, Roger
   Tully, Claire Maria
   Jarrossay, David
   Ndungu, Francis Maina
   Wambua, Juliana
   Bejon, Philip
   Fregni, Chiara Silacci
   Fernandez-Rodriguez, Blanca
   Barbieri, Sonia
   Bianchi, Siro
   Marsh, Kevin
   Thathy, Vandana
   Corti, Davide
   Sallusto, Federica
   Bull, Peter
   Lanzavecchia, Antonio
TI A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens
SO NATURE
LA English
DT Article
ID plasmodium-falciparum; v(d)j recombinase; life-cycle; gene; transposition; deletions; lymphoma; targets; surface; genome
AB Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies(1-4). Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 98 amino acid collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B-cell clone and carry distinct somatic mutations in the LAIR1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine.
C1 [Tan, Joshua; Pieper, Kathrin; Piccoli, Luca; Foglierini, Mathilde; Geiger, Roger; Jarrossay, David; Fregni, Chiara Silacci; Fernandez-Rodriguez, Blanca; Barbieri, Sonia; Sallusto, Federica; Lanzavecchia, Antonio] Univ Svizzera Italiana, Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
   [Tan, Joshua; Abdi, Abdirahman; Tully, Claire Maria; Ndungu, Francis Maina; Wambua, Juliana; Bejon, Philip; Marsh, Kevin; Thathy, Vandana; Bull, Peter] CGMRC, KEMRI Wellcome Trust Res Programme, POB 230, Kilifi 80108, Kenya.
   [Tan, Joshua; Bejon, Philip; Marsh, Kevin; Bull, Peter] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England.
   [Geiger, Roger; Lanzavecchia, Antonio] Swiss Fed Inst Technol, Inst Microbiol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland.
   [Bianchi, Siro; Corti, Davide] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland.
C3 Universita della Svizzera Italiana; University of Oxford; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Lanzavecchia, A (corresponding author), Univ Svizzera Italiana, Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.; Bull, P (corresponding author), CGMRC, KEMRI Wellcome Trust Res Programme, POB 230, Kilifi 80108, Kenya.; Bull, P (corresponding author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England.; Lanzavecchia, A (corresponding author), Swiss Fed Inst Technol, Inst Microbiol, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland.
EM pb642@cam.ac.uk; lanzavecchia@irb.usi.ch
FU European Research Council [250348, 670955]; Swiss National Science Foundation [160279]; Swiss Vaccine Research Institute; Wellcome Trust [084535, 077092, 084538, 084113/Z/07/Z, 084378/Z/07/A, 092741, 099811]; Helmut Horten Foundation; MRC [G1002624] Funding Source: UKRI; European Research Council (ERC) [670955, 250348] Funding Source: European Research Council (ERC); Medical Research Council [G1002624] Funding Source: researchfish; Wellcome Trust [084378/Z/07/A, 084113/Z/07/Z] Funding Source: Wellcome Trust
NR 19
TC 130
Z9 158
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 105
EP +
DI 10.1038/nature16450
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900036
PM 26700814
DA 2026-03-09
ER

PT J
AU Fiedorczuk, K
   Letts, JA
   Degliesposti, G
   Kaszuba, K
   Skehel, M
   Sazanov, LA
AF Fiedorczuk, Karol
   Letts, James A.
   Degliesposti, Gianluca
   Kaszuba, Karol
   Skehel, Mark
   Sazanov, Leonid A.
TI Atomic structure of the entire mammalian mitochondrial complex I
SO NATURE
LA English
DT Article
ID crystal-structure; membrane domain; nadh; ubiquinone; prediction; model; architecture; resolution; mechanism; site
AB Mitochondrial complex I (also known as NADH: ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane(1,2). It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons(3). Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 angstrom resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations.
C1 [Fiedorczuk, Karol; Letts, James A.; Kaszuba, Karol; Sazanov, Leonid A.] IST Austria, A-3400 Klosterneuburg, Austria.
   [Fiedorczuk, Karol] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
   [Degliesposti, Gianluca; Skehel, Mark] MRC, Mol Biol Lab, Cambridge CB2 OQH, England.
C3 Institute of Science & Technology - Austria
RP Sazanov, LA (corresponding author), IST Austria, A-3400 Klosterneuburg, Austria.
EM sazanov@ist.ac.at
FU Medical Research Council UK; FEBS; European Union [701309]; MRC [MC_U105674180, MC_U105178788] Funding Source: UKRI; Marie Curie Actions (MSCA) [701309] Funding Source: Marie Curie Actions (MSCA); Medical Research Council [MC_U105674180, 1601061, 1373852, MC_U105178788] Funding Source: researchfish
NR 54
TC 400
Z9 446
U1 3
U2 178
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 406
EP +
DI 10.1038/nature19794
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100044
PM 27595392
DA 2026-03-09
ER

PT J
AU Cheung, E
   Bundy, K
   Cappellari, M
   Peirani, S
   Rujopakarn, W
   Westfall, K
   Yan, RB
   Bershady, M
   Greene, JE
   Heckman, TM
   Drory, N
   Law, DR
   Masters, KL
   Thomas, D
   Wake, DA
   Weijmans, AM
   Rubin, K
   Belfiore, F
   Vulcani, B
   Chen, YM
   Zhang, K
   Gelfand, JD
   Bizyaev, D
   Roman-Lopes, A
   Schneider, DP
AF Cheung, Edmond
   Bundy, Kevin
   Cappellari, Michele
   Peirani, Sebastien
   Rujopakarn, Wiphu
   Westfall, Kyle
   Yan, Renbin
   Bershady, Matthew
   Greene, Jenny E.
   Heckman, Timothy M.
   Drory, Niv
   Law, David R.
   Masters, Karen L.
   Thomas, Daniel
   Wake, David A.
   Weijmans, Anne-Marie
   Rubin, Kate
   Belfiore, Francesco
   Vulcani, Benedetta
   Chen, Yan-mei
   Zhang, Kai
   Gelfand, Joseph D.
   Bizyaev, Dmitry
   Roman-Lopes, A.
   Schneider, Donald P.
TI Suppressing star formation in quiescent galaxies with supermassive black hole winds
SO NATURE
LA English
DT Article
ID multi-gaussian expansion; active galactic nuclei; formation history; stellar masses; cooling flows; red-sequence; models; gas; evolution; emission
AB Quiescent galaxies with little or no ongoing star formation dominate the population of galaxies with masses above 2 x 10(10) times that of the Sun; the number of quiescent galaxies has increased by a factor of about 25 over the past ten billion years (refs 1-4). Once star formation has been shut down, perhaps during the quasar phase of rapid accretion onto a supermassive black hole(5-7), an unknown mechanism must remove or heat the gas that is subsequently accreted from either stellar mass loss(8) or mergers and that would otherwise cool to form stars(9,10). Energy output from a black hole accreting at a low rate has been proposed(11-13), but observational evidence for this in the form of expanding hot gas shells is indirect and limited to radio galaxies at the centres of clusters(14,15), which are too rare to explain the vast majority of the quiescent population(16). Here we report bisymmetric emission features co-aligned with strong ionized-gas velocity gradients from which we infer the presence of centrally driven winds in typical quiescent galaxies that host low-luminosity active nuclei. These galaxies are surprisingly common, accounting for as much as ten per cent of the quiescent population with masses around 2 x 10(10) times that of the Sun. In a prototypical example, we calculate that the energy input from the galaxy's low-level active supermassive black hole is capable of driving the observed wind, which contains sufficient mechanical energy to heat ambient, cooler gas (also detected) and thereby suppress star formation.
C1 [Cheung, Edmond; Bundy, Kevin; Peirani, Sebastien; Rujopakarn, Wiphu; Vulcani, Benedetta] Univ Tokyo, World Premier Int Res Ctr Initiative, Kavli Inst Phys & Math Universe, Inst Adv Study, Kashiwa, Chiba 2778583, Japan.
   [Cappellari, Michele] Univ Oxford, Subdept Astrophys, Dept Phys, Denys Wilkinson Bldg,Keble Rd, Oxford OX1 3RH, England.
   [Peirani, Sebastien] CNRS, UMR 7095, Inst Astrophys Paris, 98 Bis Blvd Arago, F-75014 Paris, France.
   [Peirani, Sebastien] UPMC, 98 Bis Blvd Arago, F-75014 Paris, France.
   [Rujopakarn, Wiphu] Chulalongkorn Univ, Dept Phys, Fac Sci, 254 Phayathai Rd, Bangkok 10330, Thailand.
   [Westfall, Kyle; Masters, Karen L.; Thomas, Daniel] Univ Portsmouth, Inst Cosmol & Gravitat, Dennis Sciama Bldg,Burnaby Rd, Portsmouth PO1 3FX, Hants, England.
   [Yan, Renbin; Zhang, Kai] Univ Kentucky, Dept Phys & Astron, 505 Rose St, Lexington, KY 40506 USA.
   [Bershady, Matthew; Wake, David A.] Univ Wisconsin, Dept Astron, 475 North Charter St, Madison, WI 53706 USA.
   [Greene, Jenny E.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Heckman, Timothy M.] Johns Hopkins Univ, Dept Phys & Astron, Ctr Astrophys Sci, Baltimore, MD 21218 USA.
   [Drory, Niv] Univ Texas Austin, Dept Astron, McDonald Observ, 1 Univ Stn, Austin, TX 78712 USA.
   [Law, David R.] Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
   [Wake, David A.] Open Univ, Dept Phys Sci, Milton Keynes MK7 6AA, Bucks, England.
   [Weijmans, Anne-Marie] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Rubin, Kate] Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
   [Belfiore, Francesco] Univ Cambridge, Cavendish Lab, 19 JJ Thomson Ave, Cambridge CB3 0HE, England.
   [Belfiore, Francesco] Univ Cambridge, Kavli Inst Cosmol, Cambridge CB3 0HE, England.
   [Chen, Yan-mei] Nanjing Univ, Dept Astron, Nanjing 210093, Jiangsu, Peoples R China.
   [Gelfand, Joseph D.] New York Univ Abu Dhabi, POB 129188, Abu Dhabi, U Arab Emirates.
   [Gelfand, Joseph D.] NYU, Ctr Cosmol & Particle Phys, Meyer Hall Phys,4 Washington Pl, New York, NY 10003 USA.
   [Bizyaev, Dmitry] Apache Point Observ, POB 59, Sunspot, NM 88349 USA.
   [Bizyaev, Dmitry] New Mexico State Univ, POB 59, Sunspot, NM 88349 USA.
   [Bizyaev, Dmitry] Moscow MV Lomonosov State Univ, Sternberg Astron Inst, Moscow, Russia.
   [Roman-Lopes, A.] Univ La Serena, Fac Ciencias, Dept Fis & Astron, Cisternas 1200, La Serena, Chile.
   [Schneider, Donald P.] Penn State Univ, Dept Astron & Astrophys, 525 Davey Lab, University Pk, PA 16802 USA.
   [Schneider, Donald P.] Penn State Univ, Inst Gravitat & Cosmos, University Pk, PA 16802 USA.
C3 University of Tokyo; University of Oxford; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Sorbonne Universite; Chulalongkorn University; University of Portsmouth; University of Kentucky; University of Wisconsin System; University of Wisconsin Madison; Princeton University; Johns Hopkins University; University of Texas System; University of Texas Austin; Space Telescope Science Institute; Open University - UK; University of St Andrews; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; University of Cambridge; University of Cambridge; Nanjing University; New York University; New York University Abu Dhabi; New York University; New Mexico State University; Lomonosov Moscow State University; Universidad de La Serena; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Cheung, E (corresponding author), Univ Tokyo, World Premier Int Res Ctr Initiative, Kavli Inst Phys & Math Universe, Inst Adv Study, Kashiwa, Chiba 2778583, Japan.
EM ec2250@gmail.com
FU World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan; JSPS KAKENHI [15K17603]; Leverhulme Trust; Japan Society for the Promotion of Science (JSPS); Royal Society; Chulalongkorn University; Alfred P. Sloan Foundation; US Department of Energy Office of Science; Center for High-Performance Computing at the University of Utah; Brazilian Participation Group; Carnegie Institution for Science; Carnegie Mellon University; Chilean Participation Group; French Participation Group; Harvard-Smithsonian Center for Astrophysics; Instituto de Astrofisica de Canarias; Johns Hopkins University; Kavli Institute for the Physics and Mathematics of the Universe (IPMU)/University of Tokyo; Lawrence Berkeley National Laboratory; Leibniz Institut fur Astrophysik Potsdam (AIP); Max-Planck-Institut fur Astronomie (MPIA Heidelberg); Max-Planck-Institut fur Astrophysik (MPA Garching); Max-Planck-Institut fur Extraterrestrische Physik (MPE); National Astronomical Observatory of China; New Mexico State University; New York University; University of Notre Dame; Observatorio Nacional/MCTI; Ohio State University; Pennsylvania State University; Shanghai Astronomical Observatory; UK Participation Group; Universidad Nacional Autonoma de Mexico; University of Arizona; University of Colorado Boulder; University of Oxford; University of Portsmouth; University of Utah; University of Virginia; University of Washington; University of Wisconsin; Vanderbilt University; Yale University; Science and Technology Facilities Council [ST/K00090X/1, ST/N000668/1, 1363788] Funding Source: researchfish; Russian Science Foundation [14-50-00043] Funding Source: Russian Science Foundation; STFC [ST/N000668/1, ST/K00090X/1] Funding Source: UKRI; Grants-in-Aid for Scientific Research [15K17603] Funding Source: KAKEN
NR 69
TC 173
Z9 190
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2016
VL 533
IS 7604
BP 504
EP +
DI 10.1038/nature18006
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM6EJ
UT WOS:000376443100034
PM 27225122
DA 2026-03-09
ER

PT J
AU Kim, J
   McMillan, E
   Kim, HS
   Venkateswaran, N
   Makkar, G
   Rodriguez-Canales, J
   Villalobos, P
   Neggers, JE
   Mendiratta, S
   Wei, SG
   Landesman, Y
   Senapedis, W
   Baloglu, E
   Chow, CWB
   Frink, RE
   Gao, BN
   Roth, M
   Minna, JD
   Daelemans, D
   Wistuba, II
   Posner, BA
   Scaglioni, PP
   White, MA
AF Kim, Jimi
   McMillan, Elizabeth
   Kim, Hyun Seok
   Venkateswaran, Niranjan
   Makkar, Gurbani
   Rodriguez-Canales, Jaime
   Villalobos, Pamela
   Neggers, Jasper Edgar
   Mendiratta, Saurabh
   Wei, Shuguang
   Landesman, Yosef
   Senapedis, William
   Baloglu, Erkan
   Chow, Chi-Wan B.
   Frink, Robin E.
   Gao, Boning
   Roth, Michael
   Minna, John D.
   Daelemans, Dirk
   Wistuba, Ignacio I.
   Posner, Bruce A.
   Scaglioni, Pier Paolo
   White, Michael A.
TI XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer
SO NATURE
LA English
DT Article
ID mutations; models; target; yap; identification; activation; inhibitors; crm1/xpo1; kinase
AB The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity(1). However, advances have been hindered by the pervasive inter-and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear I kappa B alpha (also known as NFKBIA), with consequent inhibition of NF kappa B transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5-Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1-TEAD inhibitor. These findings indicate that clinically available XPO1 inhibitors are a promising therapeutic strategy for a considerable cohort of patients with lung cancer when coupled to genomics-guided patient selection and observation.
C1 [Kim, Jimi; McMillan, Elizabeth; Makkar, Gurbani; Mendiratta, Saurabh; White, Michael A.] UTSW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA.
   [Kim, Hyun Seok] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea.
   [Venkateswaran, Niranjan; Scaglioni, Pier Paolo] UTSW Med Ctr, Internal Med, Dallas, TX 75390 USA.
   [Rodriguez-Canales, Jaime; Villalobos, Pamela; Chow, Chi-Wan B.; Wistuba, Ignacio I.] MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
   [Neggers, Jasper Edgar; Daelemans, Dirk] Katholieke Univ Leuven, Dept Microbiol & Immunol, B-3000 Leuven, Belgium.
   [Wei, Shuguang; Roth, Michael; Posner, Bruce A.] UTSW Med Ctr, Biochem, Dallas, TX 75390 USA.
   [Landesman, Yosef; Senapedis, William; Baloglu, Erkan] Karyopharm Therapeut, Newton, MA 02459 USA.
   [Frink, Robin E.; Gao, Boning; Minna, John D.] UTSW Med Ctr, Hamon Ctr, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Yonsei University; Yonsei University Health System; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; UTMD Anderson Cancer Center; KU Leuven; University of Texas System; University of Texas Southwestern Medical Center; Karyopharm Therapeutics; University of Texas System; University of Texas Southwestern Medical Center
RP White, MA (corresponding author), UTSW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA.
EM michael.white@utsouthwestern.edu
FU NCI; CPRIT; UT-Lung SPORE; National Cancer Institute [P50CA070907] Funding Source: NIH RePORTER
NR 35
TC 169
Z9 199
U1 3
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2016
VL 538
IS 7623
BP 114
EP +
DI 10.1038/nature19771
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX8LD
UT WOS:000384638900045
PM 27680702
DA 2026-03-09
ER

PT J
AU Ye, CX
   Zhou, XL
   Pu, D
   Stutz, J
   Festa, J
   Spolaor, M
   Tsai, C
   Cantrell, C
   Mauldin, RL
   Campos, T
   Weinheimer, A
   Hornbrook, RS
   Apel, EC
   Guenther, A
   Kaser, L
   Yuan, B
   Karl, T
   Haggerty, J
   Hall, S
   Ullmann, K
   Smith, JN
   Ortega, J
   Knote, C
AF Ye, Chunxiang
   Zhou, Xianliang
   Pu, Dennis
   Stutz, Jochen
   Festa, James
   Spolaor, Max
   Tsai, Catalina
   Cantrell, Christopher
   Mauldin, Roy L., III
   Campos, Teresa
   Weinheimer, Andrew
   Hornbrook, Rebecca S.
   Apel, Eric C.
   Guenther, Alex
   Kaser, Lisa
   Yuan, Bin
   Karl, Thomas
   Haggerty, Julie
   Hall, Samuel
   Ullmann, Kirk
   Smith, James N.
   Ortega, John
   Knote, Christoph
TI Rapid cycling of reactive nitrogen in the marine boundary layer
SO NATURE
LA English
DT Article
ID master chemical mechanism; nitric-acid photolysis; mcm v3 part; tropospheric degradation; photochemical production; air-quality; dust storm; gas-phase; hono; surface
AB Nitrogen oxides are essential for the formation of secondary atmospheric aerosols and of atmospheric oxidants such as ozone and the hydroxyl radical, which controls the self-cleansing capacity of the atmosphere(1). Nitric acid, a major oxidation product of nitrogen oxides, has traditionally been considered to be a permanent sink of nitrogen oxides(1). However, model studies predict higher ratios of nitric acid to nitrogen oxides in the troposphere than are observed(2,3). A 'renoxification' process that recycles nitric acid into nitrogen oxides has been proposed to reconcile observations with model studies(2-4), but the mechanisms responsible for this process remain uncertain(5-9). Here we present data from an aircraft measurement campaign over the North Atlantic Ocean and find evidence for rapid recycling of nitric acid to nitrous acid and nitrogen oxides in the clean marine boundary layer via particulate nitrate photolysis. Laboratory experiments further demonstrate the photolysis of particulate nitrate collected on filters at a rate more than two orders of magnitude greater than that of gaseous nitric acid, with nitrous acid as the main product. Box model calculations based on the Master Chemical Mechanism(10,11) suggest that particulate nitrate photolysis mainly sustains the observed levels of nitrous acid and nitrogen oxides at midday under typical marine boundary layer conditions. Given that oceans account for more than 70 per cent of Earth's surface, we propose that particulate nitrate photolysis could be a substantial tropospheric nitrogen oxide source. Recycling of nitrogen oxides in remote oceanic regions with minimal direct nitrogen oxide emissions could increase the formation of tropospheric oxidants and secondary atmospheric aerosols on a global scale.
C1 [Ye, Chunxiang; Zhou, Xianliang] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
   [Zhou, Xianliang; Pu, Dennis] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA.
   [Stutz, Jochen; Festa, James; Spolaor, Max; Tsai, Catalina] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90024 USA.
   [Cantrell, Christopher; Mauldin, Roy L., III] Univ Colorado, Dept Atmospher & Ocean Sci, Boulder, CO 80309 USA.
   [Mauldin, Roy L., III] Univ Helsinki, Dept Phys, Helsinki, Finland.
   [Campos, Teresa; Weinheimer, Andrew; Hornbrook, Rebecca S.; Apel, Eric C.; Kaser, Lisa; Haggerty, Julie; Hall, Samuel; Ullmann, Kirk; Smith, James N.; Ortega, John; Knote, Christoph] Natl Ctr Atmospher Res, POB 3000, Boulder, CO 80307 USA.
   [Guenther, Alex] Pacific NW Natl Lab, Richland, WA 99352 USA.
   [Yuan, Bin] NOAA, Earth Syst Res Lab, Div Chem Sci, Boulder, CO USA.
   [Yuan, Bin] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Karl, Thomas] Univ Innsbruck, Inst Meteorol & Geophys, A-6020 Innsbruck, Austria.
   [Smith, James N.] Univ Eastern Finland, Kuopio, Finland.
   [Knote, Christoph] Univ Munich, Inst Meteorol, Marchioninistr 15, D-81377 Munich, Germany.
C3 Wadsworth Center; State University of New York (SUNY) System; State University of New York (SUNY) System; University at Albany, SUNY; University of California System; University of California Los Angeles; University of Colorado System; University of Colorado Boulder; University of Helsinki; National Center Atmospheric Research (NCAR) - USA; United States Department of Energy (DOE); Pacific Northwest National Laboratory; National Oceanic Atmospheric Admin (NOAA) - USA; University of Colorado System; University of Colorado Boulder; University of Innsbruck; University of Eastern Finland; University of Munich
RP Zhou, XL (corresponding author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.; Zhou, XL (corresponding author), SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA.
EM xianliang.zhou@health.ny.gov
FU National Science Foundation (NSF) [AGS-1216166, AGS-1215712, AGS-1216743]; National Science Foundation; Directorate For Geosciences [1215712] Funding Source: National Science Foundation; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1216743] Funding Source: National Science Foundation; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1216166] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1215712] Funding Source: National Science Foundation
NR 51
TC 181
Z9 212
U1 13
U2 485
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 489
EP 491
DI 10.1038/nature17195
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900044
PM 27064904
DA 2026-03-09
ER

PT J
AU Abraham, SA
   Hopcroft, LEM
   Carrick, E
   Drotar, ME
   Dunn, K
   Williamson, AJK
   Korfi, K
   Baquero, P
   Park, LE
   Scott, MT
   Pellicano, F
   Pierce, A
   Copland, M
   Nourse, C
   Grimmond, SM
   Vetrie, D
   Whetton, AD
   Holyoake, TL
AF Abraham, Sheela A.
   Hopcroft, Lisa E. M.
   Carrick, Emma
   Drotar, Mark E.
   Dunn, Karen
   Williamson, Andrew J. K.
   Korfi, Koorosh
   Baquero, Pablo
   Park, Laura E.
   Scott, Mary T.
   Pellicano, Francesca
   Pierce, Andrew
   Copland, Mhairi
   Nourse, Craig
   Grimmond, Sean M.
   Vetrie, David
   Whetton, Anthony D.
   Holyoake, Tessa L.
TI Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells
SO NATURE
LA English
DT Article
ID chronic myeloid-leukemia; tyrosine kinase; cd34(+) cells; cancer; inhibition; expression; imatinib; tumor; combination; microarray
AB Chronic myeloid leukaemia (CML) arises after transformation of a haemopoietic stem cell (HSC) by the protein-tyrosine kinase BCR-ABL. Direct inhibition of BCR-ABL kinase has revolutionized disease management, but fails to eradicate leukaemic stem cells (LSCs), which maintain CML. LSCs are independent of BCR-ABL for survival, providing a rationale for identifying and targeting kinase-independent pathways. Here we show-using proteomics, transcriptomics and network analyses-that in human LSCs, aberrantly expressed proteins, in both imatinib-responder and non-responder patients, are modulated in concert with p53 (also known as TP53) and c-MYC regulation. Perturbation of both p53 and c-MYC, and not BCR-ABL itself, leads to synergistic cell kill, differentiation, and near elimination of transplantable human LSCs in mice, while sparing normal HSCs. This unbiased systems approach targeting connected nodes exemplifies a novel precision medicine strategy providing evidence that LSCs can be eradicated.
C1 [Abraham, Sheela A.; Hopcroft, Lisa E. M.; Drotar, Mark E.; Dunn, Karen; Korfi, Koorosh; Park, Laura E.; Scott, Mary T.; Pellicano, Francesca; Copland, Mhairi; Holyoake, Tessa L.] Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Inst Canc Sci, Gartnavel Gen Hosp, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
   [Carrick, Emma; Williamson, Andrew J. K.; Pierce, Andrew; Whetton, Anthony D.] Univ Manchester, Stem Cell & Leukaemia Prote Lab, Manchester M20 3LJ, Lancs, England.
   [Carrick, Emma; Williamson, Andrew J. K.; Pierce, Andrew; Whetton, Anthony D.] Univ Manchester, Manchester Precis Med Inst, Manchester M20 3LJ, Lancs, England.
   [Korfi, Koorosh; Baquero, Pablo; Nourse, Craig; Vetrie, David] Univ Glasgow, Inst Canc Sci, Glasgow G61 1QH, Lanark, Scotland.
   [Grimmond, Sean M.] Univ Melbourne, Ctr Canc Res, Melbourne, Vic 3010, Australia.
   [Whetton, Anthony D.] Univ Manchester, Stoller Biomarker Discovery Ctr, Manchester M20 3LJ, Lancs, England.
C3 University of Glasgow; Gartnavel Royal Hospital; University of Manchester; University of Manchester; University of Glasgow; University of Melbourne; University of Manchester
RP Holyoake, TL (corresponding author), Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Inst Canc Sci, Gartnavel Gen Hosp, 1053 Great Western Rd, Glasgow G12 0YN, Lanark, Scotland.
EM Tessa.Holyoake@glasgow.ac.uk
FU Constellation Pharmaceuticals; Roche; Glasgow and Manchester Experimental Cancer Medicine Centres (ECMC) - CR-UK; Chief Scientist's Office (Scotland); MRC; CR-UK [C11074/A11008, LLR08071, LLR11017, SCD/04, LLR13035, LLR14005, KKL690, KKL698, LLR08004]; MRC CiC; Howat Foundation; Friends of Paul O'Gorman [ELF 67954]; British Society for Haematology [MR/K014854/1]; MRC [MR/K014854/1, MR/M008959/1, MR/N00583X/1, MC_PC_13063, G0600782] Funding Source: UKRI; Cancer Research UK [11008] Funding Source: researchfish; Chief Scientist Office [CZB/4/690] Funding Source: researchfish; Medical Research Council [MR/M008959/1, MC_PC_13063, 1515962, MR/N00583X/1, G0600782, MR/K014854/1] Funding Source: researchfish
NR 57
TC 190
Z9 217
U1 1
U2 94
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 341
EP +
DI 10.1038/nature18288
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800026
PM 27281222
DA 2026-03-09
ER

PT J
AU Newton, K
   Wickliffe, KE
   Maltzman, A
   Dugger, DL
   Strasser, A
   Pham, VC
   Lill, JR
   Roose-Girma, M
   Warming, S
   Solon, M
   Ngu, H
   Webster, JD
   Dixit, VM
AF Newton, Kim
   Wickliffe, Katherine E.
   Maltzman, Allie
   Dugger, Debra L.
   Strasser, Andreas
   Pham, Victoria C.
   Lill, Jennie R.
   Roose-Girma, Merone
   Warming, Soren
   Solon, Margaret
   Ngu, Hai
   Webster, Joshua D.
   Dixit, Vishva M.
TI RIPK1 inhibits ZBP1-driven necroptosis during development
SO NATURE
LA English
DT Article
ID kappa-b activation; tnf-alpha; programmed necrosis; cell-death; apoptosis; inflammation; innate; trif; phosphorylation; ubiquitination
AB Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis(1-3). However, mice expressing catalytically inactive RIPK1 are viable(2,4,5), and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL. Ripk1(RHIM/RHIM) mice that expressed mutant RIPK1 with critical RHIM residues IQIG mutated to AAAA died around birth and exhibited RIPK3 autophosphorylation on Thr231 and Ser232, which is a hallmark of necroptosis(6), in the skin and thymus. Blocking necroptosis with catalytically inactive RIPK3(D161N), RHIM mutant RIPK3, RIPK3 deficiency, or MLKL deficiency prevented lethality in Ripk1(RHIM/RHIM) mice. Loss of ZBP1, which engages RIPK3 in response to certain viruses(7,8) but previously had no defined role in development, also prevented perinatal lethality in Ripk1(RHIM/RHIM) mice. Consistent with the RHIM of RIPK1 functioning as a brake that prevents ZBP1 from engaging the RIPK3 RHIM, ZBP1 interacted with RIPK3 in Ripk1(RHIM/RHIM)Mlkl(-/-) macrophages, but not in wild-type, Mlkl(-/-) or Ripk1(RHIM/RHIM)Ripk3(RHIM/RHIM) macrophages. Collectively, these findings indicate that the RHIM of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development.
C1 [Newton, Kim; Wickliffe, Katherine E.; Maltzman, Allie; Dugger, Debra L.; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA.
   [Strasser, Andreas] Walter & Eliza Hall Inst Med Res, Mol Genet Canc Div, 1G Royal Parade, Parkville, Vic 3052, Australia.
   [Strasser, Andreas] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia.
   [Pham, Victoria C.; Lill, Jennie R.] Genentech Inc, Dept Prote & Biol Resources, 1 DNA Way, San Francisco, CA 94080 USA.
   [Roose-Girma, Merone; Warming, Soren] Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
   [Solon, Margaret; Ngu, Hai; Webster, Joshua D.] Genentech Inc, Dept Pathol, 1 DNA Way, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Walter & Eliza Hall Institute; University of Melbourne; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA
RP Newton, K; Dixit, VM (corresponding author), Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA.
EM knewton@gene.com; dixit@gene.com
NR 32
TC 327
Z9 362
U1 1
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2016
VL 540
IS 7631
BP 129
EP +
DI 10.1038/nature20559
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA ED5UA
UT WOS:000388916600062
PM 27819682
DA 2026-03-09
ER

PT J
AU Xu, JW
   Gui, M
   Wang, DH
   Xiang, Y
AF Xu, Jingwei
   Gui, Miao
   Wang, Dianhong
   Xiang, Ye
TI The bacteriophage φ29 tail possesses a pore-forming loop for cell membrane penetration
SO NATURE
LA English
DT Article
ID virus; release; peptide; system; entry
AB Most bacteriophages are tailed bacteriophages with an isometric or a prolate head attached to a long contractile, long non-contractile, or short non-contractile tail(1). The tail is a complex machine that plays a central role in host cell recognition and attachment, cell wall and membrane penetration, and viral genome ejection. The mechanisms involved in the penetration of the inner host cell membrane by bacteriophage tails are not well understood. Here we describe structural and functional studies of the bacteriophage phi 29 tail knob protein gene product 9 (gp9). The 2.0 angstrom crystal structure of gp9 shows that six gp9 molecules form a hexameric tube structure with six flexible hydrophobic loops blocking one end of the tube before DNA ejection. Sequence and structural analyses suggest that the loops in the tube could be membrane active. Further biochemical assays and electron microscopy structural analyses show that the six hydrophobic loops in the tube exit upon DNA ejection and form a channel that spans the lipid bilayer of the membrane and allows the release of the bacteriophage genomic DNA, suggesting that cell membrane penetration involves a pore-forming mechanism similar to that of certain non-enveloped eukaryotic viruses(2-4). A search of other phage tail proteins identified similar hydrophobic loops, which indicates that a common mechanism might be used for membrane penetration by prokaryotic viruses. These findings suggest that although prokaryotic and eukaryotic viruses use apparently very different mechanisms for infection, they have evolved similar mechanisms for breaching the cell membrane.
C1 [Xu, Jingwei; Gui, Miao; Wang, Dianhong; Xiang, Ye] Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China.
C3 Tsinghua University; Collaborative Innovation Center for Diagnosis & Treatment of Infectious Diseases
RP Xiang, Y (corresponding author), Tsinghua Univ, Ctr Infect Dis Res, Collaborat Innovat Ctr Diag & Treatment Infect Di, Dept Basic Med Sci,Sch Med,Beijing Adv Innovat Ct, Beijing 100084, Peoples R China.
EM yxiang@mail.tsinghua.edu.cn
FU 973 program [2015CB910102]; National Natural Science Foundation of China [31470721, 81550001]; Junior Thousand Talents Program of China [20131770418]; Beijing Advanced Innovation Center for Structural Biology
NR 37
TC 25
Z9 37
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2016
VL 534
IS 7608
BP 544
EP +
DI 10.1038/nature18017
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP1SS
UT WOS:000378270300052
PM 27309813
DA 2026-03-09
ER

PT J
AU Taylor, NMI
   Prokhorov, NS
   Guerrero-Ferreira, RC
   Shneider, MM
   Browning, C
   Goldie, KN
   Stahlberg, H
   Leiman, PG
AF Taylor, Nicholas M. I.
   Prokhorov, Nikolai S.
   Guerrero-Ferreira, Ricardo C.
   Shneider, Mikhail M.
   Browning, Christopher
   Goldie, Kenneth N.
   Stahlberg, Henning
   Leiman, Petr G.
TI Structure of the T4 baseplate and its function in triggering sheath contraction
SO NATURE
LA English
DT Article
ID vi secretion system; protein homology detection; bacteriophage-t4 baseplate; 3-dimensional structure; genetic-control; pseudomonas-aeruginosa; tail; phage; morphogenesis; implementation
AB Several systems, including contractile tail bacteriophages, the type VI secretion system and R-type pyocins, use a multiprotein tubular apparatus to attach to and penetrate host cell membranes. This macromolecular machine resembles a stretched, coiled spring (or sheath) wound around a rigid tube with a spike-shaped protein at its tip. A baseplate structure, which is arguably the most complex part of this assembly, relays the contraction signal to the sheath. Here we present the atomic structure of the approximately 6-megadalton bacteriophage T4 baseplate in its pre- and post-host attachment states and explain the events that lead to sheath contraction in atomic detail. We establish the identity and function of a minimal set of components that is conserved in all contractile injection systems and show that the triggering mechanism is universally conserved.
C1 [Taylor, Nicholas M. I.; Prokhorov, Nikolai S.; Guerrero-Ferreira, Ricardo C.; Shneider, Mikhail M.; Browning, Christopher; Leiman, Petr G.] Ecole Polytech Fed Lausanne, BSP 415, CH-1015 Lausanne, Switzerland.
   [Prokhorov, Nikolai S.] Russian Acad Sci, Winogradsky Inst Microbiol, Biotechnol Res Ctr, Pr 60 Letiya Oktyabrya,7 Bldg 2, Moscow 117312, Russia.
   [Shneider, Mikhail M.] Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Mol Bioengn, 16-10 Miklukho Maklaya St, Moscow 117997, Russia.
   [Goldie, Kenneth N.; Stahlberg, Henning] Univ Basel, Ctr Cellular Imaging & NanoAnalyt C CINA, Biozentrum, Mattenstr 26, CH-4058 Basel, Switzerland.
   [Browning, Christopher] Vertex Pharmaceut Europe Ltd, 86-88 Jubilee Ave,Milton Pk, Abingdon OX14 4RW, Oxon, England.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Russian Academy of Sciences; Research Center of Biotechnology RAS; Russian Academy of Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; University of Basel; Vertex Pharmaceuticals
RP Leiman, PG (corresponding author), Ecole Polytech Fed Lausanne, BSP 415, CH-1015 Lausanne, Switzerland.
EM petr.leiman@epfl.ch
FU EPFL SCITAS (high performance computing); EPFL Centre for Interdisciplinary Electron Microscopy; EPFL Proteomics Core Facility; Swiss National Science Foundation [310030_144243]; Swiss National Science Foundation (SNF) [310030_144243] Funding Source: Swiss National Science Foundation (SNF)
NR 85
TC 228
Z9 273
U1 1
U2 102
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2016
VL 533
IS 7603
BP 346
EP +
DI 10.1038/nature17971
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DM0AH
UT WOS:000376004300039
PM 27193680
DA 2026-03-09
ER

PT J
AU Lee, WCA
   Bonin, V
   Reed, M
   Graham, BJ
   Hood, G
   Glattfelder, K
   Reid, RC
AF Lee, Wei-Chung Allen
   Bonin, Vincent
   Reed, Michael
   Graham, Brett J.
   Hood, Greg
   Glattfelder, Katie
   Reid, R. Clay
TI Anatomy and function of an excitatory network in the visual cortex
SO NATURE
LA English
DT Article
ID serial electron-microscopy; action-potentials; receptive-fields; dendritic spines; neurons; ampa; specialization; connectivity; organization; expression
AB Circuits in the cerebral cortex consist of thousands of neurons connected by millions of synapses. A precise understanding of these local networks requires relating circuit activity with the underlying network structure. For pyramidal cells in superficial mouse visual cortex (V1), a consensus is emerging that neurons with similar visual response properties excite each other(1-5), but the anatomical basis of this recurrent synaptic network is unknown. Here we combined physiological imaging and large-scale electron microscopy to study an excitatory network in V1. We found that layer 2/3 neurons organized into subnetworks defined by anatomical connectivity, with more connections within than between groups. More specifically, we found that pyramidal neurons with similar orientation selectivity preferentially formed synapses with each other, despite the fact that axons and dendrites of all orientation selectivities pass near (<5 mu m) each other with roughly equal probability. Therefore, we predict that mechanisms of functionally specific connectivity take place at the length scale of spines. Neurons with similar orientation tuning formed larger synapses, potentially enhancing the net effect of synaptic specificity. With the ability to study thousands of connections in a single circuit, functional connectomics is proving a powerful method to uncover the organizational logic of cortical networks.
C1 [Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael; Graham, Brett J.; Reid, R. Clay] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Bonin, Vincent] VIB, Neuroelect Res Flanders, B-3001 Louvain, Belgium.
   [Bonin, Vincent] KU, B-3001 Louvain, Belgium.
   [Hood, Greg] Carnegie Mellon Univ, Pittsburgh Supercomp Ctr, Biomed Applicat Grp, Pittsburgh, PA 15213 USA.
   [Glattfelder, Katie; Reid, R. Clay] Allen Inst Brain Sci, Seattle, WA 98103 USA.
C3 Harvard University; Harvard Medical School; Flanders Institute for Biotechnology (VIB); KU Leuven; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Carnegie Mellon University; Allen Institute for Brain Science
RP Lee, WCA; Reid, RC (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.; Reid, RC (corresponding author), Allen Inst Brain Sci, Seattle, WA 98103 USA.
EM wei-chung_lee@hms.harvard.edu; clayr@alleninstitute.org
FU NIH [R01 EY10115, R01 NS075436, R21 NS085320]; HMS Vision Core Grant [P30 EY12196]; AIBS; Bertarelli Program in Translational Neuroscience and Neuroengineering; Edward R. and Anne G. Lefler Center; Stanley and Theodora Feldberg Fund; Neuro-Electronics Research Flanders; NIH; National Eye Institute [R01EY010115, P30EY012196] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103712] Funding Source: NIH RePORTER
NR 47
TC 339
Z9 408
U1 4
U2 110
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2016
VL 532
IS 7599
BP 370
EP +
DI 10.1038/nature17192
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DJ7WU
UT WOS:000374424700032
PM 27018655
DA 2026-03-09
ER

PT J
AU Kataoka, K
   Shiraishi, Y
   Takeda, Y
   Sakata, S
   Matsumoto, M
   Nagano, S
   Maeda, T
   Nagata, Y
   Kitanaka, A
   Mizuno, S
   Tanaka, H
   Chiba, K
   Ito, S
   Watatani, Y
   Kakiuchi, N
   Suzuki, H
   Yoshizato, T
   Yoshida, K
   Sanada, M
   Itonaga, H
   Imaizumi, Y
   Totoki, Y
   Munakata, W
   Nakamura, H
   Hama, N
   Shide, K
   Kubuki, Y
   Hidaka, T
   Kameda, T
   Masuda, K
   Minato, N
   Kashiwase, K
   Izutsu, K
   Takaori-Kondo, A
   Miyazaki, Y
   Takahashi, S
   Shibata, T
   Kawamoto, H
   Akatsuka, Y
   Shimoda, K
   Takeuchi, K
   Seya, T
   Miyano, S
   Ogawa, S
AF Kataoka, Keisuke
   Shiraishi, Yuichi
   Takeda, Yohei
   Sakata, Seiji
   Matsumoto, Misako
   Nagano, Seiji
   Maeda, Takuya
   Nagata, Yasunobu
   Kitanaka, Akira
   Mizuno, Seiya
   Tanaka, Hiroko
   Chiba, Kenichi
   Ito, Satoshi
   Watatani, Yosaku
   Kakiuchi, Nobuyuki
   Suzuki, Hiromichi
   Yoshizato, Tetsuichi
   Yoshida, Kenichi
   Sanada, Masashi
   Itonaga, Hidehiro
   Imaizumi, Yoshitaka
   Totoki, Yasushi
   Munakata, Wataru
   Nakamura, Hiromi
   Hama, Natsuko
   Shide, Kotaro
   Kubuki, Yoko
   Hidaka, Tomonori
   Kameda, Takuro
   Masuda, Kyoko
   Minato, Nagahiro
   Kashiwase, Koichi
   Izutsu, Koji
   Takaori-Kondo, Akifumi
   Miyazaki, Yasushi
   Takahashi, Satoru
   Shibata, Tatsuhiro
   Kawamoto, Hiroshi
   Akatsuka, Yoshiki
   Shimoda, Kazuya
   Takeuchi, Kengo
   Seya, Tsukasa
   Miyano, Satoru
   Ogawa, Seishi
TI Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers
SO NATURE
LA English
DT Article
ID genomic rearrangements; polymorphism; gene; activation; oncogenes; blockade; antibody; safety; cells; risk
AB Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD-L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1-mediated immune escape in cancer development(1-6). However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma(6-10). Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' region of the PD-L1 gene. Widely affecting multiple common human cancer types, including adult T-cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR). Disruption of the Pd-l1 3'-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3'-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti-tumour immunity through PD-L1 overexpression.
C1 [Kataoka, Keisuke; Nagata, Yasunobu; Watatani, Yosaku; Kakiuchi, Nobuyuki; Suzuki, Hiromichi; Yoshizato, Tetsuichi; Yoshida, Kenichi; Ogawa, Seishi] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan.
   [Shiraishi, Yuichi; Tanaka, Hiroko; Chiba, Kenichi; Ito, Satoshi; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab DNA Informat Anal, Tokyo 1088639, Japan.
   [Takeda, Yohei; Matsumoto, Misako; Seya, Tsukasa] Hokkaido Univ, Grad Sch Med, Dept Microbiol & Immunol, Sapporo, Hokkaido 0608638, Japan.
   [Sakata, Seiji; Takeuchi, Kengo] Japanese Fdn Canc Res, Inst Canc, Pathol Project Mol Targets, Tokyo 1358550, Japan.
   [Nagano, Seiji; Maeda, Takuya; Masuda, Kyoko; Kawamoto, Hiroshi] Kyoto Univ, Inst Frontier Med Sci, Dept Immunol, Kyoto 6068507, Japan.
   [Kitanaka, Akira; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kameda, Takuro; Shimoda, Kazuya] Miyazaki Univ, Dept Gastroenterol & Hematol, Fac Med, Miyazaki 8891692, Japan.
   [Mizuno, Seiya; Takahashi, Satoru] Univ Tsukuba, Lab Anim Resource Ctr, Tsukuba, Ibaraki 3058575, Japan.
   [Mizuno, Seiya; Takahashi, Satoru] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki 3058575, Japan.
   [Sanada, Masashi] Nagoya Med Ctr, Dept Adv Diag, Clin Res Ctr, Nagoya, Aichi 4600001, Japan.
   [Itonaga, Hidehiro] Sasebo City Gen Hosp, Dept Hematol, Sasebo 8578511, Japan.
   [Imaizumi, Yoshitaka; Miyazaki, Yasushi] Nagasaki Univ, Atom Bomb Dis Inst, Atom Bomb Dis & Hibakusya Med Unit, Dept Hematol, Nagasaki 8528523, Japan.
   [Totoki, Yasushi; Nakamura, Hiromi; Hama, Natsuko; Shibata, Tatsuhiro] Natl Canc Ctr, Div Canc Genom, Tokyo 1040045, Japan.
   [Munakata, Wataru] Natl Canc Ctr, Dept Hematol, Tokyo 1040045, Japan.
   [Minato, Nagahiro] Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto 6068501, Japan.
   [Kashiwase, Koichi] Japanese Red Cross Kanto Koshinetsu Block Blood C, Dept HLA Lab, Tokyo 1358639, Japan.
   [Izutsu, Koji] Toranomon Gen Hosp, Dept Hematol, Tokyo 1058470, Japan.
   [Takaori-Kondo, Akifumi] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto 6068501, Japan.
   [Shibata, Tatsuhiro] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo 1088639, Japan.
   [Akatsuka, Yoshiki] Fujita Hlth Univ, Sch Med, Sch Med, Toyoake, Aichi 4701192, Japan.
   [Akatsuka, Yoshiki] Aichi Canc Ctr, Div Immunol, Res Inst, Nagoya, Aichi 4648681, Japan.
C3 Kyoto University; University of Tokyo; Hokkaido University; Japanese Foundation for Cancer Research; Kyoto University; University of Miyazaki; University of Tsukuba; University of Tsukuba; Nagoya Medical Center; Nagasaki University; National Cancer Center - Japan; National Cancer Center - Japan; Kyoto University; Toranomon Hospital; Kyoto University; University of Tokyo; Fujita Health University; Aichi Cancer Center
RP Ogawa, S (corresponding author), Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan.
EM sogawa-tky@umin.ac.jp
FU Japan Agency for Medical Research and Development [15Ack0106014h0002, 15im0210102h0001]; KAKENHI [22134006, 15H05909, 25250020]; National Cancer Center Research and Development Funds [26-A-6]; RIKEN Advanced Institute for Computational Science through the HPCI System Research project [hp140230, hp160219, hp150232]; Grants-in-Aid for Scientific Research [15H05912, 26220207, 15H04743, 24111008, 24111001, 25250020] Funding Source: KAKEN
NR 40
TC 531
Z9 582
U1 4
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2016
VL 534
IS 7607
BP 402
EP +
DI 10.1038/nature18294
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DO5XQ
UT WOS:000377856800039
PM 27281199
DA 2026-03-09
ER

PT J
AU Burkhardt, C
   Borg, LE
   Brennecka, GA
   Shollenberger, QR
   Dauphas, N
   Kleine, T
AF Burkhardt, C.
   Borg, L. E.
   Brennecka, G. A.
   Shollenberger, Q. R.
   Dauphas, N.
   Kleine, T.
TI A nucleosynthetic origin for the Earth's anomalous 142Nd composition
SO NATURE
LA English
DT Article
ID solar protoplanetary disk; heterogeneous distribution; isotopic heterogeneity; enstatite chondrites; bulk composition; half-life; nebula; systematics; nd; differentiation
AB A long-standing paradigm assumes that the chemical and isotopic compositions of many elements in the bulk silicate Earth are the same as in chondrites(1-4). However, the accessible Earth has a greater Nd-142/Nd-144 ratio than do chondrites. Because Nd-142 is the decay product of the now-extinct Sm-146 (which has a half-life of 103 million years(5)), this Nd-142 difference seems to require a higher-than-chondritic Sm/Nd ratio for the accessible Earth. This must have been acquired during global silicate differentiation within the first 30 million years of Solar System formation(6) and implies the formation of a complementary Nd-142-depleted reservoir that either is hidden in the deep Earth(6), or lost to space by impact erosion(3,7). Whether this complementary reservoir existed, and whether or not it has been lost from Earth, is a matter of debate(3,8,9), and has implications for determining the bulk composition of Earth, its heat content and structure, as well as for constraining the modes and timescales of its geodynamical evolution(3,7,9,10). Here we show that, compared with chondrites, Earth's precursor bodies were enriched in neodymium that was produced by the slow neutron capture process (s-process) of nucleosynthesis. This s-process excess leads to higher Nd-142/Nd-144 ratios; after correction for this effect, the Nd-142/Nd-144 ratios of chondrites and the accessible Earth are indistinguishable within five parts per million. The Nd-142 offset between the accessible silicate Earth and chondrites therefore reflects a higher proportion of s-process neodymium in the Earth, and not early differentiation processes. As such, our results obviate the need for hidden-reservoir or super-chondritic Earth models and imply a chondritic Sm/Nd ratio for the bulk Earth. Although chondrites formed at greater heliocentric distances and contain a different mix of presolar components than Earth, they nevertheless are suitable proxies for Earth's bulk chemical composition.
C1 [Burkhardt, C.; Dauphas, N.] Univ Chicago, Dept Geophys Sci, Origins Lab, 5734 South Ellis Ave, Chicago, IL 60637 USA.
   [Burkhardt, C.; Dauphas, N.] Univ Chicago, Enrico Fermi Inst, 5734 South Ellis Ave, Chicago, IL 60637 USA.
   [Burkhardt, C.; Brennecka, G. A.; Shollenberger, Q. R.; Kleine, T.] Univ Munster, Inst Planetol, Wilhelm Klemm Str 10, D-48149 Munster, Germany.
   [Borg, L. E.; Brennecka, G. A.; Shollenberger, Q. R.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
C3 University of Chicago; University of Chicago; University of Munster; United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Burkhardt, C (corresponding author), Univ Chicago, Dept Geophys Sci, Origins Lab, 5734 South Ellis Ave, Chicago, IL 60637 USA.; Burkhardt, C (corresponding author), Univ Chicago, Enrico Fermi Inst, 5734 South Ellis Ave, Chicago, IL 60637 USA.; Burkhardt, C (corresponding author), Univ Munster, Inst Planetol, Wilhelm Klemm Str 10, D-48149 Munster, Germany.
EM burkhardt@uni-muenster.de
FU SNF [PBE2PZ-145946]; NASA [NNX14AK09G, OJ-30381-0036A, NNX15AJ25G, NNH12AT84I]; NSF [EAR144495, EAR150259]; ERC [616564]; US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; European Research Council (ERC) [616564] Funding Source: European Research Council (ERC)
NR 43
TC 135
Z9 148
U1 0
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2016
VL 537
IS 7620
BP 394
EP +
DI 10.1038/nature18956
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DV7EC
UT WOS:000383098000052
PM 27629643
DA 2026-03-09
ER

PT J
AU Parikshak, NN
   Swarup, V
   Belgard, TG
   Irimia, M
   Ramaswami, G
   Gandal, MJ
   Hartl, C
   Leppa, V
   Ubieta, LD
   Huang, J
   Lowe, JK
   Blencowe, BJ
   Horvath, S
   Geschwind, DH
AF Parikshak, Neelroop N.
   Swarup, Vivek
   Belgard, T. Grant
   Irimia, Manuel
   Ramaswami, Gokul
   Gandal, Michael J.
   Hartl, Christopher
   Leppa, Virpi
   Ubieta, Luis de la Torre
   Huang, Jerry
   Lowe, Jennifer K.
   Blencowe, Benjamin J.
   Horvath, Steve
   Geschwind, Daniel H.
TI Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism
SO NATURE
LA English
DT Article
ID spectrum disorders; coding mutations; network; transcriptome; risk; cortex; architecture; insights; neurons; disease
AB Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood(1-3). Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge(4-7), we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder.
C1 [Parikshak, Neelroop N.; Swarup, Vivek; Belgard, T. Grant; Ramaswami, Gokul; Gandal, Michael J.; Hartl, Christopher; Leppa, Virpi; Ubieta, Luis de la Torre; Huang, Jerry; Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.
   [Parikshak, Neelroop N.; Swarup, Vivek; Belgard, T. Grant; Ramaswami, Gokul; Gandal, Michael J.; Hartl, Christopher; Leppa, Virpi; Ubieta, Luis de la Torre; Huang, Jerry; Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Parikshak, Neelroop N.; Swarup, Vivek; Belgard, T. Grant; Ramaswami, Gokul; Gandal, Michael J.; Hartl, Christopher; Ubieta, Luis de la Torre; Huang, Jerry; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 695 Charles E Young Dr South, Los Angeles, CA 90095 USA.
   [Irimia, Manuel] BIST, Ctr Genom Regulat, 88 Dr Aiguader, Barcelona 08003, Spain.
   [Irimia, Manuel] UPF, Barcelona, Spain.
   [Blencowe, Benjamin J.] Univ Toronto, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada.
   [Blencowe, Benjamin J.] Univ Toronto, Dept Mol Genet, 1 Kings Coll Circle, Toronto, ON M5S IA8, Canada.
   [Horvath, Steve; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA.
   [Belgard, T. Grant] Verge Genom, 42A Dore St, San Francisco, CA 94103 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; University of Toronto; University of Toronto; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Geschwind, DH (corresponding author), Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.; Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA.; Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 695 Charles E Young Dr South, Los Angeles, CA 90095 USA.; Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
EM dhg@mednet.ucla.edu
FU Simons Foundation; University of Maryland Brain and Tissue Bank; NIMH [5R37 MH060233, 5R01 MH09714, 5R01 MH100027]; NRSA [F30 MH099886]; CIHR; Alzheimer's Research Foundation; University of Toronto McLaughlin Centre;  [5T32 MH073526];  [ERC-StG-LS2-637591]; National Institute of Mental Health [R01MH100027] Funding Source: NIH RePORTER
NR 58
TC 503
Z9 587
U1 2
U2 120
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2016
VL 540
IS 7633
BP 423
EP +
DI 10.1038/nature20612
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EE6JR
UT WOS:000389716800040
PM 27919067
DA 2026-03-09
ER

PT J
AU Dong, D
   Ren, K
   Qiu, XL
   Zheng, JL
   Guo, MH
   Guan, XY
   Liu, HN
   Li, NN
   Zhang, BL
   Yang, DJ
   Ma, C
   Wang, S
   Wu, D
   Ma, YF
   Fan, SL
   Wang, JW
   Gao, N
   Huang, ZW
AF Dong, De
   Ren, Kuan
   Qiu, Xiaolin
   Zheng, Jianlin
   Guo, Minghui
   Guan, Xiaoyu
   Liu, Hongnan
   Li, Ningning
   Zhang, Bailing
   Yang, Daijun
   Ma, Chuang
   Wang, Shuo
   Wu, Dan
   Ma, Yunfeng
   Fan, Shilong
   Wang, Jiawei
   Gao, Ning
   Huang, Zhiwei
TI The crystal structure of Cpf1 in complex with CRISPR RNA
SO NATURE
LA English
DT Article
ID target dna recognition; bacterial immunity; adaptive immunity; cas systems; prokaryotes; endonuclease; archaea; bacteriophage; tools
AB The CRISPR-Cas systems, as exemplified by CRISPR-Cas9, are RNA-guided adaptive immune systems used by bacteria and archaea to defend against viral infection(1-7). The CRISPR-Cpf1 system, a new class 2 CRISPR-Cas system, mediates robust DNA interference in human cells(1,8-10). Although functionally conserved, Cpf1 and Cas9 differ in many aspects including their guide RNAs and substrate specificity. Here we report the 2.38 A crystal structure of the CRISPR RNA (crRNA)-bound Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1). LbCpf1 has a triangle-shaped architecture with a large positively charged channel at the centre. Recognized by the oligonucleotide-binding domain of LbCpf1, the crRNA adopts a highly distorted conformation stabilized by extensive intramolecular interactions and the (Mg(H2O)(6))(2+) ion. The oligonucleotide-binding domain also harbours a looped-out helical domain that is important for LbCpf1 substrate binding. Binding of crRNA or crRNA lacking the guide sequence induces marked conformational changes but no oligomerization of LbCpf1. Our study reveals the crRNA recognition mechanism and provides insight into crRNA-guided substrate binding of LbCpf1, establishing a framework for engineering LbCpf1 to improve its efficiency and specificity for genome editing.
C1 [Dong, De; Ren, Kuan; Qiu, Xiaolin; Zheng, Jianlin; Guo, Minghui; Guan, Xiaoyu; Liu, Hongnan; Zhang, Bailing; Yang, Daijun; Ma, Chuang; Wang, Shuo; Wu, Dan; Ma, Yunfeng; Huang, Zhiwei] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Peoples R China.
   [Li, Ningning; Fan, Shilong; Wang, Jiawei; Gao, Ning] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China.
C3 Harbin Institute of Technology; Tsinghua University
RP Huang, ZW (corresponding author), Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Peoples R China.
EM huangzhiwei@hit.edu.cn
FU National Natural Science Foundation of China [31422014, 31450001, 31300605]
NR 36
TC 320
Z9 434
U1 19
U2 334
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2016
VL 532
IS 7600
BP 522
EP +
DI 10.1038/nature17944
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DK3KQ
UT WOS:000374815900052
PM 27096363
DA 2026-03-09
ER

PT J
AU Middlemiss, RP
   Samarelli, A
   Paul, DJ
   Hough, J
   Rowan, S
   Hammond, GD
AF Middlemiss, R. P.
   Samarelli, A.
   Paul, D. J.
   Hough, J.
   Rowan, S.
   Hammond, G. D.
TI Measurement of the Earth tides with a MEMS gravimeter
SO NATURE
LA English
DT Article
ID gravity; eruption; volcano; silicon
AB The ability to measure tiny variations in the local gravitational acceleration allows, besides other applications, the detection of hidden hydrocarbon reserves, magma build-up before volcanic eruptions, and subterranean tunnels. Several technologies are available that achieve the sensitivities required for such applications (tens of microgal per hertz(1/2)): free-fall gravimeters(1), spring-based gravimeters(2,3), superconducting gravimeters(4), and atom interferometers(5). All of these devices can observe the Earth tides(6): the elastic deformation of the Earth's crust as a result of tidal forces. This is a universally predictable gravitational signal that requires both high sensitivity and high stability over timescales of several days to measure. All present gravimeters, however, have limitations of high cost (more than 100,000 US dollars) and high mass (more than 8 kilograms). Here we present a microelectromechanical system (MEMS) device with a sensitivity of 40 microgal per hertz(1/2) only a few cubic centimetres in size. We use it to measure the Earth tides, revealing the long-term stability of our instrument compared to any other MEMS device. MEMS accelerometers-found in most smart phones(7)-can be mass-produced remarkably cheaply, but none are stable enough to be called a gravimeter. Our device has thus made the transition from accelerometer to gravimeter. The small size and low cost of this MEMS gravimeter suggests many applications in gravity mapping. For example, it could be mounted on a drone instead of low-flying aircraft for distributed land surveying and exploration, deployed to monitor volcanoes, or built into multi-pixel density-contrast imaging arrays.
C1 [Middlemiss, R. P.; Samarelli, A.; Hough, J.; Rowan, S.; Hammond, G. D.] Univ Glasgow, Sch Phys & Astron, SUPA, Kelvin Bldg,Univ Ave, Glasgow G12 8QQ, Lanark, Scotland.
   [Middlemiss, R. P.; Paul, D. J.] Univ Glasgow, Sch Engn, Rankine Bldg,Oakfield Ave, Glasgow G12 8LT, Lanark, Scotland.
C3 University of Glasgow; University of Glasgow
RP Middlemiss, RP; Hammond, GD (corresponding author), Univ Glasgow, Sch Phys & Astron, SUPA, Kelvin Bldg,Univ Ave, Glasgow G12 8QQ, Lanark, Scotland.
EM richard.middlemiss@glasgow.ac.uk; giles.hammond@glasgow.ac.uk
FU Royal Society Paul Instrument Fund; STFC [ST/M000427/1]; EPSRC [EP/N003225/1, EP/M01326X/1] Funding Source: UKRI; STFC [Gravitational Waves, ST/N005422/1, ST/M000427/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/M01326X/1, EP/N003225/1] Funding Source: researchfish; Science and Technology Facilities Council [ST/N005422/1, Gravitational Waves, ST/M000427/1] Funding Source: researchfish
NR 37
TC 293
Z9 320
U1 10
U2 252
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2016
VL 531
IS 7596
BP 614
EP +
DI 10.1038/nature17397
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8EX
UT WOS:000373027400033
PM 27029276
DA 2026-03-09
ER

PT J
AU Kottakis, F
   Nicolay, BN
   Roumane, A
   Karnik, R
   Gu, HC
   Nagle, JM
   Boukhali, M
   Hayward, MC
   Li, YY
   Chen, T
   Liesa, M
   Hammerman, PS
   Wong, KK
   Hayes, DN
   Shirihai, OS
   Dyson, NJ
   Haas, W
   Meissner, A
   Bardeesy, N
AF Kottakis, Filippos
   Nicolay, Brandon N.
   Roumane, Ahlima
   Karnik, Rahul
   Gu, Hongcang
   Nagle, Julia M.
   Boukhali, Myriam
   Hayward, Michele C.
   Li, Yvonne Y.
   Chen, Ting
   Liesa, Marc
   Hammerman, Peter S.
   Wong, Kwok Kin
   Hayes, D. Neil
   Shirihai, Orian S.
   Dyson, Nicholas J.
   Haas, Wilhelm
   Meissner, Alexander
   Bardeesy, Nabeel
TI LKB1 loss links serine metabolism to DNA methylation and tumorigenesis
SO NATURE
LA English
DT Article
ID cancer; pathway; growth; differentiation; biosynthesis; progression; mutations; supports; glycine; cells
AB Intermediary metabolism generates substrates for chromatin modification, enabling the potential coupling of metabolic and epigenetic states. Here we identify a network linking metabolic and epigenetic alterations that is central to oncogenic transformation downstream of the liver kinase B1 (LKB1, also known as STK11) tumour suppressor, an integrator of nutrient availability, metabolism and growth. By developing genetically engineered mouse models and primary pancreatic epithelial cells, and employing transcriptional, proteomics, and metabolic analyses, we find that oncogenic cooperation between LKB1 loss and KRAS activation is fuelled by pronounced mTOR-dependent induction of the serine-glycine-one-carbon pathway coupled to S-adenosylmethionine generation. At the same time, DNA methyltransferases are upregulated, leading to elevation in DNA methylation with particular enrichment at retrotransposon elements associated with their transcriptional silencing. Correspondingly, LKB1 deficiency sensitizes cells and tumours to inhibition of serine biosynthesis and DNA methylation. Thus, we define a hypermetabolic state that incites changes in the epigenetic landscape to support tumorigenic growth of LKB1-mutant cells, while resulting in potential therapeutic vulnerabilities.
C1 [Kottakis, Filippos; Nicolay, Brandon N.; Roumane, Ahlima; Nagle, Julia M.; Boukhali, Myriam; Dyson, Nicholas J.; Haas, Wilhelm; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.
   [Kottakis, Filippos; Roumane, Ahlima; Nagle, Julia M.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
   [Kottakis, Filippos; Nicolay, Brandon N.; Roumane, Ahlima; Nagle, Julia M.; Boukhali, Myriam; Dyson, Nicholas J.; Haas, Wilhelm; Bardeesy, Nabeel] Harvard Med Sch, Dept Med, Boston, MA 02114 USA.
   [Karnik, Rahul; Gu, Hongcang; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Karnik, Rahul; Gu, Hongcang; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Karnik, Rahul; Gu, Hongcang; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Hayward, Michele C.; Hayes, D. Neil] UNC, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Li, Yvonne Y.; Chen, Ting; Hammerman, Peter S.; Wong, Kwok Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Li, Yvonne Y.; Chen, Ting; Hammerman, Peter S.; Wong, Kwok Kin] Harvard Med Sch, Boston, MA 02115 USA.
   [Li, Yvonne Y.; Chen, Ting; Hammerman, Peter S.; Wong, Kwok Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Chen, Ting; Wong, Kwok Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA.
   [Liesa, Marc; Shirihai, Orian S.] Boston Univ, Sch Med, Mitochondria ARC, Evans Ctr Interdisciplinary Res,Dept Med, Boston, MA 02118 USA.
   [Liesa, Marc; Shirihai, Orian S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Dept Med, Los Angeles, CA 90095 USA.
   [Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Boston University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Bardeesy, N (corresponding author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.; Bardeesy, N (corresponding author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.; Bardeesy, N (corresponding author), Harvard Med Sch, Dept Med, Boston, MA 02114 USA.
EM bardeesy.nabeel@mgh.harvard.edu
FU Granara-Skerry Trust; Linda J. Verville Foundation; Begg Family; NIH [P01 CA117969-07, R01 CA133557-05, P50CA1270003]; Hirshberg Foundation; National Cancer Institute [P01CA117969] Funding Source: NIH RePORTER
NR 39
TC 269
Z9 312
U1 2
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 390
EP 395
DI 10.1038/nature20132
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700046
PM 27799657
DA 2026-03-09
ER

PT J
AU Flavahan, WA
   Drier, Y
   Liau, BB
   Gillespie, SM
   Venteicher, AS
   Stemmer-Rachamimov, AO
   Suvà, ML
   Bernstein, BE
AF Flavahan, William A.
   Drier, Yotam
   Liau, Brian B.
   Gillespie, Shawn M.
   Venteicher, Andrew S.
   Stemmer-Rachamimov, Anat O.
   Suva, Mario L.
   Bernstein, Bradley E.
TI Insulator dysfunction and oncogene activation in IDH mutant gliomas
SO NATURE
LA English
DT Article
ID integrated genomic analysis; methylation; expression; 2-hydroxyglutarate; demethylation; architecture; maintenance; principles; landscape; phenotype
AB Gain-of-function IDH mutations are initiating events that define major clinical and prognostic classes of gliomas(1,2). Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5'-methylcytosine hydroxylases(3-7). TET enzymes catalyse a key step in the removal of DNA methylation(8,9). IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP)(10,11), although the functional importance of this altered epigenetic state remains unclear. Here we show that human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein. Reduced CTCF binding is associated with loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to interact aberrantly with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with a demethylating agent partially restores insulator function and downregulates PDGFRA. Conversely, CRISPR-mediated disruption of the CTCF motif in IDH wild-type gliomaspheres upregulates PDGFRA and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.
C1 [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
   [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Stemmer-Rachamimov, Anat O.; Suva, Mario L.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Venteicher, Andrew S.; Suva, Mario L.; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Flavahan, William A.; Drier, Yotam; Liau, Brian B.; Gillespie, Shawn M.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Bernstein, BE (corresponding author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Bernstein, BE (corresponding author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.; Bernstein, BE (corresponding author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Bernstein, BE (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Bernstein, BE (corresponding author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM bernstein.bradley@mgh.harvard.edu
FU American Brain Tumor Association; Jane Coffin Childs fellowship; Howard Hughes Medical Institute; National Brain Tumor Society; National Human Genome Research Institute; National Cancer Institute [P50CA165962] Funding Source: NIH RePORTER
NR 44
TC 975
Z9 1230
U1 5
U2 221
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2016
VL 529
IS 7584
BP 110
EP +
DI 10.1038/nature16490
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA6VY
UT WOS:000367944900037
PM 26700815
DA 2026-03-09
ER

PT J
AU Session, AM
   Uno, Y
   Kwon, T
   Hapman, JAC
   Toyoda, A
   Takahashi, S
   Fukui, A
   Hikosaka, A
   Suzuki, A
   Kondo, M
   van Heeringen, SJ
   Quigley, I
   Heinz, S
   Ogino, H
   Ochi, H
   Hellsten, U
   Lyons, JB
   Simakov, O
   Putnam, N
   Stites, J
   Kuroki, Y
   Tanaka, T
   Michiue, T
   Watanabe, M
   Ogdanovic, OB
   Lister, R
   Georgiou, G
   Paranjpe, SS
   Van Kruijsbergen, I
   Shu, SQ
   Carlson, J
   Kinoshita, T
   Ohta, Y
   Mawaribuchi, S
   Jenkins, J
   Grimwood, J
   Schmutz, J
   Mitros, T
   Mozaffari, SV
   Suzuki, Y
   Haramoto, Y
   Yamamoto, TS
   Takagi, C
   Heald, R
   Miller, K
   Haudenschild, C
   Kitzman, J
   Nakayama, T
   Zutsu, YI
   Robert, J
   Fortriede, J
   Burns, K
   Lotay, V
   Karimi, K
   Yasuoka, Y
   Dichmann, DS
   Flajnik, MF
   Houston, DW
   Shendure, J
   DuPasquier, L
   Vize, PD
   Zorn, AM
   Ito, M
   Marcotte, EM
   Wallingford, JB
   Ito, Y
   Asashima, M
   Ueno, N
   Matsuda, Y
   Veenstra, GJC
   Fujiyama, A
   Harland, RM
   Taira, M
   Rokhsar, DS
AF Session, Adam M.
   Uno, Yoshinobu
   Kwon, Taejoon
   Hapman, Jarrod A. C.
   Toyoda, Atsushi
   Takahashi, Shuji
   Fukui, Akimasa
   Hikosaka, Akira
   Suzuki, Atsushi
   Kondo, Mariko
   van Heeringen, Simon J.
   Quigley, Ian
   Heinz, Sven
   Ogino, Hajime
   Ochi, Haruki
   Hellsten, Uffe
   Lyons, Jessica B. .
   Simakov, Oleg
   Putnam, Nicholas
   Stites, Jonathan
   Kuroki, Yoko
   Tanaka, Toshiaki
   Michiue, Tatsuo
   Watanabe, Minoru
   Ogdanovic, Ozren B.
   Lister, Ryan
   Georgiou, Georgios
   Paranjpe, Sarita S.
   Van Kruijsbergen, Ila
   Shu, Shengquiang
   Carlson, Joseph
   Kinoshita, Tsutomu
   Ohta, Yuko
   Mawaribuchi, Shuuji
   Jenkins, Jerry
   Grimwood, Jane
   Schmutz, Jeremy
   Mitros, Therese
   Mozaffari, Sahar V.
   Suzuki, Yutaka
   Haramoto, Yoshikazu
   Yamamoto, Takamasa S.
   Takagi, Chiyo
   Heald, Rebecca
   Miller, Kelly
   Haudenschild, Christian
   Kitzman, Jacob
   Nakayama, Takuya
   Zutsu, Yumi I.
   Robert, Jacques
   Fortriede, Joshua
   Burns, Kevin
   Lotay, Vaneet
   Karimi, Kamran
   Yasuoka, Yuuri
   Dichmann, Darwin S.
   Flajnik, Martin F.
   Houston, Douglas W.
   Shendure, Jay
   DuPasquier, Louis
   Vize, Peter D.
   Zorn, Aaron M.
   Ito, Michihiko
   Marcotte, Edward M.
   Wallingford, John B. .
   Ito, Yuzuru
   Asashima, Makoto
   Ueno, Naoto
   Matsuda, Yoichi
   Veenstra, Gert Jan C. .
   Fujiyama, Asao
   Harland, Richard M.
   Taira, Masanori
   Rokhsar, Daniel S.
TI Genome evolution in the allotetraploid frog Xenopus laevis
SO NATURE
LA English
DT Article
ID gene duplications; chromosm; polyploidy; tropicalis; origin; subfunctionalization; differentiation; fractionation; transcriptome; consequences
AB To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.
C1 [Session, Adam M.; Lyons, Jessica B. .; Mitros, Therese; Dichmann, Darwin S.; Harland, Richard M.; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Life Sci Addit 3200, Berkeley, CA 94720 USA.
   [Session, Adam M.; Lyons, Jessica B. .; Mitros, Therese; Dichmann, Darwin S.; Harland, Richard M.; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Life Sci Addit 3200, Berkeley, CA 94720 USA.
   [Session, Adam M.; Hapman, Jarrod A. C.; Hellsten, Uffe; Shu, Shengquiang; Carlson, Joseph; Jenkins, Jerry; Grimwood, Jane; Schmutz, Jeremy; Rokhsar, Daniel S.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Uno, Yoshinobu; Matsuda, Yoichi] Nagoya Univ, Grad Sch Bioagr Sci, Dept Appl Mol Biosci, Chikusa Ku, Furo Cho, Nagoya, Aichi 4648601, Japan.
   [Kwon, Taejoon; Marcotte, Edward M.; Wallingford, John B. .] Univ Texas Austin, Ctr Syst & Synthet Biol, Dept Mol Biosci, Austin, TX 78712 USA.
   [Kwon, Taejoon] Ulsan Natl Inst Sci & Technol, Sch Life Sci, Dept Biomed Engn, Ulsan 689798, South Korea.
   [Toyoda, Atsushi; Fujiyama, Asao] Natl Inst Genet, Ctr Informat Biol, 1111 Yata, Mishima, Shizuoka 4118540, Japan.
   [Toyoda, Atsushi; Fujiyama, Asao] Natl Inst Genet, Adv Genom Ctr, 1111 Yata, Mishima, Shizuoka 4118540, Japan.
   [Takahashi, Shuji; Suzuki, Atsushi] Hiroshima Univ, Grad Sch Sci, Amphibian Res Ctr, 1-3-1 Kagamiyama, Hiroshima 7398526, Japan.
   [Fukui, Akimasa] Hokkaido Univ, Fac Adv Life Sci, Lab Tissue & Polymer Sci, Kita Ku, N10W8, Sapporo, Hokkaido 0600810, Japan.
   [Hikosaka, Akira] Hiroshima Univ, Grad Sch Integrated Arts & Sci, Div Human Sci, 1-7-1 Kagamiyama, Hiroshima 7398521, Japan.
   [Kondo, Mariko] Univ Tokyo, Grad Sch Sci, MMBS, 1024 Koajiro, Miura, Kanagawa 2380225, Japan.
   [van Heeringen, Simon J.; Georgiou, Georgios; Paranjpe, Sarita S.; Van Kruijsbergen, Ila; Veenstra, Gert Jan C. .] Radboud Univ Nijmegen, Fac Sci, Dept Mol Dev Biol, 259 RIMLS,M850-2-97,Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands.
   [Quigley, Ian] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
   [Heinz, Sven] Salk Inst Biol Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA.
   [Ogino, Hajime] Nagahama Inst Biosci & Technol, Dept Anim Biosci, 1266 Tamura, Nagahama, Shiga 5260829, Japan.
   [Ochi, Haruki] Yamagata Univ, Fac Med, Inst Promot Med Sci Res, 2-2-2 Iida Nishi, Yamagata, Yamagata 9909585, Japan.
   [Simakov, Oleg; Rokhsar, Daniel S.] Okinawa Inst Sci & Technol Grad Univ, Mol Genet Unit, Onna, Okinawa 9040495, Japan.
   [Putnam, Nicholas; Stites, Jonathan] Dovetail Genom LLC, Santa Cruz, CA 95060 USA.
   [Kuroki, Yoko] NCCHD, Natl Res Inst Child Hlth & Dev, Dept Genome Med, Setagaya Ku, 2-10-1 Okura, Tokyo 1578535, Japan.
   [Tanaka, Toshiaki] Tokyo Inst Technol, Dept Life Sci & Technol, Midori Ku, 4259 Nagatsuta, Yokohama, Kanagawa 2268501, Japan.
   [Michiue, Tatsuo] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Meguro Ku, 3-8-1 Komaba, Tokyo 1538902, Japan.
   [Watanabe, Minoru] Univ Tokushima, Inst Inst Liberal Arts & Fundamental Educ, 1-1 Minamijosanjima Cho, Tokushima 7708502, Japan.
   [Ogdanovic, Ozren B.; Lister, Ryan] Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA 6009, Australia.
   [Ogdanovic, Ozren B.; Lister, Ryan] Univ Western Australia, ARC Ctr Excellence Plant Energy Biol, Perth, WA 6009, Australia.
   [Kinoshita, Tsutomu] Rikkyo Univ, Fac Sci, Dept Life Sci, Toshima Ku, 3-34-1 Nishi Ikebukuro, Tokyo 1718501, Japan.
   [Ohta, Yuko; Flajnik, Martin F.] Univ Maryland, Dept Microbiol & Immunol, 655 W Baltimore St, Baltimore, MD 21201 USA.
   [Mawaribuchi, Shuuji] Kitasato Univ, Kitasato Inst Life Sci, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan.
   [Jenkins, Jerry; Grimwood, Jane; Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Mozaffari, Sahar V.] Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 431F, Chicago, IL 60637 USA.
   [Suzuki, Yutaka] Univ Tokyo, Dept Computat Biol & Med Sci, 5-1-5 Kashiwanoha, Kashiwa, Chiba 2778568, Japan.
   [Haramoto, Yoshikazu; Ito, Yuzuru; Asashima, Makoto] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery, Cent 5,1-1-1 Higashi, Tsukuba, Ibaraki 3058565, Japan.
   [Yamamoto, Takamasa S.; Takagi, Chiyo; Ueno, Naoto] Natl Inst Basic Biol, Dept Dev Biol, Div Morphogenesis, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan.
   [Heald, Rebecca; Miller, Kelly] Univ Calif Berkeley, Dept Mol & Cell Biol, Life Sci Addit 3200, Berkeley, CA 94701 USA.
   [Haudenschild, Christian] Illumina Inc, 25861 Ind Blvd, Hayward, CA 94545 USA.
   [Kitzman, Jacob; Shendure, Jay] Univ Washington, Dept Genome Sci, Foege Bldg S-250,Box 355065,3720 15th Ave NE, Seattle, WA 98195 USA.
   [Nakayama, Takuya] Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA.
   [Zutsu, Yumi I.] Niigata Univ, Fac Sci, Dept Biol, Nishi Ku, 8050,Ikarashi 2 No Cho, Niigata 9502181, Japan.
   [Robert, Jacques] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA.
   [Fortriede, Joshua; Burns, Kevin; Zorn, Aaron M.] Cincinnati Childrens Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Lotay, Vaneet; Karimi, Kamran; Vize, Peter D.] Univ Calgary, Dept Biol Sci, 2500 Univ Dr 1 NW, Calgary, AB T2N 1N4, Canada.
   [Yasuoka, Yuuri] Okinawa Inst Sci & Technol Grad Univ, Marine Genom Unit, 1919-1 Tancha, Onna, Okinawa 9040495, Japan.
   [Houston, Douglas W.] Univ Iowa, Dept Biol, 257 Biol Bldg, Iowa City, IA 52242 USA.
   [DuPasquier, Louis] Univ Basel, Dept Zool & Evolutionary Biol, CH-4051 Basel, Switzerland.
   [Ito, Michihiko] Kitasato Univ, Sch Sci, Dept Biol Sci, 1-15-1 Minamiku, Sagamihara, Kanagawa 2520373, Japan.
   [Ueno, Naoto] SOKENDAI, Dept Basic Biol, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan.
   [Fujiyama, Asao] Natl Inst Informat, Principles Informat, Chiyoda Ku, 2-1-2 Hitotsubashi, Tokyo 1018430, Japan.
   [Fujiyama, Asao] SOKENDAI, Dept Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan.
   [Taira, Masanori] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
   [Haudenschild, Christian] Personalis Inc, 1330 OBrien Dr, Menlo Pk, CA 94025 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; Nagoya University; University of Texas System; University of Texas Austin; Ulsan National Institute of Science & Technology (UNIST); Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Hiroshima University; Hokkaido University; Hiroshima University; University of Tokyo; Radboud University Nijmegen; Salk Institute; Salk Institute; Nagahama Institute of Bio-Science & Technology; Yamagata University; Okinawa Institute of Science & Technology Graduate University; National Center for Child Health & Development - Japan; Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo; Tokushima University; University of Western Australia; Harry Perkins Institute of Medical Research; University of Western Australia; ARC Centre of Excellence in Plant Energy Biology; Rikkyo University; University System of Maryland; University of Maryland Baltimore; Kitasato University; HudsonAlpha Institute for Biotechnology; University of Chicago; University of Tokyo; National Institute of Advanced Industrial Science & Technology (AIST); National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB); University of California System; University of California Berkeley; Illumina; University of Washington; University of Washington Seattle; University of Virginia; Niigata University; University of Rochester; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; University of Calgary; Okinawa Institute of Science & Technology Graduate University; University of Iowa; University of Basel; Kitasato University; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB); Okazaki Institute for Integrative Bioscience (OIIB); Graduate University for Advanced Studies - Japan; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan; Graduate University for Advanced Studies - Japan; University of Tokyo
RP Harland, RM (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Life Sci Addit 3200, Berkeley, CA 94720 USA.; Harland, RM (corresponding author), Univ Calif Berkeley, Ctr Integrat Genom, Life Sci Addit 3200, Berkeley, CA 94720 USA.; Rokhsar, DS (corresponding author), US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.; Rokhsar, DS (corresponding author), Okinawa Inst Sci & Technol Grad Univ, Mol Genet Unit, Onna, Okinawa 9040495, Japan.; Taira, M (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM harland@berkeley.edu; m_taira@bs.s.u-tokyo.ac.jp; dsrokhsar@gmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P41HD064556] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [R01HL117164] Funding Source: NIH RePORTER; National Human Genome Research Institute [T32HG000047] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R35GM118183] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [26440115, 16H04828, 16H04794, 15H03526, 26440048, 16K21559, 16K08444, 26650087, 15K07082, 16H06279, 15K14521] Funding Source: KAKEN; NHGRI NIH HHS [T32 HG000047] Funding Source: Medline; NHLBI NIH HHS [R01 HL117164] Funding Source: Medline; NICHD NIH HHS [R21 HD084072, R01 HD080708, P41 HD064556, R01 HD069344] Funding Source: Medline; NIGMS NIH HHS [R21 GM119021, R01 GM086627, R01 GM104853, R01 GM042341, R01 GM086321, R35 GM118183] Funding Source: Medline; NIH HHS [R01 OD010549] Funding Source: Medline; United States [HD065705, HD080708, GM086321] Funding Source: Medline
NR 57
TC 726
Z9 932
U1 3
U2 164
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2016
VL 538
IS 7625
BP 336
EP +
DI 10.1038/nature19840
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EA5PJ
UT WOS:000386673100030
PM 27762356
DA 2026-03-09
ER

PT J
AU Dever, DP
   Bak, RO
   Reinisch, A
   Camarena, J
   Washington, G
   Nicolas, CE
   Pavel-Dinu, M
   Saxena, N
   Wilkens, AB
   Mantri, S
   Uchida, N
   Hendel, A
   Narla, A
   Majeti, R
   Weinberg, KI
   Porteus, MH
AF Dever, Daniel P.
   Bak, Rasmus O.
   Reinisch, Andreas
   Camarena, Joab
   Washington, Gabriel
   Nicolas, Carmencita E.
   Pavel-Dinu, Mara
   Saxena, Nivi
   Wilkens, Alec B.
   Mantri, Sruthi
   Uchida, Nobuko
   Hendel, Ayal
   Narla, Anupama
   Majeti, Ravindra
   Weinberg, Kenneth I.
   Porteus, Matthew H.
TI CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells
SO NATURE
LA English
DT Article
ID homologous recombination; donor lymphocytes; progenitor cells; messenger-rna; therapy; transplantation; endonuclease
AB The beta-haemoglobinopathies, such as sickle cell disease and beta-thalassaemia, are caused by mutations in the beta-globin (HBB) gene and affect millions of people worldwide. Ex vivo gene correction in patient-derived haematopoietic stem cells followed by autologous transplantation could be used to cure beta-haemoglobinopathies. Here we present a CRISPR/Cas9 gene-editing system that combines Cas9 ribonucleoproteins and adeno-associated viral vector delivery of a homologous donor to achieve homologous recombination at the HBB gene in haematopoietic stem cells. Notably, we devise an enrichment model to purify a population of haematopoietic stem and progenitor cells with more than 90% targeted integration. We also show efficient correction of the Glu6Val mutation responsible for sickle cell disease by using patient-derived stem and progenitor cells that, after differentiation into erythrocytes, express adult beta-globin (HbA) messenger RNA, which confirms intact transcriptional regulation of edited HBB alleles. Collectively, these preclimical studies outline a CRISPR-based methodology for targeting haematopoietic stem cells by homologous recombination at the HBB locus to advance the development of next-generation therapies for beta-haemoglobinopathies.
C1 [Dever, Daniel P.; Bak, Rasmus O.; Camarena, Joab; Washington, Gabriel; Nicolas, Carmencita E.; Pavel-Dinu, Mara; Saxena, Nivi; Wilkens, Alec B.; Mantri, Sruthi; Hendel, Ayal; Weinberg, Kenneth I.; Porteus, Matthew H.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
   [Reinisch, Andreas; Majeti, Ravindra] Stanford Univ, Inst Canc, Div Hematol, Dept Med, Stanford, CA 94305 USA.
   [Reinisch, Andreas; Majeti, Ravindra] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Uchida, Nobuko] Stem Cells Inc, 7707 Gateway Blvd,Suite 140, Newark, CA 94560 USA.
   [Narla, Anupama] Stanford Univ, Sch Med, Dept Pediat, Div Hematol Oncol, Stanford, CA 94035 USA.
   [Uchida, Nobuko] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
RP Porteus, MH (corresponding author), Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
EM mporteus@stanford.edu
FU Stanford Child Health Research Institute (CHRI); Danish Council for Independent Research, Medical Sciences [DFF-1333-00106B, DFF-1331-00735B]; Amon Carter Foundation; Laurie Kraus Lacob Faculty Scholar Award in Pediatric Translational Research; NIH [PN2EY018244, R01-AI097320, R01-AI120766]; Austrian Science Fund (FWF) [J 3358] Funding Source: researchfish; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER
NR 42
TC 706
Z9 863
U1 7
U2 377
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2016
VL 539
IS 7629
BP 384
EP 389
DI 10.1038/nature20134
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA EC5GP
UT WOS:000388161700045
PM 27820943
DA 2026-03-09
ER

