PT J
AU Kusumbe, AP
   Ramasamy, SK
   Adams, RH
AF Kusumbe, Anjali P.
   Ramasamy, Saravana K.
   Adams, Ralf H.
TI Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; lindau tumor-suppressor; endothelial-cells; fracture repair; vascular contribution; angiocrine factors; plasma-membrane; trabecular bone; marrow; hypoxia
AB The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.
C1 [Kusumbe, Anjali P.; Ramasamy, Saravana K.; Adams, Ralf H.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
   [Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
C3 Max Planck Society; University of Munster
RP Adams, RH (corresponding author), Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
EM 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 AngioBone]
NR 50
TC 1697
Z9 1955
U1 24
U2 537
PU NATURE PUBLISHING 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 20
PY 2014
VL 507
IS 7492
BP 323
EP +
DI 10.1038/nature13145
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000026
PM 24646994
DA 2026-03-09
ER

PT J
AU Yamada, M
   Johannesson, B
   Sagi, I
   Burnett, LC
   Kort, DH
   Prosser, RW
   Paull, D
   Nestor, MW
   Freeby, M
   Greenberg, E
   Goland, RS
   Leibel, RL
   Solomon, SL
   Benvenisty, N
   Sauer, MV
   Egli, D
AF Yamada, Mitsutoshi
   Johannesson, Bjarki
   Sagi, Ido
   Burnett, Lisa Cole
   Kort, Daniel H.
   Prosser, Robert W.
   Paull, Daniel
   Nestor, Michael W.
   Freeby, Matthew
   Greenberg, Ellen
   Goland, Robin S.
   Leibel, Rudolph L.
   Solomon, Susan L.
   Benvenisty, Nissim
   Sauer, Mark V.
   Egli, Dieter
TI Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells
SO NATURE
LA English
DT Article
ID in-vitro; mouse; maturation; stability; hotspots; protein; memory; model; es
AB The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells(1-3), holding promise for autologous cell replacement therapy(4,5). Although methods to induce pluripotent stem cells from somatic cells by transcription factors(6) are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported(7-11), potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.
C1 [Yamada, Mitsutoshi; Johannesson, Bjarki; Paull, Daniel; Nestor, Michael W.; Solomon, Susan L.; Egli, Dieter] New York Stem Cell Fdn Res Inst, New York, NY 10032 USA.
   [Sagi, Ido; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, Stem Cell Unit, IL-91904 Jerusalem, Israel.
   [Burnett, Lisa Cole; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S.; Leibel, Rudolph L.] Columbia Univ, Coll Phys & Surg, Dept Pediat, Naomi Berrie Diabet Ctr, New York, NY 10032 USA.
   [Kort, Daniel H.; Prosser, Robert W.; Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Ctr Womens Reprod Care, New York, NY 10019 USA.
   [Kort, Daniel H.; Prosser, Robert W.; Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10019 USA.
C3 Hebrew University of Jerusalem; Columbia University; Columbia University; Columbia University
RP Egli, D (corresponding author), New York Stem Cell Fdn Res Inst, New York, NY 10032 USA.
EM d.egli@nyscf.org
FU New York Stem Cell Foundation (NYSCF); New York State Stem Cell Science (NYSTEM) IIRP [C026184]; Russell Berrie Foundation Program in Cellular Therapies of Diabetes; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007647] Funding Source: NIH RePORTER
NR 38
TC 136
Z9 164
U1 1
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 26
PY 2014
VL 510
IS 7506
BP 533
EP +
DI 10.1038/nature13287
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300046
PM 24776804
DA 2026-03-09
ER

PT J
AU Keller, SC
   Bessell, MS
   Frebel, A
   Casey, AR
   Asplund, M
   Jacobson, HR
   Lind, K
   Norris, JE
   Yong, D
   Heger, A
   Magic, Z
   Da Costa, GS
   Schmidt, BP
   Tisserand, P
AF Keller, S. C.
   Bessell, M. S.
   Frebel, A.
   Casey, A. R.
   Asplund, M.
   Jacobson, H. R.
   Lind, K.
   Norris, J. E.
   Yong, D.
   Heger, A.
   Magic, Z.
   Da Costa, G. S.
   Schmidt, B. P.
   Tisserand, P.
TI A single low-energy, iron-poor supernova as the source of metals in the star SMSS J031300.36-670839.3
SO NATURE
LA English
DT Article
ID hole-forming supernovae; galactic halo; sky survey; 1st stars; evolution; spectrograph; signatures
AB The element abundance ratios of four low-mass stars with extremely low metallicities (abundances of elements heavier than helium) indicate that the gas out of which the stars formed was enriched in each case by at most a few-and potentially only one-low-energy supernova(1-4). Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae seems surprising, because it had been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron(5). What has remained unclear is the yield of iron from the first supernovae, because hitherto no star has been unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36-670839.3, which shows no evidence of iron (with an upper limit of 10(-7.1) times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass about 60 times that of the Sun (and that the supernova left behind a black hole). Taken together with the four previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yielded light-element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.
C1 [Keller, S. C.; Bessell, M. S.; Casey, A. R.; Asplund, M.; Norris, J. E.; Yong, D.; Magic, Z.; Da Costa, G. S.; Schmidt, B. P.; Tisserand, P.] Mt Stromlo & Siding Spring Observ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Frebel, A.; Jacobson, H. R.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Frebel, A.; Jacobson, H. R.] Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Lind, K.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Heger, A.] Monash Univ, Sch Math Sci, Clayton, Vic 3800, Australia.
   [Magic, Z.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
C3 Australian National University; Massachusetts Institute of Technology (MIT); University of Cambridge; Monash University; Max Planck Society
RP Keller, SC (corresponding author), Mt Stromlo & Siding Spring Observ, Res Sch Astron & Astrophys, Cotter Rd, Weston, ACT 2611, Australia.
EM stefan.keller@anu.edu.au
FU Australian Research Council [DP120101237, DP0984924, DP0878137, LF0992131]; NSF [AST-1255160]; Australian Prime Minister's Endeavour Award Research Fellowship; European Union FP7 programme through ERC [320360]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1255160] Funding Source: National Science Foundation
NR 36
TC 319
Z9 344
U1 0
U2 20
PU NATURE PUBLISHING 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 27
PY 2014
VL 506
IS 7489
BP 463
EP +
DI 10.1038/nature12990
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100032
PM 24509711
DA 2026-03-09
ER

PT J
AU Brawand, D
   Wagner, CE
   Li, YI
   Malinsky, M
   Keller, I
   Fan, SH
   Simakov, O
   Ng, AY
   Lim, ZW
   Bezault, E
   Turner-Maier, J
   Johnson, J
   Alcazar, R
   Noh, HJ
   Russell, P
   Aken, B
   Alföldi, J
   Amemiya, C
   Azzouzi, N
   Baroiller, JF
   Barloy-Hubler, F
   Berlin, A
   Bloomquist, R
   Carleton, KL
   Conte, MA
   D'Cotta, H
   Eshel, O
   Gaffney, L
   Galibert, F
   Gante, HF
   Gnerre, S
   Greuter, L
   Guyon, R
   Haddad, NS
   Haerty, W
   Harris, RM
   Hofmann, HA
   Hourlier, T
   Hulata, G
   Jaffe, DB
   Lara, M
   Lee, AP
   MacCallum, I
   Mwaiko, S
   Nikaido, M
   Nishihara, H
   Ozouf-Costaz, C
   Penman, DJ
   Przybylski, D
   Rakotomanga, M
   Renn, SCP
   Ribeiro, FJ
   Ron, M
   Salzburger, W
   Sanchez-Pulido, L
   Santos, ME
   Searle, S
   Sharpe, T
   Swofford, R
   Tan, FJ
   Williams, L
   Young, S
   Yin, SY
   Okada, N
   Kocher, TD
   Miska, EA
   Lander, ES
   Venkatesh, B
   Fernald, RD
   Meyer, A
   Ponting, CP
   Streelman, JT
   Lindblad-Toh, K
   Seehausen, O
   Di Palma, F
AF Brawand, David
   Wagner, Catherine E.
   Li, Yang I.
   Malinsky, Milan
   Keller, Irene
   Fan, Shaohua
   Simakov, Oleg
   Ng, Alvin Y.
   Lim, Zhi Wei
   Bezault, Etienne
   Turner-Maier, Jason
   Johnson, Jeremy
   Alcazar, Rosa
   Noh, Hyun Ji
   Russell, Pamela
   Aken, Bronwen
   Alfoeldi, Jessica
   Amemiya, Chris
   Azzouzi, Naoual
   Baroiller, Jean-Francois
   Barloy-Hubler, Frederique
   Berlin, Aaron
   Bloomquist, Ryan
   Carleton, Karen L.
   Conte, Matthew A.
   D'Cotta, Helena
   Eshel, Orly
   Gaffney, Leslie
   Galibert, Francis
   Gante, Hugo F.
   Gnerre, Sante
   Greuter, Lucie
   Guyon, Richard
   Haddad, Natalie S.
   Haerty, Wilfried
   Harris, Rayna M.
   Hofmann, Hans A.
   Hourlier, Thibaut
   Hulata, Gideon
   Jaffe, David B.
   Lara, Marcia
   Lee, Alison P.
   MacCallum, Iain
   Mwaiko, Salome
   Nikaido, Masato
   Nishihara, Hidenori
   Ozouf-Costaz, Catherine
   Penman, David J.
   Przybylski, Dariusz
   Rakotomanga, Michaelle
   Renn, Suzy C. P.
   Ribeiro, Filipe J.
   Ron, Micha
   Salzburger, Walter
   Sanchez-Pulido, Luis
   Santos, M. Emilia
   Searle, Steve
   Sharpe, Ted
   Swofford, Ross
   Tan, Frederick J.
   Williams, Louise
   Young, Sarah
   Yin, Shuangye
   Okada, Norihiro
   Kocher, Thomas D.
   Miska, Eric A.
   Lander, Eric S.
   Venkatesh, Byrappa
   Fernald, Russell D.
   Meyer, Axel
   Ponting, Chris P.
   Streelman, J. Todd
   Lindblad-Toh, Kerstin
   Seehausen, Ole
   Di Palma, Federica
TI The genomic substrate for adaptive radiation in African cichlid fish
SO NATURE
LA English
DT Article
ID lake-victoria; sexual selection; evolution; age; duplication; tanganyika; speciation; conflict; trait
AB Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
C1 [Brawand, David; Turner-Maier, Jason; Johnson, Jeremy; Noh, Hyun Ji; Alfoeldi, Jessica; Berlin, Aaron; Gaffney, Leslie; Gnerre, Sante; Jaffe, David B.; Lara, Marcia; MacCallum, Iain; Przybylski, Dariusz; Ribeiro, Filipe J.; Sharpe, Ted; Swofford, Ross; Williams, Louise; Young, Sarah; Yin, Shuangye; Lander, Eric S.; Lindblad-Toh, Kerstin; Di Palma, Federica] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Brawand, David; Li, Yang I.; Haerty, Wilfried; Sanchez-Pulido, Luis; Ponting, Chris P.] Univ Oxford, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Wagner, Catherine E.; Greuter, Lucie; Mwaiko, Salome; Seehausen, Ole] Eawag Swiss Fed Inst Aquat Sci & Technol, Ctr Ecol Evolut & Biogeochemis, Dept Fish Ecol & Evolut, CH-6047 Kastanienbaum, Switzerland.
   [Wagner, Catherine E.; Keller, Irene; Greuter, Lucie; Seehausen, Ole] Univ Bern, Inst Ecol & Evolut, Div Aquat Ecol, CH-3012 Bern, Switzerland.
   [Malinsky, Milan; Miska, Eric A.] Gurdon Inst, Cambridge CB2 1QN, England.
   [Malinsky, Milan; Aken, Bronwen; Hourlier, Thibaut; Searle, Steve] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Fan, Shaohua; Simakov, Oleg; Meyer, Axel] Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
   [Simakov, Oleg] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Ng, Alvin Y.; Lim, Zhi Wei; Lee, Alison P.; Venkatesh, Byrappa] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Bezault, Etienne; Renn, Suzy C. P.] Reed Coll, Dept Biol, Portland, OR 97202 USA.
   [Alcazar, Rosa; Fernald, Russell D.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Russell, Pamela] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
   [Amemiya, Chris] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA.
   [Azzouzi, Naoual; Barloy-Hubler, Frederique; Galibert, Francis; Guyon, Richard; Rakotomanga, Michaelle] Univ Rennes, Inst Genet & Dev, F-35043 Rennes, France.
   [Baroiller, Jean-Francois; D'Cotta, Helena] CIRAD, F-34398 Montpellier 5, France.
   [Bloomquist, Ryan; Haddad, Natalie S.; Streelman, J. Todd] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Carleton, Karen L.; Conte, Matthew A.; Kocher, Thomas D.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Eshel, Orly; Hulata, Gideon; Ron, Micha] Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel.
   [Gante, Hugo F.; Salzburger, Walter; Santos, M. Emilia] Univ Basel, Inst Zool, CH-4051 Basel, Switzerland.
   [Harris, Rayna M.; Hofmann, Hans A.] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Dept Integrat Biol, Austin, TX 78712 USA.
   [Nikaido, Masato; Nishihara, Hidenori; Okada, Norihiro] Tokyo Inst Technol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan.
   [Ozouf-Costaz, Catherine] Natl Museum Nat Hist, F-75005 Paris, France.
   [Penman, David J.] Univ Stirling, Inst Aquaculture, Stirling FK9 4LA, Scotland.
   [Tan, Frederick J.] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
   [Okada, Norihiro] Natl Cheng Kung Univ, Tainan 704, Taiwan.
   [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75123 Uppsala, Sweden.
   [Di Palma, Federica] Genome Anal Ctr, Norwich NR18 7UH, Norfolk, England.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Oxford; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); University of Bern; Wellcome Trust Sanger Institute; University of Konstanz; European Molecular Biology Laboratory (EMBL); Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Reed College - Portland; Stanford University; California Institute of Technology; Benaroya Research Institute; Virginia Mason Medical Center; Universite de Rennes; CIRAD; University System of Georgia; Georgia Institute of Technology; University System of Maryland; University of Maryland College Park; Volcani Institute of Agricultural Research; University of Basel; University of Texas System; University of Texas Austin; Institute of Science Tokyo; Tokyo Institute of Technology; Museum National d'Histoire Naturelle (MNHN); University of Stirling; Carnegie Institution for Science; National Cheng Kung University; Uppsala University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute
RP Di Palma, F (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM todd.streelman@biology.gatech.edu; Kersli@broadinstitute.org; ole.seehausen@eawag.ch; Federica.di-palma@tgac.ac.uk
FU National Human Genome Research Institute (NHGRI); Swiss National Science Foundation [PBLAP3-142774, 31003A-118293, 31003A-144046]; University of Oxford Nuffield Department of Medicine Prize Studentship; German Science Foundation (DFG); European Research Council (ERC) [29700]; Biomedical Research Council of A*STAR, Singapore; ERC; Wellcome Trust;  [2R01DE019637-04]; BBSRC [BBS/E/T/000PR5885, BBS/E/T/000PR6193] Funding Source: UKRI; MRC [MC_UU_12021/1, MC_U137761446] Funding Source: UKRI; Swiss National Science Foundation (SNF) [PBLAP3_142774, 31003A-118293] Funding Source: Swiss National Science Foundation (SNF); Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR5885, BBS/E/T/000PR6193] Funding Source: researchfish; Cancer Research UK [11832] Funding Source: researchfish; Medical Research Council [MC_U137761446, MC_UU_12021/1] Funding Source: researchfish; National Institute of Dental and Craniofacial Research [R01DE019637] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Environmental Biology [1021582, 1143920] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [1021582] Funding Source: National Health and Medical Research Council (NHMRC); Grants-in-Aid for Scientific Research [26106004, 26291075] Funding Source: KAKEN
NR 39
TC 752
Z9 829
U1 7
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 SEP 18
PY 2014
VL 513
IS 7518
BP 375
EP +
DI 10.1038/nature13726
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900051
PM 25186727
DA 2026-03-09
ER

PT J
AU Behjati, S
   Huch, M
   van Boxtel, R
   Karthaus, W
   Wedge, DC
   Tamuri, AU
   Martincorena, I
   Petljak, M
   Alexandrov, LB
   Gundem, G
   Tarpey, PS
   Roerink, S
   Blokker, J
   Maddison, M
   Mudie, L
   Robinson, B
   Nik-Zainal, S
   Campbell, P
   Goldman, N
   van de Wetering, M
   Cuppen, E
   Clevers, H
   Stratton, MR
AF Behjati, Sam
   Huch, Meritxell
   van Boxtel, Ruben
   Karthaus, Wouter
   Wedge, David C.
   Tamuri, Asif U.
   Martincorena, Inigo
   Petljak, Mia
   Alexandrov, Ludmil B.
   Gundem, Gunes
   Tarpey, Patrick S.
   Roerink, Sophie
   Blokker, Joyce
   Maddison, Mark
   Mudie, Laura
   Robinson, Ben
   Nik-Zainal, Serena
   Campbell, Peter
   Goldman, Nick
   van de Wetering, Marc
   Cuppen, Edwin
   Clevers, Hans
   Stratton, Michael R.
TI Genome sequencing of normal cells reveals developmental lineages and mutational processes
SO NATURE
LA English
DT Article
ID lgr5(+ve) stem-cells; 21 breast cancers; somatic mutations; small-intestine; self-renewal; in-vitro; lgr5; colon; fate; homeostasis
AB The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree(1), the number of divisions that each cell has undergone and the mutational processes that have been operative(2). Here we describe whole genomes of clonal lines(3) derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.
C1 [Behjati, Sam; Wedge, David C.; Martincorena, Inigo; Petljak, Mia; Alexandrov, Ludmil B.; Gundem, Gunes; Tarpey, Patrick S.; Roerink, Sophie; Maddison, Mark; Mudie, Laura; Robinson, Ben; Nik-Zainal, Serena; Campbell, Peter; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England.
   [Behjati, Sam] Univ Cambridge, Dept Paediat, Cambridge CB2 2XY, England.
   [Huch, Meritxell; van Boxtel, Ruben; Karthaus, Wouter; Blokker, Joyce; van de Wetering, Marc; Cuppen, Edwin; Clevers, Hans] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, CancerGenom Nl, NL-3584 CT Utrecht, Netherlands.
   [Huch, Meritxell; van Boxtel, Ruben; Karthaus, Wouter; Blokker, Joyce; van de Wetering, Marc; Cuppen, Edwin; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Goldman, Nick] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SA, Cambs, England.
   [Nik-Zainal, Serena] Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 0QQ, England.
C3 Wellcome Trust Sanger Institute; University of Cambridge; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Cambridge
RP Stratton, MR (corresponding author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.
EM mrs@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; Kadoorie Charitable Foundation; Louis-Jeantet Foundation; Marie Curie IEF fellowship [EU/236954]; ERC [232814]; Netherlands Genomics Initiative [935.12.003]; Centre for Biomedical Genetics, Utrecht; EMBO Long Term Fellowship [ALTF-1287-2012]; Wellcome Trust Intermediate Clinical Fellowship [WT100183MA]; Wellcome-Beit Prize Fellowship; Wellcome Trust Research Training Fellowship for Clinicians; Wellcome Trust Senior Research Fellowship in Clinical Science; Wellcome Trust [104151/Z/14/Z] Funding Source: researchfish; European Research Council (ERC) [232814] Funding Source: European Research Council (ERC)
NR 30
TC 275
Z9 330
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 SEP 18
PY 2014
VL 513
IS 7518
BP 422
EP +
DI 10.1038/nature13448
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900061
PM 25043003
DA 2026-03-09
ER

PT J
AU Martin, E
   Palmic, N
   Sanquer, S
   Lenoir, C
   Hauck, F
   Mongellaz, C
   Fabrega, S
   Nitschké, P
   Degli Esposti, M
   Schwartzentruber, J
   Taylor, N
   Majewski, J
   Jabado, N
   Wynn, RF
   Picard, C
   Fischer, A
   Arkwright, PD
   Latour, S
AF Martin, Emmanuel
   Palmic, Noe
   Sanquer, Sylvia
   Lenoir, Christelle
   Hauck, Fabian
   Mongellaz, Cedric
   Fabrega, Sylvie
   Nitschke, Patrick
   Degli Esposti, Mauro
   Schwartzentruber, Jeremy
   Taylor, Naomi
   Majewski, Jacek
   Jabado, Nada
   Wynn, Robert F.
   Picard, Capucine
   Fischer, Alain
   Arkwright, Peter D.
   Latour, Sylvain
TI CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation
SO NATURE
LA English
DT Article
ID novo pyrimidine synthesis; epstein-barr-virus; killer t-cells; de-novo; saccharomyces-cerevisiae; signal-transduction; viral-infection; synthetase; activation; pathway
AB Lymphocyte functions triggered by antigen recognition and costimulation signals are associated with a rapid and intense cell division, and hence with metabolism adaptation(1). The nucleotide cytidine 5' triphosphate (CTP) is a precursor required for the metabolism of DNA, RNA and phospholipids(2-4). CTP originates from two sources: a salvage pathway and a de novo synthesis pathway that depends on two enzymes, the CTP synthases (or synthetases) 1 and 2 (CTPS1 with CTPS2); the respective roles of these two enzymes are not known(5-7). CTP synthase activity is a potentially important step for DNA synthesis in lymphocytes(8,9). Here we report the identification of a loss-of- function homozygous mutation (rs145092287) in CTPS1 in humans that causes a novel and life-threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. In contrast, proximal and distal T-cell receptor (TCR) signalling events and responses were only weakly affected by the absence of CTPS1. Activated CTPS1-deficient cells had decreased levels of CTP. Normal T-cell proliferation was restored in CTPS1-deficient cells by expressing wild-type CTPS1 or by addition of exogenous CTP or its nucleoside precursor, cytidine. CTPS1 expression was found to be low in resting T cells, but rapidly upregulated following TCR activation. These results highlight a key and specific role of CTPS1 in the immune system by its capacity to sustain the proliferation of activated lymphocytes during the immune response. CTPS1 may therefore represent a therapeutic target of immunosuppressive drugs that could specifically dampen lymphocyte activation.
C1 [Martin, Emmanuel; Palmic, Noe; Lenoir, Christelle; Hauck, Fabian; Fischer, Alain; Latour, Sylvain] Hop Necker Enfants Malad, Lab Activat Lymphocytaire & Susceptibilite EBV, INSERM, UMR 1163, F-75015 Paris, France.
   [Martin, Emmanuel; Palmic, Noe; Lenoir, Christelle; Hauck, Fabian; Fabrega, Sylvie; Nitschke, Patrick; Picard, Capucine; Fischer, Alain; Latour, Sylvain] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, France.
   [Sanquer, Sylvia; Latour, Sylvain] Hop Necker Enfants Malad, Lab Biochim Metabol & Proteom, F-75015 Paris, France.
   [Mongellaz, Cedric; Taylor, Naomi] Inst Genet Mol Montpellier, CNRS, UMR 5535, F-34293 Montpellier, France.
   [Fabrega, Sylvie] Hop Necker Enfants Malad, Plateforme Vecteurs Viraux & Transfert Genes, IFR94, F-75015 Paris, France.
   [Nitschke, Patrick] Hop Necker Enfants Malad, Serv Bioinformat, F-75015 Paris, France.
   [Degli Esposti, Mauro; Wynn, Robert F.; Arkwright, Peter D.] Univ Manchester, Royal Manchester Childrens Hosp, Manchester M13 0WL, Lancs, England.
   [Degli Esposti, Mauro] Italian Inst Technol, I-16163 Genoa, Italy.
   [Schwartzentruber, Jeremy; Majewski, Jacek; Jabado, Nada] McGill Univ, Montreal, PQ H3A 0G1, Canada.
   [Schwartzentruber, Jeremy; Majewski, Jacek; Jabado, Nada] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
   [Jabado, Nada] McGill Univ, Hlth Ctr Res Inst, Dept Pediat, Montreal, PQ H3H 1P3, Canada.
   [Picard, Capucine] Hop Necker Enfants Malad, AP HP, Ctr Etude Deficits Immunitaires, F-75015 Paris, France.
   [Picard, Capucine] Hop Necker Enfants Malad, INSERM, Lab Genet Humaine Malad Infect, UMR 1163, F-75015 Paris, France.
   [Fischer, Alain] Hop Necker Enfants Malad, AP HP, Unite Immunol & Hematol Pediat, F-75015 Paris, France.
   [Fischer, Alain] Coll France, F-75005 Paris, France.
C3 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); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Manchester University NHS Foundation Trust; Royal Manchester Children's Hospital; University of Manchester; Istituto Italiano di Tecnologia - IIT; McGill University; McGill University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Universite PSL; College de France
RP Latour, S (corresponding author), Hop Necker Enfants Malad, Lab Activat Lymphocytaire & Susceptibilite EBV, INSERM, UMR 1163, F-75015 Paris, France.
EM sylvain.latour@inserm.fr
FU INSERM; ANR [ANR-08-MIEN-012-01, ANR-2010-MIDI-005-02, ANR-10-IAHU-01]; Fondation ARC (France); European Research Council [ERC-2009-AdG_20090506, FP7-249816]; Rare Diseases Fondation (France); ANR (France); Ligue contre le cancer (France); Wellcome Trust; Medical Research Council [WT095219MA, G1001799]; MRC [G1001799] Funding Source: UKRI; Medical Research Council [G1001799] Funding Source: researchfish
NR 33
TC 178
Z9 212
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 JUN 12
PY 2014
VL 510
IS 7504
BP 288
EP +
DI 10.1038/nature13386
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400054
PM 24870241
DA 2026-03-09
ER

PT J
AU Burrows, MT
   Schoeman, DS
   Richardson, AJ
   Molinos, JG
   Hoffmann, A
   Buckley, LB
   Moore, PJ
   Brown, CJ
   Bruno, JF
   Duarte, CM
   Halpern, BS
   Hoegh-Guldberg, O
   Kappel, CV
   Kiessling, W
   O'Connor, MI
   Pandolfi, JM
   Parmesan, C
   Sydeman, W
   Ferrier, S
   Williams, KJ
   Poloczanska, ES
AF Burrows, Michael T.
   Schoeman, David S.
   Richardson, Anthony J.
   Molinos, Jorge Garcia
   Hoffmann, Ary
   Buckley, Lauren B.
   Moore, Pippa J.
   Brown, Christopher J.
   Bruno, John F.
   Duarte, Carlos M.
   Halpern, Benjamin S.
   Hoegh-Guldberg, Ove
   Kappel, Carrie V.
   Kiessling, Wolfgang
   O'Connor, Mary I.
   Pandolfi, John M.
   Parmesan, Camille
   Sydeman, WilliamJ.
   Ferrier, Simon
   Williams, Kristen J.
   Poloczanska, Elvira S.
TI Geographical limits to species-range shifts are suggested by climate velocity
SO NATURE
LA English
DT Article
ID biodiversity; conservation; marine; distributions; impacts; analog
AB The reorganization of patterns of species diversity driven by anthropogenic climate change, and the consequences for humans(1), are not yet fully understood or appreciated(2,3). Nevertheless, changes in climate conditions are useful for predicting shifts in species distributions at global(4) and local scales(5). Here we use the velocity of climate change(6,7) to derive spatial trajectories for climatic niches from 1960 to 2009 (ref. 7) and from 2006 to 2100, and use the properties of these trajectories to infer changes in species distributions. Coastlines act as barriers and locally cooler areas act as attractors for trajectories, creating source and sink areas for local climatic conditions. Climate source areas indicate where locally novel conditions are not connected to areas where similar climates previously occurred, and are thereby inaccessible to climate migrants tracking isotherms: 16% of global surface area for 1960 to 2009, and 34% of ocean for the 'business as usual' climate scenario (representative concentration pathway (RCP) 8.5)(8) representing continued use of fossil fuels without mitigation. Climate sink areas are where climate conditions locally disappear, potentially blocking the movement of climate migrants. Sink areas comprise 1.0% of ocean area and 3.6% of land and are prevalent on coasts and high ground. Using this approach to infer shifts in species distributions gives global and regional maps of the expected direction and rate of shifts of climate migrants, and suggests areas of potential loss of species richness.
C1 [Burrows, Michael T.; Molinos, Jorge Garcia] Scottish Assoc Marine Sci, Scottish Marine Inst, Dept Ecol, Oban PA37 1QA, Argyll, Scotland.
   [Schoeman, David S.] Univ Sunshine Coast, Sch Sci & Engn, Maroochydore, Qld 4558, Australia.
   [Richardson, Anthony J.; Poloczanska, Elvira S.] CSIRO Marine & Atmospher Res, Ecosci Precinct, Climate Adaptat Flagship, Brisbane, Qld 4001, Australia.
   [Richardson, Anthony J.] Univ Queensland, Sch Math & Phys, Ctr Applicat Nat Resource Math CARM, St Lucia, Qld 4072, Australia.
   [Hoffmann, Ary] Univ Melbourne, Dept Genet, Parkville, Vic 3010, Australia.
   [Buckley, Lauren B.; Bruno, John F.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Moore, Pippa J.] Aberystwyth Univ, Inst Biol Environm & Rural Sci, Aberystwyth SY23 3DA, Dyfed, Wales.
   [Moore, Pippa J.] Edith Cowan Univ, Ctr Marine Ecosyst Res, Perth, WA 6027, Australia.
   [Brown, Christopher J.; Hoegh-Guldberg, Ove] Univ Queensland, Global Change Inst, Brisbane, Qld 4072, Australia.
   [Duarte, Carlos M.] Univ Western Australia, UWA Oceans Inst, Crawley, WA 6009, Australia.
   [Duarte, Carlos M.] IMEDEA UIB CSIC, Dept Global Change Res, Inst Mediterraneo Estudios Avanzados, Esporles 07190, Spain.
   [Duarte, Carlos M.] King Abdulaziz Univ, Fac Marine Sci, Dept Marine Biol, Jeddah 21589, Saudi Arabia.
   [Halpern, Benjamin S.; Kappel, Carrie V.] Univ Calif Santa Barbara, Bren Sch Environm Sci & Management, Santa Barbara, CA 93106 USA.
   [Halpern, Benjamin S.] Univ London Imperial Coll Sci Technol & Med, Ascot SL5 7PY, Berks, England.
   [Kiessling, Wolfgang] Univ Erlangen Nurnberg, GeoZentrum Nordbayern, D-91054 Erlangen, Germany.
   [Kiessling, Wolfgang] Museum Nat Kunde, D-10115 Berlin, Germany.
   [O'Connor, Mary I.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [O'Connor, Mary I.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Pandolfi, John M.] Univ Queensland, Sch Biol Sci, Australian Res Council Ctr Excellence Coral Reef, Brisbane, Qld 4072, Australia.
   [Parmesan, Camille] Univ Texas Austin, Austin, TX 78712 USA.
   [Parmesan, Camille] Univ Plymouth, Marine Inst, Plymouth PL4 8AA, Devon, England.
   [Sydeman, WilliamJ.] Farallon Inst Adv Ecosyst Res, Petaluma, CA 94952 USA.
   [Ferrier, Simon; Williams, Kristen J.] CSIRO Ecosyst Sci, Climate Adaptat Flagship, Canberra, ACT 2601, Australia.
C3 University of the Highlands & Islands; University of the Sunshine Coast; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Queensland; University of Melbourne; University of North Carolina; University of North Carolina Chapel Hill; Aberystwyth University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Institute of Biological, Environmental, Rural & Sciences (IBERS); Edith Cowan University; University of Queensland; University of Western Australia; Consejo Superior de Investigaciones Cientificas (CSIC); ATTITUS Educacao; King Abdulaziz University; University of California System; University of California Santa Barbara; Imperial College London; University of Erlangen Nuremberg; Leibniz Institut fur Evolutions und Biodiversitatsforschung; University of British Columbia; University of British Columbia; University of Queensland; University of Texas System; University of Texas Austin; University of Plymouth; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Ecosystem Sciences
RP Burrows, MT (corresponding author), Scottish Assoc Marine Sci, Scottish Marine Inst, Dept Ecol, Oban PA37 1QA, Argyll, Scotland.
EM mtb@sams.ac.uk
FU National Center for Ecological Analysis and Synthesis; NSF [EF-0553768]; University of California, Santa Barbara; State of California; UK Natural Environment Research Council [NE/J024082/1]; Australian Research Council's Collaborative Research Network; Australian Research Council Centre of Excellence for Coral Reef Studies; Australian Research Council [DP0879365]; Future Fellowship [FT0991722]; NERC [NE/J021938/1, NE/L013029/1, NE/J024082/1, NE/J022446/1] Funding Source: UKRI; Australian Research Council [DP0879365, FT0991722] Funding Source: Australian Research Council; Natural Environment Research Council [NE/J021938/1, NE/J024082/1, NE/J022446/1, NE/L013029/1] Funding Source: researchfish
NR 24
TC 454
Z9 527
U1 6
U2 624
PU NATURE PUBLISHING 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 27
PY 2014
VL 507
IS 7493
BP 492
EP +
DI 10.1038/nature12976
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000039
PM 24509712
DA 2026-03-09
ER

PT J
AU Li, CW
   Ciston, J
   Kanan, MW
AF Li, Christina W.
   Ciston, Jim
   Kanan, Matthew W.
TI Electroreduction of carbon monoxide to liquid fuel on oxide-derived nanocrystalline copper
SO NATURE
LA English
DT Article
ID electrochemical reduction; co2 electroreduction; conversion; hydrocarbons; catalysts; electrode; insights; dioxide
AB The electrochemical conversion of CO2 and H2O into liquid fuel is ideal for high-density renewable energy storage and could provide an incentive for CO2 capture. However, efficient electrocatalysts for reducing CO2 and its derivatives into a desirable fuel(1-3) are not available at present. Although many catalysts(4-11) can reduce CO2 to carbon monoxide (CO), liquid fuel synthesis requires that CO is reduced further, using H2O as a H+ source. Copper (Cu) is the only known material with an appreciable CO electroreduction activity, but in bulk form its efficiency and selectivity for liquid fuel are far too low for practical use. In particular, H2O reduction to H-2 outcompetes CO reduction on Cu electrodes unless extreme overpotentials are applied, at which point gaseous hydrocarbons are the major CO reduction products(12,13). Here we show that nanocrystalline Cu prepared from Cu2O ('oxide-derivedCu') produces multi-carbon oxygenates (ethanol, acetate and n-propanol) with up to 57% Faraday efficiency at modest potentials (-0.25 volts to -0.5 volts versus the reversible hydrogen electrode) in CO-saturated alkaline H2O. By comparison, when prepared by traditional vapour condensation, Cu nanoparticles with an average crystallite size similar to that of oxide-derived copper produce nearly exclusive H-2 (96% Faraday efficiency) under identical conditions. Our results demonstrate the ability to change the intrinsic catalytic properties of Cu for this notoriously difficult reaction by growing interconnected nanocrystallites from the constrained environment of an oxide lattice. The selectivity for oxygenates, with ethanol as the major product, demonstrates the feasibility of a two-step conversion of CO2 to liquid fuel that could be powered by renewable electricity.
C1 [Li, Christina W.; Kanan, Matthew W.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Ciston, Jim] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Ctr Electron Microscopy, Berkeley, CA 94720 USA.
C3 Stanford University; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Kanan, MW (corresponding author), Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
EM mkanan@stanford.edu
FU Stanford University; NSF [CHE-1266401]; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1266401] Funding Source: National Science Foundation
NR 32
TC 1481
Z9 1680
U1 19
U2 2150
PU NATURE PUBLISHING 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 24
PY 2014
VL 508
IS 7497
BP 504
EP +
DI 10.1038/nature13249
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600032
PM 24717429
DA 2026-03-09
ER

PT J
AU Küppers, M
   O'Rourke, L
   Bockelée-Morvan, D
   Zakharov, V
   Lee, S
   von Allmen, P
   Carry, B
   Teyssier, D
   Marston, A
   Müller, T
   Crovisier, J
   Barucci, MA
   Moreno, R
AF Kueppers, Michael
   O'Rourke, Laurence
   Bockelee-Morvan, Dominique
   Zakharov, Vladimir
   Lee, Seungwon
   von Allmen, Paul
   Carry, Benoit
   Teyssier, David
   Marston, Anthony
   Mueller, Thomas
   Crovisier, Jacques
   Barucci, M. Antonietta
   Moreno, Raphael
TI Localized sources of water vapour on the dwarf planet (1) Ceres
SO NATURE
LA English
DT Article
ID dawn mission; surface; ice; organics
AB The 'snowline' conventionally divides Solar System objects into dry bodies, ranging out to the main asteroid belt, and icy bodies beyond the belt. Models suggest that some of the icy bodies may have migrated into the asteroid belt(1). Recent observations indicate the presence of water ice on the surface of some asteroids(2-4), with sublimation(5) a potential reason for the dust activity observed on others. Hydrated minerals have been found(6-8) on the surface of the largest object in the asteroid belt, the dwarf planet (1) Ceres, which is thought to be differentiated into a silicate core with an icy mantle(9-11). The presence of water vapour around Ceres was suggested by a marginal detection of the photodissociation product of water, hydroxyl (ref. 12), but could not be confirmed by later, more sensitive observations(13). Here we report the detection of water vapour around Ceres, with at least 10(26) molecules being produced per second, originating from localized sources that seem to be linked to mid-latitude regions on the surface(14,15). The water evaporation could be due to comet-like sublimation or to cryo-volcanism, in which volcanoes erupt volatiles such as water instead of molten rocks.
C1 [Kueppers, Michael; O'Rourke, Laurence; Carry, Benoit; Teyssier, David; Marston, Anthony] European Space Agcy, European Space Astron Ctr, Villanueva De La Canada 28691, Spain.
   [Bockelee-Morvan, Dominique; Zakharov, Vladimir; Crovisier, Jacques; Barucci, M. Antonietta; Moreno, Raphael] Univ Paris Diderot, Univ Paris 06, Observ Paris, CNRS,Lab Etud Spatiales & Instrumentat Astrophys, F-92195 Meudon, France.
   [Lee, Seungwon; von Allmen, Paul] Jet Prop Lab, La Canada Flintridge, CA 91011 USA.
   [Carry, Benoit] CNRS, Observ Paris, Inst Mecan Celeste & Calcul Ephemerides, Unite Mixte Rech UMR 8028, F-75014 Paris, France.
   [Mueller, Thomas] Max Planck Inst Extraterr Phys MPE, D-85748 Garching, Germany.
C3 European Space Agency; European Space Astronomy Center; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; Universite PSL; Observatoire de Paris; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Max Planck Society
RP Küppers, M (corresponding author), European Space Agcy, European Space Astron Ctr, POB 78, Villanueva De La Canada 28691, Spain.
EM michael.kueppers@sciops.esa.int
FU CEA (France); CNES (France); CNRS (France); ASI (Italy); DLR (Germany); ESA; faculty of the European Space Astronomy Centre (ESAC)
NR 28
TC 227
Z9 258
U1 1
U2 68
PU NATURE PUBLISHING 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 23
PY 2014
VL 505
IS 7484
BP 525
EP +
DI 10.1038/nature12918
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000034
PM 24451541
DA 2026-03-09
ER

PT J
AU Olszak, T
   Neves, JF
   Dowds, CM
   Baker, K
   Glickman, J
   Davidson, NO
   Lin, CS
   Jobin, C
   Brand, S
   Sotlar, K
   Wada, K
   Katayama, K
   Nakajima, A
   Mizuguchi, H
   Kawasaki, K
   Nagata, K
   Müller, W
   Snapper, SB
   Schreiber, S
   Kaser, A
   Zeissig, S
   Blumberg, RS
AF Olszak, Torsten
   Neves, Joana F.
   Dowds, C. Marie
   Baker, Kristi
   Glickman, Jonathan
   Davidson, Nicholas O.
   Lin, Chyuan-Sheng
   Jobin, Christian
   Brand, Stephan
   Sotlar, Karl
   Wada, Koichiro
   Katayama, Kazufumi
   Nakajima, Atsushi
   Mizuguchi, Hiroyuki
   Kawasaki, Kunito
   Nagata, Kazuhiro
   Mueller, Werner
   Snapper, Scott B.
   Schreiber, Stefan
   Kaser, Arthur
   Zeissig, Sebastian
   Blumberg, Richard S.
TI Protective mucosal immunity mediated by epithelial CD1d and IL-10
SO NATURE
LA English
DT Article
ID inflammatory-bowel-disease; triglyceride transfer protein; killer t-cells; ulcerative-colitis; cytoplasmic tail; barrier function; mice; gene; expression; molecules
AB The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host(1,2). CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease(3-8). As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref. 9), decreased epithelial CD1d expression-as observed ininflammatory bowel disease(10,11)-may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1 delicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP)(12,13), as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease.
C1 [Olszak, Torsten; Neves, Joana F.; Baker, Kristi; Snapper, Scott B.; Zeissig, Sebastian; Blumberg, Richard S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
   [Dowds, C. Marie; Schreiber, Stefan; Zeissig, Sebastian] Univ Med Ctr Schleswig Holstein, Dept Internal Med 1, D-24105 Kiel, Germany.
   [Glickman, Jonathan] GI Pathol, Miraca Life Sci, Newton, MA 02464 USA.
   [Davidson, Nicholas O.] Washington Univ, Sch Med, Div Gastroenterol, St Louis, MO 63110 USA.
   [Lin, Chyuan-Sheng] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
   [Jobin, Christian] Univ Florida, Dept Med, Dept Infect Dis & Pathol, Gainesville, FL 32611 USA.
   [Brand, Stephan] Univ Munich, Dept Med Grosshadern 2, D-81377 Munich, Germany.
   [Sotlar, Karl] Univ Munich, Inst Pathol, D-80377 Munich, Germany.
   [Wada, Koichiro; Katayama, Kazufumi] Osaka Univ, Dept Pharmacol, Grad Sch Dent, Suita, Osaka 5650871, Japan.
   [Nakajima, Atsushi] Yokohama City Univ, Div Gastroenterol, Sch Med, Yokohama, Kanagawa 2360027, Japan.
   [Mizuguchi, Hiroyuki] Osaka Univ, Lab Biochem & Mol Biol, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan.
   [Kawasaki, Kunito; Nagata, Kazuhiro] Kyoto Sangyo Univ, Fac Life Sci, Dept Mol Biosci, Kita Ku, Kyoto 6038555, Japan.
   [Mueller, Werner] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England.
   [Snapper, Scott B.] Childrens Hosp, Dept Med, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02115 USA.
   [Kaser, Arthur] Univ Cambridge, Addenbrooke Hosp, Div Gastroenterol, Cambridge CB2 0QQ, England.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; University of Kiel; Schleswig Holstein University Hospital; Washington University (WUSTL); Columbia University; State University System of Florida; University of Florida; University of Munich; University of Munich; University of Osaka; Yokohama City University; University of Osaka; Kyoto Sangyo University; University of Manchester; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Cambridge
RP Blumberg, RS (corresponding author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
EM szeissig@1med.uni-kiel.de; rblumberg@partners.org
FU National Institutes of Health (NIH) [DK044319, DK051362, DK053056, DK088199]; Harvard Digestive Diseases Center [DK0034854]; European Research Council (ERC Starting Grant) [336528]; Deutsche Forschungsgemeinschaft (DFG) [ZE 814/4-1, ZE 814/5-1, ZE 814/6-1]; Crohn's and Colitis Foundation of America; European Commission (Marie Curie International Reintegration Grant) [256363]; DFG Excellence Cluster "Inflammation at Interfaces"; DFG [OL 324/1-1, BR 1912/6-1]; Washington University DDRCC [HL38180, DK56260, P30DK52574]; HDDC Pilot and Feasibility Grant; NCI [P30CA013696]; Else Kroener-Fresenius-Stiftung (Else Kroener-Exzellenzstipendium) [2010_EKES.32]; Japan Society for Promotion of Science [24659823]; ERC under the European Community's Seventh Framework Programme (FP7/ERC) [260961]; National Institute for Health Research Cambridge Biomedical Research Centre; Austrian Science Fund; START [Y446-B18]; Innsbruck Medical University [MFI 2007-407]; Addenbrooke's Charitable Trust, CiCRA; European Community's Seventh Framework Programme (FP7) under grant agreement SysmedIBD [305564]; NIH [HL59561, DK034854, AI50950]; Helmsley Charitable Trust; Wolpow Family Chair in IBD Treatment and Research; Ministry of Science [P21530-B18]; European Research Council (ERC) [336528] Funding Source: European Research Council (ERC); Grants-in-Aid for Scientific Research [24659823] Funding Source: KAKEN; National Cancer Institute [P30CA013696] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854, R01DK053056, R01DK088199, R01DK044319, P30DK052574, R01DK051362] Funding Source: NIH RePORTER; Austrian Science Fund (FWF) [P 21530] Funding Source: researchfish; Austrian Science Fund (FWF) [P21530] Funding Source: Austrian Science Fund (FWF)
NR 38
TC 169
Z9 194
U1 1
U2 85
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 497
EP +
DI 10.1038/nature13150
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000040
PM 24717441
DA 2026-03-09
ER

PT J
AU Sabò, A
   Kress, TR
   Pelizzola, M
   de Pretis, S
   Gorski, MM
   Tesi, A
   Morelli, MJ
   Bora, P
   Doni, M
   Verrecchia, A
   Tonelli, C
   Fagà, G
   Bianchi, V
   Ronchi, A
   Low, D
   Müller, H
   Guccione, E
   Campaner, S
   Amati, B
AF Sabo, Arianna
   Kress, Theresia R.
   Pelizzola, Mattia
   de Pretis, Stefano
   Gorski, Marcin M.
   Tesi, Alessandra
   Morelli, Marco J.
   Bora, Pranami
   Doni, Mirko
   Verrecchia, Alessandro
   Tonelli, Claudia
   Faga, Giovanni
   Bianchi, Valerio
   Ronchi, Alberto
   Low, Diana
   Mueller, Heiko
   Guccione, Ernesto
   Campaner, Stefano
   Amati, Bruno
TI Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis
SO NATURE
LA English
DT Article
ID c-myc; protein-synthesis; global regulation; gene-expression; binding; genome; activation; network; cells; size
AB The c-myc proto-oncogene product, Myc, is a transcription factor that binds thousands of genomic loci(1). Recent work suggested that rather than up-and downregulating selected groups of genes(1-3), Myc targets all active promoters and enhancers in the genome (a phenomenon termed 'invasion') and acts as a general amplifier of transcription(4,5). However, the available data did not readily discriminate between direct and indirect effects of Myc on RNA biogenesis. We addressed this issue with genome-wide chromatin immunoprecipitation and RNA expression profiles during B-cell lymphomagenesis in mice, in cultured B cells and fibroblasts. Consistent with long-standing observations(6), we detected general increases in total RNA or messenger RNA copies per cell (hereby termed 'amplification')(4,5) when comparing actively proliferating cells with control quiescent cells: this was true whether cells were stimulated by mitogens (requiring endogenous Myc for a proliferative response)(7,8) or by deregulated, oncogenic Myc activity. RNA amplification and promoter/enhancer invasion by Myc were separable phenomena that could occur without one another. Moreover, whether or not associated with RNA amplification, Myc drove the differential expression of distinct subsets of target genes. Hence, although having the potential to interact with all active or poised regulatory elements in the genome(4,5,9-11), Myc does not directly act as a global transcriptional amplifier(4,5). Instead, our results indicate that Myc activates and represses transcription of discrete gene sets, leading to changes in cellular state that can in turn feed back on global RNA production and turnover.
C1 [Sabo, Arianna; Kress, Theresia R.; Pelizzola, Mattia; de Pretis, Stefano; Tesi, Alessandra; Morelli, Marco J.; Bora, Pranami; Bianchi, Valerio; Ronchi, Alberto; Mueller, Heiko; Campaner, Stefano; Amati, Bruno] Fdn Ist Italiano Tecnol IIT, Ctr Genom Sci IIT SEMM, I-20139 Milan, Italy.
   [Sabo, Arianna; Kress, Theresia R.; Gorski, Marcin M.; Doni, Mirko; Verrecchia, Alessandro; Tonelli, Claudia; Faga, Giovanni; Amati, Bruno] European Inst Oncol IEO, Dept Expt Oncol, I-20139 Milan, Italy.
   [Low, Diana; Guccione, Ernesto] Inst Mol & Cell Biol, Singapore 138673, Singapore.
C3 Istituto Italiano di Tecnologia - IIT; Center for Genomic Science IIT; IRCCS European Institute of Oncology (IEO); Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB)
RP Amati, B (corresponding author), Fdn Ist Italiano Tecnol IIT, Ctr Genom Sci IIT SEMM, Via Adamello 16, I-20139 Milan, Italy.
EM bruno.amati@iit.it
FU European School of Molecular Medicine; European Community [305626, 200720, 259743]; European Research Council; Association for International Cancer Research (AICR); Italian Health Ministry; Fondazione Cariplo; Italian Association for Cancer Research (AIRC)
NR 56
TC 383
Z9 453
U1 0
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 JUL 24
PY 2014
VL 511
IS 7510
BP 488
EP +
DI 10.1038/nature13537
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700051
PM 25043028
DA 2026-03-09
ER

PT J
AU Dutta, S
   Whicher, JR
   Hansen, DA
   Hale, WA
   Chemler, JA
   Congdon, GR
   Narayan, ARH
   Håkansson, K
   Sherman, DH
   Smith, JL
   Skiniotis, G
AF Dutta, Somnath
   Whicher, Jonathan R.
   Hansen, Douglas A.
   Hale, Wendi A.
   Chemler, Joseph A.
   Congdon, Grady R.
   Narayan, Alison R. H.
   Hakansson, Kristina
   Sherman, David H.
   Smith, Janet L.
   Skiniotis, Georgios
TI Structure of a modular polyketide synthase
SO NATURE
LA English
DT Article
ID particle electron cryomicroscopy; acyl carrier protein; 6-deoxyerythronolide b synthase; iterative chain elongation; near-atomic-resolution; fatty-acid synthase; cryo-em structure; crystal-structure; docking domains; substrate-specificity
AB Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.
C1 [Dutta, Somnath; Whicher, Jonathan R.; Hansen, Douglas A.; Chemler, Joseph A.; Congdon, Grady R.; Narayan, Alison R. H.; Sherman, David H.; Smith, Janet L.; Skiniotis, Georgios] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA.
   [Whicher, Jonathan R.] Univ Michigan, Chem Biol Grad Program, Ann Arbor, MI 48109 USA.
   [Hansen, Douglas A.; Sherman, David H.] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA.
   [Hale, Wendi A.; Sherman, David H.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
   [Sherman, David H.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Smith, Janet L.; Skiniotis, Georgios] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Skiniotis, G (corresponding author), Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA.
EM skinioti@umich.edu
FU Pew Scholar Program in Biomedical Sciences; University of Michigan Biological Sciences Scholars Program; Rackham Merit fellowship; American Foundation for Pharmaceutical Education predoctoral fellowship; National Research Service Award postdoctoral fellowship; Life Sciences Research Foundation; National Institutes of Health [1R21CA138331-01A1, GM076477, DK042303, DK090165]; Hans W. Vahlteich Professorship; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK042303] Funding Source: NIH RePORTER
NR 64
TC 239
Z9 336
U1 2
U2 218
PU NATURE PUBLISHING 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 26
PY 2014
VL 510
IS 7506
BP 512
EP +
DI 10.1038/nature13423
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300041
PM 24965652
DA 2026-03-09
ER

PT J
AU Brunner, JD
   Lim, NK
   Schenck, S
   Duerst, A
   Dutzler, R
AF Brunner, Janine D.
   Lim, Novandy K.
   Schenck, Stephan
   Duerst, Alessia
   Dutzler, Raimund
TI X-ray structure of a calcium-activated TMEM16 lipid scramblase
SO NATURE
LA English
DT Article
ID ca2+-activated cl-channel; chloride channel; protein; family; identification; substructure; purification; transporter; precursors; software
AB The TMEM16 family of proteins, also known as anoctamins, features a remarkable functional diversity. This family contains the long sought-after Ca2+-activated chloride channels as well as lipid scramblases and cation channels. Here we present the crystal structure of a TMEM16 family member from the fungus Nectria haematococca that operates as a Ca2+-activated lipid scramblase. Each subunit of the homodimeric protein contains ten transmembrane helices and a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer as a potential site of catalysis. This cavity harbours a conserved Ca2+-binding site located within the hydrophobic core of the membrane. Mutations of residues involved in Ca2+ coordination affect both lipid scrambling in N. haematococca TMEM16 and ion conduction in the Cl- channel TMEM16A. The structure reveals the general architecture of the family and its mode of Ca2+ activation. It also provides insight into potential scrambling mechanisms and serves as a framework to unravel the conduction of ions in certain TMEM16 proteins.
C1 [Brunner, Janine D.; Lim, Novandy K.; Schenck, Stephan; Duerst, Alessia; Dutzler, Raimund] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
C3 University of Zurich
RP Dutzler, R (corresponding author), Univ Zurich, Dept Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM dutzler@bioc.uzh.ch
FU European Research Council (AnoBest) [339116]; Swiss National Science Foundation through the National Centre of Competence in Research TransCure; European Research Council (ERC) [339116] Funding Source: European Research Council (ERC)
NR 67
TC 359
Z9 413
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 DEC 11
PY 2014
VL 516
IS 7530
BP 207
EP +
DI 10.1038/nature13984
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500036
PM 25383531
DA 2026-03-09
ER

PT J
AU Pellegrino, MW
   Nargund, AM
   Kirienko, NV
   Gillis, R
   Fiorese, CJ
   Haynes, CM
AF Pellegrino, Mark W.
   Nargund, Amrita M.
   Kirienko, Natalia V.
   Gillis, Reba
   Fiorese, Christopher J.
   Haynes, Cole M.
TI Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; translational inhibition; genes; pathways; import; kinase
AB Metazoans identify and eliminate bacterial pathogens in microbe-rich environments such as the intestinal lumen; however, the mechanisms are unclear. Host cells could potentially use intracellular surveillance or stress response programs to detect pathogens that target monitored cellular activities and then initiate innate immune responses(1-3). Mitochondrial function is evaluated by monitoring mitochondrial protein import efficiency of the transcription factor ATFS-1, which mediates the mitochondrial unfolded protein response (UPRmt). During mitochondrial stress, mitochondrial import is impaired(4), allowing ATFS-1 to traffic to the nucleus where it mediates a transcriptional response to re-establish mitochondrial homeostasis(5). Here we examined the role of ATFS-1 in Caenorhabditis elegans during pathogen exposure, because during mitochondrial stress ATFS-1 induced not only mitochondrial protective genes but also innate immune genes that included a secreted lysozyme and anti-microbial peptides. Exposure to the pathogen Pseudomonas aeruginosa caused mitochondrial dysfunction and activation of the UPRmt. C. elegans lacking atfs-1 were susceptible to P. aeruginosa, whereas hyper-activation of ATFS-1 and the UPRmt improved clearance of P. aeruginosa from the intestine and prolonged C. elegans survival in a manner mainly independent of known innate immune pathways(6,7). We propose that ATFS-1 import efficiency and the UPRmt is a means to detect pathogens that target mitochondria and initiate a protective innate immune response.
C1 [Pellegrino, Mark W.; Nargund, Amrita M.; Gillis, Reba; Haynes, Cole M.] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA.
   [Kirienko, Natalia V.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Kirienko, Natalia V.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Fiorese, Christopher J.; Haynes, Cole M.] Weill Cornell Med Coll, BCMB Allied Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Cornell University; Weill Cornell Medicine
RP Haynes, CM (corresponding author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, 1275 York Ave, New York, NY 10065 USA.
EM haynesc@mskcc.org
FU Ellison Medical Foundation; Lucille Castori Center for Microbes, Inflammation and Cancer at MSKCC; National Institutes of Health [R01AG040061, F32AI100501, R01AI085581]
NR 36
TC 293
Z9 336
U1 2
U2 99
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 414
EP +
DI 10.1038/nature13818
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800051
PM 25274306
DA 2026-03-09
ER

PT J
AU Higham, T
   Douka, K
   Wood, R
   Ramsey, CB
   Brock, F
   Basell, L
   Camps, M
   Arrizabalaga, A
   Baena, J
   Barroso-Ruíz, C
   Bergman, C
   Boitard, C
   Boscato, P
   Caparrós, M
   Conard, NJ
   Draily, C
   Froment, A
   Galván, B
   Gambassini, P
   Garcia-Moreno, A
   Grimaldi, S
   Haesaerts, P
   Holt, B
   Iriarte-Chiapusso, MJ
   Jelinek, A
   Pardo, JFJ
   Maíllo-Fernández, JM
   Marom, A
   Maroto, J
   Menéndez, M
   Metz, L
   Morin, E
   Moroni, A
   Negrino, F
   Panagopoulou, E
   Peresani, M
   Pirson, S
   de la Rasilla, M
   Riel-Salvatore, J
   Ronchitelli, A
   Santamaria, D
   Semal, P
   Slimak, L
   Soler, J
   Soler, N
   Villaluenga, A
   Pinhasi, R
   Jacobi, R
AF Higham, Tom
   Douka, Katerina
   Wood, Rachel
   Ramsey, Christopher Bronk
   Brock, Fiona
   Basell, Laura
   Camps, Marta
   Arrizabalaga, Alvaro
   Baena, Javier
   Barroso-Ruiz, Cecillio
   Bergman, Christopher
   Boitard, Coralie
   Boscato, Paolo
   Caparros, Miguel
   Conard, Nicholas J.
   Draily, Christelle
   Froment, Alain
   Galvan, Bertila
   Gambassini, Paolo
   Garcia-Moreno, Alejandro
   Grimaldi, Stefano
   Haesaerts, Paul
   Holt, Brigitte
   Iriarte-Chiapusso, Maria-Jose
   Jelinek, Arthur
   Jorda Pardo, Jesus F.
   Maillo-Fernandez, Jose-Manuel
   Marom, Anat
   Maroto, Julia
   Menendez, Mario
   Metz, Laure
   Morin, Eugene
   Moroni, Adriana
   Negrino, Fabio
   Panagopoulou, Eleni
   Peresani, Marco
   Pirson, Stephane
   de la Rasilla, Marco
   Riel-Salvatore, Julien
   Ronchitelli, Annamaria
   Santamaria, David
   Semal, Patrick
   Slimak, Ludovic
   Soler, Joaquim
   Soler, Narcis
   Villaluenga, Aritza
   Pinhasi, Ron
   Jacobi, Roger
TI The timing and spatiotemporal patterning of Neanderthal disappearance
SO NATURE
LA English
DT Article
ID radiocarbon-dates; chronology; middle; bone; pretreatment; sequence; europe; grotte; renne; age
AB The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology(1,2). Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at 50,000 years ago(3). Here we apply improved accelerator mass spectrometry C-14 techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years BP (at 95.4% probability) across Europe. Wealso demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Chatelperronian)(4), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex(5), allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.
C1 [Higham, Tom; Douka, Katerina; Wood, Rachel; Ramsey, Christopher Bronk; Brock, Fiona; Marom, Anat] Univ Oxford, Oxford Radiocarbon Accelerator Unit, Res Lab Archaeol & Hist Art, Oxford OX1 3QY, England.
   [Wood, Rachel] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Basell, Laura] Queens Univ Belfast, Sch Geog Archaeol & Palaeoecol GAP, Belfast BT7 1NN, Antrim, North Ireland.
   [Camps, Marta] Univ Maryland, Sch Languages Literatures & Cultures, College Pk, MD 20742 USA.
   [Arrizabalaga, Alvaro; Iriarte-Chiapusso, Maria-Jose] Univ Basque Country UPV EHU, IKERBASQUE, Res Team Prehist IT 622 13, Vitoria 01006, Spain.
   [Baena, Javier] Univ Autonoma Madrid, Departimento Prehist & Arqueol, E-28049 Madrid, Spain.
   [Barroso-Ruiz, Cecillio] Fdn Inst Invest Prehist & Evoluc Humana, Cordoba 14900, Spain.
   [Bergman, Christopher] URS, Cincinnati, OH 45202 USA.
   [Boscato, Paolo; Gambassini, Paolo; Moroni, Adriana; Ronchitelli, Annamaria] Univ Siena, UR Preistoria & Antropol, Dipartimento Sci Fis Terra & Ambiente, I-53100 Siena, Italy.
   [Caparros, Miguel] Museum Natl Hist Nat, Dept Prehist, F-75013 Paris, France.
   [Conard, Nicholas J.] Univ Tubingen, Abt Altere Urgeschichte & Quartarokol, D-72070 Tubingen, Germany.
   [Conard, Nicholas J.] Tubingen Senckenberg Ctr Human Evolut & Paleoecol, D-72070 Tubingen, Germany.
   [Draily, Christelle] Serv Archeol, Serv Publ Wallonie, DGO4, B-6700 Arlon, Belgium.
   [Froment, Alain] Musee Homme Paris, Lab Ecoantropol & Ethnobiol, F-75116 Paris, France.
   [Galvan, Bertila] Univ La Laguna, Dept Prehist Arqueol Antropol & Hist Antigua, Tenerife 38071, Spain.
   [Garcia-Moreno, Alejandro; Villaluenga, Aritza] Monrepos Archaeol Res Ctr, D-56567 Neuwied, Germany.
   [Garcia-Moreno, Alejandro; Villaluenga, Aritza] Museum Human Behav Evolut, D-56567 Neuwied, Germany.
   [Grimaldi, Stefano] Univ Trento, Dipartimento Lettere & Filosofia, Lab Preistoria B Bagolini, I-38122 Trento, Italy.
   [Haesaerts, Paul] Inst Royal Sci Nat Belgique, B-1000 Brussels, Belgium.
   [Holt, Brigitte] Univ Massachusetts, Dept Anthropol, Amherst, MA 01003 USA.
   [Jelinek, Arthur] Univ Arizona, Sch Anthropol, Tucson, AZ 85721 USA.
   [Jorda Pardo, Jesus F.; Maillo-Fernandez, Jose-Manuel; Menendez, Mario] UNED, Dept Prehist & Arqueol, Madrid 20840, Spain.
   [Marom, Anat] Weizmann Inst Sci, Kimmel Ctr Archaeol Sci, IL-76100 Rehovot, Israel.
   [Maroto, Julia; Soler, Joaquim; Soler, Narcis] Univ Girona, Area Prehist, Girona 17071, Spain.
   [Metz, Laure; Slimak, Ludovic] Toulouse Jean Jaures Univ, CNRS, TRACES, UMR 5608, F-31058 Toulouse 9, France.
   [Morin, Eugene] Trent Univ, Dept Anthropol, Peterborough, ON K9J 7B8, Canada.
   [Negrino, Fabio] Univ Genoa, Dipartimento Antichita Filosofia & Storia, I-16126 Genoa, Italy.
   [Panagopoulou, Eleni] Ephoreia Paleoanthropol Southern Greece, Athens 11636, Greece.
   [Peresani, Marco] Univ Ferrara, Dipartimento Studi Umanist, Sez Sci Preistor & Antropol, I-44100 Ferrara, Italy.
   [Pirson, Stephane] Serv Publ Wallonie, DGO4, Direct Archeol, B-5100 Jambes, Belgium.
   [de la Rasilla, Marco; Santamaria, David] Univ Oviedo, Dept Hist, Oviedo 33011, Spain.
   [Riel-Salvatore, Julien] Univ Montreal, Dept Anthropol, Montreal, PQ H3T 1N8, Canada.
   [Semal, Patrick] Royal Belgian Inst Nat Sci, Serv Sci Heritage, B-1000 Brussels, Belgium.
   [Pinhasi, Ron] Natl Univ Ireland Univ Coll Dublin, UCD Earth Inst, Dublin 4, Ireland.
   [Pinhasi, Ron] Natl Univ Ireland Univ Coll Dublin, Sch Archaeol, Dublin 4, Ireland.
   [Jacobi, Roger] British Museum, Dept Prehist & Europe, London N1 5QJ, England.
   [Jacobi, Roger] Nat Hist Museum, London SW7 5BD, England.
   [Garcia-Moreno, Alejandro] Univ Cantabria, Cantabria Int Inst Prehist Res IIIPC, E-39005 Santander, Spain.
C3 University of Oxford; Australian National University; Queens University Belfast; University System of Maryland; University of Maryland College Park; Basque Foundation for Science; University of Basque Country; Autonomous University of Madrid; University of Siena; Museum National d'Histoire Naturelle (MNHN); Eberhard Karls University of Tubingen; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Museum National d'Histoire Naturelle (MNHN); Universidad de la Laguna; University of Trento; University of Massachusetts System; University of Massachusetts Amherst; University of Arizona; Universidad Nacional de Educacion a Distancia (UNED); Weizmann Institute of Science; Universitat de Girona; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Trent University; University of Genoa; University of Ferrara; University of Oviedo; Universite de Montreal; Royal Belgian Institute of Natural Sciences; University College Dublin; University College Dublin; Natural History Museum London; Universidad de Cantabria; Instituto Internacional de Investigaciones Prehistoricas de Cantabria (IIIPC)
RP Higham, T (corresponding author), Univ Oxford, Oxford Radiocarbon Accelerator Unit, Res Lab Archaeol & Hist Art, S Parks Rd, Oxford OX1 3QY, England.
EM thomas.higham@rlaha.ox.ac.uk
FU Natural Environment Research Council (NERC) [NE/D014077/1]; Leverhulme Trust through the Ancient Human Occupation of Britain (AHOB) project; NRCF (NERC Radiocarbon Facility) programme, Keble College (Oxford); European Research Council; Natural Environment Research Council [NE/D014077/1, NRCF010002] Funding Source: researchfish; NERC [NRCF010002, NE/D014077/1] Funding Source: UKRI
NR 29
TC 622
Z9 709
U1 2
U2 332
PU NATURE PUBLISHING 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 21
PY 2014
VL 512
IS 7514
BP 306
EP 309
DI 10.1038/nature13621
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200034
PM 25143113
DA 2026-03-09
ER

PT J
AU Pradel, A
   Maisey, JG
   Tafforeau, P
   Mapes, RH
   Mallatt, J
AF Pradel, Alan
   Maisey, John G.
   Tafforeau, Paul
   Mapes, Royal H.
   Mallatt, Jon
TI A Palaeozoic shark with osteichthyan-like branchial arches
SO NATURE
LA English
DT Article
ID evolution; jaw; chondrichthyan; origin
AB The evolution of serially arranged, jointed endoskeletal supports internal to the gills-the visceral branchial arches-represents one of the key events in early jawed vertebrate (gnathostome) history, because it provided the morphological basis for the subsequent evolution of jaws. However, until now little was known about visceral arches in early gnathostomes, and theories about gill arch evolution were driven by information gleaned mostly from both modern cartilaginous (chondrichthyan) and bony (osteichthyan) fishes. New fossil discoveries can profoundly affect our understanding of evolutionary history, by revealing hitherto unseen combinations of primitive and derived characters. Here we describe a 325 million year (Myr)-old Palaeozoic shark-like fossil that represents, to our knowledge, the earliest identified chondrichthyan in which the complete gill skeleton is three-dimensionally preserved in its natural position. Its visceral arch arrangement is remarkably osteichthyan-like, suggesting that this may represent the common ancestral condition for crown gnathostomes. Our findings thus reinterpret the polarity of some arch features of the crown jawed vertebrates and invert the classic hypothesis, in which modern sharks retain the ancestral condition. This study underscores the importance of early chondrichthyans in resolving the evolutionary history of jawed vertebrates.
C1 [Pradel, Alan; Maisey, John G.] Amer Museum Nat Hist, Dept Vertebrate Paleontol, New York, NY 10024 USA.
   [Tafforeau, Paul] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
   [Mapes, Royal H.] Ohio Univ, Dept Geol Sci, Athens, OH 45701 USA.
   [Mallatt, Jon] Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA.
C3 American Museum of Natural History (AMNH); European Synchrotron Radiation Facility (ESRF); University System of Ohio; Ohio University; Washington State University
RP Pradel, A (corresponding author), Amer Museum Nat Hist, Dept Vertebrate Paleontol, Cent Pk West 79th St, New York, NY 10024 USA.
EM apradel@amnh.org; maisey@amnh.org
FU H. R. & E. Axelrod Research Chair in paleoichthyology at the AMNH
NR 30
TC 49
Z9 52
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 MAY 29
PY 2014
VL 509
IS 7502
BP 608
EP +
DI 10.1038/nature13195
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100056
PM 24739974
DA 2026-03-09
ER

PT J
AU Yang, Y
   Lisberger, SG
AF Yang, Yan
   Lisberger, Stephen G.
TI Purkinje-cell plasticity and cerebellar motor learning are graded by complex-spike duration
SO NATURE
LA English
DT Article
ID parallel fibers; climbing fibers; oscillations; dendrites; model
AB Behavioural learning is mediated by cellular plasticity, such as changes in the strength of synapses at specific sites in neural circuits. The theory of cerebellar motor learning(1-3) relies on movement errors signalled by climbing-fibre inputs to cause long-term depression of synapses from parallel fibres to Purkinje cells(4,5). However, a recent review(6) has called into question the widely held view that the climbing-fibre input is an 'all-or-none' event. In anaesthetized animals, there is wide variation in the duration of the complex spike (CS) caused in Purkinje cells by a climbing-fibre input(7). Furthermore, the amount of plasticity in Purkinje cells is graded according to the duration of electrically controlled bursts in climbing fibres(8,9). The duration of bursts depends on the 'state' of the inferior olive and therefore may be correlated across climbing fibres(8,10). Here we provide a potential functional context for these mechanisms during motor learning in behaving monkeys. The magnitudes of both plasticity and motor learning depend on the duration of the CS responses. Furthermore, the duration of CS responses seems to be a meaningful signal that is correlated across the Purkinje-cell population during motor learning. We suggest that during learning, longer bursts in climbing fibres lead to longer-duration CS responses in Purkinje cells, more calcium entry into Purkinje cells, larger synaptic depression, and stronger learning. The same graded impact of instructive signals for plasticity and learning might occur throughout the nervous system.
C1 [Yang, Yan; Lisberger, Stephen G.] Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
   [Lisberger, Stephen G.] Duke Univ, Howard Hughes Med Inst, Durham, NC 27710 USA.
C3 Duke University; Howard Hughes Medical Institute; Duke University
RP Lisberger, SG (corresponding author), Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
EM yanyang@neuro.duke.edu; lisberger@neuro.duke.edu
FU Howard Hughes Medical Institute; National Eye Institute of the National Institutes of Health [R01-EY003878]
NR 29
TC 158
Z9 183
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 JUN 26
PY 2014
VL 510
IS 7506
BP 529
EP +
DI 10.1038/nature13282
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300045
PM 24814344
DA 2026-03-09
ER

PT J
AU Bachetti, M
   Harrison, FA
   Walton, DJ
   Grefenstette, BW
   Chakrabarty, D
   Fürst, F
   Barret, D
   Beloborodov, A
   Boggs, SE
   Christensen, FE
   Craig, WW
   Fabian, AC
   Hailey, CJ
   Hornschemeier, A
   Kaspi, V
   Kulkarni, SR
   Maccarone, T
   Miller, JM
   Rana, V
   Stern, D
   Tendulkar, SP
   Tomsick, J
   Webb, NA
   Zhang, WW
AF Bachetti, M.
   Harrison, F. A.
   Walton, D. J.
   Grefenstette, B. W.
   Chakrabarty, D.
   Fuerst, F.
   Barret, D.
   Beloborodov, A.
   Boggs, S. E.
   Christensen, F. E.
   Craig, W. W.
   Fabian, A. C.
   Hailey, C. J.
   Hornschemeier, A.
   Kaspi, V.
   Kulkarni, S. R.
   Maccarone, T.
   Miller, J. M.
   Rana, V.
   Stern, D.
   Tendulkar, S. P.
   Tomsick, J.
   Webb, N. A.
   Zhang, W. W.
TI An ultraluminous X-ray source powered by an accreting neutron star
SO NATURE
LA English
DT Article
ID strong magnetic-field; xmm-newton; galaxy m82; discovery; pulsars; chandra; pulsations; radiation; models; system
AB The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical infall (the Eddington limit) onto stellar-mass black holes(1,2). Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second(3). Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems(1,2). The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 x 10(39) ergs per second. The pulsating source is spatially coincident with a variable source(4) that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 x 10(40) ergs per second(1). This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.
C1 [Bachetti, M.; Barret, D.; Webb, N. A.] Univ Toulouse, UPS OMP, Inst Rech Astrophys & Planetol, F-31028 Toulouse 4, France.
   [Bachetti, M.; Barret, D.; Webb, N. A.] CNRS, Inst Rech Astrophys & Planetol, F-31028 Toulouse 4, France.
   [Harrison, F. A.; Walton, D. J.; Grefenstette, B. W.; Fuerst, F.; Kulkarni, S. R.; Rana, V.; Tendulkar, S. P.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Chakrabarty, D.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Beloborodov, A.] Columbia Univ, Dept Phys, New York, NY 10027 USA.
   [Boggs, S. E.; Tomsick, J.] Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA.
   [Christensen, F. E.] Tech Univ Denmark, Natl Space Inst, DTU Space, DK-2800 Lyngby, Denmark.
   [Craig, W. W.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Fabian, A. C.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Hailey, C. J.] Columbia Univ, Columbia Astrophys Lab, New York, NY 10027 USA.
   [Hornschemeier, A.; Zhang, W. W.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Kaspi, V.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Maccarone, T.] Texas Tech Univ, Dept Phys, Lubbock, TX 79409 USA.
   [Miller, J. M.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Stern, D.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); California Institute of Technology; Massachusetts Institute of Technology (MIT); Columbia University; University of California System; University of California Berkeley; Technical University of Denmark; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Cambridge; Columbia University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; McGill University; Texas Tech University System; Texas Tech University; University of Michigan System; University of Michigan; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Bachetti, M (corresponding author), Univ Toulouse, UPS OMP, Inst Rech Astrophys & Planetol, 9 Ave Colonel Roche,BP 44346, F-31028 Toulouse 4, France.
EM mbachett@oa-cagliari.inaf.it; fiona@srl.caltech.edu
FU NASA [NNG08FD60C]; NASA; Centre National d'Etudes Spatiales (CNES); Centre National de la Recherche Scientifique (CNRS); Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009987] Funding Source: National Science Foundation; UK Space Agency [ST/L005611/1] Funding Source: researchfish
NR 34
TC 552
Z9 577
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 OCT 9
PY 2014
VL 514
IS 7521
BP 202
EP +
DI 10.1038/nature13791
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100036
PM 25297433
DA 2026-03-09
ER

PT J
AU Zhang, QF
   Siegel, TN
   Martins, RM
   Wang, F
   Cao, J
   Gao, Q
   Cheng, X
   Jiang, LB
   Hon, CC
   Scheidig-Benatar, C
   Sakamoto, H
   Turner, L
   Jensen, ATR
   Claes, A
   Guizetti, J
   Malmquist, NA
   Scherf, A
AF Zhang, Qingfeng
   Siegel, T. Nicolai
   Martins, Rafael M.
   Wang, Fei
   Cao, Jun
   Gao, Qi
   Cheng, Xiu
   Jiang, Lubin
   Hon, Chung-Chau
   Scheidig-Benatar, Christine
   Sakamoto, Hiroshi
   Turner, Louise
   Jensen, Anja T. R.
   Claes, Aurelie
   Guizetti, Julien
   Malmquist, Nicholas A.
   Scherf, Artur
TI Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria
SO NATURE
LA English
DT Article
ID mutually exclusive expression; antigenic variation; virulence genes; plasmodium; exoribonuclease; transcription; domains; binding; subset; shows
AB Antigenic variation of the Plasmodium falciparum multicopy vargene family enables parasite evasion of immune destruction by host antibodies(1),(2). Expression of a particularvar subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebralmalaria(3-6). The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfR Nase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-lengthups Avar transcripts and intron-derived antisense longnon-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II andupsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.
C1 [Zhang, Qingfeng; Wang, Fei] Tongji Univ Sch Med, Shanghai East Hosp, Res Ctr Translat Med, Shanghai 200120, Peoples R China.
   [Zhang, Qingfeng; Wang, Fei] Tongji Univ Sch Med, Inst Infect Dis & Vaccine Dev, Shanghai 200120, Peoples R China.
   [Zhang, Qingfeng; Siegel, T. Nicolai; Martins, Rafael M.; Scheidig-Benatar, Christine; Sakamoto, Hiroshi; Claes, Aurelie; Guizetti, Julien; Malmquist, Nicholas A.; Scherf, Artur] Inst Pasteur, Unite Biol Interact Hote Paras, F-75724 Paris, France.
   [Zhang, Qingfeng; Siegel, T. Nicolai; Martins, Rafael M.; Scheidig-Benatar, Christine; Sakamoto, Hiroshi; Claes, Aurelie; Guizetti, Julien; Malmquist, Nicholas A.; Scherf, Artur] CNRS, URA 2581, F-75724 Paris, France.
   [Cao, Jun; Gao, Qi] Jiangsu Inst Parasit Dis, Key Lab Parasit Dis Control & Prevent, Minist Hlth, Wuxi 214064, Peoples R China.
   [Cao, Jun; Gao, Qi] Jiangsu Prov Key Lab Parasite Mol Biol, Wuxi 214064, Peoples R China.
   [Cheng, Xiu; Jiang, Lubin] Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China.
   [Hon, Chung-Chau] Inst Pasteur, Cell Biol Parasitism Unit, F-75724 Paris, France.
   [Hon, Chung-Chau] Inst Pasteur, INSERM, U786, F-75724 Paris, France.
   [Turner, Louise; Jensen, Anja T. R.] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Med Parasitol, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
   [Turner, Louise; Jensen, Anja T. R.] Rigshosp, Copenhagen Univ Hosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
C3 Tongji University; Tongji University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Chinese Academy of Sciences; Shanghai Institute of Immunity and Infection, CAS; Pasteur Network; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; University of Copenhagen; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital
RP Scherf, A (corresponding author), Inst Pasteur, Unite Biol Interact Hote Paras, F-75724 Paris, France.
EM qfzhangsh@aliyun.com; artur.scherf@pasteur.fr
FU European Research Council [250320]; French Parasitology consortium ParaFrap [ANR-11-LABX0024]; National Natural Science Foundation of China (NSFC) [31271388]; French National Research Agency-NSFC [13-ISV3-0003-01, 81361130411]; Fundamental Research Funds for the Central Universities of China [20123283]; Human Frontier Science Program; European Molecular Biology Organization long-term fellowship; NSFC [81271870]; European Research Council (ERC) [250320] Funding Source: European Research Council (ERC); National Health and Medical Research Council (NHMRC) [250320] Funding Source: National Health and Medical Research Council (NHMRC); Novo Nordisk Fonden [NNF13OC0006249] Funding Source: researchfish; Academy of Finland (AKA) [250320] Funding Source: Academy of Finland (AKA)
NR 39
TC 64
Z9 73
U1 1
U2 68
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2014
VL 513
IS 7518
BP 431
EP +
DI 10.1038/nature13468
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900063
PM 25043062
DA 2026-03-09
ER

PT J
AU Trujillo, CA
   Sheppard, SS
AF Trujillo, Chadwick A.
   Sheppard, Scott S.
TI A Sedna-like body with a perihelion of 80 astronomical units
SO NATURE
LA English
DT Article
ID kuiper-belt objects; outer solar-system; extended scattered disk; trans-neptunian belt; inner oort cloud; stellar encounters; birth cluster; giant planets; origin; perturbations
AB The observable Solar System can be divided into three distinct regions: the rocky terrestrial planets including the asteroids at 0.39 to 4.2 astronomical units (AU) from the Sun (where 1 AU is the mean distance between Earth and the Sun), the gas giant planets at 5 to 30 AU from the Sun, and the icy Kuiper belt objects at 30 to 50 AU from the Sun. The 1,000-kilometre-diameter dwarf planet Sedna was discovered ten years ago and was unique in that its closest approach to the Sun (perihelion) is 76 AU, far greater than that of any other Solar System body(1). Formation models indicate that Sedna could be a link between the Kuiper belt objects and the hypothesized outer Oort cloud at around 10,000 AU from the Sun(2-6). Here we report the presence of a second Sedna-like object, 2012 VP113, whose perihelion is 80 AU. The detection of 2012 VP113 confirms that Sedna is not an isolated object; instead, both bodies may be members of the inner Oort cloud, whose objects could outnumber all other dynamically stable populations in the Solar System.
C1 [Trujillo, Chadwick A.] Gemini Observ, Hilo, HI 96720 USA.
   [Sheppard, Scott S.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 Carnegie Institution for Science
RP Trujillo, CA (corresponding author), Gemini Observ, 670 North Aohoku Pl, Hilo, HI 96720 USA.
EM trujillo@gemini.edu
FU National Science Foundation; NASA [NNX12AG26G]; Gemini Observatory; NASA [NNX12AG26G, 75641] Funding Source: Federal RePORTER
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   Dukes D, 2012, ASTROPHYS J, V754, P0, DOI 10.1088/0004-637X/754/1/56
   Gladman B, 2006, ASTROPHYS J, V643, PL135, DOI 10.1086/505214
   Gladman B, 2002, ICARUS, V157, P269, DOI 10.1006/icar.2002.6860
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   Gomes RS, 2006, ICARUS, V184, P589, DOI 10.1016/j.icarus.2006.05.026
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   Pfalzner S, 2013, ASTRON ASTROPHYS, V549, P0, DOI 10.1051/0004-6361/201218792
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   Soares JS, 2013, ASTRON ASTROPHYS, V553, P0, DOI 10.1051/0004-6361/201219840
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NR 42
TC 247
Z9 274
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 27
PY 2014
VL 507
IS 7493
BP 471
EP +
DI 10.1038/nature13156
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000034
PM 24670765
DA 2026-03-09
ER

PT J
AU Hasenclever, J
   Theissen-Krah, S
   Rüpke, LH
   Morgan, JP
   Iyer, K
   Petersen, S
   Devey, CW
AF Hasenclever, Joerg
   Theissen-Krah, Sonja
   Ruepke, Lars H.
   Morgan, Jason P.
   Iyer, Karthik
   Petersen, Sven
   Devey, Colin W.
TI Hybrid shallow on-axis and deep off-axis hydrothermal circulation at fast-spreading ridges
SO NATURE
LA English
DT Article
ID east pacific rise; vent fluids; crustal accretion; phase-separation; midocean ridges; oman ophiolite; oceanic-crust; temperature; model; flow
AB Hydrothermal flow at oceanic spreading centres accounts for about ten per cent of all heat flux in the oceans(1,2) and controls the thermal structure of young oceanic plates. It also influences ocean and crustal chemistry, provides a basis for chemosynthetic ecosystems, and has formed massive sulphide ore deposits throughout Earth's history. Despite this, how and under what conditions heat is extracted, in particular from the lower crust, remains largely unclear. Here we present high-resolution, whole-crust, two-and three-dimensional simulations of hydrothermal flow beneath fast-spreading ridges that predict the existence of two interacting flow components, controlled by different physical mechanisms, that merge above the melt lens to feed ridge-centred vent sites. Shallow on-axis flow structures develop owing to the thermodynamic properties of water, whereas deeper off-axis flow is strongly shaped by crustal permeability, particularly the brittleductile transition. About 60 per cent of the discharging fluid mass is replenished on-axis by warm (up to 300 degrees Celsius) recharge flow surrounding the hot thermal plumes, and the remaining 40 per cent or so occurs as colder and broader recharge up to several kilometres away from the axis that feeds hot (500-700 degrees Celsius) deep-rooted off-axis flow towards the ridge. Despite its lower contribution to the total mass flux, this deep off-axis flow carries about 70 per cent of the thermal energy released at the ridge axis. This combination of two flow components explains the seismically determined thermal structure of the crust and reconciles previously incompatible models favouring either shallower on-axis(3-5) or deeper off-axis hydrothermal circulation(6-8).
C1 [Hasenclever, Joerg; Ruepke, Lars H.; Iyer, Karthik; Petersen, Sven; Devey, Colin W.] Helmholtz Ctr Ocean Res Kiel, GEOMAR, D-24148 Kiel, Germany.
   [Theissen-Krah, Sonja] Univ Oslo, Dept Geosci, N-0316 Oslo, Norway.
   [Theissen-Krah, Sonja] Univ Oslo, CEED, N-0316 Oslo, Norway.
   [Morgan, Jason P.] Univ London, Dept Earth Sci, Egham TW20 0EX, Surrey, England.
C3 Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Oslo; University of Oslo; University of London; Royal Holloway University London
RP Hasenclever, J (corresponding author), Helmholtz Ctr Ocean Res Kiel, GEOMAR, Wischhofstr 1-3, D-24148 Kiel, Germany.
EM jhasenclever@geomar.de
NR 46
TC 90
Z9 105
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 24
PY 2014
VL 508
IS 7497
BP 508
EP +
DI 10.1038/nature13174
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600033
PM 24759413
DA 2026-03-09
ER

PT J
AU Fleurie, A
   Lesterlin, C
   Manuse, S
   Zhao, C
   Cluze, C
   Lavergne, JP
   Franz-Wachtel, M
   Macek, B
   Combet, C
   Kuru, E
   Van Nieuwenhze, MS
   Bruns, YV
   Sherratt, D
   Grangeasse, C
AF Fleurie, Aurore
   Lesterlin, Christian
   Manuse, Sylvie
   Zhao, Chao
   Cluze, Caroline
   Lavergne, Jean-Pierre
   Franz-Wachtel, Mirita
   Macek, Boris
   Combet, Christophe
   Kuru, Erkin
   Van Nieuwenhze, Michael S.
   Bruns, Yves V.
   Sherratt, David
   Grangeasse, Christophe
TI MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae
SO NATURE
LA English
DT Article
ID ser/thr protein-kinase; cell-division; membrane-protein; binding; growth; stkp; identification; morphogenesis; peptidoglycan; maintenance
AB In every living organism, cell division requires accurate identification of the division site and placement of the division machinery. In bacteria, this process is traditionally considered to begin with the polymerization of the highly conserved tubulin-like protein FtsZinto a ring that locates precisely at mid-cell(1). Over the past decades, several systems have been reported to regulate the spatiotemporal assembly and placement of the FtsZ ring(2-5). However, the human pathogen Streptococcus pneumoniae, in common with many other organisms, is devoid of these canonical systems and the mechanisms of positioning the division machinery remain unknown(4,6). Here we characterize a novel factor that locates at the division site before FtsZ and guides septum positioning in pneumococcus. Mid-cell-anchored protein Z (MapZ) forms ring structures at the cell equator and moves apart as the cell elongates, therefore behaving as a permanent beacon of division sites. MapZ then positions the FtsZ ring through direct protein-protein interactions. MapZ-mediated control differs from previously described systems mostly on the basis of negative regulation of FtsZ assembly. Furthermore, MapZ is an endogenous target of the Ser/Thr kinase StkP, which was recently shown to have a central role in cytokinesis and morphogenesis of S. pneumoniae(7-9). We show that both phosphorylated and non-phosphorylated forms of MapZ are required for proper Z-ring formation and dynamics. Altogether, this work uncovers a new mechanism for bacterial cell division that is regulated by phosphorylation and illustrates that nature has evolved a diversity of cell division mechanisms adapted to the different bacterial clades.
C1 [Fleurie, Aurore; Manuse, Sylvie; Zhao, Chao; Lavergne, Jean-Pierre; Combet, Christophe; Grangeasse, Christophe] Univ Lyon 1, CNRS, UMR 5086, IBCP, F-69007 Lyon, France.
   [Lesterlin, Christian; Sherratt, David] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [Cluze, Caroline] Univ Lyon 1, CNRS, UMR 5305, Lab Biol Tissulaire & Ingn Threrapeut,IBCP, F-69007 Lyon, France.
   [Franz-Wachtel, Mirita; Macek, Boris] Univ Tubingen, Proteome Ctr Tubingen, D-72076 Tubingen, Germany.
   [Kuru, Erkin; Van Nieuwenhze, Michael S.; Bruns, Yves V.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Kuru, Erkin; Van Nieuwenhze, Michael S.; Bruns, Yves V.] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Lyon 1; University of Oxford; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Eberhard Karls University of Tubingen; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington
RP Grangeasse, C (corresponding author), Univ Lyon 1, CNRS, UMR 5086, IBCP, F-69007 Lyon, France.
EM christian.lesterlin@bioch.ox.ac.uk; c.grangeasse@ibcp.fr
FU CNRS; Universite Claude Bernard Lyon 1; FINOVI foundation; Agence National de la Recherche [ANR-12-BSV3-0008-01]; Region Rhone-Alpes [ARC1]; Wellcome Trust [WT083469MA, 091911]; National Institutes of Health [GM051986]; Medical Research Council [1514510] Funding Source: researchfish; Agence Nationale de la Recherche (ANR) [ANR-12-BSV3-0008] Funding Source: Agence Nationale de la Recherche (ANR)
NR 50
TC 167
Z9 197
U1 0
U2 231
PU NATURE PUBLISHING 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 11
PY 2014
VL 516
IS 7530
BP 259
EP +
DI 10.1038/nature13966
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500048
PM 25470041
DA 2026-03-09
ER

PT J
AU Lukens, JR
   Gurung, P
   Vogel, P
   Johnson, GR
   Carter, RA
   McGoldrick, DJ
   Bandi, SR
   Calabrese, CR
   Vande Walle, L
   Lamkanfi, M
   Kanneganti, TD
AF Lukens, John R.
   Gurung, Prajwal
   Vogel, Peter
   Johnson, Gordon R.
   Carter, Robert A.
   McGoldrick, Daniel J.
   Bandi, Srinivasa Rao
   Calabrese, Christopher R.
   Vande Walle, Lieselotte
   Lamkanfi, Mohamed
   Kanneganti, Thirumala-Devi
TI Dietary modulation of the microbiome affects autoinflammatory disease
SO NATURE
LA English
DT Article
ID il-1-beta; caspase-8; mice; cell; inflammasome; proteinase-3; homeostasis; activation; deficient; receptors
AB The incidences of chronic inflammatory disorders have increased considerably over the past three decades(1). Recent shifts in dietary consumption may have contributed importantly to this surge, but how dietary consumption modulates inflammatory disease is poorly defined. Pstpip2(cmo) mice, which express a homozygous Leu98Pro missense mutation in the Pombe Cdc15 homology family protein PSTPIP2 (proline-serine-threonine phosphatase interacting protein 2), spontaneously develop osteomyelitis that resembles chronic recurrent multifocal osteomyelitis in humans(2-4). Recent reports demonstrated a crucial role for interleukin-1 beta (IL-1 beta) in osteomyelitis, but deletion of the inflammasome components caspase-1 and NLRP3 failed to rescue Pstpip2(cmo) mice from inflammatory bone disease(5,6). Thus, the upstream mechanisms controlling IL-1 beta production in Pstpip2(cmo) mice remain to be identified. In addition, the environmental factors driving IL-1 beta-dependent inflammatory bone erosion are unknown. Here we show that the intestinal microbiota of diseased Pstpip2(cmo) mice was characterized by an outgrowth of Prevotella. Notably, Pstpip2(cmo) mice that were fed a diet rich in fat and cholesterol maintained a normal body weight, but were markedly protected against inflammatory bone disease and bone erosion. Diet-induced protection against osteomyelitis was accompanied by marked reductions in intestinal Prevotella levels and significantly reduced pro-IL-1 beta expression in distant neutrophils. Furthermore, pro-IL-1 beta expression was also decreased in Pstpip2(cmo) mice treated with antibiotics, and in wild-type mice that were kept under germ-free conditions. We further demonstrate that combined deletion of caspases 1 and 8 was required for protection against IL-1 beta-dependent inflammatory bone disease, whereas the deletion of either caspase alone or of elastase or neutrophil proteinase 3 failed to prevent inflammatory disease. Collectively, this work reveals diet-associated changes in the intestinal microbiome as a crucial factor regulating inflammasome- and caspase-8-mediated maturation of IL-1 beta and osteomyelitis in Pstpip2cmo mice.
C1 [Lukens, John R.; Gurung, Prajwal; Johnson, Gordon R.; Bandi, Srinivasa Rao; Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Anim Resources Ctr, Memphis, TN 38105 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Vet Pathol Core, Memphis, TN 38105 USA.
   [Carter, Robert A.; McGoldrick, Daniel J.] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [Calabrese, Christopher R.] St Jude Childrens Res Hosp, Small Anim Imaging Core, Memphis, TN 38105 USA.
   [Vande Walle, Lieselotte; Lamkanfi, Mohamed] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Vande Walle, Lieselotte; Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University
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 Ghent University [BOF 01N02313, 01J11113]; European Research Council [281600]; National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health [AR056296]; National Cancer Institute, part of the National Institutes of Health [CA163507]; National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health [AI101935]; ALSAC; European Research Council (ERC) [281600] Funding Source: European Research Council (ERC); National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R37AI101935] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR056296] Funding Source: NIH RePORTER
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NR 29
TC 257
Z9 283
U1 0
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 DEC 11
PY 2014
VL 516
IS 7530
BP 246
EP +
DI 10.1038/nature13788
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500045
PM 25274309
DA 2026-03-09
ER

PT J
AU Mellnik, AR
   Lee, JS
   Richardella, A
   Grab, JL
   Mintun, PJ
   Fischer, MH
   Vaezi, A
   Manchon, A
   Kim, EA
   Samarth, N
   Ralph, DC
AF Mellnik, A. R.
   Lee, J. S.
   Richardella, A.
   Grab, J. L.
   Mintun, P. J.
   Fischer, M. H.
   Vaezi, A.
   Manchon, A.
   Kim, E. -A.
   Samarth, N.
   Ralph, D. C.
TI Spin-transfer torque generated by a topological insulator
SO NATURE
LA English
DT Article
ID magnetization dynamics; orientation; electrons
AB Magnetic devices are a leading contender for the implementation of memory and logic technologies that are non-volatile, that can scale to high density and high speed, and that do not wear out. However, widespread application of magnetic memory and logic devices will require the development of efficient mechanisms for reorienting their magnetization using the least possible current and power(1). There has been considerable recent progress in this effort; in particular, it has been discovered that spin-orbit interactions in heavy-metal/ferromagnet bilayers can produce strong current-driven torques on the magnetic layer(2-11), via the spin Hall effect(12,13) in the heavy metal or the Rashba-Edelstein effect(14,15) in the ferromagnet. In the search for materials to provide even more efficient spin-orbit-induced torques, some proposals(16-19) have suggested topological insulators(20,21), which possess a surface state in which the effects of spin-orbit coupling are maximal in the sense that an electron's spin orientation is fixed relative to its propagation direction. Here we report experiments showing that charge current flowing in-plane in a thin film of the topological insulator bismuth selenide (Bi2Se3) at room temperature can indeed exert a strong spin-transfer torque on an adjacent ferromagnetic permalloy (Ni81Fe19) thin film, with a direction consistent with that expected from the topological surface state. We find that the strength of the torque per unit charge current density in Bi2Se3 is greater than for any source of spin-transfer torque measured so far, even for non-ideal topological insulator films in which the surface states coexist with bulk conduction. Our data suggest that topological insulators could enable very efficient electrical manipulation of magnetic materials at room temperature, for memory and logic applications.
C1 [Mellnik, A. R.; Grab, J. L.; Mintun, P. J.; Fischer, M. H.; Vaezi, A.; Kim, E. -A.; Ralph, D. C.] Cornell Univ, Ithaca, NY 14853 USA.
   [Lee, J. S.; Richardella, A.; Samarth, N.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
   [Fischer, M. H.] Weizmann Inst Sci, IL-76100 Rehovot, Israel.
   [Manchon, A.] King Abdullah Univ Sci & Technol, Phys Sci & Engn Div, Thuwal 239556900, Saudi Arabia.
   [Ralph, D. C.] Kavli Inst Cornell, Ithaca, NY 14853 USA.
C3 Cornell University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Weizmann Institute of Science; King Abdullah University of Science & Technology
RP Ralph, DC (corresponding author), Cornell Univ, Ithaca, NY 14853 USA.
EM dcr14@cornell.edu
FU DARPA [N66001-11-1-4110]; NSF/MRSEC [DMR-1120296]; Army Research Office [W911NF-08-2-0032]; NSF [DMR-1010768, ECS-0335765]; Office of Naval Research [N00014-12-1-0117]; C-SPIN, one of six centres of STARnet, a Semiconductor Research Corporation program - MARCO; DARPA; Division Of Materials Research; Direct For Mathematical & Physical Scien [1010768] Funding Source: National Science Foundation
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NR 44
TC 1263
Z9 1438
U1 18
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 JUL 24
PY 2014
VL 511
IS 7510
BP 449
EP +
DI 10.1038/nature13534
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700042
PM 25056062
DA 2026-03-09
ER

PT J
AU Lee, YN
   Barsbold, R
   Currie, PJ
   Kobayashi, Y
   Lee, HJ
   Godefroit, P
   Escuillié, F
   Chinzorig, T
AF Lee, Yuong-Nam
   Barsbold, Rinchen
   Currie, Philip J.
   Kobayashi, Yoshitsugu
   Lee, Hang-Jae
   Godefroit, Pascal
   Escuillie, Francois
   Chinzorig, Tsogtbaatar
TI Resolving the long-standing enigmas of a giant ornithomimosaur Deinocheirus mirificus
SO NATURE
LA English
DT Article
ID north-america; dinosaurs; theropoda; ecomorphology; pygostyle; desert
AB The holotype of Deinocheirus mirificus was collected by the 1965 Polish-Mongolian Palaeontological Expedition at Altan Uul III in the southern Gobi of Mongolia(1). Because the holotype consists mostly of giant forelimbs (2.4 min length) with scapulocoracoids(2), for almost 50 years Deinocheirus has remained one of the most mysterious dinosaurs. The mosaic of ornithomimosaur and nonornithomimosaur characters in the holotype has made it difficult to resolve the phylogenetic status of Deinocheirus(3,4). Here we describe two new specimens of Deinocheirus that were discovered in the Nemegt Formation of Altan Uul IV in 2006 and Bugiin Tsav in 2009. The Bugiin Tsav specimen (MPC-D100/127) includes a left forelimb clearly identifiable as Deinocheirus and is 6% longer than the holotype. The Altan Uul IV specimen(MPC-D100/128) is approximately 74% the size of MPC-D 100/127. Cladistic analysis indicates that Deinocheirus is the largest member of the Ornithomimosauria; however, it has many unique skeletal features unknown in other ornithomimosaurs, indicating that Deinocheirus was a heavily built, non-cursorial animal with an elongate snout, a deep jaw, tall neural spines, a pygostyle, a U-shaped furcula, an expanded pelvis for strong muscle attachments, a relatively short hind limb and broad-tipped pedal unguals. Ecomorphological features in the skull, more than a thousand gastroliths, and stomach contents (fish remains) suggest that Deinocheirus was a megaomnivore that lived in mesic environments.
C1 [Lee, Yuong-Nam; Lee, Hang-Jae] Korea Inst Geosci & Mineral Resources, Geol Museum, Taejon 305350, South Korea.
   [Barsbold, Rinchen; Chinzorig, Tsogtbaatar] Mongolian Acad Sci, Paleontol Ctr, Ulaanbaatar 210351, Mongolia.
   [Currie, Philip J.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
   [Kobayashi, Yoshitsugu] Hokkaido Univ, Hokkaido Univ Museum, Sapporo, Hokkaido 0600810, Japan.
   [Godefroit, Pascal] Royal Belgian Inst Nat Sci, B-1000 Brussels, Belgium.
   [Escuillie, Francois] Eldonia, F-3800 Gannat, France.
C3 Korea Institute of Geoscience & Mineral Resources (KIGAM); Mongolian Academy of Sciences; University of Alberta; Hokkaido University; Royal Belgian Institute of Natural Sciences
RP Lee, YN (corresponding author), Korea Inst Geosci & Mineral Resources, Geol Museum, Taejon 305350, South Korea.
EM ylee@kigam.re.kr
FU Hwaseong City, Gyeonggi Province, South Korea; Korea Institute of Geosciences and Mineral Resources, Korea; Paleontological Center of Mongolian Academy of Sciences, Mongolia; Grants-in-Aid for Scientific Research [24540494] Funding Source: KAKEN
NR 28
TC 91
Z9 103
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 NOV 13
PY 2014
VL 515
IS 7526
BP 257
EP U231
DI 10.1038/nature13874
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400048
PM 25337880
DA 2026-03-09
ER

PT J
AU Alcaide, M
   Scordato, ESC
   Price, TD
   Irwin, DE
AF Alcaide, Miguel
   Scordato, Elizabeth S. C.
   Price, Trevor D.
   Irwin, Darren E.
TI Genomic divergence in a ring species complex
SO NATURE
LA English
DT Article
ID phylloscopus-trochiloides; speciation; evolution; adaptation; component; sympatry; software; distance
AB Ring species provide particularly clear demonstrations of how one species can gradually evolve into two, but are rare in nature(1-3). In the greenish warbler (Phylloscopus trochiloides) species complex, a ring of populations wraps around Tibet. Two reproductively isolated forms co-exist in central Siberia, with a gradient of genetic and phenotypic characteristics through the southern chain of populations connecting them(4-6). Previous genetic evidence has proven inconclusive, however, regarding whether species divergence took place in the face of continuous gene flow and whether hybridization between the terminal forms of the ring ever occurred(7-9). Here we use genome-wide analyses to show that, although spatial patterns of genetic variation are currently mostly as expected of a ring species, historical breaks in gene flow have existed at more than one location around the ring, and the two Siberian forms have occasionally interbred. Substantial periods of geographical isolation occurred not only in the north but also in the western Himalayas, where there is now an extensive hybrid zone between genetically divergent forms. Limited asymmetric introgression has occurred directly between the Siberian forms, although it has not caused a blending of those forms, suggesting selection against introgressed genes in the novel genetic background. Levels of reproductive isolation and genetic introgression are consistent with levels of phenotypic divergence around the ring, with phenotypic similarity and extensive interbreeding across the southwestern contact zone and strong phenotypic divergence and nearly complete reproductive isolation across the northern contact zone. These results cast doubt on the hypothesis that the greenish warbler should be viewed as a rare example of speciation by distance(6), but demonstrate that the greenish warbler displays a continuum from slightly divergent neighbouring populations to almost fully reproductively isolated species.
C1 [Alcaide, Miguel; Irwin, Darren E.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [Alcaide, Miguel; Irwin, Darren E.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Alcaide, Miguel] CSIC, Dept Evolutionary Ecol, Estn Biol Donana, Seville 41092, Spain.
   [Scordato, Elizabeth S. C.; Price, Trevor D.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Scordato, Elizabeth S. C.] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
C3 University of British Columbia; University of British Columbia; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); University of Chicago; University of Colorado System; University of Colorado Boulder
RP Irwin, DE (corresponding author), Univ British Columbia, Dept Zool, 6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada.
EM irwin@zoology.ubc.ca
FU Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [273773]; NSERC discovery grant [311931]; US NSF
NR 34
TC 110
Z9 123
U1 0
U2 217
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 3
PY 2014
VL 511
IS 7507
BP 83
EP U433
DI 10.1038/nature13285
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400040
PM 24870239
DA 2026-03-09
ER

PT J
AU Dai, XL
   Zhang, ZX
   Jin, YZ
   Niu, Y
   Cao, HJ
   Liang, XY
   Chen, LW
   Wang, JP
   Peng, XG
AF Dai, Xingliang
   Zhang, Zhenxing
   Jin, Yizheng
   Niu, Yuan
   Cao, Hujia
   Liang, Xiaoyong
   Chen, Liwei
   Wang, Jianpu
   Peng, Xiaogang
TI Solution-processed, high-performance light-emitting diodes based on quantum dots
SO NATURE
LA English
DT Article
ID colloidal nanocrystals; efficiency; polymer; electroluminescence; devices; dependence; electron; state
AB Solution-processed optoelectronic and electronic devices are attractive owing to the potential for low-cost fabrication of large-area devices and the compatibility with lightweight, flexible plastic substrates. Solution-processed light-emitting diodes (LEDs) using conjugated polymers or quantum dots as emitters have attracted great interest over the past two decades(1,2). However, the overall performance of solution-processed LEDs(2-5)-including their efficiency, efficiency roll-off at high current densities, turn-on voltage and lifetime under operational conditions-remains inferior to that of the best vacuum deposited organic LEDs(6-8). Here we report a solution-processed, multilayer quantum-dot-based LED with excellent performance and reproducibility. It exhibits colour-saturated deep-redemission, subband gap turn-on at 1.7 volts, high external quantum efficiencies of up to 20.5 per cent, low efficiency roll-off (up to 15.1 per cent of the external quantum efficiency at 100 mA cm(-2)), anda long operational lifetime of more than 100,000 hours at 100 cd m(-2), making this device the best-performing solution-processed red LED so far, comparable to state-of-the-art vacuum-deposited organic LEDs(2-8). This optoelectronic performance is achieved by inserting an insulating layer between the quantum dot layer and the oxide electron-transport layer to optimize charge balance in the device and preserve the superior emissive properties of the quantum dots. We anticipate that our results will be a starting point for further research, leading to high-performance, all-solution-processed quantum-dot-based LEDs ideal for next-generation display and solid-state lighting technologies.
C1 [Dai, Xingliang; Jin, Yizheng; Liang, Xiaoyong] Zhejiang Univ, Sch Mat Sci & Engn, Ctr Chem High Performance & Novel Mat, State Key Lab Silicon Mat,Cyrus Tang Ctr Sensor M, Hangzhou 310027, Zhejiang, Peoples R China.
   [Zhang, Zhenxing; Niu, Yuan; Cao, Hujia; Peng, Xiaogang] Zhejiang Univ, Dept Chem, Ctr Chem High Performance & Novel Mat, Hangzhou 310027, Zhejiang, Peoples R China.
   [Chen, Liwei] Chinese Acad Sci, I Lab, Suzhou Inst Nanotech & Nanobion, Suzhou 215123, Peoples R China.
   [Wang, Jianpu] Nanjing Tech Univ NanjingTech, Key Lab Flexible Elect KLOFE, Nanjing 211816, Peoples R China.
   [Wang, Jianpu] Nanjing Tech Univ NanjingTech, Natl Jiangsu Synergist Innovat Ctr Adv Mat SICAM, Inst Adv Mat IAM, Nanjing 211816, Peoples R China.
C3 Zhejiang University; Zhejiang University; Chinese Academy of Sciences; Suzhou Institute of Nano-Tech & Nano-Bionics, CAS; Nanjing Tech University; Nanjing Tech University
RP Jin, YZ (corresponding author), Zhejiang Univ, Sch Mat Sci & Engn, Ctr Chem High Performance & Novel Mat, State Key Lab Silicon Mat,Cyrus Tang Ctr Sensor M, Hangzhou 310027, Zhejiang, Peoples R China.
EM yizhengjin@zju.edu.cn; xpeng@zju.edu.cn
FU National High Technology Research and Development Program of China [2011AA050520]; National Natural Science Foundation of China [21233005, 51172203]; Natural Science Funds for Distinguished Young Scholar of Zhejiang Province [R4110189]; Public Welfare Project of Zhejiang Province [2013C31057]; Jiangsu Natural Science Foundation [BK20130006, BK20131413]; National Basic Research Program of China [2015CB932200]; Jiangsu Specially-Appointed Professor programme
NR 34
TC 2360
Z9 2688
U1 31
U2 2829
PU NATURE PUBLISHING 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 6
PY 2014
VL 515
IS 7525
BP 96
EP 99
DI 10.1038/nature13829
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500036
PM 25363773
DA 2026-03-09
ER

PT J
AU Schachner, ER
   Cieri, RL
   Butler, JP
   Farmer, CG
AF Schachner, Emma R.
   Cieri, Robert L.
   Butler, James P.
   Farmer, C. G.
TI Unidirectional pulmonary airflow patterns in the savannah monitor lizard
SO NATURE
LA English
DT Article
ID body-size; lung; evolution; ventilation; mechanics; anatomy; origin
AB The unidirectional airflow patterns in the lungs of birds have long been considered a unique and specialized trait associated with the oxygen demands of flying, their endothermic metabolism(1) and unusual pulmonary architecture(2,3). However, the discovery of similar flow patterns in the lungs of crocodilians indicates that this character is probably ancestral for all archosaurs-the group that includes extant birds and crocodilians as well as their extinct relatives, such as pterosaurs and dinosaurs(4-6). Unidirectional flow in birds results from aerodynamic valves, rather than from sphincters or other physical mechanisms(7,8), and similar aerodynamic valves seem to be present in crocodilians(4-6). The anatomical and developmental similarities in the primary and secondary bronchi of birds and crocodilians suggest that these structures and airflow patterns may be homologous(4-6,9). The origin of this pattern is at least as old as the split between crocodilians and birds, which occurred in the Triassic period(10). Alternatively, this pattern of flow may be even older; this hypothesis can be tested by investigating patterns of airflow in members of the outgroup to birds and crocodilians, the Lepidosauromorpha (tuatara, lizards and snakes). Here we demonstrate region-specific unidirectional airflow in the lungs of the savannah monitor lizard (Varanus exanthematicus). The presence of unidirectional flow in the lungs of V. exanthematicus thus gives rise to two possible evolutionary scenarios: either unidirectional airflow evolved independently in archosaurs and monitor lizards, or these flow patterns are homologous in archosaurs and V. exanthematicus, having evolved only once in ancestral diapsids (the clade encompassing snakes, lizards, crocodilians and birds). If unidirectional airflow is plesiomorphic for Diapsida, this respiratory character can be reconstructed for extinct diapsids, and evolved in a small ectothermic tetrapod during the Palaeozoic era at least a hundred million years before the origin of birds.
C1 [Schachner, Emma R.; Cieri, Robert L.; Farmer, C. G.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Butler, James P.] Harvard Univ, Sch Med, Dept Med, Div Sleep Med, Boston, MA 02215 USA.
   [Butler, James P.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA.
C3 Utah System of Higher Education; University of Utah; Harvard University; Harvard Medical School; Harvard University; Harvard T.H. Chan School of Public Health
RP Schachner, ER (corresponding author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
EM eschachner@gmail.com; cg.frmr@gmail.com
FU American Association of Anatomists Postdoctoral Fellowship; American Philosophical Society Franklin Research Grant; National Science Foundation [IOS-1055080, IOS-0818973]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1055080] Funding Source: National Science Foundation; Direct For Education and Human Resources; Division Of Graduate Education [0841233] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0818973] Funding Source: National Science Foundation
NR 26
TC 69
Z9 76
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 20
PY 2014
VL 506
IS 7488
BP 367
EP +
DI 10.1038/nature12871
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800041
PM 24336209
DA 2026-03-09
ER

PT J
AU Zhou, LJ
   Hang, J
   Zhou, YL
   Wan, RX
   Lu, GF
   Yin, P
   Yan, CY
   Shi, YG
AF Zhou, Lijun
   Hang, Jing
   Zhou, Yulin
   Wan, Ruixue
   Lu, Guifeng
   Yin, Ping
   Yan, Chuangye
   Shi, Yigong
TI Crystal structures of the Lsm complex bound to the 3′ end sequence of U6 small nuclear RNA
SO NATURE
LA English
DT Article
ID sm-like proteins; snrna; u1; yeast; core; u2; u4; ribonucleoproteins; chaperone; domain
AB Splicing of precursor messenger RNA (pre-mRNA) in eukaryotic cells is carried out by the spliceosome(1), which consists of five small nuclear ribonucleoproteins (snRNPs) and a number of accessory factors and enzymes(2). Each snRNP contains a ring-shaped subcomplex of seven proteins and a specific RNA molecule(2-4). The U6 snRNP contains a unique heptameric Lsm protein complex, which specifically recognizes the U6 small nuclear RNA at its 3' end. Here we report the crystal structures of the heptameric Lsm complex, both by itself and in complex with a 3' fragment of U6 snRNA, at 2.8 angstrom resolution. Each of the seven Lsm proteins interacts with two neighbouring Lsm components to form a doughnut-shaped assembly, with the order Lsm3-2-8-4-7-5-6. The four uridine nucleotides at the 3' end of U6 snRNA are modularly recognized by Lsm3, Lsm2, Lsm8 and Lsm4, with the uracil base specificity conferred by a highly conserved asparagine residue. The uracil base at the extreme 3' end is sandwiched by His 36 and Arg 69 from Lsm3, through pi-pi and cation-pi interactions, respectively. The distinctive end-recognition of U6 snRNA by the Lsm complex contrasts with RNA binding by the Sm complex in the other snRNPs. The structural features and associated biochemical analyses deepen mechanistic understanding of the U6 snRNP function in pre-mRNA splicing.
C1 [Zhou, Lijun; Zhou, Yulin; Shi, Yigong] Tsinghua Univ, Minist Educ, Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Zhou, Lijun; Hang, Jing; Yin, Ping; Yan, Chuangye; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
   [Zhou, Lijun; Hang, Jing; Yin, Ping; Yan, Chuangye; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Hang, Jing; Wan, Ruixue; Lu, Guifeng; Yan, Chuangye] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
RP Shi, YG (corresponding author), Tsinghua Univ, Minist Educ, Key Lab Prot Sci, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU National Natural Science Foundation of China [31130002, 31021002]
NR 37
TC 84
Z9 105
U1 0
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 FEB 6
PY 2014
VL 506
IS 7486
BP 116
EP +
DI 10.1038/nature12803
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100043
PM 24240276
DA 2026-03-09
ER

PT J
AU Dohm, JC
   Minoche, AE
   Holtgräwe, D
   Capella-Gutiérrez, S
   Zakrzewski, F
   Tafer, H
   Rupp, O
   Sörensen, T
   Stracke, R
   Reinhardt, R
   Goesmann, A
   Kraft, T
   Schulz, B
   Stadler, PF
   Schmidt, T
   Gabaldón, T
   Lehrach, H
   Weisshaar, B
   Himmelbauer, H
AF Dohm, Juliane C.
   Minoche, Andre E.
   Holtgraewe, Daniela
   Capella-Gutierrez, Salvador
   Zakrzewski, Falk
   Tafer, Hakim
   Rupp, Oliver
   Soerensen, ThomasRosleff
   Stracke, Ralf
   Reinhardt, Richard
   Goesmann, Alexander
   Kraft, Thomas
   Schulz, Britta
   Stadler, Peter F.
   Schmidt, Thomas
   Gabaldon, Toni
   Lehrach, Hans
   Weisshaar, Bernd
   Himmelbauer, Heinz
TI The genome of the recently domesticated crop plant sugar beet (Beta vulgaris)
SO NATURE
LA English
DT Article
ID resistance gene analogs; de-novo identification; integration; program; l.; chromosome; alignment; family; database; map
AB Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world's annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n=18 chromosomes, has an estimated genome size of 714-758 megabases(1) and shares an ancient genome triplication with other eudicot plants(2). Leafy beets have been cultivated since Roman times, but sugar beet is one of the most recently domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet(3). Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated(4) to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant's potential in energy biotechnology.
C1 [Dohm, Juliane C.; Minoche, Andre E.; Lehrach, Hans; Himmelbauer, Heinz] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Dohm, Juliane C.; Minoche, Andre E.; Capella-Gutierrez, Salvador; Gabaldon, Toni; Himmelbauer, Heinz] Ctr Genom Regulat CRG, Barcelona 08003, Spain.
   [Dohm, Juliane C.; Minoche, Andre E.; Capella-Gutierrez, Salvador; Gabaldon, Toni; Himmelbauer, Heinz] UPF, Barcelona 08003, Spain.
   [Holtgraewe, Daniela; Rupp, Oliver; Soerensen, ThomasRosleff; Stracke, Ralf; Goesmann, Alexander; Weisshaar, Bernd] Univ Bielefeld, CeBiTec, D-33615 Bielefeld, Germany.
   [Holtgraewe, Daniela; Rupp, Oliver; Soerensen, ThomasRosleff; Stracke, Ralf; Goesmann, Alexander; Weisshaar, Bernd] Univ Bielefeld, Dept Biol, D-33615 Bielefeld, Germany.
   [Zakrzewski, Falk; Schmidt, Thomas] Tech Univ Dresden, Dept Biol, D-01217 Dresden, Germany.
   [Tafer, Hakim; Stadler, Peter F.] Univ Leipzig, Dept Comp Sci, D-04107 Leipzig, Germany.
   [Reinhardt, Richard] Max Planck Genome Ctr Cologne, D-50829 Cologne, Germany.
   [Kraft, Thomas] Syngenta, S-26123 Landskrona, Sweden.
   [Schulz, Britta] KWS SAAT AG, D-37574 Einbeck, Germany.
   [Gabaldon, Toni] ICREA, Barcelona 08010, Spain.
C3 Max Planck Society; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; University of Bielefeld; University of Bielefeld; Technische Universitat Dresden; Leipzig University; Max Planck Society; Syngenta; KWS Saat AG; ICREA
RP Himmelbauer, H (corresponding author), Max Planck Inst Mol Genet, Ihnestr 63-73, D-14195 Berlin, Germany.
EM bernd.weisshaar@uni-bielefeld.de; Heinz.himmelbauer@crg.es
FU BMBF [FKZ 0315069A, 0315069B, FKZ 0315962 A, 0315962 B, 0315962 C]; ICREA Funding Source: Custom
NR 45
TC 513
Z9 664
U1 4
U2 247
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 23
PY 2014
VL 505
IS 7484
BP 546
EP +
DI 10.1038/nature12817
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000039
PM 24352233
DA 2026-03-09
ER

PT J
AU Gray, JM
   Frolking, S
   Kort, EA
   Ray, DK
   Kucharik, CJ
   Ramankutty, N
   Friedl, MA
AF Gray, Josh M.
   Frolking, Steve
   Kort, Eric A.
   Ray, Deepak K.
   Kucharik, Christopher J.
   Ramankutty, Navin
   Friedl, Mark A.
TI Direct human influence on atmospheric CO2 seasonality from increased cropland productivity
SO NATURE
LA English
DT Article
ID net primary production; carbon sequestration; harvest index; northern ecosystems; use efficiency; grain-yield; mauna-loa; agriculture; climate; trends
AB Ground- and aircraft-based measurements show that the seasonal amplitude of Northern Hemisphere atmospheric carbon dioxide (CO2) concentrations has increased by as much as 50 per cent over the past 50 years(1-3). This increase has been linked to changes in temperate, boreal and arctic ecosystem properties and processes such as enhanced photosynthesis, increased heterotrophic respiration, and expansion of woody vegetation(4-6). However, the precise causal mechanisms behind the observed changes in atmospheric CO2 seasonality remain unclear(2-4). Here we use production statistics and a carbon accounting model to show that increases in agricultural productivity, which have been largely overlooked in previous investigations, explain as much as a quarter of the observed changes in atmospheric CO2 seasonality. Specifically, Northern Hemisphere extratropical maize, wheat, rice, and soybean production grew by 240 per cent between 1961 and 2008, thereby increasing the amount of net carbon uptake by croplands during the Northern Hemisphere growing season by 0.33 petagrams. Maize alone accounts for two-thirds of this change, owing mostly to agricultural intensification within concentrated production zones in the midwestern United States and northern China. Maize, wheat, rice, and soybeans account for about 68 per cent of extratropical dry biomass production, so it is likely that the total impact of increased agricultural production exceeds the amount quantified here.
C1 [Gray, Josh M.; Friedl, Mark A.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Frolking, Steve] Univ New Hampshire, Earth Syst Res Ctr, Durham, NH 03824 USA.
   [Kort, Eric A.] Univ Michigan, Dept Atmospher Ocean & Space Sci, Ann Arbor, MI 48109 USA.
   [Ray, Deepak K.] Univ Minnesota, Inst Environm, St Paul, MN 55108 USA.
   [Kucharik, Christopher J.] Univ Wisconsin, Dept Agron, Madison, WI 53706 USA.
   [Kucharik, Christopher J.] Univ Wisconsin, Nelson Inst Ctr Sustainabil & Global Environm, Madison, WI 53706 USA.
   [Ramankutty, Navin] McGill Univ, Dept Geog, Montreal, PQ H3A 0B9, Canada.
C3 Boston University; University System Of New Hampshire; University of New Hampshire; University of Michigan System; University of Michigan; University of Minnesota System; University of Minnesota Twin Cities; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; McGill University
RP Gray, JM (corresponding author), Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
EM joshgray@bu.edu
FU CFCAS; NSERC; BIOCAP; Environment Canada; NRCan; CarboEuropelP; FAO-GTOS-TCO; iLEAPS; Max Planck Institute for Biogeochemistry; National Science Foundation; University of Tuscia; Universite Laval; US Department of Energy; NASA [NNX11AE75G]; NSF [EF-1064614, EAR-1038818]; Gordon and Betty Moore Foundation; Institute on Environment at the University of Minnesota; NASA [147139, NNX11AE75G] Funding Source: Federal RePORTER; Direct For Biological Sciences; Emerging Frontiers [1064614, 1065734] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1038907] Funding Source: National Science Foundation; Emerging Frontiers; Direct For Biological Sciences [1065029] Funding Source: National Science Foundation
NR 57
TC 120
Z9 143
U1 0
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 NOV 20
PY 2014
VL 515
IS 7527
BP 398
EP +
DI 10.1038/nature13957
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600042
PM 25409830
DA 2026-03-09
ER

PT J
AU Engineer, CB
   Ghassemian, M
   Anderson, JC
   Peck, SC
   Hu, HH
   Schroeder, JI
AF Engineer, Cawas B.
   Ghassemian, Majid
   Anderson, Jeffrey C.
   Peck, Scott C.
   Hu, Honghong
   Schroeder, Julian I.
TI Carbonic anhydrases, EPF2 and a novel protease mediate CO2 control of stomatal development
SO NATURE
LA English
DT Article
ID asymmetric cell-division; signal-transduction; secretory peptide; abscisic-acid; density; kinase; differentiation; reveals
AB Environmental stimuli, including elevated carbon dioxide levels, regulate stomatal development(1-3); however, the key mechanisms mediating the perception and relay of the CO2 signal to the stomatal development machinery remain elusive. To adapt CO2 intake to water loss, plants regulate the development of stomatal gas exchange pores in the aerial epidermis. A diverse range of plant species show a decrease in stomatal density in response to the continuing rise in atmospheric CO2 (ref. 4). To date, one mutant that exhibits deregulation of this CO2-controlled stomatal development response, hic (which is defective in cell-wall wax biosynthesis, ref. 5), has been identified. Here we show that recently isolated Arabidopsis thaliana beta-carbonic anhydrase double mutants (cal ca4)(6) exhibit an inversion in their response to elevated CO2, showing increased stomatal development at elevated CO2 levels. We characterized the mechanisms mediating this response and identified an extracellular signalling pathway involved in the regulation of CO2-controlled stomatal development by carbonic anhydrases. RNA-seq analyses of transcripts show that the extracellular pro-peptide-encoding gene EPIDERMAL PATTERNING FACTOR 2 (EPF2)(7,8), but not EPFI (ref. 9), is induced in wild-type leaves but not in cal ca4 mutant leaves at elevated CO2 levels. Moreover, EPF2 is essential for CO2 control of stomatal development. Using cell-wall proteomic analyses and CO2-dependent transcriptomic analyses, we identified a novel CO2-induced extracellular protease, CRSP (CO2 RESPONSE SECRETED PROTEASE), as a mediator of CO2-controlled stomatal development. Our results identify mechanisms and genes that function in the repression of stomatal development in leaves during atmospheric CO2 elevation, including the carbonic-anhydrase-encoding genes CA1 and CA4 and the secreted protease CRSP, which cleaves the pro-peptide EPF2, in turn repressing stomatal development. Elucidation of these mechanisms advances the understanding of how plants perceive and relay the elevated CO2 signal and provides a framework to guide future research into how environmental challenges can modulate gas exchange in plants.
C1 [Engineer, Cawas B.; Hu, Honghong; Schroeder, Julian I.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Ghassemian, Majid] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Anderson, Jeffrey C.; Peck, Scott C.] Univ Missouri, Dept Chem, Columbia, MO 65211 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of Missouri System; University of Missouri Columbia
RP Schroeder, JI (corresponding author), Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
EM jischroeder@ucsd.edu
FU National Science Foundation [MCB0918220, MCB1414339, IOS-1025837]; National Institutes of Health [GM060396-ES010337]; BAYER-UC Discovery grant; seed grant from the UCSD-SDCSB [GM085764]; Systems Biology Center; Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the US Department of Energy [DE-FG02-03ER15449]; National Institute of Environmental Health Sciences [P42ES010337] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM060396] Funding Source: NIH RePORTER; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1025837, 1051286] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1414339] Funding Source: National Science Foundation
NR 40
TC 195
Z9 244
U1 0
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 SEP 11
PY 2014
VL 513
IS 7517
BP 246
EP +
DI 10.1038/nature13452
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800053
PM 25043023
DA 2026-03-09
ER

PT J
AU Whelan, R
   Watts, R
   Orr, CA
   Althoff, RR
   Artiges, E
   Banaschewski, T
   Barker, GJ
   Bokde, ALW
   Büchel, C
   Carvalho, FM
   Conrod, PJ
   Flor, H
   Fauth-Bühler, M
   Frouin, V
   Gallinat, J
   Gan, G
   Gowland, P
   Heinz, A
   Ittermann, B
   Lawrence, C
   Mann, K
   Martinot, JL
   Nees, F
   Ortiz, N
   Paillère-Martinot, ML
   Paus, T
   Pausova, Z
   Rietschel, M
   Robbins, TW
   Smolka, MN
   Ströhle, A
   Schumann, G
   Garavan, H
AF Whelan, Robert
   Watts, Richard
   Orr, Catherine A.
   Althoff, Robert R.
   Artiges, Eric
   Banaschewski, Tobias
   Barker, Gareth J.
   Bokde, Arun L. W.
   Buechel, Christian
   Carvalho, Fabiana M.
   Conrod, Patricia J.
   Flor, Herta
   Fauth-Buehler, Mira
   Frouin, Vincent
   Gallinat, Juergen
   Gan, Gabriela
   Gowland, Penny
   Heinz, Andreas
   Ittermann, Bernd
   Lawrence, Claire
   Mann, Karl
   Martinot, Jean-Luc
   Nees, Frauke
   Ortiz, Nick
   Paillere-Martinot, Marie-Laure
   Paus, Tomas
   Pausova, Zdenka
   Rietschel, Marcella
   Robbins, Trevor W.
   Smolka, Michael N.
   Stroehle, Andreas
   Schumann, Gunter
   Garavan, Hugh
TI Neuropsychosocial profiles of current and future adolescent alcohol misusers
SO NATURE
LA English
DT Article
ID substance use; brain; risk; reinforcement; endophenotypes; reliability; impulsivity; dysfunction; inhibition; dependence
AB A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models(1) can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers(2) in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence(3). A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms(4). Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.
C1 [Whelan, Robert; Ortiz, Nick; Garavan, Hugh] Univ Vermont, Dept Psychiat, Burlington, VT 05401 USA.
   [Whelan, Robert] Natl Univ Ireland Univ Coll Dublin, Dept Psychol, Dublin 4, Ireland.
   [Watts, Richard] Univ Vermont, Dept Radiol, Burlington, VT 05401 USA.
   [Orr, Catherine A.] Univ Vermont, Vermont Ctr Children Youth & Families, Burlington, VT 05401 USA.
   [Althoff, Robert R.] Univ Vermont, Dept Pediat, Burlington, VT 05401 USA.
   [Althoff, Robert R.; Garavan, Hugh] Univ Vermont, Dept Psychol, Burlington, VT 05401 USA.
   [Artiges, Eric; Martinot, Jean-Luc] Univ Paris 11, CEA, INSERM, Imaging & Psychiat U1000, F-91400 Orsay, France.
   [Artiges, Eric] Orsay Hosp, Dept Psychiat, F-91400 Orsay, France.
   [Banaschewski, Tobias; Flor, Herta; Fauth-Buehler, Mira; Mann, Karl; Nees, Frauke; Rietschel, Marcella] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Cognit & Clin Neurosci, D-68159 Mannheim, Germany.
   [Barker, Gareth J.; Carvalho, Fabiana M.; Conrod, Patricia J.; Schumann, Gunter] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Bokde, Arun L. W.; Garavan, Hugh] Univ Dublin Trinity Coll, Inst Neurosci, Dublin 2, Ireland.
   [Buechel, Christian; Gallinat, Juergen] Univ Klinikum Hamburg Eppendorf, Dept Syst Neurosci, D-20246 Hamburg, Germany.
   [Buechel, Christian] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
   [Conrod, Patricia J.] Univ Montreal, CHU Ste Justine Hosp, Dept Psychiat, Montreal, PQ H3T 1C5, Canada.
   [Fauth-Buehler, Mira] Heidelberg Univ, Dept Addict Behav & Addict Med, D-68159 Mannheim, Germany.
   [Frouin, Vincent] 14 CEA, DSV, I2BM, F-91191 Gif Sur Yvette, France.
   [Gallinat, Juergen; Heinz, Andreas; Paillere-Martinot, Marie-Laure; Stroehle, Andreas] Charite, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany.
   [Gan, Gabriela; Smolka, Michael N.] Tech Univ Dresden, Dept Psychiat, D-01062 Dresden, Germany.
   [Gan, Gabriela; Smolka, Michael N.] Tech Univ Dresden, Neuroimaging Ctr, D-01062 Dresden, Germany.
   [Gowland, Penny] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Ittermann, Bernd] Phys Tech Bundesanstalt PTB, D-10587 Berlin, Germany.
   [Lawrence, Claire] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England.
   [Martinot, Jean-Luc; Paillere-Martinot, Marie-Laure] Univ Paris 05, AP HP, Dept Adolescent Psychopathol & Med, F-75006 Paris, France.
   [Ortiz, Nick] Univ Vermont, Neurosci Grad Program, Burlington, VT 05401 USA.
   [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON M5R 0A3, Canada.
   [Paus, Tomas] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
   [Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 0A4, Canada.
   [Robbins, Trevor W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England.
   [Robbins, Trevor W.] Univ Cambridge, Dept Psychol, Cambridge CB2 1TN, England.
   [Schumann, Gunter] MRC Social Genet & Dev Psychiat SGDP Ctr, London WC2R 2LS, England.
C3 University of Vermont; University College Dublin; University of Vermont; University of Vermont; University of Vermont; University of Vermont; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); CEA; Central Institute of Mental Health; Ruprecht Karls University Heidelberg; University of London; King's College London; Trinity College Dublin; University of Hamburg; University Medical Center Hamburg-Eppendorf; Stanford University; Universite de Montreal; Ruprecht Karls University Heidelberg; Universite Paris Saclay; CEA; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Technische Universitat Dresden; Technische Universitat Dresden; University of Nottingham; Physikalisch-Technische Bundesanstalt (PTB); University of Nottingham; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; University of Vermont; University of Toronto; Baycrest; McGill University; University of Toronto; Hospital for Sick Children (SickKids); University of Cambridge; University of Cambridge
RP Whelan, R (corresponding author), Univ Vermont, Dept Psychiat, Burlington, VT 05401 USA.
EM Robert.whelan@ucd.ie; Hugh.garavan@uvm.edu
FU European Union [LSHM-CT- 2007-037286]; FP7 projects IMAGEMEND [602450]; MATRICS [603016]; Innovative Medicine Initiative Project EU-AIMS [115300-2]; Medical Research Council Programme Grant "Developmental pathways into adolescent substance abuse" [93558]; Swedish funding agency FORMAS; Medical Research Council; Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge); National Institute for Health Research (NIHR) Biomedical Research Centre at South London; Maudsley NHS Foundation Trust; King's College London; Bundesministerium fur Bildung und Forschung (BMBF) [01GS08152, 01EV0711, eMED SysAlc 01ZX1311A]; Deutsche Forschungsgemeinschaft (DFG) [SP 383/5-1, SM 80/7-1, SFB 940/1, FOR 1617]; French MILDT (Mission Interministerielle de Lutte contre la Drogue et la Toxicomanie); CENIR (Centre de NeuroImagerie de Recherche) within the ICM institute; National Institute of Mental Health [MH082116]; National Institutes of Health Center of Biomedical Research Excellence award from the National Institute of General Medical Sciences [P20GM103644]; Tobacco Centers of Regulatory Science award [P50DA036114]; NASA at University of Vermont [NNX 06AC88G]; National Institute of General Medical Sciences [P20GM103644] Funding Source: NIH RePORTER; Medical Research Council [G0001354, G1000183, G1000183B, G0001354B, G0901858] Funding Source: researchfish; MRC [G0901858] Funding Source: UKRI
NR 43
TC 354
Z9 401
U1 2
U2 198
PU NATURE PUBLISHING 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 14
PY 2014
VL 512
IS 7513
BP 185
EP +
DI 10.1038/nature13402
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700030
PM 25043041
DA 2026-03-09
ER

PT J
AU Lu, PL
   Bai, XC
   Ma, D
   Xie, T
   Yan, CY
   Sun, LF
   Yang, GH
   Zhao, YY
   Zhou, R
   Scheres, SHW
   Shi, YG
AF Lu, Peilong
   Bai, Xiao-chen
   Ma, Dan
   Xie, Tian
   Yan, Chuangye
   Sun, Linfeng
   Yang, Guanghui
   Zhao, Yanyu
   Zhou, Rui
   Scheres, Sjors H. W.
   Shi, Yigong
TI Three-dimensional structure of human γ-secretase
SO NATURE
LA English
DT Article
ID intramembrane proteolysis; transmembrane domain-4; presenilin; nicastrin; complex; binding; protein; resolution; aph-1; model
AB The gamma-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-beta, which accumulates in the brain and consequently causes Alzheimer's disease. Here we report the three-dimensional structure of an intact human gamma-secretase complex at 4.5 angstrom resolution, determined by cryo-electron-microscopy single-particle analysis. The gamma-secretase complex comprises a horseshoe-shaped transmembrane domain, which contains 19 transmembrane segments (TMs), and a large extracellular domain (ECD) from nicastrin, which sits immediately above the hollow space formed by the TM horseshoe. Intriguingly, nicastrin ECD is structurally similar to a large family of peptidases exemplified by the glutamate carboxypeptidase PSMA. This structure serves as an important basis for understanding the functional mechanisms of the gamma-secretase complex.
C1 [Lu, Peilong; Ma, Dan; Xie, Tian; Sun, Linfeng; Zhao, Yanyu; Zhou, Rui; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Lu, Peilong; Ma, Dan; Xie, Tian; Yan, Chuangye; Sun, Linfeng; Yang, Guanghui; Zhao, Yanyu; Zhou, Rui; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Lu, Peilong; Ma, Dan; Xie, Tian; Yan, Chuangye; Sun, Linfeng; Yang, Guanghui; Zhao, Yanyu; Zhou, Rui; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Struct Biol Ctr, Beijing 100084, Peoples R China.
   [Bai, Xiao-chen; Scheres, Sjors H. W.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Yan, Chuangye; Yang, Guanghui] Tsinghua Univ, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Sch Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; MRC Laboratory Molecular Biology; Tsinghua University
RP Scheres, SHW (corresponding author), MRC Lab Mol Biol, Cambridge Biomed Campus, Cambridge CB2 0QH, England.
EM scheres@mrc-lmb.cam.ac.uk; shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2009CB918801]; National Natural Science Foundation of China [30888001, 31021002, 31130002]; European Union Marie Curie Fellowship; UK Medical Research Council [MC_UP_A025_1013]; MRC [MC_UP_A025_1013] Funding Source: UKRI; Medical Research Council [MC_UP_A025_1013] Funding Source: researchfish
NR 60
TC 295
Z9 359
U1 2
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 AUG 14
PY 2014
VL 512
IS 7513
BP 166
EP +
DI 10.1038/nature13567
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700025
PM 25043039
DA 2026-03-09
ER

PT J
AU Acton, SE
   Farrugia, AJ
   Astarita, JL
   Mourao-Sá, D
   Jenkins, RP
   Nye, E
   Hooper, S
   van Blijswijk, J
   Rogers, NC
   Snelgrove, KJ
   Rosewell, I
   Moita, LF
   Stamp, G
   Turley, SJ
   Sahai, E
   Sousa, CRE
AF Acton, Sophie E.
   Farrugia, Aaron J.
   Astarita, Jillian L.
   Mourao-Sa, Diego
   Jenkins, Robert P.
   Nye, Emma
   Hooper, Steven
   van Blijswijk, Janneke
   Rogers, Neil C.
   Snelgrove, Kathryn J.
   Rosewell, Ian
   Moita, Luis F.
   Stamp, Gordon
   Turley, Shannon J.
   Sahai, Erik
   Reis e Sousa, Caetano
TI Dendritic cells control fibroblastic reticular network tension and lymph node expansion
SO NATURE
LA English
DT Article
ID t-cells; in-vivo; b-cells; activation; invasion; rho; migration; proteins; motility; clec-2
AB After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion(1,2). Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes(3) also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion-driven by lymphocyte influx and proliferation-that is the critical hallmark of adaptive immunity.
C1 [Acton, Sophie E.; Farrugia, Aaron J.; Mourao-Sa, Diego; van Blijswijk, Janneke; Rogers, Neil C.; Snelgrove, Kathryn J.; Reis e Sousa, Caetano] Canc Res UK London Res Inst, Immunobiol Lab, London WC2A 3LY, England.
   [Acton, Sophie E.] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England.
   [Farrugia, Aaron J.; Jenkins, Robert P.; Hooper, Steven; Sahai, Erik] Canc Res UK London Res Inst, Tumour Cell Biol Lab, London WC2A 3LY, England.
   [Astarita, Jillian L.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
   [Nye, Emma; Stamp, Gordon] Canc Res UK London Res Inst, Expt Histopathol Lab, London WC2A 3LY, England.
   [Rosewell, Ian] Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK London Res Inst, Transgen Lab, Potters Bar EN6 3LD, Herts, England.
   [Moita, Luis F.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal.
   [Moita, Luis F.] Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal.
   [Turley, Shannon J.] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA.
C3 Cancer Research UK; University of London; University College London; Cancer Research UK; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Cancer Research UK; Cancer Research UK; Instituto Gulbenkian de Ciencia; Universidade de Lisboa; Roche Holding; Roche Holding USA; Genentech
RP Acton, SE (corresponding author), Canc Res UK London Res Inst, Immunobiol Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM sophie.acton@cancer.org.uk; caetano@cancer.org.uk
FU Henry Wellcome Postdoctoral fellowship; Cancer Research UK; Cancer Research UK [15154, 15689] Funding Source: researchfish
NR 28
TC 232
Z9 268
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 OCT 23
PY 2014
VL 514
IS 7523
BP 498
EP +
DI 10.1038/nature13814
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900042
PM 25341788
DA 2026-03-09
ER

PT J
AU Laurance, WF
   Clements, GR
   Sloan, S
   O'Connell, CS
   Mueller, ND
   Goosem, M
   Venter, O
   Edwards, DP
   Phalan, B
   Balmford, A
   Van Der Ree, R
   Arrea, IB
AF Laurance, William F.
   Clements, Gopalasamy Reuben
   Sloan, Sean
   O'Connell, Christine S.
   Mueller, Nathan D.
   Goosem, Miriam
   Venter, Oscar
   Edwards, David P.
   Phalan, Ben
   Balmford, Andrew
   Van Der Ree, Rodney
   Arrea, Irene Burgues
TI A global strategy for road building
SO NATURE
LA English
DT Article
ID brazilian amazon; protected areas; deforestation; conservation; environment; yield
AB The number and extent of roads will expand dramatically this century(1). Globally, at least 25 million kilometres of new roads are anticipated by 2050; a 60% increase in the total length of roads over that in 2010. Nine-tenths of all road construction is expected to occur in developing nations(1), including many regions that sustain exceptional biodiversity and vital ecosystem services. Roads penetrating into wilderness or frontier areas are a major proximate driver of habitat loss and fragmentation, wildfires, overhunting and other environmental degradation, often with irreversible impacts on ecosystems'. Unfortunately, much road proliferation is chaotic or poorly planned(3,4,6), and the rate of expansion is so great that it often overwhelms the capacity of environmental planners and managers(2-7). Here we present a global scheme for prioritizing road building. This large-scale zoning plan seeks to limit the environmental costs of road expansion while maximizing its benefits for human development, by helping to increase agricultural production, which is an urgent priority given that global food demand could double by mid-century(8,9). Our analysis identifies areas with high environmental values where future road building should be avoided if possible, areas where strategic road improvements could promote agricultural development with relatively modest environmental costs, and 'conflict areas' where road building could have sizeable benefits for agriculture but with serious environmental damage. Our plan provides a template for proactively zoning and prioritizing roads during the most explosive era of road expansion in human history.
C1 [Laurance, William F.; Clements, Gopalasamy Reuben; Sloan, Sean; Goosem, Miriam; Venter, Oscar] James Cook Univ, Ctr Trop Environm & Sustainabil Sci, Cairns, Qld 4878, Australia.
   [Laurance, William F.; Clements, Gopalasamy Reuben; Sloan, Sean; Goosem, Miriam; Venter, Oscar] James Cook Univ, Coll Marine & Environm Sci, Cairns, Qld 4878, Australia.
   [Clements, Gopalasamy Reuben] Univ Malaysia Terengganu, Kenyir Res Inst, Kuala Terengganu 21030, Malaysia.
   [O'Connell, Christine S.] Univ Minnesota, Inst Environm, St Paul, MN 55108 USA.
   [O'Connell, Christine S.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Mueller, Nathan D.] Harvard Univ, Ctr Environm, Cambridge, MA 02138 USA.
   [Edwards, David P.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Phalan, Ben; Balmford, Andrew] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Van Der Ree, Rodney] Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia.
   [Van Der Ree, Rodney] Univ Melbourne, Sch Bot, Melbourne, Vic 3010, Australia.
   [Arrea, Irene Burgues] Conservat Strategy Fund, San Jose, Costa Rica.
C3 James Cook University; James Cook University; Universiti Malaysia Terengganu; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Harvard University; University of Sheffield; University of Cambridge; University of Melbourne
RP Laurance, WF (corresponding author), James Cook Univ, Ctr Trop Environm & Sustainabil Sci, Cairns, Qld 4878, Australia.
EM bill.laurance@jcu.edu.au
FU Australian Research Council
NR 30
TC 652
Z9 743
U1 6
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 SEP 11
PY 2014
VL 513
IS 7517
BP 229
EP +
DI 10.1038/nature13717
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800049
PM 25162528
DA 2026-03-09
ER

PT J
AU Perry, RJ
   Samuel, VT
   Petersen, KF
   Shulman, GI
AF Perry, Rachel J.
   Samuel, Varman T.
   Petersen, Kitt F.
   Shulman, Gerald I.
TI The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
SO NATURE
LA English
DT Article
ID nonalcoholic fatty liver; de-novo lipogenesis; c3 gene variants; skeletal-muscle; pyruvate-carboxylase; cellular mechanisms; energy-expenditure; metabolic syndrome; cgi-58 knockdown; weight-reduction
AB Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase C epsilon in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.
C1 [Perry, Rachel J.; Samuel, Varman T.; Petersen, Kitt F.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
   [Samuel, Varman T.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA.
   [Petersen, Kitt F.; Shulman, Gerald I.] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
   [Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06535 USA.
C3 Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System; Novo Nordisk Foundation; University of Copenhagen; Yale University; Yale University; Howard Hughes Medical Institute
RP Shulman, GI (corresponding author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA.
EM gerald.shulman@yale.edu
FU National Institutes of Health [R01 DK-40936, R01 DK-49230, R24 DK-085836, R01 AG-23686, U24 DK-059635, UL1 RR-024139, P30 DK-45735, T32-DK101019, I01-BX000901]; Novo Nordisk Foundation for Basic Metabolic Research, University of Copenhagen; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034989, P30DK045735] Funding Source: NIH RePORTER
NR 121
TC 940
Z9 1062
U1 8
U2 388
PU NATURE PUBLISHING 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 5
PY 2014
VL 510
IS 7503
BP 84
EP 91
DI 10.1038/nature13478
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900035
PM 24899308
DA 2026-03-09
ER

PT J
AU Goldner, A
   Herold, N
   Huber, M
AF Goldner, A.
   Herold, N.
   Huber, M.
TI Antarctic glaciation caused ocean circulation changes at the Eocene-Oligocene transition
SO NATURE
LA English
DT Article
ID circumpolar current; drake passage; onset; parameterization; sensitivity; greenhouse; initiation; impacts; gateway; model
AB Two main hypotheses compete to explain global cooling and the abrupt growth of the Antarctic ice sheet across the Eocene-Oligocene transition about 34 million years ago: thermal isolation of Antarctica due to southern ocean gateway opening(1-4), and declining atmospheric CO2 (refs 5, 6). Increases in ocean thermal stratification and circulation in proxies across the Eocene-Oligocene transition have been interpreted as a unique signature of gateway opening(2,4),but at present both mechanisms remain possible. Here, using a coupled ocean-atmosphere model, we show that the rise of Antarctic glaciation, rather than altered palaeogeography, is best able to explain the observed oceanographic changes. We find that growth of the Antarctic ice sheet caused enhanced northward transport of Antarctic intermediate water and invigorated the formation of Antarctic bottom water, fundamentally reorganizing ocean circulation. Conversely, gateway openings had much less impact on ocean thermal stratification and circulation. Our results support available evidence that CO2 draw down not gateway opening-caused Antarctic ice sheet growth, and further show that these feedbacks in turn altered ocean circulation. The precise timing and rate of glaciation, and thus its impacts on ocean circulation, reflect the balance between potentially positive feedbacks (increases in sea ice extent and enhanced primary productivity) and negative feedbacks (stronger southward heat transport and localized high-latitude warming). The Antarctic ice sheet had a complex, dynamic role in ocean circulation and heat fluxes during its initiation, and these processes are likely to operate in the future.
C1 [Goldner, A.] Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
   [Goldner, A.] Amer Geophys Union, Washington, DC 20009 USA.
   [Herold, N.; Huber, M.] Univ New Hampshire, Dept Earth Sci, Durham, NH 03824 USA.
   [Huber, M.] Univ New Hampshire, Earth Syst Res Ctr, Inst Earth Ocean & Space Sci, Durham, NH 03824 USA.
C3 Purdue University System; Purdue University; University System Of New Hampshire; University of New Hampshire; University System Of New Hampshire; University of New Hampshire
RP Goldner, A (corresponding author), Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
EM aarongoldner@gmail.com; matthew.huber@unh.edu
FU Graduate Assistance in Areas of National Need (GAANN) fellowship through the Computational Sciences and Engineering Program at Purdue University; National Science Foundation (NSF) [OCE 0902882, EAR 1049921]; National Center for Atmospheric Research; NSF; Directorate For Geosciences; Division Of Earth Sciences [1445404] Funding Source: National Science Foundation; EPSCoR; Office Of The Director [1101245] Funding Source: National Science Foundation
NR 46
TC 151
Z9 178
U1 1
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 JUL 30
PY 2014
VL 511
IS 7511
BP 574
EP +
DI 10.1038/nature13597
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300031
PM 25079555
DA 2026-03-09
ER

PT J
AU Igarashi, KM
   Lu, L
   Colgin, LL
   Moser, MB
   Moser, EI
AF Igarashi, Kei M.
   Lu, Li
   Colgin, Laura L.
   Moser, May-Britt
   Moser, Edvard I.
TI Coordination of entorhinal-hippocampal ensemble activity during associative learning
SO NATURE
LA English
DT Article
ID gamma-oscillations; spatial representation; olfactory-bulb; behaving rat; cortex; synchronization; discrimination; information; memory; frequency
AB Accumulating evidence points to cortical oscillations as a mechanism for mediating interactions among functionally specialized neurons in distributed brain circuits(1-6). A brain function that may use such interactions is declarative memory-that is, memory that can be consciously recalled, such as episodes and facts. Declarative memory is enabled by circuits in the entorhinal cortex that interface the hippocampus with the neocortex(7,8). During encoding and retrieval of declarative memories, entorhinal and hippocampal circuits are thought to interact via theta and gamma oscillations(4,6,8), which in awake rodents predominate frequency spectra in both regions(9-12). In favour of this idea, theta-gamma coupling has been observed between entorhinal cortex and hippocampus under steady-state conditions inwell-trained rats(12); however, the relationship between interregional coupling and memory formation remains poorly understood. Here we show, by multisite recording at successive stages of associative learning, that the coherence of firing patterns in directly connected entorhinal-hippocampus circuits evolves as rats learn to use an odour cue to guide navigational behaviour, and that such coherence is invariably linked to the development of ensemble representations for unique trial outcomes in each area. Entorhinal-hippocampal coupling was observed specifically in the 20-40-hertz frequency band and specifically between the distal part of hippocampal area CA1 and the lateral part of entorhinal cortex, the subfields that receive the predominant olfactory input to the hippocampal region(13). Collectively, the results identify 20-40-hertz oscillations as a mechanism for synchronizing evolving representations in dispersed neural circuits during encoding and retrieval of olfactory-spatial associative memory.
C1 [Igarashi, Kei M.; Lu, Li; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, N-7491 Trondheim, Norway.
   [Igarashi, Kei M.; Lu, Li; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Ctr Neural Computat, N-7491 Trondheim, Norway.
   [Colgin, Laura L.] Univ Texas Austin, Ctr Learning & Memory, Austin, TX 78712 USA.
C3 Norwegian University of Science & Technology (NTNU); Norwegian University of Science & Technology (NTNU); University of Texas System; University of Texas Austin
RP Moser, EI (corresponding author), Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, Olav Kyrres Gate 9,MTFS,7491, N-7491 Trondheim, Norway.
EM kei.igarashi@ntnu.no; edvard.moser@ntnu.no
FU European Research Council [232608, 268598]; Kavli Foundation; Centre of Excellence scheme of the Research Council of Norway (Centre for the Biology of Memory and Centre for Neural Computation); Mishima Kaiun Memorial Foundation; Japan Society for the Promotion of Science; European Research Council (ERC) [232608, 268598] Funding Source: European Research Council (ERC)
NR 45
TC 316
Z9 403
U1 2
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 JUN 5
PY 2014
VL 510
IS 7503
BP 143
EP +
DI 10.1038/nature13162
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900045
PM 24739966
DA 2026-03-09
ER

PT J
AU Richerme, P
   Gong, ZX
   Lee, A
   Senko, C
   Smith, J
   Foss-Feig, M
   Michalakis, S
   Gorshkov, AV
   Monroe, C
AF Richerme, Philip
   Gong, Zhe-Xuan
   Lee, Aaron
   Senko, Crystal
   Smith, Jacob
   Foss-Feig, Michael
   Michalakis, Spyridon
   Gorshkov, Alexey V.
   Monroe, Christopher
TI Non-local propagation of correlations in quantum systems with long-range interactions
SO NATURE
LA English
DT Article
ID trapped ions; entanglement; dynamics
C1 [Richerme, Philip; Gong, Zhe-Xuan; Lee, Aaron; Senko, Crystal; Smith, Jacob; Foss-Feig, Michael; Gorshkov, Alexey V.; Monroe, Christopher] Univ Maryland, Dept Phys, Joint Quantum Inst, College Pk, MD 20742 USA.
   [Richerme, Philip; Gong, Zhe-Xuan; Lee, Aaron; Senko, Crystal; Smith, Jacob; Foss-Feig, Michael; Gorshkov, Alexey V.; Monroe, Christopher] NIST, College Pk, MD 20742 USA.
   [Michalakis, Spyridon] CALTECH, Inst Quantum Informat & Matter, Pasadena, CA 91125 USA.
C3 University System of Maryland; University of Maryland College Park; National Institute of Standards & Technology (NIST) - USA; California Institute of Technology
RP Richerme, P (corresponding author), Univ Maryland, Dept Phys, Joint Quantum Inst, College Pk, MD 20742 USA.
EM richerme@umd.edu
FU US Army Research Office (ARO) [W911NF0710576]; DARPA Optical Lattice Emulator Program; ARO [W911NF0410234]; IARPA MQCO Program; USNSF Physics Frontier Center at JQI; NRC; Institute for Quantum Information and Matter, an NSF Physics Frontier Center; Gordon and Betty Moore Foundation [GBMF1250]; Direct For Mathematical & Physical Scien; Division Of Physics [0822671] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1125565, 1430094] Funding Source: National Science Foundation
NR 30
TC 662
Z9 720
U1 2
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 JUL 10
PY 2014
VL 511
IS 7508
BP 198
EP +
DI 10.1038/nature13450
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800038
PM 25008525
DA 2026-03-09
ER

PT J
AU Busche, C
   Vilà-Nadal, L
   Yan, J
   Miras, HN
   Long, DL
   Georgiev, VP
   Asenov, A
   Pedersen, RH
   Gadegaard, N
   Mirza, MM
   Paul, DJ
   Poblet, JM
   Cronin, L
AF Busche, Christoph
   Vila-Nadal, Laia
   Yan, Jun
   Miras, Haralampos N.
   Long, De-Liang
   Georgiev, Vihar P.
   Asenov, Asen
   Pedersen, Rasmus H.
   Gadegaard, Nikolaj
   Mirza, Muhammad M.
   Paul, Douglas J.
   Poblet, Josep M.
   Cronin, Leroy
TI Design and fabrication of memory devices based on nanoscale polyoxometalate clusters
SO NATURE
LA English
DT Article
ID transistor
AB Flash memory devices that is, non-volatile computer storage media that can be electrically erased and reprogrammed are vital for portable electronics, but the scaling down of metal-oxide-semiconductor (MOS) flash memory to sizes of below ten nanometres per data cell presents challenges. Molecules have been proposed to replace MOS flash memory(1), but they suffer from low electrical conductivity, high resistance, low device yield, and finite thermal stability, limiting their integration into current MOS technologies. Although great advances have been made in the pursuit of molecule-based flash memory(2), there are a number of significant barriers to the realization of devices using conventional MOS technologies(3-7). Here we show that core-shell polyoxometalate (POM) molecules(8) can act as candidate storage nodes for MOS flash memory. Realistic, industry-standard device simulations validate our approach at the nanometre scale, where the device performance is determined mainly by the number of molecules in the storage media and not by their position. To exploit the nature of the core-shell POM clusters, we show, at both the molecular and device level, that embedding [(Se(IV)O-3)(2)](4-) as an oxidizable dopant in the cluster core allows the oxidation of the molecule to a [Se(V)(2)O-6](2-) moiety containing a {Se(v)-Se(v)} bond (where curly brackets indicate a moiety, not a molecule) and reveals a new 5 + oxidation state for selenium. This new oxidation state can be observed at the device level, resulting in a new type of memory, which we call 'write-once-erase'. Taken together, these results show that POMs have the potential to be used as a realistic nanoscale flash memory. Also, the configuration of the doped POM core may lead to new types of electrical behaviour(9-11). This work suggests a route to the practical integration of configurable molecules in MOS technologies as the lithographic scales approach the molecular limit(12).
C1 [Busche, Christoph; Vila-Nadal, Laia; Yan, Jun; Miras, Haralampos N.; Long, De-Liang; Cronin, Leroy] Univ Glasgow, Sch Chem, WestCHEM, Glasgow G12 8QQ, Lanark, Scotland.
   [Georgiev, Vihar P.; Asenov, Asen; Pedersen, Rasmus H.; Gadegaard, Nikolaj; Mirza, Muhammad M.; Paul, Douglas J.] Univ Glasgow, Sch Engn, Glasgow G12 8LT, Lanark, Scotland.
   [Poblet, Josep M.] Univ Rovira & Virgili, Dept Quim Fis & Inorgan, E-43007 Tarragona, Spain.
C3 University of Glasgow; University of Glasgow; Universitat Rovira i Virgili
RP Cronin, L (corresponding author), Univ Glasgow, Sch Chem, WestCHEM, Glasgow G12 8QQ, Lanark, Scotland.
EM lee.cronin@glasgow.ac.uk
FU EPSRC [EP/H024107/1, EP/I033459/1, EP/J015156/1]; COST Action [CM1203]; Royal Society Wolfson Foundation for a Merit Award; University of Glasgow; EPSRC [EP/J015156/1, EP/I033459/1, EP/H024107/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/J015156/1, EP/I033459/1, EP/H024107/1] Funding Source: researchfish
NR 17
TC 301
Z9 320
U1 2
U2 452
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 545
EP 549
DI 10.1038/nature13951
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600050
PM 25409147
DA 2026-03-09
ER

PT J
AU Faehnle, CR
   Walleshauser, J
   Joshua-Tor, L
AF Faehnle, Christopher R.
   Walleshauser, Jack
   Joshua-Tor, Leemor
TI Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway
SO NATURE
LA English
DT Article
ID yeast exosome core; perlman syndrome; rna degradation; maturation; zcchc11; subunit; lin-28; phenix; tut4
AB The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs(1-4). Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development(5), glucose metabolism(6) and tissue regeneration(7). Over-expression of Lin28 is correlated with the onset of numerous cancers(8), whereas let-7, a tumour suppressor, silences several human oncogenes(5). Lin28 binds to precursor let-7 (pre-let-7) hairpins(9), triggering the 39 oligo-uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.
C1 [Faehnle, Christopher R.; Walleshauser, Jack; Joshua-Tor, Leemor] WM Keck Struct Biol Lab, Cold Spring Harbor, NY 11724 USA.
   [Faehnle, Christopher R.; Walleshauser, Jack; Joshua-Tor, Leemor] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Walleshauser, Jack; Joshua-Tor, Leemor] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Joshua-Tor, Leemor] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
RP Joshua-Tor, L (corresponding author), WM Keck Struct Biol Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM leemor@cshl.edu
FU Watson School of Biological Sciences; Louis Morin Charitable Trust; Robertson Research Fund of Cold Spring Harbor Laboratory; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM065094] Funding Source: NIH RePORTER
NR 43
TC 102
Z9 129
U1 2
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 OCT 9
PY 2014
VL 514
IS 7521
BP 252
EP +
DI 10.1038/nature13553
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100047
PM 25119025
DA 2026-03-09
ER

PT J
AU Srivastava, A
   Yano, J
   Hirozane, Y
   Kefala, G
   Gruswitz, F
   Snell, G
   Lane, W
   Ivetac, A
   Aertgeerts, K
   Nguyen, J
   Jennings, A
   Okada, K
AF Srivastava, Ankita
   Yano, Jason
   Hirozane, Yoshihiko
   Kefala, Georgia
   Gruswitz, Franz
   Snell, Gyorgy
   Lane, Weston
   Ivetac, Anthony
   Aertgeerts, Kathleen
   Nguyen, Jasmine
   Jennings, Andy
   Okada, Kengo
TI High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875
SO NATURE
LA English
DT Article
ID free fatty-acids; crystal-structure; membrane-proteins; binding; gpcr; identification; activation; rhodopsin; discovery; complex
AB Human GPR40 receptor (hGPR40), also known as free fatty-acid receptor 1 (FFAR1), is a G-protein-coupled receptor that binds long-chain free fatty acids to enhance glucose-dependent insulin secretion(1). Novel treatments for type-2 diabetes mellitus(2) are therefore possible by targeting hGPR40 with partial or full agonists. TAK-875, or fasiglifam, is an orally available, potent and selective partial agonist(3) of hGPR40 receptor, which reached phase III clinical trials for the potential treatment of type-2 diabetes mellitus(4). Data from clinical studies indicate that TAK-875, which is anago-allosteric modulator of hGPR40 (ref. 3), demonstrates improved glycaemic control and low hypoglycaemic risk in diabetic patients(5). Here we report the crystal structure of hGPR40 receptor bound to TAK-875 at 2.3 angstrom resolution. The co-complex structure reveals a unique binding mode of TAK-875 and suggests that entry to the non-canonical binding pocket most probably occurs via the lipid bilayer. The atomic details of the extensive charge network in the ligand binding pocket reveal additional interactions not identified in previous studies and contribute to a clear understanding of TAK-875 binding to the receptor. The hGPR40-TAK-875 structure also provides insights into the plausible binding of multiple ligands to the receptor, which has been observed in radioligand binding(6) and Ca2+ influx assay studies(3). Comparison of the transmembrane helix architecture with other G-protein-coupled receptors suggests that the crystallized TAK-875-bound hGPR40 complex is in an inactive-like state.
C1 [Srivastava, Ankita; Yano, Jason; Kefala, Georgia; Gruswitz, Franz; Snell, Gyorgy; Lane, Weston; Ivetac, Anthony; Aertgeerts, Kathleen; Nguyen, Jasmine; Jennings, Andy] Takeda Calif, Dept Struct Biol & Core Sci & Technol, San Diego, CA 92121 USA.
   [Hirozane, Yoshihiko; Okada, Kengo] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Biomol Res Labs, Fujisawa, Kanagawa 2518555, Japan.
C3 Takeda Pharmaceutical Company Ltd; Takeda Pharmaceuticals USA Inc. (TPUSA); Takeda California Inc; Takeda Pharmaceutical Company Ltd
RP Srivastava, A (corresponding author), Takeda Calif, Dept Struct Biol & Core Sci & Technol, 10410 Sci Ctr Dr, San Diego, CA 92121 USA.
EM ankita.srivastava@takeda.com
FU National Institutes of Health and National Institute of General Medical Sciences; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231, DE-AC02-06CH11357]
NR 41
TC 303
Z9 338
U1 0
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 4
PY 2014
VL 513
IS 7516
BP 124
EP +
DI 10.1038/nature13494
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800043
PM 25043059
DA 2026-03-09
ER

PT J
AU Shlush, LI
   Zandi, S
   Mitchell, A
   Chen, WC
   Brandwein, JM
   Gupta, V
   Kennedy, JA
   Schimmer, AD
   Schuh, AC
   Yee, KW
   McLeod, JL
   Doedens, M
   Medeiros, JJF
   Marke, R
   Kim, HJ
   Lee, K
   McPherson, JD
   Hudson, TJ
   Brown, AMK
   Trinh, QM
   Stein, LD
   Minden, MD
   Wang, JCY
   Dick, JE
AF Shlush, Liran I.
   Zandi, Sasan
   Mitchell, Amanda
   Chen, Weihsu Claire
   Brandwein, Joseph M.
   Gupta, Vikas
   Kennedy, James A.
   Schimmer, Aaron D.
   Schuh, Andre C.
   Yee, Karen W.
   McLeod, Jessica L.
   Doedens, Monica
   Medeiros, Jessie J. F.
   Marke, Rene
   Kim, Hyeoung Joon
   Lee, Kwon
   McPherson, John D.
   Hudson, Thomas J.
   Brown, Andrew M. K.
   Trinh, Quang M.
   Stein, Lincoln D.
   Minden, Mark D.
   Wang, Jean C. Y.
   Dick, John E.
TI Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; clonal evolution; dnmt3a mutations; dna methyltransferase; origin; differentiation; heterogeneity; pathogenesis; architecture; metastasis
AB In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.
C1 [Shlush, Liran I.; Zandi, Sasan; Mitchell, Amanda; Chen, Weihsu Claire; Brandwein, Joseph M.; Gupta, Vikas; Kennedy, James A.; Schimmer, Aaron D.; Schuh, Andre C.; Yee, Karen W.; McLeod, Jessica L.; Doedens, Monica; Medeiros, Jessie J. F.; Marke, Rene; Minden, Mark D.; Wang, Jean C. Y.; Dick, John E.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [Brandwein, Joseph M.; Gupta, Vikas; Schimmer, Aaron D.; Schuh, Andre C.; Yee, Karen W.; Minden, Mark D.; Wang, Jean C. Y.] Univ Toronto, Dept Med, Toronto, ON M5S 2J7, Canada.
   [Brandwein, Joseph M.; 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, Toronto, ON M5G 2M9, Canada.
   [Schimmer, Aaron D.; McPherson, John D.; Hudson, Thomas J.; Minden, Mark D.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
   [Marke, Rene] Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands.
   [Kim, Hyeoung Joon; Lee, Kwon] Chonnam Natl Univ, Hwasun Hosp, Genome Res Ctr Hematopoiet Dis, Gwangju 519809, South Korea.
   [McPherson, John D.; Hudson, Thomas J.; Brown, Andrew M. K.; Trinh, Quang M.; Stein, Lincoln D.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Hudson, Thomas J.; Stein, Lincoln D.; Dick, John E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University of Toronto; University Health Network Toronto; University of Toronto; Radboud University Nijmegen; Chonnam National University; Ontario Institute for Cancer Research; University of Toronto; University of Toronto
RP Dick, JE (corresponding author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
EM jdick@uhnresearch.ca
FU McEwen Centre for Regenerative Medicine; Gentle Ben Charity; Canadian Institutes for Health Research (CIHR); Aplastic Anemia and Myelodysplasia Association of Canada; Vetenskapsradet; CIHR; Canadian Cancer Society; Terry Fox Foundation; Genome Canada through the Ontario Genomics Institute; Ontario Institute for Cancer Research; province of Ontario; Canada Research Chair; Ontario Ministry of Health and Long Term Care (OMOHLTC); Cancer Stem Cell Consortium; Government of Canada through Genome Canada; Government of Canada through Ontario Genomics Institute [OGI-047]; Government of Canada through Canadian Institutes of Health Research [CSC-105367]
NR 51
TC 1162
Z9 1338
U1 2
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 FEB 20
PY 2014
VL 506
IS 7488
BP 328
EP +
DI 10.1038/nature13038
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800033
PM 24522528
DA 2026-03-09
ER

PT J
AU Jacobs, FMJ
   Greenberg, D
   Nguyen, N
   Haeussler, M
   Ewing, AD
   Katzman, S
   Paten, B
   Salama, SR
   Haussler, D
AF Jacobs, Frank M. J.
   Greenberg, David
   Ngan Nguyen
   Haeussler, Maximilian
   Ewing, Adam D.
   Katzman, Sol
   Paten, Benedict
   Salama, Sofie R.
   Haussler, David
TI An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons
SO NATURE
LA English
DT Article
ID multiple sequence alignment; embryonic stem-cells; transposable elements; insertions; family
AB Throughout evolution primate genomes have been modified by waves of retrotransposon insertions(1-3). For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger(KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them(4,5). KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons(6,7). However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA)(8) and long interspersed nuclear element 1 (L1)(9), is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until similar to 12.5 million years ago when the L1PA3-subfamily of retrotransposons escaped ZNF93's restriction through the removal of the ZNF93-binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.
C1 [Jacobs, Frank M. J.; Greenberg, David; Ngan Nguyen; Haeussler, Maximilian; Ewing, Adam D.; Katzman, Sol; Paten, Benedict; Salama, Sofie R.; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Greenberg, David; Ngan Nguyen] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
   [Salama, Sofie R.; Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute
RP Haussler, D (corresponding author), Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
EM haussler@soe.ucsc.edu
FU California Institute of Regenerative Medicine (CIRM) [FA1-00617, CL1-00506-1.2, TG2-01157]; Human Frontier Science Program Postdoctoral fellowship [LT000689]; California Institute for Quantitative Biosciences; TCGA [U24 24010-443720]; EMBO ALTF [292-2011]; ENCODE [U41HG004568]
NR 45
TC 352
Z9 427
U1 0
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 DEC 11
PY 2014
VL 516
IS 7530
BP 242
EP +
DI 10.1038/nature13760
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500044
PM 25274305
DA 2026-03-09
ER

PT J
AU Steuber, J
   Vohl, G
   Casutt, MS
   Vorburger, T
   Diederichs, K
   Fritz, G
AF Steuber, Julia
   Vohl, Georg
   Casutt, Marco S.
   Vorburger, Thomas
   Diederichs, Kay
   Fritz, Guenter
TI Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase
SO NATURE
LA English
DT Article
ID nadh-quinone oxidoreductase; translocating nadh; ubiquinone oxidoreductase; crystal-structure; vibrio-cholerae; nqrc subunits; protein; crystallization; mechanism; electron
AB NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium -translocattng NADH:quinone oxidoreductase (Na+-NQR), amembrane protein complex widespread among pathogenic bacteria' consists of six subunits, NqrA, B, C, D, E and F. our knowledge, no structural information on the Na+-NQR complex has been available until now. Here we present the crystal structure of the Na+-NQR complex at 3.5 angstrom resolution. The arrangement of cofactors both at the cytoplasmic and the periplastnic side of the complex, together with a hitherto unknown iron centre in the midst of the membrane-embedded part, reveals an electron transfer pathway from the NADH- oxidizing cytoplasmic NqrF subunit across the membrane to the petiplasmic NqrC, and back to the qui none reduction site on NqrA located in the cytoplasm. A soditun channel was localized in subunit Nqr13, which represents the largest membrane subunit of the Na+-NQR and is structurally related to urea and ammonia transporters. On the basis of the structure we propose a mechanism of redox-driven Na+ translocation where the change in redox state of the flavin mononucleotide cofactor in NqrB triggers the transport of Na+ through the observed channel.
C1 [Steuber, Julia; Vorburger, Thomas] Univ Hohenheim, Dept Microbiol, D-70599 Stuttgart, Germany.
   [Vohl, Georg; Casutt, Marco S.; Fritz, Guenter] Univ Freiburg, Inst Neuropathol, D-79106 Freiburg, Germany.
   [Vohl, Georg] Univ Freiburg, Hermann Staudinger Grad Sch, D-79104 Freiburg, Germany.
   [Diederichs, Kay] Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
C3 University Hohenheim; University of Freiburg; University of Freiburg; University of Konstanz
RP Fritz, G (corresponding author), Univ Freiburg, Inst Neuropathol, Breisacher Str 64, D-79106 Freiburg, Germany.
EM guenter.fritz@uniklinik-freiburg.de
FU 'Methoden in den Lebenswissenschaften' of the Baden-Wurttemberg Stiftung P-LS-Meth/4; Deutsche Forschungsgemeinschaft [FR 1321/3-1, FR 1488/3-2]
NR 56
TC 121
Z9 142
U1 2
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 DEC 4
PY 2014
VL 516
IS 7529
BP 62
EP U379
DI 10.1038/nature14003
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800038
PM 25471880
DA 2026-03-09
ER

PT J
AU Pearson, DG
   Brenker, FE
   Nestola, F
   McNeill, J
   Nasdala, L
   Hutchison, MT
   Matveev, S
   Mather, K
   Silversmit, G
   Schmitz, S
   Vekemans, B
   Vincze, L
AF Pearson, D. G.
   Brenker, F. E.
   Nestola, F.
   McNeill, J.
   Nasdala, L.
   Hutchison, M. T.
   Matveev, S.
   Mather, K.
   Silversmit, G.
   Schmitz, S.
   Vekemans, B.
   Vincze, L.
TI Hydrous mantle transition zone indicated by ringwoodite included within diamond
SO NATURE
LA English
DT Article
ID mineral inclusions; electrical-conductivity; water-content; wadsleyite; pressure; olivine; phase; iron; gamma-mg2sio4; spectroscopy
AB The ultimate origin of water in the Earth's hydrosphere is in the deep Earth-the mantle. Theory(1) and experiments(2-4) have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine-wadsleyite and ringwoodite-to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics(5-7), yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results(8-10), and the issue of whether the transition zone contains abundant water remains highly controversial(11). Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juina, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.
C1 [Pearson, D. G.; Matveev, S.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Brenker, F. E.; Schmitz, S.] Goethe Univ Frankfurt, Geosci Inst Mineral, D-60438 Frankfurt, Germany.
   [Nestola, F.] Univ Padua, Dipartimento Geosci, I-35137 Padua, Italy.
   [McNeill, J.; Mather, K.] Univ Durham, Dept Earth Sci, Durham DH1 3LE, England.
   [Nasdala, L.] Univ Vienna, Inst Mineral & Kristallog, A-1090 Vienna, Austria.
   [Hutchison, M. T.] Trigon GeoServ Ltd, Las Vegas, NV 89146 USA.
   [Silversmit, G.; Vekemans, B.; Vincze, L.] Univ Ghent, Dept Analyt Chem, B-9000 Ghent, Belgium.
C3 University of Alberta; Goethe University Frankfurt; University of Padua; Durham University; University of Vienna; Ghent University
RP Pearson, DG (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, 1-26 Earth Sci Bldg, Edmonton, AB T6G 2E3, Canada.
EM gdpearso@ualberta.ca
FU CERC; ERC [307322]; Alfred P. Sloan Foundation
NR 47
TC 632
Z9 757
U1 14
U2 487
PU NATURE PUBLISHING 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 13
PY 2014
VL 507
IS 7491
BP 221
EP +
DI 10.1038/nature13080
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800036
PM 24622201
DA 2026-03-09
ER

PT J
AU Christophorou, MA
   Castelo-Branco, G
   Halley-Stott, RP
   Oliveira, CS
   Loos, R
   Radzisheuskaya, A
   Mowen, KA
   Bertone, P
   Silva, JCR
   Zernicka-Goetz, M
   Nielsen, ML
   Gurdon, JB
   Kouzarides, T
AF Christophorou, Maria A.
   Castelo-Branco, Goncalo
   Halley-Stott, Richard P.
   Oliveira, Clara Slade
   Loos, Remco
   Radzisheuskaya, Aliaksandra
   Mowen, Kerri A.
   Bertone, Paul
   Silva, Jose C. R.
   Zernicka-Goetz, Magdalena
   Nielsen, Michael L.
   Gurdon, John B.
   Kouzarides, Tony
TI Citrullination regulates pluripotency and histone H1 binding to chromatin
SO NATURE
LA English
DT Article
ID peptidylarginine deiminase 4; mass; expression; pad4; identification; localization; nucleosome; proteins; nanog; state
AB Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline(1). This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs)(2) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis(2,3). Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response(4-8). PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal(9), was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection(10). Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin(11), as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.
C1 [Christophorou, Maria A.; Castelo-Branco, Goncalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Zernicka-Goetz, Magdalena; Gurdon, John B.; Kouzarides, Tony] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
   [Castelo-Branco, Goncalo] Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, SE-17177 Stockholm, Sweden.
   [Halley-Stott, Richard P.; Gurdon, John B.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Oliveira, Clara Slade] EMBRAPA Dairy Cattle Res Ctr, Juiz De Fora, Brazil.
   [Oliveira, Clara Slade; Zernicka-Goetz, Magdalena] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 1QN, England.
   [Loos, Remco; Bertone, Paul] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Radzisheuskaya, Aliaksandra; Bertone, Paul; Silva, Jose C. R.] Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Cambridge CB2 1QR, England.
   [Radzisheuskaya, Aliaksandra; Silva, Jose C. R.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QR, England.
   [Mowen, Kerri A.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Bertone, Paul] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Bertone, Paul] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
   [Nielsen, Michael L.] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Dept Prote, Fac Hlth Sci, DK-2200 Copenhagen, Denmark.
   [Kouzarides, Tony] Univ Cambridge, Dept Pathol, Cambridge CB2 1QN, England.
C3 University of Cambridge; Karolinska Institutet; University of Cambridge; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); University of Cambridge; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Cambridge; University of Cambridge; Scripps Research Institute; European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); University of Copenhagen; University of Cambridge
RP Kouzarides, T (corresponding author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM t.kouzarides@gurdon.cam.ac.uk
FU Cancer Research UK; EMBL; Medical Research Council [G1001690]; Wellcome Trust; EMBO; European Union; Swedish Research Council; Human Frontier Science Programme Long-Term Post-Doctoral Fellowship; FAPESP (Foundation for Research Support of the State of Sao Paulo); Novo Nordisk Foundation Center for Protein Research; Lundbeck Foundation; European Commission [HEALTH-F7-2010-242129/SYBOSS]; NIH [AI099728]; MRC [G1001690] Funding Source: UKRI; Wellcome Trust [101861/Z/13/Z] Funding Source: Wellcome Trust; Biotechnology and Biological Sciences Research Council [BBS/B/14647] Funding Source: researchfish; Cancer Research UK [17001, 12475] Funding Source: researchfish; Cancer Research UK; The Francis Crick Institute [10827] Funding Source: researchfish; Medical Research Council [G1001690] Funding Source: researchfish; Novo Nordisk Fonden [NNF13OC0006477] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Michael Lund Nielsen] Funding Source: researchfish; Wellcome Trust [101861/Z/13/Z, 101050/Z/13/Z] Funding Source: researchfish
NR 55
TC 338
Z9 438
U1 2
U2 118
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2014
VL 507
IS 7490
BP 104
EP +
DI 10.1038/nature12942
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400051
PM 24463520
DA 2026-03-09
ER

PT J
AU Xue, ZH
   Ye, QH
   Anson, SR
   Yang, JC
   Xiao, G
   Kowbel, D
   Glass, NL
   Crosthwaite, SK
   Liu, Y
AF Xue, Zhihong
   Ye, Qiaohong
   Anson, Simon R.
   Yang, Jichen
   Xiao, Guanghua
   Kowbel, David
   Glass, N. Louise
   Crosthwaite, Susan K.
   Liu, Yi
TI Transcriptional interference by antisense RNA is required for circadian clock function
SO NATURE
LA English
DT Article
ID neurospora-crassa; polymerase-ii; temperature compensation; white collar-1; light; frequency; gene; frq; inactivation; methylation
AB Eukaryotic circadian oscillators consist of negative feedback loops that generate endogenous rhythmicities(1). Natural antisense RNAs are found in a wide range of eukaryotic organisms(2-5). Nevertheless, the physiological importance and mode of action of most antisense RNAs are not clear(6-9). frequency (frq) encodes a component of the Neurospora core circadian negative feedback loop, which was thought to generate sustained rhythmicity(10). Transcription of qrf, the long non-coding frq antisense RNA, is induced by light, and its level oscillates in antiphase to frq sense RNA(3). Here we show that qrf transcription is regulated by both light-dependent and light-independent mechanisms. Light-dependent qrf transcription represses frq expression and regulates clock resetting. Light-independent qrf expression, on the other hand, is required for circadian rhythmicity. frq transcription also inhibits qrf expression and drives the antiphasic rhythm of qrf transcripts. The mutual inhibition of frq and qrf transcription thus forms a double negative feedback loop that is interlocked with the core feedback loop. Genetic and mathematical modelling analyses indicate that such an arrangement is required for robust and sustained circadian rhythmicity. Moreover, our results suggest that antisense transcription inhibits sense expression by mediating chromatin modifications and premature termination of transcription. Taken together, our results establish antisense transcription as an essential feature in a circadian system and shed light on the importance and mechanism of antisense action.
C1 [Xue, Zhihong; Ye, Qiaohong; Liu, Yi] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Anson, Simon R.; Crosthwaite, Susan K.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [Yang, Jichen; Xiao, Guanghua] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Kowbel, David; Glass, N. Louise] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Manchester; University of Texas System; University of Texas Southwestern Medical Center; University of California System; University of California Berkeley
RP Liu, Y (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Yi.Liu@UTsouthwestern.edu
FU National Institutes of Health [GM068496, GM062591, GM081597]; Welch Foundation [I-1560]; Cancer Prevention Research Institute of Texas [RP101496]; Biotechnology and Biological Sciences Research Council [BBS/S/C2005/13012]; Biotechnology and Biological Sciences Research Council [BBS/B/11710] Funding Source: researchfish; National Institute of General Medical Sciences [R35GM118118] Funding Source: NIH RePORTER
NR 44
TC 81
Z9 96
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 OCT 30
PY 2014
VL 514
IS 7524
BP 650
EP +
DI 10.1038/nature13671
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500054
PM 25132551
DA 2026-03-09
ER

PT J
AU Chin, RM
   Fu, XD
   Pai, MY
   Vergnes, L
   Hwang, H
   Deng, G
   Diep, S
   Lomenick, B
   Meli, VS
   Monsalve, GC
   Hu, E
   Whelan, SA
   Wang, JX
   Jung, G
   Solis, GM
   Fazlollahi, F
   Kaweeteerawat, C
   Quach, A
   Nili, M
   Krall, AS
   Godwin, HA
   Chang, HR
   Faull, KF
   Guo, F
   Jiang, MS
   Trauger, SA
   Saghatelian, A
   Braas, D
   Christofk, HR
   Clarke, CF
   Teitell, MA
   Petrascheck, M
   Reue, K
   Jung, ME
   Frand, AR
   Huang, J
AF Chin, Randall M.
   Fu, Xudong
   Pai, Melody Y.
   Vergnes, Laurent
   Hwang, Heejun
   Deng, Gang
   Diep, Simon
   Lomenick, Brett
   Meli, Vijaykumar S.
   Monsalve, Gabriela C.
   Hu, Eileen
   Whelan, Stephen A.
   Wang, Jennifer X.
   Jung, Gwanghyun
   Solis, Gregory M.
   Fazlollahi, Farbod
   Kaweeteerawat, Chitrada
   Quach, Austin
   Nili, Mahta
   Krall, Abby S.
   Godwin, Hilary A.
   Chang, Helena R.
   Faull, Kym F.
   Guo, Feng
   Jiang, Meisheng
   Trauger, Sunia A.
   Saghatelian, Alan
   Braas, Daniel
   Christofk, Heather R.
   Clarke, Catherine F.
   Teitell, Michael A.
   Petrascheck, Michael
   Reue, Karen
   Jung, Michael E.
   Frand, Alison R.
   Huang, Jing
TI The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; caloric restriction; developmental arrest; dietary restriction; phosphorylation; autophagy; longevity; genetics; deficiency; pha-4/foxa
AB Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms(1,2). Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits(3,4). Recently, several metabolites have been identified that modulate ageing(5,6); however, the molecular mechanisms underlying this are largely undefined. Here we show that alpha-ketoglutarate (alpha-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit beta is identified as a novel binding protein of alpha-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS)(7). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy generating machinery and is highly conserved throughout evolution(8,9). Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan(10-13). We show that alpha-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by alpha-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by alpha-KG requires ATP synthase subunit b and is dependent on target of rapamycin (TOR) downstream. Endogenous alpha-KG levels are increased on starvation and alpha-KG does not extend the lifespan of dietary-restricted animals, indicating that alpha-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.
C1 [Chin, Randall M.; Pai, Melody Y.; Clarke, Catherine F.; Teitell, Michael A.; Reue, Karen; Jung, Michael E.; Huang, Jing] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Fu, Xudong; Hwang, Heejun; Diep, Simon; Lomenick, Brett; Hu, Eileen; Jung, Gwanghyun; Quach, Austin; Krall, Abby S.; Jiang, Meisheng; Braas, Daniel; Christofk, Heather R.; Huang, Jing] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
   [Vergnes, Laurent; Reue, Karen] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Deng, Gang; Clarke, Catherine F.; Jung, Michael E.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Meli, Vijaykumar S.; Monsalve, Gabriela C.; Guo, Feng; Frand, Alison R.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Whelan, Stephen A.; Chang, Helena R.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90095 USA.
   [Wang, Jennifer X.; Trauger, Sunia A.] Harvard Univ, FAS Div Sci, Small Mol Mass Spectrometry Facil, Cambridge, MA 02138 USA.
   [Solis, Gregory M.; Petrascheck, Michael] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Fazlollahi, Farbod; Faull, Kym F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA.
   [Fazlollahi, Farbod; Faull, Kym F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
   [Kaweeteerawat, Chitrada; Godwin, Hilary A.] Univ Calif Los Angeles, Dept Environm Hlth Sci, Los Angeles, CA 90095 USA.
   [Nili, Mahta; Teitell, Michael A.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   [Saghatelian, Alan] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Braas, Daniel; Christofk, Heather R.] Univ Calif Los Angeles, UCLA Metabol Ctr, 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; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Harvard University; Scripps Research Institute; 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; Harvard University; University of California System; University of California Los Angeles
RP Huang, J (corresponding author), Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
EM jinghuang@mednet.ucla.edu
FU National Institutes of Health (NIH) Office of Research Infrastructure Programs [P40 OD010440]; NIH [T32 GM007104, T32 GM007185, T32 GM008496, T32 CA009120]; China Scholarship Council Scholarship; Ford Foundation; National Science Foundation; National Cancer Institute [T32CA009120] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of General Medical Sciences [P40OD010440] Funding Source: NIH RePORTER
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   Long XM, 2002, CURR BIOL, V12, P1448, DOI 10.1016/S0960-9822(02)01091-6
   Lucanic M, 2011, NATURE, V473, P226, DOI 10.1038/nature10007
   MacKenzie ED, 2007, MOL CELL BIOL, V27, P3282, DOI 10.1128/MCB.01927-06
   Mattison JA, 2012, NATURE, V489, P318, DOI 10.1038/nature11432
   Meléndez A, 2003, SCIENCE, V301, P1387, DOI 10.1126/science.1087782
   Panowski SH, 2007, NATURE, V447, P550, DOI 10.1038/nature05837
   Pathare PP, 2012, PLOS GENET, V8, P333, DOI 10.1371/journal.pgen.1002645
   Pullen N, 1997, FEBS LETT, V410, P78, DOI 10.1016/S0014-5793(97)00323-2
   Rogers GW, 2011, PLOS ONE, V6, P0, DOI 10.1371/journal.pone.0021746
   Sarbassov DD, 2005, SCIENCE, V307, P1098, DOI 10.1126/science.1106148
   Schneider CA, 2012, NAT METHODS, V9, P671, DOI 10.1038/nmeth.2089
   Sheaffer KL, 2008, CURR BIOL, V18, P1355, DOI 10.1016/j.cub.2008.07.097
   Stanfel MN, 2009, BBA-GEN SUBJECTS, V1790, P1067, DOI 10.1016/j.bbagen.2009.06.007
   Stubbs CJ, 2009, J MED CHEM, V52, P2799, DOI 10.1021/jm900285r
   Sutphin George L, 2009, J VIS EXP, V0, P0, DOI DOI 10.3791/1152
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   Williams DS, 2009, AGING CELL, V8, P765, DOI 10.1111/j.1474-9726.2009.00527.x
   Wu M, 2007, AM J PHYSIOL-CELL PH, V292, PC125, DOI 10.1152/ajpcell.00247.2006
   Wullschleger S, 2006, CELL, V124, P471, DOI 10.1016/j.cell.2006.01.016
   Xu W, 2011, CANCER CELL, V19, P17, DOI 10.1016/j.ccr.2010.12.014
   Yamamoto H, 2011, CELL, V147, P827, DOI 10.1016/j.cell.2011.10.017
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   Zhao SM, 2009, SCIENCE, V324, P261, DOI 10.1126/science.1170944
NR 59
TC 514
Z9 599
U1 10
U2 244
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 397
EP 401
DI 10.1038/nature13264
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200035
PM 24828042
DA 2026-03-09
ER

PT J
AU Birsoy, K
   Possemato, R
   Lorbeer, FK
   Bayraktar, EC
   Thiru, P
   Yucel, B
   Wang, T
   Chen, WW
   Clish, CB
   Sabatini, DM
AF Birsoy, Kivanc
   Possemato, Richard
   Lorbeer, Franziska K.
   Bayraktar, Erol C.
   Thiru, Prathapan
   Yucel, Burcu
   Wang, Tim
   Chen, Walter W.
   Clish, Clary B.
   Sabatini, David M.
TI Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides
SO NATURE
LA English
DT Article
ID oxidative-phosphorylation; complex i; respiratory-chain; pancreatic-cancer; diabetic-patients; breast-cancer; metformin; mutations; deficiency; tumors
AB As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues(1,2), cancer cells must adapt their metabolism to the tumour microenvironment. Abetter understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS3,4, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function(5). Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.
C1 [Birsoy, Kivanc; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Birsoy, Kivanc; Possemato, Richard; Wang, Tim; Chen, Walter W.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Birsoy, Kivanc; Possemato, Richard; Wang, Tim; Chen, Walter W.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Birsoy, Kivanc; Possemato, Richard; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Birsoy, Kivanc; Possemato, Richard; Wang, Tim; Chen, Walter W.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT)
RP Sabatini, DM (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU Leukemia and Lymphoma Society; Jane Coffin Childs Fund; Council of Higher Education Turkey; Karadeniz T. University Scholarships; David H. Koch Institute for Integrative Cancer Research at MIT; Alexander and Margaret Stewart Trust Fund; NIH [K99 CA168940, CA103866, CA129105, AI07389]; Starr Cancer Consortium; National Cancer Institute [R01CA129105, R01CA103866] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 27
TC 601
Z9 709
U1 0
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 3
PY 2014
VL 508
IS 7494
BP 108
EP +
DI 10.1038/nature13110
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900052
PM 24670634
DA 2026-03-09
ER

PT J
AU Hennig, J
   Militti, C
   Popowicz, GM
   Wang, I
   Sonntag, M
   Geerlof, A
   Gabel, F
   Gebauer, F
   Sattler, M
AF Hennig, Janosch
   Militti, Cristina
   Popowicz, Grzegorz M.
   Wang, Iren
   Sonntag, Miriam
   Geerlof, Arie
   Gabel, Frank
   Gebauer, Fatima
   Sattler, Michael
TI Structural basis for the assembly of the Sxl-Unr translation regulatory complex
SO NATURE
LA English
DT Article
ID msl-2 messenger-rna; angle scattering data; sex-lethal; dosage compensation; crystal-structure; x-ray; biological macromolecules; neutron-scattering; nmr experiments; drosophila unr
AB Genetic equality between males and females is established by chromosome-wide dosage-compensation mechanisms. In the fruit-fly Drosophila melanogaster, the dosage-compensation complex promotes two fold hypertranscription of the singlemale X-chromosome and is silenced in females by inhibition of the translation of msl2, which codes for the limiting component of the dosage-compensation complex(1,2). The female-specific protein Sex-lethal (Sxl) recruits Upstream of-N-ras(Unr) to the 39 untranslated region of msl2 messenger RNA, preventing the engagement of the small ribosomal subunit(3). Here we report the 2.8 angstrom crystal structure, NMR and small-angle X-ray and neutron scattering data of the ternary Sxl-Unr-msl2 ribonucleoprotein complex featuring unprecedented intertwined interactions of two Sxl RNA recognition motifs, a Unr cold-shock domain and RNA. Cooperative complex formation is associated with a 1,000-fold increase of RNA binding affinity for the Unr cold-shock domain and involves novel ternary interactions, as well as non-canonical RNA contacts by the alpha 1 helix of Sxl RNA recognition motif 1. Our results suggest that repression of dosage compensation, necessary for female viability, is triggered by specific, cooperative molecular interactions that lock a ribonucleoprotein switch to regulate translation. The structure serves as a paradigm for how a combination of general and widespread RNA binding domains expands the code for specific single-stranded RNA recognition in the regulation of gene expression.
C1 [Hennig, Janosch; Popowicz, Grzegorz M.; Wang, Iren; Sonntag, Miriam; Geerlof, Arie; Sattler, Michael] Helmholtz Zentrum Munchen, Inst Struct Biol, DE-85764 Munich, Germany.
   [Hennig, Janosch; Popowicz, Grzegorz M.; Wang, Iren; Sonntag, Miriam; Sattler, Michael] Tech Univ Munich, Dept Chem, Ctr Integrated Prot Sci Munich Biomol NMR Spect, DE-85747 Garching, Germany.
   [Militti, Cristina; Gebauer, Fatima] Ctr Genom Regulat, Gene Regulat Stem Cells & Canc Programme, Barcelona 08003, Spain.
   [Militti, Cristina; Gebauer, Fatima] Univ Pompeu Fabra, Barcelona 08003, Spain.
   [Gabel, Frank] Univ Grenoble Alpes, Inst Biol Struct, F-38044 Grenoble, France.
   [Gabel, Frank] CNRS, Inst Biol Struct, F-38044 Grenoble, France.
   [Gabel, Frank] Commissariat Energie Atom & Energies Alternat, Inst Biol Struct, F-38044 Grenoble, France.
   [Gabel, Frank] Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Institut Laue-Langevin (ILL)
RP Sattler, M (corresponding author), Helmholtz Zentrum Munchen, Inst Struct Biol, Ingolstadter Landstr 1, DE-85764 Munich, Germany.
EM fatima.gebauer@crg.eu; sattler@helmholtz-muenchen.de
FU Swedish Research Council (Vetenskapsradet); European Molecular Biology Organization (EMBO) [ALTF276-2010]; Spanish Ministry of Economy and Competitiveness [BFU2009-08243, Consolider CSD2009-00080]; Deutsche Forschungsgemeinschaft [SFB1035, GRK1721]
NR 60
TC 100
Z9 111
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 NOV 13
PY 2014
VL 515
IS 7526
BP 287
EP U343
DI 10.1038/nature13693
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400055
PM 25209665
DA 2026-03-09
ER

PT J
AU Qiao, S
   Luo, QS
   Zhao, Y
   Zhang, XJC
   Huang, YH
AF Qiao, Shuai
   Luo, Qingshan
   Zhao, Yan
   Zhang, Xuejun Cai
   Huang, Yihua
TI Structural basis for lipopolysaccharide insertion in the bacterial outer membrane
SO NATURE
LA English
DT Article
ID functional-analysis; protein complex; cell-envelope; transport; identification; mutagenesis; biogenesis; export; plug; lptd
AB One of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. In Gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (LPS)(1). The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surfac(2)e. Of the seven Lpt proteins, the LptD-LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane(3,4). Here we report the crystal structure of the similar to 110-kilodalton membrane protein complex LptD-LptE from Shigella flexneri at 2.4 angstrom resolution. The structure reveals an unprecedented two-protein plug-and-barrel architecture with LptE embedded into a 26-stranded beta-barrel formed by LptD. Importantly, the secondary structures of the first two beta-strands are distorted by two proline residues, weakening their interactions with neighbouring beta-strands and creating a potential portal on the barrel wall that could allow lateral diffusion of LPS into the outer membrane. The crystal structure of the LptD-LptE complex opens the door to new antibiotic strategies targeting the bacterial outer membrane.
C1 [Qiao, Shuai; Luo, Qingshan; Zhao, Yan; Zhang, Xuejun Cai; Huang, Yihua] Chinese Acad Sci, Inst Biophys, Natl Ctr Prot Sci Beijing, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Qiao, Shuai; Luo, Qingshan] Univ Chinese Acad Sci, Beijing 100101, Peoples R China.
   [Zhao, Yan] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, 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; University of Science & Technology of China, CAS
RP Huang, YH (corresponding author), Chinese Acad Sci, Inst Biophys, Natl Ctr Prot Sci Beijing, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
EM yihuahuang@sun5.ibp.ac.cn
FU Ministry of Science and Technology [2012CB917302, 2013CB910603]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB080203]; National Natural Science Foundation of China [31170698]
NR 30
TC 230
Z9 286
U1 1
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 JUL 3
PY 2014
VL 511
IS 7507
BP 108
EP U523
DI 10.1038/nature13484
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400046
PM 24990751
DA 2026-03-09
ER

PT J
AU Braga-Ribas, F
   Sicardy, B
   Ortiz, JL
   Snodgrass, C
   Roques, F
   Vieira-Martins, R
   Camargo, JIB
   Assafin, M
   Duffard, R
   Jehin, E
   Pollock, J
   Leiva, R
   Emilio, M
   Machado, DI
   Colazo, C
   Lellouch, E
   Skottfelt, J
   Gillon, M
   Ligier, N
   Maquet, L
   Benedetti-Rossi, G
   Gomes, AR
   Kervella, P
   Monteiro, H
   Sfair, R
   El Moutamid, M
   Tancredi, G
   Spagnotto, J
   Maury, A
   Morales, N
   Gil-Hutton, R
   Roland, S
   Ceretta, A
   Gu, SH
   Wang, XB
   Harpsoe, K
   Rabus, M
   Manfroid, J
   Opitom, C
   Vanzi, L
   Mehret, L
   Lorenzini, L
   Schneiter, EM
   Melia, R
   Lecacheux, J
   Colas, F
   Vachier, F
   Widemann, T
   Almenares, L
   Sandness, RG
   Char, F
   Perez, V
   Lemos, P
   Martinez, N
   Jorgensen, UG
   Dominik, M
   Roig, F
   Reichart, DE
   LaCluyze, AP
   Haislip, JB
   Ivarsen, KM
   Moore, JP
   Frank, NR
   Lambas, DG
AF Braga-Ribas, F.
   Sicardy, B.
   Ortiz, J. L.
   Snodgrass, C.
   Roques, F.
   Vieira-Martins, R.
   Camargo, J. I. B.
   Assafin, M.
   Duffard, R.
   Jehin, E.
   Pollock, J.
   Leiva, R.
   Emilio, M.
   Machado, D. I.
   Colazo, C.
   Lellouch, E.
   Skottfelt, J.
   Gillon, M.
   Ligier, N.
   Maquet, L.
   Benedetti-Rossi, G.
   Gomes, A. Ramos, Jr.
   Kervella, P.
   Monteiro, H.
   Sfair, R.
   El Moutamid, M.
   Tancredi, G.
   Spagnotto, J.
   Maury, A.
   Morales, N.
   Gil-Hutton, R.
   Roland, S.
   Ceretta, A.
   Gu, S. -H.
   Wang, X. -B.
   Harpsoe, K.
   Rabus, M.
   Manfroid, J.
   Opitom, C.
   Vanzi, L.
   Mehret, L.
   Lorenzini, L.
   Schneiter, E. M.
   Melia, R.
   Lecacheux, J.
   Colas, F.
   Vachier, F.
   Widemann, T.
   Almenares, L.
   Sandness, R. G.
   Char, F.
   Perez, V.
   Lemos, P.
   Martinez, N.
   Jorgensen, U. G.
   Dominik, M.
   Roig, F.
   Reichart, D. E.
   LaCluyze, A. P.
   Haislip, J. B.
   Ivarsen, K. M.
   Moore, J. P.
   Frank, N. R.
   Lambas, D. G.
TI A ring system detected around the Centaur (10199) Chariklo
SO NATURE
LA English
DT Article
ID trans-neptunian objects; stellar occultation; albedo; photometry; evolution; chiron; region; origin
AB Hitherto, rings have been found exclusively around the four giant planets in the Solar System(1). Rings are natural laboratories in which to study dynamical processes analogous to those that take place during the formation of planetary systems and galaxies. Their presence also tells us about the origin and evolution of the body they encircle. Here we report observations of a multichord stellar occultation that revealed the presence of a ring system around (10199) Chariklo, which is a Centaur-that is, one of a class of small objects orbiting primarily between Jupiter and Neptune-with an equivalent radius of 124 +/- 9 kilometres (ref. 2). There are two dense rings, with respective widths of about 7 and 3 kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405 kilometres. The present orientation of the ring is consistent with an edge-on geometry in 2008, which provides a simple explanation for the dimming(3) of the Chariklo system between 1997 and 2008, and for the gradual disappearance of ice and other absorption features in its spectrum over the same period(4,5). This implies that the rings are partly composed of water ice. They may be the remnants of a debris disk, possibly confined by embedded, kilometre-sized satellites.
C1 [Braga-Ribas, F.; Vieira-Martins, R.; Camargo, J. I. B.; Benedetti-Rossi, G.; Roig, F.] MCTI, Observatorio Nacl, BR-20921400 Rio De Janeiro, Brazil.
   [Sicardy, B.; Roques, F.; Lellouch, E.; Ligier, N.; Maquet, L.; Kervella, P.; El Moutamid, M.; Lecacheux, J.; Widemann, T.] Univ Paris 06, CNRS, UMR 8109, LESIA,Observatoire Paris, F-92195 Meudon, France.
   [Ortiz, J. L.; Duffard, R.; Morales, N.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [Snodgrass, C.] Max Planck Inst Solar Syst Res, D-37077 Gottingen, Germany.
   [Vieira-Martins, R.; Assafin, M.; Gomes, A. Ramos, Jr.] Univ Fed Rio de Janeiro, Observatorio Valongo, BR-20080090 Rio de Janeiro, Brazil.
   [Vieira-Martins, R.; El Moutamid, M.; Colas, F.; Vachier, F.] CNRS, IMCCE, UPMC, Observatoire Paris, F-75014 Paris, France.
   [Jehin, E.; Gillon, M.; Manfroid, J.; Opitom, C.] Univ Liege, Inst Astrophys, B-4000 Liege, Belgium.
   [Pollock, J.] Appalachian State Univ, Dept Phys & Astron, Boone, NC 28608 USA.
   [Leiva, R.; Rabus, M.] Pontificia Univ Catolica Chile, Fac Fis, Inst Astrofis, Santiago 7820436, Chile.
   [Emilio, M.; Mehret, L.] Univ Estadual Ponta Grossa, DEGEO, BR-84030900 Ponta Grossa, Brazil.
   [Machado, D. I.; Lorenzini, L.] FPTI BR, Polo Astronom Casimiro Montenegro Filho, BR-85867900 Foz Do Iguacu, Brazil.
   [Machado, D. I.] Univ Estadual Oeste Parana, BR-8580650 Foz Do Iguacu, Brazil.
   [Colazo, C.] Ministerio Educ Provincia Cordoba, RA-5000 Cordoba, Argentina.
   [Colazo, C.; Schneiter, E. M.; Melia, R.; Lambas, D. G.] Univ Nacl Cordoba, Astron Observ, RA-5000 Cordoba, Argentina.
   [Skottfelt, J.; Harpsoe, K.; Jorgensen, U. G.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Skottfelt, J.; Harpsoe, K.; Jorgensen, U. G.] Geol Museum, Ctr Star & Planet Format, DK-1350 Copenhagen, Denmark.
   [Monteiro, H.] Inst Fis & Quim, BR-37500903 Itajuba, MG, Brazil.
   [Sfair, R.] Univ Estadual Paulista, UNESP, BR-12516410 Guaratingueta, SP, Brazil.
   [Tancredi, G.; Roland, S.; Almenares, L.; Perez, V.; Martinez, N.] DICYT, MEC, Observatorio Astronom Molinos, Montevideo 12400, Uruguay.
   [Tancredi, G.; Ceretta, A.; Almenares, L.; Perez, V.; Lemos, P.; Martinez, N.] Univ Republica, Fac Ciencias, Dept Astron, Montevideo 11300, Uruguay.
   [Spagnotto, J.] Observatorio El Catalejo, RA-6300 La Pampa, Argentina.
   [Maury, A.; Sandness, R. G.] San Pedro Atacama Celestial Explorat, San Pedro De Atacama 1410000, Chile.
   [Gil-Hutton, R.] CASLEO, San Juan, Argentina.
   [Gil-Hutton, R.] San Juan Natl Univ, San Juan, Argentina.
   [Ceretta, A.] Consejo Formac Educ, Observatorio IPA, Montevideo 11800, Uruguay.
   [Gu, S. -H.; Wang, X. -B.] Chinese Acad Sci, Yunnan Observat, Kunming 650011, Peoples R China.
   [Gu, S. -H.; Wang, X. -B.] Chinese Acad Sci, Key Lab Struct & Evolut Celestial Objects, Kunming 650011, Peoples R China.
   [Rabus, M.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Vanzi, L.] Pontificia Univ Catolica Chile, Dept Elect Engn, Santiago 7820436, Chile.
   [Vanzi, L.] Pontificia Univ Catolica Chile, Ctr Astroengn, Santiago 7820436, Chile.
   [Schneiter, E. M.] Consejo Nacl Invest Cient & Tecn, RA-5000 Cordoba, Argentina.
   [Schneiter, E. M.; Lambas, D. G.] Consejo Nacl Invest Cient & Tecn, IATE, RA-5000 Cordoba, Argentina.
   [Schneiter, E. M.] Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, RA-5000 Cordoba, Argentina.
   [Char, F.] Univ Antofagasta, Fac Ciencias Basicas, Unidad Astron, Antofagasta, Chile.
   [Dominik, M.] Univ St Andrews, Scottish Univ Phys Alliance, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Reichart, D. E.; LaCluyze, A. P.; Haislip, J. B.; Ivarsen, K. M.; Moore, J. P.; Frank, N. R.] Univ N Carolina, Dept Phys & Astron, Chapel Hill, NC 27599 USA.
C3 Sorbonne Universite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Max Planck Society; Universidade Federal do Rio de Janeiro; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; University of Liege; University of North Carolina; Appalachian State University; Pontificia Universidad Catolica de Chile; Universidade Estadual de Ponta Grossa; Universidade Estadual do Oeste do Parana; National University of Cordoba; University of Copenhagen; Niels Bohr Institute; Universidade Estadual Paulista; Universidad de la Republica, Uruguay; Universidad Nacional de San Juan; Chinese Academy of Sciences; Chinese Academy of Sciences; Max Planck Society; Pontificia Universidad Catolica de Chile; Pontificia Universidad Catolica de Chile; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); National University of Cordoba; Universidad de Antofagasta; University of St Andrews; University of North Carolina; University of North Carolina Chapel Hill
RP Braga-Ribas, F (corresponding author), MCTI, Observatorio Nacl, Rua Gen Jose Cristino 77, BR-20921400 Rio De Janeiro, Brazil.
EM ribas@on.br
FU LIneA (Laboratorio Interinstitucional de e-Astronomia) of CNPq, Brazil [150541/2013-9]; Danish Natural Science Research Council (FNU); Centre for Star and Planet Formation (StarPlan); French grant 'Beyond Neptune II'; Spanish AYA grants; FEDER funds; National Natural Science Foundation of China [10873031, 11073051]; Belgian Fund for Scientific Research (FRS-FNRS); Swiss National Science Foundation (SNF); Belgian FNRS; CNPq [302657/2010-0, 482080/2009-4 478318/2007-3, 304124/2007-9]; European Union [268421]; FONDECYT [3120097]; National Aeronautics and Space Administration (NASA); National Science Foundation (NSF); NASA; NSF [0959447, 1009052, 1211782]; CONICYT [Anillo ACT-86]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1211782, 1009052, 0959447] Funding Source: National Science Foundation; Division Of Human Resource Development; Direct For Education and Human Resources [1238809] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/J001651/1] Funding Source: researchfish; STFC [ST/J001651/1] Funding Source: UKRI
NR 27
TC 232
Z9 252
U1 1
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 APR 3
PY 2014
VL 508
IS 7494
BP 72
EP +
DI 10.1038/nature13155
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900044
PM 24670644
DA 2026-03-09
ER

PT J
AU Ali, MN
   Xiong, J
   Flynn, S
   Tao, J
   Gibson, QD
   Schoop, LM
   Liang, T
   Haldolaarachchige, N
   Hirschberger, M
   Ong, NP
   Cava, RJ
AF Ali, Mazhar N.
   Xiong, Jun
   Flynn, Steven
   Tao, Jing
   Gibson, Quinn D.
   Schoop, Leslie M.
   Liang, Tian
   Haldolaarachchige, Neel
   Hirschberger, Max
   Ong, N. P.
   Cava, R. J.
TI Large, non-saturating magnetoresistance in WTe2
SO NATURE
LA English
DT Article
ID colossal magnetoresistance; giant magnetoresistance; electrical-property; nanoparticles; transition; ws2
AB Magnetoresistance is the change in a material's electrical resistance in response to an applied magnetic field. Materials with large magnetoresistance have found use as magnetic sensors(1), in magnetic memory(2), and in hard drives(3) at room temperature, and their rarity has motivated many fundamental studies in materials physics at low temperatures(4). Here we report the observation of an extremely large positive magnetoresistance at low temperatures in the non-magnetic layered transition-metal dichalcogenide WTe2: 452,700 per cent at 4.5 kelvins in a magnetic field of 14.7 teslas, and 13 million per cent at 0.53 kelvins in a magnetic field of 60 teslas. In contrast with other materials, there is no saturation of the magnetoresistance value even at very high applied fields. Determination of the origin and consequences of this effect, and the fabrication of thin films, nanostructures and devices based on the extremely large positive magnetoresistance of WTe2, will represent a significant new direction in the study of magnetoresistivity.
C1 [Ali, Mazhar N.; Flynn, Steven; Gibson, Quinn D.; Schoop, Leslie M.; Haldolaarachchige, Neel; Cava, R. J.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Xiong, Jun; Liang, Tian; Hirschberger, Max; Ong, N. P.] Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
   [Xiong, Jun; Liang, Tian; Hirschberger, Max; Ong, N. P.] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Tao, Jing] Brookhaven Natl Lab, Dept Condensed Matter Phys & Mat Sci, Upton, NY 11973 USA.
C3 Princeton University; Princeton University; Princeton University; United States Department of Energy (DOE); Brookhaven National Laboratory
RP Ali, MN (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
EM mnali@princeton.edu
FU Army Research Office [W911NF-12-1-0461, W911NF-11-1-0379]; NSF MRSEC Program Grant [DMR-0819860]; National Science Foundation [DMR-1157490]; State of Florida; US Department of Energy; US Department of Energy's Basic Energy Sciences (DOE BES) project 'Science at 100 Tesla'; DOE BES, by the Materials Sciences and Engineering Division [DE-AC02-98CH10886]
NR 33
TC 1500
Z9 1667
U1 8
U2 1448
PU NATURE PUBLISHING 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 9
PY 2014
VL 514
IS 7521
BP 205
EP +
DI 10.1038/nature13763
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100037
PM 25219849
DA 2026-03-09
ER

PT J
AU Root, CM
   Denny, CA
   Hen, R
   Axel, R
AF Root, Cory M.
   Denny, Christine A.
   Hen, Rene
   Axel, Richard
TI The participation of cortical amygdala in innate, odour-driven behaviour
SO NATURE
LA English
DT Article
ID olfactory-bulb; piriform cortex; representations; mouse; drosophila; gene; information; circuits; neurons; pathway
AB Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined(1-3), but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours. Moreover, we use the promoter of the activity-dependent gene arcto express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odours that elicit innate behaviours. Optical activation of these neurons leads to appropriate behaviours that recapitulate the responses to innate odours. These data indicate that the cortical amygdala plays a critical role in generating innate odour-driven behaviours but do not preclude its participation in learned olfactory behaviours.
C1 [Root, Cory M.; Axel, Richard] Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
   [Root, Cory M.; Axel, Richard] Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Denny, Christine A.] New York State Psychiat Inst & Hosp, Dept Biol Sci, New York, NY 10032 USA.
   [Denny, Christine A.; Hen, Rene] New York State Psychiat Inst & Hosp, Dept Neurosci & Psychiat, New York, NY 10032 USA.
   [Denny, Christine A.; Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA.
   [Hen, Rene] Columbia Univ, New York State Psychiat Inst, Dept Pharmacol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; New York State Psychiatry Institute; New York State Psychiatry Institute; New York State Psychiatry Institute; Columbia University; New York State Psychiatry Institute
RP Axel, R (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
EM ra27@columbia.edu
FU Howard Hughes Medical Institute; Mathers Foundation
NR 34
TC 219
Z9 283
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 NOV 13
PY 2014
VL 515
IS 7526
BP 269
EP U274
DI 10.1038/nature13897
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400051
PM 25383519
DA 2026-03-09
ER

PT J
AU Dutrey, A
   Di Folco, E
   Guilloteau, S
   Boehler, Y
   Bary, J
   Beck, T
   Beust, H
   Chapillon, E
   Gueth, F
   Huré, JM
   Pierens, A
   Piétu, V
   Simon, M
   Tang, YW
AF Dutrey, Anne
   Di Folco, Emmanuel
   Guilloteau, Stephane
   Boehler, Yann
   Bary, Jeff
   Beck, Tracy
   Beust, Herve
   Chapillon, Edwige
   Gueth, Frederic
   Hure, Jean-Marc
   Pierens, Arnaud
   Pietu, Vincent
   Simon, Michal
   Tang, Ya-Wen
TI Possible planet formation in the young, low-mass, multiple stellar system GG Tau A
SO NATURE
LA English
DT Article
ID gas accretion; protoplanetary discs; spectroscopic survey; binary-systems; line emission; disks; dynamics; evolution; migration; spectra
AB The formation of planets around binary stars may be more difficult than around single stars(1-3). In a close binary star (with a separation of less than a hundred astronomical units), theory predicts the presence of circumstellar disks around each star, and an outer circum-binary disk surrounding a gravitationally cleared inner cavity around the stars(4,5). Given that the inner disks are depleted by accretion onto the stars on timescales of a few thousand years, any replenishing material must be transferred from the outer reservoir to fuel planet formation (which occurs on timescales of about one million years). Gas flowing through disk cavities has been detected in single star systems(6). A circumbinary disk was discovered around the young low-mass binary system GG Tau A(ref. 7), which has recently been shown to be a hierarchical triple system(8). It has one large inner disk(9) around the single star, GG Tau Aa, and shows small amounts of shocked hydrogen gas residing within the central cavity(10), but other than a single weak detection(11), the distribution of cold gas in this cavity or in any other binary or multiple star system has not hitherto been determined. Here we report imaging of gas fragments emitting radiation characteristic of carbon monoxide within the GG Tau A cavity. From the kinematics we conclude that the flow appears capable of sustaining the inner disk (around GG Tau Aa) beyond the accretion lifetime, leaving time for planet formation to occur there. These results show the complexity of planet formation around multiple stars and confirm the general picture predicted by numerical simulations.
C1 [Dutrey, Anne; Di Folco, Emmanuel; Guilloteau, Stephane; Chapillon, Edwige; Hure, Jean-Marc; Pierens, Arnaud] Univ Bordeaux, LAB, UMR 5804, F-33270 Floirac, France.
   [Dutrey, Anne; Di Folco, Emmanuel; Guilloteau, Stephane; Hure, Jean-Marc; Pierens, Arnaud] CNRS, UMR 5804, LAB, F-33270 Floirac, France.
   [Boehler, Yann] Univ Mexico, CRyA, Morelia 58089, Michoacan, Mexico.
   [Bary, Jeff] Colgate Univ, Dept Phys & Astron, Hamilton, NY 13346 USA.
   [Beck, Tracy] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Beust, Herve] IPAG, UMR 5274, F-38041 Grenoble 9, France.
   [Chapillon, Edwige; Gueth, Frederic; Pietu, Vincent] IRAM, F-38046 St Martin Dheres, France.
   [Simon, Michal] SUNY Stony Brook, Stony Brook, NY 11794 USA.
   [Tang, Ya-Wen] Acad Sinica, Inst Astron & Astrophys, Taipei 106, Taiwan.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Bordeaux; Colgate University; Space Telescope Science Institute; Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); State University of New York (SUNY) System; Stony Brook University; Academia Sinica - Taiwan
RP Dutrey, A (corresponding author), Univ Bordeaux, LAB, UMR 5804, F-33270 Floirac, France.
EM Anne.Dutrey@obs.u-bordeaux1.fr
FU INSU/CNRS (France); MPG (Germany); IGN (Spain); French programme PNP; French programme PCMI; French programme PNPS; French programme ASA
NR 49
TC 58
Z9 62
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 OCT 30
PY 2014
VL 514
IS 7524
BP 600
EP +
DI 10.1038/nature13822
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500042
PM 25355359
DA 2026-03-09
ER

PT J
AU Hovenden, MJ
   Newton, PCD
   Wills, KE
AF Hovenden, Mark J.
   Newton, Paul C. D.
   Wills, Karen E.
TI Seasonal not annual rainfall determines grassland biomass response to carbon dioxide
SO NATURE
LA English
DT Article
ID elevated co2; climate-change; nitrogen interactions; water relations; ecosystems; productivity; limitation; rangelands; lessons; trends
AB The rising atmospheric concentration of carbon dioxide (CO2) should stimulate ecosystem productivity, but to what extent is highly uncertain, particularly when combined with changing temperature and precipitation(1). Ecosystem response to CO2 is complicated by biogeochemical feedbacks(2) but must be understood if carbon storage and associated dampening of climate warming are to be predicted(3). Feedbacks through the hydrological cycle are particularly important(4) and the physiology is well known; elevated CO2 reduces stomatal conductance and increases plant water use efficiency (the amount of water required to produce a unit of plant dry matter)(5). The CO2 response should consequently be strongest when water is limiting(6); although this has been shown in some experiments(7), it is absent frommany(8-11). Here we show that large annual variation in the stimulation of above-ground biomass by elevated CO2 in a mixed C-3/C-4 temperate grassland can be predicted accurately using seasonal rainfall totals; summer rainfall had a positive effect but autumn and spring rainfall had negative effects on the CO2 response. Thus, the elevated CO2 effect mainly depended upon the balance between summer and autumn/spring rainfall. This is partly because high rainfall during cool, moist seasons leads to nitrogen limitation, reducing or even preventing biomass stimulation by elevated CO2. Importantly, the prediction held whether plots were warmed by 2 degrees C or left unwarmed, and was similar for C-3 plants and total biomass, allowing us to make a powerful generalization about ecosystem responses to elevated CO2. This new insight is particularly valuable because climate projections predict large changes in the timing of rainfall, even where annual totals remain static(12). Our findings will help resolve apparent differences in the outcomes of CO2 experiments and improve the formulation and interpretation of models that are insensitive to differences in the seasonal effects of rainfall on the CO2 response(7,13,14).
C1 [Hovenden, Mark J.; Wills, Karen E.] Univ Tasmania, Sch Biol Sci, Hobart, Tas 7001, Australia.
   [Newton, Paul C. D.] AgResearch, Land & Environm Management, Palmerston North 4474, New Zealand.
C3 University of Tasmania; AgResearch - New Zealand
RP Hovenden, MJ (corresponding author), Univ Tasmania, Sch Biol Sci, Hobart, Tas 7001, Australia.
EM Mark.Hovenden@utas.edu.au
FU Australian Research Council
NR 34
TC 143
Z9 174
U1 0
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 30
PY 2014
VL 511
IS 7511
BP 583
EP +
DI 10.1038/nature13281
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300033
PM 24870242
DA 2026-03-09
ER

PT J
AU Pan, L
   Wang, S
   Lu, TL
   Weng, CJ
   Song, XQ
   Park, JK
   Sun, J
   Yang, ZH
   Yu, JJ
   Tang, H
   McKearin, DM
   Chamovitz, DA
   Ni, JQ
   Xie, T
AF Pan, Lei
   Wang, Su
   Lu, Tinglin
   Weng, Changjiang
   Song, Xiaoqing
   Park, Joseph K.
   Sun, Jin
   Yang, Zhi-Hao
   Yu, Junjing
   Tang, Hong
   McKearin, Dennis M.
   Chamovitz, Daniel A.
   Ni, Jianquan
   Xie, Ting
TI Protein competition switches the function of COP9 from self-renewal to differentiation
SO NATURE
LA English
DT Article
ID germline stem-cells; bag-of-marbles; drosophila ovary; signalosome; melanogaster; maintenance; division; niche; transcription; degradation
AB The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals(1,2). In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation(3). However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. mel-anogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins(4,5). Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.
C1 [Pan, Lei; Wang, Su; Weng, Changjiang; Song, Xiaoqing; Yu, Junjing; Xie, Ting] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Pan, Lei; Yu, Junjing; Tang, Hong] Chinese Acad Sci, Key Lab Infect & Immun, Inst Biophys, Beijing 100101, Peoples R China.
   [Wang, Su; Xie, Ting] Univ Kansas, Sch Med, Dept Cell Biol & Anat, Kansas City, KS 66160 USA.
   [Lu, Tinglin; Sun, Jin; Yang, Zhi-Hao; Ni, Jianquan] Tsinghua Univ, Sch Med, Ctr Life Sci, Beijing 100084, Peoples R China.
   [Park, Joseph K.; McKearin, Dennis M.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Park, Joseph K.; McKearin, Dennis M.] Univ Texas SW Med Ctr Dallas, Grad Sch Biomed Sci, Dallas, TX 75390 USA.
   [Park, Joseph K.; McKearin, Dennis M.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Chamovitz, Daniel A.] Tel Aviv Univ, Dept Plant Sci, IL-69978 Tel Aviv, Israel.
C3 Stowers Institute for Medical Research; Chinese Academy of Sciences; Institute of Biophysics, CAS; University of Kansas; University of Kansas Medical Center; Tsinghua University; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Tel Aviv University
RP Xie, T (corresponding author), Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA.
EM tgx@stowers.org
FU Stowers Institute for Medical Research; National Institutes of Health [GM64428]; National Natural Science Foundation of China [31370909]; Ministry of Science and Technology of China [2012CB518900]
NR 28
TC 45
Z9 55
U1 5
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 OCT 9
PY 2014
VL 514
IS 7521
BP 233
EP +
DI 10.1038/nature13562
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100043
PM 25119050
DA 2026-03-09
ER

PT J
AU Patra, PK
   Krol, MC
   Montzka, SA
   Arnold, T
   Atlas, EL
   Lintner, BR
   Stephens, BB
   Xiang, B
   Elkins, JW
   Fraser, PJ
   Ghosh, A
   Hintsa, EJ
   Hurst, DF
   Ishijima, K
   Krummel, PB
   Miller, BR
   Miyazaki, K
   Moore, FL
   Mühle, J
   O'Doherty, S
   Prinn, RG
   Steele, LP
   Takigawa, M
   Wang, HJ
   Weiss, RF
   Wofsy, SC
   Young, D
AF Patra, P. K.
   Krol, M. C.
   Montzka, S. A.
   Arnold, T.
   Atlas, E. L.
   Lintner, B. R.
   Stephens, B. B.
   Xiang, B.
   Elkins, J. W.
   Fraser, P. J.
   Ghosh, A.
   Hintsa, E. J.
   Hurst, D. F.
   Ishijima, K.
   Krummel, P. B.
   Miller, B. R.
   Miyazaki, K.
   Moore, F. L.
   Muehle, J.
   O'Doherty, S.
   Prinn, R. G.
   Steele, L. P.
   Takigawa, M.
   Wang, H. J.
   Weiss, R. F.
   Wofsy, S. C.
   Young, D.
TI Observational evidence for interhemispheric hydroxyl-radical parity
SO NATURE
LA English
DT Article
ID atmospheric hydroxyl; sulfur-hexafluoride; methyl chloroform; tropospheric oh; model; variability; climate; methane; assimilation; circulation
AB The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere(1-3). The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane(4-6). It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4,7-10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 +/- 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns(11-13). Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated.
C1 [Patra, P. K.; Ghosh, A.; Ishijima, K.; Miyazaki, K.; Takigawa, M.] JAMSTEC, Dept Environm Geochem Cycle Res, Yokohama, Kanagawa 2360001, Japan.
   [Patra, P. K.] Tohoku Univ, Grad Sch Studies, CAOS, Sendai, Miyagi 9808578, Japan.
   [Krol, M. C.] Wageningen Univ, NL-6708 PB Wageningen, Netherlands.
   [Montzka, S. A.; Elkins, J. W.; Hintsa, E. J.; Hurst, D. F.; Miller, B. R.; Moore, F. L.] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Arnold, T.; Muehle, J.; Weiss, R. F.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Atlas, E. L.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA.
   [Lintner, B. R.] Rutgers State Univ, New Brunswick, NJ 08901 USA.
   [Stephens, B. B.] Natl Ctr Atmospher Res, Boulder, CO 80301 USA.
   [Xiang, B.; Wofsy, S. C.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Fraser, P. J.; Krummel, P. B.; Steele, L. P.] Commonwealth Sci & Ind Res Org CSIRO Oceans & Atm, Ctr Australian Weather & Climate Res, Aspendale, Vic 3195, Australia.
   [Ghosh, A.] Natl Inst Polar Res, Tachikawa, Tokyo 1908518, Japan.
   [Hintsa, E. J.; Hurst, D. F.; Miller, B. R.; Moore, F. L.] Univ Colorado, CIRES, Boulder, CO 80309 USA.
   [O'Doherty, S.; Young, D.] Univ Bristol, Sch Chem, Cantocks Close BS8 1TS, Avon, England.
   [Prinn, R. G.] MIT, Cambridge, MA 02139 USA.
   [Wang, H. J.] Georgia Inst Technol, Sch Earth & Atmospher Sci, Atlanta, GA 30332 USA.
C3 Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Tohoku University; Wageningen University & Research; National Oceanic Atmospheric Admin (NOAA) - USA; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Miami; Rutgers University System; Rutgers University New Brunswick; National Center Atmospheric Research (NCAR) - USA; Harvard University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan; University of Colorado System; University of Colorado Boulder; University of Bristol; Massachusetts Institute of Technology (MIT); University System of Georgia; Georgia Institute of Technology
RP Patra, PK (corresponding author), JAMSTEC, Dept Environm Geochem Cycle Res, Yokohama, Kanagawa 2360001, Japan.
EM prabir@jamstec.go.jp
FU Japan Society for the Promotion of Science [22241008]; Ministry of Education, Culture, Sports, Science and Technology (MEXT); National Science Foundation (NSF); NSF grants [ATM-0628575, ATM-0628519, ATM-0628388 ATM-0628452, ATM-1036399]; NASA [NNX11AF36G, NNX11AF17G]; NCAR; EU FP7 project PEGASOS; Scripps Institution of Oceanography [NNX11AF16G]; NOAA; CSIRO; Department of Energy and Climate Change [GA0201]; CSIRO Oceans and Atmosphere Flagship; Bureau of Meteorology; Grants-in-Aid for Scientific Research [22241008] Funding Source: KAKEN; NASA [NNX11AF36G, 146831] Funding Source: Federal RePORTER
NR 48
TC 108
Z9 117
U1 3
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 SEP 11
PY 2014
VL 513
IS 7517
BP 219
EP 223
DI 10.1038/nature13721
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800047
PM 25209800
DA 2026-03-09
ER

PT J
AU Doria-Rose, NA
   Schramm, CA
   Gorman, J
   Moore, PL
   Bhiman, JN
   DeKosky, BJ
   Ernandes, MJ
   Georgiev, IS
   Kim, HJ
   Pancera, M
   Staupe, RP
   Altae-Tran, HR
   Bailer, RT
   Crooks, ET
   Cupo, A
   Druz, A
   Garrett, NJ
   Hoi, KH
   Kong, R
   Louder, MK
   Longo, NS
   McKee, K
   Nonyane, M
   O'Dell, S
   Roark, RS
   Rudicell, RS
   Schmidt, SD
   Sheward, DJ
   Soto, C
   Wibmer, CK
   Yang, YP
   Zhang, ZH
   Mullikin, JC
   Binley, JM
   Sanders, RW
   Wilson, IA
   Moore, JP
   Ward, AB
   Georgiou, G
   Williamson, C
   Karim, SSA
   Morris, L
   Kwong, PD
   Shapiro, L
   Mascola, JR
AF Doria-Rose, Nicole A.
   Schramm, Chaim A.
   Gorman, Jason
   Moore, Penny L.
   Bhiman, Jinal N.
   DeKosky, Brandon J.
   Ernandes, Michael J.
   Georgiev, Ivelin S.
   Kim, Helen J.
   Pancera, Marie
   Staupe, Ryan P.
   Altae-Tran, Han R.
   Bailer, Robert T.
   Crooks, Ema T.
   Cupo, Albert
   Druz, Aliaksandr
   Garrett, Nigel J.
   Hoi, Kam H.
   Kong, Rui
   Louder, Mark K.
   Longo, Nancy S.
   McKee, Krisha
   Nonyane, Molati
   O'Dell, Sijy
   Roark, Ryan S.
   Rudicell, Rebecca S.
   Schmidt, Stephen D.
   Sheward, Daniel J.
   Soto, Cinque
   Wibmer, Constantinos Kurt
   Yang, Yongping
   Zhang, Zhenhai
   Mullikin, James C.
   Binley, James M.
   Sanders, Rogier W.
   Wilson, Ian A.
   Moore, John P.
   Ward, Andrew B.
   Georgiou, George
   Williamson, Carolyn
   Karim, Salim S. Abdool
   Morris, Lynn
   Kwong, Peter D.
   Shapiro, Lawrence
   Mascola, John R.
TI Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; human monoclonal-antibody; maximum-likelihood; hiv-1-neutralizing antibody; vaccine efficacy; structural basis; broad; recognition; immunoglobulin; generation
AB Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.
C1 [Doria-Rose, Nicole A.; Gorman, Jason; Ernandes, Michael J.; Georgiev, Ivelin S.; Pancera, Marie; Staupe, Ryan P.; Altae-Tran, Han R.; Bailer, Robert T.; Druz, Aliaksandr; Kong, Rui; Louder, Mark K.; Longo, Nancy S.; McKee, Krisha; O'Dell, Sijy; Roark, Ryan S.; Rudicell, Rebecca S.; Schmidt, Stephen D.; Soto, Cinque; Yang, Yongping; Kwong, Peter D.; Shapiro, Lawrence; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Schramm, Chaim A.; Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem, New York, NY 10032 USA.
   [Moore, Penny L.; Bhiman, Jinal N.; Nonyane, Molati; Wibmer, Constantinos Kurt; Morris, Lynn] NHLS, Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa.
   [Moore, Penny L.; Bhiman, Jinal N.; Wibmer, Constantinos Kurt; Morris, Lynn] Univ Witwatersrand, Fac Hlth Sci, ZA-2050 Johannesburg, South Africa.
   [Moore, Penny L.; Garrett, Nigel J.; Williamson, Carolyn; Karim, Salim S. Abdool; Morris, Lynn] Univ KwaZulu Natal, CAPRISA, ZA-4013 Congella, South Africa.
   [DeKosky, Brandon J.; Georgiou, George] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.
   [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
   [Kim, Helen J.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Crooks, Ema T.; Binley, James M.] Torrey Pines Inst, San Diego, CA 92037 USA.
   [Cupo, Albert; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
   [Hoi, Kam H.; Georgiou, George] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
   [Sheward, Daniel J.] Univ Cape Town, Inst Infect Dis & Mol Med, Div Med Virol, ZA-7701 Cape Town, South Africa.
   [Sheward, Daniel J.] NHLS, ZA-7701 Cape Town, South Africa.
   [Mullikin, James C.] NIH, NISC Comparat Sequencing Program, Bethesda, MD 20892 USA.
   [Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
   [Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands.
   [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Georgiou, George] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
   [Karim, Salim S. Abdool] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Columbia University; National Institute for Communicable Diseases (NICD); National Health Laboratory Service; University of Witwatersrand; University of Kwazulu Natal; University of Texas System; University of Texas Austin; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; International AIDS Vaccine Initiative; Torrey Pines Institute for Molecular Studies; Cornell University; Weill Cornell Medicine; University of Texas System; University of Texas Austin; University of Cape Town; National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Amsterdam; Academic Medical Center Amsterdam; Scripps Research Institute; University of Texas System; University of Texas Austin; Columbia University
RP Morris, L (corresponding author), NHLS, Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa.
EM lynnm@nicd.ac.za; pdkwong@nih.gov; lss8@columbia.edu; jrmascola@nih.gov
FU Vaccine Research Center; NIAID; Fogarty International Center; NHGRI; NIGMS of the National Institutes of Health, USA; International AIDS Vaccine Initiative; National Science Foundation; Scripps CHAV-ID; South African Department of Science and Technology; Wellcome Trust; Hertz Foundation; Donald D. Harrington Foundation; Poliomyelitis Research Foundation; National Research Foundation of South Africa; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Human Genome Research Institute [ZIBHG000196] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI005022, ZICAI005111] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Allergy and Infectious Diseases [ZIAAI005095] Funding Source: NIH RePORTER
NR 83
TC 607
Z9 707
U1 0
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 MAY 1
PY 2014
VL 509
IS 7498
BP 55
EP +
DI 10.1038/nature13036
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100038
PM 24590074
DA 2026-03-09
ER

PT J
AU Sofikitis, D
   Bougas, L
   Katsoprinakis, GE
   Spiliotis, AK
   Loppinet, B
   Rakitzis, TP
AF Sofikitis, Dimitris
   Bougas, Lykourgos
   Katsoprinakis, Georgios E.
   Spiliotis, Alexandros K.
   Loppinet, Benoit
   Rakitzis, T. Peter
TI Evanescent-wave and ambient chiral sensing by signal-reversing cavity ringdown polarimetry
SO NATURE
LA English
DT Article
ID optical-activity; molecules
AB Detecting and quantifying chirality is important in fields ranging from analytical and biological chemistry to pharmacology(1) and fundamental physics(2): it can aid drug design and synthesis, contribute to protein structure determination, and help detect parity violation of the weak force. Recent developments employ microwaves(3), femto-second pulses(4), superchiral light(5) or photoionization(6) to determine chirality, yet the most widely used methods remain the traditional methods of measuring circular dichroism and optical rotation. However, these signals are typically very weak against larger time-dependent backgrounds(7). Cavity-enhanced optical methods can be used to amplify weak signals by passing them repeatedly through anoptical cavity, and two-mirror cavities achieving up to 10(5) cavity passes have enabled absorption and birefringence measurements with record sensitivities(8-10). But chiral signals cancel when passing back and forth through a cavity, while the ubiquitous spurious linear birefringence background is enhanced. Even when intracavity optics overcome these problems(11-15), absolute chirality measurements remain difficult and sometimes impossible. Here we use a pulsed-laser bowtie cavity ringdown polarimeter with counter-propagating beams(16,17) to enhance chiral signals by a factor equal to the number of cavity passes (typically > 10(3)); to suppress the effects of linear birefringence by means of a large induced intracavity Faraday rotation; and to effect rapid signal reversals by reversing the Faraday rotation and subtracting signals from the counter-propagating beams. These features allow absolute chiral signal measurements in environments where background subtraction is not feasible: we determine optical rotation from a-pinene vapour in open air, and from maltodextrin and fructose solutions in the evanescent wave produced by total internal reflection at a prism surface. The limits of the present polarimeter, when using a continuous-wave laser locked to a stable, high-finesse cavity, should match the sensitivity of linear birefringence measurements(8) (3 x 10(-13) radians), which is several orders of magnitude more sensitive than current chiral detection limits(7,14,15) and is expected to transform chiral sensing in many fields.
C1 [Sofikitis, Dimitris; Bougas, Lykourgos; Katsoprinakis, Georgios E.; Spiliotis, Alexandros K.; Loppinet, Benoit; Rakitzis, T. Peter] Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece.
   [Sofikitis, Dimitris; Bougas, Lykourgos; Katsoprinakis, Georgios E.; Spiliotis, Alexandros K.; Rakitzis, T. Peter] Univ Crete, Dept Phys, Iraklion 71003, Greece.
C3 Foundation for Research & Technology - Hellas (FORTH); University of Crete
RP Rakitzis, TP (corresponding author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece.
EM ptr@iesl.forth.gr
FU ERC grant TRICEPS [207542]; FP7 IAPP Programme SOFORT [PIAPGA-2009-251598]; FP7 Infrastructure programme ESMI [CPCSA-2010-262348]
NR 23
TC 113
Z9 121
U1 0
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 OCT 2
PY 2014
VL 514
IS 7520
BP 76
EP +
DI 10.1038/nature13680
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800038
PM 25209661
DA 2026-03-09
ER

PT J
AU McCracken, KW
   Catá, EM
   Crawford, CM
   Sinagoga, KL
   Schumacher, M
   Rockich, BE
   Tsai, YH
   Mayhew, CN
   Spence, JR
   Zavros, Y
   Wells, JM
AF McCracken, Kyle W.
   Cata, Emily M.
   Crawford, Calyn M.
   Sinagoga, Katie L.
   Schumacher, Michael
   Rockich, Briana E.
   Tsai, Yu-Hwai
   Mayhew, Christopher N.
   Spence, Jason R.
   Zavros, Yana
   Wells, James M.
TI Modelling human development and disease in pluripotent stem-cell-derived gastric organoids
SO NATURE
LA English
DT Article
ID helicobacter-pylori infection; epidermal growth-factor; in-vitro; definitive endoderm; duodenal-ulcer; specification; morphogenesis; integration; epithelium; mesoderm
AB Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection(1-3). Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis(4), and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland-and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signalling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. UsinghGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease.
C1 [McCracken, Kyle W.; Cata, Emily M.; Crawford, Calyn M.; Sinagoga, Katie L.; Mayhew, Christopher N.; Wells, James M.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Schumacher, Michael; Zavros, Yana] Univ Cincinnati, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA.
   [Rockich, Briana E.; Spence, Jason R.] Univ Michigan, Dept Cell & Dev Biol, Sch Med, Ann Arbor, MI 48109 USA.
   [Tsai, Yu-Hwai; Spence, Jason R.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Wells, James M.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA.
C3 Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Cincinnati Children's Hospital Medical Center
RP Wells, JM (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM zavrosya@ucmail.uc.edu; james.wells@cchmc.org
FU National Institutes of Health [R01DK080823, R01DK092456, K01DK091415]; NIGMS Medical Scientist Training Program [T32 GM063483]; American Gastroenterological Association: Robert and Sally Funderburg Research Award in Gastric Cancer; Cincinnati Digestive Disease Center Award [P30 DK0789392]; Clinical Translational Science Award [U54 RR025216]; Michigan Gastrointestinal Peptide Research Center (MGPRC) [NIDDK 5P30DK034933]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034933, P30DK078392] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM063483] Funding Source: NIH RePORTER
NR 42
TC 768
Z9 939
U1 5
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 DEC 18
PY 2014
VL 516
IS 7531
BP 400
EP +
DI 10.1038/nature13863
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800048
PM 25363776
DA 2026-03-09
ER

PT J
AU Bass, AJ
   Thorsson, V
   Shmulevich, I
   Reynolds, SM
   Miller, M
   Bernard, B
   Hinoue, T
   Laird, PW
   Curtis, C
   Shen, H
   Weisenberger, DJ
   Schultz, N
   Shen, RL
   Weinhold, N
   Keiser, DP
   Bowlby, R
   Sipahimalani, P
   Cherniack, AD
   Getz, G
   Liu, YC
   Noble, MS
   Pedamallu, C
   Sougnez, C
   Taylor-Weiner, A
   Akbani, R
   Lee, JS
   Liu, WB
   Mills, GB
   Yang, D
   Zhang, W
   Pantazi, A
   Parfenov, M
   Gulley, M
   Piazuelo, MB
   Schneider, BG
   Kim, J
   Boussioutas, A
   Sheth, M
   Demchok, JA
   Rabkin, CS
   Willis, JE
   Ng, S
   Garman, K
   Beer, DG
   Pennathur, A
   Raphael, BJ
   Wu, HT
   Odze, R
   Kim, HK
   Bowen, J
   Leraas, KM
   Lichtenberg, TM
   Weaver, L
   McLellan, M
   Wiznerowicz, M
   Sakai, R
   Getz, G
   Sougnez, C
   Lawrence, MS
   Cibulskis, K
   Lichtenstein, L
   Fisher, S
   Gabriel, SB
   Lander, ES
   Ding, L
   Niu, BF
   Ally, A
   Balasundaram, M
   Birol, I
   Bowlby, R
   Brooks, D
   Butterfield, YSN
   Carlsen, R
   Chu, A
   Chu, J
   Chuah, E
   Chun, HJE
   Clarke, A
   Dhalla, N
   Guin, R
   Holt, RA
   Jones, SJM
   Kasaian, K
   Lee, D
   Li, HYA
   Lim, E
   Ma, Y
   Marra, MA
   Mayo, M
   Moore, RA
   Mungall, AJ
   Mungall, KL
   Nip, KM
   Robertson, AG
   Schein, JE
   Sipahimalani, P
   Tam, A
   Thiessen, N
   Beroukhim, R
   Carter, SL
   Cherniack, AD
   Cho, J
   Cibulskis, K
   DiCara, D
   Frazer, S
   Fisher, S
   Gabriel, SB
   Gehlenborg, N
   Heiman, DI
   Jung, J
   Kim, J
   Lander, ES
   Lawrence, MS
   Lichtenstein, L
   Lin, P
   Meyerson, M
   Ojesina, AI
   Pedamallu, CS
   Saksena, G
   Schumacher, SE
   Sougnez, C
   Stojanov, P
   Tabak, B
   Taylor-Weiner, A
   Voet, D
   Rosenberg, M
   Zack, TI
   Zhang, HL
   Zou, LH
   Protopopov, A
   Santoso, N
   Parfenov, M
   Lee, S
   Zhang, J
   Mahadeshwar, HS
   Tang, JB
   Ren, XJ
   Seth, S
   Yang, LX
   Xu, AW
   Song, XZ
   Pantazi, A
   Xi, RB
   Bristow, CA
   Hadjipanayis, A
   Seidman, J
   Chin, L
   Park, PJ
   Kucherlapati, R
   Akbani, R
   Ling, SY
   Liu, WB
   Rao, A
   Weinstein, JN
   Kim, SB
   Lee, JS
   Lu, YL
   Mills, G
   Hinoue, T
   Weisenberger, DJ
   Bootwalla, MS
   Lai, PH
   Shen, H
   Triche, T
   Van Den Berg, DJ
   Baylin, SB
   Herman, JG
   Getz, G
   Chin, L
   Liu, YC
   Murray, BA
   Noble, MS
   Askoy, BA
   Ciriello, G
   Dresdner, G
   Gao, JJ
   Gross, B
   Jacobsen, A
   Lee, W
   Ramirez, R
   Sander, C
   Schultz, N
   Senbabaoglu, Y
   Sinha, R
   Sumer, SO
   Sun, YC
   Weinhold, N
   Thorsson, V
   Bernard, B
   Iype, L
   Kramer, RW
   Kreisberg, R
   Miller, M
   Reynolds, SM
   Rovira, H
   Tasman, N
   Shmulevich, I
   Ng, S
   Haussler, D
   Stuart, JM
   Akbani, R
   Ling, SY
   Liu, WB
   Rao, A
   Weinstein, JN
   Verhaak, RGW
   Mills, GB
   Leiserson, MDM
   Raphael, BJ
   Wu, HT
   Taylor, BS
   Black, AD
   Bowen, J
   Carney, JA
   Gastier-Foster, JM
   Helsel, C
   Leraas, KM
   Lichtenberg, TM
   McAllister, C
   Ramirez, NC
   Tabler, TR
   Wise, L
   Zmuda, E
   Penny, R
   Crain, D
   Gardner, J
   Lau, K
   Curely, E
   Mallery, D
   Morris, S
   Paulauskis, J
   Shelton, T
   Shelton, C
   Sherman, M
   Benz, C
   Lee, JH
   Fedosenko, K
   Manikhas, G
   Voronina, O
   Belyaev, D
   Dolzhansky, O
   Rathmell, WK
   Brzezinski, J
   Ibbs, M
   Korski, K
   Kycler, W
   Lazniak, R
   Leporowska, E
   Mackiewicz, A
   Murawa, D
   Murawa, P
   Spychala, A
   Suchorska, WM
   Tatka, H
   Teresiak, M
   Wiznerowicz, M
   Abdel-Misih, R
   Bennett, J
   Brown, J
   Iacocca, M
   Rabeno, B
   Kwon, SY
   Penny, R
   Gardner, J
   Kemkes, A
   Mallery, D
   Morris, S
   Shelton, T
   Shelton, C
   Curley, E
   Alexopoulou, I
   Engel, J
   Bartlett, J
   Albert, M
   Park, DY
   Dhir, R
   Luketich, J
   Landreneau, R
   Janjigian, YY
   Kelsen, DP
   Cho, E
   Ladanyi, M
   Tang, L
   McCall, SJ
   Park, YS
   Cheong, JH
   Ajani, J
   Camargo, MC
   Alonso, S
   Ayala, B
   Jensen, MA
   Pihl, T
   Raman, R
   Walton, J
   Wan, YH
   Demchok, JA
   Eley, G
   Shaw, KRM
   Sheth, M
   Tarnuzzer, R
   Wang, ZN
   Yang, LM
   Zenklusen, JC
   Davidsen, T
   Hutter, CM
   Sofia, HJ
   Burton, R
   Chudamani, S
   Liu, J
AF Bass, Adam J.
   Thorsson, Vesteinn
   Shmulevich, Ilya
   Reynolds, Sheila M.
   Miller, Michael
   Bernard, Brady
   Hinoue, Toshinori
   Laird, Peter W.
   Curtis, Christina
   Shen, Hui
   Weisenberger, Daniel J.
   Schultz, Nikolaus
   Shen, Ronglai
   Weinhold, Nils
   Keiser, David P.
   Bowlby, Reanne
   Sipahimalani, Payal
   Cherniack, Andrew D.
   Getz, Gad
   Liu, Yingchun
   Noble, Michael S.
   Pedamallu, Chandra
   Sougnez, Carrie
   Taylor-Weiner, Amaro
   Akbani, Rehan
   Lee, Ju-Seog
   Liu, Wenbin
   Mills, Gordon B.
   Yang, Da
   Zhang, Wei
   Pantazi, Angeliki
   Parfenov, Michael
   Gulley, Margaret
   Piazuelo, M. Blanca
   Schneider, Barbara G.
   Kim, Jihun
   Boussioutas, Alex
   Sheth, Margi
   Demchok, John A.
   Rabkin, Charles S.
   Willis, Joseph E.
   Ng, Sam
   Garman, Katherine
   Beer, David G.
   Pennathur, Arjun
   Raphael, Benjamin J.
   Wu, Hsin-Ta
   Odze, Robert
   Kim, Hark K.
   Bowen, Jay
   Leraas, Kristen M.
   Lichtenberg, Tara M.
   Weaver, Lichtenberg
   McLellan, Michael
   Wiznerowicz, Maciej
   Sakai, Ryo
   Getz, Gad
   Sougnez, Carrie
   Lawrence, Michael S.
   Cibulskis, Kristian
   Lichtenstein, Lee
   Fisher, Sheila
   Gabriel, Stacey B.
   Lander, Eric S.
   Ding, Li
   Niu, Beifang
   Ally, Adrian
   Balasundaram, Miruna
   Birol, Inanc
   Bowlby, Reanne
   Brooks, Denise
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Chu, Andy
   Chu, Justin
   Chuah, Eric
   Chun, Hye-Jung E.
   Clarke, Amanda
   Dhalla, Noreen
   Guin, Ranabir
   Holt, Robert A.
   Jones, Steven J. M.
   Kasaian, Katayoon
   Lee, Darlene
   Li, Haiyan A.
   Lim, Emilia
   Ma, Yussanne
   Marra, Marco A.
   Mayo, Michael
   Moore, Richard A.
   Mungall, Andrew J.
   Mungall, Karen L.
   Nip, Ka Ming
   Robertson, A. Gordon
   Schein, Jacqueline E.
   Sipahimalani, Payal
   Tam, Angela
   Thiessen, Nina
   Beroukhim, Rameen
   Carter, Scott L.
   Cherniack, Andrew D.
   Cho, Juok
   Cibulskis, Kristian
   DiCara, Daniel
   Frazer, Scott
   Fisher, Sheila
   Gabriel, Stacey B.
   Gehlenborg, Nils
   Heiman, David I.
   Jung, Joonil
   Kim, Jaegil
   Lander, Eric S.
   Lawrence, Michael S.
   Lichtenstein, Lee
   Lin, Pei
   Meyerson, Matthew
   Ojesina, Akinyemi I.
   Pedamallu, Chandra Sekhar
   Saksena, Gordon
   Schumacher, Steven E.
   Sougnez, Carrie
   Stojanov, Petar
   Tabak, Barbara
   Taylor-Weiner, Amaro
   Voet, Doug
   Rosenberg, Mara
   Zack, Travis I.
   Zhang, Hailei
   Zou, Lihua
   Protopopov, Alexei
   Santoso, Netty
   Parfenov, Michael
   Lee, Semin
   Zhang, Jianhua
   Mahadeshwar, Harshad S.
   Tang, Jiabin
   Ren, Xiaojia
   Seth, Sahil
   Yang, Lixing
   Xu, Andrew W.
   Song, Xingzhi
   Pantazi, Angeliki
   Xi, Ruibin
   Bristow, Christopher A.
   Hadjipanayis, Angela
   Seidman, Jonathan
   Chin, Lynda
   Park, Peter J.
   Kucherlapati, Raju
   Akbani, Rehan
   Ling, Shiyun
   Liu, Wenbin
   Rao, Arvind
   Weinstein, John N.
   Kim, Sang-Bae
   Lee, Ju-Seog
   Lu, Yiling
   Mills, Gordon
   Hinoue, Toshinori
   Weisenberger, Daniel J.
   Bootwalla, Moiz S.
   Lai, Phillip H.
   Shen, Hui
   Triche, Timothy, Jr.
   Van Den Berg, David J.
   Baylin, Stephen B.
   Herman, James G.
   Getz, Gad
   Chin, Lynda
   Liu, Yingchun
   Murray, Bradley A.
   Noble, Michael S.
   Askoy, B. Arman
   Ciriello, Giovanni
   Dresdner, Gideon
   Gao, Jianjiong
   Gross, Benjamin
   Jacobsen, Anders
   Lee, William
   Ramirez, Ricardo
   Sander, Chris
   Schultz, Nikolaus
   Senbabaoglu, Yasin
   Sinha, Rileen
   Sumer, S. Onur
   Sun, Yichao
   Weinhold, Nils
   Thorsson, Vesteinn
   Bernard, Brady
   Iype, Lisa
   Kramer, Roger W.
   Kreisberg, Richard
   Miller, Michael
   Reynolds, Sheila M.
   Rovira, Hector
   Tasman, Natalie
   Shmulevich, Ilya
   Ng, Sam
   Haussler, David
   Stuart, Josh M.
   Akbani, Rehan
   Ling, Shiyun
   Liu, Wenbin
   Rao, Arvind
   Weinstein, John N.
   Verhaak, Roeland G. W.
   Mills, Gordon B.
   Leiserson, Mark D. M.
   Raphael, Benjamin J.
   Wu, Hsin-Ta
   Taylor, Barry S.
   Black, Aaron D.
   Bowen, Jay
   Carney, Julie Ann
   Gastier-Foster, Julie M.
   Helsel, Carmen
   Leraas, Kristen M.
   Lichtenberg, Tara M.
   McAllister, Cynthia
   Ramirez, Nilsa C.
   Tabler, Teresa R.
   Wise, Lisa
   Zmuda, Erik
   Penny, Robert
   Crain, Daniel
   Gardner, Johanna
   Lau, Kevin
   Curely, Erin
   Mallery, David
   Morris, Scott
   Paulauskis, Joseph
   Shelton, Troy
   Shelton, Candace
   Sherman, Mark
   Benz, Christopher
   Lee, Jae-Hyuk
   Fedosenko, Konstantin
   Manikhas, Georgy
   Voronina, Olga
   Belyaev, Dmitry
   Dolzhansky, Oleg
   Rathmell, W. Kimryn
   Brzezinski, Jakub
   Ibbs, Matthew
   Korski, Konstanty
   Kycler, Witold
   Lazniak, Radoslaw
   Leporowska, Ewa
   Mackiewicz, Andrzej
   Murawa, Dawid
   Murawa, Pawel
   Spychala, Arkadiusz
   Suchorska, Wiktoria M.
   Tatka, Honorata
   Teresiak, Marek
   Wiznerowicz, Maciej
   Abdel-Misih, Raafat
   Bennett, Joseph
   Brown, Jennifer
   Iacocca, Mary
   Rabeno, Brenda
   Kwon, Sun-Young
   Penny, Robert
   Gardner, Johanna
   Kemkes, Ariane
   Mallery, David
   Morris, Scott
   Shelton, Troy
   Shelton, Candace
   Curley, Erin
   Alexopoulou, Iakovina
   Engel, Jay
   Bartlett, John
   Albert, Monique
   Park, Do-Youn
   Dhir, Rajiv
   Luketich, James
   Landreneau, Rodney
   Janjigian, Yelena Y.
   Kelsen, David P.
   Cho, Eunjung
   Ladanyi, Marc
   Tang, Laura
   McCall, Shannon J.
   Park, Young S.
   Cheong, Jae-Ho
   Ajani, Jaffer
   Camargo, M. Constanza
   Alonso, Shelley
   Ayala, Brenda
   Jensen, Mark A.
   Pihl, Todd
   Raman, Rohini
   Walton, Jessica
   Wan, Yunhu
   Demchok, John A.
   Eley, Greg
   Shaw, Kenna R. Mills
   Sheth, Margi
   Tarnuzzer, Roy
   Wang, Zhining
   Yang, Liming
   Zenklusen, Jean Claude
   Davidsen, Tanja
   Hutter, Carolyn M.
   Sofia, Heidi J.
   Burton, Robert
   Chudamani, Sudha
   Liu, Jia
TI Comprehensive molecular characterization of gastric adenocarcinoma
SO NATURE
LA English
DT Article
ID gene-expression; ebv-infection; cancer; mutations; exome; methylation; subtypes; kinase; lymphomas; effectors
AB Gastric cancer is a leading cause of cancer deaths, but analysis of molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roalmap for patient stratification and trials of targeted therapies.
C1 [Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Bass, Adam J.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA.
   [Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Rovira, Hector; Tasman, Natalie] Inst Syst Biol, Seattle, WA 98109 USA.
   [Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Triche, Timothy, Jr.; Van Den Berg, David J.] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90033 USA.
   [Curtis, Christina] Univ So Calif, Dept Prevent Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
   [Schultz, Nikolaus; Weinhold, Nils; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Shen, Ronglai] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   [Keiser, David P.; Janjigian, Yelena Y.; Kelsen, David P.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Bowlby, Reanne; Sipahimalani, Payal; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J. M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Tam, Angela; Thiessen, Nina] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
   [Cherniack, Andrew D.; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Beroukhim, Rameen; Carter, Scott L.; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Stojanov, Petar; Tabak, Barbara; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Murray, Bradley A.] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
   [Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Ling, Shiyun; Rao, Arvind; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Mills, Gordon B.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   [Yang, Da; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Pantazi, Angeliki; Parfenov, Michael; Santoso, Netty; Ren, Xiaojia; Hadjipanayis, Angela; Seidman, Jonathan; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
   [Gulley, Margaret] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Piazuelo, M. Blanca; Schneider, Barbara G.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA.
   [Kim, Jihun; Park, Young S.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea.
   [Boussioutas, Alex] Univ Melbourne, Sir Peter MacCallum Canc Dept Oncol, East Melbourne 3002, Australia.
   [Sheth, Margi; Demchok, John A.; Eley, Greg; Shaw, Kenna R. Mills; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude] NCI, Bethesda, MD 20892 USA.
   [Rabkin, Charles S.; Camargo, M. Constanza] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Willis, Joseph E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
   [Ng, Sam; Haussler, David; Stuart, Josh M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Haussler, David; Stuart, Josh M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Garman, Katherine] Duke Univ, Dept Med, Div Gastroenterol, Durham, NC 27710 USA.
   [Beer, David G.] Univ Michigan, Ctr Canc, Dept Thorac Surg, Ann Arbor, MI 48109 USA.
   [Pennathur, Arjun; Dhir, Rajiv; Luketich, James; Landreneau, Rodney] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
   [Raphael, Benjamin J.; Wu, Hsin-Ta; Leiserson, Mark D. M.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Wu, Hsin-Ta; Leiserson, Mark D. M.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
   [Odze, Robert] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Kim, Hark K.] Natl Canc Ctr, Goyang 410769, South Korea.
   [Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Lichtenberg; Black, Aaron D.; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
   [McLellan, Michael; Ding, Li; Niu, Beifang] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Wiznerowicz, Maciej; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; Lazniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychala, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek] Greater Poland Canc Ctr, PL-61866 Poznan, Poland.
   [Sakai, Ryo] Katholieke Univ Leuven, Dept Elect Engn ESAT STADIUS, Leuven, Belgium.
   [Protopopov, Alexei; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Seth, Sahil; Song, Xingzhi; Bristow, Christopher A.; Chin, Lynda; Verhaak, Roeland G. W.] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77054 USA.
   [Lee, Semin; Yang, Lixing; Xu, Andrew W.; Xi, Ruibin; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Baylin, Stephen B.; Herman, James G.] Johns Hopkins Univ, Canc Biol Div, Baltimore, MD 21231 USA.
   [Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Kemkes, Ariane] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Benz, Christopher] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Lee, Jae-Hyuk] Chonnam Natl Univ, Sch Med, Kwangju 501746, South Korea.
   [Fedosenko, Konstantin; Manikhas, Georgy] City Clin Oncol Dispensary, St Petersburg 198255, Russia.
   [Voronina, Olga; Belyaev, Dmitry; Dolzhansky, Oleg] Cureline Inc, San Francisco, CA 94080 USA.
   [Rathmell, W. Kimryn] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Rathmell, W. Kimryn] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda] Christiana Care Hlth Syst, Helen Graham Canc Ctr & Res Inst, Newark, DE 19713 USA.
   [Kwon, Sun-Young] Keimyung Univ, Sch Med, Taegu 700712, South Korea.
   [Alexopoulou, Iakovina] St Josephs Healthcare Hamilton, Ontario Tumour Bank, Hamilton, ON L8N 3Z5, Canada.
   [Engel, Jay] Kingston Gen Hosp, Ontario Tumour Bank, Kingston, ON K7L 5H6, Canada.
   [Bartlett, John; Albert, Monique] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.
   [Park, Do-Youn] Pusan Natl Univ Hosp, Pusan 602739, South Korea.
   [Cho, Eunjung; Ladanyi, Marc; Tang, Laura] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [McCall, Shannon J.] Duke Univ, Dept Pathol, Durham, NC 27710 USA.
   [Cheong, Jae-Ho] Yonsei Univ, Coll Med, Dept Surg, Seoul 120752, South Korea.
   [Ajani, Jaffer] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
   [Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA.
   [Davidsen, Tanja] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20850 USA.
   [Hutter, Carolyn M.; Sofia, Heidi J.] NHGRI, Bethesda, MD 20892 USA.
   [Burton, Robert; Chudamani, Sudha; Liu, Jia] SAIC Frederick Inc, Frederick, MD 21702 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Institute for Systems Biology (ISB); University of Southern California; University of Southern California; University Southern California Hospital; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; British Columbia Cancer Agency; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard Medical School; University of North Carolina; University of North Carolina Chapel Hill; Vanderbilt University; University of Ulsan; Asan Medical Center; University of Melbourne; Peter Maccallum Cancer Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; University System of Ohio; Case Western Reserve University; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Duke University; University of Michigan System; University of Michigan; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Brown University; Brown University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; National Cancer Center - Korea (NCC); University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; Washington University (WUSTL); Wielkopolskie Centrum Onkologii; KU Leuven; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard Medical School; Johns Hopkins University; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; International Genomics Consortium; Buck Institute for Research on Aging; Chonnam National University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Helen F. Graham Cancer Center & Research Institute; Christiana Care Health System; Keimyung University; McMaster University; Queens University - Canada; Queens University Hospital; University of Toronto; Ontario Institute for Cancer Research; Pusan National University; Pusan National University Hospital; Memorial Sloan Kettering Cancer Center; Duke University; Yonsei University; Yonsei University Health System; University of Texas System; UTMD Anderson Cancer Center; SRA International; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Science Applications International Corporation (SAIC); SAIC-Frederick
RP Bass, AJ (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM adam_bass@dfci.harvard.edu
FU Intramural Research Program; United States National Institutes of Health [5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, U54HG003273, P30CA16672]; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [1016648] Funding Source: National Science Foundation; National Cancer Institute [P30CA006973, P30CA016672] Funding Source: NIH RePORTER
NR 40
TC 5147
Z9 5744
U1 16
U2 573
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 11
PY 2014
VL 513
IS 7517
BP 202
EP 209
DI 10.1038/nature13480
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800044
PM 25079317
DA 2026-03-09
ER

PT J
AU Collisson, EA
   Campbell, JD
   Brooks, AN
   Berger, AH
   Lee, W
   Chmielecki, J
   Beer, DG
   Cope, L
   Creighton, CJ
   Danilova, L
   Ding, L
   Getz, G
   Hammerman, PS
   Hayes, DN
   Hernandez, B
   Herman, JG
   Heymach, JV
   Jurisica, I
   Kucherlapati, R
   Kwiatkowski, D
   Ladanyi, M
   Robertson, G
   Schultz, N
   Shen, RL
   Sinha, R
   Sougnez, C
   Tsao, MS
   Travis, WD
   Weinstein, JN
   Wigle, DA
   Wilkerson, MD
   Chu, AD
   Cherniack, AD
   Hadjipanayis, A
   Rosenberg, M
   Weisenberger, DJ
   Laird, PW
   Radenbaugh, A
   Ma, SG
   Stuart, JM
   Byers, LA
   Baylin, SB
   Govindan, R
   Meyerson, M
   Rosenberg, M
   Gabriel, SB
   Cibulskis, K
   Sougnez, C
   Kim, J
   Stewart, C
   Lichtenstein, L
   Lander, ES
   Lawrence, MS
   Getz
   Kandoth, C
   Fulton, R
   Fulton, LL
   McLellan, MD
   Wilson, RK
   Ye, K
   Fronick, CC
   Maher, CA
   Miller, CA
   Wendl, MC
   Cabanski, C
   Ding, L
   Mardis, E
   Govindan, R
   Creighton, CJ
   Wheeler, D
   Balasundaram, M
   Butterfield, YSN
   Carlsen, R
   Chu, AD
   Chuah, E
   Dhalla, N
   Guin, R
   Hirst, C
   Lee, D
   Li, HYI
   Mayo, M
   Moore, RA
   Mungall, AJ
   Schein, JE
   Sipahimalani, P
   Tam, A
   Varhol, R
   Robertson, AG
   Wye, N
   Thiessen, N
   Holt, RA
   Jones, SJM
   Marra, MA
   Campbell, JD
   Brooks, AN
   Chmielecki, J
   Imielinski, M
   Onofrio, RC
   Hodis, E
   Zack, T
   Sougnez, C
   Helman, E
   Pedamallu, CS
   Mesirov, J
   Cherniack, AD
   Saksena, G
   Schumacher, SE
   Carter, SL
   Hernandez, B
   Garraway, L
   Beroukhim, R
   Gabriel, SB
   Getz, G
   Meyerson, M
   Hadjipanayis, A
   Lee, S
   Mahadeshwar, HS
   Pantazi, A
   Protopopov, A
   Ren, XJ
   Seth, S
   Song, XZ
   Tang, JB
   Yang, LX
   Zhang, JH
   Chen, PC
   Parfenov, M
   Xu, AW
   Santoso, N
   Chin, L
   Park, PJ
   Kucherlapati, R
   Hoadley, KA
   Auman, JT
   Meng, SW
   Shi, Y
   Buda, E
   Waring, S
   Veluvolu, U
   Tan, DH
   Mieczkowski, PA
   Jones, CD
   Simons, JV
   Soloway, MG
   Bodenheimer, T
   Jefferys, SR
   Roach, J
   Hoyle, AP
   Wu, JY
   Balu, S
   Singh, D
   Prins, JF
   Marron, JS
   Parker, JS
   Hayes, DN
   Perou, CM
   Liu, JZ
   Cope, L
   Danilova, L
   Weisenberger, DJ
   Maglinte, DT
   Lai, PH
   Bootwalla, MS
   Van Den Berg, DJ
   Triche, T
   Baylin, SB
   Laird, PW
   Rosenberg, M
   Chin, L
   Zhang, JH
   Cho, J
   DiCara, D
   Heiman, D
   Lin, P
   Mallard, W
   Voet, D
   Zhang, HL
   Zou, LH
   Noble, MS
   Lawrence, MS
   Saksena, G
   Gehlenborg, N
   Thorvaldsdottir, H
   Mesirov, J
   Nazaire, MD
   Robinson, J
   Getz, G
   Lee, W
   Aksoy, BA
   Ciriello, G
   Taylor, BS
   Dresdner, G
   Gao, JJ
   Gross, B
   Seshan, VE
   Ladanyi, M
   Reva, B
   Sinha, R
   Sumer, SO
   Weinhold, N
   Schultz, N
   Shen, RL
   Sander, C
   Ng, S
   Ma, S
   Zhu, JC
   Radenbaugh, A
   Stuart, JM
   Benz, CC
   Yau, C
   Haussler, D
   Spellman, PT
   Wilkerson, MD
   Parker, JS
   Hoadley, KA
   Kimes, PK
   Hayes, DN
   Perou, CM
   Broom, BM
   Wang, J
   Lu, YL
   Ng, PKS
   Diao, LX
   Byers, LA
   Liu, WB
   Heymach, JV
   Amos, CI
   Weinstein, JN
   Akbani, R
   Mills, GB
   Curley, E
   Paulauskis, J
   Lau, K
   Morris, S
   Shelton, T
   Mallery, D
   Gardner, J
   Penny, R
   Saller, C
   Tarvin, K
   Richards, WG
   Cerfolio, R
   Bryant, A
   Raymond, DP
   Pennell, NA
   Farver, C
   Czerwinski, C
   Huelsenbeck-Dill, L
   Iacocca, M
   Petrelli, N
   Rabeno, B
   Brown, J
   Bauer, T
   Dolzhanskiy, O
   Potapova, O
   Rotin, D
   Voronina, O
   Nemirovich-Danchenko, E
   Fedosenko, KV
   Gal, A
   Behera, M
   Ramalingam, SS
   Sica, G
   Flieder, D
   Boyd, J
   Weaver, J
   Kohl, B
   Thinh, DHQ
   Sandusky, G
   Juhl, H
   Duhig, E
   Illei, P
   Gabrielson, E
   Shin, J
   Lee, B
   Rogers, K
   Trusty, D
   Brock, MV
   Williamson, C
   Burks, E
   Rieger-Christ, K
   Holway, A
   Sullivan, T
   Wigle, DA
   Asiedu, MK
   Kosari, F
   Travis, WD
   Rekhtman, N
   Zakowski, M
   Rusch, VW
   Zippile, P
   Suh, J
   Pass, H
   Goparaju, C
   Owusu-Sarpong, Y
   Bartlett, JMS
   Kodeeswaran, S
   Parfitt, J
   Sekhon, H
   Albert, M
   Eckman, J
   Myers, JB
   Cheney, R
   Morrison, C
   Gaudioso, C
   Borgia, JA
   Bonomi, P
   Pool, M
   Liptay, MJ
   Moiseenko, F
   Zaytseva, I
   Dienemann, H
   Meister, M
   Schnabel, PA
   Muley, TR
   Peifer, M
   Gomez-Fernandez, C
   Herbert, L
   Egea, S
   Huang, M
   Thorne, LB
   Boice, L
   Salazar, AH
   Funkhouser, WK
   Rathmell, WK
   Dhir, R
   Yousem, SA
   Dacic, S
   Schneider, F
   Siegfried, JM
   Hajek, R
   Watson, MA
   McDonald, S
   Meyers, B
   Clarke, B
   Yang, IA
   Fong, KM
   Hunter, L
   Windsor, M
   Bowman, RV
   Peters, S
   Letovanec, I
   Khan, KZ
   Jensen, MA
   Snyder, EE
   Srinivasan, D
   Kahn, AB
   Baboud, J
   Pot, DA
   Shaw, KRM
   Sheth, M
   Davidsen, T
   Demchok, JA
   Yang, LM
   Wang, ZN
   Tarnuzzer, R
   Zenklusen, JC
   Ozenberger, BA
   Sofia, HJ
   Travis, WD
   Cheney, R
   Clarke, B
   Sanja Dacic
   Duhig, E
   Funkhouser, WK
   Illei, P
   Farver, C
   Rekhtman, N
   Sica, G
   Suh, J
   Tsao, MS
AF Collisson, Eric A.
   Campbell, Joshua D.
   Brooks, Angela N.
   Berger, Alice H.
   Lee, William
   Chmielecki, Juliann
   Beer, David G.
   Cope, Leslie
   Creighton, Chad J.
   Danilova, Ludmila
   Ding, Li
   Getz, Gad
   Hammerman, Peter S.
   Hayes, D. Neil
   Hernandez, Bryan
   Herman, James G.
   Heymach, John V.
   Jurisica, Igor
   Kucherlapati, Raju
   Kwiatkowski, David
   Ladanyi, Marc
   Robertson, Gordon
   Schultz, Nikolaus
   Shen, Ronglai
   Sinha, Rileen
   Sougnez, Carrie
   Tsao, Ming-Sound
   Travis, William D.
   Weinstein, John N.
   Wigle, Dennis A.
   Wilkerson, Matthew D.
   Chu, Andy
   Cherniack, Andrew D.
   Hadjipanayis, Angela
   Rosenberg, Mara
   Weisenberger, Daniel J.
   Laird, Peter W.
   Radenbaugh, Amie
   Ma, Singer
   Stuart, Joshua M.
   Byers, Lauren Averett
   Baylin, Stephen B.
   Govindan, Ramaswamy
   Meyerson, Matthew
   Rosenberg, Mara
   Gabriel, Stacey B.
   Cibulskis, Kristian
   Sougnez, Carrie
   Kim, Jaegil
   Stewart, Chip
   Lichtenstein, Lee
   Lander, Eric S.
   Lawrence, Michael S.
   Getz
   Kandoth, Cyriac
   Fulton, Robert
   Fulton, Lucinda L.
   McLellan, Michael D.
   Wilson, Richard K.
   Ye, Kai
   Fronick, Catrina C.
   Maher, Christopher A.
   Miller, Christopher A.
   Wendl, Michael C.
   Cabanski, Christopher
   Ding, Li
   Mardis, Elaine
   Govindan, Ramaswamy
   Creighton, Chad J.
   Wheeler, David
   Balasundaram, Miruna
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Chu, Andy
   Chuah, Eric
   Dhalla, Noreen
   Guin, Ranabir
   Hirst, Carrie
   Lee, Darlene
   Li, Haiyan I.
   Mayo, Michael
   Moore, Richard A.
   Mungall, Andrew J.
   Schein, Jacqueline E.
   Sipahimalani, Payal
   Tam, Angela
   Varhol, Richard
   Robertson, A. Gordon
   Wye, Natasja
   Thiessen, Nina
   Holt, Robert A.
   Jones, Steven J. M.
   Marra, Marco A.
   Campbell, Joshua D.
   Brooks, Angela N.
   Chmielecki, Juliann
   Imielinski, Marcin
   Onofrio, Robert C.
   Hodis, Eran
   Zack, Travis
   Sougnez, Carrie
   Helman, Elena
   Pedamallu, Chandra Sekhar
   Mesirov, Jill
   Cherniack, Andrew D.
   Saksena, Gordon
   Schumacher, Steven E.
   Carter, Scott L.
   Hernandez, Bryan
   Garraway, Levi
   Beroukhim, Rameen
   Gabriel, Stacey B.
   Getz, Gad
   Meyerson, Matthew
   Hadjipanayis, Angela
   Lee, Semin
   Mahadeshwar, Harshad S.
   Pantazi, Angeliki
   Protopopov, Alexei
   Ren, Xiaojia
   Seth, Sahil
   Song, Xingzhi
   Tang, Jiabin
   Yang, Lixing
   Zhang, Jianhua
   Chen, Peng-Chieh
   Parfenov, Michael
   Xu, Andrew Wei
   Santoso, Netty
   Chin, Lynda
   Park, Peter J.
   Kucherlapati, Raju
   Hoadley, Katherine A.
   Auman, J. Todd
   Meng, Shaowu
   Shi, Yan
   Buda, Elizabeth
   Waring, Scot
   Veluvolu, Umadevi
   Tan, Donghui
   Mieczkowski, Piotr A.
   Jones, Corbin D.
   Simons, Janae V.
   Soloway, Matthew G.
   Bodenheimer, Tom
   Jefferys, Stuart R.
   Roach, Jeffrey
   Hoyle, Alan P.
   Wu, Junyuan
   Balu, Saianand
   Singh, Darshan
   Prins, Jan F.
   Marron, J. S.
   Parker, Joel S.
   Hayes, D. Neil
   Perou, Charles M.
   Liu, Jinze
   Cope, Leslie
   Danilova, Ludmila
   Weisenberger, Daniel J.
   Maglinte, Dennis T.
   Lai, Philip H.
   Bootwalla, Moiz S.
   Van Den Berg, David J.
   Triche, Timothy, Jr.
   Baylin, Stephen B.
   Laird, Peter W.
   Rosenberg, Mara
   Chin, Lynda
   Zhang, Jianhua
   Cho, Juok
   DiCara, Daniel
   Heiman, David
   Lin, Pei
   Mallard, William
   Voet, Douglas
   Zhang, Hailei
   Zou, Lihua
   Noble, Michael S.
   Lawrence, Michael S.
   Saksena, Gordon
   Gehlenborg, Nils
   Thorvaldsdottir, Helga
   Mesirov, Jill
   Nazaire, Marc-Danie
   Robinson, Jim
   Getz, Gad
   Lee, William
   Aksoy, B. Arman
   Ciriello, Giovanni
   Taylor, Barry S.
   Dresdner, Gideon
   Gao, Jianjiong
   Gross, Benjamin
   Seshan, Venkatraman E.
   Ladanyi, Marc
   Reva, Boris
   Sinha, Rileen
   Sumer, S. Onur
   Weinhold, Nils
   Schultz, Nikolaus
   Shen, Ronglai
   Sander, Chris
   Sam Ng
   Ma, Singer
   Zhu, Jingchun
   Radenbaugh, Amie
   Stuart, Joshua M.
   Benz, Christopher C.
   Yau, Christina
   Haussler, David
   Spellman, Paul T.
   Wilkerson, Matthew D.
   Parker, Joel S.
   Hoadley, Katherine A.
   Kimes, Patrick K.
   Hayes, D. Neil
   Perou, Charles M.
   Broom, Bradley M.
   Wang, Jing
   Lu, Yiling
   Patrick Kwok Shing Ng
   Diao, Lixia
   Byers, Lauren Averett
   Liu, Wenbin
   Heymach, John V.
   Amos, Christopher I.
   Weinstein, John N.
   Akbani, Rehan
   Mills, Gordon B.
   Curley, Erin
   Paulauskis, Joseph
   Lau, Kevin
   Morris, Scott
   Shelton, Troy
   Mallery, David
   Gardner, Johanna
   Penny, Robert
   Saller, Charles
   Tarvin, Katherine
   Richards, William G.
   Cerfolio, Robert
   Bryant, Ayesha
   Raymond, Daniel P.
   Pennell, Nathan A.
   Farver, Carol
   Czerwinski, Christine
   Huelsenbeck-Dill, Lori
   Iacocca, Mary
   Petrelli, Nicholas
   Rabeno, Brenda
   Brown, Jennifer
   Bauer, Thomas
   Dolzhanskiy, Oleg
   Potapova, Olga
   Rotin, Daniil
   Voronina, Olga
   Nemirovich-Danchenko, Elena
   Fedosenko, Konstantin V.
   Gal, Anthony
   Behera, Madhusmita
   Ramalingam, Suresh S.
   Sica, Gabriel
   Flieder, Douglas
   Boyd, Jeff
   Weaver, JoEllen
   Kohl, Bernard
   Dang Huy Quoc Thinh
   Sandusky, George
   Juhl, Hartmut
   Duhig, Edwina
   Illei, Peter
   Gabrielson, Edward
   Shin, James
   Lee, Beverly
   Rogers, Kristen
   Trusty, Dante
   Brock, Malcolm V.
   Williamson, Christina
   Burks, Eric
   Rieger-Christ, Kimberly
   Holway, Antonia
   Sullivan, Travis
   Wigle, Dennis A.
   Asiedu, Michael K.
   Kosari, Farhad
   Travis, William D.
   Rekhtman, Natasha
   Zakowski, Maureen
   Rusch, Valerie W.
   Zippile, Paul
   Suh, James
   Pass, Harvey
   Goparaju, Chandra
   Owusu-Sarpong, Yvonne
   Bartlett, John M. S.
   Kodeeswaran, Sugy
   Parfitt, Jeremy
   Sekhon, Harmanjatinder
   Albert, Monique
   Eckman, John
   Myers, Jerome B.
   Cheney, Richard
   Morrison, Carl
   Gaudioso, Carmelo
   Borgia, Jeffrey A.
   Bonomi, Philip
   Pool, Mark
   Liptay, Michael J.
   Moiseenko, Fedor
   Zaytseva, Irina
   Dienemann, Hendrik
   Meister, Michael
   Schnabel, Philipp A.
   Muley, Thomas R.
   Peifer, Martin
   Gomez-Fernandez, Carmen
   Herbert, Lynn
   Egea, Sophie
   Huang, Mei
   Thorne, Leigh B.
   Boice, Lori
   Salazar, Ashley Hill
   Funkhouser, William K.
   Rathmell, W. Kimryn
   Dhir, Rajiv
   Yousem, Samuel A.
   Dacic, Sanja
   Schneider, Frank
   Siegfried, Jill M.
   Hajek, Richard
   Watson, Mark A.
   McDonald, Sandra
   Meyers, Bryan
   Clarke, Belinda
   Yang, Ian A.
   Fong, Kwun M.
   Hunter, Lindy
   Windsor, Morgan
   Bowman, Rayleen V.
   Peters, Solange
   Letovanec, Igor
   Khan, Khurram Z.
   Jensen, Mark A.
   Snyder, Eric E.
   Srinivasan, Deepak
   Kahn, Ari B.
   Baboud, Julien
   Pot, David A.
   Shaw, Kenna R. Mills
   Sheth, Margi
   Davidsen, Tanja
   Demchok, John A.
   Yang, Liming
   Wang, Zhining
   Tarnuzzer, Roy
   Zenklusen, Jean Claude
   Ozenberger, Bradley A.
   Sofia, Heidi J.
   Travis, William D.
   Cheney, Richard
   Clarke, Belinda
   Dacic, Sanja
   Duhig, Edwina
   Funkhouser, William K.
   Illei, Peter
   Farver, Carol
   Rekhtman, Natasha
   Sica, Gabriel
   Suh, James
   Tsao, Ming-Sound
TI Comprehensive molecular profiling of lung adenocarcinoma
SO NATURE
LA English
DT Article
ID cancer genome; cell-lines; mutations; expression; gene; reveals; classification; inactivation; landscape; discovery
AB Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen(mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
C1 [Collisson, Eric A.; Taylor, Barry S.] Univ Calif San Francisco, San Francisco, CA 94158 USA.
   [Brooks, Angela N.; Garraway, Levi; Beroukhim, Rameen; Meyerson, Matthew; Spellman, Paul T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Brooks, Angela N.; Lee, William; Ladanyi, Marc; Schultz, Nikolaus; Shen, Ronglai; Travis, William D.; Aksoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Seshan, Venkatraman E.; Reva, Boris; Sinha, Rileen; Sumer, S. Onur; Weinhold, Nils; Schultz, Nikolaus; Sander, Chris; Rekhtman, Natasha; Zakowski, Maureen; Rusch, Valerie W.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Beer, David G.] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Cope, Leslie; Danilova, Ludmila; Herman, James G.; Baylin, Stephen B.; Illei, Peter; Gabrielson, Edward; Shin, James; Lee, Beverly; Rogers, Kristen; Trusty, Dante; Brock, Malcolm V.] Johns Hopkins Univ, Baltimore, MD 21287 USA.
   [Creighton, Chad J.; Wheeler, David] Baylor Coll Med, Houston, TX 77030 USA.
   [Ding, Li; Govindan, Ramaswamy; Kandoth, Cyriac; Fulton, Robert; Fulton, Lucinda L.; McLellan, Michael D.; Wilson, Richard K.; Ye, Kai; Fronick, Catrina C.; Maher, Christopher A.; Miller, Christopher A.; Wendl, Michael C.; Cabanski, Christopher; Mardis, Elaine; Watson, Mark A.; McDonald, Sandra; Meyers, Bryan] Washington Univ, St Louis, MO 63108 USA.
   [Getz, Gad; Kucherlapati, Raju; Hadjipanayis, Angela; Getz; Imielinski, Marcin; Hodis, Eran; Garraway, Levi; Beroukhim, Rameen; Meyerson, Matthew; Hadjipanayis, Angela; Lee, Semin; Pantazi, Angeliki; Ren, Xiaojia; Yang, Lixing; Chen, Peng-Chieh; Parfenov, Michael; Xu, Andrew Wei; Santoso, Netty; Park, Peter J.; Kucherlapati, Raju] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Getz, Gad; Getz; Imielinski, Marcin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Hayes, D. Neil; Wilkerson, Matthew D.; Hoadley, Katherine A.; Auman, J. Todd; Meng, Shaowu; Shi, Yan; Buda, Elizabeth; Waring, Scot; Veluvolu, Umadevi; Tan, Donghui; Mieczkowski, Piotr A.; Jones, Corbin D.; Simons, Janae V.; Soloway, Matthew G.; Bodenheimer, Tom; Jefferys, Stuart R.; Roach, Jeffrey; Hoyle, Alan P.; Wu, Junyuan; Balu, Saianand; Singh, Darshan; Prins, Jan F.; Marron, J. S.; Parker, Joel S.; Perou, Charles M.; Kimes, Patrick K.; Huang, Mei; Thorne, Leigh B.; Boice, Lori; Salazar, Ashley Hill; Funkhouser, William K.; Rathmell, W. Kimryn] Univ N Carolina, Chapel Hill, NC 27599 USA.
   [Heymach, John V.; Sinha, Rileen; Weinstein, John N.; Byers, Lauren Averett; Holt, Robert A.; Mahadeshwar, Harshad S.; Protopopov, Alexei; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zhang, Jianhua; Chin, Lynda; Broom, Bradley M.; Wang, Jing; Lu, Yiling; Patrick Kwok Shing Ng; Diao, Lixia; Liu, Wenbin; Amos, Christopher I.; Akbani, Rehan; Mills, Gordon B.; Hajek, Richard] Univ Texas MD Anderson Canc Ctr, Houston, TX 77054 USA.
   [Jurisica, Igor; Tsao, Ming-Sound] Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [Kwiatkowski, David; Hadjipanayis, Angela; Lee, Semin; Pantazi, Angeliki; Parfenov, Michael; Xu, Andrew Wei; Santoso, Netty; Park, Peter J.; Kucherlapati, Raju; Richards, William G.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Robertson, Gordon; Chu, Andy; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Varhol, Richard; Robertson, A. Gordon; Wye, Natasja; Thiessen, Nina; Jones, Steven J. M.; Marra, Marco A.] BC Canc Agcy, Vancouver, BC V5Z 4S6, Canada.
   [Wigle, Dennis A.; Asiedu, Michael K.; Kosari, Farhad] Mayo Clin, Rochester, MN 55905 USA.
   [Weisenberger, Daniel J.; Laird, Peter W.; Maglinte, Dennis T.; Lai, Philip H.; Bootwalla, Moiz S.; Van Den Berg, David J.; Triche, Timothy, Jr.] Univ So Calif, Los Angeles, CA 90033 USA.
   [Radenbaugh, Amie; Ma, Singer; Stuart, Joshua M.; Sam Ng; Zhu, Jingchun; Radenbaugh, Amie; Haussler, David] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
   [Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
   [Liu, Jinze] Univ Kentucky, Lexington, KY 40515 USA.
   [Benz, Christopher C.; Yau, Christina] Buck Inst Age Res, Novato, CA 94945 USA.
   [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Spellman, Paul T.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Curley, Erin; Paulauskis, Joseph; Lau, Kevin; Morris, Scott; Shelton, Troy; Mallery, David; Gardner, Johanna; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Saller, Charles; Tarvin, Katherine] Analyt Biol Serv Inc, Wilmington, DE 19801 USA.
   [Cerfolio, Robert; Bryant, Ayesha] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
   [Raymond, Daniel P.; Pennell, Nathan A.; Farver, Carol] Cleveland Clin, Cleveland, OH 44195 USA.
   [Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Brown, Jennifer; Bauer, Thomas] Christiana Care, Newark, DE 19713 USA.
   [Dolzhanskiy, Oleg; Potapova, Olga; Rotin, Daniil; Voronina, Olga; Nemirovich-Danchenko, Elena; Fedosenko, Konstantin V.] Cureline Inc, San Francisco, CA 94080 USA.
   [Gal, Anthony; Behera, Madhusmita; Ramalingam, Suresh S.; Sica, Gabriel] Emory Univ, Atlanta, GA 30322 USA.
   [Flieder, Douglas; Boyd, Jeff; Weaver, JoEllen] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
   [Kohl, Bernard; Dang Huy Quoc Thinh] ILSbio, Chestertown, MD 21620 USA.
   [Sandusky, George] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
   [Juhl, Hartmut] Individumed, Silver Spring, MD 20910 USA.
   [Duhig, Edwina; Clarke, Belinda; Yang, Ian A.; Fong, Kwun M.; Hunter, Lindy; Windsor, Morgan; Bowman, Rayleen V.; Duhig, Edwina] Prince Charles Hosp, Brisbane, Qld 4032, Australia.
   [Duhig, Edwina; Clarke, Belinda; Fong, Kwun M.; Hunter, Lindy; Windsor, Morgan; Bowman, Rayleen V.; Duhig, Edwina] Univ Queensland, Thorac Res Ctr, Brisbane, Qld 4032, Australia.
   [Duhig, Edwina] Sullivan Nicolaides Pathol, Tugun 4680, Australia.
   [Duhig, Edwina] John Flynn Hosp, Tugun 4680, Australia.
   [Williamson, Christina; Burks, Eric; Rieger-Christ, Kimberly; Holway, Antonia; Sullivan, Travis] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA.
   [Zippile, Paul; Suh, James; Pass, Harvey; Goparaju, Chandra; Owusu-Sarpong, Yvonne] NYU Langone Med Ctr, New York, NY 10016 USA.
   [Bartlett, John M. S.; Kodeeswaran, Sugy; Parfitt, Jeremy; Sekhon, Harmanjatinder; Albert, Monique] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.
   [Eckman, John; Myers, Jerome B.] Penrose St Francis Hlth Serv, Colorado Springs, CO 80907 USA.
   [Cheney, Richard; Morrison, Carl; Gaudioso, Carmelo] Roswel Pk Canc Ctr, Buffalo, NY 14263 USA.
   [Borgia, Jeffrey A.; Bonomi, Philip; Pool, Mark; Liptay, Michael J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
   [Moiseenko, Fedor; Zaytseva, Irina] St Petersburg Acad Univ, St Petersburg 199034, Russia.
   [Dienemann, Hendrik; Meister, Michael; Muley, Thomas R.] Univ Klinikum Heidelberg, Thoraxklin, D-69126 Heidelberg, Germany.
   [Schnabel, Philipp A.] Heidelberg Univ, D-69120 Heidelberg, Germany.
   [Peifer, Martin] Univ Cologne, D-50931 Cologne, Germany.
   [Gomez-Fernandez, Carmen; Herbert, Lynn; Egea, Sophie] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
   [Dhir, Rajiv; Yousem, Samuel A.; Dacic, Sanja; Schneider, Frank; Siegfried, Jill M.] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
   [Peters, Solange; Letovanec, Igor] CHU Vaudois, Lausanne & European Thorac Oncol Platform, CH-1011 Lausanne, Switzerland.
   [Khan, Khurram Z.] Ziauddin Univ Hosp, Karachi 75300, Pakistan.
   [Jensen, Mark A.; Snyder, Eric E.; Srinivasan, Deepak; Kahn, Ari B.; Baboud, Julien; Pot, David A.] SRA Int Inc, Fairfax, VA 22033 USA.
   [Shaw, Kenna R. Mills; Sheth, Margi; Davidsen, Tanja; Demchok, John A.; Yang, Liming; Wang, Zhining; Tarnuzzer, Roy; Zenklusen, Jean Claude] NCI, NIH, Bethesda, MD 20892 USA.
   [Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 University of California System; University of California San Francisco; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Memorial Sloan Kettering Cancer Center; University of Michigan System; University of Michigan; Johns Hopkins University; Baylor College of Medicine; Washington University (WUSTL); Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of North Carolina; University of North Carolina Chapel Hill; University of Texas System; UTMD Anderson Cancer Center; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; British Columbia Cancer Agency; Mayo Clinic; University of Southern California; University of California System; University of California Santa Cruz; Massachusetts Institute of Technology (MIT); University of Kentucky; Buck Institute for Research on Aging; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; Oregon Health & Science University; International Genomics Consortium; University of Alabama System; University of Alabama Birmingham; Cleveland Clinic Foundation; Christiana Care Health System; Emory University; Fox Chase Cancer Center; Indiana University System; Indiana University Bloomington; Prince Charles Hospital; University of Queensland; Lahey Hospital & Medical Center; NYU Langone Medical Center; University of Toronto; Ontario Institute for Cancer Research; Rush University; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; St Petersburg Academic University; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; University of Cologne; University of Miami; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Ziauddin University; SRA International; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Meyerson, M (corresponding author), Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
EM matthew_meyerson@dfci.harvard.edu
FU NIH [U24 CA126561, U24 CA126551, U24 CA126554, U24 CA126543, U24 CA126546, U24 CA137153, U24 CA126563, U24 CA126544, U24 CA143845, U24 CA143858, U24 CA144025, U24 CA143882, U24 CA143866]; The NIH [U24 CA143867, U24 CA143848, U24 CA143840, U24 CA143835, U24 CA143799, U24 CA143883, U24 CA143843, U54 HG003067, U54 HG003079, U54 HG003273]; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [1054631] Funding Source: National Science Foundation
NR 42
TC 2551
Z9 2609
U1 5
U2 361
PU NATURE PUBLISHING 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 30
PY 2014
VL 511
IS 7511
BP 543
EP 550
DI 10.1038/nature13385
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300025
DA 2026-03-09
ER

PT J
AU Ehn, M
   Thornton, JA
   Kleist, E
   Sipilä, M
   Junninen, H
   Pullinen, I
   Springer, M
   Rubach, F
   Tillmann, R
   Lee, B
   Lopez-Hilfiker, F
   Andres, S
   Acir, IH
   Rissanen, M
   Jokinen, T
   Schobesberger, S
   Kangasluoma, J
   Kontkanen, J
   Nieminen, T
   Kurtén, T
   Nielsen, LB
   Jorgensen, S
   Kjaergaard, HG
   Canagaratna, M
   Dal Maso, M
   Berndt, T
   Petäjä, T
   Wahner, A
   Kerminen, VM
   Kulmala, M
   Worsnop, DR
   Wildt, J
   Mentel, TF
AF Ehn, Mikael
   Thornton, Joel A.
   Kleist, Einhard
   Sipila, Mikko
   Junninen, Heikki
   Pullinen, Iida
   Springer, Monika
   Rubach, Florian
   Tillmann, Ralf
   Lee, Ben
   Lopez-Hilfiker, Felipe
   Andres, Stefanie
   Acir, Ismail-Hakki
   Rissanen, Matti
   Jokinen, Tuija
   Schobesberger, Siegfried
   Kangasluoma, Juha
   Kontkanen, Jenni
   Nieminen, Tuomo
   Kurten, Theo
   Nielsen, Lasse B.
   Jorgensen, Solvejg
   Kjaergaard, Henrik G.
   Canagaratna, Manjula
   Dal Maso, Miikka
   Berndt, Torsten
   Petaja, Tuukka
   Wahner, Andreas
   Kerminen, Veli-Matti
   Kulmala, Markku
   Worsnop, Douglas R.
   Wildt, Juergen
   Mentel, Thomas F.
TI A large source of low-volatility secondary organic aerosol
SO NATURE
LA English
DT Article
ID master chemical mechanism; mass-spectrometer; sulfuric-acid; high-resolution; alpha-pinene; atmospheric chemistry; phase; gas; size; oxidation
AB Forests emit large quantities of volatile organic compounds (VOCs) to the atmosphere. Their condensable oxidation products can form secondary organic aerosol, a significant and ubiquitous component of atmospheric aerosol(1,2), which is known to affect the Earth's radiation balance by scattering solar radiation and by acting as cloud condensation nuclei(3). The quantitative assessment of such climate effects remains hampered by a number of factors, including an incomplete understanding of how biogenic VOCs contribute to the formation of atmospheric secondary organic aerosol. The growth of newly formed particles from sizes of less than three nanometres up to the sizes of cloud condensation nuclei (about one hundred nanometres) in many continental ecosystems requires abundant, essentially nonvolatile organic vapours(4-6), but the sources and compositions of such vapours remain unknown. Here we investigate the oxidation of VOCs, in particular the terpene alpha-pinene, under atmospherically relevant conditions in chamber experiments. We find that a direct pathway leads from several biogenic VOCs, such as monoterpenes, to the formation of large amounts of extremely low-volatility vapours. These vapours format significant mass yield in the gas phase and condense irreversibly onto aerosol surfaces to produce secondary organic aerosol, helping to explain the discrepancy between the observed atmospheric burden of secondary organic aerosol and that reported by many model studies(2). We further demonstrate how these low-volatility vapours can enhance, or even dominate, the formation and growth of aerosol particles over forested regions, providing a missing link between biogenic VOCs and their conversion to aerosol particles. Our findings could help to improve assessments of biosphere-aerosol-climate feedback mechanisms(6-8), and the air quality and climate effects of biogenic emissions generally.
C1 [Ehn, Mikael; Pullinen, Iida; Springer, Monika; Rubach, Florian; Tillmann, Ralf; Andres, Stefanie; Acir, Ismail-Hakki; Wahner, Andreas; Mentel, Thomas F.] Forschungszentrum Julich, Inst Energy & Climate Res IEK 8, D-52425 Julich, Germany.
   [Ehn, Mikael; Thornton, Joel A.; Sipila, Mikko; Junninen, Heikki; Rissanen, Matti; Jokinen, Tuija; Schobesberger, Siegfried; Kangasluoma, Juha; Kontkanen, Jenni; Nieminen, Tuomo; Petaja, Tuukka; Kerminen, Veli-Matti; Kulmala, Markku; Worsnop, Douglas R.] Univ Helsinki, Dept Phys, FIN-00014 Helsinki, Finland.
   [Thornton, Joel A.; Lee, Ben; Lopez-Hilfiker, Felipe] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Kleist, Einhard; Wildt, Juergen] Forschungszentrum Julich, Inst Bio & Geosci IBG 2, D-52425 Julich, Germany.
   [Jokinen, Tuija; Berndt, Torsten] Inst Tropospher Res TROPOS, D-04318 Leipzig, Germany.
   [Nieminen, Tuomo] Univ Helsinki, Helsinki Inst Phys, FIN-00014 Helsinki, Finland.
   [Kurten, Theo] Univ Helsinki, Dept Chem, FIN-00014 Helsinki, Finland.
   [Nielsen, Lasse B.; Jorgensen, Solvejg; Kjaergaard, Henrik G.] Univ Copenhagen, Dept Chem, DK-2100 Copenhagen O, Denmark.
   [Canagaratna, Manjula; Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Dal Maso, Miikka] Tampere Univ Technol, Dept Phys, FIN-33101 Tampere, Finland.
C3 Helmholtz Association; Julich Research Centre; University of Helsinki; University of Washington; University of Washington Seattle; Helmholtz Association; Julich Research Centre; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); Helsinki Institute of Physics; University of Helsinki; University of Helsinki; University of Copenhagen; Aerodyne Research; Tampere University
RP Ehn, M (corresponding author), Forschungszentrum Julich, Inst Energy & Climate Res IEK 8, D-52425 Julich, Germany.
EM mikael.ehn@helsinki.fi
FU Emil Aaltonen foundation; US Department of Energy, Office of Science [DE-SC0006867]; ERC Advanced Grant EU-FP7-ATMNUCLE [227463]; EU-FP7 project PEGASOS [265148]; Academy of Finland [251427, 266388]; Academy of Finland Center of Excellence programme [1118615]; Academy of Finland (AKA) [266388] Funding Source: Academy of Finland (AKA); U.S. Department of Energy (DOE) [DE-SC0006867] Funding Source: U.S. Department of Energy (DOE)
NR 76
TC 1434
Z9 1646
U1 34
U2 1834
PU NATURE PUBLISHING 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 27
PY 2014
VL 506
IS 7489
BP 476
EP +
DI 10.1038/nature13032
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100035
PM 24572423
DA 2026-03-09
ER

PT J
AU Findlay, GM
   Boyle, EA
   Hause, RJ
   Klein, JC
   Shendure, J
AF Findlay, Gregory M.
   Boyle, Evan A.
   Hause, Ronald J.
   Klein, Jason C.
   Shendure, Jay
TI Saturation editing of genomic regions by multiplex homology-directed repair
SO NATURE
LA English
DT Article
ID genetic screens
AB Saturation mutagenesis(1,2)-coupled to an appropriate biological assay-represents a fundamental means of achieving a high-resolution understanding of regulatory(3) and protein-coding(4) nucleic acid sequences of interest. However, mutagenized sequences introduced in trans on episomes or via random or "safe-harbour'' integration fail to capture the native context of the endogenous chromosomal locus(5). This shortcoming markedly limits the interpretability of the resulting measurements of mutational impact. Here, we couple CRISPR/Cas9 RNA-guided cleavage(6) with multiplex homology-directed repair using a complex library of donor templates to demonstrate saturation editing of genomic regions. In exon 18 of BRCA1, we replace a six-base-pair (bp) genomic region with all possible hexamers, or the full exon with all possible single nucleotide variants (SNVs), and measure strong effects on transcript abundance attributable to nonsense-mediated decay and exonic splicing elements. We similarly perform saturation genome editing of a well-conserved coding region of an essential gene, DBR1, and measure relative effects on growth that correlate with functional impact. Measurement of the functional consequences of large numbers of mutations with saturation genome editing will potentially facilitate high-resolution functional dissection of both cis-regulatory elements and trans-acting factors, as well as the interpretation of variants of uncertain significance observed in clinical sequencing.
C1 [Findlay, Gregory M.; Boyle, Evan A.; Hause, Ronald J.; Klein, Jason C.; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Shendure, J (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM gf2@uw.edu; shendure@uw.edu
FU National Institutes of Health [DP1HG007811]; UW Medical Scientist Training Program; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER
NR 35
TC 269
Z9 384
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 SEP 4
PY 2014
VL 513
IS 7516
BP 120
EP +
DI 10.1038/nature13695
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800042
PM 25141179
DA 2026-03-09
ER

PT J
AU Casares, J
   Negueruela, I
   Ribó, M
   Ribas, I
   Paredes, JM
   Herrero, A
   Simón-Díaz, S
AF Casares, J.
   Negueruela, I.
   Ribo, M.
   Ribas, I.
   Paredes, J. M.
   Herrero, A.
   Simon-Diaz, S.
TI A Be-type star with a black-hole companion
SO NATURE
LA English
DT Article
ID x-ray binary; massive stars; neutron-star; cygnus x-1; evolution; parameters; spectra; models; masses; galaxy
AB Stellar-mass black holes have all been discovered through X-ray emission, which arises from the accretion of gas from their binary companions (this gas is either stripped from low-mass stars or supplied as winds from massive ones). Binary evolution models also predict the existence of black holes accreting from the equatorial envelope of rapidly spinning Be-type stars(1-3) (stars of the Be type are hot blue irregular variables showing characteristic spectral emission lines of hydrogen). Of the approximately 80 Be X-ray binaries known in the Galaxy, however, only pulsating neutron stars have been found as companions(2-4). A black hole was formally allowed as a solution for the companion to the Be star MWC656 (ref. 5; also known as HD 215227), although that conclusion was based on a single radial velocity curve of the Be star, a mistaken spectral classification(6) and rough estimates of the inclination angle. Here we report observations of an accretion disk line mirroring the orbit of MWC656. This, together with an improved radial velocity curve of the Be star through fitting sharp Fe II profiles from the equatorial disk, and a refined Be classification (to that of a B1.5-B2 III star), indicates that a black hole of 3.8 to 6.9 solar masses orbits MWC656, the candidate counterpart of the gamma-ray source AGL J2241+4454 (refs 5, 6). The black hole is X-ray quiescent and fed by a radiatively inefficient accretion flow giving a luminosity less than 1.6x10(-7) times the Eddington luminosity. This implies that Be binaries with black-hole companions are difficult to detect in conventional X-ray surveys.
C1 [Casares, J.; Herrero, A.; Simon-Diaz, S.] Inst Astrofis Canarias, E-28205 San Cristobal la Laguna, Santa Cruz De T, Spain.
   [Casares, J.; Herrero, A.; Simon-Diaz, S.] Univ La Laguna, Dept Astrofis, E-38206 San Cristobal la Laguna, Santa Cruz De T, Spain.
   [Negueruela, I.] Univ Alicante, Dept Fis Ingn Sistemas & Teoria Senal, E-03080 Alicante, Spain.
   [Ribo, M.; Paredes, J. M.] Univ Barcelona, Inst Ciencies Cosmos, Dept Astron & Meteorol, IEEC UB, E-08028 Barcelona, Spain.
   [Ribas, I.] IEEC CSIC, Fac Ciencies, Inst Ciencies Espai, E-08193 Bellaterra, Spain.
C3 Instituto de Astrofisica de Canarias; Universidad de la Laguna; Universitat d'Alacant; Institut d'Estudis Espacials de Catalunya (IEEC); University of Barcelona; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE)
RP Casares, J (corresponding author), Inst Astrofis Canarias, E-28205 San Cristobal la Laguna, Santa Cruz De T, Spain.
EM jorge.casares@iac.es
FU UK Science and Technology Facilities Council; Spanish MINECO; FEDER [AYA2010-18080, AYA2010-21782-C03-01, AYA2010-21967-C05-04/05, AYA2012-39364-C02-01/02, AYA2012-39612-C03-01, FPA2010-22056-C06-02, SEV2011-0187-01]; Gobierno de Canarias [PID 2010119]; ICREA Academia; Science and Technology Facilities Council [ST/M003035/1, ST/M000095/1, ST/G009465/1] Funding Source: researchfish; STFC [ST/M000095/1, ST/G009465/1, ST/M003035/1] Funding Source: UKRI
NR 54
TC 162
Z9 186
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 JAN 16
PY 2014
VL 505
IS 7483
BP 378
EP +
DI 10.1038/nature12916
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800037
PM 24429635
DA 2026-03-09
ER

PT J
AU Matsuo, Y
   Granneman, S
   Thoms, M
   Manikas, RG
   Tollervey, D
   Hurt, E
AF Matsuo, Yoshitaka
   Granneman, Sander
   Thoms, Matthias
   Manikas, Rizos-Georgios
   Tollervey, David
   Hurt, Ed
TI Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export
SO NATURE
LA English
DT Article
ID nuclear export; saccharomyces-cerevisiae; biogenesis factors; adapter protein; rna-binding; maturation; subunit; association; complex; kinase
AB Eukaryotic ribosomes are assembled by a complex pathway that extends from the nucleolus to the cytoplasm and is powered by many energy-consuming enzymes(1-3). Nuclear export is a key, irreversible step in pre-ribosome maturation(4-8), but mechanisms underlying the timely acquisition of export competence remain poorly understood. Here we show that a conserved Saccharomyces cerevisiae GTPase Nug2 (also known as Nog2, and as NGP-1, GNL2 or nucleostemin 2 in human(9)) has a key role in the timing of export competence. Nug2 binds the inter-subunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3, a key pre-60S export adaptor(10). Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G-domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodelling factors, the Rea1 ATPase and its co-substrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with nug2 mutants. Release of Nug2 from pre-60S particles requires both its K+-dependent GTPase activity and the remodelling ATPase activity of Rea1. We conclude that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery.
C1 [Matsuo, Yoshitaka; Thoms, Matthias; Manikas, Rizos-Georgios; Hurt, Ed] Heidelberg Univ, Zentrum Biochem, D-69120 Heidelberg, Germany.
   [Granneman, Sander; Tollervey, David] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
   [Granneman, Sander] Univ Edinburgh, Ctr Synthet & Syst Biol, Edinburgh EH9 3JD, Midlothian, Scotland.
C3 Ruprecht Karls University Heidelberg; University of Edinburgh; University of Edinburgh
RP Hurt, E (corresponding author), Heidelberg Univ, Zentrum Biochem, Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
EM ed.hurt@bzh.uni.heidelberg.de
FU Alexander von Humboldt Foundation; Wellcome Trust [077248]; Deutsche Forschungsgemeinschaft [DFG Hu363/10-4]
NR 47
TC 116
Z9 125
U1 0
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 JAN 2
PY 2014
VL 505
IS 7481
BP 112
EP +
DI 10.1038/nature12731
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300034
PM 24240281
DA 2026-03-09
ER

PT J
AU Smith, MR
   Ortega-Hernández, J
AF Smith, Martin R.
   Ortega-Hernandez, Javier
TI Hallucigenia's onychophoran-like claws and the case for Tactopoda
SO NATURE
LA English
DT Article
ID cambrian lobopodians; burgess shale; tardigrades; phylogeny; insights; organization; musculature; morphology; micrornas; evolution
AB The Palaeozoic form-taxon Lobopodia encompasses a diverse range of soft-bodied 'legged worms' known from exceptional fossil deposits1-. Although lobopodians occupy a deep phylogenetic position within Panarthropoda, a shortage of derived characters obscures their evolutionary relationships with extant phyla (Onychophora, Tardigrada and Euarthropoda)(2,3,5,10-15). Here we describe a complex feature in the terminal claws of the mid-Cambrian lobopodian Hallucigenia sparsa-their construction from a stack of constituent elements-and demonstrate that equivalent elements make up the jaws and claws of extant Onychophora. A cladistic analysis, informed by developmental data on panarthropod head segmentation, indicates that the stacked sclerite components in these two taxa are homologous-resolving hallucigeniid lobopodians as stem-group onychophorans. The results indicate a sister-group relationship between Tardigrada and Euarthropoda, adding palaeontological support to the neurological(16,17) and musculoskeletal(18,19) evidence uniting these disparate clades. These findings elucidate the evolutionary transformations that gave rise to the panarthropod phyla, and expound the lobopodian-like morphology of the ancestral panarthropod.
C1 [Smith, Martin R.; Ortega-Hernandez, Javier] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
C3 University of Cambridge
RP Smith, MR (corresponding author), Univ Cambridge, Dept Earth Sci, Downing Site, Cambridge CB2 3EQ, England.
EM ms609@cam.ac.uk
FU Research Fellowships at Clare College; Emmanuel College, University of Cambridge, UK; H.B. Whittington Research Grant (Paleontological Society); Willi Hennig Society
NR 39
TC 108
Z9 118
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 OCT 16
PY 2014
VL 514
IS 7522
BP 363
EP +
DI 10.1038/nature13576
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600051
PM 25132546
DA 2026-03-09
ER

PT J
AU Miller, SB
   Yildiz, FZ
   Lo, JA
   Wang, B
   D'Souza, VM
AF Miller, Sarah B.
   Yildiz, F. Zehra
   Lo, Jennifer A.
   Wang, Bo
   D'Souza, Victoria M.
TI A structure-based mechanism for tRNA and retroviral RNA remodelling during primer annealing
SO NATURE
LA English
DT Article
ID murine leukemia-virus; hiv-1 nucleocapsid protein; acid-chaperone activity; nucleotide-sequence; dna-synthesis; nmr structure; initiation; identification; transitions; trna(lys,3)
AB To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome(1,2). The residues essential for primer annealing are initially locked in intramolecular interactions(3-5); hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements(6). Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and tRNA(Pro) primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues-which are exactly complementary-for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNAPro reveal the structure-based mechanism for retroviral primer annealing and provide in sights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs. [GRAPHICS] .
C1 [Miller, Sarah B.; Yildiz, F. Zehra; Lo, Jennifer A.; Wang, Bo; D'Souza, Victoria M.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University
RP D'Souza, VM (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM dsouza@mcb.harvard.edu
FU Merck; Damon Runyon Cancer; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 38
TC 29
Z9 39
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 27
PY 2014
VL 515
IS 7528
BP 591
EP +
DI 10.1038/nature13709
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600004
PM 25209668
DA 2026-03-09
ER

PT J
AU Powles, T
   Eder, JP
   Fine, GD
   Braiteh, FS
   Loriot, Y
   Cruz, C
   Bellmunt, J
   Burris, HA
   Petrylak, DP
   Teng, SL
   Shen, XD
   Boyd, Z
   Hegde, PS
   Chen, DS
   Vogelzang, NJ
AF Powles, Thomas
   Eder, Joseph Paul
   Fine, Gregg D.
   Braiteh, Fadi S.
   Loriot, Yohann
   Cruz, Cristina
   Bellmunt, Joaquim
   Burris, Howard A.
   Petrylak, Daniel P.
   Teng, Siew-Leng
   Shen, Xiaodong
   Boyd, Zachary
   Hegde, Priti S.
   Chen, Daniel S.
   Vogelzang, Nicholas J.
TI MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
SO NATURE
LA English
DT Article
ID transitional-cell carcinoma; advanced urothelial carcinoma; phase-ii; 2nd-line treatment; single group; vinflunine; trial; paclitaxel; cloning; plus
AB There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years. Chemotherapy is still the standard of care. Patient outcomes, especially for those in whom chemotherapy is not effective or is poorly tolerated, remain poor(1,2). One hallmark of UBC is the presence of high rates of somatic mutations(3,5). These alterations may enhance the ability of the host immune system to recognize tumour cells as foreign owing to an increased number of antigens(6). However, these cancers may also elude immune surveillance and eradication through the expression of programmed death-ligand 1 (PD-Li; also called CD274 or B7-H1) in the tumour microenvironment(7,8). Therefore, we examined the anti-PDLi antibody MPDL3280A, a systemic cancer immunotherapy, for the treatment of metastatic UBC. MPDL3280A is a high-affinity engineered human anti-PD-L1 monoclonal immunoglobulin-Gl antibody that inhibits the interaction of PD-L1 with PD-1 (PDCD1) and B7.1 (CD80)9. Because PD-L1 is expressed on activated T cells, MPDL3280A was engineered with a modification in the Fc domain that eliminates antibody-dependent cellular cytotoxicity at clinically relevant doses to prevent the depletion of T cells expressing PD-Li. Here we show that MPDL3280A has noteworthy activity in metastatic UBC. Responses were often rapid, with many occurring at the time of the first response assessment (6 weeks) and nearly all were ongoing at the data cutoff. This phase I expansion study, with an adaptive design that allowed for biomarker-positive enriched cohorts, demonstrated that tumours expressing PD-L1 -positive tumour-infiltrating immune cells had particularly high response rates. Moreover, owing to the favourable toxicity profile, including a lack of renal toxicity, patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy. These results suggest that MPDL3280A may have an important role in treating UBC-the drug received breakthrough designation status by the US Food and Drug Administration (FDA) in June 2014.
C1 [Powles, Thomas] Queen Mary Univ London, Barts Canc Inst, Barts Expt Canc Med Ctr, London EC1M 6BQ, England.
   [Eder, Joseph Paul; Petrylak, Daniel P.] Yale Canc Ctr, New Haven, CT 06520 USA.
   [Fine, Gregg D.; Teng, Siew-Leng; Shen, Xiaodong; Boyd, Zachary; Hegde, Priti S.; Chen, Daniel S.] Genentech Inc, San Francisco, CA 94080 USA.
   [Braiteh, Fadi S.] Comprehens Canc Ctr Nevada, Las Vegas, NV 89169 USA.
   [Loriot, Yohann] Gustave Roussy, F-94805 Villejuif, France.
   [Cruz, Cristina] VHIO, Barcelona 08035, Spain.
   [Cruz, Cristina] Vall dHebron Univ Hosp, Barcelona 08035, Spain.
   [Bellmunt, Joaquim] Harvard Univ, Sch Med, Bladder Canc Ctr, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA.
   [Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN 37203 USA.
   [Vogelzang, Nicholas J.] Univ Nevada, Sch Med, Las Vegas, NV 89169 USA.
   [Vogelzang, Nicholas J.] Univ Nevada, US Oncol Comprehens Canc Ctr Nevada, Las Vegas, NV 89169 USA.
C3 University of London; Queen Mary University London; Yale University; Yale New Haven Hospital; Roche Holding; Genentech; Roche Holding USA; Comprehensive Cancer Centers of Nevada; UNICANCER; Gustave Roussy; Vall d'Hebron Institut d'Oncologia (VHIO); Hospital Universitari Vall d'Hebron; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Sarah Cannon Research Institute; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; Comprehensive Cancer Centers of Nevada; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas
RP Powles, T (corresponding author), Queen Mary Univ London, Barts Canc Inst, Barts Expt Canc Med Ctr, London EC1M 6BQ, England.
EM Thomas.Powles@bartshealth.nhs.uk
NR 27
TC 2001
Z9 2310
U1 0
U2 354
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 558
EP +
DI 10.1038/nature13904
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600052
PM 25428503
DA 2026-03-09
ER

PT J
AU Mooser, A
   Ulmer, S
   Blaum, K
   Franke, K
   Kracke, H
   Leiteritz, C
   Quint, W
   Rodegheri, CC
   Smorra, C
   Walz, J
AF Mooser, A.
   Ulmer, S.
   Blaum, K.
   Franke, K.
   Kracke, H.
   Leiteritz, C.
   Quint, W.
   Rodegheri, C. C.
   Smorra, C.
   Walz, J.
TI Direct high-precision measurement of the magnetic moment of the proton
SO NATURE
LA English
DT Article
ID penning trap technique; electron; mass; cpt; ion
AB One of the fundamental properties of the proton is its magnetic moment, mu(p). So far mu(p) has been measured only indirectly, by analysing the spectrum of an atomic hydrogen maser in a magnetic field(1). Here we report the direct high-precision measurement of the magnetic moment of a single proton using the double Penning-trap technique(2). We drive proton-spin quantum jumps by a magnetic radio-frequency field in a Penning trap with a homogeneous magnetic field. The induced spin transitions are detected in a second trap with a strong superimposed magnetic inhomogeneity(3). This enables the measurement of the spin-flip probability as a function of the drive frequency. In each measurement the proton's cyclotron frequency is used to determine the magnetic field of the trap. From the normalized resonance curve, we extract the particle's magnetic moment in terms of the nuclear magneton: mu(p) = 2.792847350(9)mu(N). This measurement outperforms previous Penning-trap measurements(4,5) in terms of precision by a factor of about 760. It improves the precision of the forty-year-old indirect measurement, in which significant theoretical bound state corrections(6) were required to obtain mu(p), by a factor of 3. By application of this method to the antiproton magnetic moment, the fractional precision of the recently reported value(7) can be improved by a factor of at least 1,000. Combined with the present result, this will provide a stringent test of matter/antimatter symmetry with baryons(8).
C1 [Mooser, A.; Kracke, H.; Leiteritz, C.; Rodegheri, C. C.; Walz, J.] Johannes Gutenberg Univ Mainz, Inst Phys, D-55099 Mainz, Germany.
   [Mooser, A.; Kracke, H.; Walz, J.] Helmholtz Inst Mainz, D-55099 Mainz, Germany.
   [Ulmer, S.; Franke, K.; Smorra, C.] RIKEN, Ulmer Initiat Res Unit, Wako, Saitama 3510198, Japan.
   [Blaum, K.; Franke, K.; Rodegheri, C. C.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Quint, W.] Heidelberg Univ, Fak Phys & Astron, D-69047 Heidelberg, Germany.
   [Quint, W.] GSI Helmholtzzentrum Schwerionenforsch, D-64291 Darmstadt, Germany.
C3 Johannes Gutenberg University of Mainz; RIKEN; Max Planck Society; Ruprecht Karls University Heidelberg; University of Wurzburg; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research
RP Mooser, A (corresponding author), RIKEN, Ulmer Initiat Res Unit, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM mooser@uni-mainz.de
FU BMBF; EU (ERC) [290870-MEFUCO]; Helmholtz-Gemeinschaft; HGS-HIRE; Max-Planck Society; IMPRS-PTFS; RIKEN Initiative Research Unit Program; Grants-in-Aid for Scientific Research [24000008] Funding Source: KAKEN
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NR 30
TC 80
Z9 91
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 MAY 29
PY 2014
VL 509
IS 7502
BP 596
EP 599
DI 10.1038/nature13388
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100044
PM 24870545
DA 2026-03-09
ER

PT J
AU Barry, JF
   McCarron, DJ
   Norrgard, EB
   Steinecker, MH
   DeMille, D
AF Barry, J. F.
   McCarron, D. J.
   Norrgard, E. B.
   Steinecker, M. H.
   DeMille, D.
TI Magneto-optical trapping of a diatomic molecule
SO NATURE
LA English
DT Article
ID atoms; beam; cold; gas
AB Laser cooling and trapping are central to modern atomic physics. The most used technique in cold-atomphysics is the magneto-optical trap (MOT), which combines laser cooling with a restoring force from radiation pressure. For a variety of atomic species, MOTs can capture and cool large numbers of particles to ultracold temperatures (less than similar to 1 millikelvin); this has enabled advances in areas that range fromoptical clocks to the study of ultracold collisions, while also serving as the ubiquitous starting point for further cooling into the regime of quantum degeneracy. Magneto-optical trapping of molecules could provide a similarly powerful starting point for the study and manipulation of ultracold molecular gases. The additional degrees of freedom associated with the vibration and rotation of molecules, particularly their permanent electric dipole moments, allow a broad array of applications not possible with ultracold atoms(1). Spurred by these ideas, a variety of methods has been developed to create ultracold molecules. Temperatures below 1 microkelvin have been demonstrated for diatomic molecules assembled from pre-cooled alkali atoms(2,3), but for the wider range of species amenable to direct cooling and trapping, only recently have temperatures below 100 millikelvin been achieved(4,5). The complex internal structure of molecules complicates magneto-optical trapping. However, ideas and methods necessary for creating a molecular MOT have been developed(6-11) recently. Here we demonstrate three dimensional magneto-optical trapping of a diatomic molecule, strontium monofluoride (SrF), at a temperature of approximately 2.5 millikelvin, the lowest yet achieved by direct cooling of a molecule. This method is a straightforward extension of atomic techniques and is expected to be viable for a significant number of diatomic species(6,7). With further development, we anticipate that this techniquemay be employed in any number of existing and proposed molecular experiments, in applications ranging from precision measurement(12) to quantum simulation(13) and quantum information(14) to ultracold chemistry(15).
C1 [Barry, J. F.; McCarron, D. J.; Norrgard, E. B.; Steinecker, M. H.; DeMille, D.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
C3 Yale University
RP McCarron, DJ (corresponding author), Yale Univ, Dept Phys, POB 208120, New Haven, CT 06520 USA.
EM daniel.mccarron@yale.edu
FU AFOSR (MURI); ARO; ARO (MURI); NSF GRFP
NR 37
TC 425
Z9 516
U1 0
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 AUG 21
PY 2014
VL 512
IS 7514
BP 286
EP +
DI 10.1038/nature13634
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200029
PM 25143111
DA 2026-03-09
ER

PT J
AU Cooper, KM
   Kent, AJR
AF Cooper, Kari M.
   Kent, Adam J. R.
TI Rapid remobilization of magmatic crystals kept in cold storage
SO NATURE
LA English
DT Article
ID u-series disequilibria; mount st-helens; residence times; size distribution; uranium-series; peralkaline rhyolites; lesser antilles; volcanic zone; plagioclase; crystallization
AB The processes involved in the formation and storage of magma within the Earth's upper crust are of fundamental importance to volcanology. Many volcanic eruptions, including some of the largest, result from the eruption of components stored for tens to hundreds of thousands of years before eruption(1-3). Although the physical conditions of magma storage and remobilization are of paramount importance for understanding volcanic processes, they remain relatively poorly known(4,5). Eruptions of crystal-rich magma are often suggested to require the mobilization of magma stored at near-solidus conditions(6-8); however, accumulation of significant eruptible magma volumes has also been argued to require extended storage of magma at higher temperatures(7-9). What has been lacking in this debate is clear observational evidence linking the thermal (and therefore physical) conditions within a magma reservoir to timescales of storage-that is, thermal histories. Here we present a method of constraining such thermal histories by combining timescales derived from uranium-series disequilibria, crystal sizes and trace-element zoning in crystals. At Mount Hood (Oregon, USA), only a small fraction of the total magma storage duration (at most 12 per cent and probably much less than 1 per cent) has been spent at temperatures above the critical crystallinity (40-50 per cent) at which magma is easily mobilized. Partial data sets for other volcanoes also suggest that similar conditions of magma storage are widespread and therefore that rapid mobilization of magmas stored at near-solidus temperatures is common. Magma storage at low temperatures indicates that, although thermobarometry calculations based on mineral compositions may record the conditions of crystallization, they are unlikely to reflect the conditions of most of the time that the magma is stored. Our results also suggest that largely liquid magma bodies that can be imaged geophysically will be ephemeral features and therefore their detection could indicate imminent eruption.
C1 [Cooper, Kari M.] Univ Calif Davis, Dept Earth & Planetary Sci, Davis, CA 95616 USA.
   [Kent, Adam J. R.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Ocean Adm 104, Corvallis, OR 97331 USA.
C3 University of California System; University of California Davis; Oregon State University
RP Cooper, KM (corresponding author), Univ Calif Davis, Dept Earth & Planetary Sci, One Shields Ave, Davis, CA 95616 USA.
EM kmcooper@ucdavis.edu
FU US NSF [EAR-0838389, EAR-0838421]
NR 84
TC 441
Z9 522
U1 3
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 27
PY 2014
VL 506
IS 7489
BP 480
EP +
DI 10.1038/nature12991
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100036
PM 24531766
DA 2026-03-09
ER

PT J
AU Sinha, A
   Hughes, KR
   Modrzynska, KK
   Otto, TD
   Pfander, C
   Dickens, NJ
   Religa, AA
   Bushell, E
   Graham, AL
   Cameron, R
   Kafsack, BFC
   Williams, AE
   Llinás, M
   Berriman, M
   Billker, O
   Waters, AP
AF Sinha, Abhinav
   Hughes, Katie R.
   Modrzynska, Katarzyna K.
   Otto, Thomas D.
   Pfander, Claudia
   Dickens, Nicholas J.
   Religa, Agnieszka A.
   Bushell, Ellen
   Graham, Anne L.
   Cameron, Rachael
   Kafsack, Bjorn F. C.
   Williams, April E.
   Llinas, Manuel
   Berriman, Matthew
   Billker, Oliver
   Waters, Andrew P.
TI A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium
SO NATURE
LA English
DT Article
ID malaria parasite; transcription-factor; berghei; microarrays; generation; falciparum; selection; sequence; toolkit; genes
AB Commitment to and completion of sexual development are essential for malaria parasites (protists of the genus Plasmodium) to be transmitted through mosquitoes(1). The molecular mechanism(s) responsible for commitment have been hitherto unknown. Here we show that PbAP2-G, a conserved member of the apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, is essential for the commitment of asexually replicating forms to sexual development in Plasmodium berghei, a malaria parasite of rodents. PbAP2-G was identified from mutations in its encoding gene, PBANKA_143750, which account for the loss of sexual development frequently observed in parasites transmitted artificially by blood passage. Systematic gene deletion of conserved ApiAP2 genes in Plasmodium confirmed the role of PbAP2-G and revealed a second ApiAP2 member (PBANKA_103430, here termed PbAP2-G2) that significantly modulates but does not abolish gametocytogenesis, indicating that a cascade of ApiAP2 proteins are involved in commitment to the production and maturation of gametocytes. The data suggest a mechanism of commitment to gametocytogenesis in Plasmodium consistent with a positive feedback loop involving PbAP2-G that could be exploited to prevent the transmission of this pernicious parasite.
C1 [Sinha, Abhinav; Hughes, Katie R.; Dickens, Nicholas J.; Religa, Agnieszka A.; Graham, Anne L.; Cameron, Rachael; Waters, Andrew P.] Univ Glasgow, Wellcome Trust Ctr Mol Parasitol, Glasgow G12 8QQ, Lanark, Scotland.
   [Modrzynska, Katarzyna K.; Otto, Thomas D.; Pfander, Claudia; Bushell, Ellen; Berriman, Matthew; Billker, Oliver] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Kafsack, Bjorn F. C.; Williams, April E.; Llinas, Manuel] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Williams, April E.; Llinas, Manuel] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
C3 University of Glasgow; Wellcome Trust Sanger Institute; Princeton University; Princeton University
RP Billker, O (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM OB4@sanger.ac.uk; Andy.Waters@glasgow.ac.uk
FU Wellcome Trust [083811/Z/07/Z, 085349, 098051]; Evimalar [242095]; Medical Research Council [G0501670]; National Institutes of Health [R01 AI076276]; Centre for Quantitative Biology [P50GM071508]; Howard Hughes Medical Institute fellowship of the Damon Runyon Cancer Research Foundation; National Institute of General Medical Sciences [T32GM007388] Funding Source: NIH RePORTER; MRC [G0501670] Funding Source: UKRI; Medical Research Council [G0501670] Funding Source: researchfish; Wellcome Trust [083811/Z/07/Z] Funding Source: Wellcome Trust
NR 44
TC 319
Z9 380
U1 0
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 MAR 13
PY 2014
VL 507
IS 7491
BP 253
EP +
DI 10.1038/nature12970
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800043
PM 24572359
DA 2026-03-09
ER

PT J
AU Li, XC
   Holland, DM
   Gerber, EP
   Yoo, C
AF Li, Xichen
   Holland, David M.
   Gerber, Edwin P.
   Yoo, Changhyun
TI Impacts of the north and tropical Atlantic Ocean on the Antarctic Peninsula and sea ice
SO NATURE
LA English
DT Article
ID southern annular mode; climate; circulation; oscillation; trends; variability; driven; flow
AB In recent decades, Antarctica has experienced pronounced climate changes. The Antarctic Peninsula exhibited the strongest warming(1,2) of any region on the planet, causing rapid changes in land ice(3,4). Additionally, in contrast to the sea-ice decline over the Arctic, Antarctic sea ice has not declined, but has instead undergone a perplexing redistribution(5,6). Antarctic climate is influenced by, among other factors, changes in radiative forcing(7) and remote Pacific climate variability(8,9), but none explains the observed Antarctic Peninsula warming or the sea-ice redistribution in austral winter. However, in the north and tropical Atlantic Ocean, the Atlantic Multidecadal Oscillation(10,11) (a leading mode of sea surface temperature variability) has been overlooked in this context. Here we show that sea surface warming related to the Atlantic Multidecadal Oscillation reduces the surface pressure in the Amundsen Sea and contributes to the observed dipole-like sea-ice redistribution between the Ross and Amundsen-Bellingshausen-Weddell seas and to the Antarctic Peninsula warming. Support for these findings comes from analysis of observational and reanalysis data, and independently from both comprehensive and idealized atmospheric model simulations. We suggest that the north and tropical Atlantic is important for projections of future climate change in Antarctica, and has the potential to affect the global thermohaline circulation(6) and sea-level change(3,12).
C1 [Li, Xichen; Holland, David M.; Gerber, Edwin P.; Yoo, Changhyun] NYU, Courant Inst Math Sci, New York, NY 10012 USA.
C3 New York University
RP Li, XC (corresponding author), NYU, Courant Inst Math Sci, 251 Mercer St, New York, NY 10012 USA.
EM xichen@cims.nyu.edu
FU NSF Office of Polar Programs [ANT-0732869]; NASA Polar Programs [NNX12AB69G]; New York University Abu Dhabi [G1204]; NSF Office of Atmospheric and Geospace Sciences [AGS-1264195]; National Science Foundation (NSF); Office of Science (BER) of the US Department of Energy (DOE); Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1264195] Funding Source: National Science Foundation; NASA [30944, NNX12AB69G] Funding Source: Federal RePORTER
NR 45
TC 266
Z9 289
U1 2
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 JAN 23
PY 2014
VL 505
IS 7484
BP 538
EP +
DI 10.1038/nature12945
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000037
PM 24451542
DA 2026-03-09
ER

PT J
AU Van Nostrand, JL
   Brady, CA
   Jung, HY
   Fuentes, DR
   Kozak, MM
   Johnson, TM
   Lin, CY
   Lin, CJ
   Swiderski, DL
   Vogel, H
   Bernstein, JA
   Attié-Bitach, T
   Chang, CP
   Wysocka, J
   Martin, DM
   Attardi, LD
AF Van Nostrand, Jeanine L.
   Brady, Colleen A.
   Jung, Heiyoun
   Fuentes, Daniel R.
   Kozak, Margaret M.
   Johnson, Thomas M.
   Lin, Chieh-Yu
   Lin, Chien-Jung
   Swiderski, Donald L.
   Vogel, Hannes
   Bernstein, Jonathan A.
   Attie-Bitach, Tania
   Chang, Ching-Pin
   Wysocka, Joanna
   Martin, Donna M.
   Attardi, Laura D.
TI Inappropriate p53 activation during development induces features of CHARGE syndrome
SO NATURE
LA English
DT Article
ID neural crest; embryonic lethality; phenotypic spectrum; tumor suppression; chd7 mutations; mice; gene; inhibition; expression; anomaly
AB CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities(1). Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood(2). Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54))(3), along with a wild-type allele ofp53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wildtype p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regu-lating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.
C1 [Van Nostrand, Jeanine L.; Brady, Colleen A.; Jung, Heiyoun; Kozak, Margaret M.; Johnson, Thomas M.; Attardi, Laura D.] Stanford Univ, Sch Med, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA.
   [Fuentes, Daniel R.; Wysocka, Joanna] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Lin, Chieh-Yu; Vogel, Hannes] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Lin, Chien-Jung; Wysocka, Joanna] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Swiderski, Donald L.] Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI 48109 USA.
   [Bernstein, Jonathan A.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Attie-Bitach, Tania] Hop Necker Enfants Malad, APHP, Dept Genet, F-75015 Paris, France.
   [Attie-Bitach, Tania] Univ Paris Descartes Sorbonne Paris Cite, Inst Imagine, Unite INSERM U1163, F-75015 Paris, France.
   [Chang, Ching-Pin] Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA.
   [Martin, Donna M.] Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI 48109 USA.
   [Martin, Donna M.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Attardi, Laura D.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; University of Michigan System; University of Michigan; Stanford University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Hotel-Dieu - APHP; Hopital Universitaire Necker-Enfants Malades - APHP; Hopital Universitaire Ambroise-Pare - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Indiana University System; Indiana University Bloomington; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Stanford University
RP Attardi, LD (corresponding author), Stanford Univ, Sch Med, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA.
EM attardi@stanford.edu
FU NSF; NCI [1F31CA167917-01]; NIH [RO1 GM095555, R01 HL118087, RO1 HL121197, R01 DC009410, RO1 CA140875]; American Heart Association [12EIA8960018]; March of Dimes Foundation [6-FY11-260]; ACS; LLS; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [R01HL121197] Funding Source: NIH RePORTER; American Heart Association (AHA) [12EIA8960018] Funding Source: American Heart Association (AHA)
NR 35
TC 118
Z9 132
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 OCT 9
PY 2014
VL 514
IS 7521
BP 228
EP +
DI 10.1038/nature13585
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100042
PM 25119037
DA 2026-03-09
ER

PT J
AU Sun, C
   Wang, LQ
   Huang, SD
   Heynen, GJJE
   Prahallad, A
   Robert, C
   Haanen, J
   Blank, C
   Wesseling, J
   Willems, SM
   Zecchin, D
   Hobor, S
   Bajpe, PK
   Lieftink, C
   Mateus, C
   Vagner, S
   Grernrum, W
   Hofland, I
   Schlicker, A
   Wessels, LFA
   Beijersbergen, RL
   Bardelli, A
   Di Nicolantonio, F
   Eggermont, AMM
   Bernards, R
AF Sun, Chong
   Wang, Liqin
   Huang, Sidong
   Heynen, Guus J. J. E.
   Prahallad, Anirudh
   Robert, Caroline
   Haanen, John
   Blank, Christian
   Wesseling, Jelle
   Willems, Stefan M.
   Zecchin, Davide
   Hobor, Sebastijan
   Bajpe, Prashanth K.
   Lieftink, Cor
   Mateus, Christina
   Vagner, Stephan
   Grernrum, Wipawadee
   Hofland, Ingrid
   Schlicker, Andreas
   Wessels, Lodewyk F. A.
   Beijersbergen, Roderick L.
   Bardelli, Alberto
   Di Nicolantonio, Federica
   Eggermont, Alexander M. M.
   Bernards, Rene
TI Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma
SO NATURE
LA English
DT Article
ID growth-factor receptor; improved survival; braf inhibitor; raf inhibition; c-jun; cancer; expression; cells; egfr; differentiation
AB Treatment of BRAF(V600E) mutant melanoma by small molecule drugs that target the BRAF or MEK kinases can be effective, but resistance develops invariably(1,2). In contrast, colon cancers that harbour the same BRAF(V600E) mutation are intrinsically resistant to BRAF inhibitors, due to feedback activation of the epidermal growth factor receptor (EGFR)(3,4). Here we show that 6 out of 16 melanoma tumours analysed acquired EGFR expression after the development of resistance to BRAF or MEK inhibitors. Using a chromatin-regulator-focused short hairpin RNA (shRNA) library, we find that suppression of sex determining region Y-box 10(SOX10) in melanoma causes activation of TGF-beta signalling, thus leading to upregulation of EGFR and platelet-derived growth factor receptor-beta (PDGFRB), which confer resistance to BRAF and MEK inhibitors. Expression of EGFR in melanoma or treatment with TGF-beta results in a slow-growth phenotype with cells displaying hallmarks of oncogene-induced senescence. However, EGFR expression or exposure to TGF-beta becomes beneficial for proliferation in the presence of BRAF or MEK inhibitors. In a heterogeneous population of melanoma cells having varying levels of SOX10 suppression, cells with low SOX10 and consequently high EGFR expression are rapidly enriched in the presence of drug, but this is reversed when the drug treatment is discontinued. We find evidence for SOX10 loss and/or activation of TGF-beta signalling in 4 of the 6 EGFR-positive drug-resistant melanoma patient samples. Our findings provide a rationale for why some BRAF or MEK inhibitor-resistant melanoma patients may regain sensitivity to these drugs after a 'drug holiday' and identify patients with EGFR-positive melanoma as a group that may benefit from re-treatment after a drug holiday.
C1 [Sun, Chong; Wang, Liqin; Huang, Sidong; Heynen, Guus J. J. E.; Prahallad, Anirudh; Willems, Stefan M.; Bajpe, Prashanth K.; Lieftink, Cor; Grernrum, Wipawadee; Schlicker, Andreas; Wessels, Lodewyk F. A.; Beijersbergen, Roderick L.; Bernards, Rene] Netherlands Canc Inst, Canc Syst Biol Ctr, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands.
   [Sun, Chong; Wang, Liqin; Huang, Sidong; Heynen, Guus J. J. E.; Prahallad, Anirudh; Haanen, John; Blank, Christian; Wesseling, Jelle; Willems, Stefan M.; Bajpe, Prashanth K.; Lieftink, Cor; Grernrum, Wipawadee; Hofland, Ingrid; Schlicker, Andreas; Wessels, Lodewyk F. A.; Beijersbergen, Roderick L.; Bernards, Rene] Netherlands Canc Inst, Canc Genom Ctr Netherlands, NL-1066 CX Amsterdam, Netherlands.
   [Huang, Sidong] McGill Univ, Dept Biochem, Rosalind & Morris Goodman Canc Ctr, Montreal, PQ H3G 1Y6, Canada.
   [Robert, Caroline; Mateus, Christina; Vagner, Stephan; Eggermont, Alexander M. M.] Inst Gustave Roussy, F-94800 Villejuif, France.
   [Haanen, John; Blank, Christian] Netherlands Canc Inst, Div Med Oncol, Canc Syst Biol Ctr, NL-1066 CX Amsterdam, Netherlands.
   [Wesseling, Jelle; Hofland, Ingrid] Netherlands Canc Inst, Div Pathol, Canc Syst Biol Ctr, NL-1066 CX Amsterdam, Netherlands.
   [Willems, Stefan M.] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands.
   [Zecchin, Davide; Bardelli, Alberto; Di Nicolantonio, Federica] Univ Turin, Dept Oncol, I-10060 Turin, Italy.
   [Zecchin, Davide; Hobor, Sebastijan; Bardelli, Alberto; Di Nicolantonio, Federica] IRCCS, Candiolo Canc Inst FPO, I-10060 Turin, Italy.
   [Bardelli, Alberto] FIRC Inst Mol Oncol IFOM, I-20139 Milan, Italy.
C3 Netherlands Cancer Institute; Netherlands Cancer Institute; McGill University; UNICANCER; Gustave Roussy; Netherlands Cancer Institute; Netherlands Cancer Institute; Utrecht University; Utrecht University Medical Center; University of Turin; IRCCS Fondazione del Piemonte per l'Oncologia; IFOM - FIRC Institute of Molecular Oncology
RP Bernards, R (corresponding author), Netherlands Canc Inst, Canc Syst Biol Ctr, Div Mol Carcinogenesis, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM r.bernards@nki.nl
FU European Research Council (ERC); Dutch Cancer Society (KWF); EU COLTHERES project; Netherlands Organization for Scientific Research (NWO) to Cancer Genomics Netherlands (CGC.NL); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS grant 'Farmacogenomica-5 per mille 2009 MIUR'; AIRC MFAG [11349]; AIRC IG grant [12812]; Canadian Institutes of Health Research (CIHR) [MOP-130540]
NR 29
TC 680
Z9 815
U1 0
U2 142
PU NATURE PUBLISHING 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 3
PY 2014
VL 508
IS 7494
BP 118
EP +
DI 10.1038/nature13121
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900054
PM 24670642
DA 2026-03-09
ER

PT J
AU Karasov, TL
   Kniskern, JM
   Gao, LP
   DeYoung, BJ
   Ding, J
   Dubiella, U
   Lastra, RO
   Nallu, S
   Roux, F
   Innes, RW
   Barrett, LG
   Hudson, RR
   Bergelson, J
AF Karasov, Talia L.
   Kniskern, Joel M.
   Gao, Liping
   DeYoung, Brody J.
   Ding, Jing
   Dubiella, Ullrich
   Lastra, Ruben O.
   Nallu, Sumitha
   Roux, Fabrice
   Innes, Roger W.
   Barrett, Luke G.
   Hudson, Richard R.
   Bergelson, Joy
TI The long-term maintenance of a resistance polymorphism through diffuse interactions
SO NATURE
LA English
DT Article
ID disease resistance; arabidopsis; coevolution; specificity; evolution; selection; variance
AB Plant resistance (R) genes are a crucial component in plant defence against pathogens(1). Although R genes often fail to provide durable resistance in an agricultural context, they frequently persist as long-lived balanced polymorphisms in nature(2-4). Standard theory explains the maintenance of such polymorphisms through a balance of the costs and benefits of resistance and virulence in a tightly coevolving host-pathogen pair(5,6). However, many plant-pathogen interactions lack such specificity(7). Whether, and how, balanced polymorphisms are maintained in diffusely interacting species(8) is unknown. Here we identify a naturally interacting R gene and effector pair in Arabidopsis thaliana and its facultative plant pathogen, Pseudomonas syringae. The protein encoded by the R gene RPS5 recognizes an AvrPphB homologue (AvrPphB2) and exhibits a balanced polymorphism that has been maintained for over 2 million years (ref. 3). Consistent with the presence of an ancient balanced polymorphism, the R gene confers a benefit when plants are infected with P. syringae carrying avrPphB2 but also incurs a large cost in the absence of infection. RPS5 alleles are maintained at intermediate frequencies in populations globally, suggesting ubiquitous selection for resistance. However, the presence of P. syringae carrying avrPphB is probably insufficient to explain the RPS5 polymorphism. First, avrPphB homologues occur at very low frequencies in P. syringae populations on A. thaliana. Second, AvrPphB only rarely confers a virulence benefit to P. syringae on A. thaliana. Instead, we find evidence that selection for RPS5 involves multiple non-homologous effectors and multiple pathogen species. These results and an associated model suggest that the R gene polymorphism in A. thaliana may not be maintained through a tightly coupled interaction involving a single coevolved R gene and effector pair. More likely, the stable polymorphism is maintained through complex and diffuse community-wide interactions.
C1 [Karasov, Talia L.; Kniskern, Joel M.; Gao, Liping; Ding, Jing; Lastra, Ruben O.; Nallu, Sumitha; Barrett, Luke G.; Hudson, Richard R.; Bergelson, Joy] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Karasov, Talia L.] Univ Chicago, Comm Genet Genom & Syst Biol, Chicago, IL 60637 USA.
   [DeYoung, Brody J.; Dubiella, Ullrich; Innes, Roger W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Roux, Fabrice] INRA, LIPM, F-31326 Castanet Tolosan, France.
   [Roux, Fabrice] CNRS, LIPM, F-31326 Castanet Tolosan, France.
   [Roux, Fabrice] Univ Sci & Technol Lille Lille 1, Lab Genet & Evolut Populat Vegetales, UMR CNRS 8198, F-59655 Villeneuve Dascq, France.
C3 University of Chicago; University of Chicago; Indiana University System; Indiana University Bloomington; Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Institut National des Sciences Appliquees de Toulouse; Centre National de la Recherche Scientifique (CNRS); INRAE; Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Institut National des Sciences Appliquees de Toulouse; Centre National de la Recherche Scientifique (CNRS); Universite de Lille
RP Bergelson, J (corresponding author), Univ Chicago, Dept Ecol & Evolut, 940 E 57Th St, Chicago, IL 60637 USA.
EM jbergels@uchicago.edu
FU Department of Education GAANN fellowship; Dropkin Foundation; National Institutes of Health (NIH) Postbaccalaureate Research Education Program award; Laboratory of Excellence (Labex) TULIP [ANR-10-LABX-41, ANR-11-IDEX-0002-02]; NIH-NIGMS [R01 GM046451, R01 GM057994, R01 GM083068]; NSF [MCB0603515]
CR Allen RL, 2004, SCIENCE, V306, P1957, DOI 10.1126/science.1104022
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   Barrett LG, 2011, ECOL LETT, V14, P1149, DOI 10.1111/j.1461-0248.2011.01687.x
   Barrett LG, 2009, NEW PHYTOL, V183, P513, DOI 10.1111/j.1469-8137.2009.02927.x
   Bodenhausen N, 2013, PLOS ONE, V8, P0, DOI 10.1371/journal.pone.0056329
   Bomblies K, 2007, PLOS BIOL, V5, P1962, DOI 10.1371/journal.pbio.0050236
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   Lockett SF, 2001, J ACQ IMMUN DEF SYND, V27, P277, DOI 10.1097/00126334-200107010-00010
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NR 30
TC 161
Z9 188
U1 1
U2 139
PU NATURE PUBLISHING 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 28
PY 2014
VL 512
IS 7515
BP 436
EP U472
DI 10.1038/nature13439
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600035
PM 25043057
DA 2026-03-09
ER

PT J
AU Gal-Yam, A
   Arcavi, I
   Ofek, EO
   Ben-Ami, S
   Cenko, SB
   Kasliwal, MM
   Cao, Y
   Yaron, O
   Tal, D
   Silverman, JM
   Horesh, A
   De Cia, A
   Taddia, F
   Sollerman, J
   Perley, D
   Vreeswijk, PM
   Kulkarni, SR
   Nugent, PE
   Filippenko, AV
   Wheeler, JC
AF Gal-Yam, Avishay
   Arcavi, I.
   Ofek, E. O.
   Ben-Ami, S.
   Cenko, S. B.
   Kasliwal, M. M.
   Cao, Y.
   Yaron, O.
   Tal, D.
   Silverman, J. M.
   Horesh, A.
   De Cia, A.
   Taddia, F.
   Sollerman, J.
   Perley, D.
   Vreeswijk, P. M.
   Kulkarni, S. R.
   Nugent, P. E.
   Filippenko, A. V.
   Wheeler, J. C.
TI A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind
SO NATURE
LA English
DT Article
ID supernova 2011dh; iib supernova; massive stars; discovery; evolution; model; ib/c
AB The explosive fate of massive Wolf-Rayet stars(1) (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections(4). Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 1012 centimetres, as expected for some WRSs(5). The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions(6).
C1 [Gal-Yam, Avishay; Arcavi, I.; Ofek, E. O.; Ben-Ami, S.; Yaron, O.; Tal, D.; De Cia, A.; Vreeswijk, P. M.] Weizmann Inst Sci, Dept Particle Phys & Astrophys, IL-76100 Rehovot, Israel.
   [Cenko, S. B.] NASA, Astrophys Sci Div, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Kasliwal, M. M.] Observ Carnegie Inst Sci, Pasadena, CA 91101 USA.
   [Cao, Y.; Horesh, A.; Perley, D.; Kulkarni, S. R.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Silverman, J. M.; Wheeler, J. C.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Taddia, F.; Sollerman, J.] Stockholm Univ, Oskar Klein Ctr, Dept Astron, AlbaNova, S-10691 Stockholm, Sweden.
   [Nugent, P. E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Phys, Berkeley, CA 94720 USA.
   [Filippenko, A. V.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94701 USA.
C3 Weizmann Institute of Science; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Carnegie Institution for Science; California Institute of Technology; University of Texas System; University of Texas Austin; Stockholm University; Oskar Klein Centre; 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
RP Gal-Yam, A (corresponding author), Weizmann Inst Sci, Dept Particle Phys & Astrophys, IL-76100 Rehovot, Israel.
EM avishay.gal-yam@weizmann.ac.il
FU I-CORE programme 'The Quantum Universe' of the Planning and Budgeting Committee; Israel Science Foundation; ISF; BSF; GIF; Minerva; FP7/ERC; Kimmel Investigator award; Hubble fellowship; Israeli MOST; NSF; TABASGO Foundation; Richard and Rhoda Goldman Fund; Christopher R. Redlich Fund; Swedish Research Council; W. M. Keck Foundation; Carnegie-Princeton fellowship; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1211916] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109801, 1009987] Funding Source: National Science Foundation
NR 40
TC 300
Z9 331
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 22
PY 2014
VL 509
IS 7501
BP 471
EP +
DI 10.1038/nature13304
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000034
PM 24848059
DA 2026-03-09
ER

PT J
AU Miething, C
   Scuoppo, C
   Bosbach, B
   Appelmann, I
   Nakitandwe, J
   Ma, J
   Wu, G
   Lintault, L
   Auer, M
   Premsrirut, PK
   Teruya-Feldstein, J
   Hicks, J
   Benveniste, H
   Speicher, MR
   Downing, JR
   Lowe, SW
AF Miething, Cornelius
   Scuoppo, Claudio
   Bosbach, Benedikt
   Appelmann, Iris
   Nakitandwe, Joy
   Ma, Jing
   Wu, Gang
   Lintault, Laura
   Auer, Martina
   Premsrirut, Prem K.
   Teruya-Feldstein, Julie
   Hicks, James
   Benveniste, Helene
   Speicher, Michael R.
   Downing, James R.
   Lowe, Scott W.
TI PTEN action in leukaemia dictated by the tissue microenvironment
SO NATURE
LA English
DT Article
ID ccr9 chemokine receptor; cell; gene; thymocytes; expression; pi3k; set; differentiation; antagonist; inhibitors
AB PTEN encodes a lipid phosphatase that is underexpressed in many cancers owing to deletions, mutations or gene silencing(1-3). PTEN dephosphorylates phosphatidylinositol (3,4,5)-triphosphate, thereby opposing the activity of class I phosphatidylinositol 3-kinases that mediate growth-and survival-factor signalling through phosphatidylinositol 3-kinase effectors such as AKT and mTOR(2). To determine whether continued PTEN inactivation is required to maintain malignancy, here we generate anRNA interference-based transgenic mouse model that allows tetracycline-dependent regulation of PTEN in a time-and tissue-specific manner. Postnatal Pten knockdown in the haematopoietic compartment produced highly disseminated T-cell acute lymphoblastic leukaemia. Notably, reactivation of PTEN mainly reduced T-cell leukaemia dissemination but had little effect on tumour load in haematopoietic organs. Leukaemia infiltration into the intestine was dependent on CCR9G-protein-coupled receptor signalling, which was amplified by PTEN loss. Our results suggest that in the absence of PTEN, G-protein-coupled receptors may have an unanticipated role in driving tumour growth and invasion in an unsupportive environment. They further reveal that the role of PTEN loss in tumour maintenance is not invariant and can be influenced by the tissue microenvironment, thereby producing a form of intratumoral heterogeneity that is independent of cancer genotype.
C1 [Miething, Cornelius; Bosbach, Benedikt; Appelmann, Iris; Teruya-Feldstein, Julie; Lowe, Scott W.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Miething, Cornelius; Scuoppo, Claudio; Appelmann, Iris; Lintault, Laura; Premsrirut, Prem K.; Hicks, James; Lowe, Scott W.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Nakitandwe, Joy; Ma, Jing; Wu, Gang; Downing, James R.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Lintault, Laura; Lowe, Scott W.] Howard Hughes Med Inst, New York, NY 10065 USA.
   [Auer, Martina; Speicher, Michael R.] Med Univ Graz, Inst Human Genet, A-8010 Graz, Austria.
   [Benveniste, Helene] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA.
   [Benveniste, Helene] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA.
C3 Memorial Sloan Kettering Cancer Center; Cold Spring Harbor Laboratory; St Jude Children's Research Hospital; Howard Hughes Medical Institute; Medical University of Graz; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
RP Lowe, SW (corresponding author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
EM lowes@mskcc.org
FU DFG [Mi1210/1-1]; Deutsche Krebshilfe (DKH) [109902]; Angel Foundation; National Cancer Institute, a Leukemia and Lymphoma Society Specialized Center of Research; Don Monti Foundation; Geoffrey Beene Foundation; National Cancer Institute [P01CA087497, P30CA045508, P30CA008748, P01CA013106, P30CA021765] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008444] Funding Source: NIH RePORTER; Academy of Finland (AKA) [109902] Funding Source: Academy of Finland (AKA)
NR 49
TC 41
Z9 48
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 JUN 19
PY 2014
VL 510
IS 7505
BP 402
EP +
DI 10.1038/nature13239
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200036
PM 24805236
DA 2026-03-09
ER

PT J
AU Tonge, PD
   Corso, AJ
   Monetti, C
   Hussein, SMI
   Puri, MC
   Michael, IP
   Li, M
   Lee, DS
   Mar, JC
   Cloonan, N
   Wood, DL
   Gauthier, MLE
   Korn, O
   Clancy, JL
   Preiss, T
   Grimmond, SM
   Shin, JY
   Seo, JS
   Wells, CA
   Rogers, IM
   Nagy, A
AF Tonge, Peter D.
   Corso, Andrew J.
   Monetti, Claudio
   Hussein, Samer M. I.
   Puri, Mira C.
   Michael, Iacovos P.
   Li, Mira
   Lee, Dong-Sung
   Mar, Jessica C.
   Cloonan, Nicole
   Wood, David L.
   Gauthier, Maely E.
   Korn, Othmar
   Clancy, Jennifer L.
   Preiss, Thomas
   Grimmond, Sean M.
   Shin, Jong-Yeon
   Seo, Jeong-Sun
   Wells, Christine A.
   Rogers, Ian M.
   Nagy, Andras
TI Divergent reprogramming routes lead to alternative stem-cell states
SO NATURE
LA English
DT Article
ID ips cells; self-renewal; pluripotency; expression; mice; transition; derivation; induction; distinct; genes
AB Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.
C1 [Tonge, Peter D.; Corso, Andrew J.; Monetti, Claudio; Hussein, Samer M. I.; Puri, Mira C.; Michael, Iacovos P.; Li, Mira; Rogers, Ian M.; Nagy, Andras] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
   [Corso, Andrew J.; Nagy, Andras] Univ Toronto, Inst Med Sci, Toronto, ON M5T 3H7, Canada.
   [Puri, Mira C.] Univ Toronto, Dept Med Biophys, Toronto, ON M5T 3H7, Canada.
   [Michael, Iacovos P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5T 3H7, Canada.
   [Lee, Dong-Sung; Shin, Jong-Yeon; Seo, Jeong-Sun] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea.
   [Lee, Dong-Sung; Seo, Jeong-Sun] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 110799, South Korea.
   [Lee, Dong-Sung; Seo, Jeong-Sun] Seoul Natl Univ, Dept Biochem, Coll Med, Seoul 110799, South Korea.
   [Mar, Jessica C.] Yeshiva Univ, Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
   [Cloonan, Nicole; Wood, David L.; Gauthier, Maely E.; Grimmond, Sean M.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia.
   [Korn, Othmar; Wells, Christine A.] Univ Queensland, Australina Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia.
   [Clancy, Jennifer L.; Preiss, Thomas] Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, Canberra, ACT 2601, Australia.
   [Preiss, Thomas] Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia.
   [Shin, Jong-Yeon; Seo, Jeong-Sun] Macrogen Inc, Life Sci Inst, Seoul 153781, South Korea.
   [Rogers, Ian M.] Univ Toronto, Dept Physiol, Toronto, ON M5T 3H7, Canada.
   [Rogers, Ian M.; Nagy, Andras] Univ Toronto, Dept Obstet & Gynaecol, Toronto, ON M5T 3H7, Canada.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University of Toronto; University of Toronto; Seoul National University (SNU); Seoul National University (SNU); Seoul National University (SNU); Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; University of Queensland; University of Queensland; Australian National University; John Curtin School of Medical Research; Victor Chang Cardiac Research Institute; Macrogen, Inc.; University of Toronto; University of Toronto
RP Nagy, A (corresponding author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
EM nagy@lunenfeld.ca
FU Ontario Research Fund Global Leadership Round in Genomics and Life Sciences grants [GL2]; Canadian stem cell network [9/5254 (TR3)]; Canadian Institutes of Health Research [CIHR MOP102575]; South Korean Ministry of Knowledge Economy [10037410]; SNUCM research fund [0411-20100074]; Macrogen Inc. [MGR03-11, MGR03-12]; Australian Research Council [SR110001002]; Queensland government Smart Futures Fellowship; ARC by Stem Cells Australia; NHMRC; ARC; McEwen Centre of Regenerative Medicine
NR 36
TC 107
Z9 129
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 DEC 11
PY 2014
VL 516
IS 7530
BP 192
EP +
DI 10.1038/nature14047
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500034
PM 25503232
DA 2026-03-09
ER

PT J
AU Park, E
   Ménétret, JF
   Gumbart, JC
   Ludtke, SJ
   Li, WK
   Whynot, A
   Rapoport, TA
   Akey, CW
AF Park, Eunyong
   Menetret, Jean-Francois
   Gumbart, James C.
   Ludtke, Steven J.
   Li, Weikai
   Whynot, Andrew
   Rapoport, Tom A.
   Akey, Christopher W.
TI Structure of the SecY channel during initiation of protein translocation
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; escherichia-coli; messenger-rna; electron-microscopy; molecular-dynamics; ribosome binding; er membrane; complex; insertion; visualization
AB Many secretory proteins are targeted by signal sequences to a protein-conducting channel, formed by prokaryotic SecY or eukaryotic Sec61 complexes, and are translocated across the membrane during their synthesis(1,2). Crystal structures of the inactive channel show that the SecY subunit of the heterotrimeric complex 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 the lipid phase(3-5). The closed channel has an empty cytoplasmic funnel and an extracellular funnel that is filled with a small helical domain, called the plug. During initiation of translocation, a ribosome-nascent chain complex binds to the SecY (or Sec61) complex, resulting in insertion of the nascent chain. However, the mechanism of channel opening during translocation is unclear. Here we have addressed this question by determining structures of inactive and active ribosome-channel complexes with cryo-electron microscopy. Non-translating ribosome-SecY channel complexes derived from Methanocaldococcus jannaschii or Escherichia coli show the channel in its closed state, and indicate that ribosome binding per se causes only minor changes. The structure of an active E. coli ribosome-channel complex demonstrates that the nascent chain opens the channel, causing mostly rigid body movements of the amino- and carboxy-terminal halves of SecY. In this early translocation intermediate, the polypeptide inserts as a loop into the SecY channel with the hydrophobic signal sequence intercalated into the open lateral gate. The nascent chain also forms a loop on the cytoplasmic surface of SecY rather than entering the channel directly.
C1 [Park, Eunyong; Li, Weikai; Whynot, Andrew; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Park, Eunyong; Li, Weikai; Whynot, Andrew; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Menetret, Jean-Francois; Akey, Christopher W.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA.
   [Gumbart, James C.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Ludtke, Steven J.] Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Boston University; University System of Georgia; Georgia Institute of Technology; Baylor College of Medicine
RP Rapoport, TA (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM Tom_Rapoport@hms.harvard.edu; cakey@bu.edu
FU National Institutes of Health [GM067887, GM080139, GM052586, GM45377]; National Heart Lung and Blood Institute [R01HL121718] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM045377, R01GM052586, R01GM080139] Funding Source: NIH RePORTER
NR 39
TC 128
Z9 154
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 FEB 6
PY 2014
VL 506
IS 7486
BP 102
EP +
DI 10.1038/nature12720
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100040
PM 24153188
DA 2026-03-09
ER

PT J
AU Pope, BD
   Ryba, T
   Dileep, V
   Yue, F
   Wu, WS
   Denas, O
   Vera, DL
   Wang, YL
   Hansen, RS
   Canfield, TK
   Thurman, RE
   Cheng, Y
   Gülsoy, G
   Dennis, JH
   Snyder, MP
   Stamatoyannopoulos, JA
   Taylor, J
   Hardison, RC
   Kahveci, T
   Ren, B
   Gilbert, DM
AF Pope, Benjamin D.
   Ryba, Tyrone
   Dileep, Vishnu
   Yue, Feng
   Wu, Weisheng
   Denas, Olgert
   Vera, Daniel L.
   Wang, Yanli
   Hansen, R. Scott
   Canfield, Theresa K.
   Thurman, Robert E.
   Cheng, Yong
   Guelsoy, Guenhan
   Dennis, Jonathan H.
   Snyder, Michael P.
   Stamatoyannopoulos, John A.
   Taylor, James
   Hardison, Ross C.
   Kahveci, Tamer
   Ren, Bing
   Gilbert, David M.
TI Topologically associating domains are stable units of replication-timing regulation
SO NATURE
LA English
DT Article
ID h3 lysine 27; reveals; organization; methylation; chromosome; dynamics; genm; switch; ezh2
AB Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program(1). In mammals, replication timing is cell-type-specific with at least half the genome switching replication timing during development, primarily in units of 400-800 kilobases (replication domains'), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements(2-7). Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs)(4,5,8,9). Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains(8,10). However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale(11,12). Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure(8,9,13). Here we localize boundaries of replication domains to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type-specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell-type-specific sub-nuclear compartmentalization and replication timing with developmentally stable structural domains and offer a unified model for large-scale chromosome structure and function.
C1 [Pope, Benjamin D.; Dileep, Vishnu; Vera, Daniel L.; Dennis, Jonathan H.; Gilbert, David M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
   [Ryba, Tyrone] New Coll Florida, Div Nat Sci, Sarasota, FL 34243 USA.
   [Yue, Feng] Penn State Univ, Sch Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
   [Yue, Feng; Wang, Yanli; Snyder, Michael P.] Penn State Univ, Huck Inst Life Sci, Bioinformat & Genom Program, University Pk, PA 16802 USA.
   [Wu, Weisheng; Hardison, Ross C.] Penn State Univ, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Denas, Olgert; Taylor, James] Emory Univ, O WayneRollins Res Ctr, Dept Biol, Atlanta, GA 30322 USA.
   [Denas, Olgert; Taylor, James] Emory Univ, O WayneRollins Res Ctr, Dept Math & Comp Sci, Atlanta, GA 30322 USA.
   [Hansen, R. Scott] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA.
   [Canfield, Theresa K.; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Cheng, Yong] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Guelsoy, Guenhan; Kahveci, Tamer] Univ Florida, Gainesville, FL 32611 USA.
   [Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Ren, Bing] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
C3 State University System of Florida; Florida State University; State University System of Florida; New College Florida; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; 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; Emory University; Emory University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Stanford University; State University System of Florida; University of Florida; Ludwig Institute for Cancer Research; University of California System; University of California San Diego
RP Gilbert, DM (corresponding author), Florida State Univ, Dept Biol Sci, 319 Stadium Dr, Tallahassee, FL 32306 USA.
EM gilbert@bio.fsu.edu
FU NIH [GM083337, GM085354, HG005602, HG005573, DK065806, HG003991]; National Cancer Institute of the National Institutes of Health [F31CA165863]; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [0845439] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM083337] Funding Source: NIH RePORTER
NR 36
TC 646
Z9 782
U1 0
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 20
PY 2014
VL 515
IS 7527
BP 402
EP +
DI 10.1038/nature13986
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600043
PM 25409831
DA 2026-03-09
ER

PT J
AU Standen, EM
   Du, TY
   Larsson, HCE
AF Standen, Emily M.
   Du, Trina Y.
   Larsson, Hans C. E.
TI Developmental plasticity and the origin of tetrapods
SO NATURE
LA English
DT Article
ID phenotypic plasticity; terrestrial locomotion; evolution; paleontology; fin
AB The origin of tetrapods from their fish antecedents, approximately 400 million years ago, was coupled with the origin of terrestrial locomotion and the evolution of supporting limbs. Polypterus is a member of the basal-most group of ray-finned fish (actinopterygians) and has many plesiomorphic morphologies that are comparable to elpistostegid fishes, which are stem tetrapods. Polypterus therefore serves as an extant analogue of stem tetrapods, allowing us to examine how developmental plasticity affects the 'terrestrialization' of fish. We measured the developmental plasticity of anatomical and biomechanical responses in Polypterus reared on land. Here we show the remarkable correspondence between the environmentally induced phenotypes of terrestrialized Polypterus and the ancient anatomical changes in stem tetrapods, and we provide insight into stem tetrapod behavioural evolution. Our results raise the possibility that environmentally induced developmental plasticity facilitated the origin of the terrestrial traits that led to tetrapods.
C1 [Standen, Emily M.] Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada.
   [Du, Trina Y.; Larsson, Hans C. E.] McGill Univ, Redpath Museum, Montreal, PQ H3A 0C4, Canada.
C3 University of Ottawa; McGill University
RP Standen, EM (corresponding author), Univ Ottawa, Dept Biol, Gendron Hall,30 Marie Curie Private, Ottawa, ON K1N 6N5, Canada.
EM estanden@uottawa.ca; hans.ce.larsson@mcgill.ca
FU National Sciences and Engineering Research Council of Canada [261796-2011]; Robert G. Goelet Research Award
NR 41
TC 162
Z9 183
U1 0
U2 211
PU NATURE PUBLISHING 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 4
PY 2014
VL 513
IS 7516
BP 54
EP +
DI 10.1038/nature13708
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800028
PM 25162530
DA 2026-03-09
ER

PT J
AU Venditti, JG
   Rennie, CD
   Bomhof, J
   Bradley, RW
   Little, M
   Church, M
AF Venditti, Jeremy G.
   Rennie, Colin D.
   Bomhof, James
   Bradley, Ryan W.
   Little, Malcolm
   Church, Michael
TI Flow in bedrock canyons
SO NATURE
LA English
DT Article
ID river incision; evolution; model
AB Bedrock erosion in rivers sets the pace of landscape evolution, influences the evolution of orogens and determines the size, shape and relief of mountains(1,2). A variety of models link fluid flow and sediment transport processes to bedrock incision in canyons. The model components that represent sediment transport processes are increasingly well developed(3-5). In contrast, the model components being used to represent fluid flow are largely untested because there are no observations of the flow structure in bedrock canyons. Here we present a 524-kilometre, continuous centreline, acoustic Doppler current profiler survey of the Fraser Canyon in western Canada, which includes 42 individual bedrock canyons. Our observations of three-dimensional flow structure reveal that, as water enters the canyons, a high-velocity core follows the bed surface, causing a velocity inversion (high velocities near the bed and low velocities at the surface). The plunging water then upwells along the canyon walls, resulting in counter-rotating, along-stream coherent flow structures that diverge near the bed. The resulting flow structure promotes deep scour in the bedrock channel floor and undercutting of the canyon walls. This provides a mechanism for channel widening and ensures that the base of the walls is swept clear of the debris that is often deposited there, keeping the walls nearly vertical. These observations reveal that the flow structure in bedrock canyons is more complex than assumed in the models presently used. Fluid flow models that capture the essence of the three-dimensional flow field, using simple phenomenological rules that are computationally tractable, are required to capture the dynamic coupling between flow, bedrock erosion and solid-Earth dynamics.
C1 [Venditti, Jeremy G.; Bradley, Ryan W.; Little, Malcolm] Simon Fraser Univ, Dept Geog, Burnaby, BC V5A 1S6, Canada.
   [Rennie, Colin D.; Bomhof, James] Univ Ottawa, Dept Civil Engn, Ottawa, ON K1N 6N5, Canada.
   [Church, Michael] Univ British Columbia, Dept Geog, Vancouver, BC V6T 1Z2, Canada.
C3 Simon Fraser University; University of Ottawa; University of British Columbia
RP Venditti, JG (corresponding author), Simon Fraser Univ, Dept Geog, Burnaby, BC V5A 1S6, Canada.
EM jeremy_venditti@sfu.ca
FU Natural Science and Engineering Research Council
NR 33
TC 67
Z9 71
U1 2
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 SEP 25
PY 2014
VL 513
IS 7519
BP 534
EP +
DI 10.1038/nature13779
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800037
PM 25254474
DA 2026-03-09
ER

PT J
AU Masoudi, A
   Raetz, CRH
   Zhou, P
   Pemble, CW
AF Masoudi, Ali
   Raetz, Christian R. H.
   Zhou, Pei
   Pemble, Charles W.
TI Chasing acyl carrier protein through a catalytic cycle of lipid A production
SO NATURE
LA English
DT Article
ID n-acyltransferase; binding; reveal; crystallography; biosynthesis; recognition; mechanism; complex; system; suite
AB Acyl carrier protein represents one of the most highly conserved proteins across all domains of life and is nature's way of transporting hydrocarbon chains in vivo. Notably, type II acyl carrier proteins serve as a crucial interaction hub in primary cellular metabolism(1) by communicating transiently between partner enzymes of the numerous biosynthetic pathways(2,3). However, the highly transient nature of such interactions and the inherent conformational mobility of acyl carrier protein(2) have stymied previous attempts to visualize structurally acyl carrier protein tied to an overall catalytic cycle. This is essential to understanding a fundamental aspect of cellular metabolism leading to compounds that are not only useful to the cell, but also of therapeutic value. For example, acyl carrier protein is central to the biosynthesis of the lipid A (endotoxin) component of lipopolysaccharides in Gram-negative microorganisms, which is required for their growth and survival(4,5), and is an activator of the mammalian host's immune system(6,7), thus emerging as an important therapeutic target(8-10). During lipid A synthesis (Raetz pathway), acyl carrier protein shuttles acyl intermediates linked to its prosthetic 4'-phosphopantetheine group(2) among four acyltransferases, including LpxD(11). Here we report the crystal structures of three forms of Escherichia coli acyl carrier protein engaging LpxD, which represent stalled substrate and liberated products along the reaction coordinate. The structures show the intricate interactions at the interface that optimally position acyl carrier protein for acyl delivery and that directly involve the pantetheinyl group. Conformational differences among the stalled acyl carrier proteins provide the molecular basis for the association-dissociation process. An unanticipated conformational shift of 4'-phosphopantetheine groups within the LpxD catalytic chamber shows an unprecedented role of acyl carrier protein in product release.
C1 [Masoudi, Ali; Raetz, Christian R. H.; Zhou, Pei] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
   [Pemble, Charles W.] Duke Univ, Med Ctr, HumanVaccine Inst, Durham, NC 27710 USA.
   [Pemble, Charles W.] Duke Univ, Med Ctr, Duke Macromol Crystallog Ctr, Durham, NC 27710 USA.
C3 Duke University; Duke University; Duke University
RP Pemble, CW (corresponding author), Duke Univ, Med Ctr, HumanVaccine Inst, Durham, NC 27710 USA.
EM charles.pemble@duke.edu
FU US Department of Energy, Office of Science and the Office of Basic Energy Sciences [W-31-109-Eng-38]; National Institutes of Health [GM-51310, AI-055588]; National Cancer Institute [P30CA014236] Funding Source: NIH RePORTER
NR 42
TC 63
Z9 77
U1 0
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 JAN 16
PY 2014
VL 505
IS 7483
BP 422
EP +
DI 10.1038/nature12679
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800047
PM 24196711
DA 2026-03-09
ER

PT J
AU McJeon, H
   Edmonds, J
   Bauer, N
   Clarke, L
   Fisher, B
   Flannery, BP
   Hilaire, J
   Krey, V
   Marangoni, G
   Mi, R
   Riahi, K
   Rogner, H
   Tavoni, M
AF McJeon, Haewon
   Edmonds, Jae
   Bauer, Nico
   Clarke, Leon
   Fisher, Brian
   Flannery, Brian P.
   Hilaire, Jerome
   Krey, Volker
   Marangoni, Giacomo
   Mi, Raymond
   Riahi, Keywan
   Rogner, Holger
   Tavoni, Massimo
TI Limited impact on decadal-scale climate change from increased use of natural gas
SO NATURE
LA English
DT Article
ID shale gas; change mitigation; emissions; model; technology; scenarios; economics; methane; stabilization; uncertainty
AB The most important energy development of the past decade has been the wide deployment of hydraulic fracturing technologies that enable the production of previously uneconomic shale gas resources in North America(1). If these advanced gas production technologies were to be deployed globally, the energy market could see a large influx of economically competitive unconventional gas resources(2). The climate implications of such abundant natural gas have been hotly debated. Some researchers have observed that abundant natural gas substituting for coal could reduce carbon dioxide (CO2) emissions(3-6). Others have reported that the non-CO2 greenhouse gas emissions associated with shale gas production make its lifecycle emissions higher than those of coal(7,8). Assessment of the full impact of abundant gas on climate change requires an integrated approach to the global energyeconomyclimate systems, but the literature has been limited in either its geographic scope(9,10) or its coverage of greenhouse gases(2). Here we show that market-driven increases in global supplies of unconventional natural gas do not discernibly reduce the trajectory of greenhouse gas emissions or climate forcing. Our results, based on simulations from five state-of-the-art integrated assessment models(11) of energyeconomyclimate systems independently forced by an abundant gas scenario, project large additional natural gas consumption of up to +170 per cent by 2050. The impact on CO2 emissions, however, is found to be much smaller (from -2 per cent to +11 per cent), and a majority of the models reported a small increase in climate forcing (from -0.3 per cent to +7 per cent) associated with the increased use of abundant gas. Our results show that although market penetration of globally abundant gas may substantially change the future energy system, it is not necessarily an effective substitute for climate change mitigation policy(9,10).
C1 [McJeon, Haewon; Edmonds, Jae; Clarke, Leon] Pacific NW Natl Lab, JGCRI, College Pk, MD 20740 USA.
   [Bauer, Nico; Hilaire, Jerome] Potsdam Inst Climate Impact Res, D-14412 Potsdam, Germany.
   [Fisher, Brian; Mi, Raymond] BAEconomics, Kingston, ACT 2604, Australia.
   [Flannery, Brian P.] Resources Future Inc, Washington, DC 20036 USA.
   [Krey, Volker; Riahi, Keywan; Rogner, Holger] Int Inst Appl Syst Anal, A-2361 Laxenburg, Austria.
   [Marangoni, Giacomo; Tavoni, Massimo] Ctr Euromediterraneo Cambiamenti Climat, I-20156 Milan, Italy.
   [Marangoni, Giacomo; Tavoni, Massimo] Politecn Milan, I-20156 Milan, Italy.
C3 United States Department of Energy (DOE); Pacific Northwest National Laboratory; Potsdam Institut fur Klimafolgenforschung; Resources for the Future; International Institute for Applied Systems Analysis (IIASA); Polytechnic University of Milan
RP McJeon, H (corresponding author), Pacific NW Natl Lab, JGCRI, 5825 Univ Res Court,Suite 3500, College Pk, MD 20740 USA.
EM haewon.mcjeon@pnnl.gov
FU BAEconomics; Global Technology Strategy Project; International Institute for Applied Systems Analysis; German Federal Ministry of Education and Research; Italian Ministry of Education, University and Research; Italian Ministry of Environment, Land and Sea under the GEMINA project
NR 96
TC 168
Z9 205
U1 4
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 OCT 23
PY 2014
VL 514
IS 7523
BP 482
EP +
DI 10.1038/nature13837
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900038
PM 25317557
DA 2026-03-09
ER

PT J
AU Rose, S
   Prevoteau, A
   Elzière, P
   Hourdet, D
   Marcellan, A
   Leibler, L
AF Rose, Severine
   Prevoteau, Alexandre
   Elziere, Paul
   Hourdet, Dominique
   Marcellan, Alba
   Leibler, Ludwik
TI Nanoparticle solutions as adhesives for gels and biological tissues
SO NATURE
LA English
DT Article
ID poly(ethylene glycol); hydrogels; adsorption; complexity; chemistry; polymers; layers
AB Adhesives are made of polymers(1) because, unlike other materials, polymers ensure good contact between surfaces by covering asperities, and retard the fracture of adhesive joints by dissipating energy under stress(2,3). But using polymers to 'glue' together polymer gels is difficult, requiring chemical reactions, heating, pH changes, ultraviolet irradiation or an electric field(4-7). Here we show that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel's surface and then bringing the other gel into contact with it. The method relies on the nanoparticles' ability to adsorb onto polymer gels and to act as connectors between polymer chains, and on the ability of polymer chains to reorganize and dissipate energy under stress when adsorbed onto nanoparticles. We demonstrate this approach by pressing together pieces of hydrogels, for approximately 30 seconds, that have the same or different chemical properties or rigidities, using various solutions of silica nanoparticles, to achieve a strong bond. Furthermore, we show that carbon nanotubes and cellulose nanocrystals that do not bond hydrogels together become adhesive when their surface chemistry is modified. To illustrate the promise of the method for biological tissues, we also glued together two cut pieces of calf's liver using a solution of silica nanoparticles. As a rapid, simple and efficient way to assemble gels or tissues, this method is desirable for many emerging technological and medical applications such as microfluidics, actuation, tissue engineering and surgery.
C1 [Rose, Severine; Elziere, Paul; Hourdet, Dominique; Marcellan, Alba] Univ Paris 06, Ecole Super Phys & Chim Ind, CNRS, Physicochim Polymeres & Milieux Disperses UMR7615, F-75005 Paris, France.
   [Prevoteau, Alexandre; Marcellan, Alba; Leibler, Ludwik] Ecole Super Phys & Chim Ind Ville Paris, CNRS, Matiere Molle & Chim UMR 7167, F-75005 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Sorbonne Universite; Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI)
RP Leibler, L (corresponding author), Ecole Super Phys & Chim Ind Ville Paris, CNRS, Matiere Molle & Chim UMR 7167, 10 Rue Vauquelin, F-75005 Paris, France.
EM alba.marcellan@espci.fr; ludwik.leibler@espci.fr
FU ED397, UPMC, Paris France; CNRS; ESPCI; UPMC
NR 30
TC 694
Z9 797
U1 18
U2 1773
PU NATURE PUBLISHING 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 16
PY 2014
VL 505
IS 7483
BP 382
EP +
DI 10.1038/nature12806
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800038
PM 24336207
DA 2026-03-09
ER

PT J
AU Mei, TS
   Patel, HH
   Sigman, MS
AF Mei, Tian-Sheng
   Patel, Harshkumar H.
   Sigman, Matthew S.
TI Enantioselective construction of remote quaternary stereocentres
SO NATURE
LA English
DT Article
ID oxidative palladium(ii) catalysis; carbon stereogenic centers; heck-type reaction; alkenyl alcohols; asymmetric 1,4-addition; trisubstituted enones; conjugate additions; allylic alcohols; acyclic alkenes; aryl halides
AB Small molecules that contain all-carbon quaternary stereocentres-carbon atoms bonded to four distinct carbonsubstituentsare found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted beta-, gamma-, delta-, epsilon-or zeta-aryl carbonyl compounds, because the unsaturation of the alkene is relayed to the alcohol, resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.
C1 [Mei, Tian-Sheng; Patel, Harshkumar H.; Sigman, Matthew S.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Sigman, MS (corresponding author), Univ Utah, Dept Chem, 315 South,1400 East, Salt Lake City, UT 84112 USA.
EM sigman@chem.utah.edu
FU US National Institutes of Health [NIGMS GM063540]
NR 48
TC 399
Z9 443
U1 1
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 APR 17
PY 2014
VL 508
IS 7496
BP 340
EP 344
DI 10.1038/nature13231
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000041
PM 24717439
DA 2026-03-09
ER

PT J
AU Bessede, A
   Gargaro, M
   Pallotta, MT
   Matino, D
   Servillo, G
   Brunacci, C
   Bicciato, S
   Mazza, EMC
   Macchiarulo, A
   Vacca, C
   Iannitti, R
   Tissi, L
   Volpi, C
   Belladonna, ML
   Orabona, C
   Bianchi, R
   Lanz, TV
   Platten, M
   Della Fazia, MA
   Piobbico, D
   Zelante, T
   Funakoshi, H
   Nakamura, T
   Gilot, D
   Denison, MS
   Guillemin, GJ
   DuHadaway, JB
   Prendergast, GC
   Metz, R
   Geffard, M
   Boon, L
   Pirro, M
   Iorio, A
   Veyret, B
   Romani, L
   Grohmann, U
   Fallarino, F
   Puccetti, P
AF Bessede, Alban
   Gargaro, Marco
   Pallotta, Maria T.
   Matino, Davide
   Servillo, Giuseppe
   Brunacci, Cinzia
   Bicciato, Silvio
   Mazza, Emilia M. C.
   Macchiarulo, Antonio
   Vacca, Carmine
   Iannitti, Rossana
   Tissi, Luciana
   Volpi, Claudia
   Belladonna, Maria L.
   Orabona, Ciriana
   Bianchi, Roberta
   Lanz, Tobias V.
   Platten, Michael
   Della Fazia, Maria A.
   Piobbico, Danilo
   Zelante, Teresa
   Funakoshi, Hiroshi
   Nakamura, Toshikazu
   Gilot, David
   Denison, Michael S.
   Guillemin, Gilles J.
   DuHadaway, James B.
   Prendergast, George C.
   Metz, Richard
   Geffard, Michel
   Boon, Louis
   Pirro, Matteo
   Iorio, Alfonso
   Veyret, Bernard
   Romani, Luigina
   Grohmann, Ursula
   Fallarino, Francesca
   Puccetti, Paolo
TI Aryl hydrocarbon receptor control of a disease tolerance defence pathway
SO NATURE
LA English
DT Article
ID regulatory t-cells; indoleamine 2,3-dioxygenase; tryptophan catabolism; dendritic cells; endotoxin tolerance; ligand-binding; ah receptor; kynurenine; ido; infection
AB Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to down-regulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. There sulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhRin contributing to host fitness.
C1 [Bessede, Alban; Gargaro, Marco; Pallotta, Maria T.; Matino, Davide; Servillo, Giuseppe; Brunacci, Cinzia; Vacca, Carmine; Iannitti, Rossana; Tissi, Luciana; Volpi, Claudia; Belladonna, Maria L.; Orabona, Ciriana; Bianchi, Roberta; Della Fazia, Maria A.; Piobbico, Danilo; Zelante, Teresa; Romani, Luigina; Grohmann, Ursula; Fallarino, Francesca; Puccetti, Paolo] Univ Perugia, Dept Expt Med, I-06132 Perugia, Italy.
   [Bessede, Alban; Geffard, Michel; Veyret, Bernard] Univ Bordeaux, IMS Lab, F-33607 Pessac, France.
   [Bicciato, Silvio; Mazza, Emilia M. C.] Univ Modena & Reggio Emilia, Ctr Genome Res, I-41125 Modena, Italy.
   [Macchiarulo, Antonio] Univ Perugia, Dept Chem & Technol Drugs, I-06123 Perugia, Italy.
   [Lanz, Tobias V.; Platten, Michael] German Canc Res Ctr, Expt Neuroimmunol Unit, D-69120 Heidelberg, Germany.
   [Lanz, Tobias V.; Platten, Michael] Univ Hosp, Dept Neurooncol, D-69120 Heidelberg, Germany.
   [Funakoshi, Hiroshi] Asahikawa Med Univ, Ctr Adv Res & Educ, Asahikawa, Hokkaido 0788510, Japan.
   [Nakamura, Toshikazu] Osaka Univ, Kringle Pharma Joint Res Div Regenerat Drug Disco, Ctr Adv Sci & Innovat, Suita, Osaka 5650871, Japan.
   [Gilot, David] Univ Rennes 1, CNRS UMR6290, Inst Genet & Dev Rennes, F-35043 Rennes, France.
   [Denison, Michael S.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA.
   [Guillemin, Gilles J.] Macquarie Univ, ASAM, N Ryde, NSW 2109, Australia.
   [DuHadaway, James B.; Prendergast, George C.] Lankenau Inst Med Res, Wynnewood, PA 19096 USA.
   [Metz, Richard] New Link Genetics Corp, Ames, IA 50010 USA.
   [Boon, Louis] Bioceros, NL-3584 Utrecht, Netherlands.
   [Pirro, Matteo] Univ Perugia, Dept Med, I-06132 Perugia, Italy.
   [Iorio, Alfonso] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4K1, Canada.
C3 University of Perugia; Universite de Bordeaux; Universita di Modena e Reggio Emilia; University of Perugia; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Asahikawa Medical University; University of Osaka; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Rennes; University of California System; University of California Davis; Macquarie University; Lankenau Medical Center; Lankenau Institute for Medical Research; University of Perugia; McMaster University
RP Puccetti, P (corresponding author), Univ Perugia, Dept Expt Med, I-06132 Perugia, Italy.
EM fllfnc@tin.it; plopcc@tin.it
FU Italian Association for Cancer Research (AIRC); Fondazione Italiana Sclerosi Multipla [2010/R/17]; Associazione Umbra Contro il Cancro; Bayer Grants4Target Focus [2012-03-0630]; Bayer Early Career Investigator Award from the US National Institutes of Environmental Health Sciences [R01ES007685]; Specific Targeted Research Project FUNMETA; Regione dell'Umbria [GR-2008-1138004]; Italian Ministry of Health; National Cancer Institute [P30CA056036] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [23590362] Funding Source: KAKEN
NR 50
TC 565
Z9 653
U1 4
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 JUL 10
PY 2014
VL 511
IS 7508
BP 184
EP +
DI 10.1038/nature13323
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800036
PM 24930766
DA 2026-03-09
ER

PT J
AU Foth, C
   Tischlinger, H
   Rauhut, OWM
AF Foth, Christian
   Tischlinger, Helmut
   Rauhut, Oliver W. M.
TI New specimen of Archaeopteryx provides insights into the evolution of pennaceous feathers
SO NATURE
LA English
DT Article
ID long feathers; china; dinosaur; flight; theropod; plumage; origin; birds
AB Discoveries of bird-like theropod dinosaurs and basal avialans in recent decades have helped to put the iconic 'Urvogel' Archaeopteryx(1) into context(2-6) and have yielded important new data on the origin and early evolution of feathers(7). However, the biological context under which pennaceous feathers evolved is still debated. Here we describe a new specimen of Archaeopteryx with extensive feather preservation, not only on the wings and tail, but also on the body and legs. The new specimen shows that the entire body was covered in pennaceous feathers, and that the hindlimbs had long, symmetrical feathers along the tibiotarsus but short feathers on the tarsometatarsus. Furthermore, the wing plumage demonstrates that several recent interpretations(8,9) are problematic. An analysis of the phylogenetic distribution of pennaceous feathers on the tail, hindlimb and arms of advanced maniraptorans and basal avialans strongly indicates that these structures evolved in a functional context other than flight, most probably in relation to display, as suggested by some previous studies(10-12). Pennaceous feathers thus represented an exaptation and were later, in several lineages and following different patterns, recruited for aerodynamic functions. This indicates that the origin of flight in avialans was more complex than previously thought and might have involved several convergent achievements of aerial abilities.
C1 [Foth, Christian; Rauhut, Oliver W. M.] Bayer Staatssammlung Palaontol & Geol, Staatliche Nat Wissenschaftliche Sammlungen Bayer, D-80333 Munich, Germany.
   [Foth, Christian; Rauhut, Oliver W. M.] Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
   [Foth, Christian; Rauhut, Oliver W. M.] Univ Munich, GeoBioCtr, D-80333 Munich, Germany.
C3 University of Munich; University of Munich
RP Rauhut, OWM (corresponding author), Bayer Staatssammlung Palaontol & Geol, Staatliche Nat Wissenschaftliche Sammlungen Bayer, Richard Wagner Str 10, D-80333 Munich, Germany.
EM o.rauhut@lrz.uni-muenchen.de
FU Volkswagen Foundation [I/84 640]
NR 30
TC 165
Z9 182
U1 3
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 JUL 3
PY 2014
VL 511
IS 7507
BP 79
EP U421
DI 10.1038/nature13467
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400039
PM 24990749
DA 2026-03-09
ER

PT J
AU De Raedt, T
   Beert, E
   Pasmant, E
   Luscan, A
   Brems, H
   Ortonne, N
   Helin, K
   Hornick, JL
   Mautner, V
   Kehrer-Sawatzki, H
   Clapp, W
   Bradner, J
   Vidaud, M
   Upadhyaya, M
   Legius, E
   Cichowski, K
AF De Raedt, Thomas
   Beert, Eline
   Pasmant, Eric
   Luscan, Armelle
   Brems, Hilde
   Ortonne, Nicolas
   Helin, Kristian
   Hornick, Jason L.
   Mautner, Victor
   Kehrer-Sawatzki, Hildegard
   Clapp, Wade
   Bradner, James
   Vidaud, Michel
   Upadhyaya, Meena
   Legius, Eric
   Cichowski, Karen
TI PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies
SO NATURE
LA English
DT Article
ID bet bromodomain inhibition; nf1 microdeletion patients; neurofibromatosis type-1; cancer; tumors; gene; suppressor; mutations; mice; ezh2
AB The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types(1). However, loss-of-function mutations in PRC2 components occur in a subset of haematopoietic malignancies, suggesting that this complex plays a dichotomous and poorly understood role in cancer(2,3). Here we provide genomic, cellular, and mouse modelling data demonstrating that the polycomb group gene SUZ12 functions as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras(4). We show that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras-driven transcription through effects on chromatin. Importantly, however, SUZ12 inactivation also triggers an epigenetic switch that sensitizes these cancers to bromodomain inhibitors. Collectively, these studies not only reveal an unexpected connection between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic-based therapeutic strategy that may be exploited for a variety of cancers.
C1 [De Raedt, Thomas; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [De Raedt, Thomas; Bradner, James; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [De Raedt, Thomas; Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA.
   [Beert, Eline; Brems, Hilde; Legius, Eric] Katholieke Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium.
   [Pasmant, Eric; Luscan, Armelle; Ortonne, Nicolas; Vidaud, Michel] Univ Paris 05, Sorbonne Paris Cite, Fac Sci Pharmaceut & Biol, INSERM UMR S745, F-75006 Paris, France.
   [Pasmant, Eric; Luscan, Armelle; Ortonne, Nicolas; Vidaud, Michel] Univ Paris 05, Sorbonne Paris Cite, Fac Sci Pharmaceut & Biol, EA7331, F-75006 Paris, France.
   [Pasmant, Eric; Luscan, Armelle; Ortonne, Nicolas; Vidaud, Michel] Hop Cochin, AP HP, Serv Biochim & Genet Mol, F-75014 Paris, France.
   [Helin, Kristian] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark.
   [Helin, Kristian] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark.
   [Helin, Kristian] Univ Copenhagen, Danish Stem Cell Ctr Danstem, DK-2200 Copenhagen, Denmark.
   [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Mautner, Victor] Univ Med Ctr, Dept Maxillofacial Surg, D-20246 Hamburg, Germany.
   [Kehrer-Sawatzki, Hildegard] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany.
   [Clapp, Wade] Indiana Univ Sch Med, Dept Pediat, Herman Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
   [Bradner, James] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Upadhyaya, Meena] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales.
   [Legius, Eric] Univ Hosp Leuven, Ctr Human Genet, B-3000 Leuven, Belgium.
C3 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; KU Leuven; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Cochin - APHP; University of Copenhagen; University of Copenhagen; University of Copenhagen; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Hamburg; University Medical Center Hamburg-Eppendorf; Ulm University; Indiana University System; Indiana University Bloomington; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Cardiff University; KU Leuven; University Hospital Leuven
RP Cichowski, K (corresponding author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM Eric.Legius@uzleuven.be; kcichowski@rics.bwh.harvard.edu
FU US Department of Defense [W81XWH-11-1-0138]; Ludwig Center at DF/HCC and the Children's Tumor Foundation; Children's Tumor Foundation; FWO-Flanders [G.0784.10N]; Emmanuel Vanderschueren Fellowship from the Vlaamse Liga tegen Kanker
NR 33
TC 372
Z9 413
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 OCT 9
PY 2014
VL 514
IS 7521
BP 247
EP +
DI 10.1038/nature13561
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100046
PM 25119042
DA 2026-03-09
ER

PT J
AU Pouchelon, G
   Gambino, F
   Bellone, C
   Telley, L
   Vitali, I
   Lüscher, C
   Holtmaat, A
   Jabaudon, D
AF Pouchelon, Gabrielle
   Gambino, Frederic
   Bellone, Camilla
   Telley, Ludovic
   Vitali, Ilaria
   Luescher, Christian
   Holtmaat, Anthony
   Jabaudon, Denis
TI Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons
SO NATURE
LA English
DT Article
ID neurite growth-inhibitors; somatosensory cortex; functional recovery; barrel cortex; connectivity; expression; plasticity; projection; cortices; pathways
AB During development, thalamocortical (TC) input has a critical role in the spatial delineation and patterning of cortical areas(1-6), yet the underlying cellular and molecular mechanisms that drive cortical neuron differentiation are poorly understood. In the primary (S1) and secondary (S2) somatosensory cortex, layer 4 (L4) neurons receive mutually exclusive input originating from two thalamic nuclei(7,8): the ventrobasalis (VB), which conveys tactile input(9,10), and the posterior nucleus (Po), which conveys modulatory and nociceptive input(11-14). Recently, we have shown that L4 neuron identity is not fully committed postnatally(15), implying a capacity for TC input to influence differentiation during cortical circuit assembly. Here we investigate whether the cell-type-specific molecular and functional identity of L4 neurons is instructed by the origin of their TC input. Genetic ablation of the VB at birth resulted in an anatomical and functional rewiring of Po projections onto L4 neurons in S1. This induced acquisition of Po input led to a respecification of postsynaptic L4 neurons, which developed functional molecular features of Po-target neurons while repressing VB-target traits. Respecified L4 neurons were able to respond both to touch and to noxious stimuli, in sharp contrast to the normal segregation of these sensory modalities in distinct cortical circuits. These findings reveal a behaviourally relevant TC-input-type-specific control over the molecular and functional differentiation of postsynaptic L4 neurons and cognate intracortical circuits, which instructs the development of modality-specific neuronal and circuit properties during corticogenesis.
C1 [Pouchelon, Gabrielle; Gambino, Frederic; Bellone, Camilla; Telley, Ludovic; Vitali, Ilaria; Luescher, Christian; Holtmaat, Anthony; Jabaudon, Denis] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Luescher, Christian; Jabaudon, Denis] Univ Hosp Geneva, Clin Neurol, Dept Clin Neurosci, CH-1211 Geneva, Switzerland.
   [Luescher, Christian; Jabaudon, Denis] Univ Geneva, Inst Genet & Genom Geneva IGE3, CH-1211 Geneva, Switzerland.
C3 University of Geneva; University of Geneva; University of Geneva
RP Jabaudon, D (corresponding author), Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
EM denis.jabaudon@unige.ch
FU Swiss National Science Foundation (SNF) [PP00P3_123447]; Leenaards Foundation; Synapsis Foundation; NARSAD Foundation; Ambizione grant from the SNF; Gertrude von Meissner Foundation; SNF; Simons Foundation Autism Research Initiative (SFARI); SNF [31003A-135631]; EMBO; International Foundation for Research in Paraplegia; Hans Wilsdorf Foundation; Swiss National Science Foundation (SNF) [PP00P3_123447] Funding Source: Swiss National Science Foundation (SNF)
NR 46
TC 113
Z9 127
U1 2
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 JUL 24
PY 2014
VL 511
IS 7510
BP 471
EP +
DI 10.1038/nature13390
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700047
PM 24828045
DA 2026-03-09
ER

PT J
AU Ibata, NG
   Ibata, RA
   Famaey, B
   Lewis, GF
AF Ibata, Neil G.
   Ibata, Rodrigo A.
   Famaey, Benoit
   Lewis, Geraint F.
TI Velocity anti-correlation of diametrically opposed galaxy satellites in the low-redshift Universe
SO NATURE
LA English
DT Article
ID milky-way; dwarf galaxy; local group; thin plane; andromeda; density; disk; vast
AB Recent work has shown that the Milky Way and the Andromeda galaxies both possess the unexpected property that their dwarf satellite galaxies are aligned in thin and kinematically coherent planar structures(1-7). It is interesting to evaluate the incidence of such planar structures in the larger galactic population, because the Local Group may not be a representative environment. Here we report measurements of the velocities of pairs of diametrically opposed satellite galaxies. In the local Universe (redshift z<0.05), we find that satellite pairs out to a distance of 150 kiloparsecs from the galactic centre are preferentially anti-correlated in their velocities (99.994 per cent confidence level), and that the distribution of galaxies in the larger-scale environment (out to distances of about 2 megaparsecs) is strongly clumped along the axis joining the inner satellite pair ( >7 sigma confidence). This may indicate that planes of co-rotating satellites, similar to those seen around the Andromeda galaxy, are ubiquitous, and their coherent motion suggests that they represent a substantial repository of angular momentum on scales of about 100 kiloparsecs.
C1 [Ibata, Neil G.] Lycee Int Pontonniers, F-67000 Strasbourg, France.
   [Ibata, Rodrigo A.; Famaey, Benoit] Univ Strasbourg, CNRS, UMR 7550, Observ Astron Strasbourg, F-67000 Strasbourg, France.
   [Lewis, Geraint F.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of Sydney
RP Ibata, NG (corresponding author), Lycee Int Pontonniers, 1 Rue Pontonniers, F-67000 Strasbourg, France.
EM neil.ibata@gmail.com
FU Alfred P. Sloan Foundation; National Science Foundation; US Department of Energy; National Aeronautics and Space Administration; Japanese Monbukagakusho; Max Planck Society; Higher Education Funding Council for England
NR 32
TC 90
Z9 97
U1 0
U2 3
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2014
VL 511
IS 7511
BP 563
EP +
DI 10.1038/nature13481
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300028
PM 25043008
DA 2026-03-09
ER

PT J
AU Schneider, DM
   Nelson, A
   Mooney, R
AF Schneider, David M.
   Nelson, Anders
   Mooney, Richard
TI A synaptic and circuit basis for corollary discharge in the auditory cortex
SO NATURE
LA English
DT Article
ID cortical activity; behavioral state; visual responses; modulation; brain; schizophrenia; gain; hallucinations; connections; dysfunction
AB Sensory regions of the brain integrate environmental cues with copies of motor-related signals important for imminent and ongoing movements. In mammals, signals propagating from the motor cortex to the auditory cortex are thought to have a critical role in normal hearing and behaviour, yet the synaptic and circuit mechanisms by which these motor-related signals influence auditory cortical activity remain poorly understood. Using in vivo intracellular recordings in behaving mice, we find that excitatory neurons in the auditory cortex are suppressed before and during movement, owing in part to increased activity of local parvalbumin-positive interneurons. Electrophysiology and optogenetic gain- and loss-of-function experiments reveal that motor-related changes in auditory cortical dynamics are driven by a subset of neurons in the secondary motor cortex that innervate the auditory cortex and are active during movement. These findings provide a synaptic and circuit basis for the motor-related corollary discharge hypothesized to facilitate hearing and auditory-guided behaviours.
C1 [Schneider, David M.; Nelson, Anders; Mooney, Richard] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
C3 Duke University
RP Mooney, R (corresponding author), Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
EM mooney@neuro.duke.edu
FU Holland-Trice Graduate Fellowship in Brain Sciences; NIH [NS079929]; National Institute on Deafness and Other Communication Disorders [R01DC013826] Funding Source: NIH RePORTER
NR 49
TC 396
Z9 488
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 SEP 11
PY 2014
VL 513
IS 7517
BP 189
EP +
DI 10.1038/nature13724
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800042
PM 25162524
DA 2026-03-09
ER

PT J
AU Gokhberg, K
   Kolorenc, P
   Kuleff, AI
   Cederbaum, LS
AF Gokhberg, Kirill
   Kolorenc, Premysl
   Kuleff, Alexander I.
   Cederbaum, Lorenz S.
TI Site- and energy-selective slow-electron production through intermolecular Coulombic decay
SO NATURE
LA English
DT Article
ID correlated molecular calculations; resonant auger-spectra; gaussian-basis sets; charge dependence; strand breaks; core-level; atoms; water; dna; spectroscopy
AB Irradiation of matter with light tends to electronically excite atoms and molecules, with subsequent relaxation processes determining where the photon energy is ultimately deposited and electrons and ions produced. In weakly bound systems, intermolecular Coulombic decay(1) (ICD) enables very efficient relaxation of electronic excitation through transfer of the excess energy to neighbouring atoms or molecules that then lose an electron and become ionized(2-9). Here we propose that the emission site and energy of the electrons released during this process can be controlled by coupling the ICD to a resonant core excitation. We illustrate this concept with ab initio many body calculations on the argon-krypton model system, where resonant photoabsorption produces an initial or 'parent' excitation of the argon atom, which then triggers a resonant-Auger-ICD cascade that ends with the emission of a slow electron from the krypton atom. Our calculations show that the energy of the emitted electrons depends sensitively on the initial excited state of the argon atom. The incident energy can thus be adjusted both to produce the initial excitation in a chosen atom and to realize an excitation that will result in the emission of ICD electrons with desired energies. These properties of the decay cascade might have consequences for fundamental and applied radiation biology and could be of interest in the development of new spectroscopic techniques.
C1 [Gokhberg, Kirill; Kuleff, Alexander I.; Cederbaum, Lorenz S.] Heidelberg Univ, Inst Phys Chem, D-69120 Heidelberg, Germany.
   [Kolorenc, Premysl] Charles Univ Prague, Fac Math & Phys, Inst Theoret Phys, CR-18000 Prague, Czech Republic.
C3 Ruprecht Karls University Heidelberg; Charles University Prague
RP Gokhberg, K (corresponding author), Heidelberg Univ, Inst Phys Chem, Neuenheimer Feld 229, D-69120 Heidelberg, Germany.
EM kirill.gokhberg@pci.uni-heidelberg.de; alexander.kuleff@pci.uni-heidelberg.de
FU European Research Council under the European Community [227597]; Czech Science Foundation [P208/12/0521]
NR 51
TC 136
Z9 142
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 JAN 30
PY 2014
VL 505
IS 7485
BP 661
EP +
DI 10.1038/nature12936
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000036
PM 24362566
DA 2026-03-09
ER

PT J
AU Sun, L
   Young, LN
   Zhang, XZ
   Boudko, SP
   Fokine, A
   Zbornik, E
   Roznowski, AP
   Molineux, IJ
   Rossmann, MG
   Fane, BA
AF Sun, Lei
   Young, Lindsey N.
   Zhang, Xinzheng
   Boudko, Sergei P.
   Fokine, Andrei
   Zbornik, Erica
   Roznowski, Aaron P.
   Molineux, Ian J.
   Rossmann, Michael G.
   Fane, Bentley A.
TI Icosahedral bacteriophage ΦX174 forms a tail for DNA transport during infection
SO NATURE
LA English
DT Article
ID external scaffolding protein; single-stranded-dna; h spike protein; escherichia-coli; 2nd-site suppressors; adsorption; prediction; mechanism; model; host
AB Prokaryotic viruses have evolved various mechanisms to transport their genomes across bacterial cell walls(1). Many bacteriophages use a tail to perform this function, whereas tail-less phages rely on host organelles(2-4). However, the tail-less, icosahedral, single-stranded DNA Phi X174-like coliphages do not fall into these well-defined infection processes. For these phages, DNA delivery requires a DNA pilot protein(5). Here we show that the Phi X174 pilot protein H oligomerizes to forma tube whose function is most probably to deliver the DNA genome across the host's periplasmic space to the cytoplasm. The 2.4 angstrom resolution crystal structure of the in vitro assembled H protein's central domain consists of a 170 angstrom-long alpha-helical barrel. The tube is constructed of ten alpha-helices with their amino termini arrayed in a right-handed super-helical coiled-coil and their carboxy termini arrayed in a left-handed super-helical coiled-coil. Genetic and biochemical studies demonstrate that the tube is essential for infectivity but does not affect in vivo virus assembly. Cryo-electron tomograms show that tubes span the periplasmic space and are present while the genome is being delivered into the host cell's cytoplasm. Both ends of the H protein contain transmembrane domains, which anchor the assembled tubes into the inner and outer cell membranes. The central channel of the H-protein tube is lined with amide and guanidinium side chains. This may be a general property of viral DNA conduits and is likely to be critical for efficient genome translocation into the host.
C1 [Sun, Lei; Zhang, Xinzheng; Boudko, Sergei P.; Fokine, Andrei; Zbornik, Erica; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Young, Lindsey N.; Roznowski, Aaron P.; Fane, Bentley A.] Univ Arizona, Sch Plant Sci, Tucson, AZ 85721 USA.
   [Young, Lindsey N.; Roznowski, Aaron P.; Fane, Bentley A.] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA.
   [Molineux, Ian J.] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.
C3 Purdue University System; Purdue University; University of Arizona; University of Arizona; University of Texas System; University of Texas Austin
RP Rossmann, MG (corresponding author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM mr@purdue.edu; bfane@email.arizona.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DEAC02-06CH11357]; National Science Foundation [MCB-0948399, MCB-0443899]; US Department of Agriculture; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1014547] Funding Source: National Science Foundation
NR 45
TC 91
Z9 113
U1 0
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 16
PY 2014
VL 505
IS 7483
BP 432
EP +
DI 10.1038/nature12816
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800049
PM 24336205
DA 2026-03-09
ER

PT J
AU Pappas, L
   Foglierini, M
   Piccoli, L
   Kallewaard, NL
   Turrini, F
   Silacci, C
   Fernandez-Rodriguez, B
   Agatic, G
   Giacchetto-Sasselli, I
   Pellicciotta, G
   Sallusto, F
   Zhu, Q
   Vicenzi, E
   Corti, D
   Lanzavecchia, A
AF Pappas, Leontios
   Foglierini, Mathilde
   Piccoli, Luca
   Kallewaard, Nicole L.
   Turrini, Filippo
   Silacci, Chiara
   Fernandez-Rodriguez, Blanca
   Agatic, Gloria
   Giacchetto-Sasselli, Isabella
   Pellicciotta, Gabriele
   Sallusto, Federica
   Zhu, Qing
   Vicenzi, Elisa
   Corti, Davide
   Lanzavecchia, Antonio
TI Rapid development of broadly influenza neutralizing antibodies through redundant mutations
SO NATURE
LA English
DT Article
ID memory b-cells; monoclonal-antibody; affinity maturation; sequence-analysis; germinal-centers; immune-response; virus; generation; hemagglutinin; expression
AB The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem(1-6). Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region(HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals(6,7), suggesting that several somatic mutations may be required for their development(8,9). To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.
C1 [Pappas, Leontios; Foglierini, Mathilde; Piccoli, Luca; Silacci, Chiara; Fernandez-Rodriguez, Blanca; Giacchetto-Sasselli, Isabella; Sallusto, Federica; Corti, Davide; Lanzavecchia, Antonio] Univ Svizzera Italiana, Insitute Res Biomed, CH-6500 Bellinzona, Switzerland.
   [Kallewaard, Nicole L.; Zhu, Qing] Dis & Vaccines MedImmune LLC, Dept Infect, Gaithersburg, MD 20878 USA.
   [Vicenzi, Elisa] Ist Sci San Raffaele, Viral Pathogens & Biosafety Unit, I-20132 Milan, Italy.
   [Agatic, Gloria; Corti, Davide] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland.
   [Pellicciotta, Gabriele] Ist Sci San Raffaele, Unit Prevent Med, I-20132 Milan, Italy.
   [Lanzavecchia, Antonio] ETH, Insitute Microbiol, CH-8093 Zurich, Switzerland.
C3 Universita della Svizzera Italiana; AstraZeneca; Medimmune; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Lanzavecchia, A (corresponding author), Univ Svizzera Italiana, Insitute Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
EM lanzavecchia@irb.usi.ch
FU European Research Council IMMUNExplore [250348]; Swiss National Science Foundation [141254]; Fondazione Cariplo Vaccine Program [2009-3594]; Human Frontiers Science Program [RGP0009/2007-C]; European Commission ADITEC [FP7-HEALTH-2011-280873]; National Institutes of Health [AI-057266]; Helmut Horten Foundation; National Institute of Allergy and Infectious Diseases [U19AI057266] Funding Source: NIH RePORTER; European Research Council (ERC) [250348] Funding Source: European Research Council (ERC)
NR 39
TC 256
Z9 293
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 DEC 18
PY 2014
VL 516
IS 7531
BP 418
EP +
DI 10.1038/nature13764
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800052
PM 25296253
DA 2026-03-09
ER

PT J
AU Watanabe, S
   Trimbuch, T
   Camacho-Pérez, M
   Rost, BR
   Brokowski, B
   Söhl-Kielczynski, B
   Felies, A
   Davis, MW
   Rosenmund, C
   Jorgensen, EM
AF Watanabe, Shigeki
   Trimbuch, Thorsten
   Camacho-Perez, Marcial
   Rost, Benjamin R.
   Brokowski, Bettina
   Soehl-Kielczynski, Berit
   Felies, Annegret
   Davis, M. Wayne
   Rosenmund, Christian
   Jorgensen, Erik M.
TI Clathrin regenerates synaptic vesicles from endosomes
SO NATURE
LA English
DT Article
ID frog neuromuscular-junction; hippocampal synapses; mediated endocytosis; physiological temperatures; caenorhabditis-elegans; membrane retrieval; terminals; release; dynamin; trafficking
AB Ultrafast endocytosis can retrieve a single, large endocytic vesicle as fast as 50-100 ms after synaptic vesicle fusion. However, the fate of the large endocytic vesicles is not known. Here we demonstrate that these vesicles transition to a synaptic endosome about one second after stimulation. The endosome is resolved into coated vesicles after 3 s, which in turn become small-diameter synaptic vesicles 5-6 s after stimulation. We disrupted clathrin function using RNA interference (RNAi) and found that clathrin is not required for ultrafast endocytosis but is required to generate synaptic vesicles from the endosome. Ultrafast endocytosis fails when actin polymerization is disrupted, or when neurons are stimulated at room temperature instead of physiological temperature. In the absence of ultrafast endocytosis, synaptic vesicles are retrieved directly from the plasma membrane by clathrin-mediated endocytosis. These results may explain discrepancies among published experiments concerning the role of clathrin in synaptic vesicle endocytosis.
C1 [Watanabe, Shigeki; Davis, M. Wayne; Jorgensen, Erik M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Watanabe, Shigeki; Davis, M. Wayne; Jorgensen, Erik M.] Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA.
   [Trimbuch, Thorsten; Camacho-Perez, Marcial; Rost, Benjamin R.; Brokowski, Bettina; Soehl-Kielczynski, Berit; Felies, Annegret; Rosenmund, Christian] Charite, Neurosci Res Ctr, D-10117 Berlin, Germany.
   [Brokowski, Bettina] German Ctr Neurodegenerat Dis DZNE, D-10117 Berlin, Germany.
C3 Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Howard Hughes Medical Institute; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE)
RP Jorgensen, EM (corresponding author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
EM christian.rosenmund@charite.de; jorgensen@biology.utah.edu
FU EMBO; US National Institutes of Health [NS034307]; European Research Council grant [249939 SYNVGLUT]; German Research Council grants [Neurocure EXC 257, SFB 665, SFB 958]; National Institute of Neurological Disorders and Stroke [R01NS034307] Funding Source: NIH RePORTER
NR 50
TC 233
Z9 282
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 NOV 13
PY 2014
VL 515
IS 7526
BP 228
EP U168
DI 10.1038/nature13846
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400041
PM 25296249
DA 2026-03-09
ER

PT J
AU Lisowski, L
   Dane, AP
   Chu, K
   Zhang, Y
   Cunningham, SC
   Wilson, EM
   Nygaard, S
   Grompe, M
   Alexander, IE
   Kay, MA
AF Lisowski, Leszek
   Dane, Allison P.
   Chu, Kirk
   Zhang, Yue
   Cunningham, Sharon C.
   Wilson, Elizabeth M.
   Nygaard, Sean
   Grompe, Markus
   Alexander, Ian E.
   Kay, Mark A.
TI Selection and evaluation of clinically relevant AAV variants in a xenograft liver model
SO NATURE
LA English
DT Article
ID enhanced gene delivery; adenoassociated virus; efficient transduction; factor-ix; directed evolution; viral vectors; in-vitro; hemophilia; expression; therapy
AB Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials(1-3). The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome(4-8). Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies(4,5,8), rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.
C1 [Lisowski, Leszek; Chu, Kirk; Zhang, Yue; Kay, Mark A.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Lisowski, Leszek; Chu, Kirk; Zhang, Yue; Kay, Mark A.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Dane, Allison P.; Cunningham, Sharon C.; Alexander, Ian E.] Childrens Hosp Westmead, Gene Therapy Res Unit, Westmead, NSW 2145, Australia.
   [Dane, Allison P.; Cunningham, Sharon C.; Alexander, Ian E.] Childrens Med Res Inst, Westmead, NSW 2145, Australia.
   [Wilson, Elizabeth M.] Yecuris Corp, Portland, OR 97062 USA.
   [Nygaard, Sean; Grompe, Markus] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Portland, OR 97239 USA.
   [Alexander, Ian E.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2145, Australia.
C3 Stanford University; Stanford University; NSW Health; Sydney Childrens Hospitals Network; The Children's Hospital at Westmead; University of Sydney; Children's Medical Research Institute - Australia; Oregon Health & Science University; University of Sydney
RP Kay, MA (corresponding author), Stanford Univ, Sch Med, Dept Pediat, 269 Campus Dr, Stanford, CA 94305 USA.
EM markay@stanford.edu
FU National Institutes of Health [HL092096, HL064274, DK048252]; Berry Fellowship Foundation; Australian National Health and Medical Research Council (NHMRC) [1008021]; National Heart Lung and Blood Institute [R01HL064274] Funding Source: NIH RePORTER; National Health and Medical Research Council (NHMRC) [1008021] Funding Source: National Health and Medical Research Council (NHMRC)
NR 35
TC 376
Z9 478
U1 1
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 FEB 20
PY 2014
VL 506
IS 7488
BP 382
EP +
DI 10.1038/nature12875
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800044
PM 24390344
DA 2026-03-09
ER

PT J
AU Michaletz, ST
   Cheng, DL
   Kerkhoff, AJ
   Enquist, BJ
AF Michaletz, Sean T.
   Cheng, Dongliang
   Kerkhoff, Andrew J.
   Enquist, Brian J.
TI Convergence of terrestrial plant production across global climate gradients
SO NATURE
LA English
DT Article
ID net primary production; general quantitative theory; temperature-dependence; tropical forests; tree size; growth; ecosystem; respiration; consequences; efficiency
AB Variation in terrestrial net primary production (NPP) with climate is thought to originate from a direct influence of temperature and precipitation on plant metabolism. However, variation in NPP may also result from an indirect influence of climate by means of plant age, stand biomass, growing season length and local adaptation. To identify the relative importance of direct and indirect climate effects, we extend metabolic scaling theory to link hypothesized climate influences with NPP, and assess hypothesized relationships using a global compilation of ecosystem woody plant biomass and production data. Notably, age and biomass explained most of the variation in production whereas temperature and precipitation explained almost none, suggesting that climate indirectly (not directly) influences production. Furthermore, our theory shows that variation in NPP is characterized by a common scaling relationship, suggesting that global change models can incorporate the mechanisms governing this relationship to improve predictions of future ecosystem function.
C1 [Michaletz, Sean T.; Enquist, Brian J.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [Cheng, Dongliang] Fujian Normal Univ, Minist Educ, Key Lab Humid Subtrop Ecogeog Proc, Fuzhou 350007, Fujian, Peoples R China.
   [Kerkhoff, Andrew J.] Kenyon Coll, Dept Biol, Gambier, OH 43022 USA.
   [Enquist, Brian J.] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Enquist, Brian J.] The iPlant Collaborat, Tucson, AZ 85721 USA.
   [Enquist, Brian J.] Aspen Ctr Environm Studies, Aspen, CO 81611 USA.
C3 University of Arizona; Fujian Normal University; University System of Ohio; Kenyon College; The Santa Fe Institute
RP Enquist, BJ (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
EM chengdl@fjnu.edu.cn; benquist@email.arizona.edu
FU NSF [1065861]; Aspen Center for Environmental Studies; National Natural Science Foundation of China [31170374, 31370589]; Fujian Natural Science Funds for Distinguished Young Scholar [2013J06009]; National Science Foundation [1065861]; Emerging Frontiers; Direct For Biological Sciences [1065861] Funding Source: National Science Foundation
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NR 49
TC 322
Z9 365
U1 5
U2 421
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2014
VL 512
IS 7512
BP 39
EP +
DI 10.1038/nature13470
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000026
PM 25043056
DA 2026-03-09
ER

PT J
AU Rasmussen, M
   Anzick, SL
   Waters, MR
   Skoglund, P
   DeGiorgio, M
   Stafford, TW
   Rasmussen, S
   Moltke, I
   Albrechtsen, A
   Doyle, SM
   Poznik, GD
   Gudmundsdottir, V
   Yadav, R
   Malaspinas, AS
   White, SS
   Allentoft, ME
   Cornejo, OE
   Tambets, K
   Eriksson, A
   Heintzman, PD
   Karmin, M
   Korneliussen, TS
   Meltzer, DJ
   Pierre, TL
   Stenderup, J
   Saag, L
   Warmuth, VM
   Lopes, MC
   Malhi, RS
   Brunak, S
   Sicheritz-Ponten, T
   Barnes, I
   Collins, M
   Orlando, L
   Balloux, F
   Manica, A
   Gupta, R
   Metspalu, M
   Bustamante, CD
   Jakobsson, M
   Nielsen, R
   Willerslev, E
AF Rasmussen, Morten
   Anzick, Sarah L.
   Waters, Michael R.
   Skoglund, Pontus
   DeGiorgio, Michael
   Stafford, Thomas W., Jr.
   Rasmussen, Simon
   Moltke, Ida
   Albrechtsen, Anders
   Doyle, Shane M.
   Poznik, G. David
   Gudmundsdottir, Valborg
   Yadav, Rachita
   Malaspinas, Anna-Sapfo
   White, Samuel Stockton
   Allentoft, Morten E.
   Cornejo, Omar E.
   Tambets, Kristiina
   Eriksson, Anders
   Heintzman, Peter D.
   Karmin, Monika
   Korneliussen, Thorfinn Sand
   Meltzer, David J.
   Pierre, Tracey L.
   Stenderup, Jesper
   Saag, Lauri
   Warmuth, Vera M.
   Lopes, Margarida C.
   Malhi, Ripan S.
   Brunak, Soren
   Sicheritz-Ponten, Thomas
   Barnes, Ian
   Collins, Matthew
   Orlando, Ludovic
   Balloux, Francois
   Manica, Andrea
   Gupta, Ramneek
   Metspalu, Mait
   Bustamante, Carlos D.
   Jakobsson, Mattias
   Nielsen, Rasmus
   Willerslev, Eske
TI The genome of a Late Pleistocene human from a Clovis burial site in western Montana
SO NATURE
LA English
DT Article
ID dna; tree; age
AB Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 C-14 years before present (BP) (13,000 to 12,600 calendar years BP)(1,2). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology(3). However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans(2). An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum(4). Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 +/- 35 C-14 years BP (approximately 12,707-12,556 calendar years BP) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4x and show that the gene flow from the Siberian Upper Palaeolithic Mal'ta population(5) into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years BP. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.
C1 [Rasmussen, Morten; Stafford, Thomas W., Jr.; Malaspinas, Anna-Sapfo; Allentoft, Morten E.; Korneliussen, Thorfinn Sand; Pierre, Tracey L.; Stenderup, Jesper; Orlando, Ludovic; Willerslev, Eske] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen K, Denmark.
   [Anzick, Sarah L.] Anzick Family, Livingston, MT 59047 USA.
   [Waters, Michael R.] Texas A&M Univ, Dept Anthropol, Ctr Study Amer 1, College Stn, TX 77843 USA.
   [Waters, Michael R.] Texas A&M Univ, Dept Geog, Ctr Study Amer 1, College Stn, TX 77843 USA.
   [Skoglund, Pontus; Jakobsson, Mattias] Uppsala Univ, Dept Evolutionary Biol, S-75236 Uppsala, Sweden.
   [DeGiorgio, Michael; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Stafford, Thomas W., Jr.] Univ Aarhus, Dept Phys & Astron, AMS Dating Ctr 14C, DK-8000 Aarhus C, Denmark.
   [Rasmussen, Simon; Gudmundsdottir, Valborg; Yadav, Rachita; Brunak, Soren; Sicheritz-Ponten, Thomas; Gupta, Ramneek] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Moltke, Ida; Albrechtsen, Anders] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen N, Denmark.
   [Moltke, Ida] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Doyle, Shane M.] Montana State Univ, Dept Educ, Bozeman, MT 59717 USA.
   [Poznik, G. David] Stanford Univ, Program Biomed Informat, Stanford, CA 94305 USA.
   [Poznik, G. David] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
   [White, Samuel Stockton] Univ Montana, PhD Program, Anthropol Dept, Missoula, MT 59808 USA.
   [Cornejo, Omar E.] Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA.
   [Tambets, Kristiina; Karmin, Monika; Saag, Lauri; Metspalu, Mait] Estonian Bioctr, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Tambets, Kristiina; Karmin, Monika; Saag, Lauri; Metspalu, Mait] Univ Tartu, EE-51010 Tartu, Estonia.
   [Eriksson, Anders; Warmuth, Vera M.; Manica, Andrea] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Eriksson, Anders] King Abdullah Univ Sci & Technol, Integrat Syst Biol Lab, Thuwal 239556900, Saudi Arabia.
   [Heintzman, Peter D.; Barnes, Ian] Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
   [Meltzer, David J.] So Methodist Univ, Dept Anthropol, Dallas, TX 75275 USA.
   [Lopes, Margarida C.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Malhi, Ripan S.] Univ Illinois, Dept Anthropol, Urbana, IL 61801 USA.
   [Malhi, Ripan S.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Collins, Matthew] Univ York, BioArCh, Dept Biol, York YO10 5DD, N Yorkshire, England.
   [Collins, Matthew] Univ York, BioArCh, Dept Archaeol, York YO10 5DD, N Yorkshire, England.
   [Collins, Matthew] Univ York, BioArCh, Dept Chem, York YO10 5DD, N Yorkshire, England.
   [Balloux, Francois] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England.
   [Bustamante, Carlos D.] Stanford Univ, Littlefield Ctr, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Bustamante, Carlos D.] Stanford Univ, Littlefield Ctr, Ctr Evolutionary & Human Genom, Stanford, CA 94305 USA.
   [Jakobsson, Mattias] Uppsala Univ, Sci Life Lab, S-75236 Uppsala, Sweden.
C3 University of Copenhagen; Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; Uppsala University; University of California System; University of California Berkeley; Aarhus University; Technical University of Denmark; University of Copenhagen; University of Chicago; Montana State University System; Montana State University Bozeman; Stanford University; Stanford University; University of Montana System; University of Montana; Washington State University; Estonian Biocentre; University of Tartu; University of Cambridge; King Abdullah University of Science & Technology; University of London; Royal Holloway University London; Southern Methodist University; University of London; University College London; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of York - UK; University of York - UK; University of York - UK; Imperial College London; Stanford University; Stanford University; Uppsala University
RP Willerslev, E (corresponding author), Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
EM ewillerslev@snm.ku.dk
FU Lundbeck Foundation; Danish National Research Foundation [DNRF94]; US National Science Foundation [DBI-1103639]; Swiss National Science foundation; National Science Foundation (NSF) [DGE-1147470]; European Regional Development Fund through the Centre of Excellence in Genomics; Estonian Basic Research [SF0270177As08]; Estonian Science Foundation [8973]; SNIC-UPPMAX [b2012063]; Biotechnology and Biological Sciences Research Council [P25032, BB/H005854/1]; North Star Archaeological Research Program, Center for the Study of the First Americans, Texas AM University; E. Hill; Stafford Research, Inc.; Division Of Mathematical Sciences; Direct For Mathematical & Physical Scien [1201234] Funding Source: National Science Foundation; National Institute of Allergy and Infectious Diseases; National Library of Medicine [T15LM007033] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/H008802/1, BB/H005854/1, BB/H008802/2] Funding Source: researchfish; Lundbeck Foundation [R109-2012-9995, R155-2013-16338, R70-2010-6286, R24-2008-2527, R38-2008-3048] Funding Source: researchfish; Villum Fonden [00007171] Funding Source: researchfish; BBSRC [BB/H008802/1, BB/H005854/1, BB/H008802/2] Funding Source: UKRI
NR 29
TC 367
Z9 442
U1 2
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 FEB 13
PY 2014
VL 506
IS 7487
BP 225
EP +
DI 10.1038/nature13025
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700039
PM 24522598
DA 2026-03-09
ER

PT J
AU Fujita, Y
   Venterink, HO
   van Bodegom, PM
   Douma, JC
   Heil, GW
   Hölzel, N
   Jablonska, E
   Kotowski, W
   Okruszko, T
   Pawlikowski, P
   de Ruiter, PC
   Wassen, MJ
AF Fujita, Yuki
   Venterink, Harry Olde
   van Bodegom, Peter M.
   Douma, Jacob C.
   Heil, Gerrit W.
   Hoelzel, Norbert
   Jablonska, Ewa
   Kotowski, Wiktor
   Okruszko, Tomasz
   Pawlikowski, Pawel
   de Ruiter, Peter C.
   Wassen, Martin J.
TI Low investment in sexual reproduction threatens plants adapted to phosphorus limitation
SO NATURE
LA English
DT Article
ID biological stoichiometry; endangered plants; mineral-nutrition; life-history; nitrogen; traits; patterns; acquisition; strategy; allocation
AB Plant species diversity in Eurasian wetlands and grasslands depends not only on productivity but also on the relative availability of nutrients, particularly of nitrogen and phosphorus(1-4). Here we show that the impacts of nitrogen: phosphorus stoichiometry on plant species richness can be explained by selected plant life-history traits, notably by plant investments in growth versus reproduction. In 599 Eurasian sites with herbaceous vegetation we examined the relationship between the local nutrient conditions and community-mean life-history traits. We found that compared with plants in nitrogen-limited communities, plants in phosphorus-limited communities invest little in sexual reproduction (for example, less investment in seed, shorter flowering period, longer lifespan) and have conservative leaf economy traits (that is, a low specific leaf area and a high leaf dry-matter content). Endangered species were more frequent in phosphorus-limited ecosystems and they too invested little in sexual reproduction. The results provide new insight into how plant adaptations to nutrient conditions can drive the distribution of plant species in natural ecosystems and can account for the vulnerability of endangered species.
C1 [Fujita, Yuki] KWR Watercycle Res Inst, NL-3430 BB Nieuwegein, Netherlands.
   [Venterink, Harry Olde] Vrije Univ Brussel, B-1050 Brussels, Belgium.
   [van Bodegom, Peter M.] Vrije Univ Amsterdam, Dept Ecol Sci, NL-1081 HV Amsterdam, Netherlands.
   [Douma, Jacob C.] Wageningen Univ, Ctr Crop Syst Anal, NL-6708 PB Wageningen, Netherlands.
   [Heil, Gerrit W.] Univ Utrecht, Fac Sci, NL-3584 CC Utrecht, Netherlands.
   [Hoelzel, Norbert] Univ Munster, Fac Geosci, Inst Landscape Ecol, D-48149 Munster, Germany.
   [Jablonska, Ewa; Kotowski, Wiktor; Pawlikowski, Pawel] Univ Warsaw, Inst Bot, Dept Plant Ecol & Environm Conservat, Warsaw, Poland.
   [Okruszko, Tomasz] Warsaw Univ Life Sci, Fac Civil & Environm Engn, PL-02722 Warsaw, Poland.
   [de Ruiter, Peter C.] Wageningen Univ, NL-6700 AC Wageningen, Netherlands.
   [Wassen, Martin J.] Univ Utrecht, Copernicus Inst Sustainable Dev, Fac Geosci, NL-3508 TC Utrecht, Netherlands.
C3 KWR Watercycle Research Institute; Vrije Universiteit Brussel; Vrije Universiteit Amsterdam; Wageningen University & Research; Utrecht University; University of Munster; University of Warsaw; Warsaw University of Life Sciences; Wageningen University & Research; Utrecht University
RP Wassen, MJ (corresponding author), Univ Utrecht, Copernicus Inst Sustainable Dev, Fac Geosci, POB 80115, NL-3508 TC Utrecht, Netherlands.
EM m.j.wassen@uu.nl
FU Utrecht Centre of Geosciences; Polish Ministry of Science and Higher Education [N304 010 31/0414]
NR 59
TC 163
Z9 180
U1 9
U2 365
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 2
PY 2014
VL 505
IS 7481
BP 82
EP +
DI 10.1038/nature12733
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300028
PM 24240278
DA 2026-03-09
ER

PT J
AU Wang, Y
   Waters, J
   Leung, ML
   Unruh, A
   Roh, W
   Shi, XQ
   Chen, K
   Scheet, P
   Vattathil, S
   Liang, H
   Multani, A
   Zhang, H
   Zhao, R
   Michor, F
   Meric-Bernstam, F
   Navin, NE
AF Wang, Yong
   Waters, Jill
   Leung, Marco L.
   Unruh, Anna
   Roh, Whijae
   Shi, Xiuqing
   Chen, Ken
   Scheet, Paul
   Vattathil, Selina
   Liang, Han
   Multani, Asha
   Zhang, Hong
   Zhao, Rui
   Michor, Franziska
   Meric-Bernstam, Funda
   Navin, Nicholas E.
TI Clonal evolution in breast cancer revealed by single nucleus genome sequencing
SO NATURE
LA English
DT Article
ID growth-rate; carcinomas; mutations; heterogeneity; rearrangement; hybridization; nucleotide; patterns; express
AB Sequencing studies of breast tumour cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumours. Here we developed a whole-genome and exome single cell sequencing approach called nuc-seq that uses G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumour nuclei from an oestrogen-receptor-positive(ER+) breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumour evolution and remained highly stable as the tumour masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Using targeted single-molecule sequencing, many of the diverse mutations were shown to occur at low frequencies (<10%) in the tumour mass. Using mathematical modelling we found that the triple-negative tumour cells had an increased mutation rate (13.3x), whereas the ER+ tumour cells did not. These findings have important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer.
C1 [Wang, Yong; Waters, Jill; Leung, Marco L.; Unruh, Anna; Roh, Whijae; Shi, Xiuqing; Multani, Asha; Navin, Nicholas E.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
   [Leung, Marco L.; Scheet, Paul; Vattathil, Selina; Navin, Nicholas E.] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.
   [Chen, Ken; Liang, Han; Navin, Nicholas E.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Zhang, Hong] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Zhao, Rui; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Zhao, Rui; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
   [Meric-Bernstam, Funda] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; University of Texas Health Science Center Houston; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; University of Texas System; UTMD Anderson Cancer Center
RP Navin, NE (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
EM nnavin@mdanderson.org
FU NIH [R21CA174397-01, TR000371, U24CA143883]; NCI [1RO1CA169244-01, RO1CA172652, CA016672]; T.C. Hsu and the Alice-Reynolds Kleberg Foundation; Center for Genetics Genomics; Susan Komen [SAC10006]; PS-OC [U54CA143798]; Dell Foundation; ALA; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER
NR 51
TC 787
Z9 964
U1 3
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 AUG 14
PY 2014
VL 512
IS 7513
BP 155
EP +
DI 10.1038/nature13600
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700023
PM 25079324
DA 2026-03-09
ER

PT J
AU Stefansson, H
   Meyer-Lindenberg, A
   Steinberg, S
   Magnusdottir, B
   Morgen, K
   Arnarsdottir, S
   Bjornsdottir, G
   BragiWalters, G
   Jonsdottir, GA
   Doyle, OM
   Tost, H
   Grimm, O
   Kristjansdottir, S
   Snorrason, H
   Davidsdottir, SR
   Gudmundsson, LJ
   Jonsson, GF
   Stefansdottir, B
   Helgadottir, I
   Haraldsson, M
   Jonsdottir, B
   Thygesen, JH
   Schwarz, AJ
   Didriksen, M
   Stensbol, TB
   Brammer, M
   Kapur, S
   Halldorsson, JG
   Hreidarsson, S
   Saemundsen, E
   Sigurdsson, E
   Stefansson, K
AF Stefansson, Hreinn
   Meyer-Lindenberg, Andreas
   Steinberg, Stacy
   Magnusdottir, Brynja
   Morgen, Katrin
   Arnarsdottir, Sunna
   Bjornsdottir, Gyda
   BragiWalters, G.
   Jonsdottir, Gudrun A.
   Doyle, Orla M.
   Tost, Heike
   Grimm, Oliver
   Kristjansdottir, Solveig
   Snorrason, Heimir
   Davidsdottir, Solveig R.
   Gudmundsson, Larus J.
   Jonsson, Gudbjorn F.
   Stefansdottir, Berglind
   Helgadottir, Isafold
   Haraldsson, Magnus
   Jonsdottir, Birna
   Thygesen, Johan H.
   Schwarz, Adam J.
   Didriksen, Michael
   Stensbol, Tine B.
   Brammer, Michael
   Kapur, Shitij
   Halldorsson, Jonas G.
   Hreidarsson, Stefan
   Saemundsen, Evald
   Sigurdsson, Engilbert
   Stefansson, Kari
TI CNVs conferring risk of autism or schizophrenia affect cognition in controls
SO NATURE
LA English
DT Article
ID spatial working-memory; recurrent microdeletions; global assessment; deficits; 16p11.2; metaanalysis; psychosis; relatives; 15q11.2
AB In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
C1 [Stefansson, Hreinn; Steinberg, Stacy; Arnarsdottir, Sunna; Bjornsdottir, Gyda; BragiWalters, G.; Jonsdottir, Gudrun A.; Kristjansdottir, Solveig; Snorrason, Heimir; Gudmundsson, Larus J.; Jonsson, Gudbjorn F.; Stefansdottir, Berglind; Stefansson, Kari] deCODE Genet Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland.
   [Meyer-Lindenberg, Andreas; Morgen, Katrin; Tost, Heike; Grimm, Oliver] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany.
   [Magnusdottir, Brynja; Arnarsdottir, Sunna; Davidsdottir, Solveig R.; Helgadottir, Isafold; Haraldsson, Magnus; Sigurdsson, Engilbert] Natl Univ Hosp Reykjavik, Dept Psychiat, Landspitali, IS-101 Reykjavik, Iceland.
   [Doyle, Orla M.; Brammer, Michael; Kapur, Shitij] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Haraldsson, Magnus; Halldorsson, Jonas G.; Saemundsen, Evald; Sigurdsson, Engilbert] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [Jonsdottir, Birna] Rontgen Domus, IS-101 Reykjavik, Iceland.
   [Thygesen, Johan H.] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, iPSYCH, DK-4000 Roskilde, Denmark.
   [Schwarz, Adam J.] Eli Lilly & Co, Tailored Therapeut, Lilly Res Labs, Lilly Corp Ctr DC 1940, Indianapolis, IN 46285 USA.
   [Didriksen, Michael; Stensbol, Tine B.] H Lundbeck & Co AS, DK-2500 Valby, Denmark.
   [Hreidarsson, Stefan; Saemundsen, Evald] State Diagnost & Counselling Ctr, IS-200 Kopavogur, Iceland.
C3 Decode Genetics; Central Institute of Mental Health; Ruprecht Karls University Heidelberg; University of London; King's College London; University of Iceland; Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH); University of Copenhagen; Copenhagen University Hospital; Eli Lilly; Lilly Research Laboratories; Lundbeck Corporation
RP Stefansson, K (corresponding author), deCODE Genet Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland.
EM A.Meyer-Lindenberg@zi-mannheim.de; kstefans@decode.is
FU Innovative Medicines Initiative Joint Undertaking [115008]; European Union; EU [PsychDPC (GA 286213)]; MRC [G0701748] Funding Source: UKRI; Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish; Medical Research Council [G0701748] Funding Source: researchfish
NR 48
TC 512
Z9 575
U1 1
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 JAN 16
PY 2014
VL 505
IS 7483
BP 361
EP +
DI 10.1038/nature12818
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800034
PM 24352232
DA 2026-03-09
ER

PT J
AU Jacobson, SA
   Morbidelli, A
   Raymond, SN
   O'Brien, DP
   Walsh, KJ
   Rubie, DC
AF Jacobson, Seth A.
   Morbidelli, Alessandro
   Raymond, Sean N.
   O'Brien, David P.
   Walsh, Kevin J.
   Rubie, David C.
TI Highly siderophile elements in Earth's mantle as a clock for the Moon-forming impact
SO NATURE
LA English
DT Article
ID terrestrial planet formation; core formation; solar-system; giant impact; isotopic composition; oxygen-isotope; late veneer; accretion; metal; silicate
AB According to the generally accepted scenario, the last giant impact on Earth formed the Moon and initiated the final phase of core formation by melting Earth's mantle. A key goal of geochemistry is to date this event, but different ages have been proposed. Some(1-3) argue for an early Moon-forming event, approximately 30 million years (Myr) after the condensation of the first solids in the Solar System, whereas others(4-6) claim a date later than 50 Myr (and possibly as late as around 100 Myr) after condensation. Here we show that a Moon-forming event at 40 Myr after condensation, or earlier, is ruled out at a 99.9 per cent confidence level. We use a large number of N-body simulations to demonstrate a relationship between the time of the last giant impact on an Earth-like planet and the amount of mass subsequently added during the era known as Late Accretion. As the last giant impact is delayed, the late-accreted mass decreases in a predictable fashion. This relationship exists within both the classical scenario(7,8) and the Grand Tack scenario(9,10) of terrestrial planet formation, and holds across a wide range of disk conditions. The concentration of highly siderophile elements (HSEs) in Earth's mantle constrains the mass of chondritic material added to Earth during Late Accretion(11,12). Using HSE abundance measurements(13,14), we determine a Moon-formation age of 95 +/- 32 Myr after condensation. The possibility exists that some late projectiles were differentiated and left an incomplete HSE record in Earth's mantle. Even in this case, various isotopic constraints strongly suggest that the late-accreted mass did not exceed 1 per cent of Earth's mass, and so the HSE clock still robustly limits the timing of the Moon-forming event to significantly later than 40 Myr after condensation.
C1 [Jacobson, Seth A.; Morbidelli, Alessandro] Observ Cote Azur, Lab Lagrange, F-06304 Nice 4, France.
   [Jacobson, Seth A.; Rubie, David C.] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
   [Raymond, Sean N.] Univ Bordeaux, Lab Astrophys Bordeaux, UMR 5804, F-33270 Floirac, France.
   [Raymond, Sean N.] CNRS, Lab Astrophys Bordeaux, UMR 5804, F-33270 Floirac, France.
   [O'Brien, David P.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Walsh, Kevin J.] Planetary Sci Directorate, SW Res Inst, Boulder, CO 80302 USA.
C3 Universite Cote d'Azur; Observatoire de la Cote d'Azur; University of Bayreuth; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Jacobson, SA (corresponding author), Observ Cote Azur, Lab Lagrange, Blvd Observ,BP 4229, F-06304 Nice 4, France.
EM seth.jacobson@oca.eu
FU European Research Council [290568]; NASA's Planetary Geology and Geophysics research programme [NNX09AE36G]; NASA Astrobiology Institute's Virtual Planetary Laboratory lead team; NASA [NNH05ZDA001C]; NASA [119851, NNX09AE36G] Funding Source: Federal RePORTER; European Research Council (ERC) [290568] Funding Source: European Research Council (ERC)
NR 80
TC 168
Z9 188
U1 0
U2 126
PU NATURE PUBLISHING 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 3
PY 2014
VL 508
IS 7494
BP 84
EP +
DI 10.1038/nature13172
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900047
PM 24695310
DA 2026-03-09
ER

PT J
AU Wang, D
   Pan, K
   Subedi, R
   Deng, X
   Ahmed, Z
   Allada, K
   Aniol, KA
   Armstrong, DS
   Arrington, J
   Bellini, V
   Beminiwattha, R
   Benesch, J
   Benmokhtar, F
   Bertozzi, W
   Camsonne, A
   Canan, M
   Cates, GD
   Chen, JP
   Chudakov, E
   Cisbani, E
   Dalton, MM
   de Jager, CW
   De Leo, R
   Deconinck, W
   Deur, A
   Dutta, C
   El Fassi, L
   Erler, J
   Flay, D
   Franklin, GB
   Friend, M
   Frullani, S
   Garibaldi, F
   Gilad, S
   Giusa, A
   Glamazdin, A
   Golge, S
   Grimm, K
   Hafidi, K
   Hansen, JO
   Higinbotham, DW
   Holmes, R
   Holmstrom, T
   Holt, RJ
   Huang, J
   Hyde, CE
   Jen, CM
   Jones, D
   Kang, H
   King, PM
   Kowalski, S
   Kumar, KS
   Lee, JH
   LeRose, JJ
   Liyanage, N
   Long, E
   McNulty, D
   Margaziotis, DJ
   Meddi, F
   Meekins, DG
   Mercado, L
   Meziani, ZE
   Michaels, R
   Mihovilovic, M
   Muangma, N
   Myers, KE
   Nanda, S
   Narayan, A
   Nelyubin, V
   Nuruzzaman
   Oh, Y
   Parno, D
   Paschke, KD
   Phillips, SK
   Qian, X
   Qiang, Y
   Quinn, B
   Rakhman, A
   Reimer, PE
   Rider, K
   Riordan, S
   Roche, J
   Rubin, J
   Russo, G
   Saenboonruang, K
   Saha, A
   Sawatzky, B
   Shahinyan, A
   Silwal, R
   Sirca, S
   Souder, PA
   Suleiman, R
   Sulkosky, V
   Sutera, CM
   Tobias, WA
   Urciuoli, GM
   Waidyawansa, B
   Wojtsekhowski, B
   Ye, L
   Zhao, B
   Zheng, X
AF Wang, D.
   Pan, K.
   Subedi, R.
   Deng, X.
   Ahmed, Z.
   Allada, K.
   Aniol, K. A.
   Armstrong, D. S.
   Arrington, J.
   Bellini, V.
   Beminiwattha, R.
   Benesch, J.
   Benmokhtar, F.
   Bertozzi, W.
   Camsonne, A.
   Canan, M.
   Cates, G. D.
   Chen, J. -P.
   Chudakov, E.
   Cisbani, E.
   Dalton, M. M.
   de Jager, C. W.
   De Leo, R.
   Deconinck, W.
   Deur, A.
   Dutta, C.
   El Fassi, L.
   Erler, J.
   Flay, D.
   Franklin, G. B.
   Friend, M.
   Frullani, S.
   Garibaldi, F.
   Gilad, S.
   Giusa, A.
   Glamazdin, A.
   Golge, S.
   Grimm, K.
   Hafidi, K. D.
   Hansen, J. O.
   Higinbotham, D. W.
   Holmes, R.
   Holmstrom, T.
   Holt, R. J.
   Huang, J.
   Hyde, C. E.
   Jen, C. M.
   Jones, D.
   Kang, Hoyoung
   King, P. M.
   Kowalski, S.
   Kumar, K. S.
   Lee, J. H.
   LeRose, J. J.
   Liyanage, N.
   Long, E.
   McNulty, D.
   Margaziotis, D. J.
   Meddi, F.
   Meekins, D. G.
   Mercado, L.
   Meziani, Z. -E.
   Michaels, R.
   Mihovilovic, M.
   Muangma, N.
   Myers, K. E.
   Nanda, S.
   Narayan, A.
   Nelyubin, V.
   Nuruzzaman
   Oh, Y.
   Parno, D.
   Paschke, K. D.
   Phillips, S. K.
   Qian, X.
   Qiang, Y.
   Quinn, B.
   Rakhman, A.
   Reimer, P. E.
   Rider, K.
   Riordan, S.
   Roche, J.
   Rubin, J.
   Russo, G.
   Saenboonruang, K.
   Saha, A.
   Sawatzky, B.
   Shahinyan, A.
   Silwal, R.
   Sirca, S.
   Souder, P. A.
   Suleiman, R.
   Sulkosky, V.
   Sutera, C. M.
   Tobias, W. A.
   Urciuoli, G. M.
   Waidyawansa, B.
   Wojtsekhowski, B.
   Ye, L.
   Zhao, B.
   Zheng, X.
TI Measurement of parity violation in electron-quark scattering
SO NATURE
LA English
DT Article
ID contact interactions; weak; conservation; collisions; nonconservation; symmetry; search; tests
AB Symmetry permeates nature and is fundamental to all laws of physics. One example is parity (mirror) symmetry, which implies that flipping left and right does not change the laws of physics. Laws for electromagnetism, gravity and the subatomic strong force respect parity symmetry, but the subatomic weak force does not(1,2). Historically, parity violation in electron scattering has been important in establishing (and now testing) the standard model of particle physics. One particular set of quantities accessible through measurements of parity-violating electron scattering are the effective weak couplings C-2q, sensitive to the quarks' chirality preference when participating in the weak force, which have been measured directly(3,4) only once in the past 40 years. Here we report a measurement of the parity-violating asymmetry in electron-quark scattering, which yields a determination of 2C(2u)-C-2d (where u and d denote up and down quarks, respectively) with a precision increased by a factor of five relative to the earlier result. These results provide evidence with greater than 95 per cent confidence that the C-2q couplings are non-zero, as predicted by the electroweak theory. They lead to constraints on new parity-violating interactions beyond the standard model, particularly those due to quark chirality. Whereas contemporary particle physics research is focused on high-energy colliders such as the Large Hadron Collider, our results provide specific chirality information on electroweak theory that is difficult to obtain at high energies. Our measurement is relatively free of ambiguity in its interpretation, and opens the door to even more precise measurements in the future.
C1 [Wang, D.; Subedi, R.; Deng, X.; Cates, G. D.; Dalton, M. M.; de Jager, C. W.; Jones, D.; Liyanage, N.; Nelyubin, V.; Paschke, K. D.; Riordan, S.; Saenboonruang, K.; Silwal, R.; Tobias, W. A.; Zheng, X.] Univ Virginia, Charlottesville, VA 22904 USA.
   [Pan, K.; Bertozzi, W.; Deconinck, W.; Gilad, S.; Huang, J.; Kowalski, S.; Muangma, N.; Sulkosky, V.] MIT, Cambridge, MA 02139 USA.
   [Ahmed, Z.; Holmes, R.; Jen, C. M.; Rakhman, A.; Souder, P. A.] Syracuse Univ, Syracuse, NY 13244 USA.
   [Allada, K.; Dutta, C.] Univ Kentucky, Lexington, KY 40506 USA.
   [Aniol, K. A.; Margaziotis, D. J.] Calif State Univ Los Angeles, Los Angeles, CA 90032 USA.
   [Armstrong, D. S.; Lee, J. H.; Zhao, B.] Coll William & Mary, Williamsburg, VA 23187 USA.
   [Arrington, J.; Holt, R. J.; Reimer, P. E.; Rubin, J.] Argonne Natl Lab, Div Phys, Argonne, IL 60439 USA.
   [Bellini, V.; Giusa, A.; Russo, G.; Sutera, C. M.] Univ Catania, Ist Nazl Fis Nucl, Dipt Fis, I-95123 Catania, Italy.
   [Beminiwattha, R.; King, P. M.; Lee, J. H.; Roche, J.; Waidyawansa, B.] Ohio Univ, Athens, OH 45701 USA.
   [Benesch, J.; Camsonne, A.; Chen, J. -P.; Chudakov, E.; de Jager, C. W.; Deur, A.; Hansen, J. O.; Higinbotham, D. W.; LeRose, J. J.; Meekins, D. G.; Michaels, R.; Nanda, S.; Saha, A.; Sawatzky, B.; Suleiman, R.; Wojtsekhowski, B.] Thomas Jefferson Natl Accelerator Facil, Newport News, VA 23606 USA.
   [Benmokhtar, F.; Franklin, G. B.; Friend, M.; Parno, D.; Quinn, B.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
   [Canan, M.; Golge, S.; Hyde, C. E.] Old Dominion Univ, Norfolk, VA 23529 USA.
   [Cisbani, E.; Frullani, S.; Garibaldi, F.] Ist Nazl Fis Nucl, Sez Roma, Grp Sanita, I-00161 Rome, Italy.
   [Cisbani, E.; Frullani, S.; Garibaldi, F.] Ist Super Sanita, I-00161 Rome, Italy.
   [De Leo, R.] Univ Bari, I-70126 Bari, Italy.
   [El Fassi, L.] Rutgers State Univ, Newark, NJ 07102 USA.
   [Erler, J.] Univ Nacl Autonoma Mexico, Inst Fis, Mexico City 04510, DF, Mexico.
   [Flay, D.; Meziani, Z. -E.] Temple Univ, Philadelphia, PA 19122 USA.
   [Glamazdin, A.] Kharkov Phys & Technol Inst, UA-61108 Kharkov, Ukraine.
   [Grimm, K.] Louisiana Tech Univ, Ruston, LA 71272 USA.
   [Holmstrom, T.; Rider, K.] Longwood Univ, Farmville, VA 23909 USA.
   [Hyde, C. E.] Univ Blaise Pascal, Clermont Univ, CNRS IN2P3, Lab Phys Corpusculaire, FR-63000 Clermont Ferrand, France.
   [Kang, Hoyoung; Oh, Y.] Seoul Natl Univ, Seoul 151742, South Korea.
   [Kumar, K. S.; McNulty, D.; Mercado, L.] Univ Massachusetts, Amherst, MA 01003 USA.
   [Long, E.] Kent State Univ, Kent, OH 44242 USA.
   [Meddi, F.; Urciuoli, G. M.] Ist Nazl Fis Nucl, Sez Roma, I-00161 Rome, Italy.
   [Meddi, F.; Urciuoli, G. M.] Univ Roma La Sapienza, I-00161 Rome, Italy.
   [Mihovilovic, M.; Sirca, S.] Jozef Stefan Inst, SI-1001 Ljubljana, Slovenia.
   [Myers, K. E.] George Washington Univ, Washington, DC 20052 USA.
   [Narayan, A.; Nuruzzaman] Mississippi State Univ, Starkeville, MS 39762 USA.
   [Phillips, S. K.] Univ New Hampshire, Durham, NH 03824 USA.
   [Qian, X.; Qiang, Y.] Duke Univ, Durham, NC 27708 USA.
   [Shahinyan, A.] Yerevan Phys Inst, Yerevan 0036, Armenia.
   [Ye, L.] China Inst Atom Energy, Beijing 102413, Peoples R China.
C3 University of Virginia; Massachusetts Institute of Technology (MIT); Syracuse University; University of Kentucky; California State University System; California State University Los Angeles; William & Mary; United States Department of Energy (DOE); Argonne National Laboratory; Istituto Nazionale di Fisica Nucleare (INFN); University of Catania; University System of Ohio; Ohio University; United States Department of Energy (DOE); Jefferson National Accelerator; Carnegie Mellon University; Old Dominion University; Istituto Nazionale di Fisica Nucleare (INFN); Istituto Superiore di Sanita (ISS); Universita degli Studi di Bari Aldo Moro; Rutgers University System; Rutgers University Newark; Rutgers University New Brunswick; Universidad Nacional Autonoma de Mexico; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; Kharkov Institute of Physics & Technology; University of Louisiana System; Louisiana Technical University; Longwood University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite Clermont Auvergne (UCA); Seoul National University (SNU); University of Massachusetts System; University of Massachusetts Amherst; University System of Ohio; Kent State University; Kent State University Salem; Kent State University Kent; Istituto Nazionale di Fisica Nucleare (INFN); Sapienza University Rome; Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute; George Washington University; Mississippi State University; University System Of New Hampshire; University of New Hampshire; Duke University; Yerevan Physics Institute; China Institute of Atomic Energy
RP Zheng, X (corresponding author), Univ Virginia, Charlottesville, VA 22904 USA.
EM xz5y@virginia.edu
FU Medium Energy Physics Group at the Argonne National Laboratory; PAPIIT (DGAPAUNAM) [IN106913]; CONACyT (Mexico) [151234]; Mainz Institute for Theoretical Physics (MITP); Jeffress Memorial Trust [J-836]; US NSF [0653347]; US DOE [DE-SC0003885, DE-AC02-06CH11357, DE-AC05-06OR23177]; Direct For Mathematical & Physical Scien; Division Of Physics [1068667, 1306376, 0653347] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1206053, 1206082] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0003885] Funding Source: U.S. Department of Energy (DOE)
NR 27
TC 97
Z9 103
U1 1
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 FEB 6
PY 2014
VL 506
IS 7486
BP 67
EP 70
DI 10.1038/nature12964
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100032
PM 24499917
DA 2026-03-09
ER

PT J
AU Warren, TK
   Wells, J
   Panchal, RG
   Stuthman, KS
   Garza, NL
   Van Tongeren, SA
   Dong, L
   Retterer, CJ
   Eaton, BP
   Pegoraro, G
   Honnold, S
   Bantia, S
   Kotian, P
   Chen, XL
   Taubenheim, BR
   Welch, LS
   Minning, DM
   Babu, YS
   Sheridan, WP
   Bavari, S
AF Warren, Travis K.
   Wells, Jay
   Panchal, Rekha G.
   Stuthman, Kelly S.
   Garza, Nicole L.
   Van Tongeren, Sean A.
   Dong, Lian
   Retterer, Cary J.
   Eaton, Brett P.
   Pegoraro, Gianluca
   Honnold, Shelley
   Bantia, Shanta
   Kotian, Pravin
   Chen, Xilin
   Taubenheim, Brian R.
   Welch, Lisa S.
   Minning, Dena M.
   Babu, Yarlagadda S.
   Sheridan, William P.
   Bavari, Sina
TI Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430
SO NATURE
LA English
DT Article
ID small-molecule inhibitor; ebola-virus infection; nonhuman-primates; hemorrhagic-fever; marburg-virus; postexposure protection; antiviral activity; mouse model; replication; challenge
AB Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats.
C1 [Warren, Travis K.; Wells, Jay; Panchal, Rekha G.; Stuthman, Kelly S.; Garza, Nicole L.; Van Tongeren, Sean A.; Dong, Lian; Retterer, Cary J.; Eaton, Brett P.; Pegoraro, Gianluca; Honnold, Shelley; Welch, Lisa S.; Bavari, Sina] US Army Med Res Inst Infect Dis USAMRIID, Therapeut Discovery Ctr, Div Mol & Translat Sci, Ft Detrick, MD 21702 USA.
   [Bantia, Shanta; Kotian, Pravin; Chen, Xilin; Taubenheim, Brian R.; Babu, Yarlagadda S.; Sheridan, William P.] BioCryst Pharmaceut Inc, Durham, NC 27703 USA.
   [Minning, Dena M.] MedExpert Consulting Inc, Indialantic, FL 32903 USA.
C3 BioCryst Pharmaceuticals, Inc.
RP Bavari, S (corresponding author), US Army Med Res Inst Infect Dis USAMRIID, Therapeut Discovery Ctr, Div Mol & Translat Sci, Ft Detrick, MD 21702 USA.
EM sina.bavari.civ@mail.mil
FU Science and Technology Office for Chemical and Biological Defense of the Defense Threat Reduction Agency [TMTI0048_09_RD_T, CB3675]; National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272201100019I]; BioQual Inc. under NIAID [HHSN27220110005I]; University of Alabama Birmingham under NIAID [HHSN272201100016I]
NR 29
TC 469
Z9 593
U1 0
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 APR 17
PY 2014
VL 508
IS 7496
BP 402
EP +
DI 10.1038/nature13027
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000053
PM 24590073
DA 2026-03-09
ER

PT J
AU Parker, HJ
   Bronner, ME
   Krumlauf, R
AF Parker, Hugo J.
   Bronner, Marianne E.
   Krumlauf, Robb
TI A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates
SO NATURE
LA English
DT Article
ID gene-expression; transcriptional control; evolution; lamprey; insights; elements; cluster; origins; genome; krox20
AB A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree(1-3). It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation(4-6). However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.
C1 [Parker, Hugo J.; Krumlauf, Robb] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Bronner, Marianne E.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
   [Krumlauf, Robb] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; California Institute of Technology; University of Kansas; University of Kansas Medical Center
RP Krumlauf, R (corresponding author), Stowers Inst Med Res, Kansas City, MO 64110 USA.
EM rek@Stowers.org
FU Stowers Institute [2013-1001];  [R01N5086907];  [R01DE017911]
NR 39
TC 81
Z9 88
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 OCT 23
PY 2014
VL 514
IS 7523
BP 490
EP +
DI 10.1038/nature13723
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900040
PM 25219855
DA 2026-03-09
ER

PT J
AU Correia, BE
   Bates, JT
   Loomis, RJ
   Baneyx, G
   Carrico, C
   Jardine, JG
   Rupert, P
   Correnti, C
   Kalyuzhniy, O
   Vittal, V
   Connell, MJ
   Stevens, E
   Schroeter, A
   Chen, M
   MacPherson, S
   Serra, AM
   Adachi, Y
   Holmes, MA
   Li, YX
   Klevit, RE
   Graham, BS
   Wyatt, RT
   Baker, D
   Strong, RK
   Crowe, JE
   Johnson, PR
   Schief, WR
AF Correia, Bruno E.
   Bates, John T.
   Loomis, Rebecca J.
   Baneyx, Gretchen
   Carrico, Chris
   Jardine, Joseph G.
   Rupert, Peter
   Correnti, Colin
   Kalyuzhniy, Oleksandr
   Vittal, Vinayak
   Connell, Mary J.
   Stevens, Eric
   Schroeter, Alexandria
   Chen, Man
   MacPherson, Skye
   Serra, Andreia M.
   Adachi, Yumiko
   Holmes, Margaret A.
   Li, Yuxing
   Klevit, Rachel E.
   Graham, Barney S.
   Wyatt, Richard T.
   Baker, David
   Strong, Roland K.
   Crowe, James E., Jr.
   Johnson, Philip R.
   Schief, William R.
TI Proof of principle for epitope-focused vaccine design
SO NATURE
LA English
DT Article
ID syncytial virus rsv; neutralizing antibody; computational design; protein; infection; motavizumab; induction; scaffolds; program; burden
AB Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.
C1 [Correia, Bruno E.; Baneyx, Gretchen; Jardine, Joseph G.; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Stevens, Eric; Schroeter, Alexandria; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Klevit, Rachel E.; Baker, David; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Correia, Bruno E.] Univ Nova Lisboa, Inst Gulbenkian Ciencia, PhD Program Computat Biol, P-2780157 Oeiras, Portugal.
   [Correia, Bruno E.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal.
   [Correia, Bruno E.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Bates, John T.; Crowe, James E., Jr.] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Med Ctr, Nashville, TN 37232 USA.
   [Loomis, Rebecca J.; Connell, Mary J.; Johnson, Philip R.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
   [Carrico, Chris; Rupert, Peter; Correnti, Colin; Strong, Roland K.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Jardine, Joseph G.; MacPherson, Skye; Serra, Andreia M.; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Jardine, Joseph G.; Kalyuzhniy, Oleksandr; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Jardine, Joseph G.; Kalyuzhniy, Oleksandr; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Li, Yuxing; Wyatt, Richard T.; Schief, William R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
   [Chen, Man; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Crowe, James E., Jr.] Vanderbilt Univ Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
   [Crowe, James E., Jr.] Vanderbilt Univ Sch Med, Dept Pediat, Nashville, TN 37232 USA.
C3 University of Washington; University of Washington Seattle; Instituto Gulbenkian de Ciencia; Universidade Nova de Lisboa; Universidade Nova de Lisboa; Scripps Research Institute; Vanderbilt University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Fred Hutchinson Cancer Center; Scripps Research Institute; Scripps Research Institute; International AIDS Vaccine Initiative; Scripps Research Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Vanderbilt University; Vanderbilt University
RP Schief, WR (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM schief@scripps.edu
FU Fundacao para a Ciencia e a Tecnologia [SFRH/BD/32958/2006]; National Institutes of Health NRSA Training Grant [T32CA080416]; Children's Hospital of Philadelphia; Bill and Melinda Gates Foundation CAVD award; International AIDS Vaccine Initiative Neutralizing Antibody Consortium; International AIDS Vaccine Initiative Neutralizing Antibody Center; March of Dimes; National Institutes of Health [2T32GM007270, U54 AI 005714]; National Institute of Allergy and Infectious Diseases [P01AI094419, 5R21AI088554, 1UM1AI100663, 1R01AI102766-01A1]; National Institute of Allergy and Infectious Diseases from the Center for AIDS Research, University of California, San Diego [P30AI36214]; Fundação para a Ciência e a Tecnologia [SFRH/BD/32958/2006] Funding Source: FCT; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Institute of Allergy and Infectious Diseases; National Institute on Minority Health and Health Disparities; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Cancer Institute; National Institute of Nursing Research [P30AI036214] Funding Source: NIH RePORTER; National Cancer Institute [T32CA080416] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Drug Abuse; National Institute on Minority Health and Health Disparities; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging [P30AI045008] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI102766] Funding Source: NIH RePORTER
NR 39
TC 428
Z9 542
U1 1
U2 228
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2014
VL 507
IS 7491
BP 201
EP 206
DI 10.1038/nature12966
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800032
PM 24499818
DA 2026-03-09
ER

PT J
AU Liu, PD
   Begley, M
   Michowski, W
   Inuzuka, H
   Ginzberg, M
   Gao, DM
   Tsou, PL
   Gan, WJ
   Papa, A
   Kim, BM
   Wan, LX
   Singh, A
   Zhai, B
   Yuan, M
   Wang, ZW
   Gygi, SP
   Lee, TH
   Lu, KP
   Toker, A
   Pandolfi, PP
   Asara, JM
   Kirschner, MW
   Sicinski, P
   Cantley, L
   Wei, WY
AF Liu, Pengda
   Begley, Michael
   Michowski, Wojciech
   Inuzuka, Hiroyuki
   Ginzberg, Miriam
   Gao, Daming
   Tsou, Peiling
   Gan, Wenjian
   Papa, Antonella
   Kim, Byeong Mo
   Wan, Lixin
   Singh, Amrik
   Zhai, Bo
   Yuan, Min
   Wang, Zhiwei
   Gygi, Steven P.
   Lee, Tae Ho
   Lu, Kun-Ping
   Toker, Alex
   Pandolfi, Pier Paolo
   Asara, John M.
   Kirschner, Marc W.
   Sicinski, Piotr
   Cantley, Lewis
   Wei, Wenyi
TI Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus
SO NATURE
LA English
DT Article
ID promotes; skp2; identification; mechanisms; inhibitor; proteins; insights; akt/pkb; pathway; complex
AB Akt, also known as protein kinase B, plays key roles in cell proliferation, survival and metabolism. Akt hyperactivation contributes to many pathophysiological conditions, including human cancers(1-3), and is closely associated with poor prognosis and chemo-or radio-therapeutic resistance(4). Phosphorylation of Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear whether further mechanisms account for full Akt activation, and whether Akt hyperactivation is linked to misregulated cell cycle progression, another cancer hallmark(7). Here we report that Akt activity fluctuates across the cell cycle, mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479 at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promotes Akt activation through facilitating, or functionally compensating for, S473 phosphorylation. Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably, cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2 in governing Akt activation. Together, the results of our study show Akt S477/T479 phosphorylation to be an essential layer of the Akt activation mechanism to regulate its physiological functions, thereby providing a new mechanistic link between aberrant cell cycle progression and Akt hyperactivation in cancer.
C1 [Liu, Pengda; Inuzuka, Hiroyuki; Gao, Daming; Gan, Wenjian; Papa, Antonella; Wan, Lixin; Wang, Zhiwei; Toker, Alex; Pandolfi, Pier Paolo; Wei, Wenyi] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Begley, Michael; Tsou, Peiling; Papa, Antonella; Yuan, Min; Lu, Kun-Ping; Pandolfi, Pier Paolo; Asara, John M.; Cantley, Lewis] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Begley, Michael; Tsou, Peiling; Kirschner, Marc W.; Cantley, Lewis] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Michowski, Wojciech; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Michowski, Wojciech; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Ginzberg, Miriam; Zhai, Bo; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Canc Genet Program, Dept Med, Boston, MA 02115 USA.
   [Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Div Genet, Dept Med, Boston, MA 02115 USA.
   [Singh, Amrik] Cell Signaling Technol, Danvers, MA 01923 USA.
   [Kim, Byeong Mo; Lee, Tae Ho] Beth Israel Deaconess Med Ctr, Div Gerontol, Dept Med, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; 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; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; 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; Cell Signaling Technology; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Wei, WY (corresponding author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
EM wwei2@bidmc.harvard.edu
FU National Institutes of Health [GM089763, GM094777, CA177910, 2P01CA120964, R01CA132740];  [5T32HL007893]; National Cancer Institute [P01CA120964, R01CA177910] Funding Source: NIH RePORTER
NR 45
TC 292
Z9 339
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 APR 24
PY 2014
VL 508
IS 7497
BP 541
EP +
DI 10.1038/nature13079
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600040
PM 24670654
DA 2026-03-09
ER

PT J
AU Fu, QM
   Li, H
   Moorjani, P
   Jay, F
   Slepchenko, SM
   Bondarev, AA
   Johnson, PLF
   Aximu-Petri, A
   Prüfer, K
   de Filippo, C
   Meyer, M
   Zwyns, N
   Salazar-García, DC
   Kuzmin, YV
   Keates, SG
   Kosintsev, PA
   Razhev, DI
   Richards, MP
   Peristov, NV
   Lachmann, M
   Douka, K
   Higham, TFG
   Slatkin, M
   Hublin, JJ
   Reich, D
   Kelso, J
   Viola, TB
   Pääbo, S
AF Fu, Qiaomei
   Li, Heng
   Moorjani, Priya
   Jay, Flora
   Slepchenko, Sergey M.
   Bondarev, Aleksei A.
   Johnson, Philip L. F.
   Aximu-Petri, Ayinuer
   Pruefer, Kay
   de Filippo, Cesare
   Meyer, Matthias
   Zwyns, Nicolas
   Salazar-Garcia, Domingo C.
   Kuzmin, Yaroslav V.
   Keates, Susan G.
   Kosintsev, Pavel A.
   Razhev, Dmitry I.
   Richards, Michael P.
   Peristov, Nikolai V.
   Lachmann, Michael
   Douka, Katerina
   Higham, Thomas F. G.
   Slatkin, Montgomery
   Hublin, Jean-Jacques
   Reich, David
   Kelso, Janet
   Viola, T. Bence
   Paeaebo, Svante
TI Genome sequence of a 45,000-year-old modern human from western Siberia
SO NATURE
LA English
DT Article
ID human-evolution; human dispersals; history; asia; divergence; admixture; europe
AB We present the high-quality genome sequence of a similar to 45,000-year-old modern human male from Siberia. This individual derives from a population that lived before-or simultaneously with-the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000-13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 x 10(-9) to 0.6 x 10(-9) per site per year, a Y chromosomal mutation rate of 0.7 x 10(-9) to 0.9 x 10(-9) per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 x 10(-8) to 3.2 x 10(-8) per site per year based on the age of the bone.
C1 [Fu, Qiaomei] Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Fu, Qiaomei; Aximu-Petri, Ayinuer; Pruefer, Kay; de Filippo, Cesare; Meyer, Matthias; Lachmann, Michael; Kelso, Janet; Viola, T. Bence; Paeaebo, Svante] Max Planck Inst Evolutionare Anthropol, Dept EvolutionaryGenet, D-04103 Leipzig, Germany.
   [Li, Heng; Moorjani, Priya; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Li, Heng; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Moorjani, Priya] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Jay, Flora; Slatkin, Montgomery] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Slepchenko, Sergey M.; Razhev, Dmitry I.] Russian Acad Sci, Siberian Branch, Inst Problems Dev North, Tyumen 625026, Russia.
   [Bondarev, Aleksei A.] Minist Internal Affairs, Omsk Div, Expert Criminalist Ctr, Omsk 644007, Russia.
   [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
   [Zwyns, Nicolas; Salazar-Garcia, Domingo C.; Richards, Michael P.; Hublin, Jean-Jacques; Viola, T. Bence] Max Planck Inst Evolutionare Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Zwyns, Nicolas] Univ Calif Davis, Dept Anthropol, Davis, CA 95616 USA.
   [Salazar-Garcia, Domingo C.] Univ Cape Town, Dept Archaeol, ZA-7701 Cape Town, South Africa.
   [Salazar-Garcia, Domingo C.] Univ Valencia, Dept Prehist & Arqueol, Valencia 46010, Spain.
   [Salazar-Garcia, Domingo C.] Max Planck Inst Evolutionare Anthropol, Res Grp Plant Foods Hominin Dietary Ecol, D-04103 Leipzig, Germany.
   [Kuzmin, Yaroslav V.; Keates, Susan G.] Russian Acad Sci, Siberian Branch, Inst Geol & Mineral, Novosibirsk 630090, Russia.
   [Kosintsev, Pavel A.] Russian Acad Sci, Urals Branch, Inst Plant & Anim Ecol, Ekaterinburg 620144, Russia.
   [Richards, Michael P.] Univ British Columbia, Dept Anthropol, Lab Archaeol, Vancouver, BC V6T 1Z1, Canada.
   [Peristov, Nikolai V.] Siberian Cultural Ctr, Omsk 644010, Russia.
   [Lachmann, Michael] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Douka, Katerina; Higham, Thomas F. G.] Univ Oxford, Res Lab Archaeol & Hist Art, Oxford Radiocarbon Accelerator Unit, Oxford OX1 3QY, England.
   [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Max Planck Society; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Columbia University; University of California System; University of California Berkeley; Russian Academy of Sciences; Tyumen Scientific Center of the Russian Academy of Sciences; Emory University; Max Planck Society; University of California System; University of California Davis; University of Cape Town; University of Valencia; Max Planck Society; Russian Academy of Sciences; Sobolev Institute of Geology & Mineralogy of the Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Russian Academy of Sciences; Institute of Plant & Animal Ecology of the Russian Academy of Sciences; University of British Columbia; The Santa Fe Institute; University of Oxford; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Fu, QM (corresponding author), Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
EM qiaomei_fu@eva.mpg.de; reich@genetics.med.harvard.edu; kelso@eva.mpg.de; bence_viola@eva.mpg.de
FU Chinese Academy of Sciences [XDA05130202]; Ministry of Science and Technology of China [2007FY110200]; Urals Branch, Russian Academy of Sciences [12-C-4-1014]; Russian Foundation for Basic Sciences [12-06-00045]; National Institutes of Health of the USA [R01-GM40282]; NIH [K99-GM104158, GM100233]; ERC [324139]; National Science Foundation [1032255]; Max Planck Society; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1032255] Funding Source: National Science Foundation; European Research Council (ERC) [324139] Funding Source: European Research Council (ERC)
NR 36
TC 719
Z9 842
U1 5
U2 285
PU NATURE PUBLISHING 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 23
PY 2014
VL 514
IS 7523
BP 445
EP +
DI 10.1038/nature13810
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900030
PM 25341783
DA 2026-03-09
ER

PT J
AU Wan, Y
   Qu, K
   Zhang, QC
   Flynn, RA
   Manor, O
   Ouyang, ZQ
   Zhang, JJ
   Spitale, RC
   Snyder, MP
   Segal, E
   Chang, HY
AF Wan, Yue
   Qu, Kun
   Zhang, Qiangfeng Cliff
   Flynn, Ryan A.
   Manor, Ohad
   Ouyang, Zhengqing
   Zhang, Jiajing
   Spitale, Robert C.
   Snyder, Michael P.
   Segal, Eran
   Chang, Howard Y.
TI Landscape and variation of RNA secondary structure across the human transcriptome
SO NATURE
LA English
DT Article
ID reveals; alignment; shape
AB In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program(1). However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic micro RNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.
C1 [Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff; Flynn, Ryan A.; Ouyang, Zhengqing; Zhang, Jiajing; Spitale, Robert C.; Chang, Howard Y.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff; Flynn, Ryan A.; Ouyang, Zhengqing; Zhang, Jiajing; Spitale, Robert C.; Chang, Howard Y.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Wan, Yue] Genome Inst Singapore, Singapore 138672, Singapore.
   [Manor, Ohad; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Snyder, Michael P.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Weizmann Institute of Science; Stanford University
RP Chang, HY (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM wany@gis.a-star.edu.sg; howchang@stanford.edu
FU NIH [R01-HG004361]; National Cancer Institute [P30CA034196, T32CA009302] Funding Source: NIH RePORTER
NR 26
TC 432
Z9 529
U1 4
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 JAN 30
PY 2014
VL 505
IS 7485
BP 706
EP +
DI 10.1038/nature12946
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000046
PM 24476892
DA 2026-03-09
ER

PT J
AU Fialkov, A
   Barkana, R
   Visbal, E
AF Fialkov, Anastasia
   Barkana, Rennan
   Visbal, Eli
TI The observable signature of late heating of the Universe during cosmic reionization
SO NATURE
LA English
DT Article
ID x-ray-emission; 1st stars; black-holes; intergalactic medium; dark-matter; ly-alpha; galaxy; hydrogen; growth; fluctuations
AB Models and simulations(1-4) of the epoch of reionization predict that spectra of the 21-centimetre transition of atomic hydrogen will show a clear fluctuation peak, at a redshift and scale, respectively, that mark the central stage of reionization and the characteristic size of ionized bubbles. This is based on the assumption(5-7) that the cosmic gas was heated by stellar remnants-particularly X-ray binaries-to temperatures well above the cosmic microwave background at that time (about 30 kelvin). Here we show instead that the hard spectra (that is, spectra with more high-energy photons than low-energy photons) of X-ray binaries(8,9) make such heating ineffective, resulting in a delayed and spatially uniform heating that modifies the 21-centimetre signature of reionization. Rather than looking for a simple rise and fall of the large-scale fluctuations (peaking at several millikelvin), we must expect a more complex signal also featuring a distinct minimum (at less than a millikelvin) that marks the rise of the cosmic mean gas temperature above the microwave background. Observing this signal, possibly with radio telescopes in operation today, will demonstrate the presence of a cosmic background of hard X-rays at that early time.
C1 [Fialkov, Anastasia; Barkana, Rennan] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Fialkov, Anastasia] Ecole Normale Super, CNRS, Dept Phys, F-75005 Paris, France.
   [Visbal, Eli] Columbia Univ, Dept Astron, New York, NY 10027 USA.
   [Visbal, Eli] Harvard Univ, Jefferson Lab Phys, Cambridge, MA 02138 USA.
   [Visbal, Eli] Harvard Univ, Inst Theory & Computat, Cambridge, MA 02138 USA.
C3 Tel Aviv University; Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Columbia University; Harvard University; Harvard University
RP Fialkov, A (corresponding author), Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
EM anastasia.fialkov@gmail.com; barkana@wise.tau.ac.il
FU Israel Science Foundation [823/09]; LabEx ENS-ICFP [ANR-10-LABX-0010, ANR-10-IDEX-0001-02 PSL*]
NR 57
TC 180
Z9 196
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 FEB 13
PY 2014
VL 506
IS 7487
BP 197
EP +
DI 10.1038/nature12999
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700032
PM 24499820
DA 2026-03-09
ER

PT J
AU Lin, MT
   Occhialini, A
   Andralojc, PJ
   Parry, MAJ
   Hanson, MR
AF Lin, Myat T.
   Occhialini, Alessandro
   Andralojc, P. John
   Parry, Martin A. J.
   Hanson, Maureen R.
TI A faster Rubisco with potential to increase photosynthesis in crops
SO NATURE
LA English
DT Article
ID synechococcus pcc7942 reveals; ribulose-1,5-bisphosphate carboxylase/oxygenase; ccmm protein; expression; tobacco; plants; chloroplasts; carboxysm; subunit; algae
AB In photosynthetic organisms, D-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the major enzyme assimilating atmospheric CO2 into the biosphere(1). Owing to the wasteful oxygenase activity and slow turnover of Rubisco, the enzyme is among the most important targets for improving the photosynthetic efficiency of vascular plants(2,3). It has been anticipated that introducing the CO2-concentrating mechanism (CCM) from cyanobacteria into plants could enhance crop yield(4-6). However, the complex nature of Rubisco's assembly has made manipulation of the enzyme extremely challenging, and attempts to replace it in plants with the enzymes from cyanobacteria and red algae have not been successful(7,8). Here we report two transplastomic tobacco lines with functional Rubisco from the cyanobacterium Synechococcus elongatus PCC7942 (Se7942). We knocked out the native tobacco gene encoding the large subunit of Rubisco by inserting the large and small subunit genes of the Se7942 enzyme, in combination with either the corresponding Se7942 assembly chaperone, RbcX, or an internal carboxysomal protein, CcmM35, which incorporates three small subunit-like domains(9,10). Se7942 Rubisco and CcmM35 formed macromolecular complexes within the chloroplast stroma, mirroring an early step in the biogenesis of cyanobacterial beta-carboxysomes(11,12). Both transformed lines were photosynthetically competent, supporting autotrophic growth, and their respective forms of Rubisco had higher rates of CO2 fixation per unit of enzyme than the tobacco control. These transplastomic tobacco lines represent an important step towards improved photosynthesis in plants and will be valuable hosts for future addition of the remaining components of the cyanobacterial CCM, such as inorganic carbon transporters and the beta-carboxysome shell proteins(4-6).
C1 [Lin, Myat T.; Hanson, Maureen R.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
   [Occhialini, Alessandro; Andralojc, P. John; Parry, Martin A. J.] Rothamsted Res, Plant Biol & Crop Sci, Harpenden AL5 2JQ, Herts, England.
C3 Cornell University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research
RP Hanson, MR (corresponding author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
EM mrh5@cornell.edu
FU National Science Foundation [EF-1105584]; Biotechnology and Biological Sciences Research Council [BB/I024488/1]; National Institute of General Medical Sciences of the National Institutes of Health [F32GM103019]; 20:20 Wheat Institute Strategic Program [BBSRC BB/J/00426X/1]; Direct For Biological Sciences; Emerging Frontiers [1105584] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BB/I024488/1, BBS/E/C/00005202] Funding Source: researchfish; BBSRC [BBS/E/C/00005202, BB/I024488/1] Funding Source: UKRI
NR 30
TC 361
Z9 437
U1 2
U2 509
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 547
EP +
DI 10.1038/nature13776
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800040
PM 25231869
DA 2026-03-09
ER

PT J
AU Morris, SC
   Caron, JB
AF Morris, Simon Conway
   Caron, Jean-Bernard
TI A primitive fish from the Cambrian of North America
SO NATURE
LA English
DT Article
ID pikaia-gracilens walcott; burgess shale; vertebrate jaw; evolution; chordate; lamprey; anatomy
AB Knowledge of the early evolution of fish largely depends on soft-bodied material from the Lower (Series 2) Cambrian period of South China(1,2). Owing to the rarity of some of these forms and a general lack of comparative material from other deposits, interpretations of various features remain controversial(3,4), as do their wider relationships amongst post-Cambrian early un-skeletonized jawless vertebrates. Here we redescribe Metaspriggina(5) on the basis of new material from the Burgess Shale and exceptionally preserved material collected near Marble Canyon, British Columbia(6), and three other Cambrian Burgess Shale-type deposits from Laurentia. This primitive fish displays unambiguous vertebrate features: a notochord, a pair of prominent camera-type eyes, paired nasal sacs, possible cranium and arcualia, W-shaped myomeres, and a post-anal tail. A striking feature is the branchial area with an array of bipartite bars. Apart from the anterior most bar, which appears to be slightly thicker, each is associated with externally located gills, possibly housed in pouches. Phylogenetic analysis places Metaspriggina as a basal vertebrate, apparently close to the Chengjiang taxa Haikouichthys(1-4) and Myllokunmingia(1), demonstrating also that this primitive group of fish was cosmopolitan during Lower-Middle Cambrian times (Series 2-3). However, the arrangement of the branchial region in Metaspriggina has wider implications for reconstructing the morphology of the primitive vertebrate. Each bipartite bar is identified as being respectively equivalent to an epibranchial and ceratobranchial. This configuration suggests that a bipartite arrangement is primitive and reinforces the view that the branchial basket of lampreys(7) is probably derived. Other features of Metaspriggina, including the external position of the gills and possible absence of a gill opposite the more robust anterior-most bar, are characteristic of gnathostomes(8) and so may be primitive within vertebrates.
C1 [Morris, Simon Conway] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
   [Caron, Jean-Bernard] Royal Ontario Museum, Dept Nat Hist Palaeobiol, Toronto, ON M5S 2C6, Canada.
   [Caron, Jean-Bernard] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada.
C3 University of Cambridge; Royal Ontario Museum; University of Toronto
RP Morris, SC (corresponding author), Univ Cambridge, Dept Earth Sci, Downing St, Cambridge CB2 3EQ, England.
EM sc113@cam.ac.uk; jcaron@rom.on.ca
FU Department of Earth Sciences and St John's College, Cambridge; Natural Sciences and Engineering Research Council [341944]; Royal Ontario Museum [53]
NR 27
TC 118
Z9 130
U1 1
U2 126
PU NATURE PUBLISHING 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 28
PY 2014
VL 512
IS 7515
BP 419
EP U413
DI 10.1038/nature13414
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600031
PM 24919146
DA 2026-03-09
ER

PT J
AU Viale, A
   Pettazzoni, P
   Lyssiotis, CA
   Ying, HQ
   Sánchez, N
   Marchesini, M
   Carugo, A
   Green, T
   Seth, S
   Giuliani, V
   Kost-Alimova, M
   Muller, F
   Colla, S
   Nezi, L
   Genovese, G
   Deem, AK
   Kapoor, A
   Yao, WT
   Brunetto, E
   Kang, Y
   Yuan, M
   Asara, JM
   Wang, YA
   Heffernan, TP
   Kimmelman, AC
   Wang, HM
   Fleming, JB
   Cantley, LC
   DePinho, RA
   Draetta, GF
AF Viale, Andrea
   Pettazzoni, Piergiorgio
   Lyssiotis, Costas A.
   Ying, Haoqiang
   Sanchez, Nora
   Marchesini, Matteo
   Carugo, Alessandro
   Green, Tessa
   Seth, Sahil
   Giuliani, Virginia
   Kost-Alimova, Maria
   Muller, Florian
   Colla, Simona
   Nezi, Luigi
   Genovese, Giannicola
   Deem, Angela K.
   Kapoor, Avnish
   Yao, Wantong
   Brunetto, Emanuela
   Kang, Ya'an
   Yuan, Min
   Asara, John M.
   Wang, Y. Alan
   Heffernan, Timothy P.
   Kimmelman, Alec C.
   Wang, Huamin
   Fleming, Jason B.
   Cantley, Lewis C.
   DePinho, Ronald A.
   Draetta, Giulio F.
TI Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
SO NATURE
LA English
DT Article
ID inhibition; metabolism; autophagy; glucose; imatinib; growth; braf
AB Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC(1), but targeting mutant KRAS has proved challenging(2). Targeting oncogene-driven signalling pathways is a clinically validated approach for several devastating diseases(3,4). Still, despite marked tumour shrinkage, the frequency of relapse indicates that a fraction of tumour cells survives shut down of oncogenic signalling(5,6). Here we explore the role of mutant KRAS in PDAC maintenance using a recently developed inducible mouse model of mutated Kras(1) (Kras(G12D), herein KRas) in a p53(LoxP/WT) background. We demonstrate that a subpopulation of dormant tumour cells surviving oncogene ablation (surviving cells) and responsible for tumour relapse has features of cancer stem cells and relies on oxidative phosphorylation for survival. Transcriptomic and metabolic analyses of surviving cells reveal prominent expression of genes governing mitochondrial function, autophagy and lysosome activity, as well as a strong reliance on mitochondrial respiration and a decreased dependence on glycolysis for cellular energetics. Accordingly, surviving cells show high sensitivity to oxidative phosphorylation inhibitors, which can inhibit tumour recurrence. Our integrated analyses illuminate a therapeutic strategy of combined targeting of the KRAS pathway and mitochondrial respiration to manage pancreatic cancer.
C1 [Viale, Andrea; Pettazzoni, Piergiorgio; Ying, Haoqiang; Sanchez, Nora; Marchesini, Matteo; Carugo, Alessandro; Green, Tessa; Muller, Florian; Colla, Simona; Nezi, Luigi; Genovese, Giannicola; Deem, Angela K.; Kapoor, Avnish; Yao, Wantong; Wang, Y. Alan; Draetta, Giulio F.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
   [Viale, Andrea; Pettazzoni, Piergiorgio; Sanchez, Nora; Marchesini, Matteo; Carugo, Alessandro; Green, Tessa; Nezi, Luigi; Yao, Wantong; Draetta, Giulio F.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Lyssiotis, Costas A.; Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
   [Carugo, Alessandro] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy.
   [Seth, Sahil; Giuliani, Virginia; Kost-Alimova, Maria; Heffernan, Timothy P.] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA.
   [Brunetto, Emanuela] Ist Sci San Raffaele, Pathol Unit, I-20132 Milan, Italy.
   [Kang, Ya'an; Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
   [Yuan, Min; Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA.
   [Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
   [Wang, Huamin] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Cornell University; Weill Cornell Medicine; IRCCS European Institute of Oncology (IEO); University of Texas System; UTMD Anderson Cancer Center; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
RP Viale, A (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
EM aviale@mdanderson.org; gdraetta@mdanderson.org
FU Cancer Center Core Grant [CA16672]; National Cancer Institute (NCI) [CA016672]; MDACC Flow Cytometry and Cellular Imaging Core Facility - NCI [P30CA16672]; FACS; Hirshberg Foundation for Pancreatic Cancer Research; Harvard Stem Cell Institute; Sheikh Ahmed Center for Pancreatic Cancer Research; American Italian Cancer Foundation; National Institutes of Health (NIH) [P01CA117969]; NIH/NCI [P01CA120964]; Viragh Family Foundation; National Cancer Institute [P01CA117969, P50CA127003, P30CA016672, P01CA120964] Funding Source: NIH RePORTER
NR 29
TC 1011
Z9 1147
U1 0
U2 238
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2014
VL 514
IS 7524
BP 628
EP +
DI 10.1038/nature13611
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500049
PM 25119024
DA 2026-03-09
ER

PT J
AU McMahon, TA
   Sears, BF
   Venesky, MD
   Bessler, SM
   Brown, JM
   Deutsch, K
   Halstead, NT
   Lentz, G
   Tenouri, N
   Young, S
   Civitello, DJ
   Ortega, N
   Fites, JS
   Reinert, LK
   Rollins-Smith, LA
   Raffel, TR
   Rohr, JR
AF McMahon, Taegan A.
   Sears, Brittany F.
   Venesky, Matthew D.
   Bessler, Scott M.
   Brown, Jenise M.
   Deutsch, Kaitlin
   Halstead, Neal T.
   Lentz, Garrett
   Tenouri, Nadia
   Young, Suzanne
   Civitello, David J.
   Ortega, Nicole
   Fites, J. Scott
   Reinert, Laura K.
   Rollins-Smith, Louise A.
   Raffel, Thomas R.
   Rohr, Jason R.
TI Amphibians acquire resistance to live and dead fungus overcoming fungal immunosuppression
SO NATURE
LA English
DT Article
ID batrachochytrium-dendrobatidis; chytrid fungus; immune defenses; infection; chytridiomycosis; frog; pathogen; declines; hosts; plant
AB Emerging fungal pathogens pose a greater threat to biodiversity than any other parasitic group(1), causing declines of many taxa, including bats, corals, bees, snakes and amphibians(1-4). Currently, there is little evidence that wild animals can acquire resistance to these pathogens(5). Batrachochytrium dendrobatidis is a pathogenic fungus implicated in the recent global decline of amphibians(6). Here we demonstrate that three species of amphibians can acquire behavioural or immunological resistance to B. dendrobatidis. Frogs learned to avoid the fungus after just one B. dendrobatidis exposure and temperature-induced clearance. In subsequent experiments in which B. dendrobatidis avoidance was prevented, the number of previous exposures was a negative predictor of B. dendrobatidis burden on frogs and B. dendrobatidis-induced mortality, and was a positive predictor of lymphocyte abundance and proliferation. These results suggest that amphibians can acquire immunity to B. dendrobatidis that overcomes pathogen-induced immunosuppression(7-9) and increases their survival. Importantly, exposure to dead fungus induced a similar magnitude of acquired resistance as exposure to live fungus. Exposure of frogs to B. dendrobatidis antigens might offer a practical way to protect pathogen-naive amphibians and facilitate the reintroduction of amphibians to locations in the wild where B. dendrobatidis persists. Moreover, given the conserved nature of vertebrate immune responses to fungi(5) and the fact that many animals are capable of learning to avoid natural enemies(10), these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity.
C1 [McMahon, Taegan A.; Sears, Brittany F.; Bessler, Scott M.; Brown, Jenise M.; Deutsch, Kaitlin; Halstead, Neal T.; Lentz, Garrett; Tenouri, Nadia; Young, Suzanne; Civitello, David J.; Ortega, Nicole; Rohr, Jason R.] Univ S Florida, Dept Integrat Biol, Tampa, FL 33620 USA.
   [McMahon, Taegan A.] Univ Tampa, Dept Biol, Tampa, FL 33606 USA.
   [Venesky, Matthew D.] Allegheny Coll, Dept Biol, Meadville, PA 16335 USA.
   [Fites, J. Scott; Rollins-Smith, Louise A.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA.
   [Reinert, Laura K.; Rollins-Smith, Louise A.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA.
   [Reinert, Laura K.; Rollins-Smith, Louise A.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA.
   [Reinert, Laura K.; Rollins-Smith, Louise A.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
   [Raffel, Thomas R.] Oakland Univ, Dept Biol, Rochester, MI 48309 USA.
C3 State University System of Florida; University of South Florida; University of Tampa; Allegheny College; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Oakland University
RP McMahon, TA (corresponding author), Univ S Florida, Dept Integrat Biol, Tampa, FL 33620 USA.
EM taeganmcmahon@gmail.com; jasonrohr@gmail.com
FU National Science Foundation [DEB 0516227, EF-1241889, IOS-1121758]; National Institutes of Health [R01GM109499]; US Department of Agriculture [NRI 2006-01370, 2009-35102-0543]; US Environmental Protection Agency [STAR R83-3835, CAREER 83518801]; NSF RCN "Refining and Diversifying Ecoimmunology"; Direct For Biological Sciences; Division Of Environmental Biology [1241889] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1121529, 1121758] Funding Source: National Science Foundation
NR 30
TC 194
Z9 237
U1 0
U2 240
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 224
EP +
DI 10.1038/nature13491
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800044
PM 25008531
DA 2026-03-09
ER

PT J
AU Sergio, F
   Tanferna, A
   De Stephanis, R
   Jiménez, LL
   Blas, J
   Tavecchia, G
   Preatoni, D
   Hiraldo, F
AF Sergio, Fabrizio
   Tanferna, Alessandro
   De Stephanis, Renaud
   Lopez Jimenez, Lidia
   Blas, Julio
   Tavecchia, Giacomo
   Preatoni, Damiano
   Hiraldo, Fernando
TI Individual improvements and selective mortality shape lifelong migratory performance
SO NATURE
LA English
DT Article
ID age; bird; flexibility; raptor; ndvi
AB Billions of organisms, from bacteria to humans, migrate each year(1) and research on their migration biology is expanding rapidly through ever more sophisticated remote sensing technologies(2-4). However, little is known about how migratory performance develops through life for any organism. To date, age variation has been almost systematically simplified into a dichotomous comparison between recently born juveniles at their first migration versus adults of unknown age(5-7). These comparisons have regularly highlighted better migratory performance by adults compared with juveniles', but it is unknown whether such variation is gradual or abrupt and whether it is driven by improvements within the individual, by selective mortality of poor performers, or both. Here we exploit the opportunity offered by long-term monitoring of individuals through Global Positioning System (GPS) satellite tracking to combine within-individual and cross-sectional data on 364 migration episodes from 92 individuals of a raptorial bird, aged 1-27 years old. We show that the development of migratory behaviour follows a consistent trajectory, more gradual and prolonged than previously appreciated, and that this is promoted by both individual improvements and selective mortality, mainly operating in early life and during the pre-breeding migration. Individuals of different age used different travelling tactics and varied in their ability to exploit tailwinds or to cope with wind drift. All individuals seemed aligned along a race with their contemporary peers, whose outcome was largely determined by the ability to depart early, affecting their subsequent recruitment, reproduction and survival. Understanding how climate change and human action can affect the migration of younger animals maybe the key to managing and forecasting the declines of many threatened migrants.
C1 [Sergio, Fabrizio; Tanferna, Alessandro; De Stephanis, Renaud; Lopez Jimenez, Lidia; Blas, Julio; Hiraldo, Fernando] CSIC, Estn Biol Donana, Dept Conservat Biol, Seville 41092, Spain.
   [Tavecchia, Giacomo] CSIC UIB, Inst Mediterranean Studies IMEDEA, Populat Ecol Grp, Esporles 07190, Spain.
   [Preatoni, Damiano] Insubria Univ, Dept Theoret & Appl Sci, I-21100 Varese, Italy.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); Universitat de les Illes Balears; Consejo Superior de Investigaciones Cientificas (CSIC); ATTITUS Educacao; University of Barcelona; University of Insubria
RP Sergio, F (corresponding author), CSIC, Estn Biol Donana, Dept Conservat Biol, Ave Amer Vespucio, Seville 41092, Spain.
EM fsergio@ebd.csic.es
FU Natural Research Ltd; Spanish Ministry of Science and Innovation/Economy and Competitiveness [CGL2008-01781, CGL2011-28103, CGL2012-32544]; FEDER; Spanish Ministry of Agriculture, Food and the Environment (Autonomous Organism of National Parks) [511/2012]; Consejeria de Medio Ambiente de la Junta de Andalucia [JA-58]; Junta de Andalucia [RNM 1790, RNM 3822, RNM 7307]; Juan de la Cierva Programme; Severo Ochoa Programme for Centres of Excellence of the Spanish Ministry of Economy and Competitiveness [SEV-2012-0262]; Ramon y Cajal contract from CSIC
NR 51
TC 287
Z9 311
U1 1
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 NOV 20
PY 2014
VL 515
IS 7527
BP 410
EP +
DI 10.1038/nature13696
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600045
PM 25252973
DA 2026-03-09
ER

PT J
AU Caricchi, L
   Simpson, G
   Schaltegger, U
AF Caricchi, Luca
   Simpson, Guy
   Schaltegger, Urs
TI Zircons reveal magma fluxes in the Earth's crust
SO NATURE
LA English
DT Article
ID igneous rock series; torres-del-paine; adamello batholith; wallowa-batholith; volcanic field; pluton; crystallization; emplacement; systems; rates
AB Magma fluxes regulate the planetary thermal budget, the growth of continents and the frequency and magnitude of volcanic eruptions, and play a part in the genesis and size of magmatic ore deposits(1-4). However, because a large fraction of the magma produced on the Earth does not erupt at the surface(2,5), determinations of magma fluxes are rare and this compromises our ability to establish a link between global heat transfer and large-scale geological processes. Here we show that age distributions of zircons, a mineral often present in crustal magmatic rocks(6), in combination with thermal modelling, provide an accurate means of retrieving magma fluxes. The characteristics of zircon age populations vary significantly and systematically as a function of the flux and total volume of magma accumulated in the Earth's crust. Our approach produces results that are consistent with independent determinations of magma fluxes and volumes of magmatic systems. Analysis of existing age population data sets using our method suggests that porphyry-type deposits, plutons and large eruptions each require magma input over different timescales at different characteristic average fluxes. We anticipate that more extensive and complete magma flux data sets will serve to clarify the control that the global heat flux exerts on the frequency of geological events such as volcanic eruptions, and to determine the main factors controlling the distribution of resources on our planet.
C1 [Caricchi, Luca; Simpson, Guy; Schaltegger, Urs] Univ Geneva, Sect Earth & Environm Sci, CH-1205 Geneva, Switzerland.
C3 University of Geneva
RP Caricchi, L (corresponding author), Univ Geneva, Sect Earth & Environm Sci, Rue Maraichers 13, CH-1205 Geneva, Switzerland.
EM luca.caricchi@unige.ch
FU University of Geneva; Swiss National Science Foundation
NR 32
TC 88
Z9 96
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 24
PY 2014
VL 511
IS 7510
BP 457
EP +
DI 10.1038/nature13532
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700044
PM 25056063
DA 2026-03-09
ER

PT J
AU Ding, BS
   Cao, ZW
   Lis, R
   Nolan, DJ
   Guo, PP
   Simons, M
   Penfold, ME
   Shido, K
   Rabbany, SY
   Rafii, S
AF Ding, Bi-Sen
   Cao, Zhongwei
   Lis, Raphael
   Nolan, Daniel J.
   Guo, Peipei
   Simons, Michael
   Penfold, Mark E.
   Shido, Koji
   Rabbany, Sina Y.
   Rafii, Shahin
TI Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis
SO NATURE
LA English
DT Article
ID beta-arrestin; cells; receptor; injury; repair; angiogenesis; cxcr4
AB Chemical or traumatic damage to the liver is frequently associated with aberrant healing (fibrosis) that overrides liver regeneration(1-5). The mechanism by which hepatic niche cells differentially modulate regeneration and fibrosis during liver repair remains to be defined(6-8). Hepatic vascular niche predominantly represented by liver sinusoidal endothelial cells deploys paracrine trophogens, known as angiocrine factors, to stimulate regeneration(9-15). Nevertheless, it is not known how pro-regenerative angiocrine signals from liver sinusoidal endothelial cells is subverted to promote fibrosis(16,17). Here, by combining an inducible endothelial-cell-specific mouse gene deletion strategy and complementary models of acute and chronic liver injury, we show that divergent angiocrine signals from liver sinusoidal endothelial cells stimulate regeneration after immediate injury and provoke fibrosis after chronic insult. The pro-fibrotic transition of vascular niche results from differential expression of stromal-derived factor-1 receptors, CXCR7 and CXCR4 (refs 18-21), in liver sinusoidal endothelial cells. After acute injury, CXCR7 upregulation in liver sinusoidal endothelial cells acts with CXCR4 to induce transcription factor Id1, deploying pro-regenerative angiocrine factors and triggering regeneration. Inducible deletion of Cxcr7 in sinusoidal endothelial cells (Cxcr7(i Delta EC/i Delta EC)) from the adult mouse liver impaired liver regeneration by diminishing Id1-mediated production of angiocrine factors(9-11). By contrast, after chronic injury inflicted by iterative hepatotoxin (carbon tetrachloride) injection and bile duct ligation, constitutive FGFR1 signalling in liver sinusoidal endothelial cells counterbalanced CXCR7-dependent pro-regenerative response and augmented CXCR4 expression. This predominance of CXCR4 over CXCR7 expression shifted angiocrine response of liver sinusoidal endothelial cells, stimulating proliferation of desmin(+) hepatic stellate-like cells(22,23) and enforcing apro-fibrotic vascular niche. Endothelial-cell-specific ablation of either Fgfr1 (Fgfr1(i Delta EC/i Delta EC)) or Cxcr4 (Cxcr4(i Delta EC/i Delta EC)) in mice restored the pro-regenerative pathway and prevented FGFR1-mediated maladaptive subversion of angiocrine factors. Similarly, selective CXCR7 activation in liver sinusoidal endothelial cells abrogated fibrogenesis. Thus, we demonstrate that in response to liver injury, differential recruitment of pro-regenerative CXCR7-Id1 versus pro-fibrotic FGFR1-CXCR4 angiocrine pathways in vascular niche balances regeneration and fibrosis. These results provide a therapeutic roadmap to achieve hepatic regeneration without provoking fibrosis(1,2,4).
C1 [Ding, Bi-Sen; Cao, Zhongwei; Lis, Raphael; Nolan, Daniel J.; Guo, Peipei; Shido, Koji; Rabbany, Sina Y.; Rafii, Shahin] Weill Cornell Med Coll, Ansary Stem Cell Inst, Howard Hughes Med Inst, Dept Med Genet, New York, NY 10065 USA.
   [Nolan, Daniel J.] Angiocrine Biosci, New York, NY 10065 USA.
   [Simons, Michael] Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT 06510 USA.
   [Penfold, Mark E.] ChemoCentryx Inc, Mountain View, CA 94043 USA.
   [Rabbany, Sina Y.] Hofstra Univ, Bioengn Program, Hempstead, NY 11549 USA.
C3 Cornell University; Weill Cornell Medicine; Howard Hughes Medical Institute; Yale University; Amgen; Hofstra University
RP Rafii, S (corresponding author), Weill Cornell Med Coll, Ansary Stem Cell Inst, Howard Hughes Med Inst, Dept Med Genet, New York, NY 10065 USA.
EM bid2004@med.cornell.edu; srafii@med.cornell.edu
FU National Scientist Development Grant from the American Heart Association [12SDG1213004]; New York Stem Cell Foundation; Ansary Stem Cell Institute; Howard Hughes Medical Institute; Empire State Stem Cell Board; New York State Department of Health [C024180, C026438, C026878, C028117]; National Heart, Lung, and Blood Institute [R01HL097797, R01HL119872, RC2HL101846, R01 HL053793]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK095039]; National Cancer Institute [U54CA163167]; Qatar National Priorities Research Foundation [NPRP08-663-3-140]; Qatar Foundation; Tri-Institutional Weill Cornell Starr Stem Cell Scholar Program
NR 32
TC 506
Z9 582
U1 5
U2 191
PU NATURE PUBLISHING 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 2
PY 2014
VL 505
IS 7481
BP 97
EP +
DI 10.1038/nature12681
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300031
PM 24256728
DA 2026-03-09
ER

PT J
AU Bos, KI
   Harkins, KM
   Herbig, A
   Coscolla, M
   Weber, N
   Comas, I
   Forrest, SA
   Bryant, JM
   Harris, SR
   Schuenemann, VJ
   Campbell, TJ
   Majander, K
   Wilbur, AK
   Guichon, RA
   Steadman, DLW
   Cook, DC
   Niemann, S
   Behr, MA
   Zumarraga, M
   Bastida, R
   Huson, D
   Nieselt, K
   Young, D
   Parkhill, J
   Buikstra, JE
   Gagneux, S
   Stone, AC
   Krause, J
AF Bos, Kirsten I.
   Harkins, Kelly M.
   Herbig, Alexander
   Coscolla, Mireia
   Weber, Nico
   Comas, Inaki
   Forrest, Stephen A.
   Bryant, Josephine M.
   Harris, Simon R.
   Schuenemann, Verena J.
   Campbell, Tessa J.
   Majander, Kerttu
   Wilbur, Alicia K.
   Guichon, Ricardo A.
   Steadman, Dawnie L. Wolfe
   Cook, Della Collins
   Niemann, Stefan
   Behr, Marcel A.
   Zumarraga, Martin
   Bastida, Ricardo
   Huson, Daniel
   Nieselt, Kay
   Young, Douglas
   Parkhill, Julian
   Buikstra, Jane E.
   Gagneux, Sebastien
   Stone, Anne C.
   Krause, Johannes
TI Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis
SO NATURE
LA English
DT Article
ID transmission; disease; dna
AB Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact(1). This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World(2). Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch(3), although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean.
C1 [Bos, Kirsten I.; Herbig, Alexander; Forrest, Stephen A.; Schuenemann, Verena J.; Majander, Kerttu; Krause, Johannes] Univ Tubingen, Dept Archaeol Sci, D-72070 Tubingen, Germany.
   [Harkins, Kelly M.; Wilbur, Alicia K.; Buikstra, Jane E.; Stone, Anne C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
   [Herbig, Alexander; Weber, Nico; Huson, Daniel; Nieselt, Kay] Univ Tubingen, Ctr Bioinformat, D-72076 Tubingen, Germany.
   [Coscolla, Mireia; Gagneux, Sebastien] Swiss Trop & Publ Hlth Inst, Dept Med Parasitol & Infect Biol, CH-4002 Basel, Switzerland.
   [Coscolla, Mireia; Gagneux, Sebastien] Univ Basel, CH-4003 Basel, Switzerland.
   [Comas, Inaki] FISABIO Publ Hlth, Genom & Hlth Unit, Valencia 46020, Spain.
   [Comas, Inaki] Inst Salud Carlos III, CIBER Ctr Invest Biomed Red Epidemiol & Publ Hlth, Madrid 28029, Spain.
   [Bryant, Josephine M.; Parkhill, Julian] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Campbell, Tessa J.] Univ Cape Town, Dept Archaeol, ZA-7701 Rondebosch, South Africa.
   [Guichon, Ricardo A.] UNMDP, FCEyN, Dept Biol, CONICET,Lab Ecologia Evolut Humana FACSO,UNCPBA, RA-7631 Quequen, Argentina.
   [Steadman, Dawnie L. Wolfe] Univ Tennessee, Dept Anthropol, Knoxville, TN 37996 USA.
   [Cook, Della Collins] Indiana Univ, Dept Anthropol, Bloomington, IN 47405 USA.
   [Niemann, Stefan] Forschungszentrum Borstel, D-23845 Borstel, Germany.
   [Niemann, Stefan] Forschungszentrum Borstel, German Ctr Infect Res, D-23845 Borstel, Germany.
   [Behr, Marcel A.] McGill Univ, McGill Int TB Ctr, Montreal, PQ H3G 1A4, Canada.
   [Zumarraga, Martin] CICVyA INTA Castelar, Inst Biotechnol, Buenos Aires, DF, Argentina.
   [Bastida, Ricardo] Univ Nacl Mar del Plata, Fac Ciencias Exactas & Nat, Inst Invest Marinas & Costeras CONICET UNMcP, RA-7600 Mar Del Plata, Buenos Aires, Argentina.
   [Young, Douglas] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W2 1PG, England.
   [Young, Douglas] MRC Natl Inst Med Res, Div Mycobacterial Res, London NW7 1AA, England.
   [Krause, Johannes] Univ Tubingen, Senckenberg Ctr Human Evolut & Palaeoenvironm, D-72070 Tubingen, Germany.
   [Krause, Johannes] Max Planck Inst Sci & Hist, D-07745 Jena, Germany.
C3 Eberhard Karls University of Tubingen; Arizona State University; Arizona State University-Tempe; Eberhard Karls University of Tubingen; Swiss School of Public Health (SSPH+); University of Basel; Swiss Tropical & Public Health Institute; University of Basel; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; Wellcome Trust Sanger Institute; University of Cape Town; National University of Mar del Plata; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Tennessee System; University of Tennessee Knoxville; Indiana University System; Indiana University Bloomington; Leibniz Association; Forschungszentrum Borstel; Leibniz Association; Forschungszentrum Borstel; German Center for Infection Research; McGill University; Instituto Nacional de Tecnologia Agropecuaria (INTA); National University of Mar del Plata; Imperial College London; MRC National Institute for Medical Research; Eberhard Karls University of Tubingen; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN)
RP Bos, KI (corresponding author), Univ Tubingen, Dept Archaeol Sci, Ruemelinstr 23, D-72070 Tubingen, Germany.
EM kirsten.bos@ifu.uni-tuebingen.de; johannes.krause@uni-tuebingen.de
FU European Research Council starting grant APGREID; National Science Foundation [NSF BCS-1063939, NSF-REU BCS-0612222, NSF BCS-0612222]; Social Sciences and Humanities Research Council of Canada [756-2011-501]; National Science Foundation Graduate Research Fellowship [DGE-1311230]; Jacob K. Javits Fellowship; Ramon y Cajal Spanish [RYC-2012-10627]; Swiss National Science Foundation [PP0033_119205]; National Institutes of Health [AI090928]; European Research Council, Argentina [309540, PICT0575]; Wadsworth Fellowship from the Wenner-Gren Foundation; Wellcome Trust [098051]; Medical Research Council; Swiss National Science Foundation (SNF) [PP0033_119205] Funding Source: Swiss National Science Foundation (SNF); Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1063939] Funding Source: National Science Foundation; Medical Research Council [MC_U117581288, 974668] Funding Source: researchfish; European Research Council (ERC) [309540] Funding Source: European Research Council (ERC); MRC [MC_U117581288] Funding Source: UKRI
NR 30
TC 385
Z9 455
U1 1
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 23
PY 2014
VL 514
IS 7523
BP 494
EP +
DI 10.1038/nature13591
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900041
PM 25141181
DA 2026-03-09
ER

PT J
AU Lindgren, J
   Sjövall, P
   Carney, RM
   Uvdal, P
   Gren, JA
   Dyke, G
   Schultz, BP
   Shawkey, MD
   Barnes, KR
   Polcyn, MJ
AF Lindgren, Johan
   Sjovall, Peter
   Carney, Ryan M.
   Uvdal, Per
   Gren, Johan A.
   Dyke, Gareth
   Schultz, Bo Pagh
   Shawkey, Matthew D.
   Barnes, Kenneth R.
   Polcyn, Michael J.
TI Skin pigmentation provides evidence of convergent melanism in extinct marine reptiles
SO NATURE
LA English
DT Article
ID soft-tissue; color; preservation; evolution; lizard; body
AB Throughout the animal kingdom, adaptive colouration serves critical functions ranging from inconspicuous camouflage to ostentatious sexual display, and can provide important information about the environment and biology of a particular organism(1,2). The most ubiquitous and abundant pigment, melanin, also has a diverse range of non-visual roles, including thermoregulation in ectotherms(3,4). However, little is known about the functional evolution of this important biochrome through deep time, owing to our limited ability to unambiguously identify traces of it in the fossil record(2). Here we present direct chemical evidence of pigmentation in fossilized skin, from three distantly related marine reptiles: a leatherback turtle(5), a mosasaur(6) and an ichthyosaur(7). We demonstrate that dark traces of soft tissue in these fossils are dominated by molecularly preserved eumelanin, in intimate association with fossilized melanosomes. In addition, we suggest that contrary to the countershading of many pelagic animals(8,9), at least some ichthyosaurs were uniformly dark-coloured in life. Our analyses expand current knowledge of pigmentation in fossil integument beyond that of feathers(2,10), allowing for the reconstruction of colour over much greater ranges of extinct taxa and anatomy. In turn, our results provide evidence of convergent melanism in three disparate lineages of secondarily aquatic tetrapods. Based on extant marine analogues, we propose that the benefits of thermoregulation and/or crypsis are likely to have contributed to this melanisation, with the former having implications for the ability of each group to exploit cold environments.
C1 [Lindgren, Johan; Gren, Johan A.] Lund Univ, Dept Geol, SE-22362 Lund, Sweden.
   [Sjovall, Peter] SP Tech Res Inst Sweden, SE-50115 Boras, Sweden.
   [Carney, Ryan M.] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02906 USA.
   [Uvdal, Per] Lund Univ, MAX IV Lab, SE-22100 Lund, Sweden.
   [Uvdal, Per] Lund Univ, Dept Chem, SE-22100 Lund, Sweden.
   [Dyke, Gareth] Univ Southampton, Southampton SO14 3ZH, Hants, England.
   [Dyke, Gareth] Univ Southampton, Inst Life Sci, Southampton SO14 3ZH, Hants, England.
   [Schultz, Bo Pagh] Nat Hist Div, MUSERUM, DK-7800 Skive, Denmark.
   [Shawkey, Matthew D.] Univ Akron, Integrated Biosci Program, Akron, OH 44325 USA.
   [Barnes, Kenneth R.] Mosasaur Ranch Museum, Lajitas, TX 79852 USA.
   [Polcyn, Michael J.] So Methodist Univ, Roy M Huffington Dept Earth Sci, Dallas, TX 75275 USA.
C3 Lund University; SP Technical Research Institute of Sweden; Brown University; Lund University; Lund University; University of Southampton; University of Southampton; University System of Ohio; University of Akron; Southern Methodist University
RP Lindgren, J (corresponding author), Lund Univ, Dept Geol, SE-22362 Lund, Sweden.
EM johan.lindgren@geol.lu.se
FU Swedish Research Council; Crafoord Foundation; Royal Swedish Academy of Sciences; VINNOVA Swedish Governmental Agency for Innovation Systems; National Geographic Society/Waitt Foundation; National Science Foundation; Human Frontiers Science Program; Air Force Office of Scientific Research; Directorate For Geosciences; Division Of Earth Sciences [1251895] Funding Source: National Science Foundation
NR 30
TC 118
Z9 133
U1 2
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 FEB 27
PY 2014
VL 506
IS 7489
BP 484
EP +
DI 10.1038/nature12899
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100037
PM 24402224
DA 2026-03-09
ER

PT J
AU Haberle, V
   Li, N
   Hadzhiev, Y
   Plessy, C
   Previti, C
   Nepal, C
   Gehrig, J
   Dong, XJ
   Akalin, A
   Suzuki, AM
   van IJcken, WFJ
   Armant, O
   Ferg, M
   Strähle, U
   Carninci, P
   Müller, F
   Lenhard, B
AF Haberle, Vanja
   Li, Nan
   Hadzhiev, Yavor
   Plessy, Charles
   Previti, Christopher
   Nepal, Chirag
   Gehrig, Jochen
   Dong, Xianjun
   Akalin, Altuna
   Suzuki, Ana Maria
   van IJcken, Wilfred F. J.
   Armant, Olivier
   Ferg, Marco
   Straehle, Uwe
   Carninci, Piero
   Mueller, Ferenc
   Lenhard, Boris
TI Two independent transcription initiation codes overlap on vertebrate core promoters
SO NATURE
LA English
DT Article
ID gene-expression; cpg islands; cap analysis; zebrafish; organization; architecture; resolution; tbp2
AB A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs(1) and recruits general transcription factors to initiate transcription(2). The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle(3-6). Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition(7). This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression(8), and determined the positions of H3K4me3-marked promoter-associated nucleosomes(9). Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (11) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts.
C1 [Haberle, Vanja] Univ Bergen, Dept Biol, N-5008 Bergen, Norway.
   [Haberle, Vanja; Lenhard, Boris] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Clin Sci, London W12 0NN, England.
   [Haberle, Vanja; Lenhard, Boris] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC Clin Sci Ctr, Fac Med, London W12 0NN, England.
   [Li, Nan; Hadzhiev, Yavor; Gehrig, Jochen; Mueller, Ferenc] Univ Birmingham, Coll Med & Dent Sci, Sch Clin & Expt Med, Birmingham, W Midlands, England.
   [Plessy, Charles; Suzuki, Ana Maria; Carninci, Piero] RIKEN Om Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Plessy, Charles; Suzuki, Ana Maria; Carninci, Piero] RIKEN Ctr Life Sci Technol, Div Genom Technol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Previti, Christopher; Nepal, Chirag; Dong, Xianjun; Akalin, Altuna] Univ Bergen, Uni Res AS, Computat Biol Unit, N-5008 Bergen, Norway.
   [van IJcken, Wilfred F. J.] Erasmus MC, Ctr Biom, NL-3015 GE Rotterdam, Netherlands.
   [Armant, Olivier; Ferg, Marco; Straehle, Uwe] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany.
   [Lenhard, Boris] Univ Bergen, Dept Informat, N-5008 Bergen, Norway.
C3 University of Bergen; Imperial College London; Imperial College London; University of Birmingham; RIKEN; RIKEN; University of Bergen; Erasmus University Rotterdam; Erasmus MC; Helmholtz Association; Karlsruhe Institute of Technology; University of Bergen
RP Lenhard, B (corresponding author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Clin Sci, London W12 0NN, England.
EM carninci@riken.jp; f.mueller@bham.ac.uk; b.lenhard@imperial.ac.uk
FU Norwegian Research Council (YFF); Bergen Research Foundation; European Union (EU); Medical Research Council UK; EU; MEXT; Medical Research Council [MC_UP_1102/1] Funding Source: researchfish; MRC [MC_UP_1102/1] Funding Source: UKRI
NR 45
TC 134
Z9 158
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 MAR 20
PY 2014
VL 507
IS 7492
BP 381
EP +
DI 10.1038/nature12974
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000039
PM 24531765
DA 2026-03-09
ER

PT J
AU Mercado-Marin, EV
   Garcia-Reynaga, P
   Romminger, S
   Pimenta, EF
   Romney, DK
   Lodewyk, MW
   Williams, DE
   Andersen, RJ
   Miller, SJ
   Tantillo, DJ
   Berlinck, RGS
   Sarpong, R
AF Mercado-Marin, Eduardo V.
   Garcia-Reynaga, Pablo
   Romminger, Stelamar
   Pimenta, Eli F.
   Romney, David K.
   Lodewyk, Michael W.
   Williams, David E.
   Andersen, Raymond J.
   Miller, Scott J.
   Tantillo, Dean J.
   Berlinck, Roberto G. S.
   Sarpong, Richmond
TI Total synthesis and isolation of citrinalin and cyclopiamine congeners
SO NATURE
LA English
DT Article
ID enantioselective total-synthesis; marine-derived fungus; oxidation; stephacidin; metabolites; derivatives; alkaloids; chemistry; secondary; revision
AB Many natural products that contain basic nitrogen atoms-for example alkaloids like morphine and quinine-have the potential to treat a broad range of human diseases. However, the presence of a nitrogen atom in a target molecule can complicate its chemical synthesis because of the basicity of nitrogen atoms and their susceptibility to oxidation. Obtaining such compounds by chemical synthesis can be further complicated by the presence of multiple nitrogen atoms, but it can be done by the selective introduction and removal of functional groups that mitigate basicity. Here we use such a strategy to complete the chemical syntheses of citrinalin B and cyclopiamine B. The chemical connections that have been realized as a result of these syntheses, in addition to the isolation of both 17-hydroxycitrinalin B and citrinalin C (which contains a bicyclo[2.2.2]diazaoctane structural unit) through carbon-13 feeding studies, support the existence of a common bicyclo[2.2.2]diazaoctane-containing biogenetic precursor to these compounds, as has been proposed previously.
C1 [Mercado-Marin, Eduardo V.; Garcia-Reynaga, Pablo; Sarpong, Richmond] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Romminger, Stelamar; Pimenta, Eli F.; Berlinck, Roberto G. S.] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil.
   [Romney, David K.; Miller, Scott J.] Yale Univ, Dept Chem, New Haven, CT 06520 USA.
   [Lodewyk, Michael W.; Tantillo, Dean J.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA.
   [Williams, David E.; Andersen, Raymond J.] Univ British Columbia, Dept Chem & Earth & Ocean Sci, Vancouver, BC V6T 1Z1, Canada.
C3 University of California System; University of California Berkeley; Universidade de Sao Paulo; Yale University; University of California System; University of California Davis; University of British Columbia
RP Berlinck, RGS (corresponding author), Univ Sao Paulo, Inst Quim Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP, Brazil.
EM rgsberlinck@iqsc.usp.br; rsarpong@berkeley.edu
FU US National Institutes of Health (NIH) [NIGMS RO1 086374]; US National Science Foundation (NSF); Brazilian National Council of Technological and Scientific Development (CNPq) [470643/2010-2]; Sao Paulo Research Foundation (FAPESP) [2012/50026-3]; NSEPC; NSF [CHE-0957416, CHE-030089]; NIH [GM096403, S10-RR027172]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1361807] Funding Source: National Science Foundation
NR 33
TC 147
Z9 172
U1 2
U2 231
PU NATURE PUBLISHING 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 15
PY 2014
VL 509
IS 7500
BP 318
EP 324
DI 10.1038/nature13273
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200030
PM 24828190
DA 2026-03-09
ER

PT J
AU Valyavin, G
   Shulyak, D
   Wade, GA
   Antonyuk, K
   Zharikov, SV
   Galazutdinov, GA
   Plachinda, S
   Bagnulo, S
   Machado, LF
   Alvarez, M
   Clark, DM
   Lopez, JM
   Hiriart, D
   Han, I
   Jeon, YB
   Zurita, C
   Mujica, R
   Burlakova, T
   Szeifert, T
   Burenkov, A
AF Valyavin, G.
   Shulyak, D.
   Wade, G. A.
   Antonyuk, K.
   Zharikov, S. V.
   Galazutdinov, G. A.
   Plachinda, S.
   Bagnulo, S.
   Machado, L. Fox
   Alvarez, M.
   Clark, D. M.
   Lopez, J. M.
   Hiriart, D.
   Han, Inwoo
   Jeon, Young-Beom
   Zurita, C.
   Mujica, R.
   Burlakova, T.
   Szeifert, T.
   Burenkov, A.
TI Suppression of cooling by strong magnetic fields in white dwarf stars
SO NATURE
LA English
DT Article
ID turbulent convection; broadening tables; space motions; evolution; wd-1953-011; hydrogen; model; feige-7; search
AB Isolated cool white dwarf stars more often have strong magnetic fields than young, hotter white dwarfs(1-4), which has been a puzzle because magnetic fields are expected to decay with time(5,6) but a cool surface suggests that the star is old. In addition, some white dwarfs with strong fields vary in brightness as they rotate(7-10), which has been variously attributed to surface brightness inhomogeneities similar to sunspots(8-12), chemical inhomogeneities(13,14) and other magneto-optical effects(15-17). Here we describe optical observations of the brightness and magnetic field of the cool white dwarf WD 1953-011 taken over about eight years, and the results of an analysis of its surface temperature and magnetic field distribution. We find that the magnetic field suppresses atmospheric convection, leading to dark spots in the most magnetized areas. We also find that strong fields are sufficient to suppress convection over the entire surface in cool magnetic white dwarfs, which inhibits their cooling evolution relative to weakly magnetic and non-magnetic white dwarfs, making them appear younger than they truly are. This explains the long-standing mystery of why magnetic fields are more common amongst cool white dwarfs, and implies that the currently accepted ages of strongly magnetic white dwarfs are systematically too young.
C1 [Valyavin, G.; Burlakova, T.; Burenkov, A.] Russian Acad Sci, Special Astrophys Observ, Nizhnii Arkhyz 369167, Zelenchukskiy R, Russia.
   [Shulyak, D.] Univ Gottingen, Inst Astrophys, D-37077 Gottingen, Germany.
   [Wade, G. A.] Royal Mil Coll Canada, Dept Phys, Kingston, ON K7K 7B4, Canada.
   [Antonyuk, K.; Plachinda, S.] Crimean Astrophys Observ, UA-98409 Nauchnyi, Crimea, Ukraine.
   [Zharikov, S. V.; Machado, L. Fox; Alvarez, M.; Clark, D. M.; Lopez, J. M.; Hiriart, D.] Univ Nacl Autonoma Mexico, Inst Astron, Observ Astron Nacl San Pedro Martir SPM, Ensenada 22860, Baja California, Mexico.
   [Galazutdinov, G. A.] Univ Catolica Norte, Inst Astron, Antofagasta, Chile.
   [Galazutdinov, G. A.] Pulkovo Observ, St Petersburg 196140, Russia.
   [Bagnulo, S.] Armagh Observ, Armagh BT61 9DG, North Ireland.
   [Han, Inwoo; Jeon, Young-Beom] Korea Astron & Space Sci Inst, Taejon 305348, South Korea.
   [Zurita, C.] Inst Astrofis Canarias, Tenerife 38200, Spain.
   [Zurita, C.] Univ La Laguna, Dept Astrofis, E-38206 Tenerife, Spain.
   [Mujica, R.] Inst Nacl Astrofis Opt & Electr, Tonantzintla 72000, Pueblo, Mexico.
   [Szeifert, T.] European So Observ, Santiago 19, Chile.
C3 Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; University of Gottingen; Royal Military College - Canada; Crimean Astrophysical Observatory; Universidad Nacional Autonoma de Mexico; Universidad Catolica del Norte; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; Pulkovo Main Astronomic Observatory; Korea Astronomy & Space Science Institute (KASI); Instituto de Astrofisica de Canarias; Universidad de la Laguna; Instituto Nacional de Astrofisica, Optica y Electronica; European Southern Observatory
RP Valyavin, G (corresponding author), Russian Acad Sci, Special Astrophys Observ, Nizhnii Arkhyz 369167, Zelenchukskiy R, Russia.
EM gvalyavin@sao.ru
FU Chilean fund FONDECYT [1120190]; CONACyT, Mexico [180817]; ministry of science and education of the Russian Federation [14.518.11.7070, 16.518.11.7073]; CRC963 Astrophysical Flow Instabilities and Turbulence [A16-A17]; Natural Sciences and Engineering Research Council (NSERC Canada); DGAPA/PAPIIT [IN100614]; CONACYT [151858]; Universidad Nacional Autonoma de Mexico [PAPIIT IN104612]
NR 40
TC 53
Z9 60
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 NOV 6
PY 2014
VL 515
IS 7525
BP 88
EP +
DI 10.1038/nature13836
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500034
PM 25327247
DA 2026-03-09
ER

PT J
AU Kaukua, N
   Shahidi, MK
   Konstantinidou, C
   Dyachuk, V
   Kaucka, M
   Furlan, A
   An, ZW
   Wang, LL
   Hultman, I
   Ahrlund-Richter, L
   Blom, H
   Brismar, H
   Lopes, NA
   Pachnis, V
   Suter, U
   Clevers, H
   Thesleff, I
   Sharpe, P
   Ernfors, P
   Fried, K
   Adameyko, I
AF Kaukua, Nina
   Shahidi, Maryam Khatibi
   Konstantinidou, Chrysoula
   Dyachuk, Vyacheslav
   Kaucka, Marketa
   Furlan, Alessandro
   An, Zhengwen
   Wang, Longlong
   Hultman, Isabell
   Ahrlund-Richter, Larsa
   Blom, Hans
   Brismar, Hjalmar
   Lopes, Natalia Assaife
   Pachnis, Vassilis
   Suter, Ueli
   Clevers, Hans
   Thesleff, Irma
   Sharpe, Paul
   Ernfors, Patrik
   Fried, Kaj
   Adameyko, Igor
TI Glial origin of mesenchymal stem cells in a tooth model system
SO NATURE
LA English
DT Article
ID cranial neural crest; regeneration; homeostasis; generation; mice
AB Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair(1). The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium(2). It has been thought for decades that the dental mesenchymal stem cells(3) giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue(4,5). Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique(6) with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.
C1 [Kaukua, Nina; Fried, Kaj] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
   [Konstantinidou, Chrysoula; Pachnis, Vassilis] Natl Inst Med Res, MRC, Div Mol Neurobiol, London NW7 1AA, England.
   [Dyachuk, Vyacheslav; Kaucka, Marketa; Adameyko, Igor] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
   [Dyachuk, Vyacheslav] Russian Acad Sci, Far Eastern Branch, AV Zhirmunsky Inst Marine Biol, Vladivostok 690041, Russia.
   [Furlan, Alessandro; Lopes, Natalia Assaife; Ernfors, Patrik] Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Unit, S-17177 Stockholm, Sweden.
   [An, Zhengwen; Wang, Longlong; Sharpe, Paul] Guys Hosp, Inst Dent, Kings Coll London, Dept Craniofacial Dev & Stem Cell Biol, London SE1 3QD, England.
   [Hultman, Isabell; Ahrlund-Richter, Larsa] Karolinska Inst, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
   [Blom, Hans; Brismar, Hjalmar] Royal Inst Technol, Sci Life Lab, S-17177 Stockholm, Sweden.
   [Suter, Ueli] Swiss Fed Inst Technol, Inst Mol Hlth Sci, Dept Biol, CH-8093 Zurich, Switzerland.
   [Clevers, Hans] Koninklijke Nederlandse Akad Wetenschappen KNAW, Hubrecht Inst, NL-3508 AD Utrecht, Netherlands.
   [Clevers, Hans] Univ Med Ctr Utrecht, Dept Mol Genet, NL-3508 GA Utrecht, Netherlands.
   [Clevers, Hans] Univ Helsinki, Dev Biol Program, Inst Biotechnol, FI-00014 Helsinki, Finland.
C3 Karolinska Institutet; MRC National Institute for Medical Research; Karolinska Institutet; Russian Academy of Sciences; National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences; Karolinska Institutet; Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London; Karolinska Institutet; Royal Institute of Technology; Swiss Federal Institutes of Technology Domain; ETH Zurich; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; University of Helsinki
RP Adameyko, I (corresponding author), Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
EM Kaj.Fried@ki.se; Igor.Adameyko@ki.se
FU Swedish Research Council; Bertil Hallsten Research Foundation; StratRegen; Wallenberg Foundation; Swiss National Science Foundation; Medical Research Council [G0901599]; Wallenberg Scholar and European Research Council; National Graduate School in Odontological Science; Swedish Dental Association; EMBO Long-Term Fellowship; Stockholm County Council; Developmental Studies Hybridoma Bank; MRC [MC_U117537087, G0901599, MR/K018035/1] Funding Source: UKRI; Medical Research Council [MC_U117537087, G0901599, MR/K018035/1] Funding Source: researchfish
NR 18
TC 352
Z9 396
U1 3
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 SEP 25
PY 2014
VL 513
IS 7519
BP 551
EP +
DI 10.1038/nature13536
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800041
PM 25079316
DA 2026-03-09
ER

PT J
AU Wolfe, AL
   Singh, K
   Zhong, Y
   Drewe, P
   Rajasekhar, VK
   Sanghvi, VR
   Mavrakis, KJ
   Jiang, M
   Roderick, JE
   Van der Meulen, J
   Schatz, JH
   Rodrigo, CM
   Zhao, CY
   Rondou, P
   de Stanchina, E
   Teruya-Feldstein, J
   Kelliher, MA
   Speleman, F
   Porco, JA
   Pelletier, J
   Rätsch, G
   Wendel, HG
AF Wolfe, Andrew L.
   Singh, Kamini
   Zhong, Yi
   Drewe, Philipp
   Rajasekhar, Vinagolu K.
   Sanghvi, Viraj R.
   Mavrakis, Konstantinos J.
   Jiang, Man
   Roderick, Justine E.
   Van der Meulen, Joni
   Schatz, Jonathan H.
   Rodrigo, Christina M.
   Zhao, Chunying
   Rondou, Pieter
   de Stanchina, Elisa
   Teruya-Feldstein, Julie
   Kelliher, Michelle A.
   Speleman, Frank
   Porco, John A., Jr.
   Pelletier, Jerry
   Raetsch, Gunnar
   Wendel, Hans-Guido
TI RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer
SO NATURE
LA English
DT Article
ID of-function mutations; c-myc; initiation; eif4e; akt; inhibition; transformation; repression; promotes; unwinds
AB The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)(4) motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.
C1 [Wolfe, Andrew L.; Singh, Kamini; Sanghvi, Viraj R.; Mavrakis, Konstantinos J.; Jiang, Man; Van der Meulen, Joni; Schatz, Jonathan H.; Zhao, Chunying; Wendel, Hans-Guido] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Wolfe, Andrew L.] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA.
   [Zhong, Yi; Drewe, Philipp; Raetsch, Gunnar] Mem Sloan Kettering Canc Ctr, Computat Biol Dept, New York, NY 10065 USA.
   [Rajasekhar, Vinagolu K.] Mem Sloan Kettering Canc Ctr, Stem Cell Ctr, New York, NY 10065 USA.
   [Rajasekhar, Vinagolu K.] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Roderick, Justine E.; Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
   [Van der Meulen, Joni; Rondou, Pieter; Speleman, Frank] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
   [Schatz, Jonathan H.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Rodrigo, Christina M.; Porco, John A., Jr.] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev, Boston, MA 02215 USA.
   [de Stanchina, Elisa] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA.
   [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Pelletier, Jerry] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
   [Pelletier, Jerry] McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada.
   [Pelletier, Jerry] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Massachusetts System; University of Massachusetts Worcester; Ghent University; Memorial Sloan Kettering Cancer Center; Boston University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; McGill University; McGill University; McGill University
RP Wendel, HG (corresponding author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
EM Ratschg@mskcc.org; wendelh@mskcc.org
FU National Cancer Institute [R01-CA142798-01]; Leukemia Research Foundation; Experimental Therapeutics Center; American Cancer Society [10284, PF-11-077-01-CDD]; European Union [PITN-GA-2012-316861]; Fund for Scientific Research FWO Flanders [G.0198.08, G.0869.10N]; GOA-UGent [12051203]; Stichting tegen Kanker; Belgian Program of Interuniversity Poles of Attraction; Belgian Foundation Against Cancer; Lymphoma Research Foundation; National Institutes of Health [GM-067041, GM-073855]; Canadian Institutes of Health Research [MOP-10653]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 56
TC 501
Z9 591
U1 3
U2 142
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2014
VL 513
IS 7516
BP 65
EP +
DI 10.1038/nature13485
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800030
PM 25079319
DA 2026-03-09
ER

PT J
AU Myburg, AA
   Grattapaglia, D
   Tuskan, GA
   Hellsten, U
   Hayes, RD
   Grimwood, J
   Jenkins, J
   Lindquist, E
   Tice, H
   Bauer, D
   Goodstein, DM
   Dubchak, I
   Poliakov, A
   Mizrachi, E
   Kullan, ARK
   Hussey, SG
   Pinard, D
   Van der Merwe, K
   Singh, P
   Van Jaarsveld, I
   Silva, OB
   Togawa, RC
   Pappas, MR
   Faria, DA
   Sansaloni, CP
   Petroli, CD
   Yang, XH
   Ranjan, P
   Tschaplinski, TJ
   Ye, CY
   Li, T
   Sterck, L
   Vanneste, K
   Murat, F
   Soler, M
   Clemente, HS
   Saidi, N
   Cassan-Wang, H
   Dunand, C
   Hefer, CA
   Bornberg-Bauer, E
   Kersting, AR
   Vining, K
   Amarasinghe, V
   Ranik, M
   Naithani, S
   Elser, J
   Boyd, AE
   Liston, A
   Spatafora, JW
   Dharmwardhana, P
   Raja, R
   Sullivan, C
   Romanel, E
   Alves-Ferreira, M
   Lheim, CK
   Foley, W
   Carocha, V
   Paiva, J
   Kudrna, D
   Brommonschenkel, SH
   Pasquali, G
   Byrne, M
   Rigault, P
   Tibbits, J
   Spokevicius, A
   Jones, RC
   Steane, DA
   Vaillancourt, RE
   Potts, BM
   Joubert, F
   Barry, K
   Pappas, GJ
   Strauss, SH
   Jaiswal, P
   Grima-Pettenati, J
   Salse, J
   Van de Peer, Y
   Rokhsar, DS
   Schmutz, J
AF Myburg, Alexander A.
   Grattapaglia, Dario
   Tuskan, Gerald A.
   Hellsten, Uffe
   Hayes, Richard D.
   Grimwood, Jane
   Jenkins, Jerry
   Lindquist, Erika
   Tice, Hope
   Bauer, Diane
   Goodstein, David M.
   Dubchak, Inna
   Poliakov, Alexandre
   Mizrachi, Eshchar
   Kullan, Anand R. K.
   Hussey, Steven G.
   Pinard, Desre
   Van der Merwe, Karen
   Singh, Pooja
   Van Jaarsveld, Ida
   Silva-Junior, Orzenil B.
   Togawa, Roberto C.
   Pappas, Marilia R.
   Faria, Danielle A.
   Sansaloni, Carolina P.
   Petroli, Cesar D.
   Yang, Xiaohan
   Ranjan, Priya
   Tschaplinski, Timothy J.
   Ye, Chu-Yu
   Li, Ting
   Sterck, Lieven
   Vanneste, Kevin
   Murat, Florent
   Soler, Maral
   Clemente, Helene San
   Saidi, Naijib
   Cassan-Wang, Hua
   Dunand, Christophe
   Hefer, Charles A.
   Bornberg-Bauer, Erich
   Kersting, Anna R.
   Vining, Kelly
   Amarasinghe, Vindhya
   Ranik, Martin
   Naithani, Sushma
   Elser, Justin
   Boyd, Alexander E.
   Liston, Aaron
   Spatafora, Joseph W.
   Dharmwardhana, Palitha
   Raja, Rajani
   Sullivan, Christopher
   Romanel, Elisson
   Alves-Ferreira, Marcio
   Lheim, Carsten Ku
   Foley, William
   Carocha, Victor
   Paiva, Jorge
   Kudrna, David
   Brommonschenkel, Sergio H.
   Pasquali, Giancarlo
   Byrne, Margaret
   Rigault, Philippe
   Tibbits, Josquin
   Spokevicius, Antanas
   Jones, Rebecca C.
   Steane, Dorothy A.
   Vaillancourt, Rene E.
   Potts, Brad M.
   Joubert, Fourie
   Barry, Kerrie
   Pappas, Georgios J., Jr.
   Strauss, Steven H.
   Jaiswal, Pankaj
   Grima-Pettenati, Jacqueline
   Salse, Jerome
   Van de Peer, Yves
   Rokhsar, Daniel S.
   Schmutz, Jeremy
TI The genome of Eucalyptus grandis
SO NATURE
LA English
DT Article
ID whole-genome; nuclear-dna; plant; alignment; tools; gene; diversity; evolution; database; tandem
AB Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.
C1 [Myburg, Alexander A.; Mizrachi, Eshchar; Kullan, Anand R. K.; Hussey, Steven G.; Pinard, Desre; Van der Merwe, Karen; Singh, Pooja] Univ Pretoria, Dept Genet, Forestry & Agr Biotechnol Inst FABI, ZA-0028 Pretoria, South Africa.
   [Myburg, Alexander A.; Mizrachi, Eshchar; Kullan, Anand R. K.; Hussey, Steven G.; Pinard, Desre; Van der Merwe, Karen; Singh, Pooja; Joubert, Fourie; Van de Peer, Yves] Univ Pretoria, Genom Res Inst GRI, ZA-0028 Pretoria, South Africa.
   [Grattapaglia, Dario; Pappas, Marilia R.; Faria, Danielle A.; Sansaloni, Carolina P.; Petroli, Cesar D.] EPQB Final W5 Norte, EMBRAPA Recursos Genet & Biotecnol, Lab Genet Vegetal, BR-70770917 Brasilia, DF, Brazil.
   [Grattapaglia, Dario] Univ Catolica Brasilia SGAN 916, Programa Ciencias Genom & Biotecnol, BR-70790160 Brasilia, DF, Brazil.
   [Tuskan, Gerald A.; Hellsten, Uffe; Hayes, Richard D.; Lindquist, Erika; Tice, Hope; Bauer, Diane; Goodstein, David M.; Dubchak, Inna; Poliakov, Alexandre; Barry, Kerrie; Rokhsar, Daniel S.; Schmutz, Jeremy] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Tuskan, Gerald A.; Yang, Xiaohan; Ranjan, Priya; Tschaplinski, Timothy J.; Ye, Chu-Yu; Li, Ting] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
   [Grimwood, Jane; Jenkins, Jerry; Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, Huntsville, AL 35801 USA.
   [Van Jaarsveld, Ida; Hefer, Charles A.; Joubert, Fourie] Univ Pretoria, Dept Biochem, Bioinformat & Computat Biol Unit, ZA-0028 Pretoria, South Africa.
   [Silva-Junior, Orzenil B.; Togawa, Roberto C.] EPQB Final W5 Norte, EMBRAPA Recursos Genet & Biotecnol, Lab Bioinformat, BR-70770917 Brasilia, DF, Brazil.
   [Sterck, Lieven; Vanneste, Kevin; Van de Peer, Yves] Univ Ghent VIB, Dept Plant Biotechnol & Bioinformat, B-9000 Ghent, Belgium.
   [Murat, Florent; Salse, Jerome] INRA UBP UMR 1095, F-63100 Clermont Ferrand, France.
   [Soler, Maral; Clemente, Helene San; Saidi, Naijib; Cassan-Wang, Hua; Dunand, Christophe; Carocha, Victor; Grima-Pettenati, Jacqueline] Univ Toulouse 3, Lab Rech Sci Vegetales, UMR 5546, CNRS, F-31326 Castanet Tolosan, France.
   [Hefer, Charles A.] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada.
   [Bornberg-Bauer, Erich; Kersting, Anna R.] Univ Munster, Inst Evolut & Biodivers, D-48149 Munster, Germany.
   [Kersting, Anna R.] Univ Dusseldorf, Inst Comp Sci, Dept Bioinformat, D-40225 Dusseldorf, Germany.
   [Vining, Kelly; Amarasinghe, Vindhya; Ranik, Martin; Strauss, Steven H.] Oregon State Univ, Dept Forest Ecosyst & Soc, Corvallis, OR 97331 USA.
   [Naithani, Sushma; Elser, Justin; Liston, Aaron; Spatafora, Joseph W.; Dharmwardhana, Palitha; Raja, Rajani; Jaiswal, Pankaj] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
   [Naithani, Sushma; Boyd, Alexander E.; Liston, Aaron; Spatafora, Joseph W.; Sullivan, Christopher; Jaiswal, Pankaj] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
   [Romanel, Elisson] Univ Fed Rio de Janeiro, Dept Genet, Lab Biol Evolut Teor & Aplicada, BR-21949900 Rio de Janeiro, Brazil.
   [Romanel, Elisson] EEL USP, Dept Biotecnol, BR-12602810 Lorena, SP, Brazil.
   [Romanel, Elisson; Alves-Ferreira, Marcio] Univ Fed Rio de Janeiro, Dept Genet, LGMV, BR-21949900 Rio de Janeiro, Brazil.
   [Lheim, Carsten Ku; Foley, William] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia.
   [Carocha, Victor; Paiva, Jorge] IICT MNE, P-1349007 Lisbon, Portugal.
   [Carocha, Victor; Paiva, Jorge] IBET ITQB, P-2781901 Oeiras, Portugal.
   [Kudrna, David] Univ Arizona, Arizona Genom Inst, Tucson, AZ 85721 USA.
   [Brommonschenkel, Sergio H.] Univ Fed Vicosa, Dep Fitopatol, BR-36570000 Vicosa, MG, Brazil.
   [Pasquali, Giancarlo] Univ Fed Rio Grande do Sul, Ctr Biotecnol, BR-91501970 Porto Alegre, RS, Brazil.
   [Byrne, Margaret] Dept Parks & Wildlife, Sci & Conservat Div, Bentley, WA 6983, Australia.
   [Rigault, Philippe] GYDLE, Quebec City, PQ G1T 1Z2, Canada.
   [Tibbits, Josquin] Victorian Govt, Dept Environm & Primary Ind, Yallambie, Vic 3085, Australia.
   [Spokevicius, Antanas] Univ Melbourne, Melbourne Sch Land & Environm, Melbourne, Vic 3010, Australia.
   [Jones, Rebecca C.; Steane, Dorothy A.; Vaillancourt, Rene E.; Potts, Brad M.] Univ Tasmania, Sch Biol Sci, Hobart, Tas 7001, Australia.
   [Jones, Rebecca C.; Steane, Dorothy A.; Vaillancourt, Rene E.; Potts, Brad M.] Univ Tasmania, Natl Ctr Future Forest Ind, Hobart, Tas 7001, Australia.
   [Steane, Dorothy A.] Univ Sunshine Coast, Fac Sci Hlth Educ & Engn, Sippy Downs, Qld 4558, Australia.
   [Pappas, Georgios J., Jr.] Univ Brasilia, Dept Biol Celular, BR-70910900 Brasilia, DF, Brazil.
C3 University of Pretoria; University of Pretoria; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); EMBRAPA Genetic Resources & Biotechnology; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; United States Department of Energy (DOE); Oak Ridge National Laboratory; HudsonAlpha Institute for Biotechnology; University of Pretoria; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); EMBRAPA Genetic Resources & Biotechnology; Flanders Institute for Biotechnology (VIB); Ghent University; INRAE; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of British Columbia; University of Munster; Heinrich Heine University Dusseldorf; Oregon State University; Oregon State University; Oregon State University; Universidade Federal do Rio de Janeiro; Universidade Federal do Rio de Janeiro; Australian National University; University of Arizona; Universidade Federal de Vicosa; Universidade Federal do Rio Grande do Sul; Government of Victoria; University of Melbourne; University of Tasmania; University of Tasmania; University of the Sunshine Coast; Universidade de Brasilia
RP Myburg, AA (corresponding author), Univ Pretoria, Dept Genet, Forestry & Agr Biotechnol Inst FABI, Private Bag X20, ZA-0028 Pretoria, South Africa.
EM zander.myburg@up.ac.za
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Office of Biological and Environmental Research in the US Department of Energy Office of Science, US DOE Bioenergy Center [DE-AC05-00OR22725]; Brazilian Ministry of Science, Technology and Innovation (MCTI) through (CNPq); Brazilian Ministry of Science, Technology and Innovation (MCTI) through (FINEP); Brazilian Federal District Research Foundation (FAP-DF); Technology and Human Resources for Industry Programme (THRIP) [UID 80118]; South African Department of Science and Technology (DST); National Research Foundation (NRF) [UID 18312, 86936]; Laboratoire d'Excellence [LABEX TULIP ANR-10-LABX-41]; Agence Nationale pour la Recherche (Project Tree For Joules) [ANR-2010-KBBE-007-01]; Fundacao para a Ciencia e Tecnologia (FCT) [P-KBBE/AGR_GPL/0001/2010]; Centre National pour la Recherche Scientifique (CNRS); University Paul Sabatier Toulouse III (UPS); Ghent University; Hercules Foundation; Flemish Government-department EWI; Fundação para a Ciência e a Tecnologia [P-KBBE/AGR-GPL/0001/2010] Funding Source: FCT; Directorate For Engineering; Div Of Industrial Innovation & Partnersh [1238305] Funding Source: National Science Foundation
NR 70
TC 711
Z9 803
U1 10
U2 390
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 356
EP +
DI 10.1038/nature13308
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200027
PM 24919147
DA 2026-03-09
ER

PT J
AU Reyes-Fox, M
   Steltzer, H
   Trlica, MJ
   McMaster, GS
   Andales, AA
   LeCain, DR
   Morgan, JA
AF Reyes-Fox, Melissa
   Steltzer, Heidi
   Trlica, M. J.
   McMaster, Gregory S.
   Andales, Allan A.
   LeCain, Dan R.
   Morgan, Jack A.
TI Elevated CO2 further lengthens growing season under warming conditions
SO NATURE
LA English
DT Article
ID climate-change; flowering time; carbon-dioxide; phenology; grassland; responses; plants
AB Observations of a longer growing season through earlier plant growth in temperate to polar regions have been thought to be a response to climate warming(1-5). However, data from experimental warming studies indicate that many species that initiate leaf growth and flowering earlier also reach seed maturation and senesce earlier, shortening their active and reproductive periods(6-10). A conceptual model to explain this apparent contradiction(11), and an analysis of the effect of elevated CO2-which can delay annual life cycle events(12-14)-on changing season length, have not been tested. Here we show that experimental warming in a temperate grassland led to a longer growing season through earlier leaf emergence by the first species to leaf, often a grass, and constant or delayed senescence by other species that were the last to senesce, supporting the conceptual model. Elevated CO2 further extended growing, but not reproductive, season length in the warmed grassland by conserving water, which enabled most species to remain active longer. Our results suggest that a longer growing season, especially in years or biomes where water is a limiting factor, is not due to warming alone, but also to higher atmospheric CO2 concentrations that extend the active period of plant annual life cycles.
C1 [Reyes-Fox, Melissa] ARS, USDA, Soil Plant Nutrient Res Unit, Ft Collins, CO 80526 USA.
   [Reyes-Fox, Melissa; McMaster, Gregory S.] Northern Plains Area, Ft Collins, CO 80526 USA.
   [Steltzer, Heidi] Ft Lewis Coll, Dept Biol, Durango, CO 81301 USA.
   [Trlica, M. J.] Colorado State Univ, Dept Forest & Rangeland Stewardship, Ft Collins, CO 80523 USA.
   [McMaster, Gregory S.] ARS, USDA, Agr Syst Res Unit, Ft Collins, CO 80526 USA.
   [Andales, Allan A.] Colorado State Univ, Dept Soil & Crop Sci, Ft Collins, CO 80523 USA.
   [LeCain, Dan R.; Morgan, Jack A.] ARS, USDA, Rangeland Resources Res Unit, Ft Collins, CO 80526 USA.
C3 United States Department of Agriculture (USDA); Fort Lewis College; Colorado State University System; Colorado State University Fort Collins; United States Department of Agriculture (USDA); Colorado State University System; Colorado State University Fort Collins; United States Department of Agriculture (USDA)
RP Steltzer, H (corresponding author), Ft Lewis Coll, Dept Biol, Durango, CO 81301 USA.
EM Melissa.reyes@ars.usda.gov; steltzer_h@fortlewis.edu
FU US Department of Agriculture Agricultural Research Center (USDA-ARS) Climate Change, Soils & Emissions Program; US Department of Energy's Office of Science through the Terrestrial Ecosystem Science Program; National Science Foundation (DEB) [1021559]; Colorado State University; Division Of Environmental Biology; Direct For Biological Sciences [1021559] Funding Source: National Science Foundation
NR 27
TC 172
Z9 206
U1 7
U2 331
PU NATURE PUBLISHING 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 12
PY 2014
VL 510
IS 7504
BP 259
EP +
DI 10.1038/nature13207
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400048
PM 24759322
DA 2026-03-09
ER

PT J
AU David, LA
   Maurice, CF
   Carmody, RN
   Gootenberg, DB
   Button, JE
   Wolfe, BE
   Ling, AV
   Devlin, AS
   Varma, Y
   Fischbach, MA
   Biddinger, SB
   Dutton, RJ
   Turnbaugh, PJ
AF David, Lawrence A.
   Maurice, Corinne F.
   Carmody, Rachel N.
   Gootenberg, David B.
   Button, Julie E.
   Wolfe, Benjamin E.
   Ling, Alisha V.
   Devlin, A. Sloan
   Varma, Yug
   Fischbach, Michael A.
   Biddinger, Sudha B.
   Dutton, Rachel J.
   Turnbaugh, Peter J.
TI Diet rapidly and reproducibly alters the human gut microbiome
SO NATURE
LA English
DT Article
ID sulfate-reducing bacteria; bile-acids; enumeration; diversity; discovery; community; patterns; database; genm; marker
AB Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut(1-5), but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals(2), reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease(6). In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
C1 [David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Dutton, Rachel J.; Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [David, Lawrence A.] Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA.
   [Ling, Alisha V.; Biddinger, Sudha B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA.
   [Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
   [Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
C3 Harvard University; Harvard University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Turnbaugh, PJ (corresponding author), Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
EM pturnbaugh@fas.harvard.edu
FU National Institutes of Health [P50 GM068763]; Boston Nutrition Obesity Research Center [DK0046200]; General Mills Bell Institute of Health and Nutrition; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854, P30DK046200] Funding Source: NIH RePORTER
NR 56
TC 7532
Z9 8994
U1 80
U2 3410
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 23
PY 2014
VL 505
IS 7484
BP 559
EP +
DI 10.1038/nature12820
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000042
PM 24336217
DA 2026-03-09
ER

PT J
AU McCully, C
   Jha, SW
   Foley, RJ
   Bildsten, L
   Fong, WF
   Kirshner, RP
   Marion, GH
   Riess, AG
   Stritzinger, MD
AF McCully, Curtis
   Jha, Saurabh W.
   Foley, Ryan J.
   Bildsten, Lars
   Fong, Wen-fai
   Kirshner, Robert P.
   Marion, G. H.
   Riess, Adam G.
   Stritzinger, Maximilian D.
TI A luminous, blue progenitor system for the type Iax supernova 2012Z
SO NATURE
LA English
DT Article
ID hubble-space-telescope; core-collapse supernova; sn 2005hk; helium nova; stars; models; 2002cx
AB Type Iax supernovae are stellar explosions that are spectroscopically similar to some type Ia supernovae at the time of maximum light emission, except with lower ejecta velocities(1,2). They are also distinguished by lower luminosities. At late times, their spectroscopic properties diverge from those of other supernovae(3-6), but their composition (dominated by iron-group and intermediate-mass elements(1,7)) suggests a physical connection to normal type Ia supernovae. Supernovae of type Iax are not rare; they occur at a rate between 5 and 30 per cent of the normal type Ia rate(1). The leading models for type Iax supernovae are thermonuclear explosions of accreting carbon-oxygen white dwarfs that do not completely unbind the star(8-10), implying that they are 'less successful' versions of normal type Ia supernovae, where complete stellar disruption is observed. Here we report the detection of the luminous, blue progenitor system of the type Iax SN 2012Z in deep pre-explosion imaging. The progenitor system's luminosity, colours, environment and similarity to the progenitor of the Galactic helium nova V445 Puppis(11-13) suggest that SN 2012Z was the explosion of a white dwarf accretingmaterial from a helium-star companion. Observations over the next few years, after SN 2012Z has faded, will either confirm this hypothesis or perhaps show that this super-nova was actually the explosive death of a massive star(14,15).
C1 [McCully, Curtis; Jha, Saurabh W.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Foley, Ryan J.] Univ Illinois, Dept Astron, Urbana, IL 61801 USA.
   [Foley, Ryan J.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Bildsten, Lars] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Bildsten, Lars] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Fong, Wen-fai; Kirshner, Robert P.; Marion, G. H.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Marion, G. H.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Riess, Adam G.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Riess, Adam G.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Stritzinger, Maximilian D.] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
C3 Rutgers University System; Rutgers University New Brunswick; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; University of Texas System; University of Texas Austin; Johns Hopkins University; Space Telescope Science Institute; Aarhus University
RP Jha, SW (corresponding author), Rutgers State Univ, Dept Phys & Astron, 136 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM saurabh@physics.rutgers.edu
FU NASA/HST [GO-12913.01, GO-12999.01]; National Science Foundation (NSF) CAREER [AST-0847157]; NSF [PHY 11-25915, AST 11-09174]; Danish Agency for Science, Technology, and Innovation; NASA from the Space Telescope Science Institute [GO-12913, GO-12999]; NASA [NAS5-26555]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109174] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0847157, 1211196] Funding Source: National Science Foundation
NR 34
TC 140
Z9 153
U1 0
U2 12
PU NATURE PUBLISHING 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 7
PY 2014
VL 512
IS 7512
BP 54
EP +
DI 10.1038/nature13615
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000029
PM 25100479
DA 2026-03-09
ER

PT J
AU Zhou, LM
   Tian, YH
   Myneni, RB
   Ciais, P
   Saatchi, S
   Liu, YY
   Piao, SL
   Chen, HS
   Vermote, EF
   Song, CH
   Hwang, TH
AF Zhou, Liming
   Tian, Yuhong
   Myneni, Ranga B.
   Ciais, Philippe
   Saatchi, Sassan
   Liu, Yi Y.
   Piao, Shilong
   Chen, Haishan
   Vermote, Eric F.
   Song, Conghe
   Hwang, Taehee
TI Widespread decline of Congo rainforest greenness in the past decade
SO NATURE
LA English
DT Article
ID microwave emission; vegetation index; tropical forests; climate; modis; drought; grace; water; products; dynamics
AB Tropical forests are global epicentres of biodiversity and important modulators of climate change(1), and are mainly constrained by rainfall patterns(1-3). The severe short-term droughts that occurred recently in Amazonia have drawn attention to the vulnerability of tropical forests to climatic disturbances(4-9). The central African rainforests, the second-largest on Earth, have experienced a long-term drying trend(10,11) whose impacts on vegetation dynamics remain mostly unknown because in situ observations are very limited. The Congolese forest, with its drier conditions and higher percentage of semi-evergreen trees(12,13), may be more tolerant to short-term rainfall reduction than are wetter tropical forests(11), but for a long-term drought there may be critical thresholds of water availability below which higher-biomass, closed-canopy forests transition to more open, lower-biomass forests(1,2,14). Here we present observational evidence for a widespread decline in forest greenness over the past decade based on analyses of satellite data (optical, thermal, microwave and gravity) from several independent sensors over the Congo basin. This decline in vegetation greenness, particularly in the northern Congolese forest, is generally consistent with decreases in rainfall, terrestrial water storage, water content in aboveground woody and leaf biomass, and the canopy backscatter anomaly caused by changes in structure and moisture in upper forest layers. It is also consistent with increases in photosynthetically active radiation and land surface temperature. These multiple lines of evidence indicate that this large-scale vegetation browning, or loss of photosynthetic capacity, may be partially attributable to the long-term drying trend. Our results suggest that a continued gradual decline of photosynthetic capacity and moisture content driven by the persistent drying trend could alter the composition and structure of the Congolese forest to favour the spread of drought-tolerant species(1,2,14).
C1 [Zhou, Liming] SUNY Albany, Dept Atmospher & Environm Sci, Albany, NY 12222 USA.
   [Tian, Yuhong] NOAA, IMSG, NESDIS, Ctr Satellite Applicat & Res,STAR, College Pk, MD 20740 USA.
   [Myneni, Ranga B.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Ciais, Philippe] UVSQ, CEA, CNRS, LSCE, F-91191 Gif Sur Yvette, France.
   [Saatchi, Sassan] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Liu, Yi Y.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Liu, Yi Y.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Piao, Shilong] Peking Univ, Dept Ecol, Coll Urban & Environm Sci, Beijing 100871, Peoples R China.
   [Chen, Haishan] Nanjing Univ Informat Sci & Technol, Minist Educ, Key Lab Meteorol Disaster, Nanjing 210044, Jiangsu, Peoples R China.
   [Vermote, Eric F.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Song, Conghe] Univ N Carolina, Dept Geog, Chapel Hill, NC 29599 USA.
   [Song, Conghe] Anhui Agr Univ, Sch Forestry & Landscape Architecture, Hefei 230036, Anhui, Peoples R China.
   [Hwang, Taehee] Univ N Carolina, Inst Environm, Chapel Hill, NC 29599 USA.
C3 State University of New York (SUNY) System; University at Albany, SUNY; National Oceanic Atmospheric Admin (NOAA) - USA; Boston University; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CEA; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; University of New South Wales Sydney; Peking University; Nanjing University of Information Science & Technology; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of North Carolina; University of North Carolina Chapel Hill; Anhui Agricultural University; University of North Carolina; University of North Carolina Chapel Hill
RP Zhou, LM (corresponding author), SUNY Albany, Dept Atmospher & Environm Sci, Albany, NY 12222 USA.
EM lzhou@albany.edu
FU NOAA NESDIS [NA11NES4400010]; University at Albany, State University of New York; NASA's Earth Science Division; National Natural Science Foundation of China [41230422]
NR 51
TC 359
Z9 404
U1 6
U2 533
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2014
VL 509
IS 7498
BP 86
EP +
DI 10.1038/nature13265
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100044
PM 24759324
DA 2026-03-09
ER

PT J
AU Borer, ET
   Seabloom, EW
   Gruner, DS
   Harpole, WS
   Hillebrand, H
   Lind, EM
   Adler, PB
   Alberti, J
   Anderson, TM
   Bakker, JD
   Biederman, L
   Blumenthal, D
   Brown, CS
   Brudvig, LA
   Buckley, YM
   Cadotte, M
   Chu, CJ
   Cleland, EE
   Crawley, MJ
   Daleo, P
   Damschen, EI
   Davies, KF
   DeCrappeo, NM
   Du, GZ
   Firn, J
   Hautier, Y
   Heckman, RW
   Hector, A
   HilleRisLambers, J
   Iribarne, O
   Klein, JA
   Knops, JMH
   La Pierre, KJ
   Leakey, ADB
   Li, W
   MacDougall, AS
   McCulley, RL
   Melbourne, BA
   Mitchell, CE
   Moore, JL
   Mortensen, B
   O'Halloran, LR
   Orrock, JL
   Pascual, J
   Prober, SM
   Pyke, DA
   Risch, AC
   Schuetz, M
   Smith, MD
   Stevens, CJ
   Sullivan, LL
   Williams, RJ
   Wragg, PD
   Wright, JP
   Yang, LH
AF Borer, Elizabeth T.
   Seabloom, Eric W.
   Gruner, Daniel S.
   Harpole, W. Stanley
   Hillebrand, Helmut
   Lind, Eric M.
   Adler, Peter B.
   Alberti, Juan
   Anderson, T. Michael
   Bakker, Jonathan D.
   Biederman, Lori
   Blumenthal, Dana
   Brown, Cynthia S.
   Brudvig, Lars A.
   Buckley, Yvonne M.
   Cadotte, Marc
   Chu, Chengjin
   Cleland, Elsa E.
   Crawley, Michael J.
   Daleo, Pedro
   Damschen, Ellen I.
   Davies, Kendi F.
   DeCrappeo, Nicole M.
   Du, Guozhen
   Firn, Jennifer
   Hautier, Yann
   Heckman, Robert W.
   Hector, Andy
   HilleRisLambers, Janneke
   Iribarne, Oscar
   Klein, Julia A.
   Knops, Johannes M. H.
   La Pierre, Kimberly J.
   Leakey, Andrew D. B.
   Li, Wei
   MacDougall, Andrew S.
   McCulley, Rebecca L.
   Melbourne, Brett A.
   Mitchell, Charles E.
   Moore, Joslin L.
   Mortensen, Brent
   O'Halloran, Lydia R.
   Orrock, John L.
   Pascual, Jesus
   Prober, Suzanne M.
   Pyke, David A.
   Risch, Anita C.
   Schuetz, Martin
   Smith, Melinda D.
   Stevens, Carly J.
   Sullivan, Lauren L.
   Williams, Ryan J.
   Wragg, Peter D.
   Wright, Justin P.
   Yang, Louie H.
TI Herbivores and nutrients control grassland plant diversity via light limitation
SO NATURE
LA English
DT Article
ID resource control; competition; growth; consumer; depends; impact
AB Human alterations to nutrient cycles(1,2) and herbivore communities(3-7) are affecting global biodiversity dramatically(2). Ecological theory predicts these changes should be strongly counteractive: nutrient addition drives plant species loss through intensified competition for light, whereas herbivores prevent competitive exclusion by increasing ground-level light, particularly in productive systems(8,9). Here we use experimental data spanning a globally relevant range of conditions to test the hypothesis that herbaceous plant species losses caused by eutrophication may be offset by increased light availability due to herbivory. This experiment, replicated in 40 grasslands on 6 continents, demonstrates that nutrients and herbivores can serve as counteracting forces to control local plant diversity through light limitation, independent of site productivity, soil nitrogen, herbivore type and climate. Nutrient addition consistently reduced local diversity through light limitation, and herbivory rescued diversity at sites where it alleviated light limitation. Thus, species loss from anthropogenic eutrophication can be ameliorated in grasslands where herbivory increases ground-level light.
C1 [Borer, Elizabeth T.; Seabloom, Eric W.; Lind, Eric M.; Hautier, Yann; Wragg, Peter D.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Gruner, Daniel S.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Harpole, W. Stanley; Biederman, Lori; Li, Wei; Mortensen, Brent; Sullivan, Lauren L.; Williams, Ryan J.] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
   [Hillebrand, Helmut] Carl von Ossietzky Univ Oldenburg, Inst Chem & Biol Marine Environm, D-26382 Oldenburg, Germany.
   [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.
   [Alberti, Juan; Daleo, Pedro; Iribarne, Oscar; Pascual, Jesus] Consejo Nacl Invest Cient & Tecn, IIMyC, RA-7600 Mar Del Plata, Argentina.
   [Anderson, T. Michael] Wake Forest Univ, Dept Biol, Winston Salem, NC 27109 USA.
   [Bakker, Jonathan D.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Blumenthal, Dana] ARS, USDA, Ft Collins, CO 80526 USA.
   [Brown, Cynthia S.; Klein, Julia A.; Smith, Melinda D.] Colorado State Univ, Dept Forest Rangeland & Watershed Stewardship, Ft Collins, CO 80523 USA.
   [Brudvig, Lars A.] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.
   [Buckley, Yvonne M.] Univ Queensland, Sch Biol Sci, ARC Ctr Excellence Environm Decis, Brisbane, Qld 4072, Australia.
   [Buckley, Yvonne M.] Trinity Coll Dublin, Sch Nat Sci, Dublin 2, Ireland.
   [Cadotte, Marc] Univ Toronto, Dept Ecol & Evolutionary Biol, Scarborough, ON M1C 1A4, Canada.
   [Chu, Chengjin; Du, Guozhen] Lanzhou Univ, Sch Life Sci, Res Stn Alpine Meadow & Wetland Ecosyst, State Key Lab Grassland & Agroecosyst, Lanzhou 730000, Gansu, Peoples R China.
   [Cleland, Elsa E.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92093 USA.
   [Crawley, Michael J.] Univ London Imperial Coll Sci Technol & Med, Dept Biol, 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.
   [DeCrappeo, Nicole M.; Pyke, David A.] US Geol Survey, Forest & Rangeland Ecosyst Sci Ctr, Corvallis, OR 97331 USA.
   [Firn, Jennifer] Queensland Univ Technol, Brisbane, Qld 4001, Australia.
   [Heckman, Robert W.; Mitchell, Charles E.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Hector, Andy] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
   [HilleRisLambers, Janneke] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Knops, Johannes M. H.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
   [La Pierre, Kimberly J.] Univ Calif Berkeley, Berkeley Initiat Global Change Biol, Berkeley, CA 94704 USA.
   [Leakey, Andrew D. B.] Univ Illinois, Dept Plant Biol, Champaign, IL 61820 USA.
   [MacDougall, Andrew S.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [McCulley, Rebecca L.] Univ Kentucky, Dept Plant & Soil Sci, Lexington, KY 40546 USA.
   [Moore, Joslin L.] Univ Melbourne, Sch Bot, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia.
   [Moore, Joslin L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [O'Halloran, Lydia R.] Oregon State Univ, Dept Zool, Corvallis, OR 97331 USA.
   [Prober, Suzanne M.] CSIRO Ecosyst Sci, Wembley, WA 6913, Australia.
   [Risch, Anita C.; Schuetz, Martin] Swiss Fed Inst Forest Snow & Landscape Res, CH-8903 Birmensdorf, Switzerland.
   [Stevens, Carly J.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Wright, Justin P.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Yang, Louie H.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University System of Maryland; University of Maryland College Park; Iowa State University; Carl von Ossietzky Universitat Oldenburg; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Wake Forest University; University of Washington; University of Washington Seattle; United States Department of Agriculture (USDA); Colorado State University System; Colorado State University Fort Collins; Michigan State University; University of Queensland; Trinity College Dublin; University of Toronto; University Toronto Scarborough; Lanzhou University; University of California System; University of California San Diego; Imperial College London; University of Wisconsin System; University of Wisconsin Madison; University of Colorado System; University of Colorado Boulder; United States Department of the Interior; United States Geological Survey; Queensland University of Technology (QUT); University of North Carolina; University of North Carolina Chapel Hill; University of Oxford; University of Washington; University of Washington Seattle; University of Nebraska System; University of Nebraska Lincoln; University of California System; University of California Berkeley; University of Illinois System; University of Illinois Urbana-Champaign; University of Guelph; University of Kentucky; University of Melbourne; Monash University; Oregon State University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Lancaster University; Duke University; University of California System; University of California Davis
RP Borer, ET (corresponding author), Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
EM borer@umn.edu
FU NSF Research Coordination Network [NSF-DEB-1042132]; 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 [0823380, 1042132, 1440484] Funding Source: National Science Foundation
NR 31
TC 786
Z9 904
U1 46
U2 1411
PU NATURE PUBLISHING 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 24
PY 2014
VL 508
IS 7497
BP 517
EP +
DI 10.1038/nature13144
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600035
PM 24670649
DA 2026-03-09
ER

PT J
AU Amari, T
   Canou, A
   Aly, JJ
AF Amari, Tahar
   Canou, Aurelien
   Aly, Jean-Jacques
TI Characterizing and predicting the magnetic environment leading to solar eruptions
SO NATURE
LA English
DT Article
ID 2006 december 13; coronal mass ejections; twisted flux tube; active-region; vector magnetograms; field; flare; model; evolution; rope
AB The physical mechanism responsible for coronal mass ejections has been uncertain for many years, in large part because of the difficulty of knowing the three-dimensional magnetic field in the low corona(1). Two possible models have emerged. In the first, a twisted flux rope moves out of equilibrium or becomes unstable, and the subsequent reconnection then powers the ejection(2-5). In the second, a new flux rope forms as a result of the reconnection of the magnetic lines of an arcade (a group of arches of field lines) during the eruption itself(6). Observational support for both mechanisms has been claimed(7-9). Here we report modelling which demonstrates that twisted flux ropes lead to the ejection, in support of the first model. After seeing a coronal mass ejection, we use the observed photospheric magnetic field in that region from four days earlier as a boundary condition to determine the magnetic field configuration. The field evolves slowly before the eruption, such that it can be treated effectively as a static solution. We find that on the fourth day a flux rope forms and grows (increasing its free energy). This solution then becomes the initial condition as we let the model evolve dynamically under conditions driven by photospheric changes (such as flux cancellation). When the magnetic energy stored in the configuration is too high, no equilibrium is possible and the flux rope is squeezed upwards. The subsequent reconnection drives a mass ejection.
C1 [Amari, Tahar; Canou, Aurelien] Ecole Polytech, Ctr Phys Theor, CNRS, F-91128 Palaiseau, France.
   [Aly, Jean-Jacques] Univ Paris 07, AIM, CNRS, Ctr Etud Saclay,UMR CEA,UMR 7158, F-91191 Gif Sur Yvette, France.
C3 Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); CEA; Universite Paris Cite; Universite Paris Saclay
RP Amari, T (corresponding author), Ecole Polytech, Ctr Phys Theor, CNRS, F-91128 Palaiseau, France.
EM amari@cpht.polytechnique.fr
FU Centre National d'Etudes Spatiales (CNES)
NR 49
TC 117
Z9 126
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 OCT 23
PY 2014
VL 514
IS 7523
BP 465
EP +
DI 10.1038/nature13815
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900034
PM 25341785
DA 2026-03-09
ER

PT J
AU Ghelfi, P
   Laghezza, F
   Scotti, F
   Serafino, G
   Capria, A
   Pinna, S
   Onori, D
   Porzi, C
   Scaffardi, M
   Malacarne, A
   Vercesi, V
   Lazzeri, E
   Berizzi, F
   Bogoni, A
AF Ghelfi, Paolo
   Laghezza, Francesco
   Scotti, Filippo
   Serafino, Giovanni
   Capria, Amerigo
   Pinna, Sergio
   Onori, Daniel
   Porzi, Claudio
   Scaffardi, Mirco
   Malacarne, Antonio
   Vercesi, Valeria
   Lazzeri, Emma
   Berizzi, Fabrizio
   Bogoni, Antonella
TI A fully photonics-based coherent radar system
SO NATURE
LA English
DT Article
ID wave-form generation; signals
AB The next generation of radar (radio detection and ranging) systems needs to be based on software-defined radio to adapt to variable environments, with higher carrier frequencies for smaller antennas and broadened bandwidth for increased resolution(1-4). Today's digital microwave components (synthesizers and analogue-to-digital converters) suffer from limited bandwidth with high noise at increasing frequencies(5-7), so that fully digital radar systems can work up to only a few gigahertz, and noisy analogue up-and downconversions are necessary for higher frequencies. In contrast, photonics provide high precision and ultrawide bandwidth(8,9), allowing both the flexible generation of extremely stable radio-frequency signals with arbitrary waveforms up to millimetre waves(10-22), and the detection of such signals and their precise direct digitization without downconversion(23-26). Until now, the photonics-based generation and detection of radio-frequency signals have been studied separately and have not been tested in a radar system. Here we present the development and the field trial results of a fully photonics-based coherent radar demonstrator carried out within the project PHODIR27. The proposed architecture exploits a single pulsed laser for generating tunable radar signals and receiving their echoes, avoiding radio-frequency up-and downconversion and guaranteeing both the software-defined approach and high resolution. Its performance exceeds state-of-the-art electronics at carrier frequencies above two gigahertz, and the detection of non-cooperating aeroplanes confirms the effectiveness and expected precision of the system.
C1 [Ghelfi, Paolo; Laghezza, Francesco; Scotti, Filippo; Scaffardi, Mirco; Malacarne, Antonio; Lazzeri, Emma; Bogoni, Antonella] Interuniv Natl Consortium Telecommun CNIT, Natl Lab Photon Networks, I-56124 Pisa, Italy.
   [Serafino, Giovanni; Pinna, Sergio; Onori, Daniel; Porzi, Claudio; Vercesi, Valeria] Scuola Super Sant Anna, TeCIP Inst, I-56124 Pisa, Italy.
   [Capria, Amerigo; Berizzi, Fabrizio] Interuniv Natl Consortium Telecommun CNIT, Natl Lab Radars & Surveillance Syst, I-56126 Pisa, Italy.
   [Berizzi, Fabrizio] Univ Pisa, Dept Informat Engn, I-56122 Pisa, Italy.
C3 Scuola Superiore Sant'Anna; University of Pisa
RP Bogoni, A (corresponding author), Interuniv Natl Consortium Telecommun CNIT, Natl Lab Photon Networks, Via Moruzzi 1, I-56124 Pisa, Italy.
EM antonella.bogoni@cnit.it
FU ERC [239640, 324629]; EU NEXPRESSO programme through the project INSIDE; Selex ES S.p.A.; European Research Council (ERC) [239640, 324629] Funding Source: European Research Council (ERC)
NR 29
TC 935
Z9 1039
U1 17
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 MAR 20
PY 2014
VL 507
IS 7492
BP 341
EP 345
DI 10.1038/nature13078
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000030
PM 24646997
DA 2026-03-09
ER

PT J
AU Cheng, Y
   Ma, ZH
   Kim, BH
   Wu, WS
   Cayting, P
   Boyle, AP
   Sundaram, V
   Xing, XY
   Dogan, N
   Li, JJ
   Euskirchen, G
   Lin, S
   Lin, Y
   Visel, A
   Kawli, T
   Yang, XQ
   Patacsil, D
   Keller, CA
   Giardine, B
   Kundaje, A
   Wang, T
   Pennacchio, LA
   Weng, ZP
   Hardison, RC
   Snyder, MP
AF Cheng, Yong
   Ma, Zhihai
   Kim, Bong-Hyun
   Wu, Weisheng
   Cayting, Philip
   Boyle, Alan P.
   Sundaram, Vasavi
   Xing, Xiaoyun
   Dogan, Nergiz
   Li, Jingjing
   Euskirchen, Ghia
   Lin, Shin
   Lin, Yiing
   Visel, Axel
   Kawli, Trupti
   Yang, Xinqiong
   Patacsil, Dorrelyn
   Keller, Cheryl A.
   Giardine, Belinda
   Kundaje, Anshul
   Wang, Ting
   Pennacchio, Len A.
   Weng, Zhiping
   Hardison, Ross C.
   Snyder, Michael P.
TI Principles of regulatory information conservation between mouse and human
SO NATURE
LA English
DT Article
ID transcription factor-binding; chromatin; enhancers; genome; sequences; elements; sites; ctcf
AB To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human-mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.
C1 [Cheng, Yong; Ma, Zhihai; Cayting, Philip; Boyle, Alan P.; Li, Jingjing; Euskirchen, Ghia; Lin, Shin; Lin, Yiing; Kawli, Trupti; Yang, Xinqiong; Patacsil, Dorrelyn; Kundaje, Anshul; Snyder, Michael P.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Kim, Bong-Hyun; Weng, Zhiping] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA.
   [Wu, Weisheng; Dogan, Nergiz; Keller, Cheryl A.; Giardine, Belinda; Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Wu, Weisheng] Univ Michigan, BRCF Bioinformat Core, Ann Arbor, MI 48105 USA.
   [Sundaram, Vasavi; Xing, Xiaoyun; Wang, Ting] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, Dept Genet, St Louis, MO 63108 USA.
   [Lin, Shin] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94304 USA.
   [Lin, Yiing] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
   [Visel, Axel; Pennacchio, Len A.] Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94701 USA.
   [Visel, Axel; Pennacchio, Len A.] Dept Energy Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Visel, Axel] Univ Calif, Sch Nat Sci, Merced, CA 95343 USA.
C3 Stanford University; University of Massachusetts System; University of Massachusetts Worcester; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Michigan System; University of Michigan; Washington University (WUSTL); Stanford University; Washington University (WUSTL); United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Merced
RP Snyder, MP (corresponding author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
EM rch8@psu.edu; mpsnyder@stanford.edu
FU National Human Genome Research Institute (NHGRI) [R01HG003988, U54HG006997]; American Recovery and Reinvestment Act; Department of Energy, University of California [DE-AC02-05CH11231];  [3RC2HG005602];  [5U54HG006996];  [1U54HG00699];  [R01DK065806];  [RC2HG005573]; National Cancer Institute [T32CA113275] Funding Source: NIH RePORTER; National Eye Institute [R01EY021482] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG007175, R01HG003988] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM083337] Funding Source: NIH RePORTER
NR 29
TC 220
Z9 282
U1 0
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 20
PY 2014
VL 515
IS 7527
BP 371
EP +
DI 10.1038/nature13985
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600036
PM 25409826
DA 2026-03-09
ER

PT J
AU Iossifov, I
   O'Roak, BJ
   Sanders, SJ
   Ronemus, M
   Krumm, N
   Levy, D
   Stessman, HA
   Witherspoon, KT
   Vives, L
   Patterson, KE
   Smith, JD
   Paeper, B
   Nickerson, DA
   Dea, J
   Dong, S
   Gonzalez, LE
   Mandell, JD
   Mane, SM
   Murtha, MT
   Sullivan, CA
   Walker, MF
   Waqar, Z
   Wei, LP
   Willsey, AJ
   Yamrom, B
   Lee, YH
   Grabowska, E
   Dalkic, E
   Wang, ZH
   Marks, S
   Andrews, P
   Leotta, A
   Kendall, J
   Hakker, I
   Rosenbaum, J
   Ma, BC
   Rodgers, L
   Troge, J
   Narzisi, G
   Yoon, S
   Schatz, MC
   Ye, K
   McCombie, WR
   Shendure, J
   Eichler, EE
   State, MW
   Wigler, M
AF Iossifov, Ivan
   O'Roak, Brian J.
   Sanders, Stephan J.
   Ronemus, Michael
   Krumm, Niklas
   Levy, Dan
   Stessman, Holly A.
   Witherspoon, Kali T.
   Vives, Laura
   Patterson, Karynne E.
   Smith, Joshua D.
   Paeper, Bryan
   Nickerson, Deborah A.
   Dea, Jeanselle
   Dong, Shan
   Gonzalez, Luis E.
   Mandell, Jeffrey D.
   Mane, Shrikant M.
   Murtha, Michael T.
   Sullivan, Catherine A.
   Walker, Michael F.
   Waqar, Zainulabedin
   Wei, Liping
   Willsey, A. Jeremy
   Yamrom, Boris
   Lee, Yoon-ha
   Grabowska, Ewa
   Dalkic, Ertugrul
   Wang, Zihua
   Marks, Steven
   Andrews, Peter
   Leotta, Anthony
   Kendall, Jude
   Hakker, Inessa
   Rosenbaum, Julie
   Ma, Beicong
   Rodgers, Linda
   Troge, Jennifer
   Narzisi, Giuseppe
   Yoon, Seungtai
   Schatz, Michael C.
   Ye, Kenny
   McCombie, W. Richard
   Shendure, Jay
   Eichler, Evan E.
   State, Matthew W.
   Wigler, Michael
TI The contribution of de novo coding mutations to autism spectrum disorder
SO NATURE
LA English
DT Article
ID copy-number variation; intellectual disability; structural variation; inherited disease; paternal age; schizophrenia; network; risk; evolution; resource
AB Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.
C1 [Iossifov, Ivan; Ronemus, Michael; Levy, Dan; Yamrom, Boris; Lee, Yoon-ha; Grabowska, Ewa; Dalkic, Ertugrul; Wang, Zihua; Marks, Steven; Andrews, Peter; Leotta, Anthony; Kendall, Jude; Hakker, Inessa; Rosenbaum, Julie; Ma, Beicong; Rodgers, Linda; Troge, Jennifer; Narzisi, Giuseppe; Yoon, Seungtai; Schatz, Michael C.; McCombie, W. Richard; Wigler, Michael] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [O'Roak, Brian J.; Krumm, Niklas; Stessman, Holly A.; Witherspoon, Kali T.; Vives, Laura; Patterson, Karynne E.; Smith, Joshua D.; Paeper, Bryan; Nickerson, Deborah A.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [O'Roak, Brian J.] Oregon Hlth & Sci Univ, Portland, OR 97208 USA.
   [Sanders, Stephan J.; Dea, Jeanselle; Mandell, Jeffrey D.; Walker, Michael F.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
   [Sanders, Stephan J.; Dong, Shan; Willsey, A. Jeremy; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Dong, Shan; Wei, Liping] Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
   [Gonzalez, Luis E.; Murtha, Michael T.; Sullivan, Catherine A.; Waqar, Zainulabedin; State, Matthew W.] Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA.
   [Mane, Shrikant M.] Yale Univ, Ctr Child Study, Yale Ctr Genom Anal, New Haven, CT 06520 USA.
   [Wei, Liping] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Grabowska, Ewa; Narzisi, Giuseppe] New York Genome Ctr, New York, NY 10013 USA.
   [Dalkic, Ertugrul] Bulent Ecevit Univ, Sch Med, Dept Med Biol, TR-67600 Zonguldak, Turkey.
   [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [State, Matthew W.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA.
C3 Cold Spring Harbor Laboratory; University of Washington; University of Washington Seattle; Oregon Health & Science University; University of California System; University of California San Francisco; Yale University; Peking University; Yale University; Yale University; National Institute of Biological Sciences, Beijing; Zonguldak Bulent Ecevit University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Howard Hughes Medical Institute; Yale University
RP Shendure, J (corresponding author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
EM shendure@uw.edu; eee@gs.washington.edu; matthew.state@ucsf.edu; wigler@cshl.edu
FU Simons Foundation Autism Research Initiative grants [SF191889, M144095 R11154, SF235988]; Howard Hughes Medical Institute (International Student Research Fellowship); Canadian Institutes of Health Research (Doctoral Foreign Study Award); NHLBI [HL-102923, HL-102924, HL-102925, HL-102926, HL-103010]
NR 49
TC 1930
Z9 2305
U1 4
U2 243
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 216
EP U136
DI 10.1038/nature13908
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400039
PM 25363768
DA 2026-03-09
ER

PT J
AU Kossin, JP
   Emanuel, KA
   Vecchi, GA
AF Kossin, James P.
   Emanuel, Kerry A.
   Vecchi, Gabriel A.
TI The poleward migration of the location of tropical cyclone maximum intensity
SO NATURE
LA English
DT Article
ID vertical wind shear; cluster-analysis; reanalysis; tracks; trends
AB Temporally inconsistent and potentially unreliable global historical data hinder the detection of trends in tropical cyclone activity(1-3). This limits our confidence in evaluating proposed linkages between observed trends in tropical cyclones and in the environment(4,5). Here we mitigate this difficulty by focusing on a metric that is comparatively insensitive to past data uncertainty, and identify a pronounced poleward migration in the average latitude at which tropical cyclones have achieved their lifetime-maximum intensity over the past 30 years. The poleward trends are evident in the global historical data in both the Northern and the Southern hemispheres, with rates of 53 and 62 kilometres per decade, respectively, and are statistically significant. When considered together, the trends in each hemisphere depict a global-average migration of tropical cyclone activity away from the tropics at a rate of about one degree of latitude per decade, which lies within the range of estimates of the observed expansion of the tropics over the same period(6). The global migration remains evident and statistically significant under a formal data homogenization procedure(3), and is unlikely to be a data artefact. The migration away from the tropics is apparently linked to marked changes in the mean meridional structure of environmental vertical wind shear and potential intensity, and can plausibly be linked to tropical expansion, which is thought to have anthropogenic contributions(6).
C1 [Kossin, James P.] Univ Wisconsin, NOAA Natl Climat Data Ctr, CIMSS, Madison, WI 53706 USA.
   [Emanuel, Kerry A.] MIT, Program Atmospheres Oceans & Climate, Cambridge, MA 02139 USA.
   [Vecchi, Gabriel A.] NOAA Geophys Fluid Dynam Lab, Princeton, NJ 08540 USA.
C3 National Oceanic Atmospheric Admin (NOAA) - USA; University of Wisconsin System; University of Wisconsin Madison; Massachusetts Institute of Technology (MIT); National Oceanic Atmospheric Admin (NOAA) - USA
RP Kossin, JP (corresponding author), Univ Wisconsin, NOAA Natl Climat Data Ctr, CIMSS, 1225 W Dayton St, Madison, WI 53706 USA.
EM james.kossin@.noaa.gov
FU Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1342810] Funding Source: National Science Foundation
NR 32
TC 583
Z9 652
U1 9
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 MAY 15
PY 2014
VL 509
IS 7500
BP 349
EP +
DI 10.1038/nature13278
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200036
PM 24828193
DA 2026-03-09
ER

PT J
AU Gao, L
   Liang, JY
   Li, CY
   Wang, LHV
AF Gao, Liang
   Liang, Jinyang
   Li, Chiye
   Wang, Lihong V.
TI Single-shot compressed ultrafast photography at one hundred billion frames per second
SO NATURE
LA English
DT Article
AB The capture of transient scenes at high imaging speed has been long sought by photographers(1-4), with early examples being the well known recording in 1878 of a horse in motion' and the 1887 photograph of a supersonic bullet(6). However, not until the late twentieth century were breakthroughs achieved in demonstrating ultrahigh-speed imaging (more than 10(5) frames per second)(7). In particular, the introduction of electronic imaging sensors based on the charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) technology revolutionized high-speed photography, enabling acquisition rates of up to 10(7) frames per second(8). Despite these sensors' widespread impact, further increasing frame rates using CCD or CMOS technology is fundamentally limited by their on-chip storage and electronic readout speed(9). Here we demonstrate a two-dimensional dynamic imaging technique, compressed ultrafast photography (CUP), which can capture non-repetitive time-evolving events at up to 10(11) frames per second. Compared with existing ultrafast imaging techniques, CUP has the prominent advantage of measuring an x-y- t (x, y, spatial coordinates; t, time) scene with a single camera snapshot, thereby allowing observation of transient events with temporal resolution as tens of picoseconds. Furthermore, akin to traditional photography, CUP is receive-only, and so does not need the specialized active illumination required by other single-shot ultrafast imagers(2,3). As a result, CUP can image a variety of luminescent such as fluorescent or bioluminescent objects. Using CUP, we visualize four fundamental physical phenomena with single laser shots only: laser pulse reflection and refraction, photon racing in two media, and fasterthan-light propagation of non-information (that is, motion that appears faster than the speed of light but cannot convey information). Given CUP's capability, we expect it to find widespread applications in both fundamental and applied sciences, including biomedical research.
C1 [Gao, Liang; Liang, Jinyang; Li, Chiye; Wang, Lihong V.] Washington Univ, Dept Biomed Engn, Opt Imaging Lab, St Louis, MO 63130 USA.
C3 Washington University (WUSTL)
RP Wang, LHV (corresponding author), Washington Univ, Dept Biomed Engn, Opt Imaging Lab, Campus Box 1097,One Brookings Dr, St Louis, MO 63130 USA.
EM lhwang@wustl.edu
FU National Institutes of Health [DP1 EB016986, R01 CA186567]
NR 26
TC 487
Z9 604
U1 15
U2 361
PU NATURE PUBLISHING 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 4
PY 2014
VL 516
IS 7529
BP 74
EP U159
DI 10.1038/nature14005
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800041
PM 25471883
DA 2026-03-09
ER

PT J
AU Bercovici, D
   Ricard, Y
AF Bercovici, David
   Ricard, Yanick
TI Plate tectonics, damage and inheritance
SO NATURE
LA English
DT Article
ID 2-phase grain-damage; dynamic recrystallization; mantle convection; growth; generation; model; size; evolution; flow; mechanisms
AB The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks(1,2)), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to forma nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.
C1 [Bercovici, David] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Ricard, Yanick] Univ Lyon 1, CNRS, ENS Lyon, Lab Geol Lyon, F-69622 Villeurbanne, France.
C3 Yale University; Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS)
RP Bercovici, D (corresponding author), Yale Univ, Dept Geol & Geophys, POB 6666, New Haven, CT 06520 USA.
EM david.bercovici@yale.edu
FU National Science Foundation; Agence Nationale de la Recherche; Division Of Earth Sciences; Directorate For Geosciences [1015229] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1135382, 1344538] Funding Source: National Science Foundation
NR 40
TC 235
Z9 264
U1 1
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 APR 24
PY 2014
VL 508
IS 7497
BP 513
EP +
DI 10.1038/nature13072
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600034
PM 24717430
DA 2026-03-09
ER

PT J
AU Moroz, LL
   Kocot, KM
   Citarella, MR
   Dosung, S
   Norekian, TP
   Povolotskaya, IS
   Grigorenko, AP
   Dailey, C
   Berezikov, E
   Buckley, KM
   Ptitsyn, A
   Reshetov, D
   Mukherjee, K
   Moroz, TP
   Bobkova, Y
   Yu, FH
   Kapitonov, VV
   Jurka, J
   Bobkov, YV
   Swore, JJ
   Girardo, DO
   Fodor, A
   Gusev, F
   Sanford, R
   Bruders, R
   Kittler, E
   Mills, CE
   Rast, JP
   Derelle, R
   Solovyev, VV
   Kondrashov, FA
   Swalla, BJ
   Sweedler, JV
   Rogaev, EI
   Halanych, KM
   Kohn, AB
AF Moroz, Leonid L.
   Kocot, Kevin M.
   Citarella, Mathew R.
   Dosung, Sohn
   Norekian, Tigran P.
   Povolotskaya, Inna S.
   Grigorenko, Anastasia P.
   Dailey, Christopher
   Berezikov, Eugene
   Buckley, Katherine M.
   Ptitsyn, Andrey
   Reshetov, Denis
   Mukherjee, Krishanu
   Moroz, Tatiana P.
   Bobkova, Yelena
   Yu, Fahong
   Kapitonov, Vladimir V.
   Jurka, Jerzy
   Bobkov, Yuri V.
   Swore, Joshua J.
   Girardo, David O.
   Fodor, Alexander
   Gusev, Fedor
   Sanford, Rachel
   Bruders, Rebecca
   Kittler, Ellen
   Mills, Claudia E.
   Rast, Jonathan P.
   Derelle, Romain
   Solovyev, Victor V.
   Kondrashov, Fyodor A.
   Swalla, Billie J.
   Sweedler, Jonathan V.
   Rogaev, Evgeny I.
   Halanych, Kenneth M.
   Kohn, Andrea B.
TI The ctenophore genome and the evolutionary origins of neural systems
SO NATURE
LA English
DT Article
ID multiple sequence alignment; capillary-electrophoresis; maximum-likelihood; complex brains; transcriptome; database; genes; phylogenomics; proteins; blast
AB The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes, and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well recognized in ctenophores, many bilaterian neuron-specific genes and genes of 'classical' neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.
C1 [Moroz, Leonid L.; Citarella, Mathew R.; Dosung, Sohn; Norekian, Tigran P.; Ptitsyn, Andrey; Mukherjee, Krishanu; Moroz, Tatiana P.; Bobkova, Yelena; Bobkov, Yuri V.; Swore, Joshua J.; Girardo, David O.; Fodor, Alexander; Sanford, Rachel; Bruders, Rebecca; Kohn, Andrea B.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
   [Moroz, Leonid L.; Yu, Fahong] Univ Florida, Dept Neurosci, Gainesville, FL 32611 USA.
   [Moroz, Leonid L.; Yu, Fahong] Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA.
   [Moroz, Leonid L.; Norekian, Tigran P.; Swore, Joshua J.; Girardo, David O.; Bruders, Rebecca; Mills, Claudia E.; Swalla, Billie J.] Univ Washington, Friday Harbor Labs, Friday Harbor, WA 98250 USA.
   [Kocot, Kevin M.; Halanych, Kenneth M.] Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA.
   [Povolotskaya, Inna S.; Derelle, Romain; Kondrashov, Fyodor A.] CRG, Barcelona 08003, Spain.
   [Povolotskaya, Inna S.; Derelle, Romain; Kondrashov, Fyodor A.] UPF, Barcelona 08003, Spain.
   [Grigorenko, Anastasia P.; Gusev, Fedor; Rogaev, Evgeny I.] Univ Massachusetts, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Sch Med, Worcester, MA 01604 USA.
   [Grigorenko, Anastasia P.; Reshetov, Denis; Gusev, Fedor; Rogaev, Evgeny I.] RAS, Vavilov Inst Gen Genet, Moscow 119991, Russia.
   [Dailey, Christopher; Sweedler, Jonathan V.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Dailey, Christopher; Sweedler, Jonathan V.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.
   [Berezikov, Eugene] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, NL-9713 AB Groningen, Netherlands.
   [Buckley, Katherine M.; Rast, Jonathan P.] Univ Toronto, Sunnybrook Res Inst, Dept Med Biophys, Toronto, ON M4N 3M5, Canada.
   [Buckley, Katherine M.; Rast, Jonathan P.] Univ Toronto, Sunnybrook Res Inst, Dept Immunol, Toronto, ON M4N 3M5, Canada.
   [Kapitonov, Vladimir V.; Jurka, Jerzy] Genet Informat Res Inst, Mountain View, CA 94043 USA.
   [Kittler, Ellen] Univ Massachusetts, Sch Med, Program Mol Med, Shrewsbury, MA 01545 USA.
   [Solovyev, Victor V.] Univ London, Dept Comp Sci, Egham TW20 0EX, Surrey, England.
   [Kondrashov, Fyodor A.] ICREA, Barcelona 08010, Spain.
   [Rogaev, Evgeny I.] RAS, Ctr Brain Neurobiol & Neurogenet, Novosibirsk 630090, Russia.
   [Rogaev, Evgeny I.] RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Rogaev, Evgeny I.] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia.
C3 State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; University of Washington; Auburn University System; Auburn University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; University of Massachusetts System; University of Massachusetts Worcester; Russian Academy of Sciences; Vavilov Institute of General Genetics; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Groningen; University of Toronto; Sunnybrook Health Science Center; Sunnybrook Research Institute; University of Toronto; Sunnybrook Health Science Center; Sunnybrook Research Institute; University of Massachusetts System; University of London; Royal Holloway University London; ICREA; Russian Academy of Sciences; Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; Lomonosov Moscow State University
RP Moroz, LL (corresponding author), Univ Florida, Whitney Lab Marine Biosci, 9505 Ocean Shore Blvd, St Augustine, FL 32080 USA.
EM moroz@whitney.ufl.edu; Evgeny.Rogaev@umassmed.edu; abkohn@msn.com
FU NSF [NSF-0744649, CNS-0821622, CHE-1111705]; NIH [1R01GM097502, R01MH097062, R21RR025699, 5R21DA030118, P30 DA018310, R01 AG029360, 1S10RR027052]; NASA [NNX13AJ31G]; NSERC [458115, 211598]; University of Florida Opportunity Funds/McKnight Brain Research; Florida Biodiversity Institute; Rostock Inc.; Russian Federation Government [14.B25.31.0033, 220]; HHMI [55007424]; EMBO; MINECO [BFU2012-31329, Sev-2012-0208]; AU Marine Biology Program [117]; NASA [NNX13AJ31G, 471996] Funding Source: Federal RePORTER; Direct For Biological Sciences; Div Of Biological Infrastructure [1306538] Funding Source: National Science Foundation; Division Of Chemistry; Direct For Mathematical & Physical Scien [1111705] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1146575] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1156528] Funding Source: National Science Foundation; National Institute on Drug Abuse [P30DA018310] Funding Source: NIH RePORTER; ICREA Funding Source: Custom; Academy of Finland (AKA) [211598] Funding Source: Academy of Finland (AKA)
NR 68
TC 520
Z9 593
U1 1
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 JUN 5
PY 2014
VL 510
IS 7503
BP 109
EP +
DI 10.1038/nature13400
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900038
PM 24847885
DA 2026-03-09
ER

PT J
AU Lee, YJ
   Dominy, JE
   Choi, YJ
   Jurczak, M
   Tolliday, N
   Camporez, JP
   Chim, H
   Lim, JH
   Ruan, HB
   Yang, XY
   Vazquez, F
   Sicinski, P
   Shulman, GI
   Puigserver, P
AF Lee, Yoonjin
   Dominy, John E.
   Choi, Yoon Jong
   Jurczak, Michael
   Tolliday, Nicola
   Camporez, Joao Paulo
   Chim, Helen
   Lim, Ji-Hong
   Ruan, Hai-Bin
   Yang, Xiaoyong
   Vazquez, Francisca
   Sicinski, Piotr
   Shulman, Gerald I.
   Puigserver, Pere
TI Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression
SO NATURE
LA English
DT Article
ID hepatic gluconeogenesis; insulin-resistance; mice lacking; phosphorylation; inhibition; expression; cdk4; pgc-1-alpha; activation; receptor
AB Insulin constitutes a principal evolutionarily conserved hormonal axis for maintaining glucose homeostasis(1-3); dysregulation of this axis causes diabetes(2,4). PGC-1 alpha(peroxisome-proliferator-activated receptor-gamma coactivator-1 alpha) links insulin signalling to the expression of glucose and lipid metabolic genes(5-7). The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1 alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1 alpha(8,9). Although insulin is a mitogenic signal in proliferative cells(10,11), whether components of the cell cycle machinery contribute to its metabolic action is poorly understood. Here we report that in mice insulin activates cyclin D1-cyclin-dependent kinase 4 (Cdk4), which, in turn, increases GCN5 acetyltransferase activity and suppresses hepatic glucose production independently of cell cycle progression. Through a cell-based high-throughput chemical screen, we identify a Cdk4 inhibitor that potently decreases PGC-1 alpha acetylation. Insulin/GSK-3 beta (glycogen synthase kinase 3-beta) signalling induces cyclin D1 protein stability by sequestering cyclin D1 in the nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 messenger RNA transcripts. Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5, which then acetylates and inhibits PGC-1 alpha activity on gluconeogenic genes. Loss of hepatic cyclin D1 results in increased gluconeogenesis and hyperglycaemia. In diabetic models, cyclin D1-Cdk4 is chronically elevated and refractory to fasting/feeding transitions; nevertheless further activation of this kinase normalizes glycaemia. Our findings show that insulin uses components of the cell cycle machinery in post-mitotic cells to control glucose homeostasis independently of cell division.
C1 [Lee, Yoonjin; Dominy, John E.; Choi, Yoon Jong; Chim, Helen; Lim, Ji-Hong; Vazquez, Francisca; Sicinski, Piotr; Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Lee, Yoonjin; Dominy, John E.; Chim, Helen; Lim, Ji-Hong; Vazquez, Francisca; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Lee, Yoonjin] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Choi, Yoon Jong; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Jurczak, Michael; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Yales Mouse Metab Phenotyping Ctr, New Haven, CT 06510 USA.
   [Jurczak, Michael; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
   [Jurczak, Michael; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
   [Tolliday, Nicola] Broad Inst Harvard & MIT, Chem Biol Platform, Cambridge Ctr 7, Cambridge, MA 02141 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard Medical School; Yale University; Yale University; Yale University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Puigserver, P (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
FU Ewha Womans University; National Research Service Award Kirschstein Fellowship from the National Institutes of Health (NIH); Dana-Farber Cancer Institute; American Diabetes Association; Department of Defense; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01069966, R24DK080261-06]; NIH [R03 MH092174, R01 CA108420, DK059635]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034989, R01DK089098] Funding Source: NIH RePORTER
NR 35
TC 204
Z9 230
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 JUN 26
PY 2014
VL 510
IS 7506
BP 547
EP +
DI 10.1038/nature13267
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300049
PM 24870244
DA 2026-03-09
ER

PT J
AU Lu, T
   Aron, L
   Zullo, J
   Pan, Y
   Kim, H
   Chen, YW
   Yang, TH
   Kim, HM
   Drake, D
   Liu, XS
   Bennett, DA
   Colaiácovo, MP
   Yankner, BA
AF Lu, Tao
   Aron, Liviu
   Zullo, Joseph
   Pan, Ying
   Kim, Haeyoung
   Chen, Yiwen
   Yang, Tun-Hsiang
   Kim, Hyun-Min
   Drake, Derek
   Liu, X. Shirley
   Bennett, David A.
   Colaiacovo, Monica P.
   Yankner, Bruce A.
TI REST and stress resistance in ageing and Alzheimer's disease
SO NATURE
LA English
DT Article
ID genome-wide analysis; sel-12 presenilin; life-span; protein; repressor; expression; cortex; transcription; suppressors; chromatin
AB Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid beta-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid beta-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
C1 [Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Colaiacovo, Monica P.; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Chen, Yiwen; Liu, X. Shirley] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Kim, Haeyoung; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
C3 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; Rush University
RP Yankner, BA (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM Bruce_Yankner@hms.harvard.edu
FU NIH [DP1OD006849, PO1AG27916, RO1AG26651, RO1GM072551, P30AG10161, R01AG15819, R01AG17917]; Glenn Foundation for Medical Research; National Institute of General Medical Sciences [R01GM072551] Funding Source: NIH RePORTER; National Institute on Aging [R01AG017917, T32AG000222, R01AG015819] Funding Source: NIH RePORTER
NR 55
TC 616
Z9 714
U1 2
U2 302
PU NATURE PUBLISHING 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 27
PY 2014
VL 507
IS 7493
BP 448
EP +
DI 10.1038/nature13163
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000031
PM 24670762
DA 2026-03-09
ER

PT J
AU Reyes, AV
   Carlson, AE
   Beard, BL
   Hatfield, RG
   Stoner, JS
   Winsor, K
   Welke, B
   Ullman, DJ
AF Reyes, Alberto V.
   Carlson, Anders E.
   Beard, Brian L.
   Hatfield, Robert G.
   Stoner, Joseph S.
   Winsor, Kelsey
   Welke, Bethany
   Ullman, David J.
TI South Greenland ice-sheet collapse during Marine Isotope Stage 11
SO NATURE
LA English
DT Article
ID ketilidian mobile belt; deep-sea sediments; north-atlantic; clay-size; continental-crust; western boundary; labrador sea; eirik drift; level rise; nd
AB Varying levels of boreal summer insolation and associated Earth system feedbacks led to differing climate and ice-sheet states during late-Quaternary interglaciations. In particular, Marine Isotope Stage (MIS) 11 was an exceptionally long interglaciation and potentially had a global mean sea level 6 to 13 metres above the present level around 410,000 to 400,000 years ago(1,2), implying substantial mass loss fromtheGreenland ice sheet (GIS). There are, however, nomodel simulations and only limitedproxy data(3,4) to constrain themagnitude of the GIS response to climate change during this 'super interglacial'(5), thus confounding efforts to assess climate/ice-sheet threshold behaviour(6,7) and associated sea-level rise(1,2). Here we show that the south GIS was drastically smaller during MIS 11 than it is now, with only a small residual ice dome over southernmost Greenland. We use the strontium-neodymium-lead isotopic composition of proglacial sediment discharged from south Greenland to constrain the provenance of terrigenous silt deposited on the Eirik Drift, a sedimentary deposit off the south Greenland margin. We identify a major reduction in sediment input derived from south Greenland's Pre-cambrian bedrock terranes, probably reflecting the cessation of sub-glacial erosion and sediment transport(8) as a result of near-complete deglaciation of south Greenland. Comparison with ice-sheet configurations from numerical models(7,9-12) suggests that the GIS lost about 4.5 to 6 metres of sea-level-equivalent volume during MIS 11. This is evidence for late-Quaternary GIS collapse after it crossed a climate/ice-sheet stability threshold that may have been no more than several degrees above pre-industrial temperatures(6,7).
C1 [Reyes, Alberto V.; Carlson, Anders E.; Beard, Brian L.; Winsor, Kelsey; Welke, Bethany; Ullman, David J.] Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
   [Reyes, Alberto V.] Queens Univ Belfast, Sch Geog Archaeol & Palaeoecol, Belfast BT7 1NN, Antrim, North Ireland.
   [Carlson, Anders E.; Hatfield, Robert G.; Stoner, Joseph S.; Ullman, David J.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Queens University Belfast; Oregon State University
RP Reyes, AV (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
EM areyes@ualberta.ca; acarlson@coas.oregonstate.edu
FU US NSF [ANS-0902571, ANS-0902751]; Canadian NSERC fellowship
NR 77
TC 95
Z9 110
U1 1
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 JUN 26
PY 2014
VL 510
IS 7506
BP 525
EP +
DI 10.1038/nature13456
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300044
PM 24965655
DA 2026-03-09
ER

PT J
AU Ben-Zvi, A
   Lacoste, B
   Kur, E
   Andreone, BJ
   Mayshar, Y
   Yan, H
   Gu, CH
AF Ben-Zvi, Ayal
   Lacoste, Baptiste
   Kur, Esther
   Andreone, Benjamin J.
   Mayshar, Yoav
   Yan, Han
   Gu, Chenghua
TI Mfsd2a is critical for the formation and function of the blood-brain barrier
SO NATURE
LA English
DT Article
ID cns; integrity; receptor; differentiation; transporter; mechanisms; expression; pericytes; mouse
AB The central nervous system(CNS) requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for neural function. This environment is maintained by the 'blood-brain barrier' (BBB), which is composed of blood vessels whose endothelial cells display specialized tight junctions and extremely low rates of transcellular vesicular transport (transcytosis)(1-3). In concert with pericytes and astrocytes, this unique brain endothelial physiological barrier seals the CNS and controls substance influx and efflux(4-6). Although BBB breakdown has recently been associated with initiation and perpetuation of various neurological disorders, an intact BBB is a major obstacle for drug delivery to the CNS7-10. A limited understanding of the molecular mechanisms that control BBB formation has hindered our ability to manipulate the BBB in disease and therapy. Here we identify mechanisms governing the establishment of a functional BBB. First, using a novel tracer-injection method for embryos, we demonstrate spatiotemporal developmental profiles of BBB functionality and find that the mouse BBB becomes functional at embryonic day 15.5 (E15.5). We then screen for BBB-specific genes expressed during BBB formation, and find that major facilitator super family domain containing 2a (Mfsd2a) is selectively expressed in BBB-containing blood vessels in the CNS. Genetic ablation of Mfsd2a results in a leaky BBB from embryonic stages through to adulthood, but the normal patterning of vascular networks is maintained. Electron microscopy examination reveals a dramatic increase in CNS-endothelial-cell vesicular transcytosis in Mfsd2a(-/-) mice, without obvious tight-junction defects. Finally we show that Mfsd2a endothelial expression is regulated by pericytes to facilitate BBB integrity. These findings identify Mfsd2a as a key regulator of BBB function that may act by suppressing transcytosis in CNS endothelial cells. Furthermore, our findings may aid in efforts to develop therapeutic approaches for CNS drug delivery.
C1 [Ben-Zvi, Ayal; Lacoste, Baptiste; Kur, Esther; Andreone, Benjamin J.; Yan, Han; Gu, Chenghua] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Mayshar, Yoav] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Gu, CH (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM chenghua_gu@hms.harvard.edu
FU Neural Imaging Center as part of an NINDS P30 Core Center grant [NS072030]; Harold Perlman postdoctoral fellowships; Goldenson postdoctoral fellowship; Lefler postdoctoral fellowship; DFG-German Research Foundation postdoctoral fellowship; Mahoney postdoctoral fellowship; NIH training grant [5T32MH20017-15]; Sloan research fellowship; Armenise junior faculty award; Genise Goldenson fund; Freudenberger award; NIH [R01NS064583]; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism [T32MH020017] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32MH020017] Funding Source: NIH RePORTER
NR 31
TC 803
Z9 961
U1 4
U2 218
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 507
EP +
DI 10.1038/nature13324
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000042
PM 24828040
DA 2026-03-09
ER

PT J
AU Lee, J
   Tymchenko, M
   Argyropoulos, C
   Chen, PY
   Lu, F
   Demmerle, F
   Boehm, G
   Amann, MC
   Alù, A
   Belkin, MA
AF Lee, Jongwon
   Tymchenko, Mykhailo
   Argyropoulos, Christos
   Chen, Pai-Yen
   Lu, Feng
   Demmerle, Frederic
   Boehm, Gerhard
   Amann, Markus-Christian
   Alu, Andrea
   Belkin, Mikhail A.
TI Giant nonlinear response from plasmonic metasurfaces coupled to intersubband transitions
SO NATURE
LA English
DT Article
ID optimized 2nd-harmonic generation; quantum; gaas
AB Intersubband transitions in n-doped multi-quantum-well semiconductor heterostructures make it possible to engineer one of the largest known nonlinear optical responses in condensed matter systems-but this nonlinear response is limited to light with electric field polarized normal to the semiconductor layers(1-7). In a different context, plasmonic metasurfaces (thin conductor-dielectric composite materials) have been proposed as a way of strongly enhancing light-matter interaction and realizing ultrathin planarized devices with exotic wave properties(8-11). Here we propose and experimentally realize metasurfaces with a record-high nonlinear response based on the coupling of electromagnetic modes in plasmonic metasurfaces with quantum-engineered electronic intersubband transitions in semiconductor heterostructures. We show that it is possible to engineer almost any element of the nonlinear susceptibility tensor of these structures, and we experimentally verify this concept by realizing a 400-nm-thick metasurface with nonlinear susceptibility of greater than 5 x 10(4) picometres per volt for second harmonic generation at a wavelength of about 8 micrometres under normal incidence. This susceptibility is many orders of magnitude larger than any second-order nonlinear response in optical metasurfaces measured so far(12-15). The proposed structures can act as ultrathin highly nonlinear optical elements that enable efficient frequency mixing with relaxed phase-matching conditions, ideal for realizing broadband frequency up-and down-conversions, phase conjugation and all-optical control and tunability over a surface.
C1 [Lee, Jongwon; Tymchenko, Mykhailo; Argyropoulos, Christos; Chen, Pai-Yen; Lu, Feng; Alu, Andrea; Belkin, Mikhail A.] Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.
   [Demmerle, Frederic; Boehm, Gerhard; Amann, Markus-Christian] Tech Univ Munich, Walter Schottky Inst, D-85748 Garching, Germany.
C3 University of Texas System; University of Texas Austin; Technical University of Munich
RP Belkin, MA (corresponding author), Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.
EM mbelkin@ece.utexas.edu
FU NSF EAGER grant [1348049]; AFOSR YIP award [FA9550-10-1-0076]; AFOSR YIP [FA9550-11-1-0009]; ONR MURI grant [N00014-10-1-0942]; Excellence Cluster 'Nano Initiative Munich (NIM)'; Div Of Electrical, Commun & Cyber Sys; Directorate For Engineering [1348049] Funding Source: National Science Foundation
NR 33
TC 599
Z9 677
U1 10
U2 604
PU NATURE PUBLISHING 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 3
PY 2014
VL 511
IS 7507
BP 65
EP U389
DI 10.1038/nature13455
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400036
PM 24990746
DA 2026-03-09
ER

PT J
AU Stasevich, TJ
   Hayashi-Takanaka, Y
   Sato, Y
   Maehara, K
   Ohkawa, Y
   Sakata-Sogawa, K
   Tokunaga, M
   Nagase, T
   Nozaki, N
   McNally, JG
   Kimura, H
AF Stasevich, Timothy J.
   Hayashi-Takanaka, Yoko
   Sato, Yuko
   Maehara, Kazumitsu
   Ohkawa, Yasuyuki
   Sakata-Sogawa, Kumiko
   Tokunaga, Makio
   Nagase, Takahiro
   Nozaki, Naohito
   McNally, James G.
   Kimura, Hiroshi
TI Regulation of RNA polymerase II activation by histone acetylation in single living cells
SO NATURE
LA English
DT Article
ID glucocorticoid-receptor; frap analysis; in-vivo; transcription; phosphorylation; chromatin; dynamics; reveals; organization; deacetylases
AB In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation 1, a variety of residue-specific modifications have now been linked to RNA polymerase II (RNAP2) activity(2,3), but it remains unclear if these markers are active regulators of transcription or just passive byproducts(4,5). This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells(2,5,6). Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response.
C1 [Stasevich, Timothy J.; Hayashi-Takanaka, Yoko; Sato, Yuko; Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan.
   [Stasevich, Timothy J.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
   [Stasevich, Timothy J.] Howard Hughes Med Inst, Transcript Imaging Consortium, Ashburn, VA 20147 USA.
   [Hayashi-Takanaka, Yoko; Ohkawa, Yasuyuki; Kimura, Hiroshi] Japan Sci & Technol Agcy JST, Core Res Evolut Sci & Technol CREST, Saitama 3320012, Japan.
   [Hayashi-Takanaka, Yoko; Sato, Yuko; Kimura, Hiroshi] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Sci, Yokohama, Kanagawa 2268501, Japan.
   [Maehara, Kazumitsu; Ohkawa, Yasuyuki] Kyushu Univ, Dept Adv Med Initiat, Fac Med, Fukuoka 8128582, Japan.
   [Sakata-Sogawa, Kumiko; Tokunaga, Makio] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan.
   [Sakata-Sogawa, Kumiko; Tokunaga, Makio] RIKEN Ctr Integrat Med Sci IMS, Yokohama, Kanagawa 2300045, Japan.
   [Nagase, Takahiro] Kazusa DNA Res Inst, Dept Biotechnol Res, Chiba 2920818, Japan.
   [Nozaki, Naohito] Mab Inst Inc, Sapporo, Hokkaido 00002, Japan.
   [McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
   [McNally, James G.] Helmholtz Zentrum Berlin, Inst Soft Matter & Funct Mat, D-14109 Berlin, Germany.
C3 University of Osaka; Colorado State University System; Colorado State University Fort Collins; Howard Hughes Medical Institute; Japan Science & Technology Agency (JST); Institute of Science Tokyo; Tokyo Institute of Technology; Kyushu University; Institute of Science Tokyo; Tokyo Institute of Technology; RIKEN; Kazusa DNA Research Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB)
RP Stasevich, TJ (corresponding author), Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan.
EM tim.stasevich@colostate.edu; hkimura@bio.titech.ac.jp
FU Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology of Japan; JSPS; Grants-in-Aid for Scientific Research [24118006, 25116007, 25650009, 24118001, 25116005, 25503002, 25118714] Funding Source: KAKEN
NR 44
TC 212
Z9 241
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 DEC 11
PY 2014
VL 516
IS 7530
BP 272
EP +
DI 10.1038/nature13714
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500051
PM 25252976
DA 2026-03-09
ER

PT J
AU Bintanja, R
   Selten, FM
AF Bintanja, R.
   Selten, F. M.
TI Future increases in Arctic precipitation linked to local evaporation and sea-ice retreat
SO NATURE
LA English
DT Article
ID climate; amplification; cycle
AB Precipitation changes projected for the end of the twenty-first century show an increase of more than 50 per cent in the Arctic regions(1,2). This marked increase, which is among the highest globally, has previously been attributed primarily to enhanced poleward moisture transport from lower latitudes(3,4). Here we use state-of-the-art global climate models(5) to show that the projected increases in Arctic precipitation over the twenty-first century, which peak in late autumn and winter, are instead due mainly to strongly intensified local surface evaporation (maximum in winter), and only to a lesser degree due to enhanced moisture inflow from lower latitudes(maximum in late summer and autumn). Moreover, we show that the enhanced surface evaporation results mainly from retreating winter sea ice, signalling an amplified Arctic hydrological cycle. This demonstrates that increases in Arctic precipitation are firmly linked to Arctic warming and sea-ice decline. As a result, the Arctic mean precipitation sensitivity (4.5 per cent increase per degree of temperature warming) is much larger than the global value (1.6 to 1.9 per cent per kelvin). The associated seasonally varying increase in Arctic precipitation is likely to increase river discharge(6-8) and snowfall over ice sheets(9) (thereby affecting global sea level), and could even affect global climate through freshening of the Arctic Ocean and subsequent modulations of the Atlantic meridional overturning circulation(10,11).
C1 [Bintanja, R.; Selten, F. M.] Royal Netherlands Meteorol Inst KNMI, NL-3731 GA De Bilt, Netherlands.
C3 Royal Netherlands Meteorological Institute
RP Bintanja, R (corresponding author), Royal Netherlands Meteorol Inst KNMI, Utrechtseweg 297, NL-3731 GA De Bilt, Netherlands.
EM bintanja@knmi.nl
NR 30
TC 516
Z9 616
U1 6
U2 257
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 22
PY 2014
VL 509
IS 7501
BP 479
EP +
DI 10.1038/nature13259
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000036
PM 24805239
DA 2026-03-09
ER

PT J
AU Ye, ZL
   Cao, T
   O'Brien, K
   Zhu, HY
   Yin, XB
   Wang, Y
   Louie, SG
   Zhang, X
AF Ye, Ziliang
   Cao, Ting
   O'Brien, Kevin
   Zhu, Hanyu
   Yin, Xiaobo
   Wang, Yuan
   Louie, Steven G.
   Zhang, Xiang
TI Probing excitonic dark states in single-layer tungsten disulphide
SO NATURE
LA English
DT Article
ID valley polarization; optical-property; carbon nanotubes; quasi-particle; mos2; semiconductors; spectra
AB Transition metal dichalcogenide (TMDC) monolayers have recently emerged as an important class of two-dimensional semiconductors with potential for electronic and optoelectronic devices(1,2). Unlike semi-metallic graphene, layered TMDCs have a sizeable bandgap(3). More interestingly, when thinned down to a monolayer, TMDCs transform from indirect-bandgap to direct-bandgap semiconductors(4,5), exhibiting a number of intriguing optical phenomena such as valley-selective circular dichroism(6-8), doping-dependent charged excitons(9,10) and strong photocurrent responses(11). However, the fundamental mechanism underlying such a strong light-matter interaction is still under intensive investigation. First-principles calculations have predicted a quasi-particle bandgap much larger than the measured optical gap, and an optical response dominated by excitonic effects(12-14). In particular, a recent study based on a GW plus Bethe-Salpeter equation (GW-BSE) approach, which employed many-body Green's-function methodology to address electron-electron and electron-hole interactions, theoretically predicted a diversity of strongly bound exdtons(14). Here we report experimental evidence of a series of excitonic dark states in single-layer WS2 using two-photon excitation spectroscopy. In combination with GW-BSE theory, we prove that the excitons are of Wannier type, meaning that each exciton wavefunction extends over multiple unit cells, but with extraordinarily large binding energy (similar to 0.7 electron-volts), leading to a quasiparticle bandgap of 2.7 electronvolts. These strongly bound exciton states are observed to be stable even at room temperature. We reveal an exciton series that deviates substantially from hydrogen models, with a novel energy dependence on the orbital angular momentum. These excitonic energy levels are experimentally found to be robust against environmental perturbations. The discovery of excitonic dark states and exceptionally large binding energy not only sheds light on the importance of many-electron effects in this two-dimensional gapped system, but also holds potential for the device application of TMDC monolayers and their heterostructures(15) in computing, communication and bio-sensing.
C1 [Ye, Ziliang; O'Brien, Kevin; Zhu, Hanyu; Yin, Xiaobo; Wang, Yuan; Zhang, Xiang] Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, Berkeley, CA 94720 USA.
   [Cao, Ting; Louie, Steven G.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Cao, Ting; Louie, Steven G.; Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Zhang, Xiang] King Abdulaziz Univ, Dept Phys, Jeddah 21589, Saudi Arabia.
   [Zhang, Xiang] Univ Calif Berkeley, Kavli Energy NanoSci Inst, Berkeley, CA 94704 USA.
   [Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94704 USA.
C3 National Science Foundation (NSF); 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; King Abdulaziz University; 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 Zhang, X (corresponding author), Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, 3112 Etcheverry Hall, Berkeley, CA 94720 USA.
EM sglouie@berkeley.edu; xzhang@me.berkeley.edu
FU Lawrence Berkeley National Laboratory through the Office of Basic Energy Sciences, US Department of Energy [DE-AC02-05CH11231]
NR 29
TC 921
Z9 1063
U1 8
U2 1049
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 11
PY 2014
VL 513
IS 7517
BP 214
EP 218
DI 10.1038/nature13734
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800046
PM 25162523
DA 2026-03-09
ER

PT J
AU Christner, BC
   Priscu, JC
   Achberger, AM
   Barbante, C
   Carter, SP
   Christianson, K
   Michaud, AB
   Mikucki, JA
   Mitchell, AC
   Skidmore, ML
   Vick-Majors, TJ
AF Christner, Brent C.
   Priscu, John C.
   Achberger, Amanda M.
   Barbante, Carlo
   Carter, Sasha P.
   Christianson, Knut
   Michaud, Alexander B.
   Mikucki, Jill A.
   Mitchell, Andrew C.
   Skidmore, Mark L.
   Vick-Majors, Trista J.
TI A microbial ecosystem beneath the West Antarctic ice sheet
SO NATURE
LA English
DT Article
ID active reservoir beneath; subglacial lake whillans; vostok; stream; thymidine; bacteria; nitrate; waters; shelf
AB Liquid water has been known to occur beneath the Antarctic ice sheet for more than 40 years(1), but only recently have these subglacial aqueous environments been recognized as microbial ecosystems that may influence biogeochemical transformations on a global scale(2-4). Here we present the first geomicrobiological description of water and surficial sediments obtained from direct sampling of a subglacial Antarctic lake. Subglacial Lake Whillans (SLW) lies beneath approximately 800m of ice on the lower portion of the Whillans Ice Stream (WIS) in West Antarctica and is part of an extensive and evolving subglacial drainage network(5). The water column of SLW contained metabolically active microorganisms and was derived primarily from glacial ice melt with solute sources from lithogenic weathering and a minor seawater component. Heterotrophic and autotrophic production data together with small subunit ribosomal RNA gene sequencing and biogeochemical data indicate that SLWis a chemosynthetically driven ecosystem inhabited by a diverse assemblage of bacteria and archaea. Our results confirm that aquatic environments beneath the Antarctic ice sheet support viablemicrobial ecosystems, corroborating previous reports suggesting that they contain globally relevant pools of carbon and microbes(2,4) that can mobilize elements from the lithosphere(6) and influence Southern Ocean geochemical and biological systems(7).
C1 [Christner, Brent C.; Achberger, Amanda M.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Priscu, John C.; Michaud, Alexander B.; Vick-Majors, Trista J.] Montana State Univ, Dept Land Resources & Environm Sci, Bozeman, MT 59717 USA.
   [Barbante, Carlo] CNR, Inst Dynam Environm Proc, I-30123 Venice, Italy.
   [Barbante, Carlo] Ca Foscari Univ Venice, Dept Environm Sci Informat & Stat, I-30123 Venice, Italy.
   [Carter, Sasha P.] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
   [Christianson, Knut] St Olaf Coll, Dept Phys, Northfield, MN 55057 USA.
   [Mikucki, Jill A.] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA.
   [Mitchell, Andrew C.] Aberystwyth Univ, Dept Geog & Earth Sci, Aberystwyth SY23 3DB, Dyfed, Wales.
   [Skidmore, Mark L.] Montana State Univ, Dept Earth Sci, Bozeman, MT 59717 USA.
C3 Louisiana State University System; Louisiana State University; Montana State University System; Montana State University Bozeman; Consiglio Nazionale delle Ricerche (CNR); Istituto per la Dinamica dei Processi Ambientali (IDPA-CNR); Universita Ca Foscari Venezia; University of California System; University of California San Diego; Scripps Institution of Oceanography; Saint Olaf College; University of Tennessee System; University of Tennessee Knoxville; Aberystwyth University; Montana State University System; Montana State University Bozeman
RP Christner, BC (corresponding author), Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
EM xner@lsu.edu; jpriscu@montana.edu
FU National Science Foundation from the Division of Polar Programs [0838933, 0838896, 0838941, 0839142, 0839059, 0838885, 0838855, 0838763, 0839107, 0838947, 0838854, 0838764, 1142123]; NSF [1023233, 1115245, 1247192]; Italian National Antarctic Program; NSF's IGERT Program [0654336]; Montana Space Grant Consortium; Directorate For Geosciences [0838947, 0839142] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Polar Programs [0838854] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Polar Programs [0838933, 1023233, 0838941] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0838763, 1142123, 0838885, 0838896, 0839059] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0839107, 0838764, 0838855] Funding Source: National Science Foundation; Office of Polar Programs (OPP) [0838947, 0839142] Funding Source: National Science Foundation
NR 50
TC 229
Z9 266
U1 7
U2 544
PU NATURE PUBLISHING 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 21
PY 2014
VL 512
IS 7514
BP 310
EP +
DI 10.1038/nature13667
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200035
PM 25143114
DA 2026-03-09
ER

PT J
AU Price, TD
   Hooper, DM
   Buchanan, CD
   Johansson, US
   Tietze, DT
   Alström, P
   Olsson, U
   Ghosh-Harihar, M
   Ishtiaq, F
   Gupta, SK
   Martens, J
   Harr, B
   Singh, P
   Mohan, D
AF Price, Trevor D.
   Hooper, Daniel M.
   Buchanan, Caitlyn D.
   Johansson, Ulf S.
   Tietze, D. Thomas
   Alstroem, Per
   Olsson, Urban
   Ghosh-Harihar, Mousumi
   Ishtiaq, Farah
   Gupta, Sandeep K.
   Martens, Jochen
   Harr, Bettina
   Singh, Pratap
   Mohan, Dhananjai
TI Niche filling slows the diversification of Himalayan songbirds
SO NATURE
LA English
DT Article
ID species richness; ecological opportunity; range limits; diversity; speciation; evolution; birds; patterns; radiation; gradient
AB Speciation generally involves a three-step process-range expansion, range fragmentation and the development of reproductive isolation between spatially separated populations(1,2). Speciation relies on cycling through these three steps and each may limit the rate at which new species form(1,3). We estimate phylogenetic relationships among all Himalayan songbirds to ask whether the development of reproductive isolation and ecological competition, both factors that limit range expansions(4), set an ultimate limit on speciation. Based on a phylogeny for all 358 species distributed along the eastern elevational gradient, here we show that body size and shape differences evolved early in the radiation, with the elevational band occupied by a species evolving later. These results are consistent with competition for niche space limiting species accumulation(5). Even the elevation dimension seems to be approaching ecological saturation, because the closest relatives both inside the assemblage and elsewhere in the Himalayas are on average separated by more than five million years, which is longer than it generally takes for reproductive isolation to be completed(2,3,6); also, elevational distributions are well explained by resource availability, notably the abundance of arthropods, and not by differences in diversification rates in different elevational zones. Our results imply that speciation rate is ultimately set by niche filling(that is, ecological competition for resources), rather than by the rate of acquisition of reproductive isolation.
C1 [Price, Trevor D.; Hooper, Daniel M.; Buchanan, Caitlyn D.; Johansson, Ulf S.; Tietze, D. Thomas] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Johansson, Ulf S.] Swedish Museum Nat Hist, Dept Zool, S-10405 Stockholm, Sweden.
   [Tietze, D. Thomas] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany.
   [Alstroem, Per] Chinese Acad Sci, Inst Zool, Key Lab Zool Systemat & Evolut, Beijing 100101, Peoples R China.
   [Alstroem, Per] Swedish Univ Agr Sci, Swedish Species Informat Ctr, S-75007 Uppsala, Sweden.
   [Olsson, Urban] Univ Gothenburg, Dept Biol & Environm Sci, S-40530 Gothenburg, Sweden.
   [Ghosh-Harihar, Mousumi; Ishtiaq, Farah; Gupta, Sandeep K.; Singh, Pratap; Mohan, Dhananjai] Wildlife Inst India, Dehra Dun 248001, Uttar Pradesh, India.
   [Martens, Jochen] Johannes Gutenberg Univ Mainz, Inst Zool, D-55099 Mainz, Germany.
   [Harr, Bettina] Max Planck Inst Evolutionary Biol, D-24306 Plon, Germany.
C3 University of Chicago; Swedish Museum of Natural History; Ruprecht Karls University Heidelberg; Chinese Academy of Sciences; Institute of Zoology, CAS; Swedish University of Agricultural Sciences; University of Gothenburg; Wildlife Institute of India; Johannes Gutenberg University of Mainz; Max Planck Society
RP Price, TD (corresponding author), Univ Chicago, Dept Ecol & Evolut, 940 E 57Th St, Chicago, IL 60637 USA.
EM pricet@uchicago.edu
FU US NSF; National Geographic Society; Jornvall Foundation, a Chinese Academy of Sciences Visiting Professorship; Swedish Research Council; Wenner-Gren Foundation; Feldbausch Foundation of Mainz University; German DFG [Ti679/1-1]
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   Rosenzweig Michael L, 1993, P52, V0, P0
   Sanders NJ, 2012, ECOGRAPHY, V35, P1, DOI 10.1111/j.1600-0587.2011.07338.x
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   Weir JT, 2011, AM NAT, V177, P462, DOI 10.1086/658910
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NR 93
TC 306
Z9 354
U1 0
U2 307
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2014
VL 509
IS 7499
BP 222
EP +
DI 10.1038/nature13272
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300038
PM 24776798
DA 2026-03-09
ER

PT J
AU Cai, WJ
   Santoso, A
   Wang, GJ
   Weller, E
   Wu, LX
   Ashok, K
   Masumoto, Y
   Yamagata, T
AF Cai, Wenju
   Santoso, Agus
   Wang, Guojian
   Weller, Evan
   Wu, Lixin
   Ashok, Karumuri
   Masumoto, Yukio
   Yamagata, Toshio
TI Increased frequency of extreme Indian Ocean Dipole events due to greenhouse warming
SO NATURE
LA English
DT Article
ID el-nino; forest-fires; short rains; variability; rainfall; impact; mode
AB The Indian Ocean dipole is a prominent mode of coupled ocean-atmosphere variability(1-4), affecting the lives of millions of people in Indian Ocean rim countries(5-15). In its positive phase, sea surface temperatures are lower than normal off the Sumatra-Java coast, but higher in the western tropical Indian Ocean. During the extreme positive-IOD (pIOD) events of 1961, 1994 and 1997, the eastern cooling strengthened and extended westward along the equatorial Indian Ocean through strong reversal of both the mean westerly winds and the associated eastward-flowing upper ocean currents(1,2). This created anomalously dry conditions from the eastern to the central Indian Ocean along the Equator and atmospheric convergence farther west, leading to catastrophic floods in eastern tropical African countries(13,14) but devastating droughts in eastern Indian Ocean rim countries(8-10,16,17). Despite these serious consequences, the response of pIOD events to greenhouse warming is unknown. Here, using an ensemble of climate models forced by a scenario of high greenhouse gas emissions (Representative Concentration Pathway 8.5), we project that the frequency of extreme pIOD events will increase by almost a factor of three, from one event every 17.3 years over the twentieth century to one event every 6.3 years over the twenty-first century. We find that a mean state change-with weakening of both equatorial westerly winds and eastward oceanic currents in association with a faster warming in the western than the eastern equatorial Indian Ocean-facilitates more frequent occurrences of wind and oceanic current reversal. This leads to more frequent extreme pIOD events, suggesting an increasing frequency of extreme climate and weather events in regions affected by the pIOD.
C1 [Cai, Wenju; Wang, Guojian; Weller, Evan] CSIRO Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
   [Cai, Wenju; Wang, Guojian; Wu, Lixin] Ocean Univ China, Qingdao Collaborat Innovat Ctr Marine Sci & Techn, Phys Oceanog Lab, Qingdao 266003, Peoples R China.
   [Santoso, Agus] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Santoso, Agus] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Ashok, Karumuri] Indian Inst Trop Meteorol, Ctr Climate Change Res, Pune 411008, Maharashtra, India.
   [Masumoto, Yukio] Univ Tokyo, Dept Earth & Planetary Sci, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Masumoto, Yukio] Japan Agcy Marine Earth Sci & Technol JAMSTEC, Climate Variat Predictabil & Applicatabil Res Pro, Kanazawa Ku, Yokohama, Kanagawa 2360001, Japan.
   [Yamagata, Toshio] JAMSTEC, Applicat Lab, Kanazawa Ku, Yokohama, Kanagawa 2360001, Japan.
C3 Commonwealth Scientific & Industrial Research Organisation (CSIRO); Ocean University of China; University of New South Wales Sydney; University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; Ministry of Earth Sciences (MoES) - India; Indian Institute of Tropical Meteorology (IITM); Centre for Climate Change Research - India; University of Tokyo; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Cai, WJ (corresponding author), CSIRO Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
EM wenju.cai@csiro.au
FU Australian Climate Change Science Program; Goyder Institute; CSIRO Office of Chief Executive Science Leader award; Australian Research Council
NR 39
TC 343
Z9 368
U1 7
U2 204
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 12
PY 2014
VL 510
IS 7504
BP 254
EP +
DI 10.1038/nature13327
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400047
PM 24919920
DA 2026-03-09
ER

PT J
AU Delbo, M
   Libourel, G
   Wilkerson, J
   Murdoch, N
   Michel, P
   Ramesh, KT
   Ganino, C
   Verati, C
   Marchi, S
AF Delbo, Marco
   Libourel, Guy
   Wilkerson, Justin
   Murdoch, Naomi
   Michel, Patrick
   Ramesh, K. T.
   Ganino, Clement
   Verati, Chrystele
   Marchi, Simone
TI Thermal fatigue as the origin of regolith on small asteroids
SO NATURE
LA English
DT Article
ID near-earth objects; temperature; spacecraft
AB Space missions(1,2) and thermal infrared observations(3) have shown that small asteroids (kilometre-sized or smaller) are covered by a layer of centimetre-sized or smaller particles, which constitute the regolith. Regolith generation has traditionally been attributed to the fall back of impact ejecta and by the break-up of boulders by micrometeoroid impact(4,5). Laboratory experiments(6) and impact models(4), however, show that crater ejecta velocities are typically greater than several tens of centimetres per second, which corresponds to the gravitational escape velocity of kilometre-sized asteroids. Therefore, impact debris cannot be the main source of regolith on small asteroids(4). Here we report that thermal fatigue(7-9), a mechanism of rock weathering and fragmentation with no subsequent ejection, is the dominant process governing regolith generation on small asteroids. We find that thermal fragmentation induced by the diurnal temperature variations breaks up rocks larger than a few centimetres more quickly than do micrometeoroid impacts. Because thermal fragmentation is independent of asteroid size, this process can also contribute to regolith production on larger asteroids. Production of fresh regolith originating in thermal fatigue fragmentation may be an important process for the rejuvenation of the surfaces of near-Earth asteroids, and may explain the observed lack of low-perihelion, carbonaceous, near-Earth asteroids(10).
C1 [Delbo, Marco; Murdoch, Naomi; Michel, Patrick] UNS, CNRS, Lab Lagrange, Observ Cote Azur, F-06304 Nice 4, France.
   [Libourel, Guy] Univ Lorraine, CRPG, CNRS, F-54501 Vandoeuvre Les Nancy, France.
   [Libourel, Guy; Ganino, Clement; Verati, Chrystele] UNS, CNRS, Observ Cote Azur, Lab Geoazur, F-06560 Valbonne, France.
   [Wilkerson, Justin; Ramesh, K. T.] Johns Hopkins Univ, Hopkins Extreme Mat Inst, Baltimore, MD 21218 USA.
   [Murdoch, Naomi] Inst Super Aeronaut & Espace, F-31055 Toulouse 4, France.
   [Marchi, Simone] SW Res Inst, Inst Sci Explorat Targets, Solar Syst Explorat Res Virtual Inst, Boulder, CO 80302 USA.
C3 Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Observatoire de la Cote d'Azur; Johns Hopkins University; Universite de Toulouse; Institut Superieur de l'Aeronautique et de l'Espace (ISAE-SUPAERO)
RP Delbo, M (corresponding author), UNS, CNRS, Lab Lagrange, Observ Cote Azur, Blvd Observ CS 34229, F-06304 Nice 4, France.
EM delbo@oca.eu; libou@oca.eu
FU French Agence National de la Recherche (ANR) SHOCKS; BQR of the Observatoire de la Cote d'Azur (OCA); University of Nice-Sophia Antipolis; Laboratory GeoAzur; French National Program of Planetology (PNP); NASA SSERVI
NR 30
TC 307
Z9 334
U1 4
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 APR 10
PY 2014
VL 508
IS 7495
BP 233
EP +
DI 10.1038/nature13153
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900041
PM 24695219
DA 2026-03-09
ER

PT J
AU Desai, TJ
   Brownfield, DG
   Krasnow, MA
AF Desai, Tushar J.
   Brownfield, Douglas G.
   Krasnow, Mark A.
TI Alveolar progenitor and stem cells in lung development, renewal and cancer
SO NATURE
LA English
DT Article
ID fetal-rat lung; distal lung; mouse lung; ii cells; k-ras; mice; epithelium; maintenance; expression; adenocarcinoma
AB Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.
C1 [Desai, Tushar J.; Brownfield, Douglas G.; Krasnow, Mark A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Desai, Tushar J.; Brownfield, Douglas G.; Krasnow, Mark A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Desai, Tushar J.] Stanford Univ, Sch Med, Dept Internal Med, Div Pulm & Crit Care, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Krasnow, MA (corresponding author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
EM tdesai@stanford.edu; krasnow@stanford.edu
FU NHLBI NIH HHS [U01 HL099995, U01 HL099999, K08 HL084095] Funding Source: Medline; NICHD NIH HHS [T32 HD007249] Funding Source: Medline
NR 52
TC 795
Z9 963
U1 3
U2 154
PU NATURE PUBLISHING 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 13
PY 2014
VL 507
IS 7491
BP 190
EP +
DI 10.1038/nature12930
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800030
PM 24499815
DA 2026-03-09
ER

PT J
AU Sadtler, PT
   Quick, KM
   Golub, MD
   Chase, SM
   Ryu, SI
   Tyler-Kabara, EC
   Yu, BM
   Batista, AP
AF Sadtler, Patrick T.
   Quick, Kristin M.
   Golub, Matthew D.
   Chase, Steven M.
   Ryu, Stephen I.
   Tyler-Kabara, Elizabeth C.
   Yu, Byron M.
   Batista, Aaron P.
TI Neural constraints on learning
SO NATURE
LA English
DT Article
ID brain-computer-interface; motor; adaptation; performance; dynamics; cortex; algorithm; responses; patterns; tasks
AB Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others(1,2), we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain-computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain-computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess(3,4).
C1 [Sadtler, Patrick T.; Quick, Kristin M.; Tyler-Kabara, Elizabeth C.; Batista, Aaron P.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA.
   [Sadtler, Patrick T.; Quick, Kristin M.; Golub, Matthew D.; Chase, Steven M.; Yu, Byron M.; Batista, Aaron P.] Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
   [Sadtler, Patrick T.; Quick, Kristin M.; Batista, Aaron P.] Univ Pittsburgh, Syst Neurosci Inst, Pittsburgh, PA 15261 USA.
   [Golub, Matthew D.; Yu, Byron M.] Carnegie Mellon Univ, Dept Elect & Comp Engn, Pittsburgh, PA 15213 USA.
   [Chase, Steven M.; Yu, Byron M.] Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA.
   [Ryu, Stephen I.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Ryu, Stephen I.] Palo Alto Med Fdn, Dept Neurosurg, Palo Alto, CA 94301 USA.
   [Tyler-Kabara, Elizabeth C.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
   [Tyler-Kabara, Elizabeth C.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Carnegie Mellon University; Carnegie Mellon University; Stanford University; Palo Alto Medical Foundation Research Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Yu, BM (corresponding author), Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
EM byronyu@cmu.edu; apb10@pitt.edu
FU NIH NICHD CRCNS [R01-HD071686]; NIH NINDS [R01-NS065065]; Burroughs Wellcome Fund; NSF [DGE-0549352]; NIH [P30-NS076405]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD071686] Funding Source: NIH RePORTER
NR 39
TC 452
Z9 576
U1 1
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 AUG 28
PY 2014
VL 512
IS 7515
BP 423
EP U428
DI 10.1038/nature13665
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600032
PM 25164754
DA 2026-03-09
ER

PT J
AU Shalek, AK
   Satija, R
   Shuga, J
   Trombetta, JJ
   Gennert, D
   Lu, DN
   Chen, PL
   Gertner, RS
   Gaublomme, JT
   Yosef, N
   Schwartz, S
   Fowler, B
   Weaver, S
   Wang, J
   Wang, XH
   Ding, RH
   Raychowdhury, R
   Friedman, N
   Hacohen, N
   Park, H
   May, AP
   Regev, A
AF Shalek, Alex K.
   Satija, Rahul
   Shuga, Joe
   Trombetta, John J.
   Gennert, Dave
   Lu, Diana
   Chen, Peilin
   Gertner, Rona S.
   Gaublomme, Jellert T.
   Yosef, Nir
   Schwartz, Schraga
   Fowler, Brian
   Weaver, Suzanne
   Wang, Jing
   Wang, Xiaohui
   Ding, Ruihua
   Raychowdhury, Raktima
   Friedman, Nir
   Hacohen, Nir
   Park, Hongkun
   May, Andrew P.
   Regev, Aviv
TI Single-cell RNA-seq reveals dynamic paracrine control of cellular variation
SO NATURE
LA English
DT Article
ID gene-expression; i interferon; immune; quantification; stochasticity; transcriptome; variability; determines; activation; principles
AB High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis and function of gene expression variation between seemingly identical cells. Here we sequence single-cell RNA-seq libraries prepared from over 1,700 primary mouse bone-marrow-derived dendritic cells spanning several experimental conditions. We find substantial variation between identically stimulated dendritic cells, in both the fraction of cells detectably expressing a given messenger RNA and the transcript's level within expressing cells. Distinct gene modules are characterized by different temporal heterogeneity profiles. In particular, a 'core' module of antiviral genes is expressed very early by a few 'precocious' cells in response to uniform stimulation with a pathogenic component, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analysing dendritic cells from knockout mice, and modulating secretion and extracellular signalling, we show that this response is coordinated by interferon-mediated paracrine signalling from these precocious cells. Notably, preventing cell-to-cell communication also substantially reduces variability between cells in the expression of an early-induced 'peaked' inflammatory module, suggesting that paracrine signalling additionally represses part of the inflammatory program. Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations can use to establish complex dynamic responses.
C1 [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Ding, Ruihua; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Ding, Ruihua; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Shalek, Alex K.; Satija, Rahul; Trombetta, John J.; Gennert, Dave; Lu, Diana; Yosef, Nir; Schwartz, Schraga; Raychowdhury, Raktima; Hacohen, Nir; Park, Hongkun; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Shuga, Joe; Chen, Peilin; Fowler, Brian; Weaver, Suzanne; Wang, Jing; Wang, Xiaohui; May, Andrew P.] Fluidigm Corp, San Francisco, CA 94080 USA.
   [Friedman, Nir] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, IL-91904 Jerusalem, Israel.
   [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
   [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA.
   [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02140 USA.
C3 Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Standard BioTools Inc.; Hebrew University of Jerusalem; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Satija, R (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM rahuls@broadinstitute.org; Hongkun_Park@harvard.edu; apmay1@gmail.com
FU NIH [1F32HD075541-01, U54 AI057159, DP2 OD002230, 5DP1OD003893-03, DP1OD003958-01]; NIH CEGS [1P50HG006193-01]; Broad Institute; Klarman Cell Observatory at the Broad Institute; ISF-Broad Grant; ERC
NR 36
TC 753
Z9 957
U1 3
U2 278
PU NATURE PUBLISHING 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 19
PY 2014
VL 510
IS 7505
BP 363
EP +
DI 10.1038/nature13437
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200028
PM 24919153
DA 2026-03-09
ER

PT J
AU Roushan, P
   Neill, C
   Chen, Y
   Kolodrubetz, M
   Quintana, C
   Leung, N
   Fang, M
   Barends, R
   Campbell, B
   Chen, Z
   Chiaro, B
   Dunsworth, A
   Jeffrey, E
   Kelly, J
   Megrant, A
   Mutus, J
   O'Malley, PJJ
   Sank, D
   Vainsencher, A
   Wenner, J
   White, T
   Polkovnikov, A
   Cleland, AN
   Martinis, JM
AF Roushan, P.
   Neill, C.
   Chen, Yu
   Kolodrubetz, M.
   Quintana, C.
   Leung, N.
   Fang, M.
   Barends, R.
   Campbell, B.
   Chen, Z.
   Chiaro, B.
   Dunsworth, A.
   Jeffrey, E.
   Kelly, J.
   Megrant, A.
   Mutus, J.
   O'Malley, P. J. J.
   Sank, D.
   Vainsencher, A.
   Wenner, J.
   White, T.
   Polkovnikov, A.
   Cleland, A. N.
   Martinis, J. M.
TI Observation of topological transitions in interacting quantum circuits
SO NATURE
LA English
DT Article
ID superconducting circuits; phase; insulators; spin
AB Topology, with its abstract mathematical constructs, often manifests itself in physics and has a pivotal role in our understanding of natural phenomena. Notably, the discovery of topological phases in condensed-matter systems has changed the modern conception of phases of matter(1-5). The global nature of topological ordering, however, makes direct experimental probing an outstanding challenge. Present experimental tools are mainly indirect and, as a result, are inadequate for studying the topology of physical systems at a fundamental level. Here we employ the exquisite control afforded by state-of-the-art superconducting quantum circuits to investigate topological properties of various quantum systems. The essence of our approach is to infer geometric curvature by measuring the deflection of quantum trajectories in the curved space of the Hamiltonian(6). Topological properties are then revealed by integrating the curvature over closed surfaces, a quantum analogue of the Gauss-Bonnet theorem. We benchmark our technique by investigating basic topological concepts of the historically important Haldane model(7) after mapping the momentum space of this condensed-matter model to the parameter space of a single-qubit Hamiltonian. In addition to constructing the topological phase diagram, we are able to visualize the microscopic spin texture of the associated states and their evolution across a topological phase transition. Going beyond non-interacting systems, we demonstrate the power of our method by studying topology in an interacting quantum system. This required anew qubit architecture(8,9) that allows for simultaneous control over every term in a two-qubit Hamiltonian. By exploring the parameter space of this Hamiltonian, we discover the emergence of an interaction-induced topological phase. Our work establishes a powerful, generalizable experimental platform to study topological phenomena in quantum systems.
C1 [Roushan, P.; Neill, C.; Chen, Yu; Quintana, C.; Leung, N.; Fang, M.; Barends, R.; Campbell, B.; Chen, Z.; Chiaro, B.; Dunsworth, A.; Jeffrey, E.; Kelly, J.; Megrant, A.; Mutus, J.; O'Malley, P. J. J.; Sank, D.; Vainsencher, A.; Wenner, J.; White, T.; Cleland, A. N.; Martinis, J. M.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Kolodrubetz, M.; Polkovnikov, A.] Boston Univ, Dept Phys, Boston, MA 02215 USA.
   [Martinis, J. M.] Google Inc, Santa Barbara, CA 93117 USA.
C3 University of California System; University of California Santa Barbara; Boston University; Alphabet Inc.; Google Incorporated
RP Martinis, JM (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM martinis@physics.ucsb.edu
FU NSF [DMR-0907039, DMR-1029764]; AFOSR [FA9550-10-1-0110]; ODNI, IARPA, through ARO grant [W911NF-10-1-0334]; NSF; Direct For Mathematical & Physical Scien; Division Of Materials Research [1206410, 1029764] Funding Source: National Science Foundation
NR 24
TC 189
Z9 213
U1 2
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 NOV 13
PY 2014
VL 515
IS 7526
BP 241
EP 244
DI 10.1038/nature13891
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400044
PM 25391961
DA 2026-03-09
ER

PT J
AU Crombie, AT
   Murrell, JC
AF Crombie, Andrew T.
   Murrell, J. Colin
TI Trace-gas metabolic versatility of the facultative methanotroph Methylocella silvestris
SO NATURE
LA English
DT Article
ID methane monooxygenase; propane; oxidation; ethane; system
AB The climate-active gas methane is generated both by biological processes and by thermogenic decomposition of fossil organic material, which forms methane and short-chain alkanes, principally ethane, propane and butane(1,2). In addition to natural sources, environments are exposed to anthropogenic inputs of all these gases from oil and gas extraction and distribution. The gases provide carbon and/or energy for a diverse range of microorganisms that can metabolize them in both anoxic(3) and oxic zones. Aerobic methanotrophs, which can assimilate methane, have been considered to be entirely distinct from utilizers of short-chain alkanes, and studies of environments exposed to mixtures of methane and multi-carbon alkanes have assumed that disparate groups of microorganisms are responsible for the metabolism of these gases. Here we describe the mechanism by which a single bacterial strain, Methylocella silvestris, can use methane or propane as a carbon and energy source, documenting a methanotroph that can utilize a short-chain alkane as an alternative to methane. Furthermore, during growth on a mixture of these gases, efficient consumption of both gases occurred at the same time. Two soluble di-iron centre monooxygenase (SDIMO) gene clusters were identified and were found to be differentially expressed during bacterial growth on these gases, although both were required for efficient propane utilization. This report of a methanotroph expressing an additional SDIMO that seems to be uniquely involved in short-chain alkane metabolism suggests that such metabolic flexibility may be important in many environments where methane and short-chain alkanes co-occur.
C1 [Crombie, Andrew T.; Murrell, J. Colin] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
C3 University of East Anglia
RP Murrell, JC (corresponding author), Univ E Anglia, Sch Environm Sci, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England.
EM j.c.murrell@uea.ac.uk
FU Natural Environmental Research Council (NERC) [NE/E016855/1]; University of East Anglia; Earth and Life Systems Alliance of the Norwich Research Park; Natural Environment Research Council [NER/A/S/2002/00876, NE/E016855/1] Funding Source: researchfish; NERC [NE/E016855/1] Funding Source: UKRI
NR 40
TC 80
Z9 92
U1 3
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 JUN 5
PY 2014
VL 510
IS 7503
BP 148
EP +
DI 10.1038/nature13192
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900046
PM 24776799
DA 2026-03-09
ER

PT J
AU Howard, M
   Wallman, J
   Veitch, V
   Emerson, J
AF Howard, Mark
   Wallman, Joel
   Veitch, Victor
   Emerson, Joseph
TI Contextuality supplies the 'magic' for quantum computation
SO NATURE
LA English
DT Article
ID hidden-variables
AB Quantum computers promise dramatic advantages over their classical counterparts, but the source of the power in quantum computing has remained elusive. Here we prove a remarkable equivalence between the onset of contextuality and the possibility of universal quantum computation via 'magic state' distillation, which is the leading model for experimentally realizing a fault-tolerant quantum computer. This is a conceptually satisfying link, because contextuality, which precludes a simple 'hidden variable' model of quantum mechanics, provides one of the fundamental characterizations of uniquely quantum phenomena. Furthermore, this connection suggests a unifying paradigm for the resources of quantum information: the non-locality of quantum theory is a particular kind of contextuality, and non-locality is already known to be a critical resource for achieving advantages with quantum communication. In addition to clarifying these fundamental issues, this work advances the resource framework for quantum computation, which has a number of practical applications, such as characterizing the efficiency and trade-offs between distinct theoretical and experimental schemes for achieving robust quantum computation, and putting bounds on the overhead cost for the classical simulation of quantum algorithms.
C1 [Howard, Mark] Natl Univ Ireland, Dept Math Phys, Maynooth, Kildare, Ireland.
   [Howard, Mark; Wallman, Joel; Veitch, Victor; Emerson, Joseph] Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
   [Howard, Mark; Wallman, Joel; Veitch, Victor; Emerson, Joseph] Univ Waterloo, Dept Appl Math, Waterloo, ON N2L 3G1, Canada.
   [Veitch, Victor] Univ Toronto, Dept Stat, Toronto, ON M5S 3G3, Canada.
C3 Maynooth University; University of Waterloo; University of Waterloo; University of Toronto
RP Emerson, J (corresponding author), Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
EM jemerson@math.uwaterloo.ca
FU Irish Research Council (IRC) as part of the Empower Fellowship programme; CIFAR; Government of Canada through NSERC
NR 48
TC 461
Z9 503
U1 2
U2 100
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 351
EP 355
DI 10.1038/nature13460
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200026
PM 24919152
DA 2026-03-09
ER

PT J
AU Chomiuk, L
   Linford, JD
   Yang, J
   O'Brien, TJ
   Paragi, Z
   Mioduszewski, AJ
   Beswick, RJ
   Cheung, CC
   Mukai, K
   Nelson, T
   Ribeiro, VARM
   Rupen, MP
   Sokoloski, JL
   Weston, J
   Zheng, Y
   Bode, MF
   Eyres, S
   Roy, N
   Taylor, GB
AF Chomiuk, Laura
   Linford, Justin D.
   Yang, Jun
   O'Brien, T. J.
   Paragi, Zsolt
   Mioduszewski, Amy J.
   Beswick, R. J.
   Cheung, C. C.
   Mukai, Koji
   Nelson, Thomas
   Ribeiro, Valerio A. R. M.
   Rupen, Michael P.
   Sokoloski, J. L.
   Weston, Jennifer
   Zheng, Yong
   Bode, Michael F.
   Eyres, Stewart
   Roy, Nirupam
   Taylor, Gregory B.
TI Binary orbits as the driver of γ-ray emission and mass ejection in classical novae
SO NATURE
LA English
DT Article
ID common envelope phase; merlin observations; evolution; radio; remnants; winds
AB Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems(1). Novae typically expel about 10(-4) solar masses of material at velocities exceeding 1,000 kilometres per second. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of thermonuclear energy(2), prolonged optically thick winds(3) or binary interaction with the nova envelope(4). Classical novae are now routinely detected at gigaelectronvolt gamma-ray wavelengths(5), suggesting that relativistic particles are accelerated by strong shocks in the ejecta. Here we report high-resolution radio imaging of the gamma-ray-emitting nova V959 Mon. We find that its ejecta were shaped by the motion of the binary system: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion(6,7). At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae(8), explaining why many novae are gamma-ray emitters(5).
C1 [Chomiuk, Laura; Linford, Justin D.] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Yang, Jun] Chalmers Univ Technol, Onsala Space Observ, Dept Earth & Space Sci, SE-43992 Onsala, Sweden.
   [Yang, Jun; Paragi, Zsolt] Joint Inst VLBI Europe, NL-7990 AA Dwingeloo, Netherlands.
   [Yang, Jun] Chinese Acad Sci, Shanghai Astron Observ, Shanghai 200030, Peoples R China.
   [O'Brien, T. J.; Beswick, R. J.] Univ Manchester, Jodrell Bank, Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Mioduszewski, Amy J.; Rupen, Michael P.] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Cheung, C. C.] Naval Res Lab, Space Sci Div, Washington, DC 20375 USA.
   [Mukai, Koji] Univ Maryland Baltimore Cty, Sch Phys & Astron, Baltimore, MD 21250 USA.
   [Mukai, Koji] NASA, Goddard Space Flight Ctr, CRESST, Greenbelt, MD 20771 USA.
   [Mukai, Koji] NASA, Goddard Space Flight Ctr, Xray Astrophys Lab, Greenbelt, MD 20771 USA.
   [Nelson, Thomas] Univ Minnesota, Sch Phys & Astron, Minneapolis, MN 55455 USA.
   [Ribeiro, Valerio A. R. M.] Univ Cape Town, Dept Astron, Astrophys Cosmol & Grav Ctr, ZA-7701 Rondebosch, South Africa.
   [Rupen, Michael P.] Natl Res Council Canada, Herzberg Astron & Astrophys, Penticton, BC V2A 6J9, Canada.
   [Sokoloski, J. L.; Weston, Jennifer; Zheng, Yong] Columbia Univ, Columbia Astrophys Lab, New York, NY 10027 USA.
   [Bode, Michael F.] Liverpool John Moores Univ, Astrophys Res Inst, Liverpool L3 5RF, Merseyside, England.
   [Eyres, Stewart] Univ Cent Lancashire, Jeremiah Horrocks Inst Math Phys & Astron, Preston PR1 2HE, Lancs, England.
   [Roy, Nirupam] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Taylor, Gregory B.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
C3 Michigan State University; Chalmers University of Technology; Chinese Academy of Sciences; Shanghai Astronomical Observatory, CAS; University of Manchester; Jodrell Bank Centre for Astrophysics; National Radio Astronomy Observatory (NRAO); United States Department of Defense; United States Navy; United States Naval Research Laboratory; University System of Maryland; University of Maryland Baltimore County; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Minnesota System; University of Minnesota Twin Cities; University of Cape Town; National Research Council Canada; Columbia University; Liverpool John Moores University; University of Lancashire; Max Planck Society; University of New Mexico
RP Chomiuk, L (corresponding author), Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
EM chomiuk@pa.msu.edu
FU European Commission [283393, RI-261525]; Moore Foundation; Norris Foundation; McDonnell Foundation; Associates of the California Institute of Technology; University of Chicago; state of California; state of Illinois; state of Maryland; NSF; NASA [DPR S-15633-Y, 10-FERMI10-C4-0060, NNX13AO91G]; NSF [AST-1211778]; South African SKA Project; Alexander von Humboldt Foundation; NASA [NNX13AO91G, 467468] Funding Source: Federal RePORTER; STFC [ST/L000768/1, ST/J001465/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/L000768/1, ST/J001465/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1211778, 1140063] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1139998, 1140031, 1139950, 1140019] Funding Source: National Science Foundation
NR 38
TC 110
Z9 118
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 OCT 16
PY 2014
VL 514
IS 7522
BP 339
EP +
DI 10.1038/nature13773
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600045
PM 25296250
DA 2026-03-09
ER

PT J
AU Greber, BJ
   Boehringer, D
   Leitner, A
   Bieri, P
   Voigts-Hoffmann, F
   Erzberger, JP
   Leibundgut, M
   Aebersold, R
   Ban, N
AF Greber, Basil J.
   Boehringer, Daniel
   Leitner, Alexander
   Bieri, Philipp
   Voigts-Hoffmann, Felix
   Erzberger, Jan P.
   Leibundgut, Marc
   Aebersold, Ruedi
   Ban, Nenad
TI Architecture of the large subunit of the mammalian mitochondrial ribosome
SO NATURE
LA English
DT Article
ID cross-linked peptides; mass-spectrometry; crystal-structure; structural basis; cryo-em; rna; proteins; visualization; component; system
AB Mitochondrial ribosomes synthesize a number of highly hydrophobic proteins encoded on the genome of mitochondria, the organelles in eukaryotic cells that are responsible for energy conversion by oxidative phosphorylation. The ribosomes in mammalian mitochondria have undergone massive structural changes throughout their evolution, including ribosomal RNA shortening and acquisition of mitochondria-specific ribosomal proteins. Here we present the three-dimensional structure of the 39S large subunit of the porcine mitochondrial ribosome determined by cryo-electron microscopy at 4.9 angstrom resolution. The structure, combined with data from chemical crosslinking and mass spectrometry experiments, reveals the unique features of the 39S subunit at near-atomic resolution and provides detailed insight into the architecture of the polypeptide exit site. This region of the mitochondrial ribosome has been considerably remodelled compared to its bacterial counterpart, providing a specialized platform for the synthesis and membrane insertion of the highly hydrophobic protein components of the respiratory chain.
C1 [Greber, Basil J.; Boehringer, Daniel; Bieri, Philipp; Voigts-Hoffmann, Felix; Erzberger, Jan P.; Leibundgut, Marc; Ban, Nenad] ETH, Dept Biol, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
   [Leitner, Alexander; Aebersold, Ruedi] ETH, Dept Biol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich
RP Ban, N (corresponding author), ETH, Dept Biol, Inst Mol Biol & Biophys, Schafmattstr 20, CH-8093 Zurich, Switzerland.
EM aebersold@imsb.biol.ethz.ch; ban@mol.biol.ethz.ch
FU Swiss National Science Foundation (SNSF); National Center of Excellence in Research (NCCR) Structural Biology program of the SNSF; European Research Council (ERC) under the European Community [250071]; Commission of the European Communities through the PROSPECTS consortium (EU) [201648, 233226]; European Research Council [ERC-2008-AdG 233226]; European Research Council (ERC) [250071] Funding Source: European Research Council (ERC)
NR 54
TC 186
Z9 209
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 JAN 23
PY 2014
VL 505
IS 7484
BP 515
EP +
DI 10.1038/nature12890
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000032
PM 24362565
DA 2026-03-09
ER

PT J
AU Roth, TL
   Nayak, D
   Atanasijevic, T
   Koretsky, AP
   Latour, LL
   McGavern, DB
AF Roth, Theodore L.
   Nayak, Debasis
   Atanasijevic, Tatjana
   Koretsky, Alan P.
   Latour, Lawrence L.
   McGavern, Dorian B.
TI Transcranial amelioration of inflammation and cell death after brain injury
SO NATURE
LA English
DT Article
ID green fluorescent protein; in-vivo; sterile inflammation; head-injury; mice; biomarkers; insertion; release; cortex; fluid
AB Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function(1,2). At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.
C1 [Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RP McGavern, DB (corresponding author), NINDS, NIH, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
FU National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS); Center for Neuroscience and Regenerative Medicine (CNRM) at the Uniformed Services University of the Health Sciences; NIH; Department of Defense; Walter Reed National Military Medical Center; National Institute of Neurological Disorders and Stroke [ZIANS003120, ZIANS002989] Funding Source: NIH RePORTER
NR 26
TC 491
Z9 568
U1 3
U2 140
PU NATURE PUBLISHING 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 9
PY 2014
VL 505
IS 7482
BP 223
EP +
DI 10.1038/nature12808
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500040
PM 24317693
DA 2026-03-09
ER

PT J
AU Giering, SLC
   Sanders, R
   Lampitt, RS
   Anderson, TR
   Tamburini, C
   Boutrif, M
   Zubkov, MV
   Marsay, CM
   Henson, SA
   Saw, K
   Cook, K
   Mayor, DJ
AF Giering, Sarah L. C.
   Sanders, Richard
   Lampitt, Richard S.
   Anderson, Thomas R.
   Tamburini, Christian
   Boutrif, Mehdi
   Zubkov, Mikhail V.
   Marsay, Chris M.
   Henson, Stephanie A.
   Saw, Kevin
   Cook, Kathryn
   Mayor, Daniel J.
TI Reconciliation of the carbon budget in the ocean's twilight zone
SO NATURE
LA English
DT Article
ID particulate organic-matter; growth efficiency; mesopelagic zone; metabolic rates; particle export; microbial loop; water-column; spring bloom; body-mass; zooplankton
AB Photosynthesis in the surface ocean produces approximately 100 gigatonnes of organic carbon per year, of which 5 to 15 per cent is exported to the deep ocean(1,2). The rate at which the sinking carbon is converted into carbon dioxide by heterotrophic organisms at depth is important in controlling oceanic carbon storage(3). It remains uncertain, however, to what extent surface ocean carbon supply meets the demand of water-column biota; the discrepancy between known carbon sources and sinks is as much as two orders of magnitude(4-8). Here we present field measurements, respiration rate estimates and a steady-state model that allow us to balance carbon sources and sinks to within observational uncertainties at the Porcupine Abyssal Plain site in the eastern North Atlantic Ocean. We find that prokaryotes are responsible for 70 to 92 per cent of the estimated remineralization in the twilight zone (depths of 50 to 1,000 metres) despite the fact that much of the organic carbon is exported in the form of large, fast-sinking particles accessible to larger zooplankton. We suggest that this occurs because zooplankton fragment and ingest half of the fast-sinking particles, of which more than 30 per cent may be released as suspended and slowly sinking matter, stimulating the deep-ocean microbial loop. The synergy between microbes and zooplankton in the twilight zone is important to our understanding of the processes controlling the oceanic carbon sink.
C1 [Giering, Sarah L. C.; Sanders, Richard; Lampitt, Richard S.; Anderson, Thomas R.; Zubkov, Mikhail V.; Henson, Stephanie A.; Saw, Kevin] Univ Southampton, Natl Oceanog Ctr, Waterfront Campus,European Way, Southampton SO14 3ZH, Hants, England.
   [Giering, Sarah L. C.; Marsay, Chris M.] Univ Southampton, Southampton SO14 3ZH, Hants, England.
   [Giering, Sarah L. C.; Mayor, Daniel J.] Univ Aberdeen, Inst Biol & Environm Sci, Oceanlab, Newburgh AB41 6AA, Scotland.
   [Tamburini, Christian; Boutrif, Mehdi] Aix Marseille Univ, Univ Toulon, CNRS INSU, IRD,MIO,UM110, F-13288 Marseille 09, France.
   [Marsay, Chris M.] Univ S Carolina, Dept Earth & Ocean Sci, Columbia, SC 29208 USA.
   [Cook, Kathryn] Scottish Govt, Marine Lab, Marine Scotland Sci, Aberdeen AB11 9DB, Scotland.
C3 University of Southampton; NERC National Oceanography Centre; University of Southampton; University of Aberdeen; Aix-Marseille Universite; Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of South Carolina System; University of South Carolina Columbia; Marine Scotland Science (MSS)
RP Anderson, TR (corresponding author), Univ Southampton, Natl Oceanog Ctr, Waterfront Campus,European Way, Southampton SO14 3ZH, Hants, England.
EM s.giering@abdn.ac.uk; tra@noc.ac.uk
FU Oceans 2025; EU [264933]; ANR-POTES program [ANR-05-BLAN-0161-01]; Agence Nationale de la Recherche (ANR, France); NERC [NE/G014744/1]; Agence Nationale de la Recherche (ANR) [ANR-05-BLAN-0161] Funding Source: Agence Nationale de la Recherche (ANR); Natural Environment Research Council [NE/H005196/1, NE/K001833/1, noc010003, noc010013, noc010009, NE/J004383/1, NE/G014744/1] Funding Source: researchfish; NERC [noc010003, noc010013, NE/J004383/1, NE/H005196/1, NE/G014744/1, NE/K001833/1, noc010009] Funding Source: UKRI
NR 53
TC 322
Z9 351
U1 3
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 MAR 27
PY 2014
VL 507
IS 7493
BP 480
EP +
DI 10.1038/nature13123
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000036
PM 24670767
DA 2026-03-09
ER

PT J
AU Pouzols, FM
   Toivonen, T
   Di Minin, E
   Kukkala, AS
   Kullberg, P
   Kuusterä, J
   Lehtomäki, J
   Tenkanen, H
   Verburg, PH
   Moilanen, A
AF Pouzols, Federico Montesino
   Toivonen, Tuuli
   Di Minin, Enrico
   Kukkala, Aija S.
   Kullberg, Peter
   Kuustera, Johanna
   Lehtomaki, Joona
   Tenkanen, Henrikki
   Verburg, Peter H.
   Moilanen, Atte
TI Global protected area expansion is compromised by projected land-use and parochialism
SO NATURE
LA English
DT Article
ID key biodiversity areas; species-richness; conservation prioritization; reserve selection; worlds; costs; scale; resolution; diversity; regions
AB Protected areas are one of the main tools for halting the continuing global biodiversity crisis(1-4) caused by habitat loss, fragmentation and other anthropogenic pressures(5-8). According to the Aichi Biodiversity Target 11 adopted by the Convention on Biological Diversity, the protected area network should be expanded to at least 17% of the terrestrial world by 2020 (http://www.cbd.int/sp/targets). To maximize conservation outcomes, it is crucial to identify the best expansion areas. Here we show that there is a very high potential to increase protection of ecoregions and vertebrate species by expanding the protected area network, but also identify considerable risk of ineffective outcomes due to land-use change and uncoordinated actions between countries. We use distribution data for 24,757 terrestrial vertebrates assessed under the International Union for the Conservation of Nature (IUCN) 'red list of threatened species' 9, and terrestrial ecoregions(10) (827), modified by land-use models for the present and 2040, and introduce techniques for global and balanced spatial conservation prioritization. First, we show that with a coordinated global protected area network expansion to 17% of terrestrial land, average protection of species ranges and ecoregions could triple. Second, if projected land-use change by 2040 (ref. 11) takes place, it becomes infeasible to reach the currently possible protection levels, and over 1,000 threatened species would lose more than 50% of their present effective ranges worldwide. Third, we demonstrate a major efficiency gap between national and global conservation priorities. Strong evidence is shown that further biodiversity loss is unavoidable unless international action is quickly taken to balance land-use and biodiversity conservation. The approach used here can serve as a framework for repeatable and quantitative assessment of efficiency, gaps and expansion of the global protected area network globally, regionally andnationally, considering current and projected land-use pressures.
C1 [Pouzols, Federico Montesino; Toivonen, Tuuli; Di Minin, Enrico; Kukkala, Aija S.; Kullberg, Peter; Kuustera, Johanna; Lehtomaki, Joona; Moilanen, Atte] Univ Helsinki, Dept Biosci, Finnish Ctr Excellence Metapopulat Biol, Bioctr, FI-00014 Helsinki, Finland.
   [Toivonen, Tuuli] Univ Helsinki, Dept Geosci & Geog, FI-00014 Helsinki, Finland.
   [Di Minin, Enrico] Univ KwaZulu Natal, Dept Life Sci, ZA-4000 Durban, South Africa.
   [Kuustera, Johanna] Reg Council Helsinki Uusimaa, FI-00240 Helsinki, Finland.
   [Verburg, Peter H.] Vrije Univ Amsterdam, Inst Environm Studies, NL-1081 HV Amsterdam, Netherlands.
C3 University of Helsinki; University of Helsinki; University of Kwazulu Natal; Vrije Universiteit Amsterdam
RP Pouzols, FM (corresponding author), Rutherford Appleton Lab, Sci & Technol Facil Council, Harwell Oxford Campus, Didcot OX11 0QX, Oxon, England.
EM federico.montesino-pouzols@stfc.ac.uk; tuuli.toivonen@helsinki.fi; atte.moilanen@helsinki.fi
FU European Research Council Starting Grant (ERC-StG) [260393]; Academy of Finland centre of excellence programme; Natural Heritage Services (Metsahallitus); ERC [311819]; CSC-IT Center for Science Ltd; European Research Council (ERC) [311819] Funding Source: European Research Council (ERC)
NR 91
TC 336
Z9 371
U1 4
U2 351
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 383
EP +
DI 10.1038/nature14032
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800044
PM 25494203
DA 2026-03-09
ER

PT J
AU Budai, JD
   Hong, JW
   Manley, ME
   Specht, ED
   Li, CW
   Tischler, JZ
   Abernathy, DL
   Said, AH
   Leu, BM
   Boatner, LA
   McQueeney, RJ
   Delaire, O
AF Budai, John D.
   Hong, Jiawang
   Manley, Michael E.
   Specht, Eliot D.
   Li, Chen W.
   Tischler, Jonathan Z.
   Abernathy, Douglas L.
   Said, Ayman H.
   Leu, Bogdan M.
   Boatner, Lynn A.
   McQueeney, Robert J.
   Delaire, Olivier
TI Metallization of vanadium dioxide driven by large phonon entropy
SO NATURE
LA English
DT Article
ID metal-insulator-transition; mott-hubbard; lattice-dynamics; vo2; peierls; rutile; view; nbo2
AB Phase competition underlies many remarkable and technologically important phenomena in transition metal oxides. Vanadium dioxide (VO2) exhibits a first-order metal-insulator transition (MIT) near room temperature, where conductivity is suppressed and the lattice changes from tetragonal to monoclinic on cooling. Ongoing attempts to explain this coupled structural and electronic transition begin with two alternative starting points: a Peierls MIT driven by instabilities in electron-lattice dynamics and a Mott MIT where strong electronelectron correlations drive charge localization'. A key missing piece of the VO2 puzzle is the role of lattice vibrations. Moreover, a comprehensive thermodynamic treatment must integrate both entropic and energetic aspects of the transition. Here we report that the entropy driving the MIT in VO2 is dominated by strongly anharmonic phonons rather than electronic contributions, and provide a direct determination of phonon dispersions. Our ab initio calculations identify softer bonding in the tetragonal phase, relative to the monoclinic phase, as the origin of the large vibrational entropy stabilizing the metallic mtile phase. They further reveal how a balance between higher entropy in the metal and orbital-driven lower energy in the insulator fully describes the thermodynamic forces controlling the MIT. Our study illustrates the critical role of anharmonic lattice dynamics in metal oxide phase competition, and provides guidance for the predictive design of new materials.
C1 [Budai, John D.; Hong, Jiawang; Manley, Michael E.; Specht, Eliot D.; Li, Chen W.; Boatner, Lynn A.; Delaire, Olivier] Oak Ridge Natl Lab, Div Mat Sci & Technol, Oak Ridge, TN 37831 USA.
   [Tischler, Jonathan Z.; Said, Ayman H.; Leu, Bogdan M.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Abernathy, Douglas L.] Oak Ridge Natl Lab, Quantum Condensed Matter Div, Oak Ridge, TN 37831 USA.
   [McQueeney, Robert J.] Oak Ridge Natl Lab, Neutron Sci Directorate, Oak Ridge, TN 37831 USA.
C3 United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory
RP Budai, JD (corresponding author), Oak Ridge Natl Lab, Div Mat Sci & Technol, Oak Ridge, TN 37831 USA.
EM budaijd@ornl.gov; delaireoa@ornl.gov
FU US Department of Energy (DOE), Basic Energy Sciences (BES), Materials Sciences and Engineering Division (MSED); Center for Accelerating Materials Modeling - US DOE, BES, MSED; Laboratory Directed Research and Development Program of ORNL; US DOE, BES, Scientific User Facilities Division; Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy; US DOE [DE-AC02-06CH11357]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]
NR 46
TC 292
Z9 339
U1 12
U2 631
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2014
VL 515
IS 7528
BP 535
EP +
DI 10.1038/nature13865
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600049
PM 25383524
DA 2026-03-09
ER

PT J
AU Liu, HP
   Moynihan, KD
   Zheng, YR
   Szeto, GL
   Li, AV
   Huang, B
   Van Egeren, DS
   Park, C
   Irvine, DJ
AF Liu, Haipeng
   Moynihan, Kelly D.
   Zheng, Yiran
   Szeto, Gregory L.
   Li, Adrienne V.
   Huang, Bonnie
   Van Egeren, Debra S.
   Park, Clara
   Irvine, Darrell J.
TI Structure-based programming of lymph-node targeting in molecular vaccines
SO NATURE
LA English
DT Article
ID delivery; oligonucleotides; vaccination; antigen; cells
AB In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes(1,2). Here we translate this 'albumin hitchhiking' approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.
C1 [Liu, Haipeng; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
   [Liu, Haipeng; Moynihan, Kelly D.; Zheng, Yiran; Szeto, Gregory L.; Li, Adrienne V.; Huang, Bonnie; Park, Clara; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Liu, Haipeng; Moynihan, Kelly D.; Zheng, Yiran; Szeto, Gregory L.; Li, Adrienne V.; Huang, Bonnie; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Van Egeren, Debra S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
   [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute
RP Irvine, DJ (corresponding author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
EM djirvine@mit.edu
FU Koch Institute from the National Cancer Institute [P30-CA14051]; National Institutes of Health [AI091693, AI104715, AI095109]; Department of Defense [W911NF-13-D-0001, W911NF-07-D-0004, T.O. 8]; Ragon Institute of Massachusetts General Hospital; Massachusetts Institute of Technology and Harvard; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 28
TC 818
Z9 987
U1 7
U2 564
PU NATURE PUBLISHING 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 27
PY 2014
VL 507
IS 7493
BP 519
EP +
DI 10.1038/nature12978
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000045
PM 24531764
DA 2026-03-09
ER

PT J
AU Knutson, HA
   Benneke, B
   Deming, D
   Homeier, D
AF Knutson, Heather A.
   Benneke, Bjoern
   Deming, Drake
   Homeier, Derek
TI A featureless transmission spectrum for the Neptune-mass exoplanet GJ 436b
SO NATURE
LA English
DT Article
ID transiting hot neptune; super-earth; hd 189733b; atmosphere; hubble; planets; spectroscopy; methane; parameters; radiation
AB GJ 436b is a warm-approximately 800 kelvin-exoplanet that periodically eclipses its low-mass (half the mass of the Sun) host star, and is one of the few Neptune-mass planets that is amenable to detailed characterization. Previous observations(1-3) have indicated that its atmosphere has a ratio of methane to carbon monoxide that is 10(5) times smaller than predicted by models for hydrogen-dominated atmospheres at these temperatures(4,5). A recent study proposed that this unusual chemistry could be explained if the planet's atmosphere is significantly enhanced in elements heavier than hydrogen and helium(6). Here we report observations of GJ 436b's atmosphere obtained during transit. The data indicate that the planet's transmission spectrum is featureless, ruling out cloud-free, hydrogen-dominated atmosphere models with an extremely high significance of 48 sigma. The measured spectrum is consistent with either a layer of high cloud located at a pressure level of approximately one millibar or with a relatively hydrogen-poor (three per cent hydrogen and helium mass fraction) atmospheric composition(7-9).
C1 [Knutson, Heather A.; Benneke, Bjoern] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Benneke, Bjoern] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Deming, Drake] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Homeier, Derek] Ctr Rech Astrophys Lyon, F-69364 Lyon, France.
C3 California Institute of Technology; Massachusetts Institute of Technology (MIT); University System of Maryland; University of Maryland College Park; Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON)
RP Knutson, HA (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM hknutson@caltech.edu
FU European Research Council under the European Community [247060]
NR 45
TC 275
Z9 329
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 JAN 2
PY 2014
VL 505
IS 7481
BP 66
EP +
DI 10.1038/nature12887
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300024
PM 24380953
DA 2026-03-09
ER

PT J
AU Wang, KL
   Jiang, K
   Chung, B
   Ouchi, T
   Burke, PJ
   Boysen, DA
   Bradwell, DJ
   Kim, H
   Muecke, U
   Sadoway, DR
AF Wang, Kangli
   Jiang, Kai
   Chung, Brice
   Ouchi, Takanari
   Burke, Paul J.
   Boysen, Dane A.
   Bradwell, David J.
   Kim, Hojong
   Muecke, Ulrich
   Sadoway, Donald R.
TI Lithium-antimony-lead liquid metal battery for grid-level energy storage
SO NATURE
LA English
DT Article
ID alloys; magnesium; systems
AB The ability to store energy on the electric grid would greatly improve its efficiency and reliability while enabling the integration of intermittent renewable energy technologies (such as wind and solar) into baseload supply(1-4). Batteries have long been considered strong candidate solutions owing to their small spatial footprint, mechanical simplicity and flexibility in siting. However, the barrier to widespread adoption of batteries is their high cost. Here we describe a lithium-antimony-lead liquid metal battery that potentially meets the performance specifications for stationary energy storage applications. This Li parallel to Sb-Pb battery comprises a liquid lithium negative electrode, a molten salt electrolyte, and a liquid antimony-lead alloy positive electrode, which self-segregate by density into three distinct layers owing to the immiscibility of the contiguous salt and metal phases. The all-liquid construction confers the advantages of higher current density, longer cycle life and simpler manufacturing of large-scale storage systems (because no membranes or separators are involved) relative to those of conventional batteries(5,6). At charge-discharge current densities of 275 milliamperes per square centimetre, the cells cycled at 450 degrees Celsius with 98 per cent Coulombic efficiency and 73 per cent round-trip energy efficiency. To provide evidence of their high power capability, the cells were discharged and charged at current densities as high as 1,000 milliamperes per square centimetre. Measured capacity loss after operation for 1,800 hours (more than 450 charge-discharge cycles at 100 per cent depth of discharge) projects retention of over 85 per cent of initial capacity after ten years of daily cycling. Our results demonstrate that alloying a high-melting-point, high-voltage metal (antimony) with a low-melting-point, low-cost metal (lead) advantageously decreases the operating temperature while maintaining a high cell voltage. Apart from the fact that this finding puts us on a desirable cost trajectory, this approach may well be more broadly applicable to other battery chemistries.
C1 [Wang, Kangli; Jiang, Kai; Chung, Brice; Ouchi, Takanari; Burke, Paul J.; Boysen, Dane A.; Bradwell, David J.; Kim, Hojong; Muecke, Ulrich; Sadoway, Donald R.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Sadoway, DR (corresponding author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM dsadoway@mit.edu
FU Advanced Research Projects Agency-Energy (US Department of Energy); Total SA
NR 16
TC 407
Z9 487
U1 17
U2 778
PU NATURE PUBLISHING 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 16
PY 2014
VL 514
IS 7522
BP 348
EP +
DI 10.1038/nature13700
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600047
PM 25252975
DA 2026-03-09
ER

PT J
AU MacArthur, DG
   Manolio, TA
   Dimmock, DP
   Rehm, HL
   Shendure, J
   Abecasis, GR
   Adams, DR
   Altman, RB
   Antonarakis, SE
   Ashley, EA
   Barrett, JC
   Biesecker, LG
   Conrad, DF
   Cooper, GM
   Cox, NJ
   Daly, MJ
   Gerstein, MB
   Goldstein, DB
   Hirschhorn, JN
   Leal, SM
   Pennacchio, LA
   Stamatoyannopoulos, JA
   Sunyaev, SR
   Valle, D
   Voight, BF
   Winckler, W
   Gunter, C
AF MacArthur, D. G.
   Manolio, T. A.
   Dimmock, D. P.
   Rehm, H. L.
   Shendure, J.
   Abecasis, G. R.
   Adams, D. R.
   Altman, R. B.
   Antonarakis, S. E.
   Ashley, E. A.
   Barrett, J. C.
   Biesecker, L. G.
   Conrad, D. F.
   Cooper, G. M.
   Cox, N. J.
   Daly, M. J.
   Gerstein, M. B.
   Goldstein, D. B.
   Hirschhorn, J. N.
   Leal, S. M.
   Pennacchio, L. A.
   Stamatoyannopoulos, J. A.
   Sunyaev, S. R.
   Valle, D.
   Voight, B. F.
   Winckler, W.
   Gunter, C.
TI Guidelines for investigating causality of sequence variants in human disease
SO NATURE
LA English
DT Article
ID de-novo mutations; rare variants; genes; phenotype; individuals; association; population; dissection; evolution; gencode
AB The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.
C1 [MacArthur, D. G.; Daly, M. J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [MacArthur, D. G.; Daly, M. J.; Hirschhorn, J. N.; Winckler, W.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Manolio, T. A.] NHGRI, Div Genom Med, Bethesda, MD 20892 USA.
   [Dimmock, D. P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA.
   [Rehm, H. L.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA 02139 USA.
   [Rehm, H. L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Shendure, J.] Univ Washington, Dept Genome Sci, Seattle, WA 98115 USA.
   [Abecasis, G. R.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Adams, D. R.] NIH, NIH Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA.
   [Adams, D. R.] NHGRI, Bethesda, MD 20892 USA.
   [Adams, D. R.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Altman, R. B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Altman, R. B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Antonarakis, S. E.] Univ Geneva, Sch Med, Dept Med Genet, CH-1211 Geneva, Switzerland.
   [Antonarakis, S. E.] iGE3 Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland.
   [Ashley, E. A.] Stanford Univ, Sch Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA.
   [Barrett, J. C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Biesecker, L. G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   [Conrad, D. F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Conrad, D. F.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA.
   [Conrad, D. F.] Washington Univ, Sch Med, Dept Immunol, St Louis, MO 63110 USA.
   [Cooper, G. M.; Gunter, C.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Cox, N. J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA.
   [Gerstein, M. B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Gerstein, M. B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Gerstein, M. B.] Yale Univ, Dept Mol Biophys, New Haven, CT 06520 USA.
   [Gerstein, M. B.] Yale Univ, Dept Biochem, New Haven, CT 06520 USA.
   [Goldstein, D. B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA.
   [Hirschhorn, J. N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
   [Hirschhorn, J. N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
   [Leal, S. M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Pennacchio, L. A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
   [Pennacchio, L. A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Stamatoyannopoulos, J. A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Sunyaev, S. R.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Sunyaev, S. R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Valle, D.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
   [Voight, B. F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
   [Voight, B. F.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Medical College of Wisconsin; Mass General Brigham; Harvard University; Harvard Medical School; University of Washington; University of Washington Seattle; University of Michigan System; University of Michigan; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Stanford University; Stanford University; University of Geneva; Stanford University; Wellcome Trust Sanger Institute; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); HudsonAlpha Institute for Biotechnology; University of Chicago; Yale University; Yale University; Yale University; Yale University; Duke University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Baylor College of Medicine; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; University of Washington; University of Washington Seattle; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Johns Hopkins University; University of Pennsylvania; University of Pennsylvania
RP MacArthur, DG (corresponding author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM macarthur@atgu.mgh.harvard.edu; drchrisgunter@gmail.com
FU National Human Genome Research Institute [ZIAHG200328, ZIAHG200387, ZIAHG200359] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020595] Funding Source: NIH RePORTER; NHGRI NIH HHS [R01 HG007022, U54 HG006997, U01 HG007301] Funding Source: Medline; NHLBI NIH HHS [R01 HL117626] Funding Source: Medline; NIDDK NIH HHS [P30 DK020595] Funding Source: Medline; NIMH NIH HHS [R01 MH101810] Funding Source: Medline
NR 60
TC 964
Z9 1142
U1 1
U2 127
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2014
VL 508
IS 7497
BP 469
EP 476
DI 10.1038/nature13127
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600026
PM 24759409
DA 2026-03-09
ER

PT J
AU Lesterlin, C
   Ball, G
   Schermelleh, L
   Sherratt, DJ
AF Lesterlin, Christian
   Ball, Graeme
   Schermelleh, Lothar
   Sherratt, David J.
TI RecA bundles mediate homology pairing between distant sisters during DNA break repair
SO NATURE
LA English
DT Article
ID escherichia-coli chromosome; double-stranded dna; in-vivo; structured illumination; single-molecule; live cells; protein; recombination; segregation; architecture
AB DNA double-strand break (DSB) repair by homologous recombination has evolved to maintain genetic integrity in all organisms(1). Although many reactions that occur during homologous recombination are known(1-3), it is unclear where, when and how they occur in cells. Here, by using conventional and super-resolution microscopy, we describe the progression of DSB repair in live Escherichia coli. Specifically, we investigate whether homologous recombination can occur efficiently between distant sister loci that have segregated to opposite halves of an E. coli cell. We show that a site-specific DSB in one sister can be repaired efficiently using distant sister homology. After RecBCD processing of the DSB, RecA is recruited to the cut locus, where it nucleates into a bundle that contains many more RecA molecules than can associate with the two single-stranded DNA regions that format the DSB. Mature bundles extend along the long axis of the cell, in the space between the bulk nucleoid and the inner membrane. Bundle formation is followed by pairing, in which the two ends of the cut locus relocate at the periphery of the nucleoid and together move rapidly towards the homology of the uncut sister. After sister locus pairing, RecA bundles disassemble and proteins that act late in homologous recombination are recruited to give viable recombinants 1-2-generation-time equivalents after formation of the initial DSB. Mutated RecA proteins that do not form bundles are defective in sister pairing and in DSB-induced repair. This work reveals an unanticipated role of RecA bundles in channelling the movement of the DNA DSB ends, thereby facilitating the long-range homology search that occurs before the strand invasion and transfer reactions.
C1 [Lesterlin, Christian; Ball, Graeme; Schermelleh, Lothar; Sherratt, David J.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
C3 University of Oxford
RP Sherratt, DJ (corresponding author), Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
EM david.sherratt@bioch.ox.ac.uk
FU EMBO long-term fellowship [LTF-535-2009]; Wellcome Trust Programme Grant [WT083469MA]; Wellcome Trust Strategic Award [091911]; Medical Research Council [1514510] Funding Source: researchfish
NR 44
TC 139
Z9 159
U1 1
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 FEB 13
PY 2014
VL 506
IS 7487
BP 249
EP +
DI 10.1038/nature12868
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700044
PM 24362571
DA 2026-03-09
ER

PT J
AU Amorisco, NC
   Evans, NW
   van de Ven, G
AF Amorisco, N. C.
   Evans, N. W.
   van de Ven, G.
TI The remnant of a merger between two dwarf galaxies in Andromeda II
SO NATURE
LA English
DT Article
ID stellar tidal stream; spheroidal galaxy; ngc 4449; halo; m31; sagittarius; kinematics; fossils; stars
AB Driven by gravity, massive structures like galaxies and clusters of galaxies are believed to grow continuously through hierarchical merging and accretion of smaller systems. Observational evidence of accretion events is provided by the coherent stellar streams crossing the outer haloes of massive galaxies, such as the Milky Way(1) or Andromeda(2). At similar mass scales, around 1011 solar masses in stars, further evidence of merging activity is also ample(3-5). Mergers of lower-mass galaxies are expected within the hierarchical process of galaxy formation(6), but have hitherto not been seen for galaxies with less than about 10(9) solar masses in stars(7,8). Here we report the kinematic detection of a stellar stream in one of the satellite galaxies of Andromeda, the dwarf spheroidal Andromeda II, which has a mass of only 10(7) solar masses in stars(9). The properties of the stream show that we are observing the remnant of a merger between two dwarf galaxies. This had a drastic influence on the dynamics of the remnant, which is now rotating around its projected major axis(10). The stellar stream in Andromeda II illustrates the scale-free character of the formation of galaxies, down to the lowest galactic mass scales.
C1 [Amorisco, N. C.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen, Denmark.
   [Evans, N. W.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [van de Ven, G.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 University of Copenhagen; Niels Bohr Institute; University of Cambridge; Max Planck Society
RP Amorisco, NC (corresponding author), Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, Juliane Maries Vej 30, DK-2100 Copenhagen, Denmark.
EM amorisco@dark-cosmology.dk
FU Danish National Research Foundation; German Research Foundation [Sonderforschungsbereich SFB 881]; Science and Technology Facilities Council [ST/H00243X/1] Funding Source: researchfish
NR 29
TC 87
Z9 93
U1 0
U2 5
PU NATURE PUBLISHING 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 20
PY 2014
VL 507
IS 7492
BP 335
EP +
DI 10.1038/nature12995
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000028
PM 24572352
DA 2026-03-09
ER

PT J
AU Xue, MS
   Atallah, BV
   Scanziani, M
AF Xue, Mingshan
   Atallah, Bassam V.
   Scanziani, Massimo
TI Equalizing excitation-inhibition ratios across visual cortical neurons
SO NATURE
LA English
DT Article
ID rectifying potassium channels; in-vivo electroporation; network activity; gene-transfer; cortex; mouse; channelrhodopsin-2; connectivity; interneurons; modulation
AB The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain(1,2). Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation-inhibition balance(3-9). However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells(10,11). Is inhibition homogeneously distributed(12) or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex each receive inhibition in a similar proportion to their excitation. As a consequence, E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between the cortex's two opposing forces is stabilized not only in time but also in space.
C1 [Xue, Mingshan; Scanziani, Massimo] Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
   [Xue, Mingshan; Scanziani, Massimo] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Atallah, Bassam V.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
   [Scanziani, Massimo] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Fundacao Champalimaud; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Xue, MS (corresponding author), Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
EM mingshanxue@gmail.com; massimo@ucsd.edu
FU Jane Coffin Childs Memorial Fund for Medical Research; Gatsby Charitable Foundation; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 50
TC 542
Z9 659
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 JUL 30
PY 2014
VL 511
IS 7511
BP 596
EP +
DI 10.1038/nature13321
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300036
PM 25043046
DA 2026-03-09
ER

PT J
AU Hautier, Y
   Seabloom, EW
   Borer, ET
   Adler, PB
   Harpole, WS
   Hillebrand, H
   Lind, EM
   MacDougall, AS
   Stevens, CJ
   Bakker, JD
   Buckley, YM
   Chu, CJ
   Collins, SL
   Daleo, P
   Damschen, EI
   Davies, KF
   Fay, PA
   Firn, J
   Gruner, DS
   Jin, VL
   Klein, JA
   Knops, JMH
   La Pierre, KJ
   Li, W
   McCulley, RL
   Melbourne, BA
   Moore, JL
   O'Halloran, LR
   Prober, SM
   Risch, AC
   Sankaran, M
   Schuetz, M
   Hector, A
AF Hautier, Yann
   Seabloom, Eric W.
   Borer, Elizabeth T.
   Adler, Peter B.
   Harpole, W. Stanley
   Hillebrand, Helmut
   Lind, Eric M.
   MacDougall, Andrew S.
   Stevens, Carly J.
   Bakker, Jonathan D.
   Buckley, Yvonne M.
   Chu, Chengjin
   Collins, Scott L.
   Daleo, Pedro
   Damschen, Ellen I.
   Davies, Kendi F.
   Fay, Philip A.
   Firn, Jennifer
   Gruner, Daniel S.
   Jin, Virginia L.
   Klein, Julia A.
   Knops, Johannes M. H.
   La Pierre, Kimberly J.
   Li, Wei
   McCulley, Rebecca L.
   Melbourne, Brett A.
   Moore, Joslin L.
   O'Halloran, Lydia R.
   Prober, Suzanne M.
   Risch, Anita C.
   Sankaran, Mahesh
   Schuetz, Martin
   Hector, Andy
TI Eutrophication weakens stabilizing effects of diversity in natural grasslands
SO NATURE
LA English
DT Article
ID ecosystem stability; plant diversity; biodiversity loss; productivity; ecology; losses; population; resistance; impact
AB Studies of experimental grassland communities(1-7) have demonstrated that plant diversity can stabilize productivity through species asynchrony, in which decreases in the biomass of some species are compensated for by increases in others(1,2). However, it remains unknown whether these findings are relevant to natural ecosystems, especially those for which species diversity is threatened by anthropogenic global change(8-11). Here we analyse diversity-stability relationships from 41 grasslands on five continents and examine how these relationships are affected by chronic fertilization, one of the strongest drivers of species loss globally(8). Unmanipulated communities with more species had greater species asynchrony, resulting in more stable biomass production, generalizing a result from biodiversity experiments to real-world grasslands. However, fertilization weakened the positive effect of diversity on stability. Contrary to expectations, this was not due to species loss after eutrophication but rather to an increase in the temporal variation of productivity in combination with a decrease in species asynchrony in diverse communities. Our results demonstrate separate and synergistic effects of diversity and eutrophication on stability, emphasizing the need to understand how drivers of global change interactively affect the reliable provisioning of ecosystem services in real-world systems.
C1 [Hautier, Yann; Seabloom, Eric W.; Borer, Elizabeth T.; Lind, Eric M.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Hautier, Yann] Univ Zurich, Inst Evolutionary Biol & Environm Studies, CH-8057 Zurich, Switzerland.
   [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] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
   [Hillebrand, Helmut] Carl von Ossietzky Univ Oldenburg, Inst Chem & Biol Marine Environm, D-26111 Oldenburg, Germany.
   [MacDougall, Andrew S.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Stevens, Carly J.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Bakker, Jonathan D.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Buckley, Yvonne M.] Univ Queensland, Sch Biol Sci, Australian Res Council Ctr Excellence Environm De, Brisbane, Qld 4072, Australia.
   [Buckley, Yvonne M.] Trinity Coll Dublin, Dept Zool, Sch Nat Sci, Dublin 2, Ireland.
   [Chu, Chengjin] Lanzhou Univ, Sch Life Sci, Res Stn Alpine Meadow & Wetland Ecosyst, State Key Lab Grassland & Agroecosyst, Lanzhou 730000, Peoples R China.
   [Collins, Scott L.] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA.
   [Daleo, Pedro] UNMdP, CONICET, IIMyC, RA-7600 Mar Del Plata, Argentina.
   [Damschen, Ellen I.] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
   [Damschen, Ellen I.] 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.] USDA ARS, Grassland Soil & Water Res Lab, Temple, TX 76502 USA.
   [Firn, Jennifer] Queensland Univ Technol, Sch Biol Sci, Brisbane, Qld 4000, Australia.
   [Gruner, Daniel S.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Jin, Virginia L.] USDA ARS, Agroecosyst Management Res Unit, Lincoln, NE 68583 USA.
   [Klein, Julia A.] Colorado State Univ, Dept Forest Rangeland & Watershed Stewardship, Ft Collins, CO 80523 USA.
   [Knops, Johannes M. H.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
   [La Pierre, Kimberly J.] Univ Calif Berkeley, Berkeley Initiat Global Change Biol, Berkeley, CA 94720 USA.
   [Li, Wei] Southwest Forestry Univ, Yunnan Acad Biodivers, Kunming 650224, Peoples R China.
   [McCulley, Rebecca L.] Univ Kentucky, Dept Plant & Soil Sci, Lexington, KY 40546 USA.
   [Moore, Joslin L.] Univ Melbourne, Sch Bot, Australian Res Ctr Urban Ecol, Melbourne, Vic 3010, Australia.
   [Moore, Joslin L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [O'Halloran, Lydia R.] Oregon State Univ, Dept Zool, Corvallis, OR 97331 USA.
   [Prober, Suzanne M.] CSIRO Ecosyst Sci, Wembley, WA 6913, Australia.
   [Risch, Anita C.; Schuetz, Martin] Swiss Fed Inst Forest Snow & Landscape Res, CH-8903 Birmensdorf, Switzerland.
   [Sankaran, Mahesh] Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England.
   [Sankaran, Mahesh] Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India.
   [Hector, Andy] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Zurich; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Iowa State University; Carl von Ossietzky Universitat Oldenburg; University of Guelph; Lancaster University; University of Washington; University of Washington Seattle; University of Queensland; Trinity College Dublin; Lanzhou University; University of New Mexico; University of Wisconsin System; University of Wisconsin Madison; 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; United States Department of Agriculture (USDA); Colorado State University System; Colorado State University Fort Collins; University of Nebraska System; University of Nebraska Lincoln; University of California System; University of California Berkeley; Southwest Forestry University - China; University of Kentucky; University of Melbourne; Monash University; Oregon State University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Leeds; Tata Institute of Fundamental Research (TIFR); National Centre for Biological Sciences (NCBS); University of Oxford
RP Hautier, Y (corresponding author), Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
EM hauti001@umn.edu
FU European Union [298935]; National Science Foundation Research Coordination Network [NSF-DEB-1042132]; Long Term Ecological Research (LTER) programme [NSF-DEB-1234162]; Institute on the Environment at the University of Minnesota [DG-0001-13]; National Health and Medical Research Council (NHMRC) [298935] Funding Source: National Health and Medical Research Council (NHMRC); Direct For Biological Sciences; Division Of Environmental Biology [1042132, 0823380, 1440484] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0823341, 1232294] Funding Source: National Science Foundation
NR 42
TC 479
Z9 543
U1 29
U2 1102
PU NATURE PUBLISHING 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 24
PY 2014
VL 508
IS 7497
BP 521
EP +
DI 10.1038/nature13014
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600036
PM 24531763
DA 2026-03-09
ER

PT J
AU Palmer, JC
   Martelli, F
   Liu, Y
   Car, R
   Panagiotopoulos, AZ
   Debenedetti, PG
AF Palmer, Jeremy C.
   Martelli, Fausto
   Liu, Yang
   Car, Roberto
   Panagiotopoulos, Athanassios Z.
   Debenedetti, Pablo G.
TI Metastable liquid-liquid transition in a molecular model of water
SO NATURE
LA English
DT Article
ID supercooled water; heat-capacity; cubic ice; st2 water; energy; simulation; dynamics; behavior; singularity; stability
AB Liquid water's isothermal compressibility(1) and isobaric heat capacity(2), and the magnitude of its thermal expansion coefficient(3), increase sharply on cooling below the equilibrium freezing point. Many experimental(4-8), theoretical(9-11) and computational(12,13) studies have sought to understand the molecular origin and implications of this anomalous behaviour. Of the different theoretical scenarios(9,14,15) put forward, one posits the existence of a first-order phase transition that involves two forms of liquid water and terminates at a critical point located at deeply supercooled conditions(9,12). Some experimental evidence is consistent with this hypothesis(4,16), but no definitive proof of a liquid-liquid transition in water has been obtained to date: rapid ice crystallization has so far prevented decisive measurements on deeply supercooled water, although this challenge has been overcome recently(16). Computer simulations are therefore crucial for exploring water's structure and behaviour in this regime, and have shown(13,17-21) that some water models exhibit liquid-liquid transitions and others do not. However, recent work(22,23) has argued that the liquid-liquid transition has been mistakenly interpreted, and is in fact a liquid-crystal transition in all atomistic models of water. Here we show, by studying the liquid-liquid transition in the ST2 model of water(24) with the use of six advanced sampling methods to compute the free-energy surface, that two metastable liquid phases and a stable crystal phase exist at the same deeply supercooled thermodynamic condition, and that the transition between the two liquids satisfies the thermodynamic criteria of a first-order transition(25). We follow the rearrangement of water's coordination shell and topological ring structure along a thermodynamically reversible path from the low-density liquid to cubic ice(26). We also show that the system fluctuates freely between the two liquid phases rather than crystallizing. These findings provide unambiguous evidence for a liquid-liquid transition in the ST2 model of water, and point to the separation of time scales between crystallization and relaxation as being crucial for enabling it.
C1 [Palmer, Jeremy C.; Liu, Yang; Panagiotopoulos, Athanassios Z.; Debenedetti, Pablo G.] Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
   [Martelli, Fausto; Car, Roberto] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University
RP Debenedetti, PG (corresponding author), Princeton Univ, Dept Chem & Biol Engn, Princeton, NJ 08544 USA.
EM pdebene@princeton.edu
FU National Science Foundation [CHE 1213343]; US Department of Energy [DE-SC0002128, DE-SC0008626]; Direct For Mathematical & Physical Scien; Division Of Chemistry [1213343] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0002128, DE-SC0008626] Funding Source: U.S. Department of Energy (DOE)
NR 57
TC 470
Z9 495
U1 5
U2 490
PU NATURE PUBLISHING 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 19
PY 2014
VL 510
IS 7505
BP 385
EP +
DI 10.1038/nature13405
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200032
PM 24943954
DA 2026-03-09
ER

PT J
AU Huo, HH
   Shen, XD
   Wang, CY
   Zhang, LL
   Röse, P
   Chen, LA
   Harms, K
   Marsch, M
   Hilt, G
   Meggers, E
AF Huo, Haohua
   Shen, Xiaodong
   Wang, Chuanyong
   Zhang, Lilu
   Roese, Philipp
   Chen, Liang-An
   Harms, Klaus
   Marsch, Michael
   Hilt, Gerhard
   Meggers, Eric
TI Asymmetric photoredox transition-metal catalysis activated by visible light
SO NATURE
LA English
DT Article
ID dual-catalysis; complexes; alkylation; electron; trifluoromethylation; aldehydes; driven; acid
AB Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries(1). And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes(2-5). For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest(2-5). Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions(6). In such systems, photoactivated sensitizers initiate a single electron transfer from(or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion(7). Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the 'green' synthesis of non-racemic chiral molecules.
C1 [Huo, Haohua; Shen, Xiaodong; Wang, Chuanyong; Zhang, Lilu; Roese, Philipp; Harms, Klaus; Marsch, Michael; Hilt, Gerhard; Meggers, Eric] Univ Marburg, Fachbereich Chem, D-35043 Marburg, Germany.
   [Chen, Liang-An; Meggers, Eric] Xiamen Univ, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China.
C3 Philipps University Marburg; Xiamen University
RP Meggers, E (corresponding author), Univ Marburg, Fachbereich Chem, Hans Meerwein Str, D-35043 Marburg, Germany.
EM meggers@chemie.uni-marburg.de
FU German Research Foundation [ME 1805/4-1]; China Scholarship Council
NR 30
TC 534
Z9 593
U1 11
U2 1017
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 6
PY 2014
VL 515
IS 7525
BP 100
EP 103
DI 10.1038/nature13892
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500037
PM 25373679
DA 2026-03-09
ER

PT J
AU Raman, AP
   Abou Anoma, M
   Zhu, LX
   Rephaeli, E
   Fan, SH
AF Raman, Aaswath P.
   Abou Anoma, Marc
   Zhu, Linxiao
   Rephaeli, Eden
   Fan, Shanhui
TI Passive radiative cooling below ambient air temperature under direct sunlight
SO NATURE
LA English
DT Article
AB Cooling is a significant end-use of energy globally and a major driver of peak electricity demand. Air conditioning, for example, accounts for nearly fifteen per cent of the primary energy used by buildings in the United States(1). A passive cooling strategy that cools without any electricity input could therefore have a significant impact on global energy consumption. To achieve cooling one needs to be able to reach and maintain a temperature below that of the ambient air. At night, passive cooling below ambient air temperature has been demonstrated using a technique known as radiative cooling, in which a device exposed to the sky is used to radiate heat to outer space through a transparency window in the atmosphere between 8 and 13 micrometres(2-11). Peak cooling demand, however, occurs during the daytime. Daytime radiative cooling to a temperature below ambient of a surface under direct sunlight has not been achieved(3,4,12,13) because sky access during the day results in heating of the radiative cooler by the Sun. Here, we experimentally demonstrate radiative cooling to nearly 5 degrees Celsius below the ambient air temperature under direct sunlight. Using a thermal photonic approach(14-25), we introduce an integrated photonic solar reflector and thermal emitter consisting of seven layers of HfO2 and SiO2 that reflects 97 per cent of incident sunlight while emitting strongly and selectively in the atmospheric transparency window. When exposed to direct sunlight exceeding 850 watts per square metre on a rooftop, the photonic radiative cooler cools to 4.9 degrees Celsius below ambient air temperature, and has a cooling power of 40.1 watts per square metre at ambient air temperature. These results demonstrate that a tailored, photonic approach can fundamentally enable new technological possibilities for energy efficiency. Further, the cold darkness of the Universe can be used as a renewable thermodynamic resource, even during the hottest hours of the day.
C1 [Raman, Aaswath P.; Rephaeli, Eden; Fan, Shanhui] Stanford Univ, Dept Elect Engn, Ginzton Lab, Stanford, CA 94305 USA.
   [Abou Anoma, Marc] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA.
   [Zhu, Linxiao] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University
RP Raman, AP; Fan, SH (corresponding author), Stanford Univ, Dept Elect Engn, Ginzton Lab, Stanford, CA 94305 USA.
EM aaswath@stanford.edu; shanhui@stanford.edu
FU Advanced Research Projects Agency-Energy (ARPA-E), Department of Energy [DE-AR0000316]; National Science Foundation through the NNIN [ECS-9731293]; Stanford Nano Center (SNC)/Stanford Nanocharacterization Laboratory (SNL)
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NR 38
TC 2840
Z9 3221
U1 190
U2 2320
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2014
VL 515
IS 7528
BP 540
EP +
DI 10.1038/nature13883
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA VL6BY
UT WOS:000892096100001
PM 25428501
DA 2026-03-09
ER

PT J
AU Edgar, GJ
   Stuart-Smith, RD
   Willis, TJ
   Kininmonth, S
   Baker, SC
   Banks, S
   Barrett, NS
   Becerro, MA
   Bernard, ATF
   Berkhout, J
   Buxton, CD
   Campbell, SJ
   Cooper, AT
   Davey, M
   Edgar, SC
   Försterra, G
   Galván, DE
   Irigoyen, AJ
   Kushner, DJ
   Moura, R
   Parnell, PE
   Shears, NT
   Soler, G
   Strain, EMA
   Thomson, RJ
AF Edgar, Graham J.
   Stuart-Smith, Rick D.
   Willis, Trevor J.
   Kininmonth, Stuart
   Baker, Susan C.
   Banks, Stuart
   Barrett, Neville S.
   Becerro, Mikel A.
   Bernard, Anthony T. F.
   Berkhout, Just
   Buxton, Colin D.
   Campbell, Stuart J.
   Cooper, Antonia T.
   Davey, Marlene
   Edgar, Sophie C.
   Foersterra, Guenter
   Galvan, David E.
   Irigoyen, Alejo J.
   Kushner, David J.
   Moura, Rodrigo
   Parnell, P. Ed
   Shears, Nick T.
   Soler, German
   Strain, Elisabeth M. A.
   Thomson, Russell J.
TI Global conservation outcomes depend on marine protected areas with five key features
SO NATURE
LA English
DT Article
ID size-structure; reserves; abundance; hotspots; network; fishes; reefs
AB In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate(1,2). MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve(3-5). Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km(2)), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.
C1 [Edgar, Graham J.; Stuart-Smith, Rick D.; Kininmonth, Stuart; Barrett, Neville S.; Berkhout, Just; Buxton, Colin D.; Cooper, Antonia T.; Davey, Marlene; Soler, German; Thomson, Russell J.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas 7001, Australia.
   [Willis, Trevor J.] Univ Portsmouth, Inst Marine Sci, Sch Biol Sci, Portsmouth PO4 9LY, Hants, England.
   [Kininmonth, Stuart] Stockholm Univ, Stockholm Resilience Ctr, SE-10691 Stockholm, Sweden.
   [Baker, Susan C.] Univ Tasmania, Sch Plant Sci, Hobart, Tas 7001, Australia.
   [Banks, Stuart] Charles Darwin Fdn, Puerto Ayora, Galapagos, Ecuador.
   [Becerro, Mikel A.] Nat Prod & Agrobiol Inst IPNA CSIC, Bites Lab, San Cristobal la Laguna 38206, Tenerife, Spain.
   [Bernard, Anthony T. F.] South African Environm Observat Network, Elwandle Node, ZA-6140 Grahamstown, South Africa.
   [Campbell, Stuart J.] Indonesia Marine Program, Wildlife Conservat Soc, Bogor 16151, Indonesia.
   [Edgar, Sophie C.] Dept Water, Perth, WA 6000, Australia.
   [Foersterra, Guenter] Pontificia Univ Catolica Valparaiso, Escuela Ciencias Mar, Fac Recursos Nat, Valparaiso, Chile.
   [Galvan, David E.; Irigoyen, Alejo J.] Consejo Nacl Invest Cient & Tecn, Ctr Nacl Patagon, RA-9120 Puerto Madryn, Argentina.
   [Kushner, David J.] Natl Pk Serv, Ventura, CA 93001 USA.
   [Moura, Rodrigo] Univ Fed Rio de Janeiro, Inst Biol, BR-21941902 Rio De Janeiro, Brazil.
   [Parnell, P. Ed] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Shears, Nick T.] Univ Auckland, Leigh Marine Lab, Leigh 0985, New Zealand.
   [Strain, Elisabeth M. A.] Univ Bologna, Dipartimento Sci Biol Geol & Ambientali, I-16348123 Ravenna, Italy.
C3 University of Tasmania; University of Portsmouth; Stockholm University; University of Tasmania; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Productos Naturales y Agrobiologia (IPNA); National Research Foundation - South Africa; South African Environmental Observation Network (SAEON); Wildlife Conservation Society - Indonesia; Pontificia Universidad Catolica de Valparaiso; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Centro Nacional Patagonico (CENPAT); United States Department of the Interior; US National Park Service; Universidade Federal do Rio de Janeiro; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Auckland; University of Bologna
RP Edgar, GJ (corresponding author), Univ Tasmania, Inst Marine & Antarctic Studies, GPO Box 252-49, Hobart, Tas 7001, Australia.
EM g.edgar@utas.edu.au
FU Australian Research Council; Fulbright Visiting Scholarship; Institute for Marine and Antarctic Studies; Marine Biodiversity Hub; Australian Government's National Environmental Research Program; National Geographic Society; Conservation International; Wildlife Conservation Society; Winifred Violet Scott Trust; Tasmanian Parks and Wildlife Service; Winston Churchill Memorial Trust; University of Tasmania; ASSEMBLE Marine
NR 35
TC 1475
Z9 1638
U1 20
U2 1168
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 13
PY 2014
VL 506
IS 7487
BP 216
EP +
DI 10.1038/nature13022
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700037
PM 24499817
DA 2026-03-09
ER

PT J
AU Wen, H
   Li, YY
   Xi, YX
   Jiang, SM
   Stratton, S
   Peng, DN
   Tanaka, K
   Ren, YF
   Xia, Z
   Wu, J
   Li, B
   Barton, MC
   Li, W
   Li, HT
   Shi, XB
AF Wen, Hong
   Li, Yuanyuan
   Xi, Yuanxin
   Jiang, Shiming
   Stratton, Sabrina
   Peng, Danni
   Tanaka, Kaori
   Ren, Yongfeng
   Xia, Zheng
   Wu, Jun
   Li, Bing
   Barton, Michelle C.
   Li, Wei
   Li, Haitao
   Shi, Xiaobing
TI ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression
SO NATURE
LA English
DT Article
ID adenovirus e1a-associated protein; high-affinity binding; pwwp domain; lysine 36; plant homeodomain; h3; recognition; bs69; methylation; mutations
AB Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin(1). H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription(2). However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies(3). Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription corepressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.
C1 [Wen, Hong; Jiang, Shiming; Stratton, Sabrina; Peng, Danni; Tanaka, Kaori; Barton, Michelle C.; Shi, Xiaobing] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Wen, Hong; Barton, Michelle C.; Shi, Xiaobing] Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Ctr Genet & Genom, Houston, TX 77030 USA.
   [Wen, Hong; Barton, Michelle C.; Shi, Xiaobing] Univ Texas MD Anderson Canc Ctr, Ctr Stem Cell & Dev Biol, Houston, TX 77030 USA.
   [Li, Yuanyuan; Ren, Yongfeng; Li, Haitao] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Li, Yuanyuan; Ren, Yongfeng; Li, Haitao] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China.
   [Xi, Yuanxin; Xia, Zheng; Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Wu, Jun; Li, Bing] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Barton, Michelle C.; Shi, Xiaobing] Univ Texas Houston, Grad Sch Biomed Sci, Genes & Dev Grad Program, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Tsinghua University; Tsinghua University; Baylor College of Medicine; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Health Science Center Houston
RP Shi, XB (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
EM hwen@mdanderson.org; WL1@bcm.edu; lht@tsinghua.edu.cn; xbshi@mdanderson.org
FU American Cancer Society [RSG-13-290-01-TBE]; National institutes of Health (NIH)/MDACC [CCSG CA016672]; Major State Basic Research Development Program in China [2011CB965300]; Program for New Century Excellent Talents in University; China Postdoctoral Science Foundation [2012M510413]; Kimmel Scholar Award;  [CPRITRP110471];  [Welch G1719];  [NIH R01HG007538];  [NIH R01GM090077];  [Welch I1713]; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER
NR 49
TC 252
Z9 334
U1 3
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 APR 10
PY 2014
VL 508
IS 7495
BP 263
EP +
DI 10.1038/nature13045
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900048
PM 24590075
DA 2026-03-09
ER

PT J
AU Kunte, K
   Zhang, W
   Tenger-Trolander, A
   Palmer, DH
   Martin, A
   Reed, RD
   Mullen, SP
   Kronforst, MR
AF Kunte, K.
   Zhang, W.
   Tenger-Trolander, A.
   Palmer, D. H.
   Martin, A.
   Reed, R. D.
   Mullen, S. P.
   Kronforst, M. R.
TI doublesex is a mimicry supergene
SO NATURE
LA English
DT Article
ID tiger swallowtail butterfly; evolution; genetics; sex; polymorphisms; diversity; discovery; framework; alignment; color
AB One of the most striking examples of sexual dimorphism is sex-limited mimicry in butterflies, a phenomenon in which one sex-usually the female-mimics a toxic model species, whereas the other sex displays a different wing pattern(1). Sex-limited mimicry is phylogenetically widespread in the swallowtail butterfly genus Papilio, in which it is often associated with female mimetic polymorphism(1-3). In multiple polymorphic species, the entire wing pattern phenotype is controlled by a single Mendelian 'supergene'(4). Although theoretical work has explored the evolutionary dynamics of supergene mimicry(5-9), there are almost no empirical data that address the critical issue of what a mimicry supergene actually is at a functional level. Using an integrative approach combining genetic and association mapping, transcriptome and genome sequencing, and gene expression analyses, we show that a single gene, doublesex, controls supergene mimicry in Papilio polytes. This is in contrast to the long-held view that supergenes are likely to be controlled by a tightly linked cluster of loci(4). Analysis of gene expression and DNA sequence variation indicates that isoform expression differences contribute to the functional differences between dsx mimicry alleles, and protein sequence evolution may also have a role. Our results combine elements from different hypotheses for the identity of supergenes, showing that a single gene can switch the entire wing pattern among mimicry phenotypes but may require multiple, tightly linked mutations to do so.
C1 [Kunte, K.] Tata Inst Fundamental Res, Natl Ctr Biol Sci, Bengaluru 560065, Karnataka, India.
   [Zhang, W.; Tenger-Trolander, A.; Kronforst, M. R.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Palmer, D. H.; Kronforst, M. R.] Univ Chicago, Comm Evolutionary Biol, Chicago, IL 60637 USA.
   [Martin, A.; Reed, R. D.] Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
   [Mullen, S. P.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
C3 Tata Institute of Fundamental Research (TIFR); National Centre for Biological Sciences (NCBS); University of Chicago; University of Chicago; Cornell University; Boston University
RP Kronforst, MR (corresponding author), Univ Chicago, Dept Ecol & Evolut, 940 E 57th St, Chicago, IL 60637 USA.
EM krushnamegh@ncbs.res.in; mkronforst@uchicago.edu
FU National Science Foundation [DEB-1316037]; Division Of Environmental Biology; Direct For Biological Sciences [1020136] Funding Source: National Science Foundation
NR 44
TC 270
Z9 330
U1 5
U2 223
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2014
VL 507
IS 7491
BP 229
EP +
DI 10.1038/nature13112
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800038
PM 24598547
DA 2026-03-09
ER

PT J
AU Roederer, M
   Keele, BF
   Schmidt, SD
   Mason, RD
   Welles, HC
   Fischer, W
   Labranche, C
   Foulds, KE
   Louder, MK
   Yang, ZY
   Todd, JPM
   Buzby, AP
   Mach, LV
   Shen, L
   Seaton, KE
   Ward, BM
   Bailer, RT
   Gottardo, R
   Gu, WJ
   Ferrari, G
   Alam, SM
   Denny, TN
   Montefiori, DC
   Tomaras, GD
   Korber, BT
   Nason, MC
   Seder, RA
   Koup, RA
   Letvin, NL
   Rao, SS
   Nabel, GJ
   Mascola, JR
AF Roederer, Mario
   Keele, Brandon F.
   Schmidt, Stephen D.
   Mason, Rosemarie D.
   Welles, Hugh C.
   Fischer, Will
   Labranche, Celia
   Foulds, Kathryn E.
   Louder, Mark K.
   Yang, Zhi-Yong
   Todd, John-Paul M.
   Buzby, Adam P.
   Mach, Linh V.
   Shen, Ling
   Seaton, Kelly E.
   Ward, Brandy M.
   Bailer, Robert T.
   Gottardo, Raphael
   Gu, Wenjuan
   Ferrari, Guido
   Alam, S. Munir
   Denny, Thomas N.
   Montefiori, David C.
   Tomaras, Georgia D.
   Korber, Bette T.
   Nason, Martha C.
   Seder, Robert A.
   Koup, Richard A.
   Letvin, Norman L.
   Rao, Srinivas S.
   Nabel, Gary J.
   Mascola, John R.
TI Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV
SO NATURE
LA English
DT Article
ID simian immunodeficiency virus; dose challenge experiments; neutralizing antibody; rhesus macaques; cell responses; efficacy trial; infection; binding; sivsme660; prevention
AB A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
C1 [Roederer, Mario; Schmidt, Stephen D.; Mason, Rosemarie D.; Welles, Hugh C.; Foulds, Kathryn E.; Louder, Mark K.; Yang, Zhi-Yong; Todd, John-Paul M.; Bailer, Robert T.; Seder, Robert A.; Koup, Richard A.; Rao, Srinivas S.; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Keele, Brandon F.] NIH, SAIC Frederick, Frederick Natl Lab, Frederick, MD 21702 USA.
   [Welles, Hugh C.] George Washington Univ, Washington, DC 20052 USA.
   [Fischer, Will; Korber, Bette T.] Los Alamos Natl Labs, Los Alamos, NM 87545 USA.
   [Labranche, Celia; Ward, Brandy M.; Ferrari, Guido; Montefiori, David C.] Duke Univ, Dept Surg, Durham, NC 27710 USA.
   [Buzby, Adam P.; Mach, Linh V.; Shen, Ling; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA.
   [Seaton, Kelly E.; Alam, S. Munir; Denny, Thomas N.; Tomaras, Georgia D.] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA.
   [Gottardo, Raphael] Fred Hutchison Canc Res Ctr, Seattle, WA 98109 USA.
   [Gu, Wenjuan; Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Science Applications International Corporation (SAIC); SAIC-Frederick; George Washington University; United States Department of Energy (DOE); Los Alamos National Laboratory; Duke University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Duke University; Fred Hutchinson Cancer Center; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Roederer, M (corresponding author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Roederer@NIH.gov
FU Intramural Research Program of the Vaccine Research Center, NIAID, NIH; NIH [HHSN261200800001E, HHSN27201100016C, AI100645]; Bill and Melinda Gates Foundation [OPP1032317]; National Institute of Allergy and Infectious Diseases [ZIAAI005073] Funding Source: NIH RePORTER; Bill and Melinda Gates Foundation [OPP1032317] Funding Source: Bill and Melinda Gates Foundation
NR 39
TC 126
Z9 138
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 JAN 23
PY 2014
VL 505
IS 7484
BP 502
EP +
DI 10.1038/nature12893
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000030
PM 24352234
DA 2026-03-09
ER

PT J
AU Kumar, MS
   Armenteros-Monterroso, E
   East, P
   Chakravorty, P
   Matthews, N
   Winslow, MM
   Downward, J
AF Kumar, Madhu S.
   Armenteros-Monterroso, Elena
   East, Philip
   Chakravorty, Probir
   Matthews, Nik
   Winslow, Monte M.
   Downward, Julian
TI RETRACTED: HMGA2 functions as a competing endogenous RNA to promote lung cancer progression (Retracted article. See vol. 523, 2015)
SO NATURE
LA English
DT Article; Retracted Publication
ID tgf-beta; messenger-rnas; expression data; gene; adenocarcinoma; binding; let-7; overexpression; transformation; inhibitor
AB Non-small-cell lung cancer (NSCLC) is the most prevalent histological cancer subtype worldwide(1). As the majority of patients present with invasive, metastatic disease(2), it is vital to understand the basis for lung cancer progression. Hmga2 is highly expressed in metastatic lung adenocarcinoma, in which it contributes to cancer progression and metastasis(3-6). Here we show that Hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous RNA (ceRNA)(7-11) for the let-7 microRNA (miRNA) family. Hmga2 can promote the transformation of lung cancer cells independent of protein-coding function but dependent upon the presence of let-7 sites; this occurs without changes in the levels of let-7 isoforms, suggesting that Hmga2 affects let-7 activity by altering miRNA targeting. These effects are also observed in vivo, where Hmga2 ceRNA activity drives lung cancer growth, invasion and dissemination. Integrated analysis of miRNA target prediction algorithms and metastatic lung cancer gene expression data reveals the TGF-beta co-receptor Tgfbr3 (ref. 12) as a putative target of Hmga2 ceRNA function. Tgfbr3 expression is regulated by the Hmga2 ceRNA through differential recruitment to Argonaute 2 (Ago2), and TGF-beta signalling driven by Tgfbr3 is important for Hmga2 to promote lung cancer progression. Finally, analysis of NSCLC-patient gene-expression data reveals that HMGA2 and TGFBR3 are coordinately regulated in NSCLC-patient material, a vital corollary to ceRNA function. Taken together, these results suggest that Hmga2 promotes lung carcinogenesis both as a protein-coding gene and as a non-coding RNA; such dual-function regulation of gene-expression networks reflects a novel means by which oncogenes promote disease progression.
C1 [Kumar, Madhu S.; Armenteros-Monterroso, Elena; Downward, Julian] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3LY, England.
   [East, Philip; Chakravorty, Probir] Canc Res UK London Res Inst, Bioinformat & Biostat Grp, London WC2A 3LY, England.
   [Matthews, Nik] Canc Res UK London Res Inst, Adv Sequencing Facil, London WC2A 3LY, England.
   [Winslow, Monte M.] Stanford Univ, Sch Med, Stanford Canc Inst, Dept Genet,Dept Pathol, Stanford, CA 94305 USA.
   [Downward, Julian] Inst Canc Res, Div Canc Biol, Lung Canc Grp, London SW3 6JB, England.
C3 Cancer Research UK; Cancer Research UK; Cancer Research UK; Stanford Cancer Institute; Stanford University; Royal Marsden NHS Foundation Trust; University of London; University College London; Institute of Cancer Research - UK
RP Downward, J (corresponding author), Canc Res UK London Res Inst, Signal Transduct Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM julian.downward@cancer.org.uk
FU Cancer Research UK; European Commission [259770]
NR 34
TC 231
Z9 260
U1 0
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 JAN 9
PY 2014
VL 505
IS 7482
BP 212
EP +
DI 10.1038/nature12785
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500038
PM 24305048
DA 2026-03-09
ER

PT J
AU Zhuravleva, I
   Churazov, E
   Schekochihin, AA
   Allen, SW
   Arévalo, P
   Fabian, AC
   Forman, WR
   Sanders, JS
   Simionescu, A
   Sunyaev, R
   Vikhlinin, A
   Werner, N
AF Zhuravleva, I.
   Churazov, E.
   Schekochihin, A. A.
   Allen, S. W.
   Arevalo, P.
   Fabian, A. C.
   Forman, W. R.
   Sanders, J. S.
   Simionescu, A.
   Sunyaev, R.
   Vikhlinin, A.
   Werner, N.
TI Turbulent heating in galaxy clusters brightest in X-rays
SO NATURE
LA English
DT Article
ID active galactic nuclei; velocity power spectra; internal gravity-waves; cooling flows; gas-density; surface brightness; perseus cluster; evolution; feedback; models
AB The hot (10(7) to 10(8) kelvin), X-ray-emitting intracluster medium (ICM) is the dominant baryonic constituent of clusters of galaxies. In the cores of many clusters, radiative energy losses from the ICM occur on timescalesmuch shorter than the age of the system(1-3). Unchecked, this cooling would lead to massive accumulations of cold gas and vigorous star formation(4), in contradiction to observations(5). Various sources of energy capable of compensating for these cooling losses have been proposed, themost promising being heating by the super-massive black holes in the central galaxies, through inflation of bubbles of relativistic plasma(6-9). Regardless of the original source of energy, the question of how this energy is transferred to the ICM remains open. Here we present a plausible solution to this question based on deep X-ray data and a new data analysis method that enable us to evaluate directly the ICM heating rate from the dissipation of turbulence. We find that turbulent heating is sufficient to offset radiative cooling and indeed appears to balance it locally at each radius-it may therefore be the key element in resolving the gas cooling problem in cluster cores and, more universally, in the atmospheres of X-ray emitting, gas-rich systems on scales from galaxy clusters to groups and elliptical galaxies.
C1 [Zhuravleva, I.; Allen, S. W.; Werner, N.] Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
   [Zhuravleva, I.; Allen, S. W.; Werner, N.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Churazov, E.; Sunyaev, R.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Churazov, E.; Sunyaev, R.] Space Res Inst IKI, Moscow 117997, Russia.
   [Schekochihin, A. A.] Univ Oxford, Rudolf Peierls Ctr Theoret Phys, Oxford OX1 3NP, England.
   [Schekochihin, A. A.] Univ Oxford, Merton Coll, Oxford OX1 4JD, England.
   [Allen, S. W.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Arevalo, P.] Univ Valparaiso, Fac Ciencias, Inst Fis & Astron, Valparaiso, Chile.
   [Arevalo, P.] Pontificia Univ Catolica Chile, Fac Fis, Inst Astrofis, Santiago 22, Chile.
   [Fabian, A. C.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Forman, W. R.; Vikhlinin, A.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Sanders, J. S.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Simionescu, A.] Japan Aerosp Explorat Agcy, Sagamihara, Kanagawa 2525210, Japan.
C3 Stanford University; Stanford University; Max Planck Society; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; University of Oxford; University of Oxford; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Universidad de Valparaiso; Pontificia Universidad Catolica de Chile; University of Cambridge; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University; Max Planck Society; Japan Aerospace Exploration Agency (JAXA)
RP Zhuravleva, I (corresponding author), Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, 452 Lomita Mall, Stanford, CA 94305 USA.
EM zhur@stanford.edu
FU NASA through Chandra award by the Chandra X-ray Observatory Center [AR4-15013X]; NASA [NAS8-03060]; US Department of Energy [DE-AC02-76SF00515]; Suzaku grants [NNX12AE05G, NNX13AI49G]; Fondecyt [1140304]; European Commission [PIRSES-GA -2010-2692 64]; Russian Scientific Foundation [14-22-00271]; STFC [ST/K000985/1, ST/F002505/2] Funding Source: UKRI; Russian Science Foundation [14-22-00271] Funding Source: Russian Science Foundation; Science and Technology Facilities Council [ST/K000985/1, ST/F002505/2] Funding Source: researchfish
NR 54
TC 298
Z9 321
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 NOV 6
PY 2014
VL 515
IS 7525
BP 85
EP +
DI 10.1038/nature13830
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500033
PM 25363764
DA 2026-03-09
ER

PT J
AU Hansen, AK
   Versolato, OO
   Klosowski, L
   Kristensen, SB
   Gingell, A
   Schwarz, M
   Windberger, A
   Ullrich, J
   López-Urrutia, JRC
   Drewsen, M
AF Hansen, A. K.
   Versolato, O. O.
   Klosowski, L.
   Kristensen, S. B.
   Gingell, A.
   Schwarz, M.
   Windberger, A.
   Ullrich, J.
   Lopez-Urrutia, J. R. Crespo
   Drewsen, M.
TI Efficient rotational cooling of Coulomb-crystallized molecular ions by a helium buffer gas
SO NATURE
LA English
DT Article
ID cooled ions; single-ion; laser; cold; spectroscopy; trap
AB The preparation of cold molecules is of great importance in many contexts, such as fundamental physics investigations(1,2), high-resolution spectroscopy of complex molecules(3-5), cold chemistry(6,7) and astrochemistry(8). One versatile and widely applied method to cool molecules is helium buffer-gas cooling in either a supersonic beam expansion(9,10) or a cryogenic trap environment(11,12). Another more recent method applicable to trapped molecular ions relies on sympathetic translational cooling, through collisional interactions with co-trapped, laser-cooled atomic ions, into spatially ordered structures called Coulomb crystals, combined with laser-controlled internal-state preparation(6,7,13-23). Here we present experimental results on helium buffer-gas cooling of the rotational degrees of freedom of MgH+ molecular ions, which have been trapped and sympathetically cooled(13) in a cryogenic linear radio-frequency quadrupole trap. With helium collision rates of only about ten per second-that is, four to five orders of magnitude lower than in typical buffer-gas cooling settings-we have cooled a single molecular ion to a rotational temperature of 7.5(-0.7)(+0.9) kelvin, the lowest such temperature so far measured. In addition, by varying the shape of, or the number of atomic and molecular ions in, larger Coulomb crystals, or both, we have tuned the effective rotational temperature from about 7 kelvin to about 60 kelvin by changing the translational micromotion energy of the ions(24). The extremely low helium collision rate may allow for sympathetic sideband cooling of single molecular ions, and eventually make quantum-logic spectroscopy(25) of buffer-gas-cooled molecular ions feasible. Furthermore, application of the present cooling scheme to complex molecular ions should enable single- or few-state manipulations of individual molecules of biological interest(4,5).
C1 [Hansen, A. K.; Kristensen, S. B.; Gingell, A.; Drewsen, M.] Aarhus Univ, Dept Phys & Astron, Danish Natl Res Fdn Ctr Quantum Opt QUANTOP, DK-8000 Aarhus C, Denmark.
   [Versolato, O. O.; Schwarz, M.; Windberger, A.; Ullrich, J.; Lopez-Urrutia, J. R. Crespo] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Klosowski, L.] Nicolaus Copernicus Univ, Inst Phys, Fac Phys Astron & Informat, PL-87100 Torun, Poland.
   [Ullrich, J.] Phys Tech Bundesanstalt, D-38116 Braunschweig, Germany.
C3 Danmarks Grundforskningsfond; Aarhus University; Max Planck Society; Nicolaus Copernicus University; Physikalisch-Technische Bundesanstalt (PTB)
RP Drewsen, M (corresponding author), Aarhus Univ, Dept Phys & Astron, Danish Natl Res Fdn Ctr Quantum Opt QUANTOP, DK-8000 Aarhus C, Denmark.
EM drewsen@phys.au.dk
FU Danish National Research Foundation Center for Quantum Optics - QUANTOP; Danish Agency for Science, Technology and Innovation; Carlsberg Foundation; Lundbeck Foundation; European Commission [FP7 GA 607491 COMIQ]; STSM; COST-Action IOTA
NR 31
TC 86
Z9 102
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 APR 3
PY 2014
VL 508
IS 7494
BP 76
EP 79
DI 10.1038/nature12996
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900045
PM 24670662
DA 2026-03-09
ER

PT J
AU Ma, H
   Morey, R
   O'Neil, RC
   He, YP
   Daughtry, B
   Schultz, MD
   Hariharan, M
   Nery, JR
   Castanon, R
   Sabatini, K
   Thiagarajan, RD
   Tachibana, M
   Kang, EJ
   Tippner-Hedges, R
   Ahmed, R
   Gutierrez, NM
   Van Dyken, C
   Polat, A
   Sugawara, A
   Sparman, M
   Gokhale, S
   Amato, P
   Wolf, DP
   Ecker, JR
   Laurent, LC
   Mitalipov, S
AF Ma, Hong
   Morey, Robert
   O'Neil, Ryan C.
   He, Yupeng
   Daughtry, Brittany
   Schultz, Matthew D.
   Hariharan, Manoj
   Nery, Joseph R.
   Castanon, Rosa
   Sabatini, Karen
   Thiagarajan, Rathi D.
   Tachibana, Masahito
   Kang, Eunju
   Tippner-Hedges, Rebecca
   Ahmed, Riffat
   Gutierrez, Nuria Marti
   Van Dyken, Crystal
   Polat, Alim
   Sugawara, Atsushi
   Sparman, Michelle
   Gokhale, Sumita
   Amato, Paula
   Wolf, Don P.
   Ecker, Joseph R.
   Laurent, Louise C.
   Mitalipov, Shoukhrat
TI Abnormalities in human pluripotent cells due to reprogramming mechanisms
SO NATURE
LA English
DT Article
ID embryonic stem-cells; coding mutations; dna methylation; dynamic changes; somatic-cells; x-chromosome; copy number; memory; lines; differentiation
AB Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stemcells (ES cells) from in vitro fertilized embryos (IVFES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.
C1 [Ma, Hong; Daughtry, Brittany; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Ctr Embryon Cell & Gene Therapy, Portland, OR 97239 USA.
   [Ma, Hong; Daughtry, Brittany; Tachibana, Masahito; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Polat, Alim; Sugawara, Atsushi; Sparman, Michelle; Wolf, Don P.; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod & Dev Sci, Beaverton, OR 97006 USA.
   [Morey, Robert; Sabatini, Karen; Thiagarajan, Rathi D.; Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
   [O'Neil, Ryan C.; He, Yupeng; Schultz, Matthew D.; Hariharan, Manoj; Nery, Joseph R.; Castanon, Rosa; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA.
   [O'Neil, Ryan C.; He, Yupeng] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA.
   [Gokhale, Sumita] Boston Univ, Sch Med, Roger Williams Med Ctr, Univ Pathologists LLC, Providence, RI 02918 USA.
   [Amato, Paula; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol, Portland, OR 97239 USA.
   [Ecker, Joseph R.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon National Primate Research Center; University of California System; University of California San Diego; Salk Institute; University of California System; University of California San Diego; Boston University; Roger Williams Medical Center; Oregon Health & Science University; Salk Institute; Howard Hughes Medical Institute
RP Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Ctr Embryon Cell & Gene Therapy, 3303 Southwest Bond Ave, Portland, OR 97239 USA.
EM ecker@salk.edu; llaurent@ucsd.edu; mitalipo@ohsu.edu
FU Leducq Foundation; OHSU; UCSD Department of Reproductive Medicine; Salk International Council Chair fund endowment; Mary K. Chapman Foundation; Swedish Research Council; Collins Medical Trust
NR 43
TC 263
Z9 306
U1 1
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 10
PY 2014
VL 511
IS 7508
BP 177
EP +
DI 10.1038/nature13551
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800035
PM 25008523
DA 2026-03-09
ER

PT J
AU Peters, AJ
   Chen, SX
   Komiyama, T
AF Peters, Andrew J.
   Chen, Simon X.
   Komiyama, Takaki
TI Emergence of reproducible spatiotemporal activity during motor learning
SO NATURE
LA English
DT Article
ID intracortical microstimulation; laminar organization; neural activity; behaving mice; in-vivo; cortex; representations; movement; neurons; information
AB The motor cortex is capable of reliably driving complex movements(1,2) yet exhibits considerable plasticity during motor learning(3-10). These observations suggest that the fundamental relationship between motor cortex activity and movement may not be fixed but is instead shaped by learning; however, to what extent and how motor learning shapes this relationship are not fully understood. Here we addressed this issue by using in vivo two-photon calcium imaging(11) to monitor the activity of the same population of hundreds of layer 2/3 neurons while mice learned a forelimb lever-press task over two weeks. Excitatory and inhibitory neurons were identified by transgenic labelling(12,13). Inhibitory neuron activity was relatively stable and balanced local excitatory neuron activity on a movement-by-movement basis, whereas excitatory neuron activity showed higher dynamism during the initial phase of learning. The dynamics of excitatory neurons during the initial phase involved the expansion of the movement-related population which explored various activity patterns even during similar movements. This was followed by a refinement into a smaller population exhibiting reproducible spatiotemporal sequences of activity. This pattern of activity associated with the learned movement was unique to expert animals and not observed during similar movements made during the naive phase, and the relationship between neuronal activity and individual movements became more consistent with learning. These changes in population activity coincided with a transient increase in dendritic spine turnover in these neurons. Our results indicate that a novel and reproducible activity-movement relationship develops as a result of motor learning, and we speculate that synaptic plasticity within the motor cortex underlies the emergence of reproducible spatiotemporal activity patterns for learned movements. These results underscore the profound influence of learning on the way that the cortex produces movements.
C1 [Peters, Andrew J.; Chen, Simon X.; Komiyama, Takaki] Univ Calif San Diego, Neurobiol Sect, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
   [Peters, Andrew J.; Chen, Simon X.; Komiyama, Takaki] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Komiyama, Takaki] Univ Calif San Diego, PRESTO, JST, La Jolla, CA 92093 USA.
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
RP Komiyama, T (corresponding author), Univ Calif San Diego, Neurobiol Sect, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
EM tkomiyama@ucsd.edu
FU Japan Science and Technology Agency (PRESTO); Pew Charitable Trusts; Alfred P. Sloan Foundation; David & Lucile Packard Foundation; Human Frontier Science Program; New York Stem Cell Foundation; Neuroplasticity of Aging Training Grant [AG000216]
NR 39
TC 353
Z9 455
U1 2
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 JUN 12
PY 2014
VL 510
IS 7504
BP 263
EP +
DI 10.1038/nature13235
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400049
PM 24805237
DA 2026-03-09
ER

PT J
AU Goubau, D
   Schlee, M
   Deddouche, S
   Pruijssers, AJ
   Zillinger, T
   Goldeck, M
   Schuberth, C
   Van der Veen, AG
   Fujimura, T
   Rehwinkel, J
   Iskarpatyoti, JA
   Barchet, W
   Ludwig, J
   Dermody, TS
   Hartmann, G
   Sousa, CRE
AF Goubau, Delphine
   Schlee, Martin
   Deddouche, Safia
   Pruijssers, Andrea J.
   Zillinger, Thomas
   Goldeck, Marion
   Schuberth, Christine
   Van der Veen, Annemarthe G.
   Fujimura, Tsutomu
   Rehwinkel, Jan
   Iskarpatyoti, Jason A.
   Barchet, Winfried
   Ludwig, Janos
   Dermody, Terence S.
   Hartmann, Gunther
   Reis e Sousa, Caetano
TI Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates
SO NATURE
LA English
DT Article
ID double-stranded-rna; inducible gene-i; 5'-triphosphate rna; dendritic cells; innate immunity; virus; infection; acid; generation; insights
AB Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection(1,2). Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-alpha and beta; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1-3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system.
C1 [Goubau, Delphine; Deddouche, Safia; Van der Veen, Annemarthe G.; Rehwinkel, Jan; Reis e Sousa, Caetano] Canc Res UK, London Res Inst, Immunobiol Lab, London WC2A 3LY, England.
   [Schlee, Martin; Zillinger, Thomas; Goldeck, Marion; Schuberth, Christine; Barchet, Winfried; Ludwig, Janos; Hartmann, Gunther] Univ Klinikum Bonn, Inst Klin Chem, D-53127 Bonn, Germany.
   [Schlee, Martin; Zillinger, Thomas; Goldeck, Marion; Schuberth, Christine; Barchet, Winfried; Ludwig, Janos; Hartmann, Gunther] Univ Klinikum Bonn, Klin Pharmakol, D-53127 Bonn, Germany.
   [Pruijssers, Andrea J.; Iskarpatyoti, Jason A.; Dermody, Terence S.] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN 37232 USA.
   [Pruijssers, Andrea J.; Iskarpatyoti, Jason A.; Dermody, Terence S.] Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA.
   [Fujimura, Tsutomu] Univ Salamanca, Inst Biol Func & Genom, Consejo Super Invest Cient, Salamanca 37007, Spain.
   [Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
C3 Cancer Research UK; University of Bonn; University of Bonn; Vanderbilt University; Vanderbilt University; University of Salamanca; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-USAL - Instituto de Biologia Funcional y Genomica (IBFG); Vanderbilt University
RP Goubau, D (corresponding author), Canc Res UK, London Res Inst, Immunobiol Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM delphine.goubau@cancer.org.uk; caetano@cancer.org.uk
FU Cancer Research UK; European Research Council (ERC Advanced Researcher Grant) [AdG-2010-268670]; Public Health Service award [R37 AI038296]; Elizabeth B. Lamb Center for Pediatric Research; Fundacion Ramon Areces; Deutsche Forschungsgemeinschaft [SFB670, DFG SCHL1930/1-1, SFB704, SFB832, KFO177]; DFG Excellence Cluster ImmunoSensation; German Center of Infectious Disease (DZIF); MRC [MC_UU_12010/8] Funding Source: UKRI; Cancer Research UK [15689] Funding Source: researchfish; Medical Research Council [MC_UU_12010/8] Funding Source: researchfish
NR 34
TC 461
Z9 571
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 OCT 16
PY 2014
VL 514
IS 7522
BP 372
EP +
DI 10.1038/nature13590
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600053
PM 25119032
DA 2026-03-09
ER

PT J
AU Pefanis, E
   Wang, JG
   Rothschild, G
   Lim, J
   Chao, J
   Rabadan, R
   Economides, AN
   Basu, U
AF Pefanis, Evangelos
   Wang, Jiguang
   Rothschild, Gerson
   Lim, Junghyun
   Chao, Jaime
   Rabadan, Raul
   Economides, Aris N.
   Basu, Uttiya
TI Noncoding RNA transcription targets AID to divergently transcribed loci in B cells
SO NATURE
LA English
DT Article
ID polymerase-ii; sequencing reveals; genome; dna; exosome; rearrangements; hypermutation; termination; mechanisms; chromatin
AB The vast majority of the mammalian genome has the potential to express noncoding RNA (ncRNA). The 11-subunit RNA exosome complex is the main source of cellular 3'-5' exoribonucleolytic activity and potentially regulates the mammalian noncoding transcriptome(1). Here we generated a mouse model in which the essential subunit Exosc3 of the RNA exosome complex can be conditionally deleted. Exosc3-deficient B cells lack the ability to undergo normal levels of class switch recombination and somatic hypermutation, two mutagenic DNA processes used to generate antibody diversity via the B-cell mutator protein activation-induced cytidine deaminase (AID)(2,3). The transcriptome of Exosc3-deficient B cells has revealed the presence of many novel RNA exosome substrate ncRNAs. RNA exosome substrate RNAs include xTSS-RNAs, transcription start site (TSS)-associated antisense transcripts that can exceed 500 base pairs in length and are transcribed divergently from cognate coding gene transcripts. xTSS-RNAs are most strongly expressed at genes that accumulate AID mediated somatic mutations and/or are frequent translocation partners of DNA double-strand breaks generated at Igh in B cells(4,5). Strikingly, translocations near TSSs or within gene bodies occur over regions of RNA exosome substrate ncRNA expression. These RNA exosome-regulated, antisense-transcribed regions of the B-cell genome recruit AID and accumulate single-strand DNA structures containing RNA-DNA hybrids. We propose that RNA exosome regulation of ncRNA recruits AID to single-strand DNA-forming sites of antisense and divergent transcription in the B-cell genome, thereby creating a link between ncRNA transcription and overall maintenance of B-cell genomic integrity.
C1 [Pefanis, Evangelos; Wang, Jiguang; Rothschild, Gerson; Lim, Junghyun; Chao, Jaime; Basu, Uttiya] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
   [Pefanis, Evangelos; Economides, Aris N.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
   [Wang, Jiguang; Rabadan, Raul] Columbia Univ Coll Phys & Surg, Dept Syst Biol, New York, NY 10032 USA.
   [Wang, Jiguang; Rabadan, Raul] Columbia Univ Coll Phys & Surg, Dept Biomed Informat, New York, NY 10032 USA.
C3 Columbia University; Regeneron; Columbia University; Columbia University
RP Rabadan, R (corresponding author), Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, 630 W 168th St, New York, NY 10032 USA.
EM rr2579@columbia.edu; ub2121@columbia.edu
FU National Institutes of Health (NIH) [1DP2OD008651-01]; National Institute of Allergy and Infectious Diseases [1R01AI099195-01A1]; NIH [1R01CA185486-01, 1R01CA179044-01A1, 1U54CA121852-05]; National Institute of Allergy and Infectious Diseases [R01AI099195] Funding Source: NIH RePORTER
NR 40
TC 149
Z9 191
U1 1
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 OCT 16
PY 2014
VL 514
IS 7522
BP 389
EP +
DI 10.1038/nature13580
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600057
PM 25119026
DA 2026-03-09
ER

PT J
AU Sandler, NG
   Bosinger, SE
   Estes, JD
   Zhu, RTR
   Tharp, GK
   Boritz, E
   Levin, D
   Wijeyesinghe, S
   Makamdop, KN
   del Prete, GQ
   Hill, BJ
   Timmer, JK
   Reiss, E
   Yarden, G
   Darko, S
   Contijoch, E
   Todd, JP
   Silvestri, G
   Nason, M
   Norgren, RB
   Keele, BF
   Rao, S
   Langer, JA
   Lifson, JD
   Schreiber, G
   Douek, DC
AF Sandler, Netanya G.
   Bosinger, Steven E.
   Estes, Jacob D.
   Zhu, Richard T. R.
   Tharp, Gregory K.
   Boritz, Eli
   Levin, Doron
   Wijeyesinghe, Sathi
   Makamdop, Krystelle Nganou
   del Prete, Gregory Q.
   Hill, Brenna J.
   Timmer, J. Katherina
   Reiss, Emma
   Yarden, Ganit
   Darko, Samuel
   Contijoch, Eduardo
   Todd, John Paul
   Silvestri, Guido
   Nason, Martha
   Norgren, Robert B., Jr.
   Keele, Brandon F.
   Rao, Srinivas
   Langer, Jerome A.
   Lifson, Jeffrey D.
   Schreiber, Gideon
   Douek, Daniel C.
TI Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression
SO NATURE
LA English
DT Article
ID persistent lcmv infection; cd4(+) t-cells; hiv-1 infection; alpha; replication; acquisition; activation; blockade; therapy; genes
AB Inflammation in HIV infection is predictive of non-AIDS morbidity and death(1), higher set point plasma virus load(2) and virus acquisition3; thus, therapeutic agents are in development to reduce its causes and consequences. However, inflammation may simultaneously confer both detrimental and beneficial effects. This dichotomy is particularly applicable to type I interferons (IFN-I) which, while contributing to innate control of infection(4-10), also provide target cells for the virus during acute infection, impair CD4 T-cell recovery, and are associated with disease progression(6,11-19). Here we manipulated IFN-I signalling in rhesus macaques (Macaca mulatta) during simian immunodeficiency virus (Sly) transmission and acute infection with two complementary in vivo interventions. We show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation. In contrast, IFN-a2a administration initially upreg-ulated expression of antiviral genes and prevented systemic infection. However, continued IFN-a2a treatment induced IFN-I desensitization and decreased antiviral gene expression, enabling infection with increased SIV reservoir size and accelerated CD4 T-cell loss. Thus, the timing of IFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation. Yet, the clinical consequences of manipulation of IFN signalling are difficult to predict in vivo and therapeutic interventions in human studies should be approached with caution.
C1 [Sandler, Netanya G.; Zhu, Richard T. R.; Boritz, Eli; Wijeyesinghe, Sathi; Makamdop, Krystelle Nganou; Hill, Brenna J.; Timmer, J. Katherina; Reiss, Emma; Darko, Samuel; Contijoch, Eduardo; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Bosinger, Steven E.; Tharp, Gregory K.; Silvestri, Guido] Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA.
   [Bosinger, Steven E.; Tharp, Gregory K.] Emory Univ, Robert W Woodruff Hlth Sci Ctr, Yerkes Natl Primate Res Ctr, Nonhuman Primate Genom Core, Atlanta, GA 30322 USA.
   [Estes, Jacob D.; del Prete, Gregory Q.; Keele, Brandon F.; Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA.
   [Levin, Doron; Yarden, Ganit; Schreiber, Gideon] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Todd, John Paul; Rao, Srinivas] NIAID, Lab Anim Med, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Nason, Martha] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
   [Norgren, Robert B., Jr.] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA.
   [Langer, Jerome A.] Rutgers Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Emory University; Emory University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Weizmann Institute of Science; 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); University of Nebraska System; University of Nebraska Medical Center; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences
RP Douek, DC (corresponding author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
FU NIH Intramural Funding; NCI/NIH [HHSN261200800001E]; NIH [R24 RR017444, AI-076174]; I-CORE Program of the Planning and Budgeting Committee; Israel Science Foundation grant [1775/12]; NIH Office of the Director [P51OD011132] Funding Source: NIH RePORTER
NR 34
TC 397
Z9 444
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 JUL 30
PY 2014
VL 511
IS 7511
BP 601
EP +
DI 10.1038/nature13554
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300037
PM 25043006
DA 2026-03-09
ER

PT J
AU Skourti-Stathaki, K
   Kamieniarz-Gdula, K
   Proudfoot, NJ
AF Skourti-Stathaki, Konstantina
   Kamieniarz-Gdula, Kinga
   Proudfoot, Nicholas J.
TI R-loops induce repressive chromatin marks over mammalian gene terminators
SO NATURE
LA English
DT Article
ID rna; methylation; hp1-gamma; g9a
AB The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potentially harmful effects on genome integrity owing to the fragility of the displaced DNA coding strand(1). However, R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes(2,3). Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements. These facilitate RNA polymerase II (Pol II) pausing before efficient termination(4). Here we reveal an unanticipated link between R-loops and RNA-interference-dependent H3K9me2 formation over pause-site termination regions in mammalian protein-coding genes. We show that R-loops induce antisense transcription over these pause elements, which in turn leads to the generation of double-stranded RNA and the recruitment of DICER, AGO1, AGO2 and the G9a histone lysine methyltransferase. Consequently, an H3K9me2 repressive mark is formed and heterochromatin protein 1 gamma (HP1 gamma) is recruited, which reinforces Pol II pausing before efficient transcriptional termination. We predict that R-loops promote a chromatin architecture that defines the termination region for a substantial subset of mammalian genes.
C1 [Skourti-Stathaki, Konstantina; Kamieniarz-Gdula, Kinga; Proudfoot, Nicholas J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
C3 University of Oxford
RP Proudfoot, NJ (corresponding author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
EM nicholas.proudfoot@path.ox.ac.uk
FU Wellcome Trust [091805/Z/10/Z]; European Research Council [339270-polyloop]; Marie Curie Actions grant from EU FP7 (REA grant) [327985]; Wellcome Trust [091805/Z/10/Z] Funding Source: Wellcome Trust
CR Aguilera A, 2012, MOL CELL, V46, P115, DOI 10.1016/j.molcel.2012.04.009
   Alló M, 2009, NAT STRUCT MOL BIOL, V16, P717, DOI 10.1038/nsmb.1620
   Bastos RN, 2012, J CELL BIOL, V198, P865, DOI 10.1083/jcb.201204107
   Frietze S, 2010, PLOS ONE, V5, P0, DOI 10.1371/journal.pone.0015082
   Gentleman RC, 2004, GENOME BIOL, V5, P0, DOI 10.1186/gb-2004-5-10-r80
   Ginno PA, 2013, GENOME RES, V23, P1590, DOI 10.1101/gr.158436.113
   Ginno PA, 2012, MOL CELL, V45, P814, DOI 10.1016/j.molcel.2012.01.017
   Gullerova M, 2008, CELL, V132, P983, DOI 10.1016/j.cell.2008.02.040
   Jenuwein T, 2006, FEBS J, V273, P3121, DOI 10.1111/j.1742-4658.2006.05343.x
   Karolchik D, 2004, NUCLEIC ACIDS RES, V32, PD493, DOI 10.1093/nar/gkh103
   Kubicek S, 2007, MOL CELL, V25, P473, DOI 10.1016/j.molcel.2007.01.017
   Mateescu B, 2008, EMBO REP, V9, P267, DOI 10.1038/embor.2008.1
   Nakama M, 2012, GENES CELLS, V17, P218, DOI 10.1111/j.1365-2443.2012.01583.x
   Nojima T, 2013, CELL REP, V3, P1080, DOI 10.1016/j.celrep.2013.03.012
   Rice JC, 2003, MOL CELL, V12, P1591, DOI 10.1016/S1097-2765(03)00479-9
   Rosenbloom KR, 2013, NUCLEIC ACIDS RES, V41, PD56, DOI 10.1093/nar/gks1172
   Saint-André V, 2011, NAT STRUCT MOL BIOL, V18, P337, DOI 10.1038/nsmb.1995
   SCHONBORN J, 1991, NUCLEIC ACIDS RES, V19, P2993, DOI 10.1093/nar/19.11.2993
   Skourti-Stathaki K, 2011, MOL CELL, V42, P794, DOI 10.1016/j.molcel.2011.04.026
   Smallwood A, 2012, GENOME RES, V22, P1426, DOI 10.1101/gr.124818.111
   Tachibana M, 2005, GENE DEV, V19, P815, DOI 10.1101/gad.1284005
   Vakoc CR, 2005, MOL CELL, V19, P381, DOI 10.1016/j.molcel.2005.06.011
   Zofall M, 2009, NATURE, V461, P419, DOI 10.1038/nature08321
NR 23
TC 307
Z9 370
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 DEC 18
PY 2014
VL 516
IS 7531
BP 436
EP +
DI 10.1038/nature13787
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800056
PM 25296254
DA 2026-03-09
ER

PT J
AU McNally, A
   Haffemayer, B
   Collins, BSL
   Gaunt, MJ
AF McNally, Andrew
   Haffemayer, Benjamin
   Collins, Beatrice S. L.
   Gaunt, Matthew J.
TI Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles
SO NATURE
LA English
DT Article
ID c(sp(3))-h bonds; functionalization; arylation; sp(2); amination
AB The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds(1-6), but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a 'directing group', which positions the metal catalyst near a particular C-H bond, so that the C-H functionalization step occurs via cyclometallation(7). Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate(8-10). Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations(11). Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and beta-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.
C1 [McNally, Andrew; Haffemayer, Benjamin; Collins, Beatrice S. L.; Gaunt, Matthew J.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
C3 University of Cambridge
RP Gaunt, MJ (corresponding author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM mjg32@cam.ac.uk
FU EPSRC; GSK; University of Cambridge; ERC; Engineering and Physical Sciences Research Council [EP/I00548X/1] Funding Source: researchfish; EPSRC [EP/I00548X/1] Funding Source: UKRI
NR 29
TC 451
Z9 488
U1 2
U2 359
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2014
VL 510
IS 7503
BP 129
EP 133
DI 10.1038/nature13389
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900042
PM 24870240
DA 2026-03-09
ER

PT J
AU Cruchaga, C
   Karch, CM
   Jin, SC
   Benitez, BA
   Cai, YF
   Guerreiro, R
   Harari, O
   Norton, J
   Budde, J
   Bertelsen, S
   Jeng, AT
   Cooper, B
   Skorupa, T
   Carrell, D
   Levitch, D
   Hsu, S
   Choi, J
   Ryten, M
   Sassi, C
   Bras, J
   Gibbs, JR
   Hernandez, DG
   Lupton, MK
   Powell, J
   Forabosco, P
   Ridge, PG
   Corcoran, CD
   Tschanz, JT
   Norton, MC
   Munger, RG
   Schmutz, C
   Leary, M
   Demirci, FY
   Bamne, MN
   Wang, XB
   Lopez, OL
   Ganguli, M
   Medway, C
   Turton, J
   Lord, J
   Braae, A
   Barber, I
   Brown, K
   Pastor, P
   Lorenzo-Betancor, O
   Brkanac, Z
   Scott, E
   Topol, E
   Morgan, K
   Rogaeva, E
   Singleton, AB
   Hardy, J
   Kamboh, MI
   St George-Hyslop, P
   Cairns, N
   Morris, JC
   Kauwe, JSK
   Goate, AM
AF Cruchaga, Carlos
   Karch, Celeste M.
   Jin, Sheng Chih
   Benitez, Bruno A.
   Cai, Yefei
   Guerreiro, Rita
   Harari, Oscar
   Norton, Joanne
   Budde, John
   Bertelsen, Sarah
   Jeng, Amanda T.
   Cooper, Breanna
   Skorupa, Tara
   Carrell, David
   Levitch, Denise
   Hsu, Simon
   Choi, Jiyoon
   Ryten, Mina
   Sassi, Celeste
   Bras, Jose
   Gibbs, J. Raphael
   Hernandez, Dena G.
   Lupton, Michelle K.
   Powell, John
   Forabosco, Paola
   Ridge, Perry G.
   Corcoran, Christopher D.
   Tschanz, Joann T.
   Norton, Maria C.
   Munger, Ronald G.
   Schmutz, Cameron
   Leary, Maegan
   Demirci, F. Yesim
   Bamne, Mikhil N.
   Wang, Xingbin
   Lopez, Oscar L.
   Ganguli, Mary
   Medway, Christopher
   Turton, James
   Lord, Jenny
   Braae, Anne
   Barber, Imelda
   Brown, Kristelle
   Pastor, Pau
   Lorenzo-Betancor, Oswaldo
   Brkanac, Zoran
   Scott, Erick
   Topol, Eric
   Morgan, Kevin
   Rogaeva, Ekaterina
   Singleton, Andrew B.
   Hardy, John
   Kamboh, M. Ilyas
   St George-Hyslop, Peter
   Cairns, Nigel
   Morris, John C.
   Kauwe, John S. K.
   Goate, Alison M.
TI Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease
SO NATURE
LA English
DT Article
ID network analysis; association; expression; trem2; age; diagnosis; dementia; insights; mutation; brain
AB Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)(1,2). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-beta precursor protein (APP) and extracellular A beta 42 and A beta 40 (the 42- and 40-residue isoforms of the amyloid-beta peptide), and knockdown of PLD3 leads to a significant increase in extracellular A beta 42 and A beta 40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.
C1 [Cruchaga, Carlos; Karch, Celeste M.; Jin, Sheng Chih; Benitez, Bruno A.; Cai, Yefei; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T.; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Goate, Alison M.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
   [Cruchaga, Carlos; Karch, Celeste M.; Cairns, Nigel; Goate, Alison M.] Washington Univ, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO 63110 USA.
   [Guerreiro, Rita; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, J. Raphael; Hernandez, Dena G.; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
   [Guerreiro, Rita; Sassi, Celeste; Gibbs, J. Raphael; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Lupton, Michelle K.; Powell, John] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Lupton, Michelle K.] QIMR Berghofer Med Res Inst, Herston, Qld 4006, Australia.
   [Forabosco, Paola] CNR, Ist Genet Popolaz, I-07100 Sassari, Italy.
   [Ridge, Perry G.; Schmutz, Cameron; Leary, Maegan; Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
   [Corcoran, Christopher D.] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA.
   [Corcoran, Christopher D.; Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA.
   [Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA.
   [Norton, Maria C.; Munger, Ronald G.] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA.
   [Munger, Ronald G.] Utah State Univ, Dept Nutr Dietet & Food Sci, Logan, UT 84322 USA.
   [Demirci, F. Yesim; Bamne, Mikhil N.; Wang, Xingbin; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA.
   [Lopez, Oscar L.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA.
   [Lopez, Oscar L.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA.
   [Ganguli, Mary] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA.
   [Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Morgan, Kevin] Univ Nottingham, Sch Mol Med Sci, Queens Med Ctr, Nottingham NG7 2UH, England.
   [Pastor, Pau; Lorenzo-Betancor, Oswaldo] Univ Navarra, Ctr Appl Med Res, Neurogenet Lab, Div Neurosci, Navarra 31008, Spain.
   [Pastor, Pau] Univ Navarra, Sch Med, Clin Univ Navarra, Dept Neurol, Pamplona 31008, Spain.
   [Pastor, Pau] Inst Salud Carlos III, CIBERNED, Madrid, Spain.
   [Brkanac, Zoran] Univ Washington, Seattle, WA 98104 USA.
   [Scott, Erick; Topol, Eric] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada.
   [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0XY, England.
   [Cairns, Nigel; Morris, John C.] Washington Univ, St Louis, MO 63110 USA.
   [Morris, John C.; Goate, Alison M.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
   [Morris, John C.; Goate, Alison M.] Washington Univ, Knight ADRC, St Louis, MO 63110 USA.
   [Goate, Alison M.] Washington Univ, Dept Genet, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of London; University College London; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of London; King's College London; QIMR Berghofer Medical Research Institute; Consiglio Nazionale delle Ricerche (CNR); Brigham Young University; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Nottingham; University of Navarra; University of Navarra; Instituto de Salud Carlos III; CIBERNED; University of Washington; University of Washington Seattle; Scripps Research Institute; University of Toronto; University of Cambridge; University of Cambridge; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Cruchaga, C (corresponding author), Washington Univ, Dept Psychiat, 425 South Euclid Ave, St Louis, MO 63110 USA.
EM ccruchaga@wustl.edu
FU National Institutes of Health [P30-NS069329, R01-AG044546, R01-AG035083, RO1-AG11380, RO1-AG18712, RO1-AG21136, R01-AG042611]; Alzheimer Association [NIRG-11-200110]; Barnes Jewish Foundation; American Federation for Aging Research; BrightFocus Foundation Alzheimer's Disease Research Grant [A2013359S]; Genentech; Pfizer; NIH [P50 AG05681, P01 AG03991, P01 AG026276, R01039700, AG041718, AG030653, AG005133, AG07562, AG023652]; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [ZO1 AG000950-11]; Alzheimer's Association [MNIRG-11-205368]; Alzheimer's Research UK (ARUK); NINDS [ZO1 AG000950-10]; Wellcome Trust/MRC [WT089698]; Big Lottery; ARUK; ASvia ABBUK Ltd.; NIHR Queen Square Dementia BRU; BRC NIHR; Canadian Institutes of Health Research; Wellcome Trust; Medical Research Council; National Institute of Health Research; Ontario Research Fund; Alzheimer Society of Ontario; UK Medical Research Council through the MRC Sudden Death Brain Bank; Department of Health of the Government of Navarra, Spain [13085, 3/2008]; UTE project FIMA, Spain; NIA [R01AG21136];  [U24AG21886];  [U24: 5U24AG026395];  [1R01AG041797];  [G0901254];  [G0802462]; Medical Research Council [G1100695, G0901254, MC_G1000735, G0802462, MC_G1000734, MR/L016400/1, G0802189, MR/K01417X/1] Funding Source: researchfish; National Institute for Health Research [ACF-2007-18-011, ACF-2012-17-017] Funding Source: researchfish; MRC [G0802189, MR/L016400/1, G0802462, MR/K01417X/1, G0901254, MC_G1000735, G1100695, MC_G1000734] Funding Source: UKRI; National Institute on Aging [U24AG021886, P01AG003991, P01AG026276] Funding Source: NIH RePORTER
NR 47
TC 359
Z9 426
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 JAN 23
PY 2014
VL 505
IS 7484
BP 550
EP +
DI 10.1038/nature12825
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000040
PM 24336208
DA 2026-03-09
ER

PT J
AU Robart, AR
   Chan, RT
   Peters, JK
   Rajashankar, KR
   Toor, N
AF Robart, Aaron R.
   Chan, Russell T.
   Peters, Jessica K.
   Rajashankar, Kanagalaghatta R.
   Toor, Navtej
TI Crystal structure of a eukaryotic group II intron lariat
SO NATURE
LA English
DT Article
ID rna; site; crystallography; nucleotides; recognition; reveals; steps
AB The formation of branched lariat RNA is an evolutionarily conserved feature of splicing reactions for both group II and spliceosomal introns. The lariat is important for the fidelity of 5' splice-site selection and consists of a 2'-5' phosphodiester bond between a bulged adenosine and the 5' end of the intron. To gain insight into this ubiquitous intramolecular linkage, we determined the crystal structure of a eukaryotic group IIB intron in the lariat form at 3.7 angstrom. This revealed that two tandem tetraloop-receptor interactions, eta-eta' and pi-pi', place domain VI in the core to position the lariat bond in the post-catalytic state. On the basis of structural and biochemical data, we propose that pi-pi' is a dynamic interaction that mediates the transition between the two steps of splicing, with pi-pi' serving an ancillary role. The structure also reveals a four-magnesium-ion cluster involved in both catalysis and positioning of the 5' end. Given the evolutionary relationship between group II and nuclear introns, it is likely that this active site configuration exists in the spliceosome as well.
C1 [Robart, Aaron R.; Chan, Russell T.; Peters, Jessica K.; Toor, Navtej] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL 60439 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Argonne, IL 60439 USA.
C3 University of California System; University of California San Diego; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory
RP Toor, N (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM ntoor@ucsd.edu
FU Cell, Molecular, and Genetics Training Program - NIH predoctoral training grant [5T32GM007240]; UCSD Molecular Biophysics Training Program - NIH predoctoral training grant [5T32GM008326]; NIH grant [8P41GM103403-10]; US DOE [DE-AC02-06CH11357]; Hellman Foundation Fellowship; NIH [5R01GM102216]
NR 46
TC 105
Z9 120
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 OCT 9
PY 2014
VL 514
IS 7521
BP 193
EP +
DI 10.1038/nature13790
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100034
PM 25252982
DA 2026-03-09
ER

PT J
AU Chen, X
   Iliopoulos, D
   Zhang, Q
   Tang, QZ
   Greenblatt, MB
   Hatziapostolou, M
   Lim, E
   Tam, WL
   Ni, M
   Chen, YW
   Mai, JH
   Shen, HF
   Hu, DZ
   Adoro, S
   Hu, B
   Song, MY
   Tan, C
   Landis, MD
   Ferrari, M
   Shin, SJ
   Brown, M
   Chang, JC
   Liu, XS
   Glimcher, LH
AF Chen, Xi
   Iliopoulos, Dimitrios
   Zhang, Qing
   Tang, Qianzi
   Greenblatt, Matthew B.
   Hatziapostolou, Maria
   Lim, Elgene
   Tam, Wai Leong
   Ni, Min
   Chen, Yiwen
   Mai, Junhua
   Shen, Haifa
   Hu, Dorothy Z.
   Adoro, Stanley
   Hu, Bella
   Song, Minkyung
   Tan, Chen
   Landis, Melissa D.
   Ferrari, Mauro
   Shin, Sandra J.
   Brown, Myles
   Chang, Jenny C.
   Liu, X. Shirley
   Glimcher, Laurie H.
TI XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway
SO NATURE
LA English
DT Article
ID unfolded protein response; stress-response; stem-cells; er stress; metastasis; phenotype; therapy; growth
AB Cancer cells induce a set of adaptive response pathways to survive in the face of stressors due to inadequate vascularization(1). One such adaptive pathway is the unfolded protein(UPR) or endoplasmic reticulum (ER) stress response mediated in part by the ER-localized transmembrane sensor IRE1 (ref. 2) and its substrate XBP1 (ref. 3). Previous studies report UPR activation in various human tumours(4-6), but the role of XBP1 in cancer progression in mammary epithelial cells is largely unknown. Triple-negative breast cancer (TNBC)-a form of breast cancer in which tumour cells do not express the genes for oestrogen receptor, progesterone receptor and HER2 (also called ERBB2 or NEU)-is a highly aggressive malignancy with limited treatment options(7,8). Here we report that XBP1 is activated in TNBC and has a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. In breast cancer cell line models, depletion of XBP1 inhibited tumour growth and tumour relapse and reduced the CD44(high)CD24(low) population. Hypoxia-inducing factor 1 alpha (HIF1 alpha) is known to be hyperactivated in TNBCs9,10. Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1 alpha that regulates the expression of HIF1 alpha targets via the recruitment of RNA polymerase II. Analysis of independent cohorts of patients with TNBC revealed a specific XBP1 gene expression signature that was highly correlated with HIF1 alpha and hypoxia-driven signatures and that strongly associated with poor prognosis. Our findings reveal a key function for the XBP1 branch of the UPR in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.
C1 [Chen, Xi; Adoro, Stanley; Song, Minkyung; Tan, Chen; Glimcher, Laurie H.] Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, New York, NY 10065 USA.
   [Chen, Xi; Adoro, Stanley; Song, Minkyung; Tan, Chen; Ferrari, Mauro; Chang, Jenny C.; Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
   [Iliopoulos, Dimitrios; Hatziapostolou, Maria] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA.
   [Iliopoulos, Dimitrios; Hatziapostolou, Maria] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   [Zhang, Qing] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Tang, Qianzi] Tongji Univ, Dept Bioinformat, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
   [Tang, Qianzi] Sichuan Agr Univ, Coll Anim Sci & Technol, Inst Anim Genet & Breeding, Yaan 625014, Sichuan, Peoples R China.
   [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Lim, Elgene; Ni, Min; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Lim, Elgene; Ni, Min; Brown, Myles] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Tam, Wai Leong] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Chen, Yiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Mai, Junhua; Shen, Haifa; Ferrari, Mauro] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA.
   [Shen, Haifa] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.
   [Hu, Dorothy Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   [Hu, Bella] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA.
   [Landis, Melissa D.; Chang, Jenny C.] Houston Methodist Canc Ctr, Houston, TX 77030 USA.
   [Shin, Sandra J.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
C3 Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; 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; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of North Carolina; University of North Carolina Chapel Hill; Tongji University; Sichuan Agricultural University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Houston Methodist; Cornell University; Weill Cornell Medicine; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Houston Methodist; Cornell University; Weill Cornell Medicine
RP Glimcher, LH (corresponding author), Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, 1300 York Ave, New York, NY 10065 USA.
EM lglimche@med.cornell.edu
FU National Institutes of Health [CA112663, AI32412, R01HG004069, K99CA175290]; Leukemia and Lymphoma Society; National Natural Science Foundation of China [NSFC31329003]; National Cancer Institute [P50CA058223, P30CA016086] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 30
TC 700
Z9 823
U1 6
U2 273
PU NATURE PUBLISHING 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 3
PY 2014
VL 508
IS 7494
BP 103
EP +
DI 10.1038/nature13119
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900051
PM 24670641
DA 2026-03-09
ER

PT J
AU Clenet, H
   Jutzi, M
   Barrat, JA
   Asphaug, EI
   Benz, W
   Gillet, P
AF Clenet, Harold
   Jutzi, Martin
   Barrat, Jean-Alix
   Asphaug, Erik I.
   Benz, Willy
   Gillet, Philippe
TI A deep crust-mantle boundary in the asteroid 4 Vesta
SO NATURE
LA English
DT Article
ID modified gaussian model; parent body; pyroxene mixtures; hed meteorites; magma ocean; olivine; diogenites; dawn; reflectance; spectroscopy
AB The asteroid 4 Vesta was recently found to have two large impact craters near its south pole, exposing subsurface material. Modelling suggested that surface material in the northern hemisphere of Vesta came from a depth of about 20 kilometres, whereas the exposed southern material comes from a depth of 60 to 100 kilometres. Large amounts of olivine from the mantle were not seen, suggesting that the outer 100 kilometres or so is mainly igneous crust. Here we analyse the data on Vesta and conclude that the crust-mantle boundary (or Moho) is deeper than 80 kilometres.
C1 [Clenet, Harold; Gillet, Philippe] Ecole Polytech Fed Lausanne, Inst Condensed Matter Phys, EPSL, Stn 3, CH-1015 Lausanne, Switzerland.
   [Jutzi, Martin; Benz, Willy] Univ Bern, Inst Phys, Ctr Space & Habitabil, CH-3012 Bern, Switzerland.
   [Barrat, Jean-Alix] Univ Bretagne Occidentale, Inst Univ Europeen Mer, CNRS, UMR 6538, F-29280 Plouzane, France.
   [Asphaug, Erik I.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Bern; Universite de Bretagne Occidentale; Institut Universitaire Europeen de la Mer (IUEM); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Arizona State University; Arizona State University-Tempe
RP Clenet, H (corresponding author), Ecole Polytech Fed Lausanne, Inst Condensed Matter Phys, EPSL, Stn 3, CH-1015 Lausanne, Switzerland.
EM harold.clenet@epfl.ch
FU Swiss National Science Foundation through the Ambizione program; INSU Programme National de Planetologie; NASA Planetary Geology and Geophysics Program
NR 45
TC 59
Z9 65
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 17
PY 2014
VL 511
IS 7509
BP 303
EP +
DI 10.1038/nature13499
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200026
PM 25030166
DA 2026-03-09
ER

PT J
AU van Berlo, JH
   Kanisicak, O
   Maillet, M
   Vagnozzi, RJ
   Karch, J
   Lin, SCJ
   Middleton, RC
   Marbán, E
   Molkentin, JD
AF van Berlo, Jop H.
   Kanisicak, Onur
   Maillet, Marjorie
   Vagnozzi, Ronald J.
   Karch, Jason
   Lin, Suh-Chin J.
   Middleton, Ryan C.
   Marban, Eduardo
   Molkentin, Jeffery D.
TI c-kit+ cells minimally contribute cardiomyocytes to the heart
SO NATURE
LA English
DT Article
ID cardiac stem-cells; c-kit; adult; fusion; regeneration; myocardium; expression; mouse; adopt
AB If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells cangenerate cardiomyocytes within the heart, although probably at a functionally insignificant level.
C1 [van Berlo, Jop H.; Kanisicak, Onur; Maillet, Marjorie; Vagnozzi, Ronald J.; Karch, Jason; Lin, Suh-Chin J.; Molkentin, Jeffery D.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
   [van Berlo, Jop H.] Univ Minnesota, Lillehei Heart Inst, Div Cardiol, Dept Med, Minneapolis, MN 55455 USA.
   [Middleton, Ryan C.; Marban, Eduardo] Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
   [Molkentin, Jeffery D.] Cincinnati Childrens Hosp Med Ctr, Howard Hughes Med Inst, Cincinnati, OH 45229 USA.
C3 Cincinnati Children's Hospital Medical Center; University of Minnesota System; University of Minnesota Twin Cities; Cedars Sinai Medical Center; Cincinnati Children's Hospital Medical Center; Howard Hughes Medical Institute
RP Molkentin, JD (corresponding author), Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
EM Jeff.Molkentin@cchmc.org
FU National Institutes of Health; National Heart Lung and Blood Institute [R01HL105924] Funding Source: NIH RePORTER
NR 27
TC 645
Z9 763
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 MAY 15
PY 2014
VL 509
IS 7500
BP 337
EP +
DI 10.1038/nature13309
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200033
PM 24805242
DA 2026-03-09
ER

PT J
AU Chowdhury, R
   Sekirnik, R
   Brissett, NC
   Krojer, T
   Ho, CH
   Ng, SS
   Clifton, IJ
   Ge, W
   Kershaw, NJ
   Fox, GC
   Muniz, JRC
   Vollmar, M
   Phillips, C
   Pilka, ES
   Kavanagh, KL
   von Delft, F
   Oppermann, U
   McDonough, MA
   Doherty, AJ
   Schofield, CJ
AF Chowdhury, Rasheduzzaman
   Sekirnik, Rok
   Brissett, Nigel C.
   Krojer, Tobias
   Ho, Chia-hua
   Ng, Stanley S.
   Clifton, Ian J.
   Ge, Wei
   Kershaw, Nadia J.
   Fox, Gavin C.
   Muniz, Joao R. C.
   Vollmar, Melanie
   Phillips, Claire
   Pilka, Ewa S.
   Kavanagh, Kathryn L.
   von Delft, Frank
   Oppermann, Udo
   McDonough, Michael A.
   Doherty, Aidan J.
   Schofield, Christopher J.
TI Ribosomal oxygenases are structurally conserved from prokaryotes to humans
SO NATURE
LA English
DT Article
ID transcription factor osterix; crystal-structure; lysyl-hydroxylation; substrate-binding; histone; protein; 2-oxoglutarate; insights; system; domain
AB 2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components(1,2) and in the hydroxylation of transcription factors(3) and splicing factor proteins(4). Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transferRNA(5-7) and ribosomal proteins(8) have been shown to be important in translation relating to cellular growth, T(H)17-cell differentiation and translational accuracy(9-12). The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans(8) raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone N-epsilon -methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases.
C1 [Chowdhury, Rasheduzzaman; Sekirnik, Rok; Ho, Chia-hua; Clifton, Ian J.; Ge, Wei; Kershaw, Nadia J.; McDonough, Michael A.; Schofield, Christopher J.] Univ Oxford, Dept Chem, Oxford OX1 3TA, England.
   [Chowdhury, Rasheduzzaman; Sekirnik, Rok; Ho, Chia-hua; Clifton, Ian J.; Ge, Wei; Kershaw, Nadia J.; McDonough, Michael A.; Schofield, Christopher J.] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England.
   [Brissett, Nigel C.; Doherty, Aidan J.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
   [Krojer, Tobias; Ng, Stanley S.; Muniz, Joao R. C.; Vollmar, Melanie; Phillips, Claire; Pilka, Ewa S.; Kavanagh, Kathryn L.; von Delft, Frank; Oppermann, Udo] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England.
   [Fox, Gavin C.] Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France.
   [Oppermann, Udo] Botnar Res Ctr, NIHR Oxford Biomed Res Unit, Oxford OX3 7LD, England.
C3 University of Oxford; University of Oxford; University of Sussex; University of Oxford; SOLEIL Synchrotron; University of Oxford
RP Schofield, CJ (corresponding author), Univ Oxford, Dept Chem, Mansfield Rd, Oxford OX1 3TA, England.
EM rasheduzzaman.chowdhury@chem.ox.ac.uk; christopher.schofield@chem.ox.ac.uk
FU Biotechnology and Biological Sciences Research Council; Wellcome Trust; European Research Council; Medical Research Council; Oxford NIHR Biomedical Research Unit; Cancer Research UK; Arthritis Research UK; Bayer Healthcare; Rosetree Foundation; Slovenian Academy of Sciences and Arts; Abbvie; Boehringer Ingelheim; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Eli Lilly; Genome Canada; GlaxoSmithKline; Ontario Ministry of Economic Development and Innovation; Janssen; Novartis Research Foundation; Pfizer; Takeda; BBSRC [BB/L009846/1, BB/J003018/1, BB/L004275/1, BB/J018643/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/L009846/1, BB/J018643/1, BB/L004275/1, BB/C518230/1, BB/J003018/1] Funding Source: researchfish; Cancer Research UK [6947] Funding Source: researchfish
NR 59
TC 95
Z9 103
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 JUN 19
PY 2014
VL 510
IS 7505
BP 422
EP +
DI 10.1038/nature13263
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200040
PM 24814345
DA 2026-03-09
ER

PT J
AU Doré, AS
   Okrasa, K
   Patel, JC
   Serrano-Vega, M
   Bennett, K
   Cooke, RM
   Errey, JC
   Jazayeri, A
   Khan, S
   Tehan, B
   Weir, M
   Wiggin, GR
   Marshall, FH
AF Dore, Andrew S.
   Okrasa, Krzysztof
   Patel, Jayesh C.
   Serrano-Vega, Maria
   Bennett, Kirstie
   Cooke, Robert M.
   Errey, James C.
   Jazayeri, Ali
   Khan, Samir
   Tehan, Ben
   Weir, Malcolm
   Wiggin, Giselle R.
   Marshall, Fiona H.
TI Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain
SO NATURE
LA English
DT Article
ID protein-coupled receptors; allosteric modulators; heptahelical domain; crystal-structure; binding pockets; activation; family; thermostabilization; antagonists; mutations
AB Metabotropic glutamate receptors are class C G-protein-coupled receptors which respond to the neurotransmitter glutamate. Structural studies have been restricted to the amino-terminal extracellular domain, providing little understanding of the membrane-spanning signal transduction domain. Metabotropic glutamate receptor 5 is of considerable interest as a drug target in the treatment of fragile X syndrome, autism, depression, anxiety, addiction and movement disorders. Here we report the crystal structure of the transmembrane domain of the human receptor in complex with the negative allosteric modulator, mavoglurant. The structure provides detailed insight into the architecture of the transmembrane domain of class C receptors including the precise location of the allosteric binding site within the transmem-branedomain and key micro-switches which regulate receptor signalling. This structure also provides a model for all class CG-protein-coupled receptors and may aid in the design of new small-molecule drugs for the treatment of brain disorders.
C1 [Dore, Andrew S.; Okrasa, Krzysztof; Patel, Jayesh C.; Serrano-Vega, Maria; Bennett, Kirstie; Cooke, Robert M.; Errey, James C.; Jazayeri, Ali; Khan, Samir; Tehan, Ben; Weir, Malcolm; Wiggin, Giselle R.; Marshall, Fiona H.] Heptares Therapeut Ltd, 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 50
TC 357
Z9 408
U1 0
U2 126
PU NATURE PUBLISHING 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 30
PY 2014
VL 511
IS 7511
BP 557
EP +
DI 10.1038/nature13396
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300027
PM 25042998
DA 2026-03-09
ER

PT J
AU Simon, AC
   Zhou, JC
   Perera, RL
   van Deursen, F
   Evrin, C
   Ivanova, ME
   Kilkenny, ML
   Renault, L
   Kjaer, S
   Matak-Vinkovic, D
   Labib, K
   Costa, A
   Pellegrini, L
AF Simon, Aline C.
   Zhou, Jin C.
   Perera, Rajika L.
   van Deursen, Frederick
   Evrin, Cecile
   Ivanova, Marina E.
   Kilkenny, Mairi L.
   Renault, Ludovic
   Kjaer, Svend
   Matak-Vinkovic, Dijana
   Labib, Karim
   Costa, Alessandro
   Pellegrini, Luca
TI A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome
SO NATURE
LA English
DT Article
ID sister-chromatid cohesion; mcm2-7 helicase; replication; complex; progression; protein; gins; stoichiometry; metabolism; activation
AB Efficient duplication of the genome requires the concerted action of helicase and DNA polymerases at replication forks(1) to avoid stalling of the replication machinery and consequent genomic instability(2-4). In eukaryotes, the physical coupling between helicase and DNA polymerases remains poorly understood. Here we define the molecular mechanism by which the yeast Ctf4 protein links the Cdc45-MCM-GINS(CMG) DNA helicase to DNA polymerase alpha (Pol alpha) within the replisome. We use X-ray crystallography and electron microscopy to show that Ctf4 self-associates in a constitutive disk-shaped trimer. Trimerization depends on a beta-propeller domain in the carboxy-terminal half of the protein, which is fused to a helical extension that protrudes from one face of the trimeric disk. Critically, Pol alpha and the CMG helicase share a common mechanism of interaction with Ctf4. We show that the amino-terminal tails of the catalytic subunit of Pol alpha and the Sld5 subunit of GINS contain a conserved Ctf4-binding motif that docks onto the exposed helical extension of a Ctf4 protomer within the trimer. Accordingly, we demonstrate that one Ctf4 trimer can support binding of up to three partner proteins, including the simultaneous association with both Pol a and GINS. Our findings indicate that Ctf4 can couple two molecules of Pol alpha to one CMG helicase within the replisome, providing a new model for lagging-strand synthesis in eukaryotes that resembles the emerging model for the simpler replisome of Escherichia coli(5-8). The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork.
C1 [Simon, Aline C.; Perera, Rajika L.; Ivanova, Marina E.; Kilkenny, Mairi L.; Pellegrini, Luca] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
   [Zhou, Jin C.; Renault, Ludovic; Costa, Alessandro] Canc Res UK London Res Inst, Clare Hall Labs, London EN6 3LD, England.
   [van Deursen, Frederick] Univ Manchester, Canc Res UK Manchester Inst, Manchester M20 4BX, Lancs, England.
   [Evrin, Cecile; Labib, Karim] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee DD1 5EH, Scotland.
   [Kjaer, Svend] Canc Res UK London Res Inst, London WC2A 3LY, England.
   [Matak-Vinkovic, Dijana] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
C3 University of Cambridge; Cancer Research UK; University of Manchester; Cancer Research UK; University of Dundee; Cancer Research UK; University of Cambridge
RP Pellegrini, L (corresponding author), Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
EM alessandro.costa@cancer.org.uk; lp212@cam.ac.uk
FU Gates Cambridge PhD program; CRUK; MRC; Wellcome Trust SRF award in basic biomedical science; Cancer Research UK [15852] Funding Source: researchfish; Medical Research Council [MC_UU_12016/13] Funding Source: researchfish; Wellcome Trust [102943/Z/13/Z] Funding Source: researchfish; Wellcome Trust [102943/Z/13/Z] Funding Source: Wellcome Trust; MRC [MC_UU_12016/13] Funding Source: UKRI
NR 44
TC 171
Z9 202
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 JUN 12
PY 2014
VL 510
IS 7504
BP 293
EP +
DI 10.1038/nature13234
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400055
PM 24805245
DA 2026-03-09
ER

PT J
AU Falenty, A
   Hansen, TC
   Kuhs, WF
AF Falenty, Andrzej
   Hansen, Thomas C.
   Kuhs, Werner F.
TI Formation and properties of ice XVI obtained by emptying a type sII clathrate hydrate
SO NATURE
LA English
DT Article
ID negative thermal-expansion; thermodynamic stability; hydrogen; phase; disorder
AB Gas hydrates are ice-like solids, in which guest molecules or atoms are trapped inside cages formed within a crystalline host framework (clathrate) of hydrogen-bonded water molecules(1). They are naturally present in large quantities on the deep ocean floor and as permafrost, can form in and block gas pipelines, and are thought to occur widely on Earth and beyond. A natural point of reference for this large and ubiquitous family of inclusion compounds is the empty hydrate lattice(1-6), which is usually regarded as experimentally inaccessible because the guest species stabilize the host framework. However, it has been suggested that sufficiently small guests may be removed to leave behind metastable empty clathrates(7,8), and guest-free Si-and Ge-clathrates have indeed been obtained(9,10). Here we show that this strategy can also be applied to water-based clathrates: five days of continuous vacuum pumping on small particles of neon hydrate (of structure sII) removes all guests, allowing us to determine the crystal structure, thermal expansivity and limit of metastability of the empty hydrate. It is the seventeenth experimentally established crystalline ice phase(11), ice XVI according to the current ice nomenclature, has a density of 0.81 grams per cubic centimetre (making it the least dense of all known crystalline water phases) and is expected(7,12) to be the stable low-temperature phase of water at negative pressures (that is, under tension). We find that the empty hydrate structure exhibits negative thermal expansion below about 55 kelvin, and that it is mechanically more stable and has at low temperatures larger lattice constants than the filled hydrate. These observations attest to the importance of kinetic effects and host-guest interactions in clathrate hydrates, with further characterization of the empty hydrate expected to improve our understanding of the structure, properties and behaviour of these unique materials.
C1 [Falenty, Andrzej; Kuhs, Werner F.] Univ Gottingen, GZG Abt Kristallog, Goldschmidtstr 1, D-37077 Gottingen, Germany.
   [Hansen, Thomas C.] Inst Max Von Laue Paul Langevin, F-38000 Grenoble, France.
C3 University of Gottingen; Institut Laue-Langevin (ILL)
RP Kuhs, WF (corresponding author), Univ Gottingen, GZG Abt Kristallog, Goldschmidtstr 1, D-37077 Gottingen, Germany.
EM wkuhs1@gwdg.de
FU Bundesministeriums fur Bildung und Forschung (BMBF)
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   Anderson BJ, 2005, J PHYS CHEM B, V109, P8153, DOI 10.1021/jp045551g
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   Koyama Y, 2005, J CHEM PHYS, V122, P0, DOI 10.1063/1.1850904
   Kuhs WF, 1992, ACTA CRYSTALLOGR A, V48, P80
   Kuhs WF, 2012, P NATL ACAD SCI USA, V109, P21259, DOI 10.1073/pnas.1210331110
   Kumar P, 2011, J PHYS CHEM A, V115, P14276, DOI 10.1021/jp2089565
   Kuo JL, 2005, J CHEM PHYS, V123, P0, DOI 10.1063/1.2036971
   Lobban C, 1998, NATURE, V391, P268, DOI 10.1038/34622
   Mao WL, 2002, SCIENCE, V297, P2247, DOI 10.1126/science.1075394
   Matsumoto M, 2011, J PHYS CHEM B, V115, P8257, DOI 10.1021/jp203478z
   Pamuk B, 2012, PHYS REV LETT, V108, P0, DOI 10.1103/PhysRevLett.108.193003
   Peters B, 2008, J AM CHEM SOC, V130, P17342, DOI 10.1021/ja802014m
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   Senadheera L, 2007, J PHYS CHEM B, V111, P12097, DOI 10.1021/jp074517+
   Sloan ED, 2008, CHEM IND-SER, V119, P0
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NR 37
TC 261
Z9 287
U1 2
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 DEC 11
PY 2014
VL 516
IS 7530
BP 231
EP +
DI 10.1038/nature14014
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500041
PM 25503235
DA 2026-03-09
ER

PT J
AU Waldherr, G
   Wang, Y
   Zaiser, S
   Jamali, M
   Schulte-Herbrüggen, T
   Abe, H
   Ohshima, T
   Isoya, J
   Du, JF
   Neumann, P
   Wrachtrup, J
AF Waldherr, G.
   Wang, Y.
   Zaiser, S.
   Jamali, M.
   Schulte-Herbrueggen, T.
   Abe, H.
   Ohshima, T.
   Isoya, J.
   Du, J. F.
   Neumann, P.
   Wrachtrup, J.
TI Quantum error correction in a solid-state hybrid spin register
SO NATURE
LA English
DT Article
ID entanglement; qubits; readout; ion
AB Error correction is important in classical and quantum computation. Decoherence caused by the inevitable interaction of quantum bits with their environment leads to dephasing or even relaxation. Correction of the concomitant errors is therefore a fundamental requirement for scalable quantum computation(1-7). Although algorithms for error correction have been known for some time, experimental realizations are scarce(2-7). Here we show quantum error correction in a heterogeneous, solid-state spin system(8-21). We demonstrate that joint initialization, projective readout and fast local and non-local gate operations can all be achieved in diamond spin systems, even under ambient conditions. High-fidelity initialization of a whole spin register (99 per cent) and single-shot readout of multiple individual nuclear spins are achieved by using the ancillary electron spin of a nitrogen-vacancy defect. Implementation of a novel non-local gate generic to our electron-nuclear quantum register allows the preparation of entangled states of three nuclear spins, with fidelities exceeding 85 per cent. With these techniques, we demonstrate three-qubit phase-flip error correction. Using optimal control, all of the above operations achieve fidelities approaching those needed for fault-tolerant quantum operation, thus paving the way to large-scale quantum computation. Besides their use with diamond spin systems, our techniques can be used to improve scaling of quantum networks relying on phosphorus in silicon(19), quantum dots(22), silicon carbide(11) or rare-earth ions in solids(20,21).
C1 [Waldherr, G.; Wang, Y.; Zaiser, S.; Jamali, M.; Neumann, P.; Wrachtrup, J.] Univ Stuttgart, Inst Phys 3, D-70569 Stuttgart, Germany.
   [Waldherr, G.; Wang, Y.; Zaiser, S.; Jamali, M.; Neumann, P.; Wrachtrup, J.] Univ Stuttgart, Res Ctr SCOPE, D-70569 Stuttgart, Germany.
   [Schulte-Herbrueggen, T.] Tech Univ Munich, Dept Chem, D-85747 Garching, Germany.
   [Abe, H.; Ohshima, T.] Japan Atom Energy Agcy, Takasaki, Gunma 3701292, Japan.
   [Isoya, J.] Univ Tsukuba, Res Ctr Knowledge Communities, Tsukuba, Ibaraki 3058550, Japan.
   [Du, J. F.] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China.
   [Du, J. F.] Univ Sci & Technol China, Dept Modern Phys, Hefei 230026, Peoples R China.
   [Wrachtrup, J.] Max Planck Inst Solid State Res, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; University of Stuttgart; Technical University of Munich; Japan Atomic Energy Agency; University of Tsukuba; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Max Planck Society
RP Waldherr, G (corresponding author), Univ Stuttgart, Inst Phys 3, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM g.waldherr@physik.uni-stuttgart.de
FU Max Planck Society; ERC; DFG [SFB/TR21]; EU; JST-DFG [FOR1482, FOR1493]; Volkswagenstiftung
NR 39
TC 506
Z9 589
U1 3
U2 285
PU NATURE PUBLISHING 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 13
PY 2014
VL 506
IS 7487
BP 204
EP +
DI 10.1038/nature12919
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700034
PM 24476818
DA 2026-03-09
ER

PT J
AU Chang, LF
   Zhang, ZG
   Yang, J
   McLaughlin, SH
   Barford, D
AF Chang, Leifu
   Zhang, Ziguo
   Yang, Jing
   McLaughlin, Stephen H.
   Barford, David
TI Molecular architecture and mechanism of the anaphase-promoting complex
SO NATURE
LA English
DT Article
ID mitotic checkpoint complex; ubiquitin chain elongation; em structure determination; cullin-ring ligases; crystal-structure; electron-microscopy; cryoelectron microscopy; structural insights; degron recognition; substrate-binding
AB The ubiquitination of cell cycle regulatory proteins by the anaphase-promoting complex/cyclosome(APC/C) controls sister chromatid segregation, cytokinesis and the establishment of the G1 phase of the cell cycle. The APC/C is an unusually large multimeric cullin-RING ligase. Its activity is strictly dependent on regulatory coactivator subunits that promote APC/C-substrate interactions and stimulate its catalytic reaction. Because the structures of many APC/C subunits and their organization within the assembly are unknown, the molecular basis for these processes is poorly understood. Here, from a cryo-electron microscopy reconstruction of a human APC/C-coactivator-substrate complex at 7.4 angstrom resolution, we have determined the complete secondary structural architecture of the complex. With this information we identified protein folds for structurally uncharacterized subunits, and the definitive location of all 20 APC/C subunits within the 1.2 MDa assembly. Comparison with apo APC/C shows that the coactivator promotes a profound allosteric transition involving displacement of the cullin-RING catalytic subunits relative to the degron-recognition module of coactivator and APC10. This transition is accompanied by increased flexibility of the cullin-RING subunits and enhanced affinity for UBCH10-ubiquitin, changes which may contribute to coactivator-mediated stimulation of APC/C E3 ligase activity.
C1 [Chang, Leifu; Zhang, Ziguo; Yang, Jing; Barford, David] Inst Canc Res, Div Struct Biol, London SW3 6JB, England.
   [Chang, Leifu; Zhang, Ziguo; Yang, Jing; McLaughlin, Stephen H.; Barford, David] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
C3 University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; MRC Laboratory Molecular Biology
RP Barford, D (corresponding author), MRC Lab Mol Biol, Cambridge CB2 0QH, England.
EM dbarford@mrc-lmb.cam.ac.uk
FU Cancer Research UK; 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 68
TC 175
Z9 219
U1 0
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 SEP 18
PY 2014
VL 513
IS 7518
BP 388
EP +
DI 10.1038/nature13543
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900053
PM 25043029
DA 2026-03-09
ER

PT J
AU Colussi, TM
   Costantino, DA
   Hammond, JA
   Ruehle, GM
   Nix, JC
   Kieft, JS
AF Colussi, Timothy M.
   Costantino, David A.
   Hammond, John A.
   Ruehle, Grant M.
   Nix, Jay C.
   Kieft, Jeffrey S.
TI The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA
SO NATURE
LA English
DT Article
ID mosaic-virus rna; minus-strand synthesis; structure validation; crystal-structure; 3' end; initiation; ribosome; binding; valine; translation
AB RNA is arguably the most functionally diverse biological macromolecule. In some cases a single discrete RNA sequence performs multiple roles, and this can be conferred by a complex three-dimensional structure. Such multifunctionality can also be driven or enhanced by the ability of a given RNA to assume different conformational (and therefore functional) states'. Despite its biological importance, a detailed structural understanding of the paradigm of RNA structure-driven multifunctionality is lacking. To address this gap it is useful to study examples from single-stranded positive-sense RNA viruses, a prototype being the tRNA-like structure (TLS) found at the 3' end of the turnip yellow mosaic virus (TYMV). This TLS not only acts like a tRNA to drive aminoacylation of the viral genomic (g)RNA(2-4), but also interacts with other structures in the 3' untranslated region of the gRNA(5), contains the promoter for negative-strand synthesis, and influences several infection-critical processes'. TLS RNA can provide a glimpse into the structural basis of RNA multifunctionality and plasticity, but for decades its high-resolution structure has remained elusive. Here we present the crystal structure of the complete TYMV TLS to 2.0 angstrom resolution. Globally, the RNA adopts a shape that mimics tRNA, but it uses a very different set of intramolecular interactions to achieve this shape. These interactions also allow the TLS to readily switch conformations. In addition, the TLS structure is 'two faced': one face closely mimics tRNA and drives aminoacylation, the other face diverges from tRNA and enables additional functionality. The TLS is thus structured to perform several functions and interact with diverse binding partners, and we demonstrate its ability to specifically bind to ribosomes.
C1 [Colussi, Timothy M.; Costantino, David A.; Hammond, John A.; Ruehle, Grant M.; Kieft, Jeffrey S.] Univ Colorado, Denver Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
   [Colussi, Timothy M.; Costantino, David A.; Kieft, Jeffrey S.] Univ Colorado, Denver Sch Med, Howard Hughes Med Inst, Aurora, CO 80045 USA.
   [Nix, Jay C.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Biol Consortium, Adv Light Source, Berkeley, CA 94720 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical Campus; University of Colorado System; University of Colorado Anschutz Medical Campus; Howard Hughes Medical Institute; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Kieft, JS (corresponding author), Univ Colorado, Denver Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
EM jeffrey.kieft@ucdenver.edu
FU UC Cancer Center [P30CA046934]; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-ACO2-05CH11231]; National Institutes of Health [GM081346, GM097333]; National Cancer Institute [P30CA046934] Funding Source: NIH RePORTER
NR 45
TC 73
Z9 85
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 JUL 17
PY 2014
VL 511
IS 7509
BP 366
EP +
DI 10.1038/nature13378
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200040
PM 24909993
DA 2026-03-09
ER

PT J
AU Pruitt, JN
   Goodnight, CJ
AF Pruitt, Jonathan N.
   Goodnight, Charles J.
TI RETRACTED: Site-specific group selection drives locally adapted group compositions (Retracted article. See MAR, 2023)
SO NATURE
LA English
DT Article; Retracted Publication
ID multilevel selection; fitness consequences; spider; population; evolution; history; traits
AB Group selection may be defined as selection caused by the differential extinction or proliferation of groups(1,2). The socially polymorphic spider Anelosimus studiosus exhibits a behavioural polymorphism in which females exhibit either a 'docile' or 'aggressive' behavioural phenotype(3,4). Natural colonies are composed of a mixture of related docile and aggressive individuals, and populations differ in colonies' characteristic docile: aggressive ratios(5,6). Using experimentally constructed colonies of known composition, here we demonstrate that population-level divergence in docile: aggressive ratios is driven by site-specific selection at the group level-certain ratios yield high survivorship at some sites but not others. Our data also indicate that colonies responded to the risk of extinction: perturbed colonies tended to adjust their composition over two generations to match the ratio characteristic of their native site, thus promoting their long-term survival in their natal habitat. However, colonies of displaced individuals continued to shift their compositions towards mixtures that would have promoted their survival had they remained at their home sites, regardless of their contemporary environment. Thus, the regulatory mechanisms that colonies use to adjust their composition appear to be locally adapted. Our data provide experimental evidence of group selection driving collective traits in wild populations.
C1 [Pruitt, Jonathan N.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
   [Goodnight, Charles J.] Univ Vermont, Dept Biol, Burlington, VT 05405 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Vermont
RP Pruitt, JN (corresponding author), Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
EM pruittj@pitt.edu
FU National Science Foundation [1352705]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1352705] Funding Source: National Science Foundation
NR 29
TC 79
Z9 87
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 OCT 16
PY 2014
VL 514
IS 7522
BP 359
EP +
DI 10.1038/nature13811
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600050
PM 25274310
DA 2026-03-09
ER

PT J
AU Moore, CW
   Obrist, D
   Steffen, A
   Staebler, RM
   Douglas, TA
   Richter, A
   Nghiem, SV
AF Moore, Christopher W.
   Obrist, Daniel
   Steffen, Alexandra
   Staebler, Ralf M.
   Douglas, Thomas A.
   Richter, Andreas
   Nghiem, Son V.
TI Convective forcing of mercury and ozone in the Arctic boundary layer induced by leads in sea ice
SO NATURE
LA English
DT Article
ID atmospheric mercury; gaseous mercury; elemental mercury; heat-transfer; troposphere; winter; ocean
AB The ongoing regime shift of Arctic sea ice from perennial to seasonal ice is associated with more dynamic patterns of opening and closing sea-ice leads (large transient channels of open water in the ice)(1-3), which may affect atmospheric and biogeochemical cycles in the Arctic(4). Mercury and ozone are rapidly removed from the atmospheric boundary layer during depletion events in the Arctic(5-7), caused by destruction of ozone along with oxidation of gaseous elemental mercury (Hg(0)) to oxidized mercury (Hg(II)) in the atmosphere and its subsequent deposition to snow and ice(5). Ozone depletion events can change the oxidative capacity of the air by affecting atmospheric hydroxyl radical chemistry(8), whereas atmospheric mercury depletion events can increase the deposition of mercury to the Arctic(6,9-11), some of which can enter ecosystems during snowmelt(12). Here we present near-surface measurements of atmospheric mercury and ozone from two Arctic field campaigns near Barrow, Alaska. We find that coastal depletion events are directly linked to sea-ice dynamics. A consolidated ice cover facilitates the depletion of Hg(0) and ozone, but these immediately recover to near-background concentrations in the upwind presence of open sea-ice leads. We attribute the rapid recoveries of Hg(0) and ozone to lead-initiated shallow convection in the stable Arctic boundary layer, which mixes Hg(0) and ozone from undepleted air masses aloft. This convective forcing provides additional Hg(0) to the surface layer at a time of active depletion chemistry, where it is subject to renewed oxidation. Future work will need to establish the degree to which large-scale changes in sea-ice dynamics across the Arctic alter ozone chemistry and mercury deposition in fragile Arctic ecosystems.
C1 [Moore, Christopher W.; Obrist, Daniel] Desert Res Inst, Div Atmospher Sci, Reno, NV 89523 USA.
   [Steffen, Alexandra; Staebler, Ralf M.] Environm Canada, Air Qual Proc Res Sect, Toronto, ON M3H 5T4, Canada.
   [Douglas, Thomas A.] US Army Cold Reg Res & Engn Lab, Ft Wainwright, AK 99703 USA.
   [Richter, Andreas] Univ Bremen, Inst Environm Phys, D-28359 Bremen, Germany.
   [Nghiem, Son V.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 Nevada System of Higher Education (NSHE); Desert Research Institute NSHE; Environment & Climate Change Canada; 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); University of Bremen; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology
RP Moore, CW (corresponding author), Desert Res Inst, Div Atmospher Sci, Reno, NV 89523 USA.
EM chris.moore@dri.edu
FU National Aeronautics and Space Administration (NASA); Desert Research Institute; Science and Technology Branch of Environment Canada; Canadian International Polar Year government programme; NASA CSP; Directorate For Geosciences; Office of Polar Programs (OPP) [1304305, 1739567] Funding Source: National Science Foundation
NR 32
TC 84
Z9 89
U1 4
U2 143
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 6
PY 2014
VL 506
IS 7486
BP 81
EP +
DI 10.1038/nature12924
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100035
PM 24429521
DA 2026-03-09
ER

PT J
AU Carvalhais, N
   Forkel, M
   Khomik, M
   Bellarby, J
   Jung, M
   Migliavacca, M
   Mu, MQ
   Saatchi, S
   Santoro, M
   Thurner, M
   Weber, U
   Ahrens, B
   Beer, C
   Cescatti, A
   Randerson, JT
   Reichstein, M
AF Carvalhais, Nuno
   Forkel, Matthias
   Khomik, Myroslava
   Bellarby, Jessica
   Jung, Martin
   Migliavacca, Mirco
   Mu, Mingquan
   Saatchi, Sassan
   Santoro, Maurizio
   Thurner, Martin
   Weber, Ulrich
   Ahrens, Bernhard
   Beer, Christian
   Cescatti, Alessandro
   Randerson, James T.
   Reichstein, Markus
TI Global covariation of carbon turnover times with climate in terrestrial ecosystems
SO NATURE
LA English
DT Article
ID soil organic-carbon; respiration; productivity; dynamics; storage; matter; stock; decomposition; sensitivity; boreal
AB The response of the terrestrial carbon cycle to climate change is among the largest uncertainties affecting future climate change projections(1,2). The feedback between the terrestrial carbon cycle and climate is partly determined by changes in the turnover time of carbon in land ecosystems, which in turn is an ecosystem property that emerges from the interplay between climate, soil and vegetation type(3-6). Here we present a global, spatially explicit and observation-based assessment of whole-ecosystem carbon turnover times that combines new estimates of vegetation and soil organic carbon stocks and fluxes. We find that the overall mean global carbon turnover time is 23(4)(+7) years (95 per cent confidence interval). Onaverage, carbon resides in the vegetation and soil near the Equator for a shorter time than at latitudes north of 75 degrees north (mean turnover times of 15 and 255 years, respectively). We identify a clear dependence of the turnover time on temperature, as expected from our present understanding of temperature controls on ecosystem dynamics. Surprisingly, our analysis also reveals a similarly strong association between turnover time and precipitation. Moreover, we find that the ecosystem carbon turnover times simulated by state-of-the-art coupled climate/carbon-cycle models vary widely and that numerical simulations, on average, tend to underestimate the global carbon turnover time by 36 per cent. The models show stronger spatial relationships with temperature than do observation-based estimates, but generally do not reproduce the strong relationships with precipitation and predict faster carbon turnover in many semiarid regions. Our findings suggest that future climate/carbon-cycle feedbacks may depend more strongly on changes in the hydrological cycle than is expected at present and is considered in Earth system models.
C1 [Carvalhais, Nuno; Forkel, Matthias; Khomik, Myroslava; Jung, Martin; Migliavacca, Mirco; Thurner, Martin; Weber, Ulrich; Ahrens, Bernhard; Beer, Christian; Reichstein, Markus] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Carvalhais, Nuno] Univ Nova Lisboa, FCT, DCEA, P-2829516 Caparica, Portugal.
   [Khomik, Myroslava] McMaster Univ, Sch Geog & Earth Sci, Hamilton, ON L8S 4K1, Canada.
   [Bellarby, Jessica] Univ Aberdeen, Sch Biol Sci, Inst Biol & Environm Sci, Aberdeen AB24 3UU, Scotland.
   [Bellarby, Jessica] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Migliavacca, Mirco] Univ Milano Bicocca, DISAT, Remote Sensing Environm Dynam Lab, I-20126 Milan, Italy.
   [Mu, Mingquan; Randerson, James T.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Saatchi, Sassan] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Santoro, Maurizio] Gamma Remote Sensing, CH-3073 Gumlingen, Switzerland.
   [Beer, Christian] Stockholm Univ, Dept Appl Environm Sci, S-10691 Stockholm, Sweden.
   [Beer, Christian] Stockholm Univ, Bolin Ctr Climate Res, S-10691 Stockholm, Sweden.
   [Cescatti, Alessandro] Commiss European Communities, Joint Res Ctr, Inst Environm & Sustainabil, Climate Risk Management Unit, I-21027 Ispra, Italy.
C3 Max Planck Society; Universidade Nova de Lisboa; McMaster University; University of Aberdeen; Lancaster University; University of Milano-Bicocca; University of California System; University of California Irvine; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; GAMMA Remote Sensing AG; Stockholm University; Stockholm University; European Commission Joint Research Centre; EC JRC ISPRA Site
RP Carvalhais, N (corresponding author), Max Planck Inst Biogeochem, Hans Knoll Str 10, D-07745 Jena, Germany.
EM nuno.carvalhais@bgc-jena.mpg.de
FU European Union (FP7) through the project GEOCARBON [283080]; ERC starting grant QUASOM [ERC-2007-StG-208516]; European Union (FP7) through the project CARBONES [242316]; European Union (FP7) through the project EMBRACE [283201]; Directorate For Geosciences [1048890] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1048890] Funding Source: National Science Foundation
NR 71
TC 721
Z9 825
U1 20
U2 1211
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2014
VL 514
IS 7521
BP 213
EP +
DI 10.1038/nature13731
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100039
PM 25252980
DA 2026-03-09
ER

PT J
AU Marusyk, A
   Tabassum, DP
   Altrock, PM
   Almendro, V
   Michor, F
   Polyak, K
AF Marusyk, Andriy
   Tabassum, Doris P.
   Altrock, Philipp M.
   Almendro, Vanessa
   Michor, Franziska
   Polyak, Kornelia
TI Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity
SO NATURE
LA English
DT Article
ID il-6 family cytokine; cancer; evolution; model; tumorigenesis; inflammation; competition; mutations; selection; leukemia
AB Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.
C1 [Marusyk, Andriy; Tabassum, Doris P.; Almendro, Vanessa; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Tabassum, Doris P.; Polyak, Kornelia] Harvard Univ, Sch Med, BBS Program, Boston, MA 02115 USA.
   [Altrock, Philipp M.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Altrock, Philipp M.; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Altrock, Philipp M.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Polyak, Kornelia] Broad Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; 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; Harvard University; Harvard University; 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 kornelia_polyak@dfci.harvard.edu
FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54CA143798]; CDRMP Breast Cancer Research Program [W81XWH-09-1-0561]; Cellex Foundation; Deutsche Akademie der Naturforscher Leopoldina [LPDS2012-12]; Breast Cancer Research Foundation
NR 29
TC 454
Z9 547
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 OCT 2
PY 2014
VL 514
IS 7520
BP 54
EP +
DI 10.1038/nature13556
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800033
PM 25079331
DA 2026-03-09
ER

PT J
AU Peisley, A
   Wu, B
   Xu, H
   Chen, ZJJ
   Hur, S
AF Peisley, Alys
   Wu, Bin
   Xu, Hui
   Chen, Zhijian J.
   Hur, Sun
TI Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I
SO NATURE
LA English
DT Article
ID rna recognition; protein; oligomerization; sequence; reveals; complex; sensors; mavs
AB Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of noncovalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ub(n)) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD)(1,2). Non-covalent binding of K63-Ub(n) to 2CARD induces its tetramer formation, a requirement for downstream signal activation(3). Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub(2). 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.
C1 [Peisley, Alys; Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Peisley, Alys; Wu, Bin; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Xu, Hui; Chen, Zhijian J.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Chen, Zhijian J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
RP Hur, S (corresponding author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM Sun.Hur@childrens.harvard.edu
FU GSK; Welch Foundation [I-1389]; NIH [R01-GM63692]; Pew Scholarship; BCH
NR 30
TC 279
Z9 318
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 MAY 1
PY 2014
VL 509
IS 7498
BP 110
EP +
DI 10.1038/nature13140
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100049
PM 24590070
DA 2026-03-09
ER

PT J
AU Trinter, F
   Schöffler, MS
   Kim, HK
   Sturm, FP
   Cole, K
   Neumann, N
   Vredenborg, A
   Williams, J
   Bocharova, I
   Guillemin, R
   Simon, M
   Belkacem, A
   Landers, AL
   Weber, T
   Schmidt-Böcking, H
   Dörner, R
   Jahnke, T
AF Trinter, F.
   Schoeffler, M. S.
   Kim, H-K
   Sturm, F. P.
   Cole, K.
   Neumann, N.
   Vredenborg, A.
   Williams, J.
   Bocharova, I.
   Guillemin, R.
   Simon, M.
   Belkacem, A.
   Landers, A. L.
   Weber, Th.
   Schmidt-Boecking, H.
   Doerner, R.
   Jahnke, T.
TI Resonant Auger decay driving intermolecular Coulombic decay in molecular dimers
SO NATURE
LA English
DT Article
ID potential-energy surface; momentum spectroscopy; recoil-ion; ab-initio; excitation; electrons; clusters
AB In 1997, it was predicted(1) that an electronically excited atom or molecule placed in a loosely bound chemical system (such as a hydrogen-bonded or van-der-Waals- bonded cluster) could efficiently decay by transferring its excess energy to a neighbouring species that would then emit a low-energy electron. This intermolecular Coulombic decay (ICD) process has since been shown to be a common phenomenon(2-12), raising questions about its role in DNA damage induced by ionizing radiation, in which low-energy electrons are known to play an important part(13,14). It was recently suggested(15) that ICD can be triggered efficiently and site-selectively by resonantly core-exciting a target atom, which then transforms through Auger decay into an ionic species with sufficiently high excitation energy to permit ICD to occur. Here we show experimentally that resonant Auger decay can indeed trigger ICD in dimers of both molecular nitrogen and carbon monoxide. By using ion and electron momentum spectroscopy to measure simultaneously the charged species created in the resonant-Auger-driven ICD cascade, we find that ICD occurs in less time than the 20 femtoseconds it would take for individual molecules to undergo dissociation. Our experimental confirmation of this process and its efficiency may trigger renewed efforts to develop resonant X-ray excitation schemes(16,17) for more localized and targeted cancer radiation therapy.
C1 [Trinter, F.; Schoeffler, M. S.; Kim, H-K; Sturm, F. P.; Cole, K.; Neumann, N.; Vredenborg, A.; Schmidt-Boecking, H.; Doerner, R.; Jahnke, T.] Goethe Univ Frankfurt, Inst Kernphys, D-60438 Frankfurt, Germany.
   [Schoeffler, M. S.; Sturm, F. P.; Bocharova, I.; Belkacem, A.; Weber, Th.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, Berkeley, CA 94720 USA.
   [Williams, J.; Landers, A. L.] Auburn Univ, Dept Phys, Auburn, AL 36849 USA.
   [Guillemin, R.; Simon, M.] UPMC, F-75005 Paris, France.
   [Guillemin, R.; Simon, M.] CNRS, UMR 7614, Lab Chim Phys Mat & Rayonnement, F-75005 Paris, France.
C3 Goethe University Frankfurt; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Auburn University System; Auburn University; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Sorbonne Universite
RP Jahnke, T (corresponding author), Goethe Univ Frankfurt, Inst Kernphys, Max Von Laue Str 1, D-60438 Frankfurt, Germany.
EM trinter@atom.uni-frankfurt.de; jahnke@atom.uni-frankfurt.de
FU Deutsche Forschungsgemeinschaft; Deutscher Akademischer Austauschdienst; Division of Chemical Sciences, Geosciences, and Biosciences of the US Department of Energy at the Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Alexander von Humboldt foundation
NR 29
TC 130
Z9 133
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 JAN 30
PY 2014
VL 505
IS 7485
BP 664
EP 666
DI 10.1038/nature12927
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000037
PM 24362568
DA 2026-03-09
ER

PT J
AU Xu, H
   Yang, JL
   Gao, WQ
   Li, L
   Li, P
   Zhang, L
   Gong, YN
   Peng, XL
   Xi, JZJ
   Chen, S
   Wang, FC
   Shao, F
AF Xu, Hao
   Yang, Jieling
   Gao, Wenqing
   Li, Lin
   Li, Peng
   Zhang, Li
   Gong, Yi-Nan
   Peng, Xiaolan
   Xi, Jianzhong Jeff
   Chen, She
   Wang, Fengchao
   Shao, Feng
TI Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome
SO NATURE
LA English
DT Article
ID familial mediterranean fever; gtp-binding proteins; clostridium-difficile; burkholderia-cenocepacia; toxin-b; actin cytoskeleton; vibrio-cholerae; rtx toxin; activation; system
AB Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex(1,2). Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever(3-5). Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB(6-8), a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrioparahaemolyticus VopS and Histophilus somnilbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activitydependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.
C1 [Xu, Hao; Yang, Jieling; Gao, Wenqing; Li, Lin; Li, Peng; Zhang, Li; Gong, Yi-Nan; Peng, Xiaolan; Chen, She; Wang, Fengchao; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Yang, Jieling; Shao, Feng] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Xi, Jianzhong Jeff] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China.
   [Shao, Feng] Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Sciences; Institute of Biophysics, CAS; Peking University
RP Shao, F (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM shaofeng@nibs.ac.cn
FU International Early Career Scientist grant from the Howard Hughes Medical Institute; National Basic Research Program of China 973 Program [2012CB518700]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08020202]; China National Science Foundation Program for Distinguished Young Scholars [31225002]
NR 39
TC 677
Z9 795
U1 1
U2 194
PU NATURE PUBLISHING 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 11
PY 2014
VL 513
IS 7517
BP 237
EP +
DI 10.1038/nature13449
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800051
PM 24919149
DA 2026-03-09
ER

PT J
AU Franz, HB
   Kim, ST
   Farquhar, J
   Day, JMD
   Economos, RC
   McKeegan, KD
   Schmitt, AK
   Irving, AJ
   Hoek, J
   Dottin, J
AF Franz, Heather B.
   Kim, Sang-Tae
   Farquhar, James
   Day, James M. D.
   Economos, Rita C.
   McKeegan, Kevin D.
   Schmitt, Axel K.
   Irving, Anthony J.
   Hoek, Joost
   Dottin, James, III
TI Isotopic links between atmospheric chemistry and the deep sulphur cycle on Mars
SO NATURE
LA English
DT Article
ID los-angeles; petrogenesis; meteorite; nakhlites; assemblages; components; regolith; alh84001; sulfate
AB The geochemistry of Martian meteorites provides a wealth of information about the solid planet and the surface and atmospheric processes that occurred on Mars. The degree to which Martian magmas may have assimilated crustal material, thus altering the geochemical signatures acquired from their mantle sources, is unclear(1). This issue features prominently in efforts to understand whether the source of light rare-earth elements in enriched shergottites lies in crustal material incorporated into melts(1,2) or in mixing between enriched and depleted mantle reservoirs(3). Sulphur isotope systematics offer insight into some aspects of crustal assimilation. The presence of igneous sulphides in Martian meteorites with sulphur isotope signatures indicative of mass-independent fractionation suggests the assimilation of sulphur both during passage of magmas through the crust of Mars and at sites of emplacement. Here we report isotopic analyses of 40 Martian meteorites that represent more than half of the distinct known Martian meteorites, including 30 shergottites (28 plus 2 pairs, where pairs are separate fragments of a single meteorite), 8 nakhlites (5 plus 3 pairs), Allan Hills 84001 and Chassigny. Our data provide strong evidence that assimilation of sulphur into Martian magmas was a common occurrence throughout much of the planet's history. The signature of mass-independent fractionation observed also indicates that the atmospheric imprint of photochemical processing preserved in Martian meteoritic sulphide and sulphate is distinct from that observed in terrestrial analogues, suggesting fundamental differences between the dominant sulphur chemistry in the atmosphere of Mars and that in the atmosphere of Earth(4).
C1 [Franz, Heather B.] NASA, Goddard Space Flight Ctr, Ctr Res & Explorat Space Sci & Technol, Greenbelt, MD 20771 USA.
   [Franz, Heather B.; Farquhar, James; Hoek, Joost; Dottin, James, III] Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
   [Franz, Heather B.; Farquhar, James; Hoek, Joost; Dottin, James, III] Univ Maryland, Earth Syst Sci Interdisciplinary Ctr, College Pk, MD 20742 USA.
   [Kim, Sang-Tae] McMaster Univ, Sch Geog & Earth Sci, Hamilton, ON L8S 4K1, Canada.
   [Day, James M. D.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Economos, Rita C.; McKeegan, Kevin D.; Schmitt, Axel K.] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Irving, Anthony J.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; McMaster University; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of California System; University of California Los Angeles; University of Washington; University of Washington Seattle
RP Franz, HB (corresponding author), NASA, Goddard Space Flight Ctr, Ctr Res & Explorat Space Sci & Technol, Greenbelt, MD 20771 USA.
EM heather.b.franz@nasa.gov
FU US National Science Foundation Instrumentation and Facilities Program; NASA Cosmochemistry grants [NNX09AF72G, NNX13AL13G]
NR 38
TC 109
Z9 125
U1 5
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 APR 17
PY 2014
VL 508
IS 7496
BP 364
EP +
DI 10.1038/nature13175
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000045
PM 24740066
DA 2026-03-09
ER

PT J
AU Zhan, S
   Zhang, W
   Niitepold, K
   Hsu, J
   Haeger, JF
   Zalucki, MP
   Altizer, S
   de Roode, JC
   Reppert, SM
   Kronforst, MR
AF Zhan, Shuai
   Zhang, Wei
   Niitepold, Kristjan
   Hsu, Jeremy
   Fernandez Haeger, Juan
   Zalucki, Myron P.
   Altizer, Sonia
   de Roode, Jacobus C.
   Reppert, Steven M.
   Kronforst, Marcus R.
TI The genetics of monarch butterfly migration and warning colouration
SO NATURE
LA English
DT Article
ID danaus-plexippus l.; col4a1 mutations; flight; lepidoptera; population; sequence; reveals; genes; orientation; phylogeny
AB The monarch butterfly, Danaus plexippus, is famous for its spectacular annual migration across North America, recent worldwide dispersal, and orange warning colouration. Despite decades of study and broad public interest, we know little about the genetic basis of these hallmark traits. Here we uncover the history of the monarch's evolutionary origin and global dispersal, characterize the genes and pathways associated with migratory behaviour, and identify the discrete genetic basis of warning colouration by sequencing 101 Danaus genomes from around the globe. The results rewrite our understanding of this classic system, showing that D. plexippus was ancestrally migratory and dispersed out of North America to occupy its broad distribution. We find the strongest signatures of selection associated with migration centre on flight muscle function, resulting in greater flight efficiency among migratory monarchs, and that variation in monarch warning colouration is controlled by a single myosin gene not previously implicated in insect pigmentation.
C1 [Zhan, Shuai] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Insect Dev & Evolutionary Biol, Shanghai 200032, Peoples R China.
   [Zhan, Shuai; Zhang, Wei; Kronforst, Marcus R.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Zhan, Shuai; Reppert, Steven M.] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
   [Niitepold, Kristjan; Hsu, Jeremy] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Niitepold, Kristjan] Univ Helsinki, Dept Biosci, FI-00014 Helsinki, Finland.
   [Fernandez Haeger, Juan] Univ Cordoba, Dept Bot Ecol & Fisiol Vegetal, E-14071 Cordoba, Spain.
   [Zalucki, Myron P.] Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
   [Altizer, Sonia] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
   [de Roode, Jacobus C.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
C3 Chinese Academy of Sciences; University of Chicago; University of Massachusetts System; University of Massachusetts Worcester; Stanford University; University of Helsinki; Universidad de Cordoba; University of Queensland; University System of Georgia; University of Georgia; Emory University
RP Zhan, S (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Insect Dev & Evolutionary Biol, Shanghai 200032, Peoples R China.
EM szhan@sibs.ac.cn; mkronforst@uchicago.edu
FU National Institutes of Health [GM086794-02S1]; National Science Foundation [IOS-134367, DEB-0643831, DEB-1019746, DEB-1316037]; Chinese Academy of Sciences; Shanghai Institutes for Biological Sciences; University of Chicago; Division Of Environmental Biology; Direct For Biological Sciences [1019746] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1343671] Funding Source: National Science Foundation
NR 83
TC 221
Z9 265
U1 2
U2 438
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 16
PY 2014
VL 514
IS 7522
BP 317
EP +
DI 10.1038/nature13812
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600041
PM 25274300
DA 2026-03-09
ER

PT J
AU Saha, SK
   Parachoniak, CA
   Ghanta, KS
   Fitamant, J
   Ross, KN
   Najem, MS
   Gurumurthy, S
   Akbay, EA
   Sia, D
   Cornella, H
   Miltiadous, O
   Walesky, C
   Deshpande, V
   Zhu, AX
   Hezel, AF
   Yen, KE
   Straley, KS
   Travins, J
   Popovici-Muller, J
   Gliser, C
   Ferrone, CR
   Apte, U
   Llovet, JM
   Wong, KK
   Ramaswamy, S
   Bardeesy, N
AF Saha, Supriya K.
   Parachoniak, Christine A.
   Ghanta, Krishna S.
   Fitamant, Julien
   Ross, Kenneth N.
   Najem, Mortada S.
   Gurumurthy, Sushma
   Akbay, Esra A.
   Sia, Daniela
   Cornella, Helena
   Miltiadous, Oriana
   Walesky, Chad
   Deshpande, Vikram
   Zhu, Andrew X.
   Hezel, Aram F.
   Yen, Katharine E.
   Straley, Kimberly S.
   Travins, Jeremy
   Popovici-Muller, Janeta
   Gliser, Camelia
   Ferrone, Cristina R.
   Apte, Udayan
   Llovet, Josep M.
   Wong, Kwok-Kin
   Ramaswamy, Sridhar
   Bardeesy, Nabeel
TI Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer
SO NATURE
LA English
DT Article
ID intrahepatic cholangiocarcinoma; liver-regeneration; mutation; growth; mice; proliferation; progenitors; homeostasis; expression
AB Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer(1-5). Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing themto convert alpha-ketoglutarate (alpha KG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple alpha KG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation(6-10). However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear. Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4 alpha, a master regulator of hepatocyte identity and quiescence. Correspondingly, genetically engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepatic injury, characterized by HNF-4 alpha silencing, impaired hepatocyte differentiation, and markedly elevated levels of cell proliferation. Moreover, IDH and Kras mutations, genetic alterations that co-exist in a subset of human IHCCs4,5, cooperate to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC. These studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis, and present a novel genetically engineered mouse model of IDH-driven malignancy.
C1 [Saha, Supriya K.; Parachoniak, Christine A.; Ghanta, Krishna S.; Fitamant, Julien; Ross, Kenneth N.; Najem, Mortada S.; Gurumurthy, Sushma; Deshpande, Vikram; Zhu, Andrew X.; Ferrone, Cristina R.; Ramaswamy, Sridhar; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
   [Akbay, Esra A.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA.
   [Sia, Daniela; Cornella, Helena; Llovet, Josep M.] Univ Barcelona, Hosp Clin, Barcelona Clin Liver Canc Grp, HCC Translat Res Lab,IDIBAPS,Liver Unit, Catalonia 08036, Spain.
   [Sia, Daniela; Miltiadous, Oriana; Llovet, Josep M.] Icahn Sch Med Mt Sinai, Dept Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY 10029 USA.
   [Sia, Daniela] Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy.
   [Sia, Daniela] Dept Expt Oncol, I-20133 Milan, Italy.
   [Walesky, Chad; Apte, Udayan] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
   [Hezel, Aram F.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Yen, Katharine E.; Straley, Kimberly S.; Travins, Jeremy; Popovici-Muller, Janeta; Gliser, Camelia] Agios Pharmaceut, Cambridge, MA 02139 USA.
   [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Catalonia, Spain.
   [Llovet, Josep M.] Univ Barcelona, Catalonia 08036, Spain.
   [Ramaswamy, Sridhar] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Icahn School of Medicine at Mount Sinai; Fondazione IRCCS Istituto Nazionale Tumori Milan; University of Kansas; University of Kansas Medical Center; University of Rochester; Agios Pharmaceuticals; ICREA; University of Barcelona; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Bardeesy, N (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
EM Bardeesy.Nabeel@mgh.harvard.edu
FU TargetCancer Foundation; National Institutes of Health [R01CA136567-02, P50CA1270003]; Cholangiocarcinoma Foundation/Conquer Cancer Foundation of ASCO Young Investigator Award; American Cancer Society Postdoctoral Fellowship [PF-13-294-01-TBG]; Canadian Institutes of Health Research postdoctoral fellowship; Asociacion Espanola para el Estudio del Cancer; ICREA Funding Source: Custom; National Cancer Institute [P50CA127003] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK098414] Funding Source: NIH RePORTER
NR 38
TC 378
Z9 444
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 SEP 4
PY 2014
VL 513
IS 7516
BP 110
EP +
DI 10.1038/nature13441
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800040
PM 25043045
DA 2026-03-09
ER

PT J
AU Courtin, J
   Chaudun, F
   Rozeske, RR
   Karalis, N
   Gonzalez-Campo, C
   Wurtz, H
   Abdi, A
   Baufreton, J
   Bienvenu, TCM
   Herry, C
AF Courtin, Julien
   Chaudun, Fabrice
   Rozeske, Robert R.
   Karalis, Nikolaos
   Gonzalez-Campo, Cecilia
   Wurtz, Helene
   Abdi, Azzedine
   Baufreton, Jerome
   Bienvenu, Thomas C. M.
   Herry, Cyril
TI Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression
SO NATURE
LA English
DT Article
ID hippocampal theta; prelimbic cortex; oscillations; synchronization; extinction; amygdala; network; modulation; circuits; reset
AB Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses(1-3). Incortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (gamma-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations(4,5). Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing(6-8), it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex(9-12) (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories(13-15). However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression.
C1 [Courtin, Julien; Chaudun, Fabrice; Rozeske, Robert R.; Karalis, Nikolaos; Gonzalez-Campo, Cecilia; Wurtz, Helene; Bienvenu, Thomas C. M.; Herry, Cyril] INSERM, Neuroctr Magendie, U862, F-33077 Bordeaux, France.
   [Courtin, Julien; Chaudun, Fabrice; Rozeske, Robert R.; Karalis, Nikolaos; Gonzalez-Campo, Cecilia; Wurtz, Helene; Bienvenu, Thomas C. M.; Herry, Cyril] Univ Bordeaux, Neuroctr Magendie, U862, F-33077 Bordeaux, France.
   [Abdi, Azzedine; Baufreton, Jerome] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France.
   [Abdi, Azzedine; Baufreton, Jerome] CNRS, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France.
C3 Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; CNRS - National Institute for Biology (INSB); Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Herry, C (corresponding author), INSERM, Neuroctr Magendie, U862, 146 Rue Leo Saignat, F-33077 Bordeaux, France.
EM cyril.herry@inserm.fr
FU French National Research Agency [ANR-2010-BLAN-1442-01, ANR-10-EQPX-08 OPTOPATH]; European Research Council (ERC) under the European Union [281168]; Fonds AXA pour la recherche doctoral fellowship; Conseil Regional d'Aquitaine; European Research Council (ERC) [281168] Funding Source: European Research Council (ERC)
NR 30
TC 390
Z9 472
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 JAN 2
PY 2014
VL 505
IS 7481
BP 92
EP +
DI 10.1038/nature12755
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300030
PM 24256726
DA 2026-03-09
ER

PT J
AU Flach, J
   Bakker, ST
   Mohrin, M
   Conroy, PC
   Pietras, EM
   Reynaud, D
   Alvarez, S
   Diolaiti, ME
   Ugarte, F
   Forsberg, EC
   Le Beau, MM
   Stohr, BA
   Méndez, J
   Morrison, CG
   Passegué, E
AF Flach, Johanna
   Bakker, Sietske T.
   Mohrin, Mary
   Conroy, Pauline C.
   Pietras, Eric M.
   Reynaud, Damien
   Alvarez, Silvia
   Diolaiti, Morgan E.
   Ugarte, Fernando
   Forsberg, E. Camilla
   Le Beau, Michelle M.
   Stohr, Bradley A.
   Mendez, Juan
   Morrison, Ciaran G.
   Passegue, Emmanuelle
TI Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells
SO NATURE
LA English
DT Article
ID dna-damage-response; origin; maintenance; deficiency; expression; mutations; proteins; complex; repair; cycle
AB Haematopoietic stem cells (HSCs) self-renew for life, thereby making them one of the few blood cells that truly age(1,2). Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in degraded blood production and impaired engraftment following transplantation(2). While many drivers of HSC ageing have been proposed(2-5), the reason why HSC function degrades with age remains unknown. Here we show that cycling old HSCs in mice have heightened levels of replication stress associated with cell cycle defects and chromosome gaps or breaks, which are due to decreased expression of mini-chromosome maintenance (MCM) helicase components and altered dynamics of DNA replication forks. Nonetheless, old HSCs survive replication unless confronted with a strong replication challenge, such as transplantation. Moreover, once old HSCs re-establish quiescence, residual replication stress on ribosomal DNA (rDNA) genes leads to the formation of nucleolar-associated gamma H2AX signals, which persist owing to ineffective H2AX dephosphorylation by mislocalized PP4c phosphatase rather than ongoing DNA damage. Persistent nucleolar gamma H2AX also acts as a histone modification marking the transcriptional silencing of rDNA genes and decreased ribosome biogenesis in quiescent old HSCs. Our results identify replication stress as a potent driver of functional decline in old HSCs, and highlight the MCM DNA helicase as a potential molecular target for rejuvenation therapies.
C1 [Flach, Johanna; Bakker, Sietske T.; Mohrin, Mary; Pietras, Eric M.; Reynaud, Damien; Passegue, Emmanuelle] Univ Calif San Francisco, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Hem Onc Div, San Francisco, CA 94143 USA.
   [Flach, Johanna] Ctr Comprehens Canc, Inst Expt Canc Res, D-89081 Ulm, Germany.
   [Conroy, Pauline C.; Morrison, Ciaran G.] Natl Univ Ireland Galway, Sch Nat Sci, Ctr Chromosome Biol, Galway, Ireland.
   [Alvarez, Silvia; Mendez, Juan] Spanish Natl Canc Res Ctr CNIO, E-28049 Madrid, Spain.
   [Diolaiti, Morgan E.; Stohr, Bradley A.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Ugarte, Fernando; Forsberg, E. Camilla] Univ Calif Santa Cruz, Inst Biol Stem Cells, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Le Beau, Michelle M.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA.
   [Le Beau, Michelle M.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA.
C3 University of California System; University of California San Francisco; Ulm University; Ollscoil na Gaillimhe-University of Galway; Centro Nacional de Investigaciones Oncologicas (CNIO); University of California System; University of California San Francisco; University of California System; University of California Santa Cruz; University of Chicago; University of Chicago; Robert H. Lurie Comprehensive Cancer Center
RP Passegué, E (corresponding author), Univ Calif San Francisco, Dept Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Hem Onc Div, San Francisco, CA 94143 USA.
EM PassegueE@stemcell.ucsf.edu
FU National Institutes of Health (NIH) [F32 HL106989]; Science Foundation Ireland PI award [10/IN.1/B2972]; CIRM New Faculty Award [RN2-00934, NIH R01 HL092471]; California Institute for Regenerative Medicine (CIRM); Science Foundation Ireland (SFI) [10/IN.1/B2972] Funding Source: Science Foundation Ireland (SFI); National Institute of Allergy and Infectious Diseases [T32AI007334] Funding Source: NIH RePORTER
NR 36
TC 507
Z9 579
U1 0
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 AUG 14
PY 2014
VL 512
IS 7513
BP 198
EP +
DI 10.1038/nature13619
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700033
PM 25079315
DA 2026-03-09
ER

PT J
AU Azim, E
   Jiang, J
   Alstermark, B
   Jessell, TM
AF Azim, Eiman
   Jiang, Juan
   Alstermark, Bror
   Jessell, Thomas M.
TI Skilled reaching relies on a V2a propriospinal internal copy circuit
SO NATURE
LA English
DT Article
ID lateral reticular nucleus; ventral spinocerebellar tract; optimal feedback-control; mouse spinal-cord; motor control; functional organization; v2-derived interneurons; limb movements; mus-musculus; pathways
AB The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PNinternal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.
C1 [Azim, Eiman; Jessell, Thomas M.] Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Mortimer B Zuckerman Mind Brain Behav Inst,Dept N, New York, NY 10032 USA.
   [Azim, Eiman; Jessell, Thomas M.] Columbia Univ, Dept Mol Biophys, New York, NY 10032 USA.
   [Jiang, Juan; Alstermark, Bror] Umea Univ, Physiol Sect, Dept Integrat Med Biol, Umea, Sweden.
C3 Howard Hughes Medical Institute; Columbia University; Columbia University; Umea University
RP Jessell, TM (corresponding author), Columbia Univ, Howard Hughes Med Inst, Kavli Inst Brain Sci, Mortimer B Zuckerman Mind Brain Behav Inst,Dept N, New York, NY 10032 USA.
EM ea2471@columbia.edu; bror.alstermark@umu.se; tmj1@columbia.edu
FU Umea University; Swedish Research Council; National Institutes of Health [NS033245]; Harold and Leila Y. Mathers Foundation; Project A.L.S.
NR 52
TC 236
Z9 310
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 APR 17
PY 2014
VL 508
IS 7496
BP 357
EP +
DI 10.1038/nature13021
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000044
PM 24487617
DA 2026-03-09
ER

PT J
AU Kotler, S
   Akerman, N
   Navon, N
   Glickman, Y
   Ozeri, R
AF Kotler, Shlomi
   Akerman, Nitzan
   Navon, Nir
   Glickman, Yinnon
   Ozeri, Roee
TI Measurement of the magnetic interaction between two bound electrons of two separate ions
SO NATURE
LA English
DT Article
ID trapped ions; spin; entanglement; states; force
AB Electrons have an intrinsic, indivisible, magnetic dipole aligned with their internal angular momentum (spin). The magnetic interaction between two electronic spins can therefore impose a change in their orientation. Similar dipolar magnetic interactions exist between other spin systems and have been studied experimentally. Examples include the interaction between an electron and its nucleus and the interaction between several multi-electron spin complexes(1-5). The challenge in observing such interactions for two electrons is twofold. First, at the atomic scale, where the coupling is relatively large, it is often dominated by the much larger Coulomb exchange counterpart(1). Second, on scales that are substantially larger than the atomic, the magnetic coupling is very weak and can be well below the ambient magnetic noise. Here we report the measurement of the magnetic interaction between the two ground-state spin-1/2 valence electrons of two Sr-88(+) ions, cotrapped in an electric Paul trap. We varied the ion separation, d, between 2.18 and 2.76 micrometres and measured the electrons' weak, millihertz-scale, magnetic interaction as a function of distance, in the presence of magnetic noise that was six orders of magnitude larger than the magnetic fields the electrons apply on each other. The cooperative spin dynamics was kept coherent for 15 seconds, during which spin entanglement was generated, as verified by a negative measured value of -0.16 for the swap entanglement witness. The sensitivity necessary for this measurement was provided by restricting the spin evolution to a decoherence-free subspace that is immune to collective magnetic field noise. Our measurements show a d(-3.0(4)) distance dependence for the coupling, consistent with the inverse-cube law.
C1 [Kotler, Shlomi; Akerman, Nitzan; Navon, Nir; Glickman, Yinnon; Ozeri, Roee] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science
RP Kotler, S (corresponding author), NIST, Phys Measurement Lab, Boulder, CO 80305 USA.
EM shlomi.kotler@weizmann.ac.il
FU Israeli Science Foundation; Crown Photonics Center; German-Israeli Science Foundation
NR 30
TC 56
Z9 65
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 JUN 19
PY 2014
VL 510
IS 7505
BP 376
EP 380
DI 10.1038/nature13403
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200030
PM 24943952
DA 2026-03-09
ER

PT J
AU Lee, CH
   Lü, W
   Michel, JC
   Goehring, A
   Du, J
   Song, XQ
   Gouaux, E
AF Lee, Chia-Hsueh
   Lu, Wei
   Michel, Jennifer Carlisle
   Goehring, April
   Du, Juan
   Song, Xianqiang
   Gouaux, Eric
TI NMDA receptor structures reveal subunit arrangement and pore architecture
SO NATURE
LA English
DT Article
ID size-exclusion chromatography; high-level expression; d-aspartate receptors; glutamate-receptor; crystal-structure; terminal domain; molecular-basis; channel; binding; acid
AB N-methyl-D-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.
C1 [Lee, Chia-Hsueh; Lu, Wei; Michel, Jennifer Carlisle; Goehring, April; Du, Juan; Song, Xianqiang; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Michel, Jennifer Carlisle; Goehring, April; Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU Oregon Brain Institute Graduate Student Fellowship; NIH; Vollum Institute
NR 68
TC 433
Z9 500
U1 2
U2 154
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2014
VL 511
IS 7508
BP 191
EP +
DI 10.1038/nature13548
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800037
PM 25008524
DA 2026-03-09
ER

PT J
AU Chen, X
   Grandont, L
   Li, HJ
   Hauschild, R
   Paque, S
   Abuzeineh, A
   Ralcusová, H
   Benkova, E
   Perrot-Rechenmann, C
   Friml, J
AF Chen, Xu
   Grandont, Laurie
   Li, Hongjiang
   Hauschild, Robert
   Paque, Sebastien
   Abuzeineh, Anas
   Ralcusova, Hana
   Benkova, Eva
   Perrot-Rechenmann, Catherine
   Friml, Jiri
TI Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules
SO NATURE
LA English
DT Article
ID binding protein-1; epidermal-cells; root-growth; arabidopsis; endocytosis; gravitropism; perception; nucleation; reveals; arrays
AB The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion(1). Cell expansion requires ordered arrangement of the cytoskeleton(2) but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin- and ABP I -mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses.
C1 [Chen, Xu; Li, Hongjiang; Hauschild, Robert; Ralcusova, Hana; Benkova, Eva; Friml, Jiri] Inst Sci Technol Austria 1ST Austria, A-3400 Klosterneuburg, Austria.
   [Chen, Xu; Li, Hongjiang; Abuzeineh, Anas; Ralcusova, Hana; Benkova, Eva; Friml, Jiri] Univ Ghent, Vlaams Inst Biotechnol VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Chen, Xu; Li, Hongjiang; Abuzeineh, Anas; Ralcusova, Hana; Benkova, Eva; Friml, Jiri] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium.
   [Grandont, Laurie; Paque, Sebastien; Perrot-Rechenmann, Catherine] CNRS, Saclay Plant Sci LabEx, Inst Sci Vegetal, UPR2355, F-91198 Gif Sur Yvette, France.
C3 Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay
RP Perrot-Rechenmann, C (corresponding author), CNRS, Saclay Plant Sci LabEx, Inst Sci Vegetal, UPR2355, 1 Ave Terrasse, F-91198 Gif Sur Yvette, France.
EM Catherine.Rechenmann@isv.cnrs-gif.fr; jiri.friml@ist.ac.at
FU European Research Council [ERC-2011-StG-20101109-PSDP]; ANR blanc AuxiWall project [ANR-11-BSV5-0007]; Agency for Innovation by Science and Technology (IWT); Conseil General de l'Essonne; Agence Nationale de la Recherche (ANR) [ANR-11-BSV5-0007] Funding Source: Agence Nationale de la Recherche (ANR)
NR 30
TC 112
Z9 132
U1 0
U2 140
PU NATURE PUBLISHING 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 4
PY 2014
VL 516
IS 7529
BP 90
EP U206
DI 10.1038/nature13889
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800045
PM 25409144
DA 2026-03-09
ER

PT J
AU Yadav, M
   Jhunjhunwala, S
   Phung, QT
   Lupardus, P
   Tanguay, J
   Bumbaca, S
   Franci, C
   Cheung, TK
   Fritsche, J
   Weinschenk, T
   Modrusan, Z
   Mellman, I
   Lill, JR
   Delamarre, L
AF Yadav, Mahesh
   Jhunjhunwala, Suchit
   Phung, Qui T.
   Lupardus, Patrick
   Tanguay, Joshua
   Bumbaca, Stephanie
   Franci, Christian
   Cheung, Tommy K.
   Fritsche, Jens
   Weinschenk, Toni
   Modrusan, Zora
   Mellman, Ira
   Lill, Jennie R.
   Delamarre, Lelia
TI Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing
SO NATURE
LA English
DT Article
ID t-cell exhaustion; analysis reveals; prostate-cancer; up-regulation; peptides; pd-1; antigens; patient; microenvironment; surveillance
AB Human tumours typically harbour a remarkable number of somatic mutations(1). If presented on major histocompatibility complex class I molecules (MHCI), peptides containing these mutations could potentially be immunogenic as they should be recognized as 'non-self neo-antigens by the adaptive immune system. Recent work has confirmed that mutant peptides can serve as T-cell epitopes'. However, few mutant epitopes have been described because their discovery required the laborious screening of patient tumour-infiltrating lymphocytes for their ability to recognize antigen libraries constructed following tumour exome sequencing. We sought to simplify the discovery of immunogenic mutant peptides by characterizing their general properties. We developed an approach that combines whole-exome and transcriptome sequencing analysis with mass spectrometry to identify neo-epitopes in two widely used murine tumour models. Of the >1,300 amino acid changes identified, 13% were predicted to bind MH CI, a small fraction of which were confirmed by mass spectrometry. The peptides were then structurally modelled bound to MHCI. Mutations that were solvent-exposed and therefore accessible to T-cell antigen receptors were predicted to be immunogenic. Vaccination of mice confirmed the approach, with each predicted immunogenic peptide yielding therapeutically active T-cell responses. The predictions also enabled the generation of peptide-MHCI dextramers that could be used to monitor the kinetics and distribution of the anti-tumour T-cell response before and after vaccination. These findings indicate that a suitable prediction algorithm may provide an approach for the pharmacodynamic monitoring of T-cell responses as well as for the development of personalized vaccines in cancer patients.
C1 [Yadav, Mahesh; Jhunjhunwala, Suchit; Phung, Qui T.; Lupardus, Patrick; Tanguay, Joshua; Bumbaca, Stephanie; Franci, Christian; Cheung, Tommy K.; Modrusan, Zora; Mellman, Ira; Lill, Jennie R.; Delamarre, Lelia] Genentech Inc, San Francisco, CA 94080 USA.
   [Fritsche, Jens; Weinschenk, Toni] Immat Biotechnol GmbH, D-72076 Tubingen, Germany.
C3 Roche Holding; Genentech; Roche Holding USA; Immatics Biotechnologies GmbH
RP Delamarre, L (corresponding author), Genentech Inc, San Francisco, CA 94080 USA.
EM lill.jennie@gene.com; delamarre.lelia@gene.com
NR 38
TC 977
Z9 1179
U1 2
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 NOV 27
PY 2014
VL 515
IS 7528
BP 572
EP +
DI 10.1038/nature14001
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600055
PM 25428506
DA 2026-03-09
ER

PT J
AU Necsulea, A
   Soumillon, M
   Warnefors, M
   Liechti, A
   Daish, T
   Zeller, U
   Baker, JC
   Grützner, F
   Kaessmann, H
AF Necsulea, Anamaria
   Soumillon, Magali
   Warnefors, Maria
   Liechti, Angelica
   Daish, Tasman
   Zeller, Ulrich
   Baker, Julie C.
   Gruetzner, Frank
   Kaessmann, Henrik
TI The evolution of lncRNA repertoires and expression patterns in tetrapods
SO NATURE
LA English
DT Article
ID long noncoding rnas; seq reveals; vertebrate; network; identification; conservation; architecture; sequences; alignment; lincrna
AB Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.
C1 [Necsulea, Anamaria; Soumillon, Magali; Warnefors, Maria; Liechti, Angelica; Kaessmann, Henrik] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Necsulea, Anamaria; Soumillon, Magali; Warnefors, Maria; Liechti, Angelica; Kaessmann, Henrik] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Daish, Tasman; Gruetzner, Frank] Univ Adelaide, Sch Mol & Biomed Sci, Robinson Inst, Adelaide, SA 5005, Australia.
   [Zeller, Ulrich] Humboldt Univ, Fac Agr & Hort, Dept Systemat Zool, D-10099 Berlin, Germany.
   [Baker, Julie C.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 University of Lausanne; Swiss Institute of Bioinformatics; Robinson Research Institute; Adelaide University; University of Adelaide; Humboldt University of Berlin; Stanford University
RP Necsulea, A (corresponding author), Ecole Polytech Fed Lausanne, Lab Dev Genom, CH-1015 Lausanne, Switzerland.
EM anamaria.necsulea@epfl.ch; henrik.kaessmann@unil.ch
FU MRC/Wellcome Trust [099175/Z/12/Z]; European Research Council [242597]; Swiss National Science Foundation [31003A_130287]; FEBS; European Research Council (ERC) [242597] Funding Source: European Research Council (ERC); MRC [MC_PC_15004, G0700089] Funding Source: UKRI; Swiss National Science Foundation (SNF) [31003A_130287] Funding Source: Swiss National Science Foundation (SNF); Medical Research Council [G0700089, MC_PC_15004] Funding Source: researchfish
NR 57
TC 793
Z9 932
U1 1
U2 309
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 30
PY 2014
VL 505
IS 7485
BP 635
EP +
DI 10.1038/nature12943
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000031
PM 24463510
DA 2026-03-09
ER

PT J
AU Cohn, A
   Fehr, E
   Marechal, MA
AF Cohn, Alain
   Fehr, Ernst
   Marechal, Michel Andre
TI Business culture and dishonesty in the banking industry
SO NATURE
LA English
DT Article
ID identity; honesty; trust
AB Trust in others' honesty is a key component of the long-term performance of firms, industries, and even whole countries(1-4). However, in recent years, numerous scandals involving fraud have undermined confidence in the financial industry(5-7). Contemporary commentators have attributed these scandals to the financial sector's business culture(8-9), but no scientific evidence supports this claim. Here we show that employees of a large, international bank behave, on average, honestly in a control condition. However, when their professional identity as bank employees is rendered salient, a significant proportion of them become dishonest. This effect is specific to bank employees because control experiments with employees from other industries and with students show that they do not become more dishonest when their professional identity or bank-related items are rendered salient. Our results thus suggest that the prevailing business culture in the banking industry weakens and undermines the honesty norm, implying that measures to re-establish an honest culture are very important.
C1 [Cohn, Alain; Fehr, Ernst; Marechal, Michel Andre] Univ Zurich, Dept Econ, CH-8006 Zurich, Switzerland.
C3 University of Zurich
RP Fehr, E (corresponding author), Univ Zurich, Dept Econ, CH-8006 Zurich, Switzerland.
EM ernst.fehr@econ.uzh.ch; michel.marechal@econ.uzh.ch
FU European Research Council Grant "Foundations of Economic Preferences"; Gottlieb Duttweiler Institute
NR 30
TC 402
Z9 535
U1 6
U2 259
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 4
PY 2014
VL 516
IS 7529
BP 86
EP U190
DI 10.1038/nature13977
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800044
PM 25409154
DA 2026-03-09
ER

PT J
AU Kang, EJ
   Wu, GM
   Ma, H
   Li, Y
   Tippner-Hedges, R
   Tachibana, M
   Sparman, M
   Wolf, DP
   Schöler, HR
   Mitalipov, S
AF Kang, Eunju
   Wu, Guangming
   Ma, Hong
   Li, Ying
   Tippner-Hedges, Rebecca
   Tachibana, Masahito
   Sparman, Michelle
   Wolf, Don P.
   Schoeler, Hans R.
   Mitalipov, Shoukhrat
TI Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos
SO NATURE
LA English
DT Article
ID stem-cells; zygotes; transplantation; blastomeres; activation; complex; oocytes; gene; mice
AB Successful mammalian cloning using somatic cell nuclear transfer (SCNT) into unfertilized, metaphase II (MII)-arrested oocytes attests to the cytoplasmic presence of reprogramming factors capable of inducing totipotency in somatic cell nuclei(1-3). However, these poorly defined maternal factors presumably decline sharply after fertilization, as the cytoplasm of pronuclear-stage zygotes is reportedly inactive(4,5). Recent evidence suggests that zygotic cytoplasm, if maintained at metaphase, can also support derivation of embryonic stem (ES) cells after SCNT6-8, albeit at low efficiency. This led to the conclusion that critical oocyte reprogramming factors present in the metaphase but not in the interphase cytoplasm are 'trapped' inside the nucleus during interphase and effectively removed during enucleation(9). Here we investigated the presence of reprogramming activity in the cytoplasm of interphase two-cell mouse embryos (I2C). First, the presence of candidate reprogramming factors was documented in both intact and enucleated metaphase and interphase zygotes and two-cell embryos. Consequently, enucleation did not provide a likely explanation for the inability of interphase cytoplasm to induce reprogramming. Second, when we carefully synchronized the cell cycle stage between the transplanted nucleus (ES cell, fetal fibroblast or terminally differentiated cumulus cell) and the recipient I2C cytoplasm, the reconstructed SCNT embryos developed into blastocysts and ES cells capable of contributing to traditional germline and tetraploid chimaeras. Last, direct transfer of cloned embryos, reconstructed with ES cell nuclei, into recipients resulted in live offspring. Thus, the cytoplasm of I2C supports efficient reprogramming, with cell cycle synchronization between the donor nucleus and recipient cytoplasm as the most critical parameter determining success. The ability to use interphase cytoplasm in SCNT could aid efforts to generate autologous human ES cells for regenerative applications, as donated or discarded embryos are more accessible than unfertilized MII oocytes.
C1 [Kang, Eunju; Ma, Hong; Li, Ying; Tippner-Hedges, Rebecca; Tachibana, Masahito; Sparman, Michelle; Wolf, Don P.; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Wu, Guangming; Schoeler, Hans R.] Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
C3 Oregon Health & Science University; Oregon National Primate Research Center; Max Planck Society
RP Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
EM mitalipo@ohsu.edu
FU National Institutes of Health [R01HD063276, R01HD057121, R01HD059946, R01EY021214, P51OD011092]; Leducq Fondation; Collins Medical Trust; NIH Office of the Director; National Institute on Aging [P51OD011092] Funding Source: NIH RePORTER
NR 30
TC 44
Z9 50
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 1
PY 2014
VL 509
IS 7498
BP 101
EP +
DI 10.1038/nature13134
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100047
PM 24670652
DA 2026-03-09
ER

PT J
AU Paolino, M
   Choidas, A
   Wallner, S
   Pranjic, B
   Uribesalgo, I
   Loeser, S
   Jamieson, AM
   Langdon, WY
   Ikeda, F
   Fededa, JP
   Cronin, SJ
   Nitsch, R
   Schultz-Fademrecht, C
   Eickhoff, J
   Menninger, S
   Unger, A
   Torka, R
   Gruber, T
   Hinterleitner, R
   Baier, G
   Wolf, D
   Ullrich, A
   Klebl, BM
   Penninger, JM
AF Paolino, Magdalena
   Choidas, Axel
   Wallner, Stephanie
   Pranjic, Blanka
   Uribesalgo, Iris
   Loeser, Stefanie
   Jamieson, Amanda M.
   Langdon, Wallace Y.
   Ikeda, Fumiyo
   Fededa, Juan Pablo
   Cronin, Shane J.
   Nitsch, Roberto
   Schultz-Fademrecht, Carsten
   Eickhoff, Jan
   Menninger, Sascha
   Unger, Anke
   Torka, Robert
   Gruber, Thomas
   Hinterleitner, Reinhard
   Baier, Gottfried
   Wolf, Dominik
   Ullrich, Axel
   Klebl, Bert M.
   Penninger, Josef M.
TI The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells
SO NATURE
LA English
DT Article
ID mouse nk cells; tyrosine kinases; in-vivo; cellular targets; identification; activation; warfarin; growth; axl; immunotherapy
AB Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy(1). New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies(2). Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology(3). This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.
C1 [Paolino, Magdalena; Pranjic, Blanka; Uribesalgo, Iris; Loeser, Stefanie; Ikeda, Fumiyo; Fededa, Juan Pablo; Cronin, Shane J.; Nitsch, Roberto; Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Choidas, Axel; Schultz-Fademrecht, Carsten; Eickhoff, Jan; Menninger, Sascha; Unger, Anke; Klebl, Bert M.] Lead Discovery Ctr GmbH, D-44227 Dortmund, Germany.
   [Wallner, Stephanie; Gruber, Thomas; Hinterleitner, Reinhard; Baier, Gottfried; Wolf, Dominik] Med Univ Innsbruck, A-6020 Innsbruck, Austria.
   [Jamieson, Amanda M.] Brown Univ, Dept Microbiol & Immunol, Providence, RI 02912 USA.
   [Langdon, Wallace Y.] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia.
   [Torka, Robert; Ullrich, Axel] Max Planck Inst Biochem, Dept Mol Biol, D-82152 Martinsried, Germany.
   [Wolf, Dominik] Univ Hosp Bonn, D-53127 Bonn, Germany.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Lead Discovery Center GmbH (LDC); Medical University of Innsbruck; Brown University; University of Western Australia; Max Planck Society; University of Bonn
RP Penninger, JM (corresponding author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
EM josef.penninger@imba.oeaw.ac.at
FU European Research Council (ERC); Era of Hope/DoD Innovator Award; Institute of Molecular Biotechnology (IMBA); Austrian National Foundation; Austrian Academy of Sciences; GEN-AU (AustroMouse); EU ERC; Austrian Science Fund (FWF) [P 25044] Funding Source: researchfish
NR 38
TC 382
Z9 474
U1 2
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 27
PY 2014
VL 507
IS 7493
BP 508
EP +
DI 10.1038/nature12998
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000043
PM 24553136
DA 2026-03-09
ER

PT J
AU Subtelny, AO
   Eichhorn, SW
   Chen, GR
   Sive, H
   Bartel, DP
AF Subtelny, Alexander O.
   Eichhorn, Stephen W.
   Chen, Grace R.
   Sive, Hazel
   Bartel, David P.
TI Poly(A)-tail profiling reveals an embryonic switch in translational control
SO NATURE
LA English
DT Article
ID messenger-rna degradation; genome-wide analysis; cytoplasmic polyadenylation; oocyte maturation; gene-expression; tail; transcription; micrornas; yeast; deadenylation
AB Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.
C1 [Subtelny, Alexander O.; Eichhorn, Stephen W.; Chen, Grace R.; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Subtelny, Alexander O.; Eichhorn, Stephen W.; Chen, Grace R.; Sive, Hazel; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Subtelny, Alexander O.; Eichhorn, Stephen W.; Chen, Grace R.; Sive, Hazel; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Subtelny, Alexander O.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University
RP Bartel, DP (corresponding author), MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
EM dbartel@wi.mit.edu
FU NIH [GM067031]; NIH Medical Scientist Training Program [T32GM007753]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 57
TC 495
Z9 611
U1 0
U2 153
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 3
PY 2014
VL 508
IS 7494
BP 66
EP +
DI 10.1038/nature13007
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900043
PM 24476825
DA 2026-03-09
ER

PT J
AU Pancera, M
   Zhou, TQ
   Druz, A
   Georgiev, IS
   Soto, C
   Gorman, J
   Huang, JH
   Acharya, P
   Chuang, GY
   Ofek, G
   Stewart-Jones, GBE
   Stuckey, J
   Bailer, RT
   Joyce, MG
   Louder, MK
   Tumba, N
   Yang, YP
   Zhang, BS
   Cohen, MS
   Haynes, BF
   Mascola, JR
   Morris, L
   Munro, JB
   Blanchard, SC
   Mothes, W
   Connors, M
   Kwong, PD
AF Pancera, Marie
   Zhou, Tongqing
   Druz, Aliaksandr
   Georgiev, Ivelin S.
   Soto, Cinque
   Gorman, Jason
   Huang, Jinghe
   Acharya, Priyamvada
   Chuang, Gwo-Yu
   Ofek, Gilad
   Stewart-Jones, Guillaume B. E.
   Stuckey, Jonathan
   Bailer, Robert T.
   Joyce, M. Gordon
   Louder, Mark K.
   Tumba, Nancy
   Yang, Yongping
   Zhang, Baoshan
   Cohen, Myron S.
   Haynes, Barton F.
   Mascola, John R.
   Morris, Lynn
   Munro, James B.
   Blanchard, Scott C.
   Mothes, Walther
   Connors, Mark
   Kwong, Peter D.
TI Structure and immune recognition of trimeric pre-fusion HIV-1 Env
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; envelope glycoprotein trimers; b-cell responses; neutralizing antibody; crystal-structure; influenza-virus; ebola-virus; potent neutralization; dependent epitope; core structure
AB The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 angstrom resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.
C1 [Pancera, Marie; Zhou, Tongqing; Druz, Aliaksandr; Georgiev, Ivelin S.; Soto, Cinque; Gorman, Jason; Acharya, Priyamvada; Chuang, Gwo-Yu; Ofek, Gilad; Stewart-Jones, Guillaume B. E.; Stuckey, Jonathan; Bailer, Robert T.; Joyce, M. Gordon; Louder, Mark K.; Yang, Yongping; Zhang, Baoshan; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Huang, Jinghe; Connors, Mark] NIAID, HIV Specif Immun Sect, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
   [Tumba, Nancy; Morris, Lynn] NHLS, Ctr HIV & STIs, Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa.
   [Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA.
   [Cohen, Myron S.] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA.
   [Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Med, Durham, NC 27710 USA.
   [Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Surg, Durham, NC 27710 USA.
   [Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Pediat, Durham, NC 27710 USA.
   [Haynes, Barton F.] Duke Univ, Human Vaccine Inst, Sch Med, Dept Immunol, Durham, NC 27710 USA.
   [Haynes, Barton F.] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC 27710 USA.
   [Morris, Lynn] Univ Witwatersrand, ZA-2000 Johannesburg, South Africa.
   [Morris, Lynn] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, ZA-4041 Durban, South Africa.
   [Munro, James B.; Mothes, Walther] Yale Univ, Dept Microbial Pathogenesis, New Haven, CT 06536 USA.
   [Blanchard, Scott C.] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 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 Health Laboratory Service; National Institute for Communicable Diseases (NICD); University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Duke University; Duke University; Duke University; Duke University; Duke University; University of Witwatersrand; University of Kwazulu Natal; Yale University; Cornell University; Weill Cornell Medicine
RP Kwong, PD (corresponding author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
FU Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Division of AIDS, NIAID, NIH [R21-AI100696, CHAVI-AI0678501, CHAVI-Immunogen Discovery-AI100645]; National Institutes of General Medical Sciences [P01-GM56550, R01-GM098859]; International AIDS Vaccine Initiative's (IAVI's) Neutralizing Antibody Consortium; Bill & Melinda Gates Foundation; Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry of Finance of Japan; Ministry of Foreign Affairs of the Netherlands; Norwegian Agency for Development Cooperation (NORAD); UK Department for International Development (DFID); United States Agency for International Development (USAID); US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Cancer Institute; National Heart Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute on Aging; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30AI050410] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZICAI005114, ZICAI005111, ZIAAI005023, ZICAI005112, ZIAAI005024] Funding Source: NIH RePORTER
NR 127
TC 626
Z9 766
U1 0
U2 253
PU NATURE PUBLISHING 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 23
PY 2014
VL 514
IS 7523
BP 455
EP +
DI 10.1038/nature13808
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900032
PM 25296255
DA 2026-03-09
ER

PT J
AU Shukla, AK
   Westfield, GH
   Xiao, KH
   Reis, RI
   Huang, LY
   Tripathi-Shukla, P
   Qian, J
   Li, S
   Blanc, A
   Oleskie, AN
   Dosey, AM
   Su, M
   Liang, CR
   Gu, LL
   Shan, JM
   Chen, X
   Hanna, R
   Choi, MJ
   Yao, XJ
   Klink, BU
   Kahsai, AW
   Sidhu, SS
   Koide, S
   Penczek, PA
   Kossiakoff, AA
   Woods, VL
   Kobilka, BK
   Skiniotis, G
   Lefkowitz, RJ
AF Shukla, Arun K.
   Westfield, Gerwin H.
   Xiao, Kunhong
   Reis, Rosana I.
   Huang, Li-Yin
   Tripathi-Shukla, Prachi
   Qian, Jiang
   Li, Sheng
   Blanc, Adi
   Oleskie, Austin N.
   Dosey, Anne M.
   Su, Min
   Liang, Cui-Rong
   Gu, Ling-Ling
   Shan, Jin-Ming
   Chen, Xin
   Hanna, Rachel
   Choi, Minjung
   Yao, Xiao Jie
   Klink, Bjoern U.
   Kahsai, Alem W.
   Sidhu, Sachdev S.
   Koide, Shohei
   Penczek, Pawel A.
   Kossiakoff, Anthony A.
   Woods, Virgil L., Jr.
   Kobilka, Brian K.
   Skiniotis, Georgios
   Lefkowitz, Robert J.
TI Visualization of arrestin recruitment by a G-protein-coupled receptor
SO NATURE
LA English
DT Article
ID beta(2) adrenergic-receptor; conformational-changes; electron-microscopy; crystal-structure; visual arrestin; activation; complex; beta-arrestin1; images; domain
AB G-protein-coupled receptors (GPCRs) are critically regulated by beta-arrestins, which not only desensitize G-protein signalling but also initiate a G-protein-independent wave of signalling(1-5). A recent surge of structural data on a number of GPCRs, including the beta(2) adrenergic receptor (beta(2)AR)-G-proteincomplex, has provided novel insights into the structural basis of receptor activation(6-11). However, complementary information has been lacking on the recruitment of beta-arrestins to activated GPCRs, primarily owing to challenges in obtaining stable receptor-beta-arrestin complexes for structural studies. Here we devised a strategy for forming and purifying a functional human beta(2)AR-beta-arrestin-1 complex that allowed us to visualize its architecture by single-particle negative-stain electron microscopy and to characterize the interactions between beta(2)AR and beta-arrestin 1 using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and chemical crosslinking. Electron microscopy two-dimensional averages and three dimensional reconstructions reveal bimodal binding of beta-arrestin 1 to the beta(2)AR, involving two separate sets of interactions, one with the phosphorylated carboxy terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of crosslinked residues suggest engagement of the finger loop of beta-arrestin 1 with the seven-transmembrane core of the receptor. In contrast, focal areas of raised HDX levels indicate regions of increased dynamics in both the N and C domains of beta-arrestin 1 when coupled to the beta(2)AR. A molecular model of the beta(2)AR-beta-arrestin signalling complex was made by docking activated beta-arrestin 1 and beta(2)AR crystal structures into the electron microscopymap densities with constraints provided by HDX-MS and crosslinking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented here provides a framework for better understanding the basis of GPCR regulation by arrestins.
C1 [Shukla, Arun K.; Xiao, Kunhong; Reis, Rosana I.; Huang, Li-Yin; Tripathi-Shukla, Prachi; Qian, Jiang; Blanc, Adi; Yao, Xiao Jie; Klink, Bjoern U.; Kahsai, Alem W.; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Westfield, Gerwin H.; Oleskie, Austin N.; Dosey, Anne M.; Su, Min; Skiniotis, Georgios] Univ Michigan, Sch Med, Life Sci Inst, Ann Arbor, MI 48109 USA.
   [Westfield, Gerwin H.; Oleskie, Austin N.; Dosey, Anne M.; Su, Min; Skiniotis, Georgios] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Li, Sheng; Woods, Virgil L., Jr.] Univ Calif San Diego, Dept Chem, La Jolla, CA 92093 USA.
   [Liang, Cui-Rong; Gu, Ling-Ling; Shan, Jin-Ming; Chen, Xin] Changzhou Univ, Sch Pharmaceut & Life Sci, Changzhou 213164, Jiangsu, Peoples R China.
   [Hanna, Rachel; Sidhu, Sachdev S.] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
   [Choi, Minjung; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
   [Koide, Shohei; Kossiakoff, Anthony A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Penczek, Pawel A.] Univ Texas Houston, Med Sch Houston, Dept Biochem & Mol Biol, Houston, TX 77054 USA.
   [Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Lefkowitz, Robert J.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
C3 Duke University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of California System; University of California San Diego; Changzhou University; University of Toronto; Duke University; University of Chicago; University of Texas System; University of Texas Health Science Center Houston; Stanford University; Duke University; Howard Hughes Medical Institute
RP Lefkowitz, RJ (corresponding author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM kobilka@stanford.edu; skinioti@umich.edu; lefko001@receptor-biol.duke.edu
FU National Institutes of Health [DK090165, NS028471, GM072688, GM087519, HL075443, HL16037, HL70631]; Mathers Foundation [GM60635]; Pew Scholars Program in Biomedical Sciences; Canadian Institutes of Health Research [MOP-93725]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; National Heart Lung and Blood Institute [R01HL016037] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 36
TC 418
Z9 488
U1 2
U2 243
PU NATURE PUBLISHING 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 14
PY 2014
VL 512
IS 7513
BP 218
EP +
DI 10.1038/nature13430
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700037
PM 25043026
DA 2026-03-09
ER

PT J
AU Glaser, A
   Barak, B
   Goldston, RJ
AF Glaser, Alexander
   Barak, Boaz
   Goldston, Robert J.
TI A zero-knowledge protocol for nuclear warhead verification
SO NATURE
LA English
DT Article
ID dosimetry
AB The verification of nuclear warheads for arms control involves a paradox: international inspectors will have to gain high confidence in the authenticity of submitted items while learning nothing about them. Proposed inspection systems featuring 'information barriers', designed to hide measurements stored in electronic systems, are at risk of tampering and snooping. Here we show the viability of a fundamentally new approach to nuclear warhead verification that incorporates a zero-knowledge protocol, which is designed in such a way that sensitive information is never measured and so does not need to be hidden. We interrogate submitted items with energetic neutrons, making, in effect, differential measurements of both neutron transmission and emission. Calculations for scenarios in which material is diverted from a test object show that a high degree of discrimination can be achieved while revealing zero information. Our ideas for a physical zero-knowledge system could have applications beyond the context of nuclear disarmament. The proposed technique suggests a way to perform comparisons or computations on personal or confidential data without measuring the data in the first place.
C1 [Glaser, Alexander] Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA.
   [Barak, Boaz] Microsoft Res, Cambridge, MA 02142 USA.
   [Goldston, Robert J.] Princeton Univ, Princeton Plasma Phys Lab, Princeton, NJ 08540 USA.
C3 Princeton University; Microsoft; Princeton University; United States Department of Energy (DOE); Princeton Plasma Physics Laboratory
RP Glaser, A (corresponding author), Princeton Univ, Dept Mech & Aerosp Engn, Olden St, Princeton, NJ 08544 USA.
EM aglaser@princeton.edu
FU Global Zero; US Department of State; Princeton Plasma Physics Laboratory (DOE) [DE-AC02-09CH11466]
NR 18
TC 53
Z9 69
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 JUN 26
PY 2014
VL 510
IS 7506
BP 497
EP 502
DI 10.1038/nature13457
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300038
PM 24965650
DA 2026-03-09
ER

PT J
AU Ding, T
   Schloss, PD
AF Ding, Tao
   Schloss, Patrick D.
TI Dynamics and associations of microbial community types across the human body
SO NATURE
LA English
DT Article
ID vaginal microbiome; gut microbiome; sex
AB A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow micro-biologists to better associate changes in the microbiome with changes in health(1). The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point(2,3). Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models(4) to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra-and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.
C1 [Ding, Tao; Schloss, Patrick D.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Schloss, PD (corresponding author), Univ Michigan, Dept Microbiol & Immunol, 1500 W Med Ctr, Ann Arbor, MI 48109 USA.
EM pschloss@umich.edu
FU National Institutes of Health [R01HG005975, R01GM099514, P30DK034933]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034933] Funding Source: NIH RePORTER
NR 32
TC 656
Z9 784
U1 0
U2 492
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2014
VL 509
IS 7500
BP 357
EP +
DI 10.1038/nature13178
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200038
PM 24739969
DA 2026-03-09
ER

PT J
AU Dong, HH
   Xiang, QJ
   Gu, YH
   Wang, ZS
   Paterson, NG
   Stansfeld, PJ
   He, C
   Zhang, YZ
   Wang, WJ
   Dong, CJ
AF Dong, Haohao
   Xiang, Quanju
   Gu, Yinghong
   Wang, Zhongshan
   Paterson, Neil G.
   Stansfeld, Phillip J.
   He, Chuan
   Zhang, Yizheng
   Wang, Wenjian
   Dong, Changjiang
TI Structural basis for outer membrane lipopolysaccharide insertion
SO NATURE
LA English
DT Article
ID transenvelope protein complex; beta-barrel; molecular simulation; functional-analysis; crystal-structure; cell-envelope; transport; biogenesis; lptd; translocon
AB Lipopolysaccharide (LPS) is essential for most Gram-negative bacteria and has crucial roles in protection of the bacteria fromharsh environments and toxic compounds, including antibiotics. Seven LPS transport proteins (that is, LptA-LptG) form a trans-envelope protein complex responsible for the transport of LPS from the inner membrane to the outer membrane, the mechanism for which is poorly understood. Here we report the first crystal structure of the unique integral membrane LPS translocon LptD-LptE complex. LptD forms a novel 26-stranded beta-barrel, which is to our knowledge the largest beta-barrel reported so far. LptE adopts a roll-like structure located inside the barrel of LptD to form an unprecedented two-protein 'barrel and plug' architecture. The structure, molecular dynamics simulations and functional assays suggest that the hydrophilic O-antigen and the core oligosaccharide of the LPS may pass through the barrel and the lipid A of the LPS may be inserted into the outer leaflet of the outer membrane through a lateral opening between strands beta 1 and beta 26 of LptD. These findings not only help us to understand important aspects of bacterial outer membrane biogenesis, but also have significant potential for the development of novel drugs against multi-drug resistant pathogenic bacteria.
C1 [Dong, Haohao; Gu, Yinghong; Wang, Zhongshan; Dong, Changjiang] Univ E Anglia, Norwich Med Sch, Biomed Res Ctr, Norwich NR4 7TJ, Norfolk, England.
   [Dong, Haohao; Xiang, Quanju; Wang, Zhongshan; He, Chuan] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
   [Xiang, Quanju] Sichuan Agr Univ, Dept Microbiol, Coll Resource & Environm Sci, Yaan 625000, Peoples R China.
   [Wang, Zhongshan; Zhang, Yizheng] Sichuan Univ, Coll Life Sci, Chengdu 610065, Peoples R China.
   [Paterson, Neil G.] Diamond Light Source, Didcot OX11 0DE, Oxon, England.
   [Stansfeld, Phillip J.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [He, Chuan] Wuhan Tech Coll Commun, Sch Elect & Informat, Wuhan 430065, Hubei, Peoples R China.
   [Wang, Wenjian] Sun Yat Sen Univ, Affiliated Hosp 1, Lab Dept Surg, Guangzhou 510080, Guangdong, Peoples R China.
C3 University of East Anglia; University of St Andrews; Sichuan Agricultural University; Sichuan University; Diamond Light Source; University of Oxford; Wuhan Technical College of Communication; 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.
EM wenjian166@googlemail.com; c.dong@uea.ac.uk
FU China Scholarship Council; BBSRC [BB/H000267/1, BB/L002558/1, BB/I019855/1] Funding Source: UKRI; EPSRC [EP/J010421/1] Funding Source: UKRI; MRC [G1100110] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/L002558/1, BEP17032, BB/H000267/1, BB/I019855/1, B19456, BBS/B/16011] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/J010421/1] Funding Source: researchfish; Medical Research Council [G1100110] Funding Source: researchfish
NR 44
TC 223
Z9 280
U1 4
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 JUL 3
PY 2014
VL 511
IS 7507
BP 52
EP U569
DI 10.1038/nature13464
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400033
PM 24990744
DA 2026-03-09
ER

PT J
AU Hsiao, A
   Ahmed, AMS
   Subramanian, S
   Griffin, NW
   Drewry, LL
   Petri, WA
   Haque, R
   Ahmed, T
   Gordon, JI
AF Hsiao, Ansel
   Ahmed, A. M. Shamsir
   Subramanian, Sathish
   Griffin, Nicholas W.
   Drewry, Lisa L.
   Petri, William A., Jr.
   Haque, Rashidul
   Ahmed, Tahmeed
   Gordon, Jeffrey I.
TI Members of the human gut microbiota involved in recovery from Vibrio cholerae infection
SO NATURE
LA English
DT Article
ID virulence gene-expression; escherichia-coli; colonization; autoinducer; toxin; o1; communication; database; harveyi; hapr
AB Given the global burden of diarrhoeal diseases(1), it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhoea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. Here we conduct a detailed time-series metagenomic study of faecal microbiota collected during the acute diarrhoeal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease(2). We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children(3). To define the underlying mechanisms, we introduce into gnotobiotic mice an artificial community composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children(3). One of the species, Ruminococcus obe urn, exhibits consistent increases in its relative abundance upon V. choleraeinfection of the mice. Follow-up analyses, including mono-and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obewn luxS (autoinducer-2 (AI-2) synthase) expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing-mediated repression of several V. cholerae colonization factors. Co-colonization with V. choleraemutants discloses that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.
C1 [Hsiao, Ansel; Subramanian, Sathish; Griffin, Nicholas W.; Drewry, Lisa L.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Ahmed, A. M. Shamsir] Univ Queensland, Sch Populat Hlth, Brisbane, Qld 4006, Australia.
   [Ahmed, A. M. Shamsir; Haque, Rashidul; Ahmed, Tahmeed] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Dhaka 1212, Bangladesh.
   [Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA.
   [Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA.
C3 Washington University (WUSTL); University of Queensland; International Centre for Diarrhoeal Disease Research (ICDDR); University of Virginia; University of Virginia; University of Virginia
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
EM jgordon@wustl.edu
FU Bill & Melinda Gates Foundation; National Institutes of Health [Al43596]; NIH [T32DK077653, T32Al007172]; Crohn's and Colitis Foundation of America; Australian Agency for International Development; Government of Bangladesh; Canadian International Development Agency; Swedish International Development Cooperation Agency; Department for International Development, UK; National Institute of Allergy and Infectious Diseases [T32AI007172, R01AI043596] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK077653] Funding Source: NIH RePORTER; Crohn&apos;s & Colitis Foundation; Action Medical Research [2158] Funding Source: researchfish
NR 40
TC 299
Z9 388
U1 1
U2 156
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2014
VL 515
IS 7527
BP 423
EP +
DI 10.1038/nature13738
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600048
PM 25231861
DA 2026-03-09
ER

PT J
AU Lowenstern, JB
   Evans, WC
   Bergfeld, D
   Hunt, AG
AF Lowenstern, J. B.
   Evans, W. C.
   Bergfeld, D.
   Hunt, A. G.
TI Prodigious degassing of a billion years of accumulated radiogenic helium at Yellowstone
SO NATURE
LA English
DT Article
ID noble-gases; continental-crust; volcanic system; national-park; co2 emissions; transport; flux; fluids; basin; groundwater
AB Helium is used as a critical tracer throughout the Earth sciences, where its relatively simple isotopic systematics is used to trace degassing from the mantle, to date groundwater and to time the rise of continents(1). The hydrothermal system at Yellowstone National Park is famous for its high helium-3/helium-4 isotope ratio, commonly cited as evidence for a deep mantle source for the Yellowstone hotspot(2). However, much of the helium emitted from this region is actually radiogenic helium-4 produced within the crust by alpha-decay of uranium and thorium. Here we show, by combining gas emission rates with chemistry and isotopic analyses, that crustal helium-4 emission rates from Yellowstone exceed (by orders of magnitude) any conceivable rate of generation within the crust. It seems that helium has accumulated for (at least) many hundreds of millions of years in Archaean (more than 2.5 billion years old) cratonic rocks beneath Yellowstone, only to be liberated over the past two million years by intense crustal metamorphism induced by the Yellowstone hotspot. Our results demonstrate the extremes in variability of crustal helium efflux on geologic time-scales and imply crustal-scale open-system behaviour of helium in tectonically and magmatically active regions.
C1 [Lowenstern, J. B.; Evans, W. C.; Bergfeld, D.] US Geol Survey, Menlo Pk, CA 94025 USA.
   [Hunt, A. G.] US Geol Survey, Denver, CO 80225 USA.
C3 United States Department of the Interior; United States Geological Survey; United States Department of the Interior; United States Geological Survey
RP Lowenstern, JB (corresponding author), US Geol Survey, 345 Middlefield Rd, Menlo Pk, CA 94025 USA.
EM jlwnstrn@usgs.gov
NR 37
TC 82
Z9 99
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 FEB 20
PY 2014
VL 506
IS 7488
BP 355
EP +
DI 10.1038/nature12992
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800038
PM 24553240
DA 2026-03-09
ER

PT J
AU Martins, VC
   Busch, K
   Juraeva, D
   Blum, C
   Ludwig, C
   Rasche, V
   Lasitschka, F
   Mastitsky, SE
   Brors, B
   Hielscher, T
   Fehling, HJ
   Rodewald, HR
AF Martins, Vera C.
   Busch, Katrin
   Juraeva, Dilafruz
   Blum, Carmen
   Ludwig, Carolin
   Rasche, Volker
   Lasitschka, Felix
   Mastitsky, Sergey E.
   Brors, Benedikt
   Hielscher, Thomas
   Fehling, Hans Joerg
   Rodewald, Hans-Reimer
TI Cell competition is a tumour suppressor mechanism in the thymus
SO NATURE
LA English
DT Article
ID molecular pathogenesis; hematopoietic stem; notch1 mutations; c-kit; mice; expression; expansion; leukemia; activation; thymocytes
AB Cell competitionis an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between 'young' bone-marrow-derived and 'old' thymus-resident progenitors that, although genetically identical, execute differential gene expression programs. Disruption of cell competition leads to progenitor self-renewal, upregulation of Hmga1, transformation, and T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in pathology, genomic lesions, leukaemia-associated transcripts, and activating mutations in Notch1. Hence, cell competition is a tumour suppressor mechanism in the thymus. Failure to select fit progenitors through cell competition may explain leukaemia in X-linked severe combined immune deficiency patients who showed thymus-autonomous T-cell development after therapy with gene-corrected autologous progenitors.
C1 [Martins, Vera C.; Busch, Katrin; Rodewald, Hans-Reimer] German Canc Res Ctr, Div Cellular Immunol, D-69120 Heidelberg, Germany.
   [Martins, Vera C.; Blum, Carmen; Ludwig, Carolin; Fehling, Hans Joerg] Univ Ulm, Inst Immunol, D-89081 Ulm, Germany.
   [Juraeva, Dilafruz; Mastitsky, Sergey E.; Brors, Benedikt] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Rasche, Volker] Univ Ulm, Core Facil Small Anim MRI, D-89081 Ulm, Germany.
   [Lasitschka, Felix] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany.
   [Hielscher, Thomas] German Canc Res Ctr, Div Biostat, D-69120 Heidelberg, Germany.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Ulm University; Helmholtz Association; German Cancer Research Center (DKFZ); Ulm University; Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Rodewald, HR (corresponding author), German Canc Res Ctr, Div Cellular Immunol, D-69120 Heidelberg, Germany.
EM hr.rodewald@dkfz.de
FU ERC Advanced Grant [233074]; DFG-SFB938-project L; Helmholtz PCCC Alliance
NR 45
TC 189
Z9 222
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 MAY 22
PY 2014
VL 509
IS 7501
BP 465
EP +
DI 10.1038/nature13317
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000033
PM 24828041
DA 2026-03-09
ER

PT J
AU Mähönen, AP
   ten Tusscher, K
   Siligato, R
   Smetana, O
   Díaz-Triviño, S
   Salojärvi, J
   Wachsman, G
   Prasad, K
   Heidstra, R
   Scheres, B
AF Maehoenen, Ari Pekka
   ten Tusscher, Kirsten
   Siligato, Riccardo
   Smetana, Ondrej
   Diaz-Trivino, Sara
   Salojaervi, Jarkko
   Wachsman, Guy
   Prasad, Kalika
   Heidstra, Renze
   Scheres, Ben
TI PLETHORA gradient formation mechanism separates auxin responses
SO NATURE
LA English
DT Article
ID inflammatory breast-cancer; chemoattractant protein-1; transcription factors; carcinoma cells; arabidopsis; root; angiogenesis; expression; transport; growth
AB During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation, thus generating three distinct developmental zones: the meristem, elongation zone and differentiation zone(1). Simultaneously, plants display tropisms, rapid adjustments of their direction of growth to adapt to environmental conditions. It is unclear how stable zonation is maintained during transient adjustments in growth direction. In Arabi-dopsis roots, many aspects of zonation are controlled by the phytohormone auxin and auxin-induced PLETHORA(PLT) transcription factors, both of which display a graded distribution with a maximum near the root tip(2-12). In addition, auxin is also pivotal for tropic responses(13,14). Here, using an iterative experimental and computational approach, we show how an interplay between auxin and PLTs controls zonation and gravitropism. We find that the PLT gradient is not a direct, proportionate readout of the auxin gradient. Rather, prolonged high auxin levels generate a narrow PLT transcription domain from which a gradient of PLT protein is subsequently generated through slow growth dilution and cell-to-cell movement. The resulting PLT levels define the location of developmental zones. In addition to slowly promoting PLT transcription, auxin also rapidly influences division, expansion and differentiation rates. We demonstrate how this specific regulatory design in which auxin cooperates with PLTs through different mechanisms and on different time scales enables both the fast tropic environmental responses and stable zonation dynamics necessary for coordinated cell differentiation.
C1 [Maehoenen, Ari Pekka; Siligato, Riccardo; Smetana, Ondrej] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
   [Maehoenen, Ari Pekka; Diaz-Trivino, Sara; Wachsman, Guy; Prasad, Kalika; Heidstra, Renze; Scheres, Ben] Univ Utrecht, Dept Biol, NL-3584 CH Utrecht, Netherlands.
   [Maehoenen, Ari Pekka; Siligato, Riccardo; Smetana, Ondrej; Salojaervi, Jarkko] Univ Helsinki, Dept Biosci, FIN-00014 Helsinki, Finland.
   [ten Tusscher, Kirsten] Univ Utrecht, NL-3584 CH Utrecht, Netherlands.
   [Diaz-Trivino, Sara; Heidstra, Renze; Scheres, Ben] Wageningen Univ Res, NL-6708 PB Wageningen, Netherlands.
C3 University of Helsinki; Utrecht University; University of Helsinki; Utrecht University; Wageningen University & Research
RP Mähönen, AP (corresponding author), Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
EM AriPekka.Mahonen@helsinki.fi; ben.scheres@wur.nl
FU Human Frontier Science Program fellowship; European Research Council Advanced Investigator Fellowship SysArc; SPINOZA award; ALW-NWO European Research Area Network Plant Genomics (ERAPG) grant [855.50.017]; Academy of Finland; Biocentrum Helsinki; University of Helsinki; Integrative Life Science Doctoral Program; Marie Curie Intra-European Fellowship [IEF-2008-237643]; Netherlands Organisation for Scientific Research (NWO)-Horizon grant; NWO-ALW grant; EMBO Long-term fellowship
NR 62
TC 333
Z9 366
U1 3
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 NOV 6
PY 2014
VL 515
IS 7525
BP 125
EP +
DI 10.1038/nature13663
PG 39
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500043
PM 25156253
DA 2026-03-09
ER

PT J
AU Ripke, S
   Neale, BM
   Corvin, A
   Walters, JTR
   Farh, KH
   Holmans, PA
   Lee, P
   Bulik-Sullivan, B
   Collier, DA
   Huang, HL
   Pers, TH
   Agartz, I
   Agerbo, E
   Albus, M
   Alexander, M
   Amin, F
   Bacanu, SA
   Begemann, M
   Belliveau, RA
   Bene, J
   Bergen, SE
   Bevilacqua, E
   Bigdeli, TB
   Black, DW
   Bruggeman, R
   Buccola, NG
   Buckner, RL
   Byerley, W
   Cahn, W
   Cai, GQ
   Campion, D
   Cantor, RM
   Carr, VJ
   Carrera, N
   Catts, SV
   Chambert, KD
   Chan, RCK
   Chen, RYL
   Chen, EYH
   Cheng, W
   Cheung, EFC
   Chong, SA
   Cloninger, CR
   Cohen, D
   Cohen, N
   Cormican, P
   Craddock, N
   Crowley, JJ
   Curtis, D
   Davidson, M
   Davis, KL
   Degenhardt, F
   Del Favero, J
   Demontis, D
   Dikeos, D
   Dinan, T
   Djurovic, S
   Donohoe, G
   Drapeau, E
   Duan, J
   Dudbridge, F
   Durmishi, N
   Eichhammer, P
   Eriksson, J
   Escott-Price, V
   Essioux, L
   Fanous, AH
   Farrell, MS
   Frank, J
   Franke, L
   Freedman, R
   Freimer, NB
   Friedl, M
   Friedman, JI
   Fromer, M
   Genovese, G
   Georgieva, L
   Giegling, I
   Giusti-Rodríguez, P
   Godard, S
   Goldstein, JI
   Golimbet, V
   Gopal, S
   Gratten, J
   de Haan, L
   Hammer, C
   Hamshere, ML
   Hansen, M
   Hansen, T
   Haroutunian, V
   Hartmann, AM
   Henskens, FA
   Herms, S
   Hirschhorn, JN
   Hoffmann, P
   Hofman, A
   Hollegaard, MV
   Hougaard, DM
   Ikeda, M
   Joa, I
   Julià, A
   Kahn, RS
   Kalaydjieva, L
   Karachanak-Yankova, S
   Karjalainen, J
   Kavanagh, D
   Keller, MC
   Kennedy, JL
   Khrunin, A
   Kim, Y
   Klovins, J
   Knowles, JA
   Konte, B
   Kucinskas, V
   Kucinskiene, ZA
   Kuzelova-Ptackova, H
   Kähler, AK
   Laurent, C
   Keong, JLC
   Lee, SH
   Legge, SE
   Lerer, B
   Li, MX
   Li, T
   Liang, KY
   Lieberman, J
   Limborska, S
   Loughland, CM
   Lubinski, J
   Lönnqvist, J
   Macek, M
   Magnusson, PKE
   Maher, BS
   Maier, W
   Mallet, J
   Marsal, S
   Mattheisen, M
   Mattingsdal, M
   McCarley, RW
   McDonald, C
   McIntosh, AM
   Meier, S
   Meijer, CJ
   Melegh, B
   Melle, I
   Mesholam-Gately, RI
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   Amin, Farooq
   Bacanu, Silviu A.
   Begemann, Martin
   Belliveau, Richard A., Jr.
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   Bergen, Sarah E.
   Bevilacqua, Elizabeth
   Bigdeli, Tim B.
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   Bruggeman, Richard
   Buccola, Nancy G.
   Buckner, Randy L.
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   Andreassen, Ole A.
   Blackwood, Douglas H. R.
   Bramon, Elvira
   Buxbaum, Joseph D.
   Borglum, Anders D.
   Cichon, Sven
   Darvasi, Ariel
   Domenici, Enrico
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   Esko, Tonu
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   Hultman, Christina M.
   Iwata, Nakao
   Jablensky, Assen V.
   Jonsson, Erik G.
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   Kirov, George
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   McQuillin, Andrew
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   Mortensen, Preben B.
   Mowry, Bryan J.
   Noethen, Markus M.
   Ophoff, Roel A.
   Owen, Michael J.
   Palotie, Aarno
   Pato, Carlos N.
   Petryshen, Tracey L.
   Posthuma, Danielle
   Rietschel, Marcella
   Riley, Brien P.
   Rujescu, Dan
   Sham, Pak C.
   Sklar, Pamela
   St Clair, David
   Weinberger, Daniel R.
   Wendland, Jens R.
   Werge, Thomas
   Daly, Mark J.
   Sullivan, Patrick F.
   O'Donovan, Michael C.
TI Biological insights from 108 schizophrenia-associated genetic loci
SO NATURE
LA English
DT Article
ID genome-wide association; common variants; conferring risk; mutations
AB Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
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   [Giegling, Ina; Rujescu, Dan] Univ Munich, Dept Psychiat, D-80336 Munich, Germany.
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   [Herms, Stefan; Hoffmann, Per; Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, CH-4058 Basel, Switzerland.
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   [Kennedy, James L.; Zai, Clement C.; Knight, Jo] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
   [Kennedy, James L.; Knight, Jo] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
   [Khrunin, Andrey; Limborska, Svetlana; Slominsky, Petr] Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia.
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   [Kuzelova-Ptackova, Hana; Macek, Milan, Jr.] Univ Hosp Motol, Prague 15006, Czech Republic.
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   [Keong, Jimmy Lee Chee] Duke NUS Grad Med Sch, Singapore 169857, Singapore.
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   [Maher, Brion S.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
   [Maier, Wolfgang] Univ Bonn, Dept Psychiat, D-53127 Bonn, Germany.
   [Mallet, Jacques] Hop La Pitie Salpetriere, CNRS, Lab Genet Mol Neurotransmiss & Proc Neurodegenera, F-75013 Paris, France.
   [Mattheisen, Manuel] Univ Bonn, Dept Genom Math, D-53127 Bonn, Germany.
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   [McIntosh, Andrew M.; Blackwood, Douglas H. R.] Univ Edinburgh, Div Psychiat, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Melle, Ingrid; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway.
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   [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, D-80336 Munich, Germany.
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   [Nestadt, Gerald; Pulver, Ann E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
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   [Thirumalai, Srinivas] Berkshire Healthcare NHS Fdn Trust, Bracknell RG12 1BQ, Berks, England.
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   [Wildenauer, Dieter B.; Jablensky, Assen V.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia.
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   [Zheng, Xuebin; Liu, Jianjun] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore.
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   [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
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   [Darvasi, Ariel] Hebrew Univ Jerusalem, Dept Genet, IL-91905 Jerusalem, Israel.
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   [Jablensky, Assen V.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Ctr Clin Res Neuropsychiat, Perth, WA 6000, Australia.
   [Kendler, Kenneth S.; Riley, Brien P.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA.
   [Kendler, Kenneth S.; Riley, Brien P.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23298 USA.
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   [Lencz, Todd; Malhotra, Anil K.] Hofstra NS LIJ Sch Med, Hempstead, NY 11549 USA.
   [Lencz, Todd; Malhotra, Anil K.] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA.
   [Liu, Jianjun] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
   [Mowry, Bryan J.] Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld 4076, Australia.
   [Petryshen, Tracey L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   [Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 Rotterdam, Netherlands.
   [Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Complex Trait Genet, NL-1081 Amsterdam, Netherlands.
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   [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
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RP O'Donovan, MC (corresponding author), Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales.
EM odonovanmc@cardiff.ac.uk
FU US National Institute of Mental Health [U01 MH094421]; MRC [G0901310, G0801418, G1000718, G0800509, G0601635, G1100583] Funding Source: UKRI; Chief Scientist Office [SCD/12] Funding Source: researchfish; Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish; Medical Research Council [G1100583, G1000718, 1247950, G0601635, G0800509, G0901310, G0801418, MR/L010305/1] Funding Source: researchfish; National Institute for Health Research [PDA/02/06/016] Funding Source: researchfish; National Institute of Mental Health [T32MH020030, R01MH100141] Funding Source: NIH RePORTER
NR 50
TC 5945
Z9 6693
U1 23
U2 1313
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2014
VL 511
IS 7510
BP 421
EP +
DI 10.1038/nature13595
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700037
PM 25056061
DA 2026-03-09
ER

PT J
AU Schiering, C
   Krausgruber, T
   Chomka, A
   Fröhlich, A
   Adelmann, K
   Wohlfert, EA
   Pott, J
   Griseri, T
   Bollrath, J
   Hegazy, AN
   Harrison, OJ
   Owens, BMJ
   Löhning, M
   Belkaid, Y
   Fallon, PG
   Powrie, F
AF Schiering, Chris
   Krausgruber, Thomas
   Chomka, Agnieszka
   Froehlich, Anja
   Adelmann, Krista
   Wohlfert, Elizabeth A.
   Pott, Johanna
   Griseri, Thibault
   Bollrath, Julia
   Hegazy, Ahmed N.
   Harrison, Oliver J.
   Owens, Benjamin M. J.
   Loehning, Max
   Belkaid, Yasmine
   Fallon, Padraic G.
   Powrie, Fiona
TI The alarmin IL-33 promotes regulatory T-cell function in the intestine
SO NATURE
LA English
DT Article
ID ameliorates experimental colitis; inflammatory-bowel-disease; transcription factor foxp3; ulcerative-colitis; dependent colitis; soluble st2; cytokine; mice; responses; complex
AB FOXP3+ regulatory T cells (T-reg cells) are abundant in the intestine, where they prevent dysregulated inflammatory responses to self and environmental stimuli. It is now appreciated that T-reg cells acquire tissue-specific adaptations that facilitate their survival and function(1); however, key host factors controlling theT(reg) response in the intestine are poorly understood. The interleukin (IL)-1 family member IL-33 is constitutively expressed in epithelial cells at barrier sites(2), where it functions as an endogenous danger signal, or alarmin, in response to tissue damage(3). Recent studies in humans have described high levels of IL-33 in inflamed lesions of inflammatory bowel disease patients(4-7), suggesting a role for this cytokine in disease pathogenesis. In the intestine, both protective and pathological roles for IL-33 have been described in murine models of acute colitis(8-11), but its contribution to chronic inflammation remains ill defined. Here we show in mice that the IL-33 receptor ST2 is preferentially expressed on colonic T-reg cells, where it promotes T-reg function and adaptation to the inflammatory environment. IL-33 signalling in T cells stimulates T-reg responses in several ways. First, it enhances transforming growth factor (TGF)-beta 1-mediated differentiation of T-reg cells and, second, it provides a necessary signal for T-reg-cell accumulation and maintenance in inflamed tissues. Strikingly, IL-23, a key pro-inflammatory cytokine in the pathogenesis of inflammatory bowel disease, restrained T-reg responses through inhibition of IL-33 responsiveness. These results demonstrate a hitherto unrecognized link between an endogenous mediator of tissue damage and a major anti-inflammatory pathway, and suggest that the balance between IL-33 and IL-23 may be a key controller of intestinal immune responses.
C1 [Schiering, Chris; Krausgruber, Thomas; Chomka, Agnieszka; Adelmann, Krista; Griseri, Thibault; Bollrath, Julia; Hegazy, Ahmed N.; Owens, Benjamin M. J.; Powrie, Fiona] Univ Oxford, John Radcliffe Hosp, Translat Gastroenterol Unit, Nuffield Dept Clin Med,Expt Med Div, Oxford OX3 9DU, England.
   [Froehlich, Anja; Loehning, Max] Charite, Dept Rheumatol & Clin Immunol, D-10117 Berlin, Germany.
   [Froehlich, Anja; Loehning, Max] German Rheumatism Res Ctr DRFZ, D-10117 Berlin, Germany.
   [Wohlfert, Elizabeth A.; Belkaid, Yasmine] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Lab Parasit Dis,NIH, Bethesda, MD 20892 USA.
   [Pott, Johanna; Harrison, Oliver J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Fallon, Padraic G.] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Dublin 2, Ireland.
C3 University of Oxford; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Oxford; Trinity College Dublin
RP Powrie, F (corresponding author), Univ Oxford, John Radcliffe Hosp, Translat Gastroenterol Unit, Nuffield Dept Clin Med,Expt Med Div, Oxford OX3 9DU, England.
EM fiona.powrie@path.ox.ac.uk
FU Wellcome Trust; Fondation Louis Jeantet; European Molecular Biology Organization long-term fellowship [ALTF 116-2012]; Science Foundation Ireland; Volkswagen Foundation (Lichtenberg Program); BMBF (e:Bio/T-Sys); Oxford-UCB Pharma Postdoctoral Fellowship; National Institute of Allergy and Infectious Diseases [ZIAAI001132, ZIAAI001133] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/I005609/1] Funding Source: researchfish; Wellcome Trust [095688/Z/11/Z] Funding Source: researchfish; BBSRC [BB/I005609/1] Funding Source: UKRI; Wellcome Trust [095688/Z/11/Z] Funding Source: Wellcome Trust
NR 36
TC 839
Z9 958
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 SEP 25
PY 2014
VL 513
IS 7519
BP 564
EP +
DI 10.1038/nature13577
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800044
PM 25043027
DA 2026-03-09
ER

PT J
AU Maksimovic, S
   Nakatani, M
   Baba, Y
   Nelson, AM
   Marshall, KL
   Wellnitz, SA
   Firozi, P
   Woo, SH
   Ranade, S
   Patapoutian, A
   Lumpkin, EA
AF Maksimovic, Srdjan
   Nakatani, Masashi
   Baba, Yoshichika
   Nelson, Aislyn M.
   Marshall, Kara L.
   Wellnitz, Scott A.
   Firozi, Pervez
   Woo, Seung-Hyun
   Ranade, Sanjeev
   Patapoutian, Ardem
   Lumpkin, Ellen A.
TI Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors
SO NATURE
LA English
DT Article
ID sensory neurons; transduction; discrimination; mechanisms; components; channels
AB Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns(1). Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters(2,3); however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells(4,5) and make 'synapse-like' contacts(5,6) with slowly adapting type I (SAI) afferents(7-9). These complexes, which encode spatial features such as edges and texture(1), localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.
C1 [Maksimovic, Srdjan; Nakatani, Masashi; Baba, Yoshichika; Nelson, Aislyn M.; Marshall, Kara L.; Lumpkin, Ellen A.] Columbia Univ, Dept Dermatol, New York, NY 10032 USA.
   [Nakatani, Masashi] Keio Univ, Grad Sch Syst Design & Management, Yokohama, Kanagawa 2238526, Japan.
   [Nelson, Aislyn M.; Wellnitz, Scott A.; Firozi, Pervez] Baylor Coll Med, Dept Neurosci, Houston, TX 77006 USA.
   [Woo, Seung-Hyun; Ranade, Sanjeev; Patapoutian, Ardem] Scripps Res Inst, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Lumpkin, Ellen A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Lumpkin, Ellen A.] Columbia Univ, Program Neurobiol & Behav, New York, NY 10032 USA.
C3 Columbia University; Keio University; Baylor College of Medicine; Howard Hughes Medical Institute; Scripps Research Institute; Columbia University; Columbia University
RP Lumpkin, EA (corresponding author), Columbia Univ, Dept Dermatol, New York, NY 10032 USA.
EM eal2166@columbia.edu
FU NIH/NIAMS [R01AR051219, R21AR062307, R01DE022358]; NIH/NINDS [F32NS080544]; JSPS [24-7585]; McNair Foundation;  [5T32HL087745-05]; Grants-in-Aid for Scientific Research [12J07585] Funding Source: KAKEN; National Cancer Institute [P30CA125123, P30CA013696] Funding Source: NIH RePORTER
NR 37
TC 427
Z9 514
U1 5
U2 190
PU NATURE PUBLISHING 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 29
PY 2014
VL 509
IS 7502
BP 617
EP 621
DI 10.1038/nature13250
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100048
PM 24717432
DA 2026-03-09
ER

PT J
AU Rozitis, B
   MacLennan, E
   Emery, JP
AF Rozitis, Ben
   MacLennan, Eric
   Emery, Joshua P.
TI Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075) 1950 DA
SO NATURE
LA English
DT Article
ID thermal infrared observations; solar-system; 101955 bennu; yarkovsky; surfaces; regolith; hayabusa; itokawa; impact; orbit
AB Space missions(1) and ground-based observations(2) have shown that some asteroids are loose collections of rubble rather than solid bodies. The physical behaviour of such 'rubble-pile' asteroids has been traditionally described using only gravitational and frictional forces within a granular material(3). Cohesive forces in the form of small van der Waals forces between constituent grains have recently been predicted to be important for small rubble piles (ten kilometres across or less), and could potentially explain fast rotation rates in the small-asteroid population(4-6). The strongest evidence so far has come from an analysis of the rotational breakup of the main-belt comet P/2013 R3 (ref. 7), although that was indirect and poorly constrained by observations. Here we report that the kilometre-sized asteroid (29075) 1950 DA(ref. 8) is a rubble pile that is rotating faster than is allowed by gravity and friction. We find that cohesive forces are required to prevent surface mass shedding and structural failure, and that the strengths of the forces are comparable to, though somewhat less than, the forces found between the grains of lunar regolith.
C1 [Rozitis, Ben; MacLennan, Eric; Emery, Joshua P.] Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA.
C3 University of Tennessee System; University of Tennessee Knoxville
RP Rozitis, B (corresponding author), Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA.
EM brozitis@utk.edu
FU Planetary Science Division of NASA; NASA [NNM10AA11C, NNX12AP32G]; STFC [ST/L000776/1] Funding Source: UKRI; NASA [13277, NNX12AP32G] Funding Source: Federal RePORTER; Science and Technology Facilities Council [ST/L000776/1] Funding Source: researchfish
NR 30
TC 161
Z9 174
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 AUG 14
PY 2014
VL 512
IS 7513
BP 174
EP +
DI 10.1038/nature13632
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700027
PM 25119234
DA 2026-03-09
ER

PT J
AU Ramasamy, SK
   Kusumbe, AP
   Wang, L
   Adams, RH
AF Ramasamy, Saravana K.
   Kusumbe, Anjali P.
   Wang, Lin
   Adams, Ralf H.
TI Endothelial Notch activity promotes angiogenesis and osteogenesis in bone
SO NATURE
LA English
DT Article
ID mesenchymal stem-cells; osteoblast differentiation; transcription; noggin; vegf; protocol; ligands; culture; jagged1; marrow
AB Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells(1,2). Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours(3,4). Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.
C1 [Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
   [Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
C3 Max Planck Society; University of Munster
RP Adams, RH (corresponding author), Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
EM 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 AngioBone]
NR 28
TC 830
Z9 1002
U1 5
U2 359
PU NATURE PUBLISHING 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 20
PY 2014
VL 507
IS 7492
BP 376
EP +
DI 10.1038/nature13146
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000038
PM 24647000
DA 2026-03-09
ER

PT J
AU Nabavi, S
   Fox, R
   Proulx, CD
   Lin, JY
   Tsien, RY
   Malinow, R
AF Nabavi, Sadegh
   Fox, Rocky
   Proulx, Christophe D.
   Lin, John Y.
   Tsien, Roger Y.
   Malinow, Roberto
TI Engineering a memory with LTD and LTP
SO NATURE
LA English
DT Article
ID long-term potentiation; fear; amygdala; expression; neurons; acquisition; receptors; induction; networks; circuits
AB It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD)(1). However, the causal link between these synaptic processes and memory has been difficult to demonstrate(2). Here we show that fear conditioning(3-8), a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning(3-8). Subsequent optogenetic delivery of LTD conditioning to the auditory input inactivates memory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.
C1 [Nabavi, Sadegh; Fox, Rocky; Proulx, Christophe D.; Malinow, Roberto] Univ Calif San Diego, Dept Neurosci, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
   [Nabavi, Sadegh; Fox, Rocky; Proulx, Christophe D.; Malinow, Roberto] Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Lin, John Y.; Tsien, Roger Y.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Tsien, Roger Y.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
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; Howard Hughes Medical Institute
RP Malinow, R (corresponding author), Univ Calif San Diego, Dept Neurosci, Ctr Neural Circuits & Behav, La Jolla, CA 92093 USA.
EM rmalinow@ucsd.edu
FU NIH [MH049159, NS27177]; Cure Alzheimer's Foundation
NR 36
TC 737
Z9 913
U1 4
U2 289
PU NATURE PUBLISHING 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 17
PY 2014
VL 511
IS 7509
BP 348
EP +
DI 10.1038/nature13294
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200036
PM 24896183
DA 2026-03-09
ER

PT J
AU Tadhunter, C
   Morganti, R
   Rose, M
   Oonk, JBR
   Oosterloo, T
AF Tadhunter, C.
   Morganti, R.
   Rose, M.
   Oonk, J. B. R.
   Oosterloo, T.
TI Jet acceleration of the fast molecular outflows in the Seyfert galaxy IC 5063
SO NATURE
LA English
DT Article
ID radio galaxy; star-formation; black-holes; cold gas; feedback; emission; quasars; nucleus; growth; warm
AB Massive outflows driven by active galactic nuclei are widely recognized to have a key role in the evolution of galaxies(1-4), by heating the ambient gas, expelling it from the nuclear regions, and thereby affecting the star-formation histories of the galaxy bulges. It has been proposed that the powerful jets of relativistic particles (such as electrons) launched by some active nuclei can both accelerate(5-7) and heat(8) the molecular gas, which often dominates the mass budgets of the outflows(5,9). Clear evidence for this mechanism, in the form of detailed associations between the molecular gas kinematics and features in the radio-emitting jets, has however been lacking. Here we report that the warm molecular hydrogen gas in the western radio lobe of the Seyfert galaxy IC 5063 is moving at high velocities-up to about 600 kilometres per second-relative to the galaxy disk. This suggests that the molecules have been accelerated by fast shocks driven into the interstellar medium by the expanding radio jets. These results demonstrate the general feasibility of accelerating molecular outflows in fast shocks driven by active nuclei.
C1 [Tadhunter, C.] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
   [Morganti, R.; Oonk, J. B. R.; Oosterloo, T.] Netherlands Inst Radio Astron, ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Morganti, R.; Oosterloo, T.] Univ Groningen, Kapteyn Astron Inst, NL-9700 AV Groningen, Netherlands.
   [Rose, M.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 University of Sheffield; University of Groningen; Kapteyn Astronomical Institute; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution
RP Tadhunter, C (corresponding author), Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
EM c.tadhunter@sheffield.ac.uk
FU European Southern Observatory, Chile [290.B-5162]; UK Science and Technology Research Council; European Research Council under the European Union [RADIOLIFE-320745]; Science and Technology Facilities Council [ST/J001589/1] Funding Source: researchfish; STFC [ST/J001589/1] Funding Source: UKRI
NR 30
TC 120
Z9 131
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 JUL 24
PY 2014
VL 511
IS 7510
BP 440
EP 443
DI 10.1038/nature13520
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700040
PM 25043049
DA 2026-03-09
ER

PT J
AU Grefenstette, BW
   Harrison, FA
   Boggs, SE
   Reynolds, SP
   Fryer, CL
   Madsen, KK
   Wik, DR
   Zoglauer, A
   Ellinger, CI
   Alexander, DM
   An, H
   Barret, D
   Christensen, FE
   Craig, WW
   Forster, K
   Giommi, P
   Hailey, CJ
   Hornstrup, A
   Kaspi, VM
   Kitaguchi, T
   Koglin, JE
   Mao, PH
   Miyasaka, H
   Mori, K
   Perri, M
   Pivovaroff, MJ
   Puccetti, S
   Rana, V
   Stern, D
   Westergaard, NJ
   Zhang, WW
AF Grefenstette, B. W.
   Harrison, F. A.
   Boggs, S. E.
   Reynolds, S. P.
   Fryer, C. L.
   Madsen, K. K.
   Wik, D. R.
   Zoglauer, A.
   Ellinger, C. I.
   Alexander, D. M.
   An, H.
   Barret, D.
   Christensen, F. E.
   Craig, W. W.
   Forster, K.
   Giommi, P.
   Hailey, C. J.
   Hornstrup, A.
   Kaspi, V. M.
   Kitaguchi, T.
   Koglin, J. E.
   Mao, P. H.
   Miyasaka, H.
   Mori, K.
   Perri, M.
   Pivovaroff, M. J.
   Puccetti, S.
   Rana, V.
   Stern, D.
   Westergaard, N. J.
   Zhang, W. W.
TI Asymmetries in core-collapse supernovae from maps of radioactive 44Ti in Cassiopeia A
SO NATURE
LA English
DT Article
ID a supernova; 3-dimensional structure; remnant cassiopeia; ray; explosion; ejecta; cas; hydrodynamics; constraints; evolution
AB Asymmetry is required by most numerical simulations of stellar core-collapse explosions, but the form it takes differs significantly among models. The spatial distribution of radioactive Ti-44, synthesized in an exploding star near the boundary between material falling back onto the collapsing core and that ejected into the surrounding medium(1), directly probes the explosion asymmetries. Cassiopeia A is a young(2), nearby(3), core-collapse(4) remnant from which Ti-44 emission has previously been detected(5-8) but not imaged. Asymmetries in the explosion have been indirectly inferred from a high ratio of observed Ti-44 emission to estimated Ni-56 emission(9), from optical light echoes(10), and from jet-like features seen in the X-ray(11) and optical(12) ejecta. Here we report spatial maps and spectral properties of the Ti-44 in Cassiopeia A. This may explain the unexpected lack of correlation between the Ti-44 and iron X-ray emission, the latter being visible only in shock-heated material. The observed spatial distribution rules out symmetric explosions even with a high level of convective mixing, as well as highly asymmetric bipolar explosions resulting from a fast-rotating progenitor. Instead, these observations provide strong evidence for the development of low-mode convective instabilities in core-collapse supernovae.
C1 [Grefenstette, B. W.; Harrison, F. A.; Madsen, K. K.; Forster, K.; Mao, P. H.; Miyasaka, H.; Rana, V.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Boggs, S. E.; Zoglauer, A.; Craig, W. W.] Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA.
   [Reynolds, S. P.] N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA.
   [Fryer, C. L.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Wik, D. R.; Zhang, W. W.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Ellinger, C. I.] Univ Texas Arlington, Dept Phys, Arlington, TX 76019 USA.
   [Alexander, D. M.] Univ Durham, Dept Phys, Durham DH1 3LE, England.
   [An, H.; Kaspi, V. M.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Barret, D.] Univ Toulouse, UPS OMP, IRAP, F-31028 Toulouse 4, France.
   [Barret, D.] CNRS, Inst Rech Astrophys & Planetol, F-31028 Toulouse 4, France.
   [Christensen, F. E.; Hornstrup, A.; Westergaard, N. J.] Tech Univ Denmark, Natl Space Inst, DTU Space, DK-2800 Lyngby, Denmark.
   [Craig, W. W.; Pivovaroff, M. J.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Giommi, P.; Perri, M.; Puccetti, S.] Agenzia Spaziale Italiana, Sci Data Ctr, I-00133 Rome, Italy.
   [Hailey, C. J.; Mori, K.] Columbia Univ, Columbia Astrophys Lab, New York, NY 10027 USA.
   [Kitaguchi, T.] RIKEN, Nishina Ctr, Wako, Saitama 3510198, Japan.
   [Koglin, J. E.] SLAC Natl Accelerator Lab, Kavli Inst Particle Astrophys & Cosmol, Menlo Pk, CA 94025 USA.
   [Perri, M.] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Stern, D.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 California Institute of Technology; University of California System; University of California Berkeley; North Carolina State University; United States Department of Energy (DOE); Los Alamos National Laboratory; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Texas System; University of Texas Arlington; Durham University; McGill University; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Technical University of Denmark; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Agenzia Spaziale Italiana (ASI); Columbia University; RIKEN; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Istituto Nazionale Astrofisica (INAF); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Grefenstette, BW (corresponding author), CALTECH, Cahill Ctr Astrophys, 1216 East Calif Blvd, Pasadena, CA 91125 USA.
EM bwgref@srl.caltech.edu; fiona@srl.caltech.edu
FU NASA [NNG08FD60C]; NASA; Grants-in-Aid for Scientific Research [24740185] Funding Source: KAKEN
NR 40
TC 197
Z9 224
U1 0
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 FEB 20
PY 2014
VL 506
IS 7488
BP 339
EP +
DI 10.1038/nature12997
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800035
PM 24553239
DA 2026-03-09
ER

PT J
AU Helmus, MR
   Mahler, DL
   Losos, JB
AF Helmus, Matthew R.
   Mahler, D. Luke
   Losos, Jonathan B.
TI Island biogeography of the Anthropocene
SO NATURE
LA English
DT Article
ID scale; model; community; speciation; evolution; dynamics; plants; could
AB For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships)(1-4). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant(5). Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene-an epoch proposed for the present time interval-island biogeography is dominated by the economic isolation of-human populations.
C1 [Helmus, Matthew R.] Vrije Univ Amsterdam, Dept Anim Ecol, Amsterdam Global Change Inst, NL-1081 HV Amsterdam, Netherlands.
   [Mahler, D. Luke] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA.
   [Losos, Jonathan B.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Losos, Jonathan B.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
C3 Vrije Universiteit Amsterdam; University of California System; University of California Davis; Harvard University; Harvard University
RP Helmus, MR (corresponding author), Vrije Univ Amsterdam, Dept Anim Ecol, Amsterdam Global Change Inst, NL-1081 HV Amsterdam, Netherlands.
EM mrhelmus@gmail.com
FU Netherlands Organisation for Scientific Research [858.14.040]; US National Science Foundation [DBI 0906011]
NR 32
TC 227
Z9 263
U1 7
U2 332
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 543
EP +
DI 10.1038/nature13739
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800039
PM 25254475
DA 2026-03-09
ER

PT J
AU Carbone, L
   Harris, RA
   Gnerre, S
   Veeramah, KR
   Lorente-Galdos, B
   Huddleston, J
   Meyer, TJ
   Herrero, J
   Roos, C
   Aken, B
   Anaclerio, F
   Archidiacono, N
   Baker, C
   Barre, D
   Batzer, M
   Beal, K
   Blancher, A
   Bohrson, CL
   Brameier, M
   Campbell, MS
   Capozzi, O
   Casola, C
   Chiatante, G
   Cree, A
   Damert, A
   de Jong, PJ
   Dumas, L
   Fernandez-Callejo, M
   Flicek, P
   Fuchs, NV
   Gue, I
   Gut, M
   Hahn, MW
   Hernandez-Rodriguez, J
   Hillier, LW
   Hubley, R
   Ianc, B
   Izsvák, Z
   Jablonski, NG
   Johnstone, LM
   Karimpour-Fard, A
   Konkel, MK
   Kostka, D
   Lazar, NH
   Lee, SL
   Lewis, LR
   Liu, Y
   Locke, DP
   Mallick, S
   Mendez, FL
   Muffato, M
   Nazareth, LV
   Nevonen, KA
   O'Bleness, M
   Ochis, C
   Odom, DT
   Pollard, KS
   Quilez, J
   Reich, D
   Rocchi, M
   Schumann, GG
   Searle, S
   Sikela, JM
   Skollar, G
   Smit, A
   Sonmez, K
   ten Hallers, B
   Terhune, E
   Thomas, GWC
   Ullmer, B
   Ventura, M
   Walker, JA
   Wall, JD
   Walter, L
   Ward, MC
   Wheelan, SJ
   Whelan, CW
   White, S
   Wilhelm, LJ
   Woerner, AE
   Yandell, M
   Zhu, BL
   Hammer, MF
   Marques-Bonet, T
   Eichler, EE
   Fulton, L
   Fronick, C
   Muzny, DM
   Warren, WC
   Worley, KC
   Rogers, J
   Wilson, RK
   Gibbs, RA
AF Carbone, Lucia
   Harris, R. Alan
   Gnerre, Sante
   Veeramah, Krishna R.
   Lorente-Galdos, Belen
   Huddleston, John
   Meyer, Thomas J.
   Herrero, Javier
   Roos, Christian
   Aken, Bronwen
   Anaclerio, Fabio
   Archidiacono, Nicoletta
   Baker, Carl
   Barre, Daniel
   Batzer, Marka.
   Beal, Kathryn
   Blancher, Antoine
   Bohrson, Craig L.
   Brameier, Markus
   Campbell, Michael S.
   Capozzi, Oronzo
   Casola, Claudio
   Chiatante, Giorgia
   Cree, Andrew
   Damert, Annette
   de Jong, Pieter J.
   Dumas, Laura
   Fernandez-Callejo, Marcos
   Flicek, Paul
   Fuchs, Nina V.
   Gue, Ivo
   Gut, Marta
   Hahn, Matthew W.
   Hernandez-Rodriguez, Jessica
   Hillier, LaDeana W.
   Hubley, Robert
   Ianc, Bianca
   Izsvak, Zsuzsanna
   Jablonski, Nina G.
   Johnstone, Laurel M.
   Karimpour-Fard, Anis
   Konkel, Miriam K.
   Kostka, Dennis
   Lazar, Nathan H.
   Lee, Sandra L.
   Lewis, Lora R.
   Liu, Yue
   Locke, Devin P.
   Mallick, Swapan
   Mendez, Fernando L.
   Muffato, Matthieu
   Nazareth, Lynne V.
   Nevonen, Kimberly A.
   O'Bleness, Majesta
   Ochis, Cornelia
   Odom, Duncan T.
   Pollard, Katherine S.
   Quilez, Javier
   Reich, David
   Rocchi, Mariano
   Schumann, Gerald G.
   Searle, Stephen
   Sikela, James M.
   Skollar, Gabriella
   Smit, Arian
   Sonmez, Kemal
   ten Hallers, Boudewijn
   Terhune, Elizabeth
   Thomas, Gregg W. C.
   Ullmer, Brygg
   Ventura, Mario
   Walker, Jerilyn A.
   Wall, Jeffrey D.
   Walter, Lutz
   Ward, Michelle C.
   Wheelan, Sarah J.
   Whelan, Christopher W.
   White, Simon
   Wilhelm, Larry J.
   Woerner, August E.
   Yandell, Mark
   Zhu, Baoli
   Hammer, Michael F.
   Marques-Bonet, Tomas
   Eichler, Evan E.
   Fulton, Lucinda
   Fronick, Catrina
   Muzny, Donna M.
   Warren, Wesley C.
   Worley, Kim C.
   Rogers, Jeffrey
   Wilson, Richard K.
   Gibbs, Richard A.
TI Gibbon genome and the fast karyotype evolution of small apes
SO NATURE
LA English
DT Article
ID chromosome instability; gene; retrotransposon; binding; mechanism; inference; regions; ctcf; rna
AB Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-checked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation similar to 5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COLIA1) that may have been involved in the adaptation of gibbons to their arboreal habitat.
C1 [Carbone, Lucia; Meyer, Thomas J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
   [Carbone, Lucia; Nevonen, Kimberly A.; Terhune, Elizabeth; Wilhelm, Larry J.] Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA.
   [Carbone, Lucia] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
   [Carbone, Lucia; Lazar, Nathan H.; Sonmez, Kemal] Oregon Hlth & Sci Univ, Bioinformat & Computat Biol Div, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA.
   [Harris, R. Alan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Gnerre, Sante] Nabsys, Providence, RI 02903 USA.
   [Veeramah, Krishna R.; Johnstone, Laurel M.; Mendez, Fernando L.; Woerner, August E.; Hammer, Michael F.] Univ Arizona, ARL Div Biotechnol, Tucson, AZ 85721 USA.
   [Veeramah, Krishna R.] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11790 USA.
   [Lorente-Galdos, Belen; Fernandez-Callejo, Marcos; Hernandez-Rodriguez, Jessica; Quilez, Javier; Marques-Bonet, Tomas] Univ Pompeu Fabra, Inst Biol Evolut UPF CSIC, IBE, Barcelona 08003, Spain.
   [Huddleston, John; Baker, Carl; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Huddleston, John; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Herrero, Javier; Aken, Bronwen; Barre, Daniel; Beal, Kathryn; Flicek, Paul; Muffato, Matthieu] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Herrero, Javier] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England.
   [Roos, Christian; Brameier, Markus; Walter, Lutz] German Primate Ctr, Leibniz Inst Primate Res, Gene Bank Primates, D-37077 Gottingen, Germany.
   [Aken, Bronwen; Barre, Daniel; Odom, Duncan T.; Searle, Stephen; White, Simon] European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Anaclerio, Fabio; Archidiacono, Nicoletta; Capozzi, Oronzo; Chiatante, Giorgia; Rocchi, Mariano; Ventura, Mario] Univ Bari, Dept Biol, I-70125 Bari, Italy.
   [Batzer, Marka.; Konkel, Miriam K.; Walker, Jerilyn A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Blancher, Antoine] Univ Toulouse 3, F-31062 Toulouse, France.
   [Bohrson, Craig L.; Wheelan, Sarah J.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Blostat & Bioinformat, Baltimore, MD 21205 USA.
   [Campbell, Michael S.; Yandell, Mark] Univ Utah, Salt Lake City, UT 84112 USA.
   [Casola, Claudio] Texas A&M Univ, Dept Ecosyst Sci & Management, College Stn, TX 77843 USA.
   [Cree, Andrew; Lee, Sandra L.; Lewis, Lora R.; Liu, Yue; Nazareth, Lynne V.; Muzny, Donna M.; Worley, Kim C.; Rogers, Jeffrey; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Damert, Annette; Ianc, Bianca; Ochis, Cornelia] Univ Babes Bolyai, Inst Interdisciplinary Res Bionanosci, Ctr Mol Biol, Cluj Napoca 400084, Romania.
   [de Jong, Pieter J.; ten Hallers, Boudewijn; Zhu, Baoli] Childrens Hosp Oakland, Res Inst, BACPAC Resources, Oakland, CA 94609 USA.
   [Dumas, Laura; Karimpour-Fard, Anis; O'Bleness, Majesta; Sikela, James M.] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
   [Fuchs, Nina V.; Izsvak, Zsuzsanna] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Gue, Ivo; Gut, Marta; Marques-Bonet, Tomas] CNAG, Barcelona 08028, Spain.
   [Hahn, Matthew W.; Thomas, Gregg W. C.] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47408 USA.
   [Hillier, LaDeana W.; Locke, Devin P.; Smit, Arian; Fulton, Lucinda; Fronick, Catrina; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [Hubley, Robert] Inst Syst Biol, Seattle, WA 98109 USA.
   [Jablonski, Nina G.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA.
   [Kostka, Dennis] Univ Pittsburgh, Sch Med, Dept Dev Biol, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA.
   [Mallick, Swapan; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Odom, Duncan T.; Ward, Michelle C.] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
   [Pollard, Katherine S.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.; Wall, Jeffrey D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Pollard, Katherine S.; Wall, Jeffrey D.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94143 USA.
   [Schumann, Gerald G.] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
   [Skollar, Gabriella] Gibbon Conservat Ctr, Santa Clarita, CA 91350 USA.
   [Sonmez, Kemal; Whelan, Christopher W.] Oregon Hlth & Sci Univ, Ctr Spoken Language Understanding, Inst Dev & Disabil, Portland, OR 97239 USA.
   [Ullmer, Brygg] Louisiana State Univ, Sch Elect Engn & Comp Sci, Baton Rouge, LA 70803 USA.
   [Yandell, Mark] Univ Utah, USTAR Ctr Genet Discovery, Salt Lake City, UT 84112 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon National Primate Research Center; Oregon Health & Science University; Oregon Health & Science University; Baylor College of Medicine; University of Arizona; State University of New York (SUNY) System; Stony Brook University; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; Leibniz Association; Deutsches Primatenzentrum (DPZ); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Universita degli Studi di Bari Aldo Moro; Louisiana State University System; Louisiana State University; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Johns Hopkins University; Utah System of Higher Education; University of Utah; Texas A&M University System; Texas A&M University College Station; Baylor College of Medicine; Babes Bolyai University from Cluj; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; University of Colorado System; University of Colorado Anschutz Medical Campus; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Indiana University System; Indiana University Bloomington; Washington University (WUSTL); Institute for Systems Biology (ISB); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard Medical School; CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Paul Ehrlich Institute; Oregon Health & Science University; Louisiana State University System; Louisiana State University; Utah System of Higher Education; University of Utah
RP Carbone, L (corresponding author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM carbone@ohsu.edu
FU National Human Genome Research Institute(NHGRI) [U54 HG003273, U54 HG003079]; National Institutes of Health NIH/NIAAA [P30 M019355]; National Institutes of Health NIH/NCRR [P51 RR000163, R01_HG005226]; NIH [P30CA006973]; National Library of Medicine Biomedical Informatics Research Training Program [R01 GM59290, U41 HG007497-01, R01 MH081203, HG002385]; National Science Foundation (NSF) [CNS-1126739, DBI-0845494]; PRIN; Futuro in ricerca [RBFR103CE3]; ERC Starting Grant [260372]; MICINN (Spain) [BFU2011-28549]; Ministry of National Education; CNCS-UEFISCDI [PN-II-ID-PCE-2012-4-0090]; Deutsche Forschungsgemeinschaft [SCHU1014/8-1]; ERC; EMBO Young Investigator Award; ERC Starting Grant; Commonwealth Scholarship Commission; Wellcome Trust [WT095908, WT098051]; BBSRC [BBS/E/T/000PR6193] Funding Source: UKRI; Division Of Computer and Network Systems; Direct For Computer & Info Scie & Enginr [1126739] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR6193] Funding Source: researchfish; Cancer Research UK [15603] Funding Source: researchfish; National Cancer Institute [P30CA006973] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG002939, R01HG002385] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases; National Library of Medicine [T15LM007088] Funding Source: NIH RePORTER
NR 46
TC 259
Z9 320
U1 0
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 SEP 11
PY 2014
VL 513
IS 7517
BP 195
EP +
DI 10.1038/nature13679
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800043
PM 25209798
DA 2026-03-09
ER

PT J
AU Jackson, MG
   Hart, SR
   Konter, JG
   Kurz, MD
   Blusztajn, J
   Farley, KA
AF Jackson, M. G.
   Hart, S. R.
   Konter, J. G.
   Kurz, M. D.
   Blusztajn, J.
   Farley, K. A.
TI Helium and lead isotopes reveal the geochemical geometry of the Samoan plume
SO NATURE
LA English
DT Article
ID deep-mantle; oceanic basalts; island basalts; trace-element; pb isotope; lavas; sr; nd; age; systematics
AB Hotspot lavas erupted at ocean islands exhibit tremendous isotopic variability, indicating that there are numerous mantle components(1,2) hosted in upwelling mantle plumes that generate volcanism at hotspots like Hawaii and Samoa(3). However, it is not known how the surface expression of the various geochemical components observed in hotspot volcanoes relates to their spatial distribution within the plume(4-10). Here we present a relationship between He and Pb isotopes in Samoan lavas that places severe constraints on the distribution of geochemical species within the plume. The Pb-isotopic compositions of the Samoan lavas reveal several distinct geochemical groups, each corresponding to a different geographic lineament of volcanoes. Each group has a signature associated with one of four mantle end members with low He-3/He-4:EMII(enriched mantle 2), EMI(enriched mantle 1), HIMU(high mu = U-238/Pb-204) and DM(depleted mantle). Critically, these four geochemical groups trend towards a common region of Pb-isotopic space with high He-3/He-4. This observation is consistent with several low-He-3/He-4 components in the plume mixing with a common high-He-3/He-4 component, but not mixing much with each other. The mixing relationships inferred from the new He and Pb isotopic data provide the clearest picture yet of the geochemical geometry of a mantle plume, and are best explained by a high-He-3/He-4 plume matrix that hosts, and mixes with, several distinct low-He-3/He-4 components.
C1 [Jackson, M. G.] Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
   [Hart, S. R.; Blusztajn, J.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
   [Konter, J. G.] Univ Hawaii Manoa, Sch Earth & Ocean Sci & Technol SOEST, Dept Geol & Geophys, Honolulu, HI 96822 USA.
   [Kurz, M. D.] Woods Hole Oceanog Inst, Dept Marine Chem, Woods Hole, MA 02543 USA.
   [Farley, K. A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
C3 University of California System; University of California Santa Barbara; Woods Hole Oceanographic Institution; University of Hawaii System; University of Hawaii Manoa; Woods Hole Oceanographic Institution; California Institute of Technology
RP Jackson, MG (corresponding author), Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
EM jackson@geol.ucsb.edu
FU NSF [OCE-1061134, OCE-1153894, EAR-1348082, EAR-1145202]; Directorate For Geosciences [1348082, 1430610] Funding Source: National Science Foundation; Division Of Earth Sciences [1348082, 1430610] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1232985, 1358875] Funding Source: National Science Foundation
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NR 68
TC 100
Z9 115
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 OCT 16
PY 2014
VL 514
IS 7522
BP 355
EP +
DI 10.1038/nature13794
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600049
PM 25318524
DA 2026-03-09
ER

PT J
AU Tully, RB
   Courtois, H
   Hoffman, Y
   Pomarède, D
AF Tully, R. Brent
   Courtois, Helene
   Hoffman, Yehuda
   Pomarede, Daniel
TI The Laniakea supercluster of galaxies
SO NATURE
LA English
DT Article
ID wiener reconstruction; iras-galaxy; density; scale; calibration; velocity; fields
AB Galaxies congregate in clusters and along filaments, and are missing from large regions referred to as voids. These structures are seen in maps derived from spectroscopic surveys(1,2) that reveal networks of structure that are interconnected with no clear boundaries. Extended regions with a high concentration of galaxies are called 'superclusters', although this term is not precise. There is, however, another way to analyse the structure. If the distance to each galaxy from Earth is directly measured, then the peculiar velocity can be derived from the subtraction of the mean cosmic expansion, the product of distance times the Hubble constant, from observed velocity. The peculiar velocity is the line-of-sight departure from the cosmic expansion and arises from gravitational perturbations; a map of peculiar velocities can be translated into a map of the distribution of matter(3). Here we report a map of structure made using a catalogue of peculiar velocities. We find locations where peculiar velocity flows diverge, as water does at watershed divides, and we trace the surface of divergent points that surrounds us. Within the volume enclosed by this surface, the motions of galaxies are inward after removal of the mean cosmic expansion and long range flows. We define a supercluster to be the volume within such a surface, and so we are defining the extent of our home supercluster, which we call Laniakea.
C1 [Tully, R. Brent] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Courtois, Helene] Univ Lyon 1, Inst Nucl Phys, CNRS IN2P3, F-69622 Lyon, France.
   [Hoffman, Yehuda] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Pomarede, Daniel] CEA Saclay, Inst Rech Lois Fondamentales Univers, F-91191 Gif Sur Yvette, France.
C3 University of Hawaii System; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite Lyon 1; Hebrew University of Jerusalem; Universite Paris Saclay; CEA
RP Tully, RB (corresponding author), Univ Hawaii, Inst Astron, 2680 Woodlawn Dr, Honolulu, HI 96822 USA.
EM tully@ifa.hawaii.edu
FU US National Science Foundation [AST09-08846]; Space Telescope Science Institute for observing time with Hubble Space Telescope; Jet Propulsion Lab for observations with Spitzer Space Telescope; NASA [NNX12AE70G]; Israel Science Foundation [1013/12]; Lyon Institute of Origins [ANR-10-LABX-66]; CNRS [PICS-06233]; NASA [75075, NNX12AE70G] Funding Source: Federal RePORTER
NR 25
TC 237
Z9 276
U1 2
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 SEP 4
PY 2014
VL 513
IS 7516
BP 71
EP +
DI 10.1038/nature13674
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800031
PM 25186900
DA 2026-03-09
ER

PT J
AU Ali, K
   Soond, DR
   Piñeiro, R
   Hagemann, T
   Pearce, W
   Lim, EL
   Bouabe, H
   Scudamore, CL
   Hancox, T
   Maecker, H
   Friedman, L
   Turner, M
   Okkenhaug, K
   Vanhaesebroeck, B
AF Ali, Khaled
   Soond, Dalya R.
   Pineiro, Roberto
   Hagemann, Thorsten
   Pearce, Wayne
   Lim, Ee Lyn
   Bouabe, Hicham
   Scudamore, Cheryl L.
   Hancox, Timothy
   Maecker, Heather
   Friedman, Lori
   Turner, Martin
   Okkenhaug, Klaus
   Vanhaesebroeck, Bart
TI Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer
SO NATURE
LA English
DT Article
ID phosphoinositide 3-kinase; suppressor-cells; inflammation; idelalisib; inhibition; isoform; delta; pi3k
AB Inhibitors against thep110 delta isoform of phosphoinositide-3-OH kinase (PI(3) K) have shown remarkable therapeutic efficacy in some human leukaemias(1,2). As p110 delta is primarily expressed in leukocytes(3), drugs against p110 delta have not been considered for the treatment of solid tumours(4). Here we report that p110 delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110 delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110 delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.
C1 [Ali, Khaled; Pineiro, Roberto; Pearce, Wayne; Vanhaesebroeck, Bart] UCL, UCL Canc Inst, London WC1E 6DD, England.
   [Soond, Dalya R.; Lim, Ee Lyn; Bouabe, Hicham; Turner, Martin; Okkenhaug, Klaus] Babraham Inst, Lab Lymphocyte Signalling & Dev, Cambridge CB22 3AT, England.
   [Hagemann, Thorsten] Queen Mary Univ London, Barts Canc Inst, Ctr Canc & Inflammat, London EC1M 6BQ, England.
   [Scudamore, Cheryl L.] MRC Harwell, Mary Lyon Ctr, Harwell OX11 0RD, Berks, England.
   [Hancox, Timothy] Piramed Pharma, Slough SL1 4NL, Berks, England.
   [Maecker, Heather; Friedman, Lori] Genentech Inc, Canc Signaling & Translat Oncol, San Francisco, CA 94080 USA.
C3 University of London; University College London; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; University of London; Queen Mary University London; MRC Harwell; Roche Holding; Genentech; Roche Holding USA
RP Ali, K (corresponding author), Amgen Inc, Oncol Res, 1120 Vet Blvd, San Francisco, CA 94080 USA.
EM khaleda@amgen.com; klaus.okkenhaug@babraham.ac.uk; bart.vanh@ucl.ac.uk
FU Cancer Research UK [C23338/A10200, C23338/A15965, C18270/A12888]; Biotechnology and Biological Sciences Research Council [BB/E009867/1]; Wellcome Trust [095691/Z/11/Z]; Wellcome Trust [095691/Z/11/Z] Funding Source: Wellcome Trust; BBSRC [BB/I007806/2, BBS/E/B/000C0407, BB/E009867/1] Funding Source: UKRI; MRC [MC_UP_1502/1, G0901338] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/B/02010, BB/I007806/2, BBS/E/B/000C0407, BB/E009867/1] Funding Source: researchfish; Cancer Research UK [14355, 12888, 15965] Funding Source: researchfish; Medical Research Council [MC_UP_1502/1, G0901338] Funding Source: researchfish
NR 23
TC 436
Z9 485
U1 1
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 19
PY 2014
VL 510
IS 7505
BP 407
EP +
DI 10.1038/nature13444
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200037
PM 24919154
DA 2026-03-09
ER

PT J
AU Letourneau, A
   Santoni, FA
   Bonilla, X
   Sailani, MR
   Gonzalez, D
   Kind, J
   Chevalier, C
   Thurman, R
   Sandstrom, RS
   Hibaoui, Y
   Garieri, M
   Popadin, K
   Falconnet, E
   Gagnebin, M
   Gehrig, C
   Vannier, A
   Guipponi, M
   Farinelli, L
   Robyr, D
   Migliavacca, E
   Borel, C
   Deutsch, S
   Feki, A
   Stamatoyannopoulos, JA
   Herault, Y
   van Steensel, B
   Guigo, R
   Antonarakis, SE
AF Letourneau, Audrey
   Santoni, Federico A.
   Bonilla, Ximena
   Sailani, M. Reza
   Gonzalez, David
   Kind, Jop
   Chevalier, Claire
   Thurman, Robert
   Sandstrom, Richard S.
   Hibaoui, Youssef
   Garieri, Marco
   Popadin, Konstantin
   Falconnet, Emilie
   Gagnebin, Maryline
   Gehrig, Corinne
   Vannier, Anne
   Guipponi, Michel
   Farinelli, Laurent
   Robyr, Daniel
   Migliavacca, Eugenia
   Borel, Christelle
   Deutsch, Samuel
   Feki, Anis
   Stamatoyannopoulos, John A.
   Herault, Yann
   van Steensel, Bas
   Guigo, Roderic
   Antonarakis, Stylianos E.
TI Domains of genome-wide gene expression dysregulation in Down's syndrome
SO NATURE
LA English
DT Article
ID partial trisomy; cell-type; chromatin; biotinylation; transcriptome; proliferation; chromosome; plasticity; phenotypes; package
AB Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs)can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina- associated (LADs)and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.
C1 [Letourneau, Audrey; Santoni, Federico A.; Bonilla, Ximena; Sailani, M. Reza; Garieri, Marco; Popadin, Konstantin; Falconnet, Emilie; Gagnebin, Maryline; Gehrig, Corinne; Vannier, Anne; Guipponi, Michel; Robyr, Daniel; Migliavacca, Eugenia; Borel, Christelle; Antonarakis, Stylianos E.] Univ Hosp Geneva, Univ Geneva Med Sch, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Gonzalez, David; Guigo, Roderic] Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona 08003, Spain.
   [Kind, Jop; van Steensel, Bas] Netherlands Canc Inst, Div Gene Regulat, NL-1066 CX Amsterdam, Netherlands.
   [Chevalier, Claire; Herault, Yann] Univ Strasbourg, INSERM, CNRS, Translat Med & Neurosci Program,IGBMC,ICS,PHENOMI, F-67404 Illkirch Graffenstaden, France.
   [Thurman, Robert; Sandstrom, Richard S.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Hibaoui, Youssef; Feki, Anis] Univ Hosp Geneva, Dept Obstet & Gynecol, Stem Cell Res Lab, CH-1211 Geneva, Switzerland.
   [Farinelli, Laurent] FASTERIS SA, CH-1228 Plan Les Ouates, Switzerland.
   [Migliavacca, Eugenia] Swiss Inst Bioinfomat, CH-1211 Geneva, Switzerland.
   [Deutsch, Samuel] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Antonarakis, Stylianos E.] iGE3 Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Netherlands Cancer Institute; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); University of Washington; University of Washington Seattle; University of Geneva; Swiss Institute of Bioinformatics; United States Department of Energy (DOE)
RP Antonarakis, SE (corresponding author), Univ Hosp Geneva, Univ Geneva Med Sch, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
EM Stylianos.Antonarakis@unige.ch
FU Swiss National Science Foundation [SNF-144082]; European Research Council [ERC-249968]; AnEUploidy grant; Lejeune foundation; ChildCare foundation; Spanish MICINN [BIO2011-26205, ERC-294653]; NWO-ALW-VICI; CNRS; INSERM; University of Strasbourg; NIH [U54HG007010]; Genico and Ernest Boninchi foundation; BluePrint EU grant;  [ANR-10-INBS-07]
NR 57
TC 237
Z9 272
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 APR 17
PY 2014
VL 508
IS 7496
BP 345
EP +
DI 10.1038/nature13200
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000042
PM 24740065
DA 2026-03-09
ER

PT J
AU Boumahdi, S
   Driessens, G
   Lapouge, G
   Rorive, S
   Nassar, D
   Le Mercier, M
   Delatte, B
   Caauwe, A
   Lenglez, S
   Nkusi, E
   Brohée, S
   Salmon, I
   Dubois, C
   del Marmol, V
   Fuks, F
   Beck, B
   Blanpain, C
AF Boumahdi, Soufiane
   Driessens, Gregory
   Lapouge, Gaelle
   Rorive, Sandrine
   Nassar, Dany
   Le Mercier, Marie
   Delatte, Benjamin
   Caauwe, Amelie
   Lenglez, Sandrine
   Nkusi, Erwin
   Brohee, Sylvain
   Salmon, Isabelle
   Dubois, Christine
   del Marmol, Veronique
   Fuks, Francois
   Beck, Benjamin
   Blanpain, Cedric
TI SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma
SO NATURE
LA English
DT Article
ID self-renewal; expression; differentiation; maintenance; populations; survival; ablation; catenin; marker; genes
AB Cancer stem cells (CSCs) have been reported in various cancers, including in skin squamous-cell carcinoma (SCC)(1-4). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here we find that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells(5,6), was the most upregulated transcription factor in the CSCs of squamous skin tumours in mice. SOX2 is absent in normal epidermis but begins to be expressed in the vast majority of mouse and human pre-neoplastic skin tumours, and continues to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In contrast to other SCCs, in which SOX2 is frequently genetically amplified(7), the expression of SOX2 in mouse and human skin SCCs is transcriptionally regulated. Conditional deletion of Sox2 in the mouse epidermis markedly decreases skin tumour formation after chemical-induced carcinogenesis. Using green fluorescent protein (GFP) as a reporter of Sox2 transcriptional expression (SOX2-GFP knock-in mice), we showed that SOX2-expressing cells in invasive SCC are greatly enriched in tumour-propagating cells, which further increase upon serial transplantations. Lineage ablation of SOX2-expressing cells within primary benign and malignant SCCs leads to tumour regression, consistent with the critical role of SOX2-expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing skin papilloma and SCC leads to tumour regression and decreases the ability of cancer cells to be propagated upon transplantation into immunodeficient mice, supporting the essential role of SOX2 in regulating CSC functions. Transcriptional profiling of SOX2-GFP expressing CSCs and of tumour epithelial cells upon Sox2 deletion uncovered a gene network regulated by SOX2 in primary tumour cells in vivo. Chromatin immunoprecipitation identified several direct SOX2 target genes controlling tumour stemness, survival, proliferation, adhesion, invasion and paraneoplastic syndrome. We demonstrate that SOX2, by marking and regulating the functions of skin tumour-initiating cells and CSCs, establishes a continuum between tumour initiation and progression in primary skin tumours.
C1 [Boumahdi, Soufiane; Driessens, Gregory; Lapouge, Gaelle; Nassar, Dany; Caauwe, Amelie; Lenglez, Sandrine; Nkusi, Erwin; Dubois, Christine; Beck, Benjamin; Blanpain, Cedric] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
   [Rorive, Sandrine; Le Mercier, Marie; Salmon, Isabelle] Univ Libre Bruxelles, Erasme Hosp, Dept Pathol, B-1070 Brussels, Belgium.
   [Rorive, Sandrine; Salmon, Isabelle] CMMI, DIAPATH, B-6041 Gosselies, Belgium.
   [Delatte, Benjamin; Fuks, Francois] Univ Libre Bruxelles, Lab Canc Epigenet, B-1070 Brussels, Belgium.
   [Brohee, Sylvain] Univ Libre Bruxelles, Fac Sci, Dept Comp Sci, Machine Learning Grp, B-1050 Brussels, Belgium.
   [del Marmol, Veronique] Univ Libre Bruxelles, Erasme Hosp, Dept Dermatol, B-1070 Brussels, Belgium.
   [Blanpain, Cedric] Univ Libre Bruxelles, WELBIO, B-1070 Brussels, Belgium.
C3 Universite Libre de Bruxelles; Universite Libre de Bruxelles; Universite Catholique Louvain; Cliniques Universitaires Saint-Luc; Universite Libre de Bruxelles; Universite Libre de Bruxelles; Universite Libre de Bruxelles; WELBIO; Universite Libre de Bruxelles
RP Blanpain, C (corresponding author), Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
EM Cedric.Blanpain@ulb.ac.be
FU FNRS/FRIA; FNRS; TELEVIE; Brussels Region through the BB2B program; BB2B; IUAP; Fondation Contre le Cancer; ULB foundation; Fonds Yvonne Boel; Fonds Gaston Ithier; foundation Bettencourt Schueller; European Research Council
NR 53
TC 544
Z9 624
U1 0
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 JUL 10
PY 2014
VL 511
IS 7508
BP 246
EP +
DI 10.1038/nature13305
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800049
PM 24909994
DA 2026-03-09
ER

PT J
AU Butz, B
   Dolle, C
   Niekiel, F
   Weber, K
   Waldmann, D
   Weber, HB
   Meyer, B
   Spiecker, E
AF Butz, Benjamin
   Dolle, Christian
   Niekiel, Florian
   Weber, Konstantin
   Waldmann, Daniel
   Weber, Heiko B.
   Meyer, Bernd
   Spiecker, Erdmann
TI Dislocations in bilayer graphene
SO NATURE
LA English
DT Article
ID band-gap; layer
AB Dislocations represent one of the most fascinating and fundamental concepts in materials science(1-3). Most importantly, dislocations are the main carriers of plastic deformation in crystalline materials(4-6). Furthermore, they can strongly affect the local electronic and optical properties of semiconductors and ionic crystals(7,8). In materials with small dimensions, they experience extensive image forces, which attract them to the surface to release strain energy(9). However, in layered crystals such as graphite, dislocation movement is mainly restricted to the basal plane. Thus, the dislocations cannot escape, enabling their confinement in crystals as thin as only two monolayers. To explore the nature of dislocations under such extreme boundary conditions, the material of choice is bilayer graphene, the thinnest possible quasi-two-dimensional crystal in which such linear defects can be confined. Homogeneous and robust graphene membranes derived from high-quality epitaxial graphene on silicon carbide(10) provide an ideal platform for their investigation. Here we report the direct observation of basal-plane dislocations in freestanding bilayer graphene using transmission electron microscopy and their detailed investigation by diffraction contrast analysis and atomistic simulations. Our investigation reveals two striking size effects. First, the absence of stacking-fault energy, a unique property of bilayer graphene, leads to a characteristic dislocation pattern that corresponds to an alternating AB <-> AC change of the stacking order. Second, our experiments in combination with atomistic simulations reveal a pronounced buckling of the bilayer graphene membrane that results directly from accommodation of strain. In fact, the buckling changes the strain state of the bilayer graphene and is of key importance for its electronic properties(11-14). Our findings will contribute to the understanding of dislocations and of their role in the structural, mechanical and electronic properties of bilayer and few-layer graphene.
C1 [Butz, Benjamin; Dolle, Christian; Niekiel, Florian; Spiecker, Erdmann] Univ Erlangen Nurnberg, Ctr Nanoanal & Electron Microscopy, D-91058 Erlangen, Germany.
   [Weber, Konstantin; Meyer, Bernd] Univ Erlangen Nurnberg, Interdisziplinares Zentrum Mol Mat, D-91052 Erlangen, Germany.
   [Weber, Konstantin; Meyer, Bernd] Univ Erlangen Nurnberg, Comp Chem Ctr, D-91052 Erlangen, Germany.
   [Waldmann, Daniel; Weber, Heiko B.] Univ Erlangen Nurnberg, Lehrstuhl Angew Phys, D-91058 Erlangen, Germany.
C3 University of Erlangen Nuremberg; University of Erlangen Nuremberg; University of Erlangen Nuremberg; University of Erlangen Nuremberg
RP Butz, B (corresponding author), Univ Erlangen Nurnberg, Ctr Nanoanal & Electron Microscopy, Cauerstr 6, D-91058 Erlangen, Germany.
EM benjamin.butz@ww.uni-erlangen.de; erdmann.spiecker@ww.uni-erlangen.de
FU Deutsche Forschungsgemeinschaft [SFB 953]; Cluster of Excellence EXC 315 'Engineering of Advanced Materials' at the Friedrich-Alexander-Universitat Erlangen-Nurnberg
NR 36
TC 205
Z9 235
U1 3
U2 492
PU NATURE PUBLISHING 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 23
PY 2014
VL 505
IS 7484
BP 533
EP +
DI 10.1038/nature12780
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000036
PM 24352231
DA 2026-03-09
ER

PT J
AU Hurricane, OA
   Callahan, DA
   Casey, DT
   Celliers, PM
   Cerjan, C
   Dewald, EL
   Dittrich, TR
   Döppner, T
   Hinkel, DE
   Hopkins, LFB
   Kline, JL
   Le Pape, S
   Ma, T
   MacPhee, AG
   Milovich, JL
   Pak, A
   Park, HS
   Patel, PK
   Remington, BA
   Salmonson, JD
   Springer, PT
   Tommasini, R
AF Hurricane, O. A.
   Callahan, D. A.
   Casey, D. T.
   Celliers, P. M.
   Cerjan, C.
   Dewald, E. L.
   Dittrich, T. R.
   Doeppner, T.
   Hinkel, D. E.
   Hopkins, L. F. Berzak
   Kline, J. L.
   Le Pape, S.
   Ma, T.
   MacPhee, A. G.
   Milovich, J. L.
   Pak, A.
   Park, H. -S.
   Patel, P. K.
   Remington, B. A.
   Salmonson, J. D.
   Springer, P. T.
   Tommasini, R.
TI Fuel gain exceeding unity in an inertially confined fusion implosion
SO NATURE
LA English
DT Article
ID rayleigh-taylor instability; national ignition facility
AB Ignition is needed to make fusion energy a viable alternative energy source, but has yet to be achieved(1). A key step on the way to ignition is to have the energy generated through fusion reactions in an inertially confined fusion plasma exceed the amount of energy deposited into the deuterium-tritium fusion fuel and hotspot during the implosion process, resulting in a fuel gain greater than unity. Here we report the achievement of fusion fuel gains exceeding unity on the US National Ignition Facility using a 'high-foot' implosion method(2,3), which is a manipulation of the laser pulse shape in a way that reduces instability in the implosion. These experiments show an order-of-magnitude improvement in yield performance over past deuterium-tritium implosion experiments. We also see a significant contribution to the yield from alpha-particle self-heating and evidence for the 'bootstrapping' required to accelerate the deuterium-tritium fusion burn to eventually 'run away' and ignite.
C1 [Hurricane, O. A.; Callahan, D. A.; Casey, D. T.; Celliers, P. M.; Cerjan, C.; Dewald, E. L.; Dittrich, T. R.; Doeppner, T.; Hinkel, D. E.; Hopkins, L. F. Berzak; Le Pape, S.; Ma, T.; MacPhee, A. G.; Milovich, J. L.; Pak, A.; Park, H. -S.; Patel, P. K.; Remington, B. A.; Salmonson, J. D.; Springer, P. T.; Tommasini, R.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Kline, J. L.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
C3 United States Department of Energy (DOE); Lawrence Livermore National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory
RP Hurricane, OA (corresponding author), Lawrence Livermore Natl Lab, POB 808, Livermore, CA 94551 USA.
EM hurricane1@llnl.gov
FU US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]
NR 29
TC 790
Z9 889
U1 5
U2 345
PU NATURE PUBLISHING 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 20
PY 2014
VL 506
IS 7488
BP 343
EP +
DI 10.1038/nature13008
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800036
PM 24522535
DA 2026-03-09
ER

PT J
AU Bagchi, R
   Gallery, RE
   Gripenberg, S
   Gurr, SJ
   Narayan, L
   Addis, CE
   Freckleton, RP
   Lewis, OT
AF Bagchi, Robert
   Gallery, Rachel E.
   Gripenberg, Sofia
   Gurr, Sarah J.
   Narayan, Lakshmi
   Addis, Claire E.
   Freckleton, Robert P.
   Lewis, Owen T.
TI Pathogens and insect herbivores drive rainforest plant diversity and composition
SO NATURE
LA English
DT Article
ID dependent seedling mortality; species shade tolerance; density-dependence; recruitment; coexistence; predation; feedback
AB Tropical forests are important reservoirs of biodiversity(1), but the processes that maintain this diversity remain poorly understood(2). The Janzen-Connell hypothesis(3,4) suggests that specialized natural enemies such as insect herbivores and fungal pathogens maintain high diversity by elevating mortality when plant species occur at high density (negative density dependence; NDD). NDD has been detected widely in tropical forests(5-9), but the prediction that NDD caused by insects and pathogens has a community-wide role in maintaining tropical plant diversity remains untested. We show experimentally that changes in plant diversity and species composition are caused by fungal pathogens and insect herbivores. Effective plant species richness increased across the seed-to-seedling transition, corresponding to large changes in species composition(5). Treating seeds and young seedlings with fungicides significantly reduced the diversity of the seedling assemblage, consistent with the Janzen-Connell hypothesis. Although suppressing insect herbivores using insecticides did not alter species diversity, it greatly increased seedling recruitment and caused a marked shift in seedling species composition. Overall, seedling recruitment was significantly reduced at high con-specific seed densities and this NDD was greatest for the species that were most abundant as seeds. Suppressing fungi reduced the negative effects of density on recruitment, confirming that the diversity enhancing effect of fungi is mediated by NDD. Our study provides an overall test of the Janzen-Connell hypothesis and demonstrates the crucial role that insects and pathogens have both in structuring tropical plant communities and in maintaining their remarkable diversity.
C1 [Bagchi, Robert; Gallery, Rachel E.; Gripenberg, Sofia; Narayan, Lakshmi; Addis, Claire E.; Lewis, Owen T.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Bagchi, Robert] ETH, Inst Terr Ecosyst, Ecosyst Management Grp, CH-8092 Zurich, Switzerland.
   [Gallery, Rachel E.] Univ Arizona, Sch Nat Resources & Environm, Tucson, AZ 85721 USA.
   [Gripenberg, Sofia] Univ Turku, Dept Biol, Sect Biodivers & Environm Res, Turku 20014, Finland.
   [Gurr, Sarah J.] Univ Exeter, Dept Biosci, Exeter EX4 4QD, Devon, England.
   [Gurr, Sarah J.] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
   [Freckleton, Robert P.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
C3 University of Oxford; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Arizona; University of Turku; University of Exeter; University of Oxford; University of Sheffield
RP Lewis, OT (corresponding author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM owen.lewis@zoo.ox.ac.uk
FU Natural Environment Research Council (NERC) [NE/DO10721/1]; Academy of Finland [126296]; Biotechnology and Biological Sciences Research Council [BB/J008923/2, BB/G00207X/1, BB/J008923/1] Funding Source: researchfish; Natural Environment Research Council [NE/D010721/1] Funding Source: researchfish; Division Of Environmental Biology; Direct For Biological Sciences [1257139] Funding Source: National Science Foundation; BBSRC [BB/J008923/1, BB/G00207X/1, BB/J008923/2] Funding Source: UKRI; NERC [NE/D010721/1] Funding Source: UKRI; Academy of Finland (AKA) [126296] Funding Source: Academy of Finland (AKA)
NR 37
TC 546
Z9 675
U1 11
U2 894
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 6
PY 2014
VL 506
IS 7486
BP 85
EP +
DI 10.1038/nature12911
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100036
PM 24463522
DA 2026-03-09
ER

PT J
AU Low, HH
   Gubellini, F
   Rivera-Calzada, A
   Braun, N
   Connery, S
   Dujeancourt, A
   Lu, F
   Redzej, A
   Fronzes, R
   Orlova, EV
   Waksman, G
AF Low, Harry H.
   Gubellini, Francesca
   Rivera-Calzada, Angel
   Braun, Nathalie
   Connery, Sarah
   Dujeancourt, Annick
   Lu, Fang
   Redzej, Adam
   Fronzes, Remi
   Orlova, Elena V.
   Waksman, Gabriel
TI Structure of a type IV secretion system
SO NATURE
LA English
DT Article
ID electron-microscopy; core complex; image; virb4; insights; atpase; visualization
AB Bacterial type IV secretion systems translocate virulence factors into eukaryotic cells(1,2), distribute genetic material between bacteria and have shown potential as a tool for the genetic modification of human cells(3). Given the complex choreography of the substrate through the secretion apparatus(4), the molecular mechanism of the type IV secretion system has proved difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy to reconstruct the type IV secretion system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form an approximately 3 megadalton nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex(1) connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of 12 VirB4 ATPase subunits organized as side-by-side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems(1,4-6).
C1 [Low, Harry H.; Rivera-Calzada, Angel; Braun, Nathalie; Connery, Sarah; Lu, Fang; Redzej, Adam; Orlova, Elena V.; Waksman, Gabriel] UCL, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Low, Harry H.; Rivera-Calzada, Angel; Braun, Nathalie; Connery, Sarah; Lu, Fang; Redzej, Adam; Orlova, Elena V.; Waksman, Gabriel] Univ London Birkbeck Coll, London WC1E 7HX, England.
   [Gubellini, Francesca; Dujeancourt, Annick; Fronzes, Remi] Inst Pasteur, F-75015 Paris, France.
   [Gubellini, Francesca; Dujeancourt, Annick; Fronzes, Remi] CNRS, UMR 3528, F-75015 Paris, France.
C3 University of London; University College London; Birkbeck University London; University of London; Birkbeck University London; 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)
RP Waksman, G (corresponding author), UCL, Inst Struct & Mol Biol, London WC1E 7HX, England.
EM remi.fronzes@pasteur.fr; e.orlova@mail.cryst.bbk.ac.uk; g.waksman@mail.cryst.bbk.ac.uk
FU Wellcome Trust [098302, 079605]; Institut Pasteur; CNRS; MRC [MR/K012401/1] Funding Source: UKRI; Medical Research Council [MR/K012401/1] Funding Source: researchfish
NR 30
TC 240
Z9 280
U1 1
U2 118
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2014
VL 508
IS 7497
BP 550
EP +
DI 10.1038/nature13081
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600042
PM 24670658
DA 2026-03-09
ER

PT J
AU Dao, A
   Yaro, AS
   Diallo, M
   Timbiné, S
   Huestis, DL
   Kassogué, Y
   Traoré, AI
   Sanogo, ZL
   Samaké, D
   Lehmann, T
AF Dao, A.
   Yaro, A. S.
   Diallo, M.
   Timbine, S.
   Huestis, D. L.
   Kassogue, Y.
   Traore, A. I.
   Sanogo, Z. L.
   Samake, D.
   Lehmann, T.
TI Signatures of aestivation and migration in Sahelian malaria mosquito populations
SO NATURE
LA English
DT Article
ID anopheles-gambiae complex; dry season; molecular-forms; sudan savanna; west-africa; mali; persistence; arabiensis; differentiation; transmission
AB During the long Sahelian dry season, mosquito vectors of malaria are expected to perish when no larval sites are available; yet, days after the first rains, mosquitoes reappear in large numbers. How these vectors persist over the 3-6-month long dry season has not been resolved, despite extensive research for over a century(1-3.) Hypotheses for vector persistence include dry-season diapause (aestivation) and long-distance migration (LDM); both are facets of vector biology that have been highly controversial owing to lack of concrete evidence. Here we show that certain species persist by a form of aestivation, while others engage in LDM. Using time-series analyses, the seasonal cycles of Anopheles coluzzii, Anopheles gambiae sensu stricto (s.s.), and Anopheles arabiensis were estimated, and their effects were found to be significant, stable and highly species-specific. Contrary to all expectations, the most complex dynamics occurred during the dry season, when the density of A. coluzzii fluctuated markedly, peaking when migration would seem highly unlikely, whereas A. gambiae s.s. was undetected. The population growth of A. coluzzii followed the first rains closely, consistent with aestivation, whereas the growth phase of both A. gambiae s.s. and A. arabiensis lagged by two months. Such a delay is incompatible with local persistence, but fits LDM. Surviving the long dry season in situ allows A. coluzzii to predominate and form the primary force of malaria transmission. Our results reveal profound ecological divergence between A. coluzzii and A. gambiae s.s., whose standing as distinct species has been challenged, and suggest that climate is one of the selective pressures that led to their speciation. Incorporating vector dormancy and LDM is key to predicting shifts in the range of malaria due to global climate change(4), and to the elimination of malaria from Africa.
C1 [Dao, A.; Yaro, A. S.; Diallo, M.; Timbine, S.; Kassogue, Y.; Traore, A. I.; Sanogo, Z. L.; Samake, D.] Univ Sci Tech & Technol, ICER, Bamako, Mali.
   [Huestis, D. L.; Lehmann, T.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
C3 University of Science & Technology of Bamako; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Lehmann, T (corresponding author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM tlehmann@niaid.nih.gov
FU Tamaki Foundation; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Institute of Allergy and Infectious Diseases [ZIAAI001196] Funding Source: NIH RePORTER
NR 31
TC 114
Z9 130
U1 0
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 DEC 18
PY 2014
VL 516
IS 7531
BP 387
EP +
DI 10.1038/nature13987
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800045
PM 25470038
DA 2026-03-09
ER

PT J
AU Hassaine, G
   Deluz, C
   Grasso, L
   Wyss, R
   Tol, MB
   Hovius, R
   Graff, A
   Stahlberg, H
   Tomizaki, T
   Desmyter, A
   Moreau, C
   Li, XD
   Poitevin, F
   Vogel, H
   Nury, H
AF Hassaine, Gherici
   Deluz, Cedric
   Grasso, Luigino
   Wyss, Romain
   Tol, Menno B.
   Hovius, Ruud
   Graff, Alexandra
   Stahlberg, Henning
   Tomizaki, Takashi
   Desmyter, Aline
   Moreau, Christophe
   Li, Xiao-Dan
   Poitevin, Frederic
   Vogel, Horst
   Nury, Hugues
TI X-ray structure of the mouse serotonin 5-HT3 receptor
SO NATURE
LA English
DT Article
ID gated ion-channel; nicotinic acetylcholine-receptor; ligand-binding domain; selectivity-filter; agonist binding; permeation; pore; determinants; mechanism; conductance
AB Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 angstrom resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 angstrom constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.
C1 [Hassaine, Gherici; Deluz, Cedric; Grasso, Luigino; Wyss, Romain; Tol, Menno B.; Hovius, Ruud; Vogel, Horst; Nury, Hugues] Ecole Polytech Fed Lausanne, Lab Phys Chem Polymers & Membranes, CH-1015 Lausanne, Switzerland.
   [Graff, Alexandra; Stahlberg, Henning] Univ Basel, Biozentrum, Ctr Cellular Imaging & NanoAnalyt, CH-4058 Basel, Switzerland.
   [Tomizaki, Takashi] Paul Scherrer Inst, Swiss Light Source, CH-5234 Villigen, Switzerland.
   [Desmyter, Aline] CNRS, UMR 7257, F-13288 Marseille, France.
   [Desmyter, Aline] Univ Aix Marseille, F-13288 Marseille, France.
   [Moreau, Christophe; Nury, Hugues] Univ Grenoble Alpes, IBS, F-38000 Grenoble, France.
   [Moreau, Christophe; Nury, Hugues] CNRS, IBS, F-38000 Grenoble, France.
   [Moreau, Christophe; Nury, Hugues] CEA, DSV, IBS, F-38000 Grenoble, France.
   [Li, Xiao-Dan] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland.
   [Poitevin, Frederic] Inst Pasteur, CNRS, UMR3528, Unite Dynam Struct Macromol, F-75015 Paris, France.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Basel; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Aix-Marseille Universite; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Nury, H (corresponding author), Ecole Polytech Fed Lausanne, Lab Phys Chem Polymers & Membranes, CH-1015 Lausanne, Switzerland.
EM horst.vogel@epfl.ch; hugues.nury@ibs.fr
FU Swiss National Science Foundation [31003A-133141]; Ecole Polytechnique Federale de Lausanne; European Community [211800]; Human Frontier Science Program; Agence Nationale de la Recherche (VenomPicoScreen project) [ANR-11-RPIB-022-04]; Swiss National Science Foundation (SNF) [31003A_133141] Funding Source: Swiss National Science Foundation (SNF)
NR 75
TC 322
Z9 356
U1 2
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 AUG 21
PY 2014
VL 512
IS 7514
BP 276
EP +
DI 10.1038/nature13552
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200027
PM 25119048
DA 2026-03-09
ER

PT J
AU Gall, C
   Hjorth, J
   Watson, D
   Dwek, E
   Maund, JR
   Fox, O
   Leloudas, G
   Malesani, D
   Day-Jones, AC
AF Gall, Christa
   Hjorth, Jens
   Watson, Darach
   Dwek, Eli
   Maund, Justyn R.
   Fox, Ori
   Leloudas, Giorgos
   Malesani, Daniele
   Day-Jones, Avril C.
TI Rapid formation of large dust grains in the luminous supernova 2010j1
SO NATURE
LA English
DT Article
ID large-magellanic-cloud; iin supernova; sn 2010jl; infrared-emission; interstellar dust; shock breakout; massive stars; milky-way; radiation; herschel
AB The origin of dust in galaxies is still a mystery(1-4). The majority of the refractory elements are produced in supernova explosions, but it is unclear how and where dust grains condense and grow, and how they avoid destruction in the harsh environments of star-forming galaxies. The recent detection of 0.1 to 0.5 solar masses of dust in nearby supernova remnants(5-7) suggests in situ dust formation, while other observations reveal very little dust in supernovae in the first few years after explosion(1,8,10). Observations of the spectral evolution of the bright SN 2010j1 have been interpreted as pre-existing dust(11), dust formationlz(12,13) or no dust at all(14). Here we report the rapid (40 to 240 days) formation of dust in its dense circumstellar medium. The wavelength-dependent extinction of this dust reveals the presence of very large (exceeding one micrometre) grains, which resist destruction(15). At later times (500 to 900 days), the near-infrared thermal emission shows an accelerated growth in dust mass, marking the transition of the dust source from the circumstellar medium to the ejecta. This provides the link between the early and late dust mass evolution in supernovae with dense circumstellar media.
C1 [Gall, Christa] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Gall, Christa; Hjorth, Jens; Watson, Darach; Maund, Justyn R.; Leloudas, Giorgos; Malesani, Daniele] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
   [Gall, Christa; Dwek, Eli] NASA, Observat Cosmol Lab, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Maund, Justyn R.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [Fox, Ori] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Leloudas, Giorgos] Stockholm Univ, Dept Phys, Oskar Klein Ctr, Albanova Univ Ctr, S-10691 Stockholm, Sweden.
   [Day-Jones, Avril C.] Univ Chile, Dept Astron, Santiago, Chile.
C3 Aarhus University; University of Copenhagen; Niels Bohr Institute; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Queens University Belfast; University of California System; University of California Berkeley; Oskar Klein Centre; Stockholm University; Universidad de Chile
RP Gall, C (corresponding author), Aarhus Univ, Dept Phys & Astron, Ny Munkegade 120, DK-8000 Aarhus C, Denmark.
EM cgall@phys.au.dk
FU ESO Telescopes at the La Silla paranal Observatory [084.C-0315(D), 087.C-0456(A)]; NASA Postdoctoral Program (NPP); Danish Agency for Science and Technology and Innovation; Swedish Research Council [623-2011-7117]; Proyecto Basal [PB06]; Joint Committee ESO-Government Chile; Danish National Research Foundation
NR 47
TC 193
Z9 204
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 JUL 17
PY 2014
VL 511
IS 7509
BP 326
EP +
DI 10.1038/nature13558
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200030
PM 25030169
DA 2026-03-09
ER

PT J
AU Geisler, JH
   Colbert, MW
   Carew, JL
AF Geisler, Jonathan H.
   Colbert, Matthew W.
   Carew, James L.
TI A new fossil species supports an early origin for toothed whale echolocation
SO NATURE
LA English
DT Article
ID functional-morphology; north-carolina; nasal complex; oligocene; cetacean; asymmetry; evolution; eocene
AB Odontocetes (toothed whales, dolphins and porpoises) hunt and navigate through dark and turbid aquatic environments using echolocation; a key adaptation that relies on the same principles as sonar(1). Among echolocating vertebrates, odontocetes are unique in producing high-frequency vocalizations at the phonic lips, a constriction in the nasal passages just beneath the blowhole, and then using air sinuses and the melon to modulate their transmission(2,3). Allextant odontocetes seem to echolocate(2,4); however, exactly when and how this complex behaviour-and its underlying anatomy-evolved is largely unknown. Here we report an odontocete fossil, Oligocene in age (approximately 28 Myr ago), from South Carolina (Cotylocara macei, gen. et sp. nov.) that has several features suggestive of echolocation: a dense, thick and downturned rostrum; air sac fossae; cranial asymmetry; and exceptionally broad maxillae. Our phylogenetic analysis places Cotylocara in a basal clade of odontocetes, leading us to infer that a rudimentary form of echolocation evolved in the early Oligocene, shortly after odontocetes diverged from the ancestors of filter-feedingwhales (mysticetes). This was followed by enlargement of the facial muscles that modulate echolocation calls, which in turn led to marked, convergent changes in skull shape in the ancestors of Cotylocara, and in the lineage leading to extant odontocetes.
C1 [Geisler, Jonathan H.] New York Inst Technol, Coll Osteopath Med, Dept Anat, Old Westbury, NY 11568 USA.
   [Colbert, Matthew W.] Univ Texas Austin, Jackson Sch Geosci, Austin, TX 78712 USA.
   [Carew, James L.] Coll Charleston, Nat Hist Museum, Dept Geol & Environm Geosci, Charleston, SC 29424 USA.
C3 New York Institute Technology; University of Texas System; University of Texas Austin; College of Charleston
RP Geisler, JH (corresponding author), New York Inst Technol, Coll Osteopath Med, Dept Anat, Northern Blvd, Old Westbury, NY 11568 USA.
EM jgeisler@nyit.edu
FU New York Institute of Technology, College of Charleston; NSF [IIS-987-4781]; Division Of Earth Sciences; Directorate For Geosciences [1258878] Funding Source: National Science Foundation
NR 30
TC 104
Z9 114
U1 0
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 APR 17
PY 2014
VL 508
IS 7496
BP 383
EP +
DI 10.1038/nature13086
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000049
PM 24670659
DA 2026-03-09
ER

PT J
AU Vande Walle, L
   Van Opdenbosch, N
   Jacques, P
   Fossoul, A
   Verheugen, E
   Vogel, P
   Beyaert, R
   Elewaut, D
   Kanneganti, TD
   van Loo, G
   Lamkanfi, M
AF Vande Walle, Lieselotte
   Van Opdenbosch, Nina
   Jacques, Peggy
   Fossoul, Amelie
   Verheugen, Eveline
   Vogel, Peter
   Beyaert, Rudi
   Elewaut, Dirk
   Kanneganti, Thirumala-Devi
   van Loo, Geert
   Lamkanfi, Mohamed
TI Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis
SO NATURE
LA English
DT Article
ID nf-kappa-b; rheumatoid-arthritis; activation; inhibitor; susceptibility; association; caspase-1; variants; receptor; tnfaip3
AB Rheumatoid arthritis is a chronic autoinflammatory disease that affects 1-2% of the world's population and is characterized by widespread joint inflammation. Interleukin-1 is an important mediator of cartilage destruction in rheumatic diseases(1), but our understanding of the upstream mechanisms leading to production of interleukin-1 beta in rheumatoid arthritis is limited by the absence of suitable mouse models of the disease in which inflammasomes contribute to pathology. Myeloid-cell-specific deletion of the rheumatoid arthritis susceptibility gene A20/Tnfaip3 in mice (A20(myel-KO) mice) triggers a spontaneous erosive polyarthritis that resembles rheumatoid arthritis in patients(2). Rheumatoid arthritis in A20(myel-KO) mice is not rescued by deletion of tumour necrosis factor receptor 1 (ref. 2). Here we show, however, that it crucially relies on the Nlrp3 inflammasome and interleukin-1 receptor signalling. Macrophages lacking A 20 have increased basal and lipopolysaccharide-induced expression levels of the inflammasome adaptor Nlrp3 and proIL-beta b. As a result, A 20-deficiency in macrophages significantly enhances Nlrp3 inflammasome- mediated caspase-1 activation, pyroptosis and interleukin-1 beta secretion by soluble and crystalline Nlrp3 stimuli. In contrast, activation of the Nlrc4 and AIM2 inflammasomes is not altered. Importantly, increased Nlrp3 inflammasome activation contributes to the pathology of rheumatoid arthritis in vivo, because deletion of Nlrp3, caspase-1 and the interleukin-1 receptor markedly protects against rheumatoid-arthritis-associated inflammation and cartilage destruction in A20(myel-KO) mice. These results reveal A20 as a novel negative regulator of Nlrp3 inflammasome activation, and describe A(20myel-KO) mice as the first experimental model to study the role of inflammasomes in the pathology of rheumatoid arthritis.
C1 [Vande Walle, Lieselotte; Van Opdenbosch, Nina; Fossoul, Amelie; Lamkanfi, Mohamed] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Vande Walle, Lieselotte; Van Opdenbosch, Nina; Fossoul, Amelie; Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Jacques, Peggy; Verheugen, Eveline; Elewaut, Dirk] Univ Ghent, Dept Rheumatol, B-9000 Ghent, Belgium.
   [Vogel, Peter; Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Beyaert, Rudi; van Loo, Geert] Univ Ghent VIB, Inflammat Res Ctr, B-9052 Ghent, Belgium.
   [Beyaert, Rudi; van Loo, Geert] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium.
C3 Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University; St Jude Children's Research Hospital; Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University
RP Lamkanfi, M (corresponding author), Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
EM mohamed.lamkanfi@vib-ugent.be
FU Ghent University [BOF14/GOA/013]; European Research Council [281600]; FWO [G030212N, 1.2.201.10.N.00, 1.5.122.11.N.00, Odysseus-G091908, G061910N, G016812N]; Queen Elisabeth Medical Foundation; Ghent University Group-ID MRP; National Institutes of Health [AR056296, CA163507, AI101935]; American Lebanese Syrian Associated Charities; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R37AI101935] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR056296] Funding Source: NIH RePORTER
NR 26
TC 429
Z9 455
U1 1
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 AUG 7
PY 2014
VL 512
IS 7512
BP 69
EP +
DI 10.1038/nature13322
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000033
PM 25043000
DA 2026-03-09
ER

PT J
AU Ghisellini, G
   Tavecchio, F
   Maraschi, L
   Celotti, A
   Sbarrato, T
AF Ghisellini, G.
   Tavecchio, F.
   Maraschi, L.
   Celotti, A.
   Sbarrato, T.
TI The power of relativistic jets is larger than the luminosity of their accretion disks
SO NATURE
LA English
DT Article
ID active galactic nuclei; large-area telescope; supermassive black-holes; digital sky survey; minimum power; fermi blazars; galaxy; catalog; quasar; energy
AB Theoretical models for the production of relativistic jets from active galactic nuclei predict that jet power arises from the spin and mass of the central supermassive black hole, as well as from the magnetic field near the event horizon(1). The physical mechanism underlying the contribution from the magnetic field is the torque exerted on the rotating black hole by the field amplified by the accreting material. If the squared magnetic field is proportional to the accretion rate, then there will be a correlation between jet power and accretion luminosity. There is evidence for such a correlation(2-8), but inadequate knowledge of the accretion luminosity of the limited and inhomogeneous samples used prevented a firm conclusion. Here we report an analysis of archival observations of a sample of blazars (quasars whose jets point towards Earth) that overcomes previous limitations. We find a clear correlation between jet power, as measured through the gamma-ray luminosity, and accretion luminosity, as measured by the broad emission lines, with the jet power dominating the disk luminosity, in agreement with numerical simulations(9). This implies that the magnetic field threading the black hole horizon reaches the maximum value sustainable by the accreting matter(10).
C1 [Ghisellini, G.; Tavecchio, F.; Maraschi, L.; Celotti, A.; Sbarrato, T.] Ist Nazl Astrofis, Osservatorio Astron Brera, I-23807 Merate, Italy.
   [Maraschi, L.] Ist Nazl Astrofis, Osservatorio Astron Brera, I-20121 Milan, Italy.
   [Celotti, A.] Scuola Int Super Studi Avanzati, I-34135 Trieste, Italy.
   [Celotti, A.] Ist Nazl Fis Nucl, Sez Trieste, I-34127 Trieste, Italy.
   [Sbarrato, T.] Univ Insubria, Dipartimento Fis & Matemat, I-22100 Como, Italy.
   [Sbarrato, T.] European So Observ, D-8578 Garching, Germany.
C3 Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); International School for Advanced Studies (SISSA); Istituto Nazionale di Fisica Nucleare (INFN); University of Insubria; European Southern Observatory
RP Ghisellini, G (corresponding author), Ist Nazl Astrofis, Osservatorio Astron Brera, Via E Bianchi 46, I-23807 Merate, Italy.
EM gabriele.ghisellini@brera.inaf.it
FU PRIN-INAF grant
NR 48
TC 372
Z9 400
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 20
PY 2014
VL 515
IS 7527
BP 376
EP +
DI 10.1038/nature13856
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600037
PM 25409827
DA 2026-03-09
ER

PT J
AU Tan, AYY
   Chen, YZ
   Scholl, B
   Seidemann, E
   Priebe, NJ
AF Tan, Andrew Y. Y.
   Chen, Yuzhi
   Scholl, Benjamin
   Seidemann, Eyal
   Priebe, Nicholas J.
TI Sensory stimulation shifts visual cortex from synchronous to asynchronous states
SO NATURE
LA English
DT Article
ID neural population responses; in-vivo; neocortical neurons; stimulus contrast; cortical circuits; auditory-cortex; barrel cortex; complex cells; networks; dynamics
AB In the mammalian cerebral cortex, neural responses are highly variable during spontaneous activity and sensory stimulation. To explain this variability, the cortex of alert animals has been proposed to be in an asynchronous high-conductance state in which irregular spiking arises from the convergence of large numbers of uncorrelated excitatory and inhibitory inputs onto individual neurons(1-4). Signatures of this state are that a neuron's membrane potential (V-m) hovers just below spike threshold, and its aggregate synaptic input is nearly Gaussian, arising from many uncorrelated inputs(1-4). Alternatively, irregular spiking could arise from infrequent correlated input events that elicit large fluctuations in V-m (refs 5, 6). To distinguish between these hypotheses, we developed a technique to perform whole-cell V-m measurements from the cortex of behaving monkeys, focusing on primary visual cortex (V1) of monkeys performing a visual fixation task. Here we show that, contrary to the predictions of an asynchronous state, mean V-m during fixation was far from threshold (14 mV) and spiking was triggered by occasional large spontaneous fluctuations. Distributions of V-m values were skewed beyond that expected for a range of Gaussian input(6,7), but were consistent with synaptic input arising from infrequent correlated events(5,6). Furthermore, spontaneous fluctuations in V-m were correlated with the surrounding network activity, as reflected in simultaneously recorded nearby local field potential. Visual stimulation, however, led to responses more consistent with an asynchronous state: mean V-m approached threshold, fluctuations became more Gaussian, and correlations between single neurons and the surrounding network were disrupted. These observations show that sensory drive can shift a common cortical circuitry from a synchronous to an asynchronous state.
C1 [Tan, Andrew Y. Y.; Chen, Yuzhi; Scholl, Benjamin; Seidemann, Eyal; Priebe, Nicholas J.] Univ Texas Austin, Ctr Perceptual Syst, Austin, TX 78712 USA.
   [Tan, Andrew Y. Y.; Chen, Yuzhi; Scholl, Benjamin; Seidemann, Eyal; Priebe, Nicholas J.] Univ Texas Austin, Coll Nat Sci, Dept Neurosci, Austin, TX 78712 USA.
   [Chen, Yuzhi; Seidemann, Eyal] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
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
RP Tan, AYY (corresponding author), Univ Texas Austin, Ctr Perceptual Syst, Austin, TX 78712 USA.
EM atyy@alum.mit.edu; nico@austin.utexas.edu
FU National Institutes of Health (NIH) [EY-019288]; Pew Charitable Trusts; NIH [EY-016454, EY-16752]; National Eye Institute [R01EY016454, T32EY021462] Funding Source: NIH RePORTER
NR 51
TC 163
Z9 199
U1 1
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 MAY 8
PY 2014
VL 509
IS 7499
BP 226
EP +
DI 10.1038/nature13159
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300039
PM 24695217
DA 2026-03-09
ER

PT J
AU Subramanian, S
   Huq, S
   Yatsunenko, T
   Haque, R
   Mahfuz, M
   Alam, MA
   Benezra, A
   DeStefano, J
   Meier, MF
   Muegge, BD
   Barratt, MJ
   VanArendonk, LG
   Zhang, QY
   Province, MA
   Petri, WA
   Ahmed, T
   Gordon, JI
AF Subramanian, Sathish
   Huq, Sayeeda
   Yatsunenko, Tanya
   Haque, Rashidul
   Mahfuz, Mustafa
   Alam, Mohammed A.
   Benezra, Amber
   DeStefano, Joseph
   Meier, Martin F.
   Muegge, Brian D.
   Barratt, Michael J.
   VanArendonk, Laura G.
   Zhang, Qunyuan
   Province, Michael A.
   Petri, William A., Jr.
   Ahmed, Tahmeed
   Gordon, Jeffrey I.
TI Persistent gut microbiota immaturity in malnourished Bangladeshi children
SO NATURE
LA English
DT Article
ID growth; malnutrition; age
AB Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem(1,2). The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying amachine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiotafor- age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
C1 [Subramanian, Sathish; Yatsunenko, Tanya; Benezra, Amber; DeStefano, Joseph; Meier, Martin F.; Muegge, Brian D.; Barratt, Michael J.; VanArendonk, Laura G.; Gordon, Jeffrey I.] Washington Univ, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Huq, Sayeeda; Haque, Rashidul; Mahfuz, Mustafa; Alam, Mohammed A.; Ahmed, Tahmeed] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Dhaka 1212, Bangladesh.
   [Benezra, Amber] New Sch Social Res, Dept Anthropol, New York, NY 10003 USA.
   [Zhang, Qunyuan; Province, Michael A.] Washington Univ, Div Stat Genom, St Louis, MO 63108 USA.
   [Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA.
   [Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Microbiol & Pathol, Charlottesville, VA 22908 USA.
C3 Washington University (WUSTL); International Centre for Diarrhoeal Disease Research (ICDDR); The New School; Washington University (WUSTL); University of Virginia; University of Virginia
RP Gordon, JI (corresponding author), Washington Univ, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
EM jgordon@wustl.edu
FU Bill & Melinda Gates Foundation; International Atomic Energy Agency; NIH [AI043596]; SBE Doctoral Dissertation Research Improvement Grant (NSF) [SES-1027035]; National Institute of Allergy and Infectious Diseases [R01AI043596] Funding Source: NIH RePORTER
NR 28
TC 967
Z9 1136
U1 2
U2 243
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 417
EP +
DI 10.1038/nature13421
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200039
PM 24896187
DA 2026-03-09
ER

PT J
AU Treutlein, B
   Brownfield, DG
   Wu, AR
   Neff, NF
   Mantalas, GL
   Espinoza, FH
   Desai, TJ
   Krasnow, MA
   Quake, SR
AF Treutlein, Barbara
   Brownfield, Doug G.
   Wu, Angela R.
   Neff, Norma F.
   Mantalas, Gary L.
   Espinoza, F. Hernan
   Desai, Tushar J.
   Krasnow, Mark A.
   Quake, Stephen R.
TI Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq
SO NATURE
LA English
DT Article
ID stem-cells; expression; reveals; landscape; alignment
AB The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers(1-3) and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations(1-5). Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.
C1 [Treutlein, Barbara; Wu, Angela R.; Neff, Norma F.; Mantalas, Gary L.; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Sch Med, Stanford, CA 94305 USA.
   [Treutlein, Barbara; Wu, Angela R.; Neff, Norma F.; Mantalas, Gary L.; Quake, Stephen R.] Stanford Univ, Dept Appl Phys, Sch Med, Stanford, CA 94305 USA.
   [Treutlein, Barbara; Brownfield, Doug G.; Wu, Angela R.; Neff, Norma F.; Mantalas, Gary L.; Espinoza, F. Hernan; Krasnow, Mark A.; Quake, Stephen R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Brownfield, Doug G.; Espinoza, F. Hernan; Krasnow, Mark A.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA.
   [Desai, Tushar J.] Stanford Univ, Div Pulm & Crit Care Med, Dept Internal Med, Sch Med, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University; Stanford University
RP Quake, SR (corresponding author), Stanford Univ, Dept Bioengn, Sch Med, Stanford, CA 94305 USA.
EM tdesai@stanford.edu; krasnow@stanford.edu; quake@stanford.edu
FU National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium Grant [U01HL099995]; National Institutes of Health (NIH) [T32HD007249]; Parker B. Francis Foundation Fellowship; NIH [5KO8HL084095, U01HL099999]
NR 41
TC 1037
Z9 1381
U1 5
U2 349
PU NATURE PUBLISHING 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 15
PY 2014
VL 509
IS 7500
BP 371
EP +
DI 10.1038/nature13173
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200041
PM 24739965
DA 2026-03-09
ER

PT J
AU Suzuki, T
   Arumugam, P
   Sakagami, T
   Lachmann, N
   Chalk, C
   Sallese, A
   Abe, S
   Trapnell, C
   Carey, B
   Moritz, T
   Malik, P
   Lutzko, C
   Wood, RE
   Trapnell, BC
AF Suzuki, Takuji
   Arumugam, Paritha
   Sakagami, Takuro
   Lachmann, Nico
   Chalk, Claudia
   Sallese, Anthony
   Abe, Shuichi
   Trapnell, Cole
   Carey, Brenna
   Moritz, Thomas
   Malik, Punam
   Lutzko, Carolyn
   Wood, Robert E.
   Trapnell, Bruce C.
TI Pulmonary macrophage transplantation therapy
SO NATURE
LA English
DT Article
ID colony-stimulating factor; bone-marrow-transplantation; receptor-deficient mice; alveolar proteinosis; gm-csf; tissue macrophages; gene-therapy; mouse model; stem-cells; lung
AB Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using granulocytemacrophage colony-stimulating factor (GM-CSF) receptor-beta-deficient (Csf2rb(-/-)) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well-tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP.
C1 [Suzuki, Takuji; Sakagami, Takuro; Chalk, Claudia; Sallese, Anthony; Abe, Shuichi; Carey, Brenna; Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Div Pulm Biol, Cincinnati, OH 45229 USA.
   [Arumugam, Paritha; Malik, Punam; Lutzko, Carolyn] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA.
   [Lachmann, Nico; Moritz, Thomas] Hannover Med Sch, Inst Expt Hematol, RG Reprograming & Gene Therapy, D-30625 Hannover, Germany.
   [Trapnell, Cole] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Trapnell, Cole] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02138 USA.
   [Wood, Robert E.; Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Med, Cincinnati, OH 45229 USA.
   [Trapnell, Bruce C.] Univ Cincinnati, Med Ctr, Div Pulm Crit Care & Sleep Med, Cincinnati, OH 45229 USA.
C3 Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Hannover Medical School; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati
RP Trapnell, BC (corresponding author), Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Div Pulm Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM Takuji.Suzuki@cchmc.org; Bruce.Trapnell@cchmc.org
FU NIH [R01 HL085453, R21 HL106134, R01HL118342, 8UL1TR000077-05, AR-47363, DK78392, DK90971]; American Thoracic Society Foundation Unrestricted Research Grant; CCHMC Foundation Trustee Grant; Deutsche Forschungsgemeinschaft (DFG) [Exc 62/1]; Else Kroner-Fresenius Stiftung; Eva-Luise Koehler Research Prize for Rare Diseases; Pulmonary Biology Division, CCHMC; Grants-in-Aid for Scientific Research [26461498] Funding Source: KAKEN; National Heart Lung and Blood Institute [R01HL085453, R01HL118342] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK078392] Funding Source: NIH RePORTER
NR 54
TC 245
Z9 296
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 OCT 23
PY 2014
VL 514
IS 7523
BP 450
EP +
DI 10.1038/nature13807
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900031
PM 25274301
DA 2026-03-09
ER

PT J
AU Meunier, E
   Dick, MS
   Dreier, RF
   Schürmann, N
   Broz, DK
   Warming, S
   Roose-Girma, M
   Bumann, D
   Kayagaki, N
   Takeda, K
   Yamamoto, M
   Broz, P
AF Meunier, Etienne
   Dick, Mathias S.
   Dreier, Roland F.
   Schuermann, Nura
   Broz, Daniela Kenzelmann
   Warming, Soren
   Roose-Girma, Merone
   Bumann, Dirk
   Kayagaki, Nobuhiko
   Takeda, Kiyoshi
   Yamamoto, Masahiro
   Broz, Petr
TI Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases
SO NATURE
LA English
DT Article
ID noncanonical inflammasome activation; toxoplasma-gondii; host-defense; immunity; salmonella; infection; autophagy; nlrp3; resistance; protects
AB Lipopolysaccharide from Gram-negative bacteria is sensed in the host cell cytoplasm by a non-canonical inflammasome pathway that ultimately results in caspase-11 activation and cell death(1-3). In mouse macrophages, activation of this pathway requires the production of type-I interferons(4,5), indicating that interferon-induced genes have a critical role in initiating this pathway. Here we report that a cluster of small interferon-inducible GTPases, the so-called guanylate-binding proteins, is required for the full activity of the non-canonical caspase-11 inflammasome during infections with vacuolar Gram-negative bacteria. We show that guanylate-binding proteins are recruited to intracellular bacterial pathogens and are necessary to induce the lysis of the pathogen-containing vacuole. Lysis of the vacuole releases bacteria into the cytosol, thus allowing the detection of their lipopolysaccharide by a yet unknown lipopolysaccharide sensor. Moreover, recognition of the lysed vacuole by the danger sensor galectin-8 initiates the uptake of bacteria into autophagosomes, which results in a reduction of caspase-11 activation. These results indicate that host-mediated lysis of pathogen-containing vacuoles is an essential immune function and is necessary for efficient recognition of pathogens by inflammasome complexes in the cytosol.
C1 [Meunier, Etienne; Dick, Mathias S.; Dreier, Roland F.; Schuermann, Nura; Bumann, Dirk; Broz, Petr] Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland.
   [Broz, Daniela Kenzelmann] Univ Basel, Dept Biomed, CH-4056 Basel, Switzerland.
   [Warming, Soren; Roose-Girma, Merone; Kayagaki, Nobuhiko] Genentech Inc, San Francisco, CA 94080 USA.
   [Takeda, Kiyoshi; Yamamoto, Masahiro] Osaka Univ, Dept Microbiol & Immunol, Suita, Osaka 5650871, Japan.
C3 University of Basel; University of Basel; Roche Holding; Genentech; Roche Holding USA; University of Osaka
RP Broz, P (corresponding author), Univ Basel, Biozentrum, Focal Area Infect Biol, CH-4056 Basel, Switzerland.
EM petr.broz@unibas.ch
FU SNSF [PP00P3_139120/1]; University of Basel [ID2153162]; Marie Heim-Voegtlin Fellowship [145516]
NR 26
TC 384
Z9 454
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 MAY 15
PY 2014
VL 509
IS 7500
BP 366
EP +
DI 10.1038/nature13157
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200040
PM 24739961
DA 2026-03-09
ER

PT J
AU Sánchez-Rivera, FJ
   Papagiannakopoulos, T
   Romero, R
   Tammela, T
   Bauer, MR
   Bhutkar, A
   Joshi, NS
   Subbaraj, L
   Bronson, RT
   Xue, W
   Jacks, T
AF Sanchez-Rivera, Francisco J.
   Papagiannakopoulos, Thales
   Romero, Rodrigo
   Tammela, Tuomas
   Bauer, Matthew R.
   Bhutkar, Arjun
   Joshi, Nikhil S.
   Subbaraj, Lakshmipriya
   Bronson, Roderick T.
   Xue, Wen
   Jacks, Tyler
TI Rapid modelling of cooperating genetic events in cancer through somatic genome editing
SO NATURE
LA English
DT Article
ID lung adenocarcinoma; sequencing data; human-cells; progression; catenin; repair; cas9; endonuclease; nucleases; hallmarks
AB Cancer is a multistep process that involves mutations and other alterations in oncogenes and tumour suppressor genes(1). Genome sequencing studies have identified a large collection of genetic alterations that occur in human cancers(2-4). However, the determination of which mutations are causally related to tumorigenesis remains a major challenge. Here we describe a novel CRISPR/Cas9-based approach for rapid functional investigation of candidate genes in well-established autochthonous mouse models of cancer. Using a Kras(G12D)-driven lung cancer model(5), we performed functional characterization of a panel of tumour suppressor genes with knownloss-of-function alterations in human lung cancer. Cre-dependent somatic activation of oncogenic Kras(G12D) combined with CRISPR/Cas9-mediated genome editing of tumour suppressor genes resulted in lung adenocarcinomas with distinct histopathological and molecular features. This rapid somatic genome engineering approach enables functional characterization of putative cancer genes in the lung and other tissues using autochthonous mouse models. We anticipate that this approach can be used to systematically dissect the complex catalogue of mutations identified in cancer genome sequencing studies.
C1 [Sanchez-Rivera, Francisco J.; Papagiannakopoulos, Thales; Romero, Rodrigo; Tammela, Tuomas; Bauer, Matthew R.; Bhutkar, Arjun; Joshi, Nikhil S.; Subbaraj, Lakshmipriya; Xue, Wen; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
   [Sanchez-Rivera, Francisco J.; Romero, Rodrigo; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Bronson, Roderick T.] Tufts Univ, Boston, MA 02115 USA.
   [Bronson, Roderick T.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Tufts University; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Jacks, T (corresponding author), MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
EM tjacks@mit.edu
FU Howard Hughes Medical Institute; Ludwig Center for Molecular Oncology at MIT; Cancer Center Support (core) grant from the National Cancer Institute [P30-CA14051]; Hope Funds for Cancer Research; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 39
TC 336
Z9 397
U1 1
U2 109
PU NATURE PUBLISHING 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 18
PY 2014
VL 516
IS 7531
BP 428
EP +
DI 10.1038/nature13906
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800054
PM 25337879
DA 2026-03-09
ER

PT J
AU Tumbale, P
   Williams, JS
   Schellenberg, MJ
   Kunkel, TA
   Williams, RS
AF Tumbale, Percy
   Williams, Jessica S.
   Schellenberg, Matthew J.
   Kunkel, Thomas A.
   Williams, R. Scott
TI Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity
SO NATURE
LA English
DT Article
ID ribonucleotide incorporation; polymerase; removal; superfamily; mutations; ataxia
AB Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases(1,2). Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions(3-6). Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-Zn complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease.
C1 [Tumbale, Percy; Williams, Jessica S.; Schellenberg, Matthew J.; Kunkel, Thomas A.; Williams, R. Scott] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
   [Williams, Jessica S.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
RP Williams, RS (corresponding author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM williamsrs@niehs.nih.gov
FU US National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) [1Z01ES102765, Z01ES065070]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; National Institute of Environmental Health Sciences [ZIAES065070, ZIAES102765] Funding Source: NIH RePORTER
NR 38
TC 89
Z9 104
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 FEB 6
PY 2014
VL 506
IS 7486
BP 111
EP +
DI 10.1038/nature12824
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100042
PM 24362567
DA 2026-03-09
ER

PT J
AU He, B
   Doubrovinski, K
   Polyakov, O
   Wieschaus, E
AF He, Bing
   Doubrovinski, Konstantin
   Polyakov, Oleg
   Wieschaus, Eric
TI Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation
SO NATURE
LA English
DT Article
ID particle-tracking microrheology; drosophila gastrulation; adherens junctions; morphogenesis; mechanics; membrane; cleavage; encodes; embryos
AB Epithelial folding mediated by apical constriction converts flat epithelial sheets into multilayered, complex tissue structures and is used throughout development inmost animals(1). Little is known, however, about how forces produced near the apical surface of the tissue are transmitted within individual cells to generate the global changes in cell shape that characterize tissue deformation. Here we apply particle tracking velocimetry in gastrulating Drosophila embryos to measure the movement of cytoplasm and plasma membrane during ventral furrow formation(2,3). We find that cytoplasmic redistribution during the lengthening phase of ventral furrow formation can be precisely described by viscous flows that quantitatively match the predictions of hydrodynamics. Cell membranes move with the ambient cytoplasm, with little resistance to, or driving force on, the flow. Strikingly, apical constriction produces similar flow patterns in mutant embryos that fail to form cells before gastrulation ('acellular' embryos), such that the global redistribution of cytoplasm mirrors the summed redistribution occurring in individual cells of wild-type embryos. Our results indicate that during the lengthening phase of ventral furrow formation, hydrodynamic behaviour of the cytoplasm provides the predominant mechanism transmitting apically generated forces deep into the tissue and that cell individualization is dispensable. [GRAPHICS] .
C1 [He, Bing; Doubrovinski, Konstantin; Wieschaus, Eric] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Polyakov, Oleg] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Wieschaus, Eric] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University; Howard Hughes Medical Institute
RP Wieschaus, E (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
EM efw@princeton.edu
FU National Institutes of Health (National Institute of Child Health and Human Development) [5R37HD15587]; Howard Hughes Medical Institute; New Jersey Commission on Cancer Research Fellowship; National Institutes of Health [P50 GM 071508]
NR 37
TC 173
Z9 201
U1 0
U2 62
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2014
VL 508
IS 7496
BP 392
EP +
DI 10.1038/nature13070
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000051
PM 24590071
DA 2026-03-09
ER

PT J
AU Madiraju, AK
   Erion, DM
   Rahimi, Y
   Zhang, XM
   Braddock, DT
   Albright, RA
   Prigaro, BJ
   Wood, JL
   Bhanot, S
   MacDonald, MJ
   Jurczak, MJ
   Camporez, JP
   Lee, HY
   Cline, GW
   Samuel, VT
   Kibbey, RG
   Shulman, GI
AF Madiraju, Anila K.
   Erion, Derek M.
   Rahimi, Yasmeen
   Zhang, Xian-Man
   Braddock, Demetrios T.
   Albright, Ronald A.
   Prigaro, Brett J.
   Wood, John L.
   Bhanot, Sanjay
   MacDonald, Michael J.
   Jurczak, Michael J.
   Camporez, Joao-Paulo
   Lee, Hui-Young
   Cline, Gary W.
   Samuel, Varman T.
   Kibbey, Richard G.
   Shulman, Gerald I.
TI Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
SO NATURE
LA English
DT Article
ID glycerol 3-phosphate dehydrogenase; activated protein-kinase; glycerol-3-phosphate dehydrogenase; redox state; hepatic gluconeogenesis; reducing equivalents; glucose-homeostasis; liver; diet; phosphorylation
AB Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia(1,2). For over half a century, this agent has been prescribed to patients with type 2 diabetes world wide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production, while increasing cytosolic redox and decreasing mitochondrial redox states. Antisense oligonucleotide knockdown of hepatic mitochondrial glycerophosphate dehydrogenase in rats resulted in a phenotype akin to chronic metformin treatment, and abrogated metformin-mediated increases in cytosolic redox state, decreases in plasma glucose concentrations, and inhibition of endogenous glucose production. These findings were replicated in whole-body mitochondrial glycerophosphate dehydrogenase knockout mice. These results have significant implications for understanding the mechanism of metformin's blood glucose lowering effects and provide a new therapeutic target for type 2 diabetes.
C1 [Madiraju, Anila K.; Erion, Derek M.; Rahimi, Yasmeen; Zhang, Xian-Man; Jurczak, Michael J.; Camporez, Joao-Paulo; Lee, Hui-Young; Cline, Gary W.; Samuel, Varman T.; Kibbey, Richard G.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
   [Madiraju, Anila K.; Erion, Derek M.; Kibbey, Richard G.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
   [Madiraju, Anila K.; Erion, Derek M.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Braddock, Demetrios T.; Albright, Ronald A.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Prigaro, Brett J.] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA.
   [Wood, John L.] Baylor Univ, Dept Chem & Biochem, Canc Prevent Res Inst Texas Scholar, Waco, TX 76798 USA.
   [Bhanot, Sanjay] ISIS Pharmaceut, Carlsbad, CA 92010 USA.
   [MacDonald, Michael J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
   [Shulman, Gerald I.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
C3 Yale University; Yale University; Yale University; Howard Hughes Medical Institute; Yale University; Colorado State University System; Colorado State University Fort Collins; Baylor University; Ionis Pharmaceuticals, Inc.; University of Wisconsin System; University of Wisconsin Madison; University of Copenhagen; Novo Nordisk Foundation
RP Shulman, GI (corresponding author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St, New Haven, CT 06520 USA.
EM gerald.shulman@yale.edu
FU National Institutes of Health [R24 DK-085638, R01 DK-40936, P30 DK-45735, P30 DK-034989, U24 DK-059635, R01 DK-28348, K01 DK-099402, R01 DK-092606]; American Diabetes Association [7-12-BS-092, 1-14-Merck-10]; VA Merit Award [I01-BX000901]; Novo Nordisk Foundation Center for Basic Metabolic Research; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK045735, P30DK034989] Funding Source: NIH RePORTER
NR 33
TC 1012
Z9 1185
U1 0
U2 316
PU NATURE PUBLISHING 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 26
PY 2014
VL 510
IS 7506
BP 542
EP +
DI 10.1038/nature13270
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300048
PM 24847880
DA 2026-03-09
ER

PT J
AU Vachieri, SG
   Xiong, XL
   Collins, PJ
   Walker, PA
   Martin, SR
   Haire, LF
   Zhang, Y
   McCauley, JW
   Gamblin, SJ
   Skehel, JJ
AF Vachieri, Sebastien G.
   Xiong, Xiaoli
   Collins, Patrick J.
   Walker, Philip A.
   Martin, Stephen R.
   Haire, Lesley F.
   Zhang, Ying
   McCauley, John W.
   Gamblin, Steven J.
   Skehel, John J.
TI Receptor binding by H10 influenza viruses
SO NATURE
LA English
DT Article
ID a virus; hemagglutinin; h5; specificity; complexes; epithelium; evolution; selection; cell; h7
AB H10N8 follows H7N9 and H5N1 as the latest in a line of avian influenza viruses that cause serious disease in humans and have become a threat to public health(1). Since December 2013, three human cases of H10N8 infection have been reported, two of whom are known to have died. To gather evidence relating to the epidemic potential of H10 we have determined the structure of the haemagglutinin of a previously isolated avian H10 virus and we present here results relating especially to its receptor-binding properties, as these are likely to be major determinants of virus transmissibility. Our results show, first, that the H10 virus possesses high avidity for human receptors and second, from the crystal structure of the complex formed by avian H10 haemagglutinin with human receptor, it is clear that the conformation of the bound receptor has characteristics of both the 1918 H1N1 pandemic virus(2) and the human H7 viruses isolated from patients in 2013 (ref. 3). We conclude that avian H10N8 virus has sufficient avidity for human receptors to account for its infection of humans but that its preference for avian receptors should make avian receptor-rich human airway mucins(4) an effective block to widespread infection. In terms of surveillance, particular attention will be paid to the detection of mutations in the receptor-binding site of the H10 haemagglutinin that decrease its avidity for avian receptor, and could enable it to be more readily transmitted between humans.
C1 [Vachieri, Sebastien G.; Xiong, Xiaoli; Collins, Patrick J.; Walker, Philip A.; Martin, Stephen R.; Haire, Lesley F.; Zhang, Ying; McCauley, John W.; Gamblin, Steven J.; Skehel, John J.] MRC Natl Inst Med Res, London NW7 1AA, England.
C3 MRC National Institute for Medical Research
RP Gamblin, SJ (corresponding author), MRC Natl Inst Med Res, Mill Hill, London NW7 1AA, England.
EM sgambli@nimr.mrc.ac.uk; skeheljj@nimr.mrc.ac.uk
FU Medical Research Council [U117584222, U117570592, U117585868]; MRC [MC_U117585868, MC_U117512723, G0600522] Funding Source: UKRI; Medical Research Council [MC_U117512723, MC_U117585868, G0600522] Funding Source: researchfish
NR 27
TC 72
Z9 78
U1 2
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 24
PY 2014
VL 511
IS 7510
BP 475
EP +
DI 10.1038/nature13443
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700048
PM 24870229
DA 2026-03-09
ER

PT J
AU Zeng, N
   Zhao, F
   Collatz, GJ
   Kalnay, E
   Salawitch, RJ
   West, TO
   Guanter, L
AF Zeng, Ning
   Zhao, Fang
   Collatz, George J.
   Kalnay, Eugenia
   Salawitch, Ross J.
   West, Tristram O.
   Guanter, Luis
TI Agricultural Green Revolution as a driver of increasing atmospheric CO2 seasonal amplitude
SO NATURE
LA English
DT Article
ID mauna-loa; carbon-dioxide; chlorophyll fluorescence; human appropriation; cycle; vegetation; 20th-century; variability; biosphere; ecosystem
AB The atmospheric carbon dioxide (CO2) record displays a prominent seasonal cycle that arises mainly from changes in vegetation growth and the corresponding CO2 uptake during the boreal spring and summer growing seasons and CO2 release during the autumn and winter seasons(1). The CO2 seasonal amplitude has increased over the past five decades, suggesting an increase in Northern Hemisphere biospheric activity(2,5,6). It has been proposed that vegetation growth may have been stimulated by higher concentrations of CO2 as well as by warming in recent decades, but such mechanisms have been unable to explain the full range and magnitude of the observed increase in CO2 seasonal amplitude(2,6-13). Here we suggest that the intensification of agriculture (the Green Revolution, in which much greater crop yield per unit area was achieved by hybridization, irrigation and fertilization) during the past five decades is a driver of changes in the seasonal characteristics of the global carbon cycle. Our analysis of CO2 data and atmospheric inversions shows a robust 15 per cent long-term increase in CO2 seasonal amplitude from 1961 to 2010, punctuated by large decadal and interannual variations. Using a terrestrial carbon cycle model that takes into account high-yield cultivars, fertilizer use and irrigation, we find that the long-term increase in CO2 seasonal amplitude arises from two major regions: the midlatitude cropland between 25 degrees N and 60 degrees N and the high-latitude natural vegetation between 50 degrees N and 70 degrees N. The long-term trend of seasonal amplitude increase is 0.311 +/- 0.027 per cent per year, of which sensitivity experiments attribute 45,29 and 26 per cent to land-use change, climate variability and change, and increased productivity due to CO2 fertilization, respectively. Vegetation growth was earlier by one to two weeks, as measured by the mid-point of vegetation carbon uptake, and took up 0.5 petagrams more carbon in July, the height of the growing season, during 2001-2010 than in 1961-1970, suggesting that human land use and management contribute to seasonal changes in the CO2 exchange between the biosphere and the atmosphere.
C1 [Zeng, Ning; Zhao, Fang; Kalnay, Eugenia; Salawitch, Ross J.] Univ Maryland, Dept Atmospher & Ocean Sci, College Pk, MD 20742 USA.
   [Zeng, Ning; Zhao, Fang; Kalnay, Eugenia; Salawitch, Ross J.] Univ Maryland, Earth Syst Sci Interdisciplinary Ctr, College Pk, MD 20742 USA.
   [Collatz, George J.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [West, Tristram O.] Pacific NW Natl Lab, Joint Global Change Res Inst, College Pk, MD 20740 USA.
   [Guanter, Luis] Free Univ Berlin, Inst Space Sci, D-12165 Berlin, Germany.
C3 University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Free University of Berlin
RP Zeng, N (corresponding author), Univ Maryland, Dept Atmospher & Ocean Sci, College Pk, MD 20742 USA.
EM zeng@atmos.umd.edu
FU NOM [NA100AR4310248, NAO9NE54400006]; NSF [AGS-1129088]; NASA [NNH12AU351]
CR Unknown -, 2013, ATMOS MEAS TECH, V0, P0, DOI DOI 10.5194/AMT-6-207-2013
   BACASTOW RB, 1985, J GEOPHYS RES-ATMOS, V90, P10529, DOI 10.1029/JD090iD06p10529
   Bondeau A, 2007, GLOBAL CHANGE BIOL, V13, P679, DOI 10.1111/j.1365-2486.2006.01305.x
   Buermann W, 2007, P NATL ACAD SCI USA, V104, P4249, DOI 10.1073/pnas.0611224104
   Cadule P, 2010, GLOBAL BIOGEOCHEM CY, V24, P0, DOI 10.1029/2009GB003556
   Cramer W, 1999, GLOBAL CHANGE BIOL, V5, P1, DOI 10.1046/j.1365-2486.1999.00009.x
   Graven HD, 2013, SCIENCE, V341, P1085, DOI 10.1126/science.1239207
   Guanter L, 2014, P NATL ACAD SCI USA, V111, PE1327, DOI 10.1073/pnas.1320008111
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   Kohlmaier GH, 1989, TELLUS B, V41, P487, DOI 10.1111/j.1600-0889.1989.tb00137.x
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   Myneni RB, 1997, NATURE, V386, P698, DOI 10.1038/386698a0
   Parazoo NC, 2013, GEOPHYS RES LETT, V40, P2829, DOI 10.1002/grl.50452
   Peters W, 2007, P NATL ACAD SCI USA, V104, P18925, DOI 10.1073/pnas.0708986104
   Piao SL, 2013, GLOBAL CHANGE BIOL, V19, P2117, DOI 10.1111/gcb.12187
   Randerson JT, 1997, GLOBAL BIOGEOCHEM CY, V11, P535, DOI 10.1029/97GB02268
   Rödenbeck C, 2003, ATMOS CHEM PHYS, V3, P1919
   Sinclair TR, 1998, CROP SCI, V38, P638, DOI 10.2135/cropsci1998.0011183X003800030002x
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   Zeng N, 2003, ADV ATMOS SCI, V20, P677, DOI 10.1007/BF02915395
NR 33
TC 164
Z9 200
U1 1
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 NOV 20
PY 2014
VL 515
IS 7527
BP 394
EP +
DI 10.1038/nature13893
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600041
PM 25409829
DA 2026-03-09
ER

PT J
AU Deuse, T
   Hua, XQ
   Wang, D
   Maegdefessel, L
   Heeren, J
   Scheja, L
   Bolaños, JP
   Rakovic, A
   Spin, JM
   Stubbendorff, M
   Ikeno, F
   Länger, F
   Zeller, T
   Schulte-Uentrop, L
   Stoehr, A
   Itagaki, R
   Haddad, F
   Eschenhagen, T
   Blankenberg, S
   Kiefmann, R
   Reichenspurner, H
   Velden, J
   Klein, C
   Yeung, A
   Robbins, RC
   Tsao, PS
   Schrepfer, S
AF Deuse, Tobias
   Hua, Xiaoqin
   Wang, Dong
   Maegdefessel, Lars
   Heeren, Joerg
   Scheja, Ludger
   Bolanos, Juan P.
   Rakovic, Aleksandar
   Spin, Joshua M.
   Stubbendorff, Mandy
   Ikeno, Fumiaki
   Laenger, Florian
   Zeller, Tanja
   Schulte-Uentrop, Leonie
   Stoehr, Andrea
   Itagaki, Ryo
   Haddad, Francois
   Eschenhagen, Thomas
   Blankenberg, Stefan
   Kiefmann, Rainer
   Reichenspurner, Hermann
   Velden, Joachim
   Klein, Christine
   Yeung, Alan
   Robbins, Robert C.
   Tsao, Philip S.
   Schrepfer, Sonja
TI Dichloroacetate prevents restenosis in preclinical animal models of vessel injury
SO NATURE
LA English
DT Article
ID mitochondria; apoptosis; mechanisms; disease; cells
AB Despite the introduction of antiproliferative drug-eluting stents, coronary heart disease remains the leading cause of death in the United States(1). In-stent restenosis and bypass graft failure are characterized by excessive smooth muscle cell (SMC) proliferation(2,3) and concomitant myointima formation with luminal obliteration. Here we show that during the development of myointimal hyperplasia in human arteries, SMCs show hyperpolarization of their mitochondrial membrane potential (Delta Psi m) and acquire a temporary state with a high proliferative rate and resistance to apoptosis. Pyruvate dehydrogenase kinase isoform 2 (PDK2) was identified as a key regulatory protein, and its activation proved necessary for relevant myointima formation. Pharmacologic PDK2 blockade with dichloroacetate or lentiviral PDK2 knockdown prevented Delta Psi m hyperpolarization, facilitated apoptosis and reduced myointima formation in injured human mammary and coronary arteries, rat aortas, rabbit iliac arteries and swine (pig) coronary arteries. In contrast to several commonly used antiproliferative drugs, dichloroacetate did not prevent vessel re-endothelialization. Targeting myointimal Delta Psi m and alleviating apoptosis resistance is a novel strategy for the prevention of proliferative vascular diseases.
C1 [Deuse, Tobias; Hua, Xiaoqin; Wang, Dong; Stubbendorff, Mandy; Itagaki, Ryo; Schrepfer, Sonja] Univ Heart Ctr Hamburg, TSI Lab, D-20246 Hamburg, Germany.
   [Deuse, Tobias; Hua, Xiaoqin; Wang, Dong; Stubbendorff, Mandy; Zeller, Tanja; Schulte-Uentrop, Leonie; Stoehr, Andrea; Itagaki, Ryo; Eschenhagen, Thomas; Blankenberg, Stefan; Kiefmann, Rainer; Reichenspurner, Hermann; Schrepfer, Sonja] Univ Med Ctr Hamburg Eppendorf, Cardiovasc Res Ctr Hamburg CVRC, D-20246 Hamburg, Germany.
   [Deuse, Tobias; Hua, Xiaoqin; Wang, Dong; Stubbendorff, Mandy; Zeller, Tanja; Schulte-Uentrop, Leonie; Stoehr, Andrea; Itagaki, Ryo; Eschenhagen, Thomas; Blankenberg, Stefan; Kiefmann, Rainer; Reichenspurner, Hermann; Schrepfer, Sonja] Univ Med Ctr Hamburg Eppendorf, Partner Site Hamburg Kiel Luebeck, DZHK German Ctr Cardiovasc Res, D-20246 Hamburg, Germany.
   [Deuse, Tobias; Reichenspurner, Hermann; Schrepfer, Sonja] Univ Heart Ctr Hamburg, D-20246 Hamburg, Germany.
   [Maegdefessel, Lars] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, S-17176 Stockholm, Sweden.
   [Heeren, Joerg; Scheja, Ludger] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany.
   [Bolanos, Juan P.] Univ Salamanca, CSIC, Inst Funct Biol & Genom, Salamanca 37007, Spain.
   [Rakovic, Aleksandar; Klein, Christine] Med Univ Lubeck, Inst Neurogenet, D-23562 Lubeck, Germany.
   [Spin, Joshua M.; Ikeno, Fumiaki; Haddad, Francois; Yeung, Alan; Tsao, Philip S.] Stanford Univ, Stanford, CA 94305 USA.
   [Spin, Joshua M.; Ikeno, Fumiaki; Haddad, Francois; Yeung, Alan; Robbins, Robert C.; Tsao, Philip S.; Schrepfer, Sonja] Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
   [Laenger, Florian] Hannover Med Sch, Inst Pathol, D-30625 Hannover, Germany.
   [Zeller, Tanja; Blankenberg, Stefan] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany.
   [Schulte-Uentrop, Leonie; Kiefmann, Rainer] Univ Med Ctr Hamburg Eppendorf, Dept Anaesthesiol, D-20246 Hamburg, Germany.
   [Stoehr, Andrea; Eschenhagen, Thomas] Univ Med Ctr Hamburg Eppendorf, Inst Expt Pharmacol & Toxicol, D-20246 Hamburg, Germany.
   [Velden, Joachim] Univ Hosp Erlangen, Inst Pathol, Dept Nephropathol, D-91054 Erlangen, Germany.
   [Robbins, Robert C.; Schrepfer, Sonja] Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA.
   [Tsao, Philip S.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
C3 University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; German Centre for Cardiovascular Research; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; Karolinska Institutet; University of Hamburg; University Medical Center Hamburg-Eppendorf; Consejo Superior de Investigaciones Cientificas (CSIC); University of Salamanca; University of Lubeck; Stanford University; Stanford University; Hannover Medical School; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Erlangen Nuremberg; Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System
RP Schrepfer, S (corresponding author), Univ Heart Ctr Hamburg, TSI Lab, Martinistr 52, D-20246 Hamburg, Germany.
EM schrepfer@stanford.edu
FU German Research Foundation (Deutsche Forschungsgemeinschaft (DFG)) [SCHR992/3-1, SCHR992/4-1]; International Society for Heart and Lung Transplantation (ISHLT); Forderverein des Universitaren Herzzentrums Hamburg; Hermann and Lilly Schilling Foundation; MINECO [SAF2013-41177-R]; NIH [NIH 1R01HL105299]
NR 16
TC 83
Z9 93
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 MAY 29
PY 2014
VL 509
IS 7502
BP 641
EP +
DI 10.1038/nature13232
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100053
PM 24747400
DA 2026-03-09
ER

PT J
AU McGinty, RK
   Henrici, RC
   Tan, S
AF McGinty, Robert K.
   Henrici, Ryan C.
   Tan, Song
TI Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
SO NATURE
LA English
DT Article
ID centromeric nucleosome; h2a ubiquitylation; core particle; e3 ligase; complex; mechanisms; proteins; reveals; system; domain
AB The Polycomb group of epigenetic enzymes represses expression of developmentally regulated genes in many eukaryotes. This group includes the Polycomb repressive complex 1 (PRC1), which ubiquitylates nucleosomal histone H2A Lys 119 using its E3 ubiquitin ligase subunits, Ring1B and Bmi1, together with an E2 ubiquitin-conjugating enzyme, UbcH5c. However, the molecular mechanism of nucleosome substrate recognition by PRC1 or other chromatin enzymes is unclear. Here we present the crystal structure of the human Ring1B-Bmi1-UbcH5c E3-E2 complex (the PRC1 ubiquitylation module) bound to its nucleosome core particle substrate. The structure shows how a chromatin enzyme achieves substrate specificity by interacting with several nucleosome surfaces spatially distinct from the site of catalysis. Our structure further reveals an unexpected role for the ubiquitin E2 enzyme in substrate recognition, and provides insight into how the related histone H2A E3 ligase, BRCA1, interacts with and ubiquitylates the nucleosome.
C1 [McGinty, Robert K.; Henrici, Ryan C.; Tan, Song] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
   [Henrici, Ryan C.] Penn State Univ, Schreyer Honors Coll, University Pk, PA 16802 USA.
C3 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 Tan, S (corresponding author), Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
EM sxt30@psu.edu
FU NIGMS [GM060489-09S1, GM088236, GM111651]; Damon Runyon Post-doctoral fellowship [DRG 2107-12]
NR 54
TC 261
Z9 317
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 OCT 30
PY 2014
VL 514
IS 7524
BP 591
EP +
DI 10.1038/nature13890
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500040
PM 25355358
DA 2026-03-09
ER

PT J
AU Jensen, ELN
   Akeson, R
AF Jensen, Eric L. N.
   Akeson, Rachel
TI Misaligned protoplanetary disks in a young binary star system
SO NATURE
LA English
DT Article
ID on circumstellar disk; t-tauri; planetary orbits; accretion discs; triple system; mu-m; evolution; perturbations; alignment; dynamics
AB Many extrasolar planets follow orbits that differ from the nearly coplanar and circular orbits found in our Solar System; their orbits may be eccentric(1) or inclined with respect to the host star's equator(2,3), and the population of giant planets orbiting close to their host stars suggests appreciable orbital migration(4). There is at present no consensus on what produces such orbits. Theoretical explanations often invoke interactions with a binary companion star in an orbit that is inclined relative to the planet's orbital plane(4,5). Such mechanisms require significant mutual inclinations between the planetary and binary star orbital planes. The protoplanetary disks in a few young binaries are misaligned(6-12), but often the measurements of these mis-alignments are sensitive only to a small portion of the inner disk, and the three-dimensional misalignment of the bulk of the planet-forming disk mass has hitherto not been determined. Here we report that the protoplanetary disks in the young binary system HK Tauri are misaligned by 60 to 68 degrees, such that one or both of the disks are significantly inclined to the binary orbital plane. Our results demonstrate that the necessary conditions exist for misalignment-driven mechanisms to modify planetary orbits, and that these conditions are present at the time of planet formation, apparently because of the binary formation process.
C1 [Jensen, Eric L. N.] Swarthmore Coll, Dept Phys & Astron, Swarthmore, PA 19081 USA.
   [Akeson, Rachel] CALTECH, IPAC, NASA, Exoplanet Sci Inst, Pasadena, CA 91125 USA.
C3 Swarthmore College; California Institute of Technology; National Aeronautics & Space Administration (NASA)
RP Jensen, ELN (corresponding author), Swarthmore Coll, Dept Phys & Astron, 500 Coll Ave, Swarthmore, PA 19081 USA.
EM ejensen1@swarthmore.edu
NR 47
TC 95
Z9 104
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 JUL 30
PY 2014
VL 511
IS 7511
BP 567
EP +
DI 10.1038/nature13521
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300029
PM 25079553
DA 2026-03-09
ER

PT J
AU Andrews, LC
   Catania, GA
   Hoffman, MJ
   Gulley, JD
   Lüthi, MP
   Ryser, C
   Hawley, RL
   Neumann, TA
AF Andrews, Lauren C.
   Catania, Ginny A.
   Hoffman, Matthew J.
   Gulley, Jason D.
   Luethi, Martin P.
   Ryser, Claudia
   Hawley, Robert L.
   Neumann, Thomas A.
TI Direct observations of evolving subglacial drainage beneath the Greenland Ice Sheet
SO NATURE
LA English
DT Article
ID haut glacier darolla; water-pressure; basal motion; ablation zone; surface; flow; system; melt; acceleration; evolution
AB Seasonal acceleration of the Greenland Ice Sheet is influenced by the dynamic response of the subglacial hydrologic system to variability in meltwater delivery to the bed(1,2) via crevasses and moulins (vertical conduits connecting supraglacial water to the bed of the ice sheet). As the melt season progresses, the subglacial hydrologic system drains supraglacial meltwater more efficiently(1-4), decreasing basal water pressure(4) and moderating the ice velocity response to surface melting(1,2). However, limited direct observations of subglacial water pressure(4-7) mean that the spatiotemporal evolution of the subglacial hydrologic system remains poorly understood. Here we show that ice velocity is well correlated with moulin hydraulic head but is out of phase with that of nearby (0.3-2 kilometres away) boreholes, indicating that moulins connect to an efficient, channelized component of the subglacial hydrologic system, which exerts the primary control on diurnal and multi-day changes in ice velocity. Our simultaneous measurements of moulin and borehole hydraulic head and ice velocity in the Paakitsoq region of western Greenland show that decreasing trends in ice velocity during the latter part of the melt season cannot be explained by changes in the ability of moulin-connected channels to convey supraglacial melt. Instead, these observations suggest that decreasing late-season ice velocity may be caused by changes in connectivity in unchannelized regions of the subglacial hydrologic system. Understanding this spatiotemporal variability in subglacial pressures is increasingly important because melt-season dynamics affect ice velocity beyond the conclusion of the melt season(8-10).
C1 [Andrews, Lauren C.; Catania, Ginny A.; Gulley, Jason D.] Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
   [Andrews, Lauren C.; Catania, Ginny A.; Ryser, Claudia] Univ Texas Austin, Dept Geol Sci, Jackson Sch Geosci, Austin, TX 78758 USA.
   [Hoffman, Matthew J.] Los Alamos Natl Lab, Fluid Dynam & Solid Mech Grp, Los Alamos, NM 87545 USA.
   [Hoffman, Matthew J.; Neumann, Thomas A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Gulley, Jason D.] Michigan Technol Univ, Dept Geol & Mining Engn & Sci, Houghton, MI 49931 USA.
   [Luethi, Martin P.] Univ Zurich, Dept Geog, Glaciol & Geomorphodynam Grp, Phys Geog Div, CH-8057 Zurich, Switzerland.
   [Luethi, Martin P.; Ryser, Claudia] Swiss Fed Inst Technol, Lab Hydraul Hydrol & Glaciol, CH-8093 Zurich, Switzerland.
   [Hawley, Robert L.] Dartmouth Coll, Dept Earth Sci, Hanover, NH 03755 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; United States Department of Energy (DOE); Los Alamos National Laboratory; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Michigan Technological University; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Dartmouth College
RP Andrews, LC (corresponding author), Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
EM landrews@ig.utexas.edu
FU United States National Science Foundation [OPP-0908156, OPP-0909454, ANT-0424589]; Swiss National Science Foundation [200021_127197]; National Geographic Society [9067-12]; UTIG; NASA Cryospheric Sciences and Climate Modeling Programs within US Department of Energy, Office of Science; NSF [EAR-0946767]; NSF; NASA [EAR-0735156]; NSF OPP [ANT-1043681]; Swiss National Science Foundation (SNF) [200021_127197] Funding Source: Swiss National Science Foundation (SNF)
NR 47
TC 250
Z9 288
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 OCT 2
PY 2014
VL 514
IS 7520
BP 80
EP +
DI 10.1038/nature13796
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800039
PM 25279921
DA 2026-03-09
ER

PT J
AU Huber, KVM
   Salah, E
   Radic, B
   Gridling, M
   Elkins, JM
   Stukalov, A
   Jemth, AS
   Göktürk, C
   Sanjiv, K
   Strömberg, K
   Pham, T
   Berglund, UW
   Colinge, J
   Bennett, KL
   Loizou, JI
   Helleday, T
   Knapp, S
   Superti-Furga, G
AF Huber, Kilian V. M.
   Salah, Eidarus
   Radic, Branka
   Gridling, Manuela
   Elkins, Jonathan M.
   Stukalov, Alexey
   Jemth, Ann-Sofie
   Gokturk, Camilla
   Sanjiv, Kumar
   Stromberg, Kia
   Pham, Therese
   Berglund, Ulrika Warpman
   Colinge, Jacques
   Bennett, Keiryn L.
   Loizou, Joanna I.
   Helleday, Thomas
   Knapp, Stefan
   Superti-Furga, Giulio
TI Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy
SO NATURE
LA English
DT Article
ID cell lung-cancer; small-molecule inhibition; human mutt homolog; ras-transformation; oxidative stress; messenger-rna; hmth1; overexpression; tumorigenesis; crizotinib
AB Activated RAS GTPase signalling is a critical driver of oncogenic transformation and malignant disease. Cellular models of RAS-dependent cancers have been used to identify experimental small molecules, such as SCH51344, but their molecular mechanism of action remains generally unknown. Here, using a chemical proteomic approach, we identify the target of SCH51344 as the human mutT homologue MTH1 (also known as NUDT1), a nucleotide pool sanitizing enzyme. Loss-of-function of MTH1 impaired growth of KRAS tumour cells, whereas MTH1 overexpression mitigated sensitivity towards SCH51344. Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 activity. Surprisingly, the clinically used (R)-enantiomer of the drug was inactive, whereas the (S)-enantiomer selectively inhibited MTH1 catalytic activity. Enzymatic assays, chemical proteomic profiling, kinome-wide activity surveys and MTH1 co-crystal structures of both enantiomers provide a rationale for this remarkable stereospecificity. Disruption of nucleotide pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand breaks, activated DNA repair in human colon carcinoma cells, and effectively suppressed tumour growth in animal models. Our results propose (S)-crizotinib as an attractive chemical entity for further pre-clinical evaluation, and small-molecule inhibitors of MTH1 in general as a promising novel class of anticancer agents.
C1 [Huber, Kilian V. M.; Radic, Branka; Gridling, Manuela; Stukalov, Alexey; Colinge, Jacques; Bennett, Keiryn L.; Loizou, Joanna I.; Superti-Furga, Giulio] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Salah, Eidarus; Elkins, Jonathan M.; Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford OX3 7DQ, England.
   [Jemth, Ann-Sofie; Gokturk, Camilla; Sanjiv, Kumar; Stromberg, Kia; Pham, Therese; Berglund, Ulrika Warpman; Helleday, Thomas] Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, S-17121 Stockholm, Sweden.
C3 Austrian Academy of Sciences; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; University of Oxford; Karolinska Institutet
RP Superti-Furga, G (corresponding author), Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria.
EM gsuperti@cemm.oeaw.ac.at
FU Austrian Academy of Sciences; GEN-AU initiative of the Austrian Federal Ministry for Science and Research; European Union; SGC, a registered charity [1097737]; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada; GlaxoSmithKline; Pfizer; Eli Lilly; Takeda; AbbVie; Novartis Research Foundation; Boehringer Ingelheim; Ontario Ministry of Research and Innovation; Wellcome Trust [092809/Z/10/Z]; European Union [278568]; Torsten and Ragnar Soderberg Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council; European Research Council; Swedish Cancer Society; European Union FP7 Career Integration Grant [PCIG11-GA-2012-321602]; FWF Grant [P24766-B20]; Austrian Science Fund (FWF) [P 24766] Funding Source: researchfish; Austrian Science Fund (FWF) [P24766] Funding Source: Austrian Science Fund (FWF)
NR 33
TC 339
Z9 392
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 APR 10
PY 2014
VL 508
IS 7495
BP 222
EP +
DI 10.1038/nature13194
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900039
PM 24695225
DA 2026-03-09
ER

PT J
AU Niwa, S
   Yu, LJ
   Takeda, K
   Hirano, Y
   Kawakami, T
   Wang-Otomo, ZY
   Miki, K
AF Niwa, Satomi
   Yu, Long-Jiang
   Takeda, Kazuki
   Hirano, Yu
   Kawakami, Tomoaki
   Wang-Otomo, Zheng-Yu
   Miki, Kunio
TI Structure of the LH1-RC complex from Thermochromatium tepidum at 3.0 Å
SO NATURE
LA English
DT Article
ID light-harvesting complex; photosynthetic reaction-center; rc-lh1 core complex; rhodospirillum-rubrum; rhodobacter-sphaeroides; crystal-structure; rhodopseudomonas-viridis; projection structure; calcium-ions; protein
AB The light-harvesting core antenna (LH1) and the reaction centre (RC) of purple photosynthetic bacteria form a supramolecular complex (LH1-RC) to use sunlight energy in a highly efficient manner. Here we report the first near-atomic structure, to our knowledge, of a LH1-RC complex, namely that of a Ca2+-bound complex from Thermochromatium tepidum, which reveals detailed information on the arrangement and interactions of the protein subunits and the cofactors. The RC is surrounded by 16 heterodimers of the LH1 alpha beta-subunit that form a completely closed structure. The Ca2+ ions are located at the periplasmic side of LH1. Thirty-two bacteriochlorophyll and 16 spirilloxanthin molecules in the LH1 ring form an elliptical assembly. The geometries of the pigment assembly involved in the absorption characteristics of the bacteriochlorophyll in LH1 and excitation energy transfer among the pigments are reported. In addition, possible ubiquinone channels in the closed LH1 complex are proposed based on the atomic structure.
C1 [Niwa, Satomi; Takeda, Kazuki; Hirano, Yu; Miki, Kunio] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan.
   [Yu, Long-Jiang; Kawakami, Tomoaki; Wang-Otomo, Zheng-Yu] Ibaraki Univ, Fac Sci, Mito, Ibaraki 3108512, Japan.
C3 Kyoto University; Ibaraki University
RP Miki, K (corresponding author), Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan.
EM wang@ml.ibaraki.ac.jp; miki@kuchem.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Takeda Science Foundation; Kurata Memorial Hitachi Science and Technology Foundation; Targeted Proteins Research Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Photon and Quantum Basic Research Coordinated Development Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Ibaraki University
NR 46
TC 185
Z9 205
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 10
PY 2014
VL 508
IS 7495
BP 228
EP +
DI 10.1038/nature13197
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900040
PM 24670637
DA 2026-03-09
ER

PT J
AU Kim, H
   Abeysirigunawarden, SC
   Chen, K
   Mayerle, M
   Ragunathan, K
   Luthey-Schulten, Z
   Ha, T
   Woodson, SA
AF Kim, Hajin
   Abeysirigunawarden, Sanjaya C.
   Chen, Ke
   Mayerle, Megan
   Ragunathan, Kaushik
   Luthey-Schulten, Zaida
   Ha, Taekjip
   Woodson, Sarah A.
TI Protein-guided RNA dynamics during early ribosome assembly
SO NATURE
LA English
DT Article
ID escherichia-coli ribosm; single-molecule; induced fit; structural dynamics; binding-site; s4; subunit; recognition; reconstitution; flexibility
AB The assembly of 30S ribosomes requires the precise addition of 20 proteins to the 16S ribosomal RNA. How early binding proteins change the ribosomal RNA structure so that later proteins may join the complex is poorly understood. Here we use single-molecule fluorescence resonance energy transfer (FRET) to observe real-time encounters between Escherichia coli ribosomal protein S4 and the 16S 5' domain RNA at an early stage of 30S assembly. Dynamic initial S4-RNA complexes pass through a stable non-native intermediate before converting to the native complex, showing that non-native structures can offer a low free-energy path to protein-RNA recognition. Three-colour FRET and molecular dynamics simulations reveal how S4 changes the frequency and direction of RNA helix motions, guiding a conformational switch that enforces the hierarchy of protein addition. These protein-guided dynamics offer an alternative explanation for induced fit in RNA-protein complexes.
C1 [Kim, Hajin; Luthey-Schulten, Zaida; Ha, Taekjip] Univ Illinois, Ctr Phys Living Cells, Dept Phys, Urbana, IL 61801 USA.
   [Kim, Hajin; Luthey-Schulten, Zaida; Ha, Taekjip] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Kim, Hajin; Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Abeysirigunawarden, Sanjaya C.; Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA.
   [Chen, Ke; Ragunathan, Kaushik; Luthey-Schulten, Zaida; Ha, Taekjip] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA.
   [Chen, Ke; Luthey-Schulten, Zaida; Ha, Taekjip] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Mayerle, Megan; Woodson, Sarah A.] Johns Hopkins Univ, CMDB Program, Baltimore, MD 21218 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; Johns Hopkins University; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Johns Hopkins University
RP Ha, T (corresponding author), Univ Illinois, Ctr Phys Living Cells, Dept Phys, Urbana, IL 61801 USA.
EM tjha@illinois.edu; swoodson@jhu.edu
FU National Institutes of Health [R01 GM60819, R01 GM65367]; National Science Foundation (NSF) [PHY0822613, MCB12-44570]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1244570] Funding Source: National Science Foundation
NR 61
TC 132
Z9 160
U1 2
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 20
PY 2014
VL 506
IS 7488
BP 334
EP +
DI 10.1038/nature13039
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800034
PM 24522531
DA 2026-03-09
ER

PT J
AU Lopez-Rios, J
   Duchesne, A
   Speziale, D
   Andrey, G
   Peterson, KA
   Germann, P
   Ünal, E
   Liu, J
   Floriot, S
   Barbey, S
   Gallard, Y
   Müller-Gerbl, M
   Courtney, AD
   Klopp, C
   Rodriguez, S
   Ivanek, R
   Beisel, C
   Wicking, C
   Iber, D
   Robert, B
   McMahon, AP
   Duboule, D
   Zeller, R
AF Lopez-Rios, Javier
   Duchesne, Amandine
   Speziale, Dario
   Andrey, Guillaume
   Peterson, Kevin A.
   Germann, Philipp
   Uenal, Erkan
   Liu, Jing
   Floriot, Sandrine
   Barbey, Sarah
   Gallard, Yves
   Mueller-Gerbl, Magdalena
   Courtney, Andrew D.
   Klopp, Christophe
   Rodriguez, Sabrina
   Ivanek, Robert
   Beisel, Christian
   Wicking, Carol
   Iber, Dagmar
   Robert, Benoit
   McMahon, Andrew P.
   Duboule, Denis
   Zeller, Rolf
TI Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
SO NATURE
LA English
DT Article
ID gene regulatory networks; sonic-hedgehog; bac library; developmental basis; digit number; expression; construction; range; morphogen; reduction
AB The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.
C1 [Lopez-Rios, Javier; Duchesne, Amandine; Speziale, Dario; Uenal, Erkan; Ivanek, Robert; Zeller, Rolf] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland.
   [Duchesne, Amandine; Floriot, Sandrine; Rodriguez, Sabrina] INRA, Genet Anim & Biol Integrat, F-78350 Jouy En Josas, France.
   [Andrey, Guillaume; Duboule, Denis] Fed Inst Technol Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland.
   [Peterson, Kevin A.; Liu, Jing; McMahon, Andrew P.] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90089 USA.
   [Germann, Philipp; Uenal, Erkan; Beisel, Christian; Iber, Dagmar] Fed Inst Technol Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
   [Germann, Philipp; Uenal, Erkan; Ivanek, Robert; Beisel, Christian; Iber, Dagmar] Swiss Inst Bioinformat, CH-4058 Basel, Switzerland.
   [Barbey, Sarah; Gallard, Yves] INRA, Domaine Expt Pin Haras, F-61310 Exmes, France.
   [Mueller-Gerbl, Magdalena] Univ Basel, Dept Biomed, Inst Anat, CH-4056 Basel, Switzerland.
   [Courtney, Andrew D.; Wicking, Carol] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
   [Klopp, Christophe] INRA, Biometrie & Intelligence Artificielle, F-31326 Castanet Tolosan, France.
   [Robert, Benoit] Inst Pasteur, F-75015 Paris, France.
   [Robert, Benoit] CNRS, URA 2578, F-75015 Paris, France.
   [Duboule, Denis] Univ Geneva, Dept Genet & Evolut, CH-1211 Geneva, Switzerland.
C3 University of Basel; INRAE; Universite Paris Saclay; AgroParisTech; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Southern California; Swiss Institute of Bioinformatics; INRAE; University of Basel; University of Queensland; INRAE; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); University of Geneva
RP Zeller, R (corresponding author), Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland.
EM amandine.duchesne@jouy.inra.fr; rolf.zeller@unibas.ch
FU SNF [31003A_130803/146248]; University of Basel; EU [PERG-GA-2009-246576]; SystemsX.ch iPhD Grant [20101078]; INRA; ANR grant [06-MRAR-027-01]; EPFL; ERC grant SystemsHox.ch; NIH grant [NS 033642]; Australian National Health; Medical Research Council [569713]; National Health and Medical Research Council (NHMRC) [569713] Funding Source: National Health and Medical Research Council (NHMRC)
NR 62
TC 96
Z9 116
U1 0
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 JUL 3
PY 2014
VL 511
IS 7507
BP 46
EP +
DI 10.1038/nature13289
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400032
PM 24990743
DA 2026-03-09
ER

PT J
AU Besnard, F
   Refahi, Y
   Morin, V
   Marteaux, B
   Brunoud, G
   Chambrier, P
   Rozier, F
   Mirabet, V
   Legrand, J
   Lainé, S
   Thévenon, E
   Farcot, E
   Cellier, C
   Das, P
   Bishopp, A
   Dumas, R
   Parcy, F
   Helariutta, Y
   Boudaoud, A
   Godin, C
   Traas, J
   Guédon, Y
   Vernoux, T
AF Besnard, Fabrice
   Refahi, Yassin
   Morin, Valerie
   Marteaux, Benjamin
   Brunoud, Geraldine
   Chambrier, Pierre
   Rozier, Frederique
   Mirabet, Vincent
   Legrand, Jonathan
   Laine, Stephanie
   Thevenon, Emmanuel
   Farcot, Etienne
   Cellier, Coralie
   Das, Pradeep
   Bishopp, Anthony
   Dumas, Renaud
   Parcy, Francois
   Helariutta, Yka
   Boudaoud, Arezki
   Godin, Christophe
   Traas, Jan
   Guedon, Yann
   Vernoux, Teva
TI Cytokinin signalling inhibitory fields provide robustness to phyllotaxis
SO NATURE
LA English
DT Article
ID shoot apical meristem; gene-expression; cell-division; auxin; model; growth; differentiation; initiation; transport; patterns
AB How biological systems generate reproducible patterns with high precision is a central question in science(1). The shoot apical meristem (SAM), a specialized tissue producing plant aerial organs, is a developmental system of choice to address this question. Organs are periodically initiated at the SAM at specific spatial positions and this spatiotemporal pattern defines phyllotaxis. Accumulation of the plant hormone auxin triggers organ initiation(2-5), whereas auxin depletion around organs generates inhibitory fields that are thought to be sufficient to maintain these patterns and their dynamics(4,6-13). Here we show that another type of hormone-based inhibitory fields, generated directly downstream of auxin by intercellular movement of the cytokinin signalling inhibitor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 6 (AHP6)(14), is involved in regulating phyllotactic patterns. We demonstrate that AHP6-based fields establish patterns of cytokinin signalling in the meristem that contribute to the robustness of phyllotaxis by imposing a temporal sequence on organ initiation. Our findings indicate that not one but two distinct hormone-based fields may be required for achieving temporal precision during formation of reiterative structures at the SAM, thus indicating an original mechanism for providing robustness to a dynamic developmental system.
C1 [Besnard, Fabrice; Morin, Valerie; Marteaux, Benjamin; Brunoud, Geraldine; Chambrier, Pierre; Rozier, Frederique; Mirabet, Vincent; Legrand, Jonathan; Laine, Stephanie; Cellier, Coralie; Das, Pradeep; Boudaoud, Arezki; Traas, Jan; Vernoux, Teva] Univ Lyon, Lab Reprod & Dev Plantes, CNRS, INRA,ENS Lyon,UCBL, F-69364 Lyon, France.
   [Refahi, Yassin; Legrand, Jonathan; Farcot, Etienne; Godin, Christophe; Guedon, Yann] Inst Biol Computat, Virtual Plants INRIA, INRA Project Team, CIRAD,UMRAGAP, F-34095 Montpellier, France.
   [Mirabet, Vincent; Legrand, Jonathan; Das, Pradeep; Boudaoud, Arezki] Univ Lyon, Lab Joliot Curie, CNRS, ENS Lyon, F-69364 Lyon, France.
   [Thevenon, Emmanuel; Dumas, Renaud; Parcy, Francois] UJF, Lab Physiol Cellulaire & Vegetale, CEA, CNRS,INRA, F-38041 Grenoble, France.
   [Bishopp, Anthony; Helariutta, Yka] Univ Helsinki, Dept Biosci, Inst Biotechnol, FIN-00014 Helsinki, Finland.
C3 INRAE; Centre National de la Recherche Scientifique (CNRS); Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; INRAE; Universite de Montpellier; CIRAD; Centre National de la Recherche Scientifique (CNRS); Ecole Normale Superieure de Lyon (ENS de LYON); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); INRAE; University of Helsinki
RP Vernoux, T (corresponding author), Univ Lyon, Lab Reprod & Dev Plantes, CNRS, INRA,ENS Lyon,UCBL, F-69364 Lyon, France.
EM teva.vernoux@ens-lyon.fr
FU Human Frontier Science Program Organization [HFSPO CDA 0047/2007]; Agence National de la Recherche [ANR-07-JCJC-0115]; AuxiFlo [ANR-12-BSV6-0005]; transnational EraSysBio Grant (iSAM); French Ministry of Research; CJS grant from INRA; Agence Nationale de la Recherche (ANR) [ANR-07-JCJC-0115] Funding Source: Agence Nationale de la Recherche (ANR)
NR 55
TC 222
Z9 237
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 JAN 16
PY 2014
VL 505
IS 7483
BP 417
EP +
DI 10.1038/nature12791
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800046
PM 24336201
DA 2026-03-09
ER

PT J
AU Zamaninasab, M
   Clausen-Brown, E
   Savolainen, T
   Tchekhovskoy, A
AF Zamaninasab, M.
   Clausen-Brown, E.
   Savolainen, T.
   Tchekhovskoy, A.
TI Dynamically important magnetic fields near accreting supermassive black holes
SO NATURE
LA English
DT Article
ID active galactic nuclei; relativistic magnetohydrodynamic simulations; radio loudness; extragalactic jet; astronomical data; kinetic power; centaurus-a; line; mass; luminosity
AB Accreting supermassive black holes at the centres of active galaxies often produce 'jets'-collimated bipolar outflows of relativistic particles(1). Magnetic fields probably play a critical role in jet formation(2,3) and in accretion disk physics(4). A dynamically important magnetic field was recently found near the Galactic Centre black hole(5). If this is common and if the field continues to near the black hole event horizon, disk structures will be affected, invalidating assumptions made in standard models(3,6,7). Here we report that jet magnetic field and accretion disk luminosity are tightly correlated over seven orders of magnitude for a sample of 76 radio-loud active galaxies. We conclude that the jet-launching regions of these radio-loud galaxies are threaded by dynamically important fields, which will affect the disk properties. These fields obstruct gas infall, compress the accretion disk vertically, slow down the disk rotation by carrying away its angular momentum in an outflow(3) and determine the directionality of jets(8).
C1 [Zamaninasab, M.; Clausen-Brown, E.; Savolainen, T.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Tchekhovskoy, A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Tchekhovskoy, A.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Tchekhovskoy, A.] Univ Calif Berkeley, Theoret Astrophys Ctr, Berkeley, CA 94720 USA.
C3 Max Planck Society; 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
RP Zamaninasab, M (corresponding author), Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
EM m.zamaninasab@gmail.com
FU German Deutsche Forschungsgemeinschaft, DFG [SFB 956]; Princeton Center for Theoretical Science fellowship; NASA through the Einstein fellowship program [PF3-140115]
NR 69
TC 234
Z9 250
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 JUN 5
PY 2014
VL 510
IS 7503
BP 126
EP +
DI 10.1038/nature13399
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900041
PM 24899311
DA 2026-03-09
ER

PT J
AU Arlet, JB
   Ribeil, JA
   Guillem, F
   Negre, O
   Hazoume, A
   Marcion, G
   Beuzard, Y
   Dussiot, M
   Moura, IC
   Demarest, S
   de Beauchêne, IC
   Belaid-Choucair, Z
   Sevin, M
   Maciel, TT
   Auclair, C
   Leboulch, P
   Chretien, S
   Tchertanov, L
   Baudin-Creuza, V
   Seigneuric, R
   Fontenay, M
   Garrido, C
   Hermine, O
   Courtois, G
AF Arlet, Jean-Benoit
   Ribeil, Jean-Antoine
   Guillem, Flavia
   Negre, Olivier
   Hazoume, Adonis
   Marcion, Guillaume
   Beuzard, Yves
   Dussiot, Michael
   Moura, Ivan Cruz
   Demarest, Samuel
   de Beauchene, Isaure Chauvot
   Belaid-Choucair, Zakia
   Sevin, Margaux
   Maciel, Thiago Trovati
   Auclair, Christian
   Leboulch, Philippe
   Chretien, Stany
   Tchertanov, Luba
   Baudin-Creuza, Veronique
   Seigneuric, Renaud
   Fontenay, Michaela
   Garrido, Carmen
   Hermine, Olivier
   Courtois, Genevieve
TI HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia
SO NATURE
LA English
DT Article
ID gamma-globin; erythroid precursors; gene-expression; protein; gata-1; differentiation; hemoglobin; apoptosis; cleavage; cells
AB beta-Thalassaemia major (beta-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of beta-globin chains of haemoglobin, leading to the accumulationof free alpha-globin chains that form toxic aggregates(1,2). Despite extensive knowledge of the molecular defects causing beta-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage(3-6). We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation(7). Although erythroid transcription factor GATA-1, themaster transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage(8). The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation(9). Here we show in vitro that during the maturation of human beta-TM erythroblasts, HSP70 interacts directly with free alpha-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GATA-1 mutant restores terminal maturation of beta-TM erythroblasts, which may provide a rationale for new targeted therapies of beta-TM.
C1 [Arlet, Jean-Benoit; Ribeil, Jean-Antoine; Guillem, Flavia; Dussiot, Michael; Moura, Ivan Cruz; Belaid-Choucair, Zakia; Maciel, Thiago Trovati; Hermine, Olivier; Courtois, Genevieve] Ctr Natl Rech Sci CNRS Equipe Rech Labellisee, UMR 1163, Lab INSERM, 24 Blvd Montparnasse, F-75015 Paris, France.
   [Arlet, Jean-Benoit] Hop Europeen Georges Pompidou, Sorbonne Paris Cite, Fac Med Paris Descartes, Serv Med Interne, F-75908 Paris, France.
   [Arlet, Jean-Benoit] Hop Europeen Georges Pompidou, AP HP, F-75908 Paris, France.
   [Arlet, Jean-Benoit; Ribeil, Jean-Antoine; Guillem, Flavia; Dussiot, Michael; Moura, Ivan Cruz; Belaid-Choucair, Zakia; Maciel, Thiago Trovati; Hermine, Olivier; Courtois, Genevieve] Paris Descartes Sorbonne Paris Cite Univ, Hop Necker, AP HP, Imagine Inst, F-75015 Paris, France.
   [Arlet, Jean-Benoit; Ribeil, Jean-Antoine; Guillem, Flavia; Dussiot, Michael; Moura, Ivan Cruz; Belaid-Choucair, Zakia; Maciel, Thiago Trovati; Fontenay, Michaela; Hermine, Olivier; Courtois, Genevieve] Lab Excellence GR Ex, F-75015 Paris, France.
   [Ribeil, Jean-Antoine] Hop Necker Enfants Malad, Sorbonne Paris Cite, Fac Med Paris Descartes, Dept Biotherapie, F-75015 Paris, France.
   [Ribeil, Jean-Antoine] Hop Necker Enfants Malad, AP HP, F-75015 Paris, France.
   [Negre, Olivier; Beuzard, Yves; Leboulch, Philippe; Chretien, Stany] CEA, Inst Emerging Dis & Innovat Therapies iMETI, F-92260 Fontenay Aux Roses, France.
   [Hazoume, Adonis; Marcion, Guillaume; Sevin, Margaux; Garrido, Carmen] INSERM, Equipe Labellisee Ligue Canc, UMR 866, F-21033 Dijon, France.
   [Hazoume, Adonis; Marcion, Guillaume; Sevin, Margaux; Garrido, Carmen] Assoc Rech Canc, F-21033 Dijon, France.
   [Hazoume, Adonis; Marcion, Guillaume; Sevin, Margaux; Garrido, Carmen] Lab Excellence Lipoprot & Sante LipSTIC, F-21033 Dijon, France.
   [Hazoume, Adonis; Marcion, Guillaume; Sevin, Margaux; Seigneuric, Renaud; Garrido, Carmen] Univ Burgundy, Fac Med & Pharm, F-21033 Dijon, France.
   [Dussiot, Michael; Moura, Ivan Cruz; Maciel, Thiago Trovati] Hop Bichat Claude Bernard, INSERM, UMR 699, F-75018 Paris, France.
   [Moura, Ivan Cruz; Maciel, Thiago Trovati] Univ Paris 06, F-75013 Paris, France.
   [Moura, Ivan Cruz; Maciel, Thiago Trovati] Univ Denis Diderot Paris VII, F-75013 Paris, France.
   [Demarest, Samuel; de Beauchene, Isaure Chauvot; Auclair, Christian; Tchertanov, Luba] Ecole Normale Super, CNRS, UMR 8113, F-94230 Cachan, France.
   [de Beauchene, Isaure Chauvot; Auclair, Christian; Tchertanov, Luba] LERMIT, Campus Paris Saclay, F-92296 Chatenay Malabry, France.
   [Leboulch, Philippe] Womens Hosp Med Ctr, Boston, MA 02115 USA.
   [Leboulch, Philippe] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Baudin-Creuza, Veronique] Univ Paris 11, INSERM, UMR 779, Le Kremlin Bicetre, France.
   [Fontenay, Michaela] Univ Paris 05, CNRS, INSERM, Inst Cochin,UMR 1016,UMR 8104, F-75014 Paris, France.
   [Fontenay, Michaela] Hop Cochin, Hop Univ Paris Ctr, AP HP, Serv Hematol Biol, F-75014 Paris, France.
   [Garrido, Carmen] Ctr Anticanc George Francois Leclerc, F-21079 Dijon, France.
   [Hermine, Olivier] Fac Med Paris Descartes, Sorbonne Paris Cite, Serv Hematol, F-75015 Paris, France.
   [Hermine, Olivier] Hop Necker Enfants Malad, AP HP, F-75015 Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Europeen Georges-Pompidou - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Europeen Georges-Pompidou - APHP; 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); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; CEA; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut Agro; Institut Agro Dijon; Universite Bourgogne Europe; Universite Bourgogne Europe; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bichat-Claude Bernard - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Universite Paris Cite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Saclay; Harvard University; Harvard Medical School; Universite Paris Saclay; 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); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Cochin - APHP; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP
RP Hermine, O (corresponding author), Ctr Natl Rech Sci CNRS Equipe Rech Labellisee, UMR 1163, Lab INSERM, 24 Blvd Montparnasse, F-75015 Paris, France.
EM ohermine@gmail.com; genevieve_courtois@yahoo.fr
FU Societe Nationale Francaise de Medecine Interne (SNFMI); Societe Francaise d'Hematologie (SFH); Centre National de la Recherche Scientifique (CNRS); Assistance publique - Hopitaux de Paris (AP-HP) (poste d'accueil APHP-CNRS); Groupe Pasteur Mutualite; Institut FARMAN (ENS de Cachan); ENS de Cachan; Conseil Regional de Bourgogne; l'Institut National du Cancer, INCa; National Research Agency under the 'Investments for the Future' program [ANR-10-IAHU-01]; Ligue nationale contre le cancer; Fondation pour la recherche medicale (FRM); Fondation de France; French National Research Agency [ANR-11-IDEX-0005-02]
NR 28
TC 124
Z9 134
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 OCT 9
PY 2014
VL 514
IS 7521
BP 242
EP +
DI 10.1038/nature13614
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100045
PM 25156257
DA 2026-03-09
ER

PT J
AU Mohtadi, M
   Prange, M
   Oppo, DW
   De Pol-Holz, R
   Merkel, U
   Zhang, X
   Steinke, S
   Lückge, A
AF Mohtadi, Mahyar
   Prange, Matthias
   Oppo, Delia W.
   De Pol-Holz, Ricardo
   Merkel, Ute
   Zhang, Xiao
   Steinke, Stephan
   Lueckge, Andreas
TI North Atlantic forcing of tropical Indian Ocean climate
SO NATURE
LA English
DT Article
ID last glacial maximum; planktonic-foraminifera; barrier layer; monsoon rainfall; millennial-scale; asian monsoon; fresh-water; sea-level; surface; variability
AB The response of the tropical climate in the Indian Ocean realm to abrupt climate change events in the North Atlantic Ocean is contentious. Repositioning of the intertropical convergence zone is thought to have been responsible for changes in tropical hydroclimate during North Atlantic cold spells(1-5), but the dearth of high-resolution records outside the monsoon realm in the Indian Ocean precludes a full understanding of this remote relationship and its underlying mechanisms. Here we show that slowdowns of the Atlantic meridional overturning circulation during Heinrich stadials and the Younger Dryas stadial affected the tropical Indian Ocean hydroclimate through changes to the Hadley circulation including a southward shift in the rising branch (the intertropical convergence zone) and an overall weakening over the southern Indian Ocean. Our results are based on new, high-resolution sea surface temperature and seawater oxygen isotope records of well-dated sedimentary archives from the tropical eastern Indian Ocean for the past 45,000 years, combined with climate model simulations of Atlantic circulation slowdown under Marine Isotope Stages 2 and 3 boundary conditions. Similar conditions in the east and west of the basin rule out a zonal dipole structure as the dominant forcing of the tropical Indian Ocean hydroclimate of millennial-scale events. Results from our simulations and proxy data suggest dry conditions in the northern Indian Ocean realm and wet and warm conditions in the southern realm during North Atlantic cold spells.
C1 [Mohtadi, Mahyar; Prange, Matthias; Merkel, Ute; Zhang, Xiao; Steinke, Stephan] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Oppo, Delia W.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [De Pol-Holz, Ricardo] Univ Concepcion, Dept Oceanog, Concepcion, Chile.
   [Lueckge, Andreas] Fed Inst Geosci & Nat Resources, D-30655 Hannover, Germany.
C3 University of Bremen; Woods Hole Oceanographic Institution; Universidad de Concepcion
RP Mohtadi, M (corresponding author), Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
EM mmohtadi@marum.de
FU German Bundesministerium fur Bildung und Forschung [03G0189A]; Deutsche Forschungsgemeinschaft (DFG) [HE3412/15-1, STE1044/4-1]; DFG Research Centre/Cluster of Excellence 'The Ocean in the Earth System'); US NSF; Chilean FONDAP [15110009/ICM Nucleus NC120066]; Division Of Ocean Sciences; Directorate For Geosciences [1060743] Funding Source: National Science Foundation
NR 84
TC 266
Z9 293
U1 3
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 MAY 1
PY 2014
VL 509
IS 7498
BP 76
EP +
DI 10.1038/nature13196
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100042
PM 24784218
DA 2026-03-09
ER

PT J
AU Rodgers, JT
   King, KY
   Brett, JO
   Cromie, MJ
   Charville, GW
   Maguire, KK
   Brunson, C
   Mastey, N
   Liu, L
   Tsai, CR
   Goodell, MA
   Rando, TA
AF Rodgers, Joseph T.
   King, Katherine Y.
   Brett, Jamie O.
   Cromie, Melinda J.
   Charville, Gregory W.
   Maguire, Katie K.
   Brunson, Christopher
   Mastey, Namrata
   Liu, Ling
   Tsai, Chang-Ru
   Goodell, Margaret A.
   Rando, Thomas A.
TI mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert
SO NATURE
LA English
DT Article
ID hepatocyte growth-factor; skeletal-muscle; molecular regulation; expression data; regeneration; progenitors; renewal; events; system; injury
AB A unique property of many adult stem cells is their ability to exist in a non-cycling, quiescent state(1). Although quiescence serves an essential role in preserving stem cell function until the stem cell is needed in tissue homeostasis or repair, defects in quiescence can lead to an impairment in tissue function(2). The extent to which stem cells can regulate quiescence is unknown. Here we show that the stem cell quiescent state is composed of two distinct functional phases, G(0) and an 'alert' phase we term G(Alert). Stem cells actively and reversibly transition between these phases in response to injury-induced systemic signals. Using genetic mouse models specific to muscle stem cells (or satellite cells), we show that mTORC1 activity is necessary and sufficient for the transition of satellite cells from G(0) into G(Alert) and that signalling through the HGF receptor cMet is also necessary. We also identify G(0)-to-G(Alert) transitions in several populations of quiescent stem cells. Quiescent stem cells that transition into GAlert possess enhanced tissue regenerative function. We propose that the transition of quiescent stem cells into G(Alert) functions as an 'alerting' mechanism, an adaptive response that positions stem cells to respond rapidly under conditions of injury and stress, priming them for cell cycle entry.
C1 [Rodgers, Joseph T.; Brett, Jamie O.; Cromie, Melinda J.; Charville, Gregory W.; Maguire, Katie K.; Brunson, Christopher; Mastey, Namrata; Liu, Ling; Rando, Thomas A.] Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA.
   [Rodgers, Joseph T.; Brett, Jamie O.; Cromie, Melinda J.; Charville, Gregory W.; Maguire, Katie K.; Brunson, Christopher; Mastey, Namrata; Liu, Ling; Rando, Thomas A.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [King, Katherine Y.; Tsai, Chang-Ru; Goodell, Margaret A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [King, Katherine Y.; Tsai, Chang-Ru; Goodell, Margaret A.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 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 Ctr Excellence, Palo Alto, CA 94304 USA.
C3 Stanford University; Stanford University; Baylor College of Medicine; Baylor College of Medicine; 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
RP Rando, TA (corresponding author), Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA.
EM rando@stanford.edu
FU Glenn Foundation for Medical Research; Department of Veterans Affairs; National Institutes of Health [K99 AG041764, K08 HL098898, R01 DK092883, P01 AG036695, R01 AG23806, R01 AR062185]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK092883] Funding Source: NIH RePORTER; National Institute on Aging [P01AG036695] Funding Source: NIH RePORTER
NR 35
TC 574
Z9 704
U1 0
U2 57
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 393
EP +
DI 10.1038/nature13255
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200034
PM 24870234
DA 2026-03-09
ER

PT J
AU Wu, WZ
   Wang, L
   Li, YL
   Zhang, F
   Lin, L
   Niu, SM
   Chenet, D
   Zhang, X
   Hao, YF
   Heinz, TF
   Hone, J
   Wang, ZL
AF Wu, Wenzhuo
   Wang, Lei
   Li, Yilei
   Zhang, Fan
   Lin, Long
   Niu, Simiao
   Chenet, Daniel
   Zhang, Xian
   Hao, Yufeng
   Heinz, Tony F.
   Hone, James
   Wang, Zhong Lin
TI Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics
SO NATURE
LA English
DT Article
ID transition-metal dichalcogenides; valley polarization; grain-boundary; graphene; monolayer; nanowire; electronics; strength
AB The piezoelectric characteristics of nanowires, thin films and bulk crystals have been closely studied for potential applications in sensors, transducers, energy conversion and electronics(1-3). With their high crystallinity and ability to withstand enormous strain(4-6), two-dimensional materials are of great interest as high-performance piezoelectric materials. Monolayer MoS2 is predicted to be strongly piezoelectric, an effect that disappears in the bulk owing to the opposite orientations of adjacent atomic layers(7,8). Here we report the first experimental study of the piezoelectric properties of two-dimensional MoS2 and show that cyclic stretching and releasing of thin MoS2 flakes with an odd number of atomic layers produces oscillating piezoelectric voltage and current outputs, whereas no output is observed for flakes with an even number of layers. A single monolayer flake strained by 0.53% generates a peak output of 15 mV and 20 pA, corresponding to a power density of 2 mW m(-2) and a 5.08% mechanical-to-electrical energy conversion efficiency. In agreement with theoretical predictions, the output increases with decreasing thickness and reverses sign when the strain direction is rotated by 90 degrees. Transport measurements show a strong piezotronic effect in single-layer MoS2, but not in bilayer and bulk MoS2. The coupling between piezoelectricity and semiconducting properties in two-dimensional nanomaterials may enable the development of applications in powering nanodevices, adaptive bioprobes and tunable/stretchable electronics/optoelectronics.
C1 [Wu, Wenzhuo; Lin, Long; Niu, Simiao; Wang, Zhong Lin] Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
   [Wang, Lei] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA.
   [Li, Yilei; Heinz, Tony F.] Columbia Univ, Dept Phys, New York, NY 10027 USA.
   [Zhang, Fan; Chenet, Daniel; Zhang, Xian; Hao, Yufeng; Hone, James] Columbia Univ, Dept Mech Engn, New York, NY 10027 USA.
   [Wang, Zhong Lin] Chinese Acad Sci, Beijing Inst Nanoenergy & Nanosyst, Beijing 100083, Peoples R China.
C3 University System of Georgia; Georgia Institute of Technology; Columbia University; Columbia University; Columbia University; Chinese Academy of Sciences; Beijing Institute of Nanoenergy & Nanosystems, CAS
RP Wang, ZL (corresponding author), Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
EM jh2228@columbia.edu; zhong.wang@mse.gatech.edu
FU US Department of Energy, Office of Basic Energy Sciences [DE-FG02-07ER46394]; US National Science Foundation [DMR-1122594]; 'Thousands Talents' programme for pioneer researcher and his innovation team, National Natural Science Foundation of China [51432005]; China and Beijing City Committee of Science and Technology [Z131100006013004, Z131100006013005]
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NR 37
TC 2055
Z9 2249
U1 32
U2 2343
PU NATURE PUBLISHING 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 23
PY 2014
VL 514
IS 7523
BP 470
EP +
DI 10.1038/nature13792
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900035
PM 25317560
DA 2026-03-09
ER

PT J
AU Chong, JJH
   Yang, XL
   Don, CW
   Minami, E
   Liu, YW
   Weyers, JJ
   Mahoney, WM
   Van Biber, B
   Cook, SM
   Palpant, NJ
   Gantz, JA
   Fugate, JA
   Muskheli, V
   Gough, GM
   Vogel, KW
   Astley, CA
   Hotchkiss, CE
   Baldessari, A
   Pabon, L
   Reinecke, H
   Gill, EA
   Nelson, V
   Kiem, HP
   Laflamme, MA
   Murry, CE
AF Chong, James J. H.
   Yang, Xiulan
   Don, Creighton W.
   Minami, Elina
   Liu, Yen-Wen
   Weyers, Jill J.
   Mahoney, William M., Jr.
   Van Biber, Benjamin
   Cook, Savannah M.
   Palpant, Nathan J.
   Gantz, Jay A.
   Fugate, James A.
   Muskheli, Veronica
   Gough, G. Michael
   Vogel, Keith W.
   Astley, Cliff A.
   Hotchkiss, Charlotte E.
   Baldessari, Audrey
   Pabon, Lil
   Reinecke, Hans
   Gill, Edward A.
   Nelson, Veronica
   Kiem, Hans-Peter
   Laflamme, Michael A.
   Murry, Charles E.
TI Human embryonic-stem-cell-derived cardiomyocytesregenerate non-humanprimate hearts
SO NATURE
LA English
DT Article
ID large animal-models; engraft
AB Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure(1) by providing human cardiomyocytes to support heart regeneration(2). Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment(3-7). However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intramyocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarctedheart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models(7), nonfatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.
C1 [Chong, James J. H.; Yang, Xiulan; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J.; Mahoney, William M., Jr.; Van Biber, Benjamin; Palpant, Nathan J.; Gantz, Jay A.; Fugate, James A.; Muskheli, Veronica; Pabon, Lil; Reinecke, Hans; Laflamme, Michael A.; Murry, Charles E.] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98109 USA.
   [Chong, James J. H.; Yang, Xiulan; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J.; Mahoney, William M., Jr.; Van Biber, Benjamin; Palpant, Nathan J.; Gantz, Jay A.; Fugate, James A.; Muskheli, Veronica; Pabon, Lil; Reinecke, Hans; Laflamme, Michael A.; Murry, Charles E.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA.
   [Chong, James J. H.] Westmead Hosp, Dept Cardiol, Westmead, NSW 2145, Australia.
   [Chong, James J. H.] Univ Sydney, Sch Med, Sydney, NSW 2006, Australia.
   [Chong, James J. H.; Yang, Xiulan; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J.; Mahoney, William M., Jr.; Van Biber, Benjamin; Palpant, Nathan J.; Gantz, Jay A.; Fugate, James A.; Muskheli, Veronica; Pabon, Lil; Reinecke, Hans; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Don, Creighton W.; Minami, Elina; Gill, Edward A.; Murry, Charles E.] Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA.
   [Cook, Savannah M.] Univ Washington, Inst Stem Cell & Regenerat Med, Dept Comparat Med, Seattle, WA 98109 USA.
   [Gantz, Jay A.; Murry, Charles E.] Univ Washington, Dept Bioengn, Seattle, WA 98109 USA.
   [Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
   [Nelson, Veronica; Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Sydney; NSW Health; Westmead Hospital; University of Sydney; 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; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center
RP Murry, CE (corresponding author), Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98109 USA.
EM murry@uw.edu
FU National Institutes of Health [P01HL094374, R01HL084642, U01HL100405, P01GM081619]; Institute of Translational Health Sciences/Primate Center Ignition Award; National Health and Medical Research Council of Australia; Australian-American Fulbright Commission; American Heart Association [12POST11940060, 12POST9330030]; Jose Carreras/E.D. Thomas Chair for Cancer Research; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK017047] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER; NIH Office of the Director [P51OD010425] Funding Source: NIH RePORTER; American Heart Association (AHA) [12POST11940060, 12POST9330030] Funding Source: American Heart Association (AHA)
NR 30
TC 1078
Z9 1348
U1 1
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 JUN 12
PY 2014
VL 510
IS 7504
BP 273
EP +
DI 10.1038/nature13233
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400051
PM 24776797
DA 2026-03-09
ER

PT J
AU Shi, JJ
   Zhao, Y
   Wang, YP
   Gao, WQ
   Ding, JJ
   Li, P
   Hu, LY
   Shao, F
AF Shi, Jianjin
   Zhao, Yue
   Wang, Yupeng
   Gao, Wenqing
   Ding, Jingjin
   Li, Peng
   Hu, Liyan
   Shao, Feng
TI Inflammatory caspases are innate immune receptors for intracellular LPS
SO NATURE
LA English
DT Article
ID lipopolysaccharide recognition; activation; protein; mechanisms; pyroptosis; flagellin; promotes; bacteria; binding; tlr4
AB The murine caspase-11 non-canonical inflammasome responds to various bacterial infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism underlying cytosolic LPS sensing and the responsible pattern recognition receptor are unknown. Here we show that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced cytotoxicity was mediated by human caspase-4 that could functionally complement murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and lipid A with high specificity and affinity. LPS associated with endogenous caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent oligomerization upon LPS binding, resulting in activation of the caspases. Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) could bind to caspase-4/11 but failed to induce their oligomerization and activation. LPS binding was mediated by the CARD domain of the caspase. Binding-deficient CARD-domain point mutants did not respond to LPS with oligomerization or activation and failed to induce pyroptosis upon LPS electroporation or bacterial infections. The function of caspase-4/5/11 represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation.
C1 [Shi, Jianjin; Shao, Feng] Natl Inst Biol Sci, Peking Univ Tsinghua Univ Natl Inst Biol Sci Join, Beijing 102206, Peoples R China.
   [Shi, Jianjin; Zhao, Yue; Wang, Yupeng; Gao, Wenqing; Ding, Jingjin; Li, Peng; Hu, Liyan; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Ding, Jingjin; Shao, Feng] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Shao, Feng] Natl Inst Biol Sci, Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China.
C3 Tsinghua University; National Institute of Biological Sciences, Beijing; National Institute of Biological Sciences, Beijing; Chinese Academy of Sciences; Institute of Biophysics, CAS; National Institute of Biological Sciences, Beijing
RP Shao, F (corresponding author), Natl Inst Biol Sci, Peking Univ Tsinghua Univ Natl Inst Biol Sci Join, Beijing 102206, Peoples R China.
EM shaofeng@nibs.ac.cn
FU International Early Career Scientist grant from the Howard Hughes Medical Institute; Beijing Scholar Program; National Basic Research Program of China 973 Program [2012CB518700]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDB08020202]; China National Science Foundation Program for Distinguished Young Scholars [31225002]
NR 39
TC 1857
Z9 2153
U1 16
U2 730
PU NATURE PUBLISHING 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 9
PY 2014
VL 514
IS 7521
BP 187
EP +
DI 10.1038/nature13683
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100033
PM 25119034
DA 2026-03-09
ER

PT J
AU Whicher, JR
   Dutta, S
   Hansen, DA
   Hale, WA
   Chemler, JA
   Dosey, AM
   Narayan, ARH
   Håkansson, K
   Sherman, DH
   Smith, JL
   Skiniotis, G
AF Whicher, Jonathan R.
   Dutta, Somnath
   Hansen, Douglas A.
   Hale, Wendi A.
   Chemler, Joseph A.
   Dosey, Annie M.
   Narayan, Alison R. H.
   Hakansson, Kristina
   Sherman, David H.
   Smith, Janet L.
   Skiniotis, Georgios
TI Structural rearrangements of a polyketide synthase module during its catalytic cycle
SO NATURE
LA English
DT Article
ID chain elongation; biosynthesis; pikromycin; resolution; recognition; reveals; design; domain
AB The polyketide synthase (PKS) mega-enzyme assembly line uses a modular architecture to synthesize diverse and bioactive natural products that often constitute the core structures or complete chemical entities for many clinically approved therapeutic agents(1). The architecture of a full-length PKS module from the pikromycin pathway of Streptomyces venezuelae creates a reaction chamber for the intra-module acyl carrier protein (ACP) domain that carries building blocks and intermediates between acyltransferase, ketosynthase and ketoreductase active sites (see accompanying paper(2)). Here we determine electron cryo-microscopy structures of a full-length pikromycin PKS module in three key biochemical states of its catalytic cycle. Each biochemical state was confirmed by bottom-up liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry. The ACP domain is differentially and precisely positioned after polyketide chain substrate loading on the active site of the ketosynthase, after extension to the beta-keto intermediate, and after beta-hydroxy product generation. The structures reveal the ACP dynamics for sequential interactions with catalytic domains within the reaction chamber, and for transferring the elongated and processed polyketide substrate to the next module in the PKS pathway. During the enzymatic cycle the ketoreductase domain undergoes dramatic conformational rearrangements that enable optimal positioning for reductive processing of the ACP-bound polyketide chain elongation intermediate. These findings have crucial implications for the design of functional PKS modules, and for the engineering of pathways to generate pharmacologically relevant molecules.
C1 [Whicher, Jonathan R.; Dutta, Somnath; Hansen, Douglas A.; Chemler, Joseph A.; Dosey, Annie M.; Narayan, Alison R. H.; Sherman, David H.; Smith, Janet L.; Skiniotis, Georgios] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Whicher, Jonathan R.] Univ Michigan, Chem Biol Grad Program, Ann Arbor, MI 48109 USA.
   [Hansen, Douglas A.; Sherman, David H.] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA.
   [Hale, Wendi A.; Hakansson, Kristina; Sherman, David H.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
   [Sherman, David H.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Smith, Janet L.; Skiniotis, Georgios] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Skiniotis, G (corresponding author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
EM kicki@umich.edu; davidhs@umich.edu; JanetSmith@umich.edu; skinioti@umich.edu
FU Pew Scholar Program in Biomedical Sciences; University of Michigan Biological Sciences Scholars Program; Rackham Merit fellowship; American Foundation for Pharmaceutical Education predoctoral fellowship; National Research Service Award postdoctoral fellowship; Life Sciences Research Foundation; National Institutes of Health [1 R21CA138331-01A1, GM076477, DK042303, DK090165]; Hans W. Vahlteich Professorship; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK042303] Funding Source: NIH RePORTER
NR 37
TC 152
Z9 207
U1 1
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 JUN 26
PY 2014
VL 510
IS 7506
BP 560
EP +
DI 10.1038/nature13409
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300052
PM 24965656
DA 2026-03-09
ER

PT J
AU Zhang, X
   Lohmann, G
   Knorr, G
   Purcell, C
AF Zhang, Xu
   Lohmann, Gerrit
   Knorr, Gregor
   Purcell, Conor
TI Abrupt glacial climate shifts controlled by ice sheet changes
SO NATURE
LA English
DT Article
ID millennial-scale changes; north-atlantic; dansgaard-oeschger; thermohaline circulation; ocean circulation; late pleistocene; mis 3; atmospheric circulation; heinrich events; rapid changes
AB During glacial periods of the Late Pleistocene, an abundance of proxy data demonstrates the existence of large and repeated millennial-scale warming episodes, known as Dansgaard-Oeschger (DO) events(1). This ubiquitous feature of rapid glacial climate change can be extended back as far as 800,000 years before present (BP) in the ice core record(2), and has drawn broad attention within the science and policy-making communities alike(3). Many studies have been dedicated to investigating the underlying causes of these changes, but no coherent mechanism has yet been identified(3-15). Here we show, by using a comprehensive fully coupled model(16), that gradual changes in the height of the Northern Hemisphere ice sheets (NHISs) canalter the coupled atmosphere ocean system and cause rapid glacial climate shifts closely resembling DO events. The simulated global climate responses-including abrupt warming in the North Atlantic, a northward shift of the tropical rain-belts, and Southern Hemisphere cooling related to the bipolar seesa ware generally consistent with empirical evidence(1,3,17). As a result of the coexistence of two glacial ocean circulation states at intermediate heights of the ice sheets, minor changes in the height of the NHISs and the amount of atmospheric CO2 can trigger the rapid climate transitions via a local positive atmosphere-ocean-sea-ice feedback in the North Atlantic. Our results, although based on a single model, thus provide a coherent concept for understanding the recorded millennial scale variability and abrupt climate changes in the coupled atmosphere ocean system, as well as their linkages to the volume of the intermediate ice sheets during glacials.
C1 [Zhang, Xu; Lohmann, Gerrit; Knorr, Gregor; Purcell, Conor] Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, D-27570 Bremerhaven, Germany.
   [Lohmann, Gerrit] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Knorr, Gregor; Purcell, Conor] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3AT, S Glam, Wales.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Bremen; Cardiff University
RP Zhang, X (corresponding author), Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, Bussestr 24, D-27570 Bremerhaven, Germany.
EM xu.zhang@awi.de
FU Polar Regions and Coasts in the Changing Earth System (PACES) programme of the AWI; 'Helmholtz Climate Initiative REKLIM' (Regional Climate Change), a joint research project of the Helmholtz Association of German research centres (HGF)
NR 99
TC 209
Z9 237
U1 4
U2 209
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 21
PY 2014
VL 512
IS 7514
BP 290
EP +
DI 10.1038/nature13592
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200030
PM 25119027
DA 2026-03-09
ER

PT J
AU Zhong, L
   Wang, JW
   Sheng, HW
   Zhang, Z
   Mao, SX
AF Zhong, Li
   Wang, Jiangwei
   Sheng, Hongwei
   Zhang, Ze
   Mao, Scott X.
TI Formation of monatomic metallic glasses through ultrafast liquid quenching
SO NATURE
LA English
DT Article
ID phase-change materials; augmented-wave method; amorphous iron; electron-diffraction; molecular-dynamics; tantalum; films; relaxation; adsorption; transport
AB It has long been conjectured that any metallic liquid can be vitrified into a glassy state provided that the cooling rate is sufficiently high(1-4). Experimentally, however, vitrification of single-element metallic liquids is notoriously difficult(5). True laboratory demonstration of the formation of monatomic metallic glass has been lacking. Here we report an experimental approach to the vitrification of monatomic metallic liquids by achieving an unprecedentedly high liquid-quenching rate of 10(14)Ks(-1). Under such a high cooling rate, melts of pure refractory body-centred cubic (bcc) metals, such as liquid tantalum and vanadium, are successfully vitrified to form metallic glasses suitable for property interrogations. Combining in situ transmission electron microscopy observation and atoms-to-continuum modelling, we investigated the formation condition and thermal stability of the monatomic metallic glasses as obtained. The availability of monatomic metallic glasses, being the simplest glass formers, offers unique possibilities for studying the structure and property relationships of glasses. Our technique also shows great control over the reversible vitrification-crystallization processes, suggesting its potential in micro-electromechanical applications. The ultrahigh cooling rate, approaching the highest liquid-quenching rate attainable in the experiment, makes it possible to explore the fast kinetics and structural behaviour of supercooled metallic liquids within the nanosecond to picosecond regimes.
C1 [Zhong, Li; Wang, Jiangwei; Mao, Scott X.] Univ Pittsburgh, Dept Mech Engn & Mat Sci, Pittsburgh, PA 15261 USA.
   [Sheng, Hongwei] George Mason Univ, Sch Phys Astron & Computat Sci, Fairfax, VA 22030 USA.
   [Sheng, Hongwei] Ctr High Pressure Sci & Technol Adv Res, Shanghai 201203, Peoples R China.
   [Zhang, Ze] Zhejiang Univ, Dept Mat Sci & Engn, Hangzhou 310027, Zhejiang, Peoples R China.
   [Zhang, Ze] Zhejiang Univ, State Key Lab Silicon Mat, Hangzhou 310027, Zhejiang, Peoples R China.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; George Mason University; Zhejiang University; Zhejiang University
RP Mao, SX (corresponding author), Univ Pittsburgh, Dept Mech Engn & Mat Sci, Pittsburgh, PA 15261 USA.
EM hsheng@gmu.edu; sxm2@pitt.edu
FU National Science Foundation (NSF) through University of Pittsburgh [CMMI 0928517]; US NSF [DMR-0907325]; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0928517] Funding Source: National Science Foundation
NR 49
TC 430
Z9 500
U1 8
U2 760
PU NATURE PUBLISHING 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 14
PY 2014
VL 512
IS 7513
BP 177
EP +
DI 10.1038/nature13617
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700028
PM 25119235
DA 2026-03-09
ER

PT J
AU Stephens, IW
   Looney, LW
   Kwon, W
   Fernández-López, M
   Hughes, AM
   Mundy, LG
   Crutcher, RM
   Li, ZY
   Rao, R
AF Stephens, Ian W.
   Looney, Leslie W.
   Kwon, Woojin
   Fernandez-Lopez, Manuel
   Hughes, A. Meredith
   Mundy, Lee G.
   Crutcher, Richard M.
   Li, Zhi-Yun
   Rao, Ramprasad
TI Spatially resolvedmagnetic field structure in the disk of a T Tauri star
SO NATURE
LA English
DT Article
ID young stellar objects; magnetic-fields; hl tauri; accretion disks; millimeter; polarization; protostar; emission; outflows; regions
AB Magnetic fields in accretion disks play a dominant part during the star formation process(1,2) but have hitherto beenobservationally poorly constrained. Field strengths have been inferred on T Tauri stars(3) and possibly in the innermost part of their accretion disks(4), but the strength and morphology of the field in the bulk of a disk have not beenobserved. Spatially unresolved measurements of polarized emission (arising from elongated dust grains aligned perpendicularly to the field(5)) imply average fields aligned with the disks(6,7). Theoretically, the fields are expected to be largely toroidal, poloidal or a mixture of the two(1,2,8-10), whichimply different mechanisms for transporting angular momentum in the disks of actively accreting young stars such as HL Tau (ref. 11). Here we report resolved measurements of the polarized 1.25-millimetre continuum emission from the disk of HL Tau. The magnetic field on a scale of 80 astronomical units is coincident with the major axis (about 210 astronomical units long(12)) of the disk. From this we conclude that the magnetic field inside the disk at this scale cannot be dominated by a vertical component, though a purely toroidal field also does not fit the data well. The unexpected morphology suggests that the role of the magnetic field in the accretion of a T Tauri star is more complex than our current theoretical understanding.
C1 [Stephens, Ian W.] Boston Univ, Inst Astrophys Res, Boston, MA 02215 USA.
   [Stephens, Ian W.; Looney, Leslie W.; Fernandez-Lopez, Manuel; Crutcher, Richard M.] Univ Illinois, Dept Astron, Urbana, IL 61801 USA.
   [Kwon, Woojin] Univ Groningen, SRON Netherlands Inst Space Res, NL-9747 AD Groningen, Netherlands.
   [Fernandez-Lopez, Manuel] CCT La Plata CONICET, Inst Argentino Radioastron, RA-1894 Villa Elisa, Argentina.
   [Hughes, A. Meredith] Wesleyan Univ, Dept Astron, Van Vleck Observ, Middletown, CT 06459 USA.
   [Mundy, Lee G.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Mundy, Lee G.] Univ Maryland, Lab Millimeter Wave Astron, College Pk, MD 20742 USA.
   [Li, Zhi-Yun] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Rao, Ramprasad] Acad Sinica, Inst Astron & Astrophys, Hilo, HI 96720 USA.
C3 Boston University; University of Illinois System; University of Illinois Urbana-Champaign; University of Groningen; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Instituto Argentino de Radioastronomia; Wesleyan University; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University of Virginia; Academia Sinica - Taiwan
RP Stephens, IW (corresponding author), Boston Univ, Inst Astrophys Res, Boston, MA 02215 USA.
EM ianws@bu.edu
FU NSF [AST-1139950, AST-1139998]; state of California; state of Illinois; state of Maryland; James S. McDonnell Foundation; Gordon and Betty Moore Foundation; Kenneth T. and Eileen L. Norris Foundation; University of Chicago; Associates of the California Institute of Technology; National Science Foundation; CARMA partner universities;  [NSF AST 08-38226]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1140063, 1007713, 1140019, 1139950] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1140031, 1139998] Funding Source: National Science Foundation
NR 32
TC 117
Z9 124
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 OCT 30
PY 2014
VL 514
IS 7524
BP 597
EP +
DI 10.1038/nature13850
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500041
PM 25337883
DA 2026-03-09
ER

PT J
AU Masamha, CP
   Xia, Z
   Yang, JX
   Albrecht, TR
   Li, M
   Shyu, AB
   Li, W
   Wagner, EJ
AF Masamha, Chioniso P.
   Xia, Zheng
   Yang, Jingxuan
   Albrecht, Todd R.
   Li, Min
   Shyu, Ann-Bin
   Li, Wei
   Wagner, Eric J.
TI CFIm25 links alternative polyadenylation to glioblastoma tumour suppression
SO NATURE
LA English
DT Article
ID 3' untranslated regions; messenger-rnas; glutamine-metabolism; prostate-cancer; antisense rna; c-myc; growth; widespread; expression; micrornas
AB The global shortening of messenger RNAs through alternative polyadenylation (APA) that occurs during enhanced cellular proliferation represents an important, yet poorly understood mechanism of regulated gene expression(1,2). The 3' untranslated region (UTR) truncation of growth-promoting mRNA transcripts that relieves intrinsic microRNA-and AU-rich-element-mediated repression has been observed to correlate with cellular transformation(3); however, the importance to tumorigenicity of RNA 3'-end-processing factors that potentially govern APA is unknown. Here we identify CFIm25 as a broad repressor of proximal poly(A) site usage that, when depleted, increases cell proliferation. Applying a regression model on standard RNA-sequencing data for novel APA events, we identified at least 1,450 genes with shortened 3'UTRs after CFIm25knockdown, representing 11% of significantly expressed mRNAs in human cells. Marked increases in the expression of several known oncogenes, including cyclin D1, are observed as a consequence of CFIm25 depletion. Importantly, we identified a subset of CFIm25-regulated APA genes with shortened 39 UTRs in glioblastoma tumours that have reduced CFIm25 expression. Downregulation of CFIm25 expression in glioblastoma cells enhances their tumorigenic properties and increases tumour size, where as CFIm25 overexpression reduces these properties and inhibits tumour growth. These findings identify a pivotal role of CFIm25 in governing APA and reveal a previously unknown connection between CFIm25 and glioblastoma tumorigenicity.
C1 [Masamha, Chioniso P.; Albrecht, Todd R.; Shyu, Ann-Bin; Wagner, Eric J.] Univ Texas Houston, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Xia, Zheng; Li, Wei] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA.
   [Xia, Zheng; Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Yang, Jingxuan; Li, Min] Univ Texas Houston, Sch Med, Vivian L Smith Dept Neurosurg, Houston, TX 77030 USA.
C3 University of Texas System; University of Texas Health Science Center Houston; Baylor College of Medicine; Baylor College of Medicine; University of Texas System; University of Texas Health Science Center Houston
RP Wagner, EJ (corresponding author), Univ Texas Houston, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
EM Ann-Bin.Shyu@uth.tmc.edu; WL1@bcm.edu; Eric.J.Wagner@uth.tmc.edu
FU CPRIT [RP100107, RP110471-C3]; Department of Defense [W81XWH-11-1-0304, W81XWH-10-1-0501]; National Institutes of Health (NIH) [GM046454, CA167752, CA166274]; Houston Endowment; NIH [R01HG007538]; Dr Marnie Rose Foundation; William and Ella Owens Medical Research Foundation; Department of Defense Postdoctoral Visionary Award [W81XWH-12-1-0218]
NR 39
TC 347
Z9 407
U1 2
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 JUN 19
PY 2014
VL 510
IS 7505
BP 412
EP +
DI 10.1038/nature13261
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200038
PM 24814343
DA 2026-03-09
ER

PT J
AU Smith, ZD
   Chan, MM
   Humm, KC
   Karnik, R
   Mekhoubad, S
   Regev, A
   Eggan, K
   Meissner, A
AF Smith, Zachary D.
   Chan, Michelle M.
   Humm, Kathryn C.
   Karnik, Rahul
   Mekhoubad, Shila
   Regev, Aviv
   Eggan, Kevin
   Meissner, Alexander
TI DNA methylation dynamics of the human preimplantation embryo
SO NATURE
LA English
DT Article
ID stem-cells; epigenetic inheritance; noncoding rna; mouse; retrotransposons; pluripotent; maintenance; landscape; mechanism; evolution
AB In mammals, cytosine methylation is predominantly restricted to CpG dinudeotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors(1-3). This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features(4-7). These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved(8-10). We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.
C1 [Smith, Zachary D.; Chan, Michelle M.; Karnik, Rahul; Regev, Aviv; Eggan, Kevin; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Smith, Zachary D.; Karnik, Rahul; Eggan, Kevin; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Smith, Zachary D.; Humm, Kathryn C.; Karnik, Rahul; Mekhoubad, Shila; Eggan, Kevin; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Smith, Zachary D.; Mekhoubad, Shila; Eggan, Kevin] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Chan, Michelle M.] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA.
   [Humm, Kathryn C.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Boston, MA 02215 USA.
   [Humm, Kathryn C.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Humm, Kathryn C.] Boston IVF, Waltham, MA 02451 USA.
   [Humm, Kathryn C.; Regev, Aviv] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
   [Regev, Aviv] MIT, Cambridge, MA 02142 USA.
   [Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Howard Hughes Medical Institute
RP Meissner, A (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM keggan@scrb.harvard.edu; alexander_meissner@harvard.edu
FU Harvard Stem Cell Institute; NIH Pioneer Award [5DP10D003958]; Burroughs Wellcome Career Award at the Scientific Interface; HHMI; Center for Excellence in Genome Science from the NHGRI [1P50HG006193-01]; New York Stem Cell Foundation;  [P01GM099117]; National Institute of General Medical Sciences [P01GM099117] Funding Source: NIH RePORTER
NR 31
TC 469
Z9 546
U1 1
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 JUL 30
PY 2014
VL 511
IS 7511
BP 611
EP +
DI 10.1038/nature13581
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300039
PM 25079558
DA 2026-03-09
ER

PT J
AU Ko, SY
   Pegu, A
   Rudicell, RS
   Yang, ZY
   Joyce, MG
   Chen, XJ
   Wang, KY
   Bao, S
   Kraemer, TD
   Rath, T
   Zeng, M
   Schmidt, SD
   Todd, JP
   Penzak, SR
   Saunders, KO
   Nason, MC
   Haase, AT
   Rao, SS
   Blumberg, RS
   Mascola, JR
   Nabel, GJ
AF Ko, Sung-Youl
   Pegu, Amarendra
   Rudicell, Rebecca S.
   Yang, Zhi-yong
   Joyce, M. Gordon
   Chen, Xuejun
   Wang, Keyun
   Bao, Saran
   Kraemer, Thomas D.
   Rath, Timo
   Zeng, Ming
   Schmidt, Stephen D.
   Todd, John-Paul
   Penzak, Scott R.
   Saunders, Kevin O.
   Nason, Martha C.
   Haase, Ashley T.
   Rao, Srinivas S.
   Blumberg, Richard S.
   Mascola, John R.
   Nabel, Gary J.
TI Enhanced neonatal Fc receptor function improves protection against primate SHIV infection
SO NATURE
LA English
DT Article
ID neutralizing antibody; half-life; hiv-1 vaccine; human igg1; monoclonal-antibody; dendritic cells; in-vivo; transport; challenge; immunity
AB To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn)(1,2), whose role in protecting against infection in vivo has not been defined. Here, we show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue localization, which improves protection against lentiviral infection in non-human primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env) protein (denoted VRC01)(3) was modified by site-directed mutagenesis to increase its binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01-LS, displayed increased transcytosis across human FcRn-expressing cellular monolayers in vitro while retaining Fc gamma RIIIa binding and function, including antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than VRC01 in non-human primates and persisted in the rectal mucosa even when it was no longer detectable in the serum. Notably, VRC01-LSmediated protection superior to that afforded by VRC01 against intrarectal infection with simian-human immunodeficiency virus (SHIV). These findings suggest that modification of FcRn binding provides a mechanism not only to increase serum half-life but also to enhance mucosal localization that confers immune protection. Mutations that enhance FcRn function could therefore increase the potency and durability of passive immunization strategies to prevent HIV-1 infection.
C1 [Ko, Sung-Youl; Pegu, Amarendra; Rudicell, Rebecca S.; Yang, Zhi-yong; Joyce, M. Gordon; Chen, Xuejun; Wang, Keyun; Bao, Saran; Schmidt, Stephen D.; Todd, John-Paul; Saunders, Kevin O.; Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Kraemer, Thomas D.; Rath, Timo; Blumberg, Richard S.] Harvard Univ, Brigham & Womens Hosp, Div Gastroenterol, Dept Med, Boston, MA 02115 USA.
   [Zeng, Ming; Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Penzak, Scott R.] NIH, Clin Pharmacokinet Lab, Dept Pharm, Bethesda, MD 20814 USA.
   [Nason, Martha C.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Minnesota System; University of Minnesota Twin Cities; National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Nabel, GJ (corresponding author), Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA.
EM jmascola@nih.gov; Gary.Nabel@sanofi.com
FU Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Foundation for the National Institutes of Health; Collaboration for AIDS Vaccine Discovery (CAVD) award from the Bill & Melinda Gates Foundation [OPP1039775]; NIH [DK044319, DK051362, DK053056, DK088199]; Harvard Digestive Diseases Center [DK0034854]; German research foundation (DFG) [RA 2040/1-1]; Bill and Melinda Gates Foundation [OPP1039775] Funding Source: Bill and Melinda Gates Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854, R01DK051362, R01DK088199, R01DK053056, R01DK044319] Funding Source: NIH RePORTER
NR 37
TC 313
Z9 378
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 OCT 30
PY 2014
VL 514
IS 7524
BP 642
EP +
DI 10.1038/nature13612
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500052
PM 25119033
DA 2026-03-09
ER

PT J
AU Marchi, S
   Bottke, WF
   Elkins-Tanton, LT
   Bierhaus, M
   Wuennemann, K
   Morbidelli, A
   Kring, DA
AF Marchi, S.
   Bottke, W. F.
   Elkins-Tanton, L. T.
   Bierhaus, M.
   Wuennemann, K.
   Morbidelli, A.
   Kring, D. A.
TI Widespread mixing and burial of Earth's Hadean crust by asteroid impacts
SO NATURE
LA English
DT Article
ID heavy bombardment; detrital zircons; lunar cataclysm; archean crust; billion years; u-pb; moon; constraints; accretion; origin
AB The history of the Hadean Earth (similar to 4.0-4.5 billion years ago) is poorly understood because few known rocks are older than similar to 3.8 billion years old(1). The main constraints from this era come from ancient submillimetre zircon grains(2,3). Some of these zircons date back to similar to 4.4 billion years ago when the Moon, and presumably the Earth, was being pummelled by an enormous flux of extraterrestrial bodies(4). The magnitude and exact timing of these early terrestrial impacts, and their effects on crustal growth and evolution, are unknown. Here we provide a new bombardment model of the Hadean Earth that has been calibrated using existing lunar(4) and terrestrial data(5). We find that the surface of the Hadean Earth was widely reprocessed by impacts through mixing and burial by impact-generated melt. This model may explain the age distribution of Hadean zircons and the absence of early terrestrial rocks. Existing oceans would have repeatedly boiled away into steam atmospheres as a result of large collisions as late as about 4 billion years ago.
C1 [Marchi, S.; Bottke, W. F.] SW Res Inst, Boulder, CO 80302 USA.
   [Elkins-Tanton, L. T.] Carnegie Inst Sci, Washington, DC 20015 USA.
   [Bierhaus, M.; Wuennemann, K.] Museum Nat Kunde, D-10115 Berlin, Germany.
   [Morbidelli, A.] Observ Cote Azur, F-06304 Nice, France.
   [Kring, D. A.] Univ Space Res Assoc, Lunar & Planetary Inst, Houston, TX 77058 USA.
C3 Carnegie Institution for Science; Leibniz Institut fur Evolutions und Biodiversitatsforschung; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Universities Space Research Association (USRA)
RP Marchi, S (corresponding author), SW Res Inst, Boulder, CO 80302 USA.
EM marchi@boulder.swri.edu
FU NASA Solar System Exploration Research Virtual Institute [NNA14AB03A, NNA14AB07A]; Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V. Alliance 'Planetary Evolution and Life'; European Research Council [290568]; European Research Council (ERC) [290568] Funding Source: European Research Council (ERC); NASA [NNA14AB03A, 685022] Funding Source: Federal RePORTER; H2020 - Industrial Leadership [685022] Funding Source: H2020 - Industrial Leadership; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0747154] Funding Source: National Science Foundation
NR 79
TC 212
Z9 232
U1 0
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 JUL 30
PY 2014
VL 511
IS 7511
BP 578
EP +
DI 10.1038/nature13539
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300032
PM 25079556
DA 2026-03-09
ER

PT J
AU King, NP
   Bale, JB
   Sheffler, W
   McNamara, DE
   Gonen, S
   Gonen, T
   Yeates, TO
   Baker, D
AF King, Neil P.
   Bale, Jacob B.
   Sheffler, William
   McNamara, Dan E.
   Gonen, Shane
   Gonen, Tamir
   Yeates, Todd O.
   Baker, David
TI Accurate design of co-assembling multi-component protein nanomaterials
SO NATURE
LA English
DT Article
ID computational design; directed evolution; dna; symmetry; nanostructures; interfaces; homodimer; container; arrays; cages
AB The self-assembly of proteins into highly ordered nanoscale architectures is a hallmark of biological systems. The sophisticated functions of these molecular machines have inspired the development of methods to engineer self-assembling protein nanostructures; however, the design of multi-component protein nanomaterials with high accuracy remains an outstanding challenge. Here we report a computational method for designing protein nanomaterials in which multiple copies of two distinct subunits co-assemble into a specific architecture. We use the method to design five 24-subunit cage-like protein nanomaterials in two distinct symmetric architectures and experimentally demonstrate that their structures are in close agreement with the computational design models. The accuracy of the method and the number and variety of two-component materials that it makes accessible suggest a route to the construction of functional protein nanomaterials tailored to specific applications.
C1 [King, Neil P.; Bale, Jacob B.; Sheffler, William; Gonen, Shane; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [King, Neil P.; Baker, David] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
   [Bale, Jacob B.] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA.
   [McNamara, Dan E.; Yeates, Todd O.] UCLA Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Gonen, Shane; Gonen, Tamir] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Yeates, Todd O.] UCLA DOE Inst Genom & Prote, Los Angeles, CA 90095 USA.
   [Yeates, Todd O.] UCLA Mol Biol Inst, Los Angeles, CA 90095 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; Howard Hughes Medical Institute; United States Department of Energy (DOE); University of California System; University of California Los Angeles; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM dabaker@u.washington.edu
FU Howard Hughes Medical Institute; JFRC; National Science Foundation [CHE-1332907]; International AIDS Vaccine Initiative, DTRA [N00024-10-D-6318/0024]; AFOSR [FA950-12-10112]; DOE [DE-SC0005155]; NIH [T32GM067555]; NSF [DGE-0718124]; BER programme of the DOE Office of Science; U.S. Department of Energy (DOE) [DE-SC0005155] Funding Source: U.S. Department of Energy (DOE); Division Of Chemistry; Direct For Mathematical & Physical Scien [1332907] Funding Source: National Science Foundation
NR 38
TC 470
Z9 609
U1 5
U2 464
PU NATURE PUBLISHING 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 5
PY 2014
VL 510
IS 7503
BP 103
EP +
DI 10.1038/nature13404
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900037
PM 24870237
DA 2026-03-09
ER

PT J
AU Takahashi, N
   Vereecke, L
   Bertrand, MJM
   Duprez, L
   Berger, SB
   Divert, T
   Gonçalves, A
   Sze, M
   Gilbert, B
   Kourula, S
   Goossens, V
   Lefebvre, S
   Gunther, C
   Becker, C
   Bertin, J
   Gough, PJ
   Declercq, W
   van Loo, G
   Vandenabeele, P
AF Takahashi, Nozomi
   Vereecke, Lars
   Bertrand, Mathieu J. M.
   Duprez, Linde
   Berger, Scott B.
   Divert, Tatyana
   Goncalves, Amanda
   Sze, Mozes
   Gilbert, Barbara
   Kourula, Stephanie
   Goossens, Vera
   Lefebvre, Sylvie
   Gunther, Claudia
   Becker, Christoph
   Bertin, John
   Gough, Peter J.
   Declercq, Wim
   van Loo, Geert
   Vandenabeele, Peter
TI RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis
SO NATURE
LA English
DT Article
ID necrosis-factor receptor-1; cell-death; kinase; inflammation; necroptosis; ubiquitination; ripoptosome; crossroads; regulator; lethality
AB Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors(1,2). RIPK1 is believed to function as a node driving NF-kappa B-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice(3). To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-kappa B activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-kappa B activation.
C1 [Takahashi, Nozomi; Vereecke, Lars; Bertrand, Mathieu J. M.; Duprez, Linde; Divert, Tatyana; Goncalves, Amanda; Sze, Mozes; Gilbert, Barbara; Kourula, Stephanie; Goossens, Vera; Lefebvre, Sylvie; Declercq, Wim; van Loo, Geert; Vandenabeele, Peter] VIB Inflammat Res Ctr, B-9052 Ghent, Belgium.
   [Takahashi, Nozomi; Vereecke, Lars; Bertrand, Mathieu J. M.; Duprez, Linde; Divert, Tatyana; Goncalves, Amanda; Sze, Mozes; Gilbert, Barbara; Kourula, Stephanie; Goossens, Vera; Lefebvre, Sylvie; Declercq, Wim; van Loo, Geert; Vandenabeele, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium.
   [Berger, Scott B.; Bertin, John; Gough, Peter J.] GlaxoSmithKline, Immunoinflammat Therapeut Area, Pattern Recognit Receptor Discovery Performance U, Collegeville, PA 19426 USA.
   [Goncalves, Amanda] VIB Bio Imaging Core Gent, B-9052 Ghent, Belgium.
   [Gunther, Claudia; Becker, Christoph] Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany.
   [Vandenabeele, Peter] Univ Ghent, Methusalem Program, B-9052 Ghent, Belgium.
C3 Flanders Institute for Biotechnology (VIB); Ghent University; GlaxoSmithKline; Glaxosmithkline USA; Flanders Institute for Biotechnology (VIB); University of Erlangen Nuremberg; Ghent University
RP Vandenabeele, P (corresponding author), VIB Inflammat Res Ctr, Technol Pk 927, B-9052 Ghent, Belgium.
EM Peter.Vandenabeele@irc.vib-ugent.be
FU Research Foundation Flanders (FWO); VIB; FWO; FWO Odysseus Grant; FWO, Foundation against Cancer; Queen Elisabeth Medical foundation; Belgian (Interuniversity Attraction Poles) [IAP 7/32]; Flemish (Research Foundation Flanders) [FWOG.0875.11, FWOG.0973.11, FWO G.0A45.12N, FWO G.0787.13N, G.0544.11N, G0C3114N]; Flemish (Methusalem grant) [BOF09/01M00709]; Ghent University (MRP); Ghent University (GROUP-ID consortium); Foundation against Cancer [F94, 2010-162]; IZKF of the FAU Erlangen-Nurnberg; DFG [SPP1656, BE3686/2, SFB796]; Methusalem
NR 41
TC 292
Z9 317
U1 2
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 SEP 4
PY 2014
VL 513
IS 7516
BP 95
EP +
DI 10.1038/nature13706
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800037
PM 25186904
DA 2026-03-09
ER

PT J
AU Malyshev, DA
   Dhami, K
   Lavergne, T
   Chen, TJ
   Dai, N
   Foster, JM
   Corrêa, IR
   Romesberg, FE
AF Malyshev, Denis A.
   Dhami, Kirandeep
   Lavergne, Thomas
   Chen, Tingjian
   Dai, Nan
   Foster, Jeremy M.
   Correa, Ivan R., Jr.
   Romesberg, Floyd E.
TI A semi-synthetic organism with an expanded genetic alphabet
SO NATURE
LA English
DT Article
ID unnatural base-pair; dna; nucleotide; replication; transport; proteins; efficient; mutation; atp/adp
AB Organisms are defined by the information encoded in their genomes, and since the origin of life this information has been encoded using a two-base-pair genetic alphabet (A-T and G-C). In vitro, the alphabet has been expanded to include several unnatural base pairs (UBPs)(1-3). We have developed a class of UBPs formed between nucleotides bearing hydrophobic nucleobases, exemplified by the pair formed between d5SICS and dNaM (d5SICS-dNaM), which is efficiently PCR-amplified(1) and transcribed(4,5) in vitro, and whose unique mechanism of replication has been characterized(6,7). However, expansion of an organism's genetic alphabet presents new and unprecedented challenges: the unnatural nucleoside triphosphates must be available inside the cell; endogenous polymerases must be able to use the unnatural triphosphates to faithfully replicate DNA containing the UBP within the complex cellular milieu; and finally, the UBP must be stable in the presence of pathways that maintain the integrity of DNA. Here we show that an exogenously expressed algal nucleotide triphosphate transporter efficiently imports the triphosphates of both d5SICS and dNaM (d5SICSTP and dNaMTP) into Escherichia coli, and that the endogenous replication machinery uses them to accurately replicate a plasmid containing d5SICS-dNaM. Neither the presence of the unnatural triphosphates nor the replication of the UBP introduces a notable growth burden. Lastly, we find that the UBP is not efficiently excised by DNA repair pathways. Thus, the resulting bacterium is the first organism to propagate stably an expanded genetic alphabet.
C1 [Malyshev, Denis A.; Dhami, Kirandeep; Lavergne, Thomas; Chen, Tingjian; Romesberg, Floyd E.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Dai, Nan; Foster, Jeremy M.; Correa, Ivan R., Jr.] New England Biolabs Inc, Ipswich, MA 01938 USA.
C3 Scripps Research Institute; New England Biolabs
RP Romesberg, FE (corresponding author), Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM floyd@scripps.edu
FU US National Institutes of Health (NIH) [GM 060005]
NR 38
TC 462
Z9 592
U1 8
U2 504
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2014
VL 509
IS 7500
BP 385
EP +
DI 10.1038/nature13314
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200044
PM 24805238
DA 2026-03-09
ER

PT J
AU Murthy, A
   Li, Y
   Peng, I
   Reichelt, M
   Katakam, AK
   Noubade, R
   Roose-Girma, M
   DeVoss, J
   Diehl, L
   Graham, RR
   Campagne, MV
AF Murthy, Aditya
   Li, Yun
   Peng, Ivan
   Reichelt, Mike
   Katakam, Anand Kumar
   Noubade, Rajkumar
   Roose-Girma, Merone
   DeVoss, Jason
   Diehl, Lauri
   Graham, Robert R.
   Campagne, Menno van Lookeren
TI A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3
SO NATURE
LA English
DT Article
ID enterocolitica induces apoptosis; host-microbe interactions; autophagy gene atg16l1; glucose deprivation; macrophages; mechanisms; cells; inflammation; common; yopp
AB Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.
C1 [Murthy, Aditya; Li, Yun; Peng, Ivan; Noubade, Rajkumar; DeVoss, Jason; Campagne, Menno van Lookeren] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
   [Reichelt, Mike; Katakam, Anand Kumar; Diehl, Lauri] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Roose-Girma, Merone] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Graham, Robert R.] Genentech Inc, ITGR Human Genet, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
RP Campagne, MV (corresponding author), Genentech Inc, Dept Immunol, 1 DNA Way, San Francisco, CA 94080 USA.
EM menno@gene.com
NR 46
TC 313
Z9 368
U1 0
U2 73
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 27
PY 2014
VL 506
IS 7489
BP 456
EP +
DI 10.1038/nature13044
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100031
PM 24553140
DA 2026-03-09
ER

PT J
AU Krajewski, WW
   Fu, X
   Wilkinson, M
   Cronin, NB
   Dillingham, MS
   Wigley, DB
AF Krajewski, Wojciech W.
   Fu, Xin
   Wilkinson, Martin
   Cronin, Nora B.
   Dillingham, Mark S.
   Wigley, Dale B.
TI Structural basis for translocation by AddAB helicase-nuclease and its arrest at χ sites
SO NATURE
LA English
DT Article
ID recbcd enzyme; bacteriophage-lambda; crystal-structures; dna translocation; reca protein; recognition; recombination; mechanism; motor; sequence
AB In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence chi (Chi)(1,2) and is catalysed by either an AddAB-or RecBCD-type helicase-nuclease (reviewed in refs 3, 4). These enzyme complexes unwind and digest the DNA duplex from the broken end until they encounter a chi sequence(5), whereupon they produce a 3' single-stranded DNA tail onto which they initiate loading of the RecA protein(6). Consequently, regulation of the AddAB/RecBCD complex by chi is a key control point in DNA repair and other processes involving genetic recombination. Here we report crystal structures of Bacillus subtilis AddAB in complex with different chi-containing DNA substrates either with or without a non-hydrolysable ATP analogue. Comparison of these structures suggests a mechanism for DNA translocation and unwinding, suggests how the enzyme binds specifically to chi sequences, and explains how chi recognition leads to the arrest of AddAB (and RecBCD) translocation that is observed in single-molecule experiments(7-9).
C1 [Krajewski, Wojciech W.; Fu, Xin; Wilkinson, Martin; Cronin, Nora B.; Wigley, Dale B.] Chester Beatty Labs, Inst Canc Res, Div Struct Biol, London SW3 6JB, England.
   [Dillingham, Mark S.] Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England.
C3 Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; University of Bristol
RP Wigley, DB (corresponding author), Chester Beatty Labs, Inst Canc Res, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England.
EM Dale.Wigley@icr.ac.uk
FU Royal Society; Wellcome Trust; European Research Council; Cancer Research UK; EMBO; Cancer Research UK [12799] Funding Source: researchfish
NR 33
TC 45
Z9 49
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 APR 17
PY 2014
VL 508
IS 7496
BP 416
EP +
DI 10.1038/nature13037
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000056
PM 24670664
DA 2026-03-09
ER

PT J
AU Huang, JH
   Kang, BH
   Pancera, M
   Lee, JH
   Tong, T
   Feng, Y
   Imamichi, H
   Georgiev, IS
   Chuang, GY
   Druz, A
   Doria-Rose, NA
   Laub, L
   Sliepen, K
   van Gils, MJ
   de la Peña, AT
   Derking, R
   Klasse, PJ
   Migueles, SA
   Bailer, RT
   Alam, M
   Pugach, P
   Haynes, BF
   Wyatt, RT
   Sanders, RW
   Binley, JM
   Ward, AB
   Mascola, JR
   Kwong, PD
   Connors, M
AF Huang, Jinghe
   Kang, Byong H.
   Pancera, Marie
   Lee, Jeong Hyun
   Tong, Tommy
   Feng, Yu
   Imamichi, Hiromi
   Georgiev, Ivelin S.
   Chuang, Gwo-Yu
   Druz, Aliaksandr
   Doria-Rose, Nicole A.
   Laub, Leo
   Sliepen, Kwinten
   van Gils, Marit J.
   de la Pena, Alba Torrents
   Derking, Ronald
   Klasse, Per-Johan
   Migueles, Stephen A.
   Bailer, Robert T.
   Alam, Munir
   Pugach, Pavel
   Haynes, Barton F.
   Wyatt, Richard T.
   Sanders, Rogier W.
   Binley, James M.
   Ward, Andrew B.
   Mascola, John R.
   Kwong, Peter D.
   Connors, Mark
TI Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; human monoclonal-antibody; b-cells; dependent epitope; env trimers; cleavage; gp120; sera; specificity; vulnerability
AB The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50)<50 mu gml(-1). The median IC50 of neutralized viruses was 0.033 mu gml(-1), among themost potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP. 664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.
C1 [Huang, Jinghe; Kang, Byong H.; Imamichi, Hiromi; Laub, Leo; Migueles, Stephen A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Pancera, Marie; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Bailer, Robert T.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Lee, Jeong Hyun; Wyatt, Richard T.; Ward, Andrew B.] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.
   [Lee, Jeong Hyun; Feng, Yu; Wyatt, Richard T.; Ward, Andrew B.] Scripps Res Inst, Int AIDS Vaccine Initiat IAVI Neutralizing Antibo, La Jolla, CA 92037 USA.
   [Tong, Tommy; Binley, James M.] San Diego Biomed Res Inst, San Diego, CA 92121 USA.
   [Sliepen, Kwinten; van Gils, Marit J.; de la Pena, Alba Torrents; Derking, Ronald; Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1100 DD Amsterdam, Netherlands.
   [Klasse, Per-Johan; Pugach, Pavel; Sanders, Rogier W.] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA.
   [Alam, Munir; Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 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); Scripps Research Institute; Scripps Research Institute; International AIDS Vaccine Initiative; University of Amsterdam; Academic Medical Center Amsterdam; Cornell University; Weill Cornell Medicine; Duke University
RP Connors, M (corresponding author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
FU Intramural Research Programs of NIAID, National Institutes of Health; NIH HIVRAD grant [P01 AI082362]; Aids Fonds Netherlands [2011032, 2012041]; Netherlands Organization for Scientific Research (NWO); European Research Council [ERC-StG-2011-280829-SHEV]; International AIDS Vaccine Initiative; NIH [AI93278, AI84714]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Institute of Allergy and Infectious Diseases [ZICAI005111, ZIAAI005022, ZIAAI001090, R01AI093278, ZIAAI005023] Funding Source: NIH RePORTER
NR 47
TC 362
Z9 458
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 NOV 6
PY 2014
VL 515
IS 7525
BP 138
EP +
DI 10.1038/nature13601
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500045
PM 25186731
DA 2026-03-09
ER

PT J
AU Fenalti, G
   Giguere, PM
   Katritch, V
   Huang, XP
   Thompson, AA
   Cherezov, V
   Roth, BL
   Stevens, RC
AF Fenalti, Gustavo
   Giguere, Patrick M.
   Katritch, Vsevolod
   Huang, Xi-Ping
   Thompson, Aaron A.
   Cherezov, Vadim
   Roth, Bryan L.
   Stevens, Raymond C.
TI Molecular control of δ-opioid receptor signalling
SO NATURE
LA English
DT Article
ID crystallizing membrane; allosteric regulation; inverse agonists; protein; sodium; binding; design; discovery; selectivity; antagonists
AB Opioids represent widely prescribed and abused medications, although their signal transduction mechanisms are not well understood. Here we present the 1.8 angstrom high-resolution crystal structure of the human delta-opioid receptor (delta-OR), revealing the presence and fundamental role of a sodium ion in mediating allosteric control of receptor functional selectivity and constitutive activity. The distinctive delta-OR sodium ion site architecture is centrally located in a polar interaction network in the seven-transmembrane bundle core, with the sodium ion stabilizing a reduced agonist affinity state, and thereby modulating signal transduction. Site-directed mutagenesis and functional studies reveal that changing the allosteric sodium site residue Asn 131 to an alanine or a valine augments constitutive beta-arrestin-mediated signalling. Asp95Ala, Asn310Ala and Asn314Ala mutations transform classical delta-opioid antagonists such as naltrindole into potent beta-arrestin-biased agonists. The data establish the molecular basis for allosteric sodium ion control in opioid signalling, revealing that sodium-coordinating residues act as 'efficacy switches' at a prototypic G-protein-coupled receptor.
C1 [Fenalti, Gustavo; Katritch, Vsevolod; Thompson, Aaron A.; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA.
   [Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Giguere, Patrick M.; Huang, Xi-Ping; Roth, Bryan L.] Univ North Carolina Chapel Hill, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
C3 Scripps Research Institute; 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 of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
RP Stevens, RC (corresponding author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM bryan_roth@med.unc.edu; stevens@scripps.edu
FU National Institutes of Health [P50 GM073197, U54 GM094618, R01 DA017204]; NIMH Psychoactive Drug Screening Program; Michael Hooker Chair for Protein Therapeutics and Translational Proteomics; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]
NR 46
TC 422
Z9 479
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 FEB 13
PY 2014
VL 506
IS 7487
BP 191
EP 196
DI 10.1038/nature12944
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700031
PM 24413399
DA 2026-03-09
ER

PT J
AU Masarwa, A
   Didier, D
   Zabrodski, T
   Schinkel, M
   Ackermann, L
   Marek, I
AF Masarwa, Ahmad
   Didier, Dorian
   Zabrodski, Tamar
   Schinkel, Marvin
   Ackermann, Lutz
   Marek, Ilan
TI Merging allylic carbon-hydrogen and selective carbon-carbon bond activation
SO NATURE
LA English
DT Article
ID quaternary stereogenic centers; heck arylations; building-blocks; metal; derivatives; products
AB Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner(1-3). Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C-H and C-C bonds(4-8), instead of the conventional construction of new C-C bonds. Here we present an approach that exploits the multifold reactivity of easily accessible substrates(9) with a single organometallic species to furnish complex molecular scaffolds through the merging of otherwise difficult transformations: allylic C-H and selective C-C bond activations(10-12). The resulting bifunctional nucleophilic species, all of which have an all-carbon quaternary stereogenic centre, can then be selectively derivatized by the addition of two different electrophiles to obtain more complex molecular architecture from these easily available starting materials.
C1 [Masarwa, Ahmad; Didier, Dorian; Zabrodski, Tamar; Marek, Ilan] Technion Israel Inst Technol, Schulich Fac Chem, Mallat Family Lab Organ Chem, IL-32000 Haifa, Israel.
   [Masarwa, Ahmad; Didier, Dorian; Zabrodski, Tamar; Marek, Ilan] Technion Israel Inst Technol, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-32000 Haifa, Israel.
   [Schinkel, Marvin; Ackermann, Lutz] Univ Gottingen, Inst Organ & Biomol Chem, D-37077 Gottingen, Germany.
C3 Technion Israel Institute of Technology; Technion Israel Institute of Technology; University of Gottingen
RP Marek, I (corresponding author), Technion Israel Inst Technol, Schulich Fac Chem, Mallat Family Lab Organ Chem, IL-32000 Haifa, Israel.
EM chilanm@tx.technion.ac.il
FU Niedersachsen-Technion Research Cooperation Program; Israel Science Foundation [140/12]; European Research Council under the European Community [338912]; European Research Council (ERC) [338912] Funding Source: European Research Council (ERC)
NR 30
TC 189
Z9 197
U1 2
U2 142
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 9
PY 2014
VL 505
IS 7482
BP 199
EP 203
DI 10.1038/nature12761
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500035
PM 24317692
DA 2026-03-09
ER

PT J
AU Svetlizky, I
   Fineberg, J
AF Svetlizky, Ilya
   Fineberg, Jay
TI Classical shear cracks drive the onset of dry frictional motion
SO NATURE
LA English
DT Article
ID stick-slip; dynamic fracture; slow earthquakes; surface; fronts; instability; ruptures; energy
AB Frictional processes entail the rupture(1,2) of the ensemble of discrete contacts defining a frictional interface(3,4). There are a variety of views on how best to describe the onset of dry frictional motion. These range from modelling friction with a single degree of freedom, a 'friction coefficient'(3,5), to theoretical treatments using dynamic fracture(5-8) to account for spatial and temporal dynamics along the interface. We investigated the onset of dry frictional motion by performing simultaneous high-speed measurements of the real contact area and the strain fields in the region surrounding propagating rupture tips within the dry (nominally flat) rough interfaces formed by brittle polymer blocks. Here we show that the transition from 'static' to 'dynamic' friction is quantitatively described by classical singular solutions for the motion of a rapid shear crack(5,9-13). We find that these singular solutions, originally derived to describe brittle fracture, are in excellent agreement with the experiments for slow propagation, whereas some significant discrepancies arise as the rupture velocity approaches the Rayleigh wave speed. In addition, the energy dissipated in the fracture of the contacts remains nearly constant throughout the entire range in which the rupture velocity is less than the Rayleigh wave speed, whereas the size of the dissipative zone undergoes a Lorentz-like contraction as the rupture velocity approaches the Rayleigh wave speed. This coupling between friction and fracture is critical to our fundamental understanding of frictional motion and related processes, such as earthquake dynamics.
C1 [Svetlizky, Ilya; Fineberg, Jay] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
C3 Hebrew University of Jerusalem
RP Fineberg, J (corresponding author), Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
EM jay@mail.huji.ac.il
FU James S. McDonnell Fund; European Research Council [267256]; Israel Science Foundation [76/11]; European Research Council (ERC) [267256] Funding Source: European Research Council (ERC)
NR 35
TC 228
Z9 245
U1 4
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 MAY 8
PY 2014
VL 509
IS 7499
BP 205
EP +
DI 10.1038/nature13202
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300034
PM 24805344
DA 2026-03-09
ER

PT J
AU Shen, EZ
   Song, CQ
   Lin, Y
   Zhang, WH
   Su, PF
   Liu, WY
   Zhang, P
   Xu, JJ
   Lin, N
   Zhan, C
   Wang, XH
   Shyr, Y
   Cheng, HP
   Dong, MQ
AF Shen, En-Zhi
   Song, Chun-Qing
   Lin, Yuan
   Zhang, Wen-Hong
   Su, Pei-Fang
   Liu, Wen-Yuan
   Zhang, Pan
   Xu, Jiejia
   Lin, Na
   Zhan, Cheng
   Wang, Xianhua
   Shyr, Yu
   Cheng, Heping
   Dong, Meng-Qiu
TI Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID mitochondria; longevity; metabolism; decline; genes
AB It has been theorized for decades that mitochondria act as the biological clock of ageing(1), but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level(2,3). Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.
C1 [Shen, En-Zhi; Song, Chun-Qing] China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China.
   [Shen, En-Zhi; Song, Chun-Qing; Zhang, Wen-Hong; Liu, Wen-Yuan; Zhang, Pan; Zhan, Cheng; Dong, Meng-Qiu] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Lin, Yuan; Xu, Jiejia; Lin, Na; Wang, Xianhua; Cheng, Heping] Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Peking Tsinghua Ctr Life Sci,Beijing Key Lab Card, Beijing 100871, Peoples R China.
   [Su, Pei-Fang] Natl Cheng Kung Univ, Dept Stat, Tainan 70101, Taiwan.
   [Shyr, Yu] Vanderbilt Univ, Vanderbilt Ctr Quantitat Sci, Nashville, TN 37232 USA.
C3 China Agricultural University; National Institute of Biological Sciences, Beijing; Peking University; National Cheng Kung University; Vanderbilt University
RP Dong, MQ (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM chengp@pku.edu.cn; dongmengqiu@nibs.ac.cn
FU Ministry of Science and Technology of China (973) [2010CB835203, 2013CB531200]; National Natural Science Foundation of China [31130067, 31221002]; municipal government of Beijing; National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]; Medical Research Council [MR/J013617/1] Funding Source: researchfish; MRC [MR/J013617/1] Funding Source: UKRI
NR 34
TC 118
Z9 132
U1 2
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 APR 3
PY 2014
VL 508
IS 7494
BP 128
EP +
DI 10.1038/nature13012
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900056
PM 24522532
DA 2026-03-09
ER

PT J
AU Seth, AC
   van den Bosch, R
   Mieske, S
   Baumgardt, H
   den Brok, M
   Strader, J
   Neumayer, N
   Chilingarian, I
   Hilker, M
   McDermid, R
   Spitler, L
   Brodie, J
   Frank, MJ
   Walsh, JL
AF Seth, Anil C.
   van den Bosch, Remco
   Mieske, Steffen
   Baumgardt, Holger
   den Brok, Mark
   Strader, Jay
   Neumayer, Nadine
   Chilingarian, Igor
   Hilker, Michael
   McDermid, Richard
   Spitler, Lee
   Brodie, Jean
   Frank, Matthias J.
   Walsh, Jonelle L.
TI A supermassive black hole in an ultra-compact dwarf galaxy
SO NATURE
LA English
DT Article
ID initial mass function; multi-gaussian expansion; globular-cluster g1; acs fornax cluster; star-clusters; stellar-systems; host galaxy; accretion; spectra; models
AB Ultra-compact dwarf galaxies are among the densest stellar systems in the Universe. These systems have masses of up to 2 x 10(8) solar masses, but half-light radii of just 3-50 parsecs(1). Dynamicalmass estimates show that many such dwarfs are more massive than expected from their luminosity(2). It remains unclear whether these high dynamical mass estimates arise because of the presence of supermassive black holes or result from a non-standard stellar initial mass function that causes the average stellar mass to be higher than expected(3,4). Here we report adaptive optics kinematic data of the ultra-compact dwarf galaxy M60-UCD1 that show a central velocity dispersion peak exceeding 100 kilometres per second and modest rotation. Dynamical modelling of these data reveals the presence of a supermassive black hole with amass of 2.1 x 10(7) solarmasses. This is 15 per cent of the object's total mass. The high black hole mass and mass fraction suggest that M60-UCD1 is the stripped nucleus of a galaxy. Our analysis also shows that M60-UCD1's stellar mass is consistent with its luminosity, implying a large population of previously unrecognized supermassive black holes in other ultra-compact dwarf galaxies(2).
C1 [Seth, Anil C.; den Brok, Mark] Univ Utah, Dept Phys & Astron, Salt Lake City, UT 84112 USA.
   [van den Bosch, Remco; Neumayer, Nadine] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Mieske, Steffen] European So Observ, Santiago 7630355, Chile.
   [Baumgardt, Holger] Univ Queensland, Sch Math & Phys, St Lucia, Qld 4072, Australia.
   [Strader, Jay] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Neumayer, Nadine; Hilker, Michael] European So Observ, D-85748 Garching, Germany.
   [Chilingarian, Igor] Smithsonian Astrophys Observ, Cambridge, MA 02138 USA.
   [Chilingarian, Igor] Moscow MV Lomonosov State Univ, Sternberg Astron Inst, Moscow 119992, Russia.
   [McDermid, Richard; Spitler, Lee] Australian Astron Observ, Sydney, NSW 2113, Australia.
   [McDermid, Richard; Spitler, Lee] Macquarie Univ, Dept Phys & Astron, Sydney, NSW 2109, Australia.
   [Brodie, Jean] Univ Calif Observ, Santa Cruz, CA 95064 USA.
   [Brodie, Jean] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Frank, Matthias J.] Heidelberg Univ, Zentrum Astron, Landessternwarte, D-69117 Heidelberg, Germany.
   [Walsh, Jonelle L.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
C3 Utah System of Higher Education; University of Utah; Max Planck Society; European Southern Observatory; University of Queensland; Michigan State University; European Southern Observatory; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Lomonosov Moscow State University; Macquarie University; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Ruprecht Karls University Heidelberg; University of Texas System; University of Texas Austin
RP Seth, AC (corresponding author), Univ Utah, Dept Phys & Astron, 115 South 1400 East, Salt Lake City, UT 84112 USA.
EM aseth@astro.utah.edu
FU NSF [AST-1350389, 1102845, AST-1109878]; German Research Foundation [Ko4161/1]; Russian Science Foundation [14-22-00041]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1102845, 1350389] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109878] Funding Source: National Science Foundation
NR 50
TC 228
Z9 249
U1 0
U2 21
PU NATURE PUBLISHING 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 18
PY 2014
VL 513
IS 7518
BP 398
EP +
DI 10.1038/nature13762
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900055
PM 25230660
DA 2026-03-09
ER

PT J
AU Carlile, TM
   Rojas-Duran, MF
   Zinshteyn, B
   Shin, H
   Bartoli, KM
   Gilbert, WV
AF Carlile, Thomas M.
   Rojas-Duran, Maria F.
   Zinshteyn, Boris
   Shin, Hakyung
   Bartoli, Kristen M.
   Gilbert, Wendy V.
TI Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; gene deletion; determinants; psi; identification; stabilization; synthetase; sequences; alignment; synthase
AB Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-codingRNAs(1), enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure(2-8). Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function-it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre(9,10). However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites aswell as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1-4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease(11-13).
C1 [Carlile, Thomas M.; Rojas-Duran, Maria F.; Zinshteyn, Boris; Shin, Hakyung; Bartoli, Kristen M.; Gilbert, Wendy V.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Gilbert, WV (corresponding author), MIT, Dept Biol, Cambridge, MA 02139 USA.
EM wgilbert@mit.edu
FU American Cancer Society - Robbie Sue Mudd Kidney Cancer Research Scholar Grant [RSG-13-396-01-RMC]; National Institutes of Health [GM094303, GM081399]; American Cancer Society New England Division (Ellison Foundation Postdoctoral Fellowship); American Cancer Society [PF-13-319-01 - RMC]; NIH Pre-Doctoral Training Grant [T32GM007287]; National Institute of General Medical Sciences [R01GM101316] Funding Source: NIH RePORTER
NR 44
TC 827
Z9 1004
U1 6
U2 179
PU NATURE PUBLISHING 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 6
PY 2014
VL 515
IS 7525
BP 143
EP +
DI 10.1038/nature13802
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500046
PM 25192136
DA 2026-03-09
ER

PT J
AU Corbett, AJ
   Eckle, SBG
   Birkinshaw, RW
   Liu, LG
   Patel, O
   Mahony, J
   Chen, ZJ
   Reantragoon, R
   Meehan, B
   Cao, HW
   Williamson, NA
   Strugnell, RA
   Van Sinderen, D
   Mak, JYW
   Fairlie, DP
   Kjer-Nielsen, L
   Rossjohn, J
   McCluskey, J
AF Corbett, Alexandra J.
   Eckle, Sidonia B. G.
   Birkinshaw, Richard W.
   Liu, Ligong
   Patel, Onisha
   Mahony, Jennifer
   Chen, Zhenjun
   Reantragoon, Rangsima
   Meehan, Bronwyn
   Cao, Hanwei
   Williamson, Nicholas A.
   Strugnell, Richard A.
   Van Sinderen, Douwe
   Mak, Jeffrey Y. W.
   Fairlie, David P.
   Kjer-Nielsen, Lars
   Rossjohn, Jamie
   McCluskey, James
TI T-cell activation by transitory neo-antigens derived from distinct microbial pathways
SO NATURE
LA English
DT Article
ID vitamin-b metabolites; salmonella-typhimurium; recognition; mr1; riboflavin; biosynthesis; synthase
AB T cells discriminate between foreign and host molecules by recognizing distinct microbial molecules, predominantly peptides and lipids(1-4). Riboflavin precursors found in many bacteria and yeast also selectively activate mucosal-associated invariant T (MAIT) cells(5,6), an abundant population of innate-like T cells in humans(7-9). However, the genesis of these small organic molecules and their mode of presentation to MAIT cells by the major histocompatibility complex (MHC)-related protein MR1 (ref. 8) are not well understood. Here we show that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-D-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis. Although 5-A-RU does not bind MR1 or activate MAIT cells directly, it does form potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways. The MAIT antigens formed by the reactions between 5-A-RU and glyoxal/methylglyoxal were simple adducts, 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes. Although 5-OP-RU and 5-OE-RU are unstable intermediates, they became trapped by MR1 as reversible covalent Schiff base complexes. Mass spectra supported the capture by MR1 of 5-OP-RU and 5-OE-RU from bacterial cultures that activate MAIT cells, but not from non-activating bacteria, indicating that these MAIT antigens are present in a range of microbes. Thus, MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells. These pyrimidine adducts are microbial signatures for MAIT-cell immunosurveillance.
C1 [Corbett, Alexandra J.; Eckle, Sidonia B. G.; Chen, Zhenjun; Reantragoon, Rangsima; Meehan, Bronwyn; Cao, Hanwei; Strugnell, Richard A.; Kjer-Nielsen, Lars; McCluskey, James] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
   [Birkinshaw, Richard W.; Patel, Onisha; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Liu, Ligong; Mak, Jeffrey Y. W.; Fairlie, David P.] Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, Brisbane, Qld 4072, Australia.
   [Mahony, Jennifer; Van Sinderen, Douwe] Natl Univ Ireland Univ Coll Cork, Sch Microbiol, Cork, Ireland.
   [Williamson, Nicholas A.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3010, Australia.
   [Van Sinderen, Douwe] Natl Univ Ireland Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland.
   [Fairlie, David P.] Univ Queensland, Australian Res Council Ctr Excellence Adv Mol Ima, Brisbane, Qld 4072, Australia.
   [Rossjohn, Jamie] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic 3800, Australia.
   [Rossjohn, Jamie] Cardiff Univ, Inst Infect & Immun, Sch Med, Cardiff CF14 4XN, S Glam, Wales.
C3 University of Melbourne; Peter Doherty Institute; Monash University; University of Queensland; University College Cork; University of Melbourne; University College Cork; University of Queensland; Monash University; Cardiff University
RP Fairlie, DP (corresponding author), Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, Brisbane, Qld 4072, Australia.
EM d.fairlie@imb.uq.edu.au; lkn@unimelb.edu.au; jamie.rossjohn@monash.edu; jamesm1@unimelb.edu.au
FU Australian Research Council (ARC); National Health and Medical Research Council of Australia (NHMRC); Science Foundation Ireland (SFI) [08/IN.1/B1909]; ARC; NHMRC [1027369]; NHMRC Australia; National Health and Medical Research Council (NHMRC) [1027369] Funding Source: National Health and Medical Research Council (NHMRC)
NR 27
TC 701
Z9 778
U1 0
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 MAY 15
PY 2014
VL 509
IS 7500
BP 361
EP +
DI 10.1038/nature13160
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200039
PM 24695216
DA 2026-03-09
ER

PT J
AU Reis, RC
   Reynolds, MT
   Miller, JM
   Walton, DJ
AF Reis, R. C.
   Reynolds, M. T.
   Miller, J. M.
   Walton, D. J.
TI Reflection from the strong gravity regime in a lensed quasar at redshift z=0.658
SO NATURE
LA English
DT Article
ID xmm-newton view; x-ray; black-hole; emission-lines; pg quasars; chandra; evolution; radio; model; disk
AB The co-evolution of a supermassive black hole with its host galaxy1 through cosmic time is encoded in its spin(2-4). At z > 2, supermassive black holes are thought to grow mostly by merger-driven accretion leading to high spin. It is not known, however, whether below z approximate to 1 these black holes continue to grow by coherent accretion or in a chaotic manner(5), though clear differences are predicted(3,4) in their spin evolution. An established method(6) of measuring the spin of black holes is through the study of relativistic reflection features(7) from the inner accretion disk. Owing to their greater distances from Earth, there has hitherto been no significant detection of relativistic reflection features in a moderate-redshift quasar. Here we report an analysis of archival X-ray data together with a deep observation of a gravitationally lensed quasar at z = 0.658. The emission originates within three or fewer gravitational radii from the black hole, implying a spin parameter (a measure of how fast the black hole is rotating) of a = 0.87(-0.15)(0. 08) at the 3 sigma confidence level and a > 0.66 at the 5 sigma level. The high spin found here is indicative of growth by coherent accretion for this black hole, and suggests that black-hole growth at 0.5 <= z <= 1 occurs principally by coherent rather than chaotic accretion episodes.
C1 [Reis, R. C.; Reynolds, M. T.; Miller, J. M.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Walton, D. J.] CALTECH, Cahill Ctr Astron & Astrophys, Pasadena, CA 91125 USA.
C3 University of Michigan System; University of Michigan; California Institute of Technology
RP Reis, RC (corresponding author), Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
EM rdosreis@umich.edu
FU Michigan Society of Fellows; NASA [PF1-120087]
NR 41
TC 45
Z9 48
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 MAR 13
PY 2014
VL 507
IS 7491
BP 207
EP +
DI 10.1038/nature13031
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800033
PM 24598545
DA 2026-03-09
ER

PT J
AU Morton, DC
   Nagol, J
   Carabajal, CC
   Rosette, J
   Palace, M
   Cook, BD
   Vermote, EF
   Harding, DJ
   North, PRJ
AF Morton, Douglas C.
   Nagol, Jyoteshwar
   Carabajal, Claudia C.
   Rosette, Jacqueline
   Palace, Michael
   Cook, Bruce D.
   Vermote, Eric F.
   Harding, David J.
   North, Peter R. J.
TI Amazon forests maintain consistent canopy structure and greenness during the dry season
SO NATURE
LA English
DT Article
ID tropical forest; leaf-area; carbon; allometry; fluxes; modis; co2; variability; emissions; drought
AB The seasonality of sunlight and rainfall regulates net primary production in tropical forests(1). Previous studies have suggested that light is more limiting than water for tropical forest productivity(2), consistent with greening of Amazon forests during the dry season in satellite data(3-7). We evaluated four potential mechanisms for the seasonal green-up phenomenon, including increases in leaf area(5-7) or leaf reflectance(3,4,6), using a sophisticated radiative transfer model(8) and independent satellite observations from lidar and optical sensors. Here we show that the apparent green up of Amazon forests in optical remote sensing data resulted from seasonal changes in near-infrared reflectance, an artefact of variations in sun-sensor geometry. Correcting this bidirectional reflectance effect eliminated seasonal changes in surface reflectance, consistent with independent lidar observations and model simulations with unchanging canopy properties. The stability of Amazon forest structure and reflectance over seasonal timescales challenges the paradigm of light-limited net primary production in Amazon forests and enhanced forest growth during drought conditions. Correcting optical remote sensing data for artefacts of sun-sensor geometry is essential to isolate the response of global vegetation to seasonal and interannual climate variability.
C1 [Morton, Douglas C.; Carabajal, Claudia C.; Rosette, Jacqueline; Cook, Bruce D.; Vermote, Eric F.; Harding, David J.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Nagol, Jyoteshwar; Rosette, Jacqueline] Univ Maryland, Dept Geog Sci, College Pk, MD 20742 USA.
   [Nagol, Jyoteshwar] Global Land Cover Facil, College Pk, MD 20740 USA.
   [Carabajal, Claudia C.] Sigma Space Corp, Lanham, MD 20706 USA.
   [Rosette, Jacqueline; North, Peter R. J.] Swansea Univ, Dept Geog, Swansea SA2 8PP, W Glam, Wales.
   [Palace, Michael] Univ New Hampshire, Earth Syst Res Ctr, Durham, NH 03824 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; Swansea University; University System Of New Hampshire; University of New Hampshire
RP Morton, DC (corresponding author), NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
EM douglas.morton@nasa.gov
FU NASA; NASA Postdoctoral Program; NERC National Centre for Earth Observation; Natural Environment Research Council [NE/F021437/1] Funding Source: researchfish; NERC [NE/F021437/1] Funding Source: UKRI
NR 49
TC 359
Z9 405
U1 7
U2 422
PU NATURE PUBLISHING 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 13
PY 2014
VL 506
IS 7487
BP 221
EP +
DI 10.1038/nature13006
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700038
PM 24499816
DA 2026-03-09
ER

PT J
AU Hosseini, P
   Wright, CD
   Bhaskaran, H
AF Hosseini, Peiman
   Wright, C. David
   Bhaskaran, Harish
TI An optoelectronic framework enabled by low-dimensional phase-change films
SO NATURE
LA English
DT Article
ID memory; nonvolatile
AB The development of materials whose refractive index can be optically transformed as desired, such as chalcogenide-based phase-change materials, has revolutionized the media and data storage industries by providing inexpensive, high-speed, portable and reliable platforms able to store vast quantities of data. Phase-change materials switch between two solid states-amorphous and crystalline-in response to a stimulus, such as heat, with an associated change in the physical properties of the material, including optical absorption, electrical conductance and Young's modulus(1-5). The initial applications of these materials(particularly the germanium antimony tellurium alloy Ge2Sb2Te5) exploited the reversible change in their optical properties in rewritable optical data storage technologies(6,7). More recently, the change in their electrical conductivity has also been extensively studied in the development of non-volatile phase-changememories(4,5). Here we show that by combining the optical and electronic property modulation of such materials, display and data visualization applications that go beyond data storage can be created. Using extremely thin phase-change materials and transparent conductors, we demonstrate electrically induced stable colour changes in both reflective and semi-transparent modes. Further, we show how a pixelated approach can be used in displays on both rigid and flexible films. This optoelectronic framework using low-dimensional phase-change materials has many likely applications, such as ultrafast, entirely solid-state displays with nanometre-scale pixels, semi-transparent 'smart' glasses, 'smart' contact lenses and artificial retina devices.
C1 [Hosseini, Peiman; Bhaskaran, Harish] Univ Oxford, Dept Mat, Oxford OX1 3PH, England.
   [Wright, C. David] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
C3 University of Oxford; University of Exeter
RP Bhaskaran, H (corresponding author), Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
EM harish.bhaskaran@materials.ox.ac.uk
FU EPSRC [EP/J018783/1, EP/J018694/1, EP/J00541X/2]; OUP John Fell Fund; Engineering and Physical Sciences Research Council [EP/J018694/1, EP/J018783/1, EP/J00541X/1, EP/J00541X/2] Funding Source: researchfish; EPSRC [EP/J00541X/2, EP/J00541X/1, EP/J018694/1, EP/L01730X/1, EP/M015173/1, EP/J018783/1, EP/M015130/1] Funding Source: UKRI
NR 30
TC 669
Z9 764
U1 31
U2 773
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 206
EP 211
DI 10.1038/nature13487
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800040
PM 25008527
DA 2026-03-09
ER

PT J
AU Ksander, BR
   Kolovou, PE
   Wilson, BJ
   Saab, KR
   Guo, Q
   Ma, J
   McGuire, SP
   Gregory, MS
   Vincent, WJB
   Perez, VL
   Cruz-Guilloty, F
   Kao, WWY
   Call, MK
   Tucker, BA
   Zhan, Q
   Murphy, GF
   Lathrop, KL
   Alt, C
   Mortensen, LJ
   Lin, CP
   Zieske, JD
   Frank, MH
   Frank, NY
AF Ksander, Bruce R.
   Kolovou, Paraskevi E.
   Wilson, Brian J.
   Saab, Karim R.
   Guo, Qin
   Ma, Jie
   McGuire, Sean P.
   Gregory, Meredith S.
   Vincent, William J. B.
   Perez, Victor L.
   Cruz-Guilloty, Fernando
   Kao, Winston W. Y.
   Call, Mindy K.
   Tucker, Budd A.
   Zhan, Qian
   Murphy, George F.
   Lathrop, Kira L.
   Alt, Clemens
   Mortensen, Luke J.
   Lin, Charles P.
   Zieske, James D.
   Frank, Markus H.
   Frank, Natasha Y.
TI ABCB5 is a limbal stem cell gene required for corneal development and repair
SO NATURE
LA English
DT Article
ID ocular surface; chemoresistance; melanoma; mice; population; deficiency; microscopy; phenotype; therapy
AB Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs)(1-3), and LSC deficiency is a major cause of blindness worldwide(4). Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts(5), a gene allowing for prospective LSC enrichment has not been identified so far(5). Here we show that ATP-binding cassette, sub-family B, member(5) (ABCB5)(6,7) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated humanor murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs2 in mice and p63 alpha-positive LSCs8 in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.
C1 [Ksander, Bruce R.; Kolovou, Paraskevi E.; McGuire, Sean P.; Gregory, Meredith S.; Vincent, William J. B.; Zieske, James D.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA.
   [Ksander, Bruce R.; Kolovou, Paraskevi E.; McGuire, Sean P.; Gregory, Meredith S.; Vincent, William J. B.; Alt, Clemens; Mortensen, Luke J.; Lin, Charles P.; Zieske, James D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Wilson, Brian J.; Saab, Karim R.; Guo, Qin; Ma, Jie; Frank, Markus H.; Frank, Natasha Y.] Boston Childrens Hosp, Div Nephrol, Transplant Res Program, Boston, MA 02115 USA.
   [Wilson, Brian J.; Saab, Karim R.; Guo, Qin; Ma, Jie; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Wilson, Brian J.; Guo, Qin; Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA.
   [Perez, Victor L.; Cruz-Guilloty, Fernando] Bascom Palmer Eye Inst, Miami, FL 33136 USA.
   [Perez, Victor L.; Cruz-Guilloty, Fernando] Univ Miami, Miller Sch Med, Dept Ophthalmol, Miami, FL 33136 USA.
   [Kao, Winston W. Y.; Call, Mindy K.] Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH 45229 USA.
   [Tucker, Budd A.] Univ Iowa, Stephen A Wynn Inst Vis Res, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
   [Zhan, Qian; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Lathrop, Kira L.] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA.
   [Lathrop, Kira L.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15213 USA.
   [Alt, Clemens; Mortensen, Luke J.; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
   [Alt, Clemens; Mortensen, Luke J.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Frank, Markus H.; Frank, Natasha Y.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02138 USA.
   [Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Schepens Eye Research Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Boston Healthcare System; Bascom Palmer Eye Institute; University of Miami; University System of Ohio; University of Cincinnati; University of Iowa; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; 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; Brigham & Women's Hospital
RP Frank, NY (corresponding author), Boston Childrens Hosp, Div Nephrol, Transplant Res Program, Boston, MA 02115 USA.
EM markus.frank@childrens.harvard.edu; nfrank@partners.org
FU National Institutes of Health (NIH)/National Institutes of Neurological Disorders and Stroke [K08NS051349]; VA BLRD [1I01BX000516]; VA RRD [1I01RX000989]; Harvard Stem Cell Institute; NIH/National Cancer Institute [R01CA113796, R01CA158467, R01CA138231]; Department of Defense [PR0332453]; NIH [R01CA138231, R01EY018624, P30EY014801, R01EY021768, DP2OD007483, R01 EB017274, U01HL100402, P41EB015903]; Corley Research Foundation; Western Pennsylvania Medical Eye Bank Core Grant for Vision Research [EY08098]; National Eye Institute [P30EY008098, P30EY014801, P30EY003790] Funding Source: NIH RePORTER; National Institute of Biomedical Imaging and Bioengineering [P41EB015903] Funding Source: NIH RePORTER
NR 32
TC 219
Z9 253
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 JUL 17
PY 2014
VL 511
IS 7509
BP 353
EP +
DI 10.1038/nature13426
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200037
PM 25030174
DA 2026-03-09
ER

PT J
AU Brown, JB
   Boley, N
   Eisman, R
   May, GE
   Stoiber, MH
   Duff, MO
   Booth, BW
   Wen, JY
   Park, S
   Suzuki, AM
   Wan, KH
   Yu, C
   Zhang, DY
   Carlson, JW
   Cherbas, L
   Eads, BD
   Miller, D
   Mockaitis, K
   Roberts, J
   Davis, CA
   Frise, E
   Hammonds, AS
   Olson, S
   Shenker, S
   Sturgill, D
   Samsonova, AA
   Weiszmann, R
   Robinson, G
   Hernandez, J
   Andrews, J
   Bickel, PJ
   Carninci, P
   Cherbas, P
   Gingeras, TR
   Hoskins, RA
   Kaufman, TC
   Lai, EC
   Oliver, B
   Perrimon, N
   Graveley, BR
   Celniker, SE
AF Brown, James B.
   Boley, Nathan
   Eisman, Robert
   May, Gemma E.
   Stoiber, Marcus H.
   Duff, Michael O.
   Booth, Ben W.
   Wen, Jiayu
   Park, Soo
   Suzuki, Ana Maria
   Wan, Kenneth H.
   Yu, Charles
   Zhang, Dayu
   Carlson, Joseph W.
   Cherbas, Lucy
   Eads, Brian D.
   Miller, David
   Mockaitis, Keithanne
   Roberts, Johnny
   Davis, Carrie A.
   Frise, Erwin
   Hammonds, Ann S.
   Olson, Sara
   Shenker, Sol
   Sturgill, David
   Samsonova, Anastasia A.
   Weiszmann, Richard
   Robinson, Garret
   Hernandez, Juan
   Andrews, Justen
   Bickel, Peter J.
   Carninci, Piero
   Cherbas, Peter
   Gingeras, Thomas R.
   Hoskins, Roger A.
   Kaufman, Thomas C.
   Lai, Eric C.
   Oliver, Brian
   Perrimon, Norbert
   Graveley, Brenton R.
   Celniker, Susan E.
TI Diversity and dynamics of the Drosophila transcriptome
SO NATURE
LA English
DT Article
ID genome-wide analysis; long noncoding rnas; expression analysis; endogenous sirnas; gene-expression; cap-analysis; identification; landscape; reveals; gencode
AB Animal transcriptomes are dynamic with each cell type, tissue and organ system expressing an ensemble of transcript forms that give rise to substantial diversity. Here we have identified new genes, transcripts and proteins using poly(A)(+) RNA sequencing from Drosophila melanogaster in cultured cell lines, dissected organ systems and under environmental perturbations. We found that a small set of mostly neural-specific genes has the potential to encode thousands of transcripts each through extensive alternative promoter usage and RNA splicing. The magnitudes of splicing changes are larger between tissues than between developmental stages, and most sex-specific splicing is gonad-specific. Gonads express hundreds of previously unknown coding and long non-coding RNAs (lncRNAs), some of which are antisense to protein-coding genes and produce short regulatory RNAs. Furthermore, previously identified pervasive intergenic transcription occurs primarily within newly identified introns. The fly transcriptome is substantially more complex than previously recognized, with this complexity arising from combinatorial usage of promoters splice sites and polyaclenylation sites.
C1 [Brown, James B.; Boley, Nathan; Stoiber, Marcus H.; Robinson, Garret; Hernandez, Juan; Bickel, Peter J.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Brown, James B.; Booth, Ben W.; Park, Soo; Wan, Kenneth H.; Yu, Charles; Carlson, Joseph W.; Frise, Erwin; Hammonds, Ann S.; Weiszmann, Richard; Hoskins, Roger A.; Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA.
   [Eisman, Robert; Cherbas, Lucy; Eads, Brian D.; Miller, David; Mockaitis, Keithanne; Andrews, Justen; Cherbas, Peter; Kaufman, Thomas C.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [May, Gemma E.; Duff, Michael O.; Olson, Sara; Graveley, Brenton R.] Univ Connecticut, Ctr Hlth, Inst Syst Genom, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
   [Wen, Jiayu; Shenker, Sol; Lai, Eric C.] Sloan Kettering Inst, Rockefeller Res Labs 1017C, New York, NY 10065 USA.
   [Suzuki, Ana Maria; Carninci, Piero] RIKEN Omics Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Suzuki, Ana Maria; Carninci, Piero] RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa 2300045, Japan.
   [Zhang, Dayu; Roberts, Johnny; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA.
   [Davis, Carrie A.; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Sturgill, David; Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Samsonova, Anastasia A.; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Samsonova, Anastasia A.; Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
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; Indiana University System; Indiana University Bloomington; University of Connecticut; Memorial Sloan Kettering Cancer Center; RIKEN; RIKEN; Indiana University System; Indiana University Bloomington; Cold Spring Harbor Laboratory; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Brown, JB (corresponding author), Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
EM benbrownofberkeley@gmail.com; graveley@neuron.uchc.edu; celniker@fruitfly.org
FU National Human Genome Research Institute; Department of Energy [U01 HG004271, U54 HG006944, R01 GM076655, DE-AC02-05CH11231]; NHGRI [K99 HG006698]; modENCODE DAC sub-award [5710003102, 1U01HG007031-01]; ENCODE DAC [5U01HG004695-04]; Indiana METACyt Initiative of Indiana University - Lilly Endowment;  [U01-HG004261];  [RC2-HG005639]; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK015600] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM083300] Funding Source: NIH RePORTER; Div Of Biological Infrastructure; Direct For Biological Sciences [1062432] Funding Source: National Science Foundation
NR 50
TC 534
Z9 643
U1 1
U2 165
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 28
PY 2014
VL 512
IS 7515
BP 393
EP 399
DI 10.1038/nature12962
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600025
PM 24670639
DA 2026-03-09
ER

PT J
AU Major, JD
   Treharne, RE
   Phillips, LJ
   Durose, K
AF Major, J. D.
   Treharne, R. E.
   Phillips, L. J.
   Durose, K.
TI A low-cost non-toxic post-growth activation step for CdTe solar cells
SO NATURE
LA English
DT Article
ID back-contact; film; recrystallization
AB Cadmium telluride, CdTe, is now firmly established as the basis for the market-leading thin-film solar-cell technology. With laboratory efficiencies approaching 20 per cent(1), the research and development targets for CdTe are to reduce the cost of power generation further to less than half a US dollar per watt (ref. 2) and to minimize the environmental impact. A central part of the manufacturing process involves doping the polycrystalline thin-film CdTe with CdCl2. This acts to form the photovoltaic junction at the CdTe/CdS interface(3,4) and to passivate the grain boundaries(5), making it essential in achieving high device efficiencies. However, although such doping has been almost ubiquitous since the development of this processing route over 25 years ago(6), CdCl2 has two severe disadvantages; it is both expensive (about 30 cents per gram) and a water-soluble source of toxic cadmium ions, presenting a risk to both operators and the environment during manufacture. Here we demonstrate that solar cells prepared using MgCl2, which is non-toxic and costs less than a cent per gram, have efficiencies (around 13%) identical to those of a CdCl2-processed control group. They have similar hole densities in the active layer (9x10(14)cm(-3)) and comparable impurity profiles for Cl and O, these elements being important p-type dopants for CdTe thin films. Contrary to expectation, CdCl2-processed and MgCl2-processed solar cells contain similar concentrations of Mg; this is because ofMgout-diffusion from the soda-lime glass substrates and is not disadvantageous to device performance. However, treatment with other low-cost chlorides such as NaCl, KCl and MnCl2 leads to the introduction of electrically active impurities that do compromise device performance. Our results demonstrate that CdCl2 may simply be replaced directly with MgCl2 in the existing fabrication process, thus both minimizing the environmental risk and reducing the cost of CdTe solar-cell production.
C1 [Major, J. D.; Treharne, R. E.; Phillips, L. J.; Durose, K.] Univ Liverpool, Sch Phys Sci, Stephenson Inst Renewable Energy, Liverpool L69 7ZF, Merseyside, England.
   [Major, J. D.; Treharne, R. E.; Phillips, L. J.; Durose, K.] Univ Liverpool, Sch Phys Sci, Dept Phys, Liverpool L69 7ZF, Merseyside, England.
C3 University of Liverpool; University of Liverpool
RP Major, JD (corresponding author), Univ Liverpool, Sch Phys Sci, Stephenson Inst Renewable Energy, Chadwick Bldg, Liverpool L69 7ZF, Merseyside, England.
EM jon.major@liverpool.ac.uk
FU Engineering and Physical Sciences Research Council
NR 26
TC 251
Z9 278
U1 4
U2 302
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2014
VL 511
IS 7509
BP 334
EP +
DI 10.1038/nature13435
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200032
PM 25030171
DA 2026-03-09
ER

PT J
AU Paszek, MJ
   DuFort, CC
   Rossier, O
   Bainer, R
   Mouw, JK
   Godula, K
   Hudak, JE
   Lakins, JN
   Wijekoon, AC
   Cassereau, L
   Rubashkin, MG
   Magbanua, MJ
   Thorn, KS
   Davidson, MW
   Rugo, HS
   Park, JW
   Hammer, DA
   Giannone, G
   Bertozzi, CR
   Weaver, VM
AF Paszek, Matthew J.
   DuFort, Christopher C.
   Rossier, Olivier
   Bainer, Russell
   Mouw, Janna K.
   Godula, Kamil
   Hudak, Jason E.
   Lakins, Jonathon N.
   Wijekoon, Amanda C.
   Cassereau, Luke
   Rubashkin, Matthew G.
   Magbanua, Mark J.
   Thorn, Kurt S.
   Davidson, Michael W.
   Rugo, Hope S.
   Park, John W.
   Hammer, Daniel A.
   Giannone, Gregory
   Bertozzi, Carolyn R.
   Weaver, Valerie M.
TI The cancer glycocalyx mechanically primes integrin-mediated growth and survival
SO NATURE
LA English
DT Article
ID cell-adhesion; x-ray; microscopy; receptor; glycopolymers; hyaluronan; scattering; nanoscale; dynamics; tension
AB Malignartcy is associated with altered expression of glycans and glycoprotems that contribute the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin dependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster metastasis by mechanically enhancing cell-surface receptor function.
C1 [Paszek, Matthew J.; DuFort, Christopher C.; Bainer, Russell; Mouw, Janna K.; Lakins, Jonathon N.; Wijekoon, Amanda C.; Cassereau, Luke; Rubashkin, Matthew G.; Weaver, Valerie M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
   [Paszek, Matthew J.; DuFort, Christopher C.; Bainer, Russell; Mouw, Janna K.; Lakins, Jonathon N.; Wijekoon, Amanda C.; Cassereau, Luke; Rubashkin, Matthew G.; Weaver, Valerie M.] Univ Calif San Francisco, Ctr Bioengn & Tissue Regenerat, San Francisco, CA 94143 USA.
   [Paszek, Matthew J.; DuFort, Christopher C.; Bainer, Russell; Wijekoon, Amanda C.; Cassereau, Luke; Rubashkin, Matthew G.; Weaver, Valerie M.] Univ Calif Berkeley, Bay Area Phys Sci Oncol Program, Berkeley, CA 94720 USA.
   [Paszek, Matthew J.] Cornell Univ, Sch Chem & Biomol Engn, Ithaca, NY 14853 USA.
   [Paszek, Matthew J.] Cornell Univ, Cornell Nanoscale Sci, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
   [Paszek, Matthew J.] Cornell Univ, Cornell Nanoscale Sci, Kavli Inst, Ithaca, NY 14853 USA.
   [Rossier, Olivier; Giannone, Gregory] Univ Bordeaux, UMR 5297, Interdisciplinary Inst Neurosci, F-33000 Bordeaux, France.
   [Rossier, Olivier; Giannone, Gregory] Univ Bordeaux, CNRS, Interdisciplinary Inst Neurosci, UMR 5297, F-33000 Bordeaux, France.
   [Godula, Kamil; Hudak, Jason E.; Bertozzi, Carolyn R.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Godula, Kamil] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, Berkeley, CA 94720 USA.
   [Magbanua, Mark J.; Rugo, Hope S.; Park, John W.; Weaver, Valerie M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Magbanua, Mark J.; Rugo, Hope S.; Park, John W.] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
   [Thorn, Kurt S.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA.
   [Hammer, Daniel A.] Univ Penn, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USA.
   [Hammer, Daniel A.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
   [Bertozzi, Carolyn R.] Univ Calif Berkeley, Dept Mol Biol, Berkeley, CA 94720 USA.
   [Bertozzi, Carolyn R.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Weaver, Valerie M.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   [Weaver, Valerie M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
   [Weaver, Valerie M.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 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 Berkeley; Cornell University; Cornell University; Cornell University; Universite de Bordeaux; 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); Universite de Bordeaux; 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 San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of California System; University of California San Francisco; University of California System; University of California San Francisco; State University System of Florida; Florida State University; State University System of Florida; Florida State University; University of Pennsylvania; University of Pennsylvania; 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 San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Weaver, VM (corresponding author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
EM Valerie.Weaver@ucsfmedctr.org
FU Kavli Institute; UCSF Program for Biomedical Breakthrough postdoctoral fellowships; DoD NDSEG Fellowship; NIH Pathway to Independence Award [K99 EB013446-02]; French Ministry of Research; CNRS; ANR grant Nanomotility; INSERM; Fondation ARC pour la Recherche sur le Cancer; Conseil Regional Aquitaine; NIH [AI082292-03A1, 2R01GM059907-13, GM59907]; Breast Cancer Research Foundation; BCRP DOD Era of Hope Scholar Expansion grant [BC122990]; NIH NCI [U54CA163155-01, U54CA143836-01, 1U01 E5019458-01, CA138818-01A1]; France BioImaging [ANR-10-INBS-04-01]; National Institute of General Medical Sciences [T32GM066698] Funding Source: NIH RePORTER; CDMRP [BC122990, 542337] Funding Source: Federal RePORTER
NR 35
TC 562
Z9 701
U1 2
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 JUL 17
PY 2014
VL 511
IS 7509
BP 319
EP +
DI 10.1038/nature13535
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200029
PM 25030168
DA 2026-03-09
ER

PT J
AU Frisch, A
   Mark, M
   Aikawa, K
   Ferlaino, F
   Bohn, JL
   Makrides, C
   Petrov, A
   Kotochigova, S
AF Frisch, Albert
   Mark, Michael
   Aikawa, Kiyotaka
   Ferlaino, Francesca
   Bohn, John L.
   Makrides, Constantinos
   Petrov, Alexander
   Kotochigova, Svetlana
TI Quantum chaos in ultracold collisions of gas-phase erbium atoms
SO NATURE
LA English
DT Article
ID feshbach resonances; random matrices; physics
AB Atomic and molecular samples reduced to temperatures below one microkelvin, yet still in the gas phase, afford unprecedented energy resolution in probing and manipulating the interactions between their constituent particles. As a result of this resolution, atoms can be made to scatter resonantly on demand, through the precise control of a magnetic field(1). For simple atoms, such as alkalis, scattering resonances are extremely well characterized(2). However, ultracold physics is now poised to enter a new regime, where much more complex species can be cooled and studied, including magnetic lanthanide atoms and even molecules. For molecules, it has been speculated(3,4) that a dense set of resonances in ultracold collision cross-sections will probably exhibit essentially random fluctuations, much as the observed energy spectra of nuclear scattering do(5). According to the Bohigas-Giannoni-Schmit conjecture, such fluctuations would imply chaotic dynamics of the underlying classical motion driving the collision(6-8). This would necessitate new ways of looking at the fundamental interactions in ultracold atomic and molecular systems, as well as perhaps new chaos-driven states of ultracold matter. Here we describe the experimental demonstration that random spectra are indeed found at ultralow temperatures. In the experiment, an ultracold gas of erbium atoms is shown to exhibit many Fano-Feshbach resonances, of the order of three per gauss for bosons. Analysis of their statistics verifies that their distribution of nearest-neighbour spacings is what one would expect from random matrix theory(9). The density and statistics of these resonances are explained by fully quantum mechanical scattering calculations that locate their origin in the anisotropy of the atoms' potential energy surface. Our results therefore reveal chaotic behaviour in the native interaction between ultracold atoms.
C1 [Frisch, Albert; Mark, Michael; Aikawa, Kiyotaka; Ferlaino, Francesca] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Bohn, John L.] Univ Colorado, JILA, Boulder, CO 80309 USA.
   [Bohn, John L.] NIST, Boulder, CO 80309 USA.
   [Makrides, Constantinos; Petrov, Alexander; Kotochigova, Svetlana] Temple Univ, Dept Phys, Philadelphia, PA 19122 USA.
   [Petrov, Alexander] St Petersburg Nucl Phys Inst, Gatchina 188300, Russia.
   [Petrov, Alexander] St Petersburg State Univ, Div Quantum Mech, St Petersburg 198904, Russia.
C3 University of Innsbruck; University of Colorado System; University of Colorado Boulder; National Institute of Standards & Technology (NIST) - USA; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; National Research Centre - Kurchatov Institute; Petersburg Nuclear Physics Institute; Saint Petersburg State University
RP Ferlaino, F (corresponding author), Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
EM francesca.ferlaino@uibk.ac.at
FU ARO MURI; Austrian Science Fund (FWF) through a START grant [Y479-N20]; European Research Council [259435]; Lise-Meitner program of the FWF; AFOSR; NSF [PHY-1308573]; Austrian Science Fund (FWF) [Y 479] Funding Source: researchfish; Division Of Physics; Direct For Mathematical & Physical Scien [1125844, 1308573] Funding Source: National Science Foundation; European Research Council (ERC) [259435] Funding Source: European Research Council (ERC); Austrian Science Fund (FWF) [Y479] Funding Source: Austrian Science Fund (FWF)
NR 34
TC 201
Z9 230
U1 4
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 27
PY 2014
VL 507
IS 7493
BP 475
EP +
DI 10.1038/nature13137
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000035
PM 24670766
DA 2026-03-09
ER

PT J
AU Sasaki, T
   Yamamoto, Y
   Koashi, M
AF Sasaki, Toshihiko
   Yamamoto, Yoshihisa
   Koashi, Masato
TI Practical quantum key distribution protocol without monitoring signal disturbance
SO NATURE
LA English
DT Article
ID single-photon source; cryptography; security
AB Quantum cryptography(1-8) exploits the fundamental laws of quantum mechanics to provide a secure way to exchange private information. Such an exchange requires a common random bit sequence, called a key, to be shared secretly between the sender and the receiver. The basic idea behind quantum key distribution (QKD) has widely been understood as the property that any attempt to distinguish encoded quantum states causes a disturbance in the signal. As a result, implementation of a QKD protocol involves an estimation of the experimental parameters influenced by the eavesdropper's intervention, which is achieved by randomly sampling the signal. If the estimation of many parameters with high precision is required, the portion of the signal that is sacrificed increases, thus decreasing the efficiency of the protocol(9,10). Here we propose a QKD protocol based on an entirely different principle. The sender encodes a bit sequence onto non-orthogonal quantum states and the receiver randomly dictates how a single bit should be calculated from the sequence. The eavesdropper, who is unable to learn the whole of the sequence, cannot guess the bit value correctly. An achievable rate of secure key distribution is calculated by considering complementary choices between quantum measurements of two conjugate observables(11). We found that a practical implementation using a laser pulse train achieves a key rate comparable to a decoy-state QKD protocol(12-14), an often-used technique for lasers. It also has a better tolerance of bit errors and of finite-sized-key effects. We anticipate that this finding will give new insight into how the probabilistic nature of quantum mechanics can be related to secure communication, and will facilitate the simple and efficient use of conventional lasers for QKD.
C1 [Sasaki, Toshihiko; Koashi, Masato] Univ Tokyo, Grad Sch Engn, Photon Sci Ctr, Bunkyo Ku, Tokyo 1138656, Japan.
   [Yamamoto, Yoshihisa] Stanford Univ, EL Ginzton Lab, Stanford, CA 94305 USA.
   [Yamamoto, Yoshihisa] Natl Inst Informat, Chiyoda Ku, Tokyo 1018430, Japan.
C3 University of Tokyo; Stanford University; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan
RP Koashi, M (corresponding author), Univ Tokyo, Grad Sch Engn, Photon Sci Ctr, Bunkyo Ku, Tokyo 1138656, Japan.
EM koashi@qi.t.u-tokyo.ac.jp
FU Funding Program for World-Leading Innovative R & D on Science and Technology (FIRST); MEXT [21102008]; Photon Frontier Network Program (MEXT); Grants-in-Aid for Scientific Research [21102008] Funding Source: KAKEN
NR 30
TC 295
Z9 326
U1 3
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 MAY 22
PY 2014
VL 509
IS 7501
BP 475
EP +
DI 10.1038/nature13303
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000035
PM 24848060
DA 2026-03-09
ER

PT J
AU Calo, S
   Shertz-Wall, C
   Lee, SC
   Bastidas, RJ
   Nicolás, FE
   Granek, JA
   Mieczkowski, P
   Torres-Martínez, S
   Ruiz-Vázquez, RM
   Cardenas, ME
   Heitman, J
AF Calo, Silvia
   Shertz-Wall, Cecelia
   Lee, Soo Chan
   Bastidas, Robert J.
   Nicolas, Francisco E.
   Granek, Joshua A.
   Mieczkowski, Piotr
   Torres-Martinez, Santiago
   Ruiz-Vazquez, Rosa M.
   Cardenas, Maria E.
   Heitman, Joseph
TI Antifungal drug resistance evoked via RNAi-dependent epimutations
SO NATURE
LA English
DT Article
ID germline epimutation; mucor-circinelloides; gene; interference; target; expression; initiation; rapamycin; python; mlh1
AB Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidylprolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin(1). Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth(2). Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants. FK506-resistant epimutants readily reverted to the drug-sensitive wild-type phenotype when grown without exposure to the drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNAs and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves the generation of a double-stranded RNA trigger intermediate using the fkbA mature mRNA as a template to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes.
C1 [Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan; Bastidas, Robert J.; Granek, Joshua A.; Cardenas, Maria E.; Heitman, Joseph] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Nicolas, Francisco E.] Reg Campus Int Excellence Campus Mare Nostrum, Murcia 30100, Spain.
   [Nicolas, Francisco E.; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M.] Univ Murcia, Fac Biol, Dept Genet & Microbiol, Murcia 30100, Spain.
   [Granek, Joshua A.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
   [Granek, Joshua A.] Duke Univ, Med Ctr, Duke Ctr Genom Microbial Syst, Durham, NC 27710 USA.
   [Mieczkowski, Piotr] Univ N Carolina, High Throughput Sequencing Facil, Chapel Hill, NC 27599 USA.
C3 Duke University; University of Murcia; Duke University; Duke University; University of North Carolina; University of North Carolina Chapel Hill
RP Heitman, J (corresponding author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM heitm001@duke.edu
FU NIH [R37 AI39115-17, R01 AI50438-10, R01 CA154499-04]; Spanish MICINN [BFU2009-07220]; MINECO [BFU2012-32246]; FEDER; National Institute of Allergy and Infectious Diseases [R01AI039115] Funding Source: NIH RePORTER
NR 44
TC 134
Z9 152
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 SEP 25
PY 2014
VL 513
IS 7519
BP 555
EP +
DI 10.1038/nature13575
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800042
PM 25079329
DA 2026-03-09
ER

PT J
AU Anthony, KMW
   Zimov, SA
   Grosse, G
   Jones, MC
   Anthony, PM
   Chapin, FS
   Finlay, JC
   Mack, MC
   Davydov, S
   Frenzel, P
   Frolking, S
AF Anthony, K. M. Walter
   Zimov, S. A.
   Grosse, G.
   Jones, M. C.
   Anthony, P. M.
   Chapin, F. S., III
   Finlay, J. C.
   Mack, M. C.
   Davydov, S.
   Frenzel, P.
   Frolking, S.
TI A shift of thermokarst lakes from carbon sources to sinks during the Holocene epoch
SO NATURE
LA English
DT Article
ID permafrost; peatlands; disturbance; landscapes; vegetation; evolution; lowland; history; climate; siberia
AB Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch(1-4). However, the same thermokarst lakes can also sequester carbon(5), and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 +/- 10 grams of carbon per square metre per year; mean +/- standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears(7-9), potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.
C1 [Anthony, K. M. Walter; Jones, M. C.; Anthony, P. M.] Univ Alaska, Water & Environm Res Ctr, Fairbanks, AK 99775 USA.
   [Zimov, S. A.; Davydov, S.] Russian Acad Sci, Far East Branch, Northeast Sci Stn, Pacific Inst Geog, Cherskii 678830, Russia.
   [Grosse, G.] Univ Alaska, Inst Geophys, Fairbanks, AK 99775 USA.
   [Jones, M. C.] US Geol Survey, Reston, VA 20192 USA.
   [Chapin, F. S., III] Univ Alaska, Inst Arctic Biol, Fairbanks, AK 99775 USA.
   [Finlay, J. C.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Mack, M. C.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Frenzel, P.] Max Planck Inst Terr Microbiol, D-35043 Marburg, Germany.
   [Frolking, S.] Univ New Hampshire, Inst Study Earth Oceans & Space, Durham, NH 03824 USA.
C3 University of Alaska System; University of Alaska Fairbanks; Russian Academy of Sciences; Pacific Geographical Institute of the Far Eastern Branch of the Russian Academy of Sciences; University of Alaska System; University of Alaska Fairbanks; United States Department of the Interior; United States Geological Survey; University of Alaska System; University of Alaska Fairbanks; University of Minnesota System; University of Minnesota Twin Cities; State University System of Florida; University of Florida; Max Planck Society; University System Of New Hampshire; University of New Hampshire
RP Anthony, KMW (corresponding author), Univ Alaska, Water & Environm Res Ctr, Fairbanks, AK 99775 USA.
EM kmwalteranthony@alaska.edu
FU NSF [OPP-0099113, OPP-0732735, ARC-1304823]; NASA [NNX08AJ37G]; NSF projects [OPP-1107892, OPP-6737545, PLR-1303940]; USGS; DOE [DE-SC0010580]; ERC [338335]; U.S. Department of Energy (DOE) [DE-SC0010580] Funding Source: U.S. Department of Energy (DOE); Division Of Environmental Biology; Direct For Biological Sciences [1026415] Funding Source: National Science Foundation; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [1209402] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1107892, 1303940] Funding Source: National Science Foundation
NR 74
TC 238
Z9 273
U1 11
U2 391
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2014
VL 511
IS 7510
BP 452
EP +
DI 10.1038/nature13560
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700043
PM 25043014
DA 2026-03-09
ER

PT J
AU Schoggins, JW
   MacDuff, DA
   Imanaka, N
   Gainey, MD
   Shrestha, B
   Eitson, JL
   Mar, KB
   Richardson, RB
   Ratushny, AV
   Litvak, V
   Dabelic, R
   Manicassamy, B
   Aitchison, JD
   Aderem, A
   Elliott, RM
   García-Sastre, A
   Racaniello, V
   Snijder, EJ
   Yokoyama, WM
   Diamond, MS
   Virgin, HW
   Rice, CM
AF Schoggins, John W.
   MacDuff, Donna A.
   Imanaka, Naoko
   Gainey, Maria D.
   Shrestha, Bimmi
   Eitson, Jennifer L.
   Mar, Katrina B.
   Richardson, R. Blake
   Ratushny, Alexander V.
   Litvak, Vladimir
   Dabelic, Rea
   Manicassamy, Balaji
   Aitchison, John D.
   Aderem, Alan
   Elliott, Richard M.
   Garcia-Sastre, Adolfo
   Racaniello, Vincent
   Snijder, Eric J.
   Yokoyama, Wayne M.
   Diamond, Michael S.
   Virgin, Herbert W.
   Rice, Charles M.
TI Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity
SO NATURE
LA English
DT Article
ID cyclic gmp-amp; interferon-stimulated genes; west-nile-virus; fluorescent protein; in-vitro; identification; 2nd-messenger; infection; effectors; mice
AB The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors(1-3). Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses(4-13). However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.
C1 [Schoggins, John W.; Imanaka, Naoko; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.
   [MacDuff, Donna A.; Diamond, Michael S.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Gainey, Maria D.; Yokoyama, Wayne M.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA.
   [Gainey, Maria D.; Yokoyama, Wayne M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
   [Shrestha, Bimmi; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, Div Infect Dis, St Louis, MO 63110 USA.
   [Shrestha, Bimmi; Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Eitson, Jennifer L.; Mar, Katrina B.; Richardson, R. Blake] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [Ratushny, Alexander V.; Litvak, Vladimir; Aitchison, John D.; Aderem, Alan] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Ratushny, Alexander V.; Aitchison, John D.] Inst Syst Biol, Seattle, WA 98109 USA.
   [Dabelic, Rea; Racaniello, Vincent] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
   [Manicassamy, Balaji] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
   [Elliott, Richard M.] Univ St Andrews, Sch Biol, St Andrews KY16 9ST, Fife, Scotland.
   [Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
   [Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
   [Garcia-Sastre, Adolfo] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA.
   [Snijder, Eric J.] Leiden Univ, Med Ctr, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands.
C3 Rockefeller University; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Howard Hughes Medical Institute; Washington University (WUSTL); Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; Center for Infectious Disease Research; Institute for Systems Biology (ISB); Columbia University; University of Chicago; University of St Andrews; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC)
RP Rice, CM (corresponding author), Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.
EM john.schoggins@utsouthwestern.edu; ricec@rockefeller.edu
FU National Institutes of Health [AI091707, AI057158, DK095031, AI057160, HHSN272200900041CU19, AI104972, AI083025, AI095611]; CEIRS [AI057160, HHSN266200700010C, GM076547, GM103511]; Greenberg Medical Research Institute; Starr Foundation; Ronald A. Shellow, M.D. Memorial Fund;  [T32 AR007279]; Medical Research Council [G0801822] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [T32AI005284] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007279] Funding Source: NIH RePORTER; MRC [G0801822] Funding Source: UKRI
NR 39
TC 769
Z9 894
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 JAN 30
PY 2014
VL 505
IS 7485
BP 691
EP +
DI 10.1038/nature12862
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000043
PM 24284630
DA 2026-03-09
ER

PT J
AU Sczepanski, JT
   Joyce, GF
AF Sczepanski, Jonathan T.
   Joyce, Gerald F.
TI A cross-chiral RNA polymerase ribozyme
SO NATURE
LA English
DT Article
ID template; ligation; oligonucleotides; polymerization; extension; selection; model; acid
AB Thirty years ago it was shown that the non-enzymatic, template-directed polymerization of activated mononudeotides proceeds readily in a homochiral system, but is severely inhibited by the presence of the opposing enantiomerl. This finding poses a severe challenge for the spontaneous emergence of RNA-based life, and has led to the suggestion that either RNA was preceded by some other genetic polymer that is not subject to chiral inhibition(2) or chiral symmetry was broken through chemical processes before the origin of RNA-based life(3,4). Once an RNA enzyme arose that could catalyse the polymerization of RNA, it would have been possible to distinguish among the two enantiomers, enabling RNA replication and RNA-based evolution to occur. It is commonly thought that the earliest RNA polymerase and its substrates would have been of the same handedness, but this is not necessarily the case. Replicating D- and L-RNA molecules may have emerged together, based on the ability of structured RNAs of one handedness to catalyse the templated polymerization of activated mononudeotides of the opposite handedness. Here we develop such a cross-chiral RNA polymerase, using in vitro evolution starting from a population of random-sequence RNAs. The El-RNA enzyme, consisting of 83 nucleotides, catalyses the joining of L-mono- or oligonudeotide substrates on a complementary L-RNA template, and similar behaviour occurs for the L-enzyme with El-substrates and a El-template. Chiral inhibition is avoided because the 10(6)-fold rate acceleration of the enzyme only pertains to cross-chiral substrates. The enzyme's activity is sufficient to generate full-length copies of its enantiomer through the templated joining of 11 component oligonudeotides.
C1 [Sczepanski, Jonathan T.; Joyce, Gerald F.] Scripps Res Inst, Dept Chem, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Joyce, GF (corresponding author), Scripps Res Inst, Dept Chem, Skaggs Inst Chem Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM gjoyce@scripps.edu
FU NASA [NNX10AQ91G]; Simons Foundation [287624]; National Institutes of Health [F32 GM101741]; NASA [NNX10AQ91G, 125589] Funding Source: Federal RePORTER
NR 21
TC 132
Z9 155
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 NOV 20
PY 2014
VL 515
IS 7527
BP 440
EP +
DI 10.1038/nature13900
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600052
PM 25363769
DA 2026-03-09
ER

PT J
AU Brünken, S
   Sipilä, O
   Chambers, ET
   Harju, J
   Caselli, P
   Asvany, O
   Honingh, CE
   Kaminski, T
   Menten, KM
   Stutzki, J
   Schlemmer, S
AF Bruenken, Sandra
   Sipilae, Olli
   Chambers, Edward T.
   Harju, Jorma
   Caselli, Paola
   Asvany, Oskar
   Honingh, Cornelia E.
   Kaminski, Tomasz
   Menten, Karl M.
   Stutzki, Juergen
   Schlemmer, Stephan
TI H2D+ observations give an age of at least one million years for a cloud core forming Sun-like stars
SO NATURE
LA English
DT Article
ID heterodyne instrument; chemistry; h-3(+); ortho-h-2; ratio; apex; constraints; depletion; sofia; water
AB The age of dense interstellar cloud cores, where stars and planets form, is a crucial parameter in star formation and difficult to measure. Some models predict rapid collapse(1,2), whereas others predict timescales of more than one million years (ref. 3). One possible approach to determining the age is through chemical changes as cloud contraction occurs, in particular through indirect measurements of the ratio of the two spin isomers (ortho/para) of molecular hydrogen, H-2, which decreases monotonically with age(4-6). This has beendone for the dense cloud core L183, for which the deuterium fractionation of diazenylium(N2H+) was used as a chemical clock to infer(7) that the core has contracted rapidly (on a timescale of less than 700,000 years). Among astronomically observable molecules, the spin isomers of the deuterated trihydrogen cation, ortho-H2D+ and para-H2D+, have the most direct chemical connections to H-2 (refs 8-12) and their abundance ratio provides a chemical clock that is sensitive to greater cloud core ages. So far this ratio has not been determined because para-H2D+ is very difficult to observe. The detection of its rotational ground-state line has only now become possible thanks to accurate measurements of its transition frequency in the laboratory(13), and recent progress in instrumentation technology(14,15). Here we report observations of ortho-and para-H2D+ emission and absorption, respectively, from the dense cloud core hosting IRAS 16293-2422 A/B, a group of nascent solar-type stars (with ages of less than 100,000 years). Using the ortho/para ratio in conjunction with chemical models, we find that the dense core has been chemically processed for at least one million years. The apparent discrepancy with the earlier N2H+ work(7) arises because that chemical clock turns off sooner than the H2D+ clock, but both results imply that star-forming dense cores have ages of about one million years, rather than 100,000 years.
C1 [Bruenken, Sandra; Chambers, Edward T.; Asvany, Oskar; Honingh, Cornelia E.; Stutzki, Juergen; Schlemmer, Stephan] Univ Cologne, Inst Phys, D-50937 Cologne, Germany.
   [Sipilae, Olli; Harju, Jorma] Univ Helsinki, Dept Phys, FIN-00014 Helsinki, Finland.
   [Sipilae, Olli; Caselli, Paola] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Caselli, Paola] Univ Leeds, Sch Phys & Astron, Leeds LS2 9JT, W Yorkshire, England.
   [Kaminski, Tomasz; Menten, Karl M.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
C3 University of Cologne; University of Helsinki; Max Planck Society; University of Leeds; Max Planck Society
RP Brünken, S (corresponding author), Univ Cologne, Inst Phys, Zulpicher Str 77, D-50937 Cologne, Germany.
EM bruenken@phl.uni-koeln.de; schlemmer@ph1.uni-koeln.de
FU NASA [NAS2-97001]; DLR [50 OK0901]; Collaborative Research Centre 956 - Deutsche Forschungsgemeinschaft (DFG); Academy of Finland [132291, 250741]; European Research Council (ERC) [PALs 320620]
NR 44
TC 112
Z9 119
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 DEC 11
PY 2014
VL 516
IS 7530
BP 219
EP +
DI 10.1038/nature13924
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500038
PM 25409140
DA 2026-03-09
ER

PT J
AU Stergachis, AB
   Neph, S
   Sandstrom, R
   Haugen, E
   Reynolds, AP
   Zhang, MH
   Byron, R
   Canfield, T
   Stelhing-Sun, S
   Lee, K
   Thurman, RE
   Vong, S
   Bates, D
   Neri, F
   Diegel, M
   Giste, E
   Dunn, D
   Vierstra, J
   Hansen, RS
   Johnson, AK
   Sabo, PJ
   Wilken, MS
   Reh, TA
   Treuting, PM
   Kaul, R
   Groudine, M
   Bender, MA
   Borenstein, E
   Stamatoyannopoulos, JA
AF Stergachis, Andrew B.
   Neph, Shane
   Sandstrom, Richard
   Haugen, Eric
   Reynolds, Alex P.
   Zhang, Miaohua
   Byron, Rachel
   Canfield, Theresa
   Stelhing-Sun, Sandra
   Lee, Kristen
   Thurman, Robert E.
   Vong, Shinny
   Bates, Daniel
   Neri, Fidencio
   Diegel, Morgan
   Giste, Erika
   Dunn, Douglas
   Vierstra, Jeff
   Hansen, R. Scott
   Johnson, Audra K.
   Sabo, Peter J.
   Wilken, Matthew S.
   Reh, Thomas A.
   Treuting, Piper M.
   Kaul, Rajinder
   Groudine, Mark
   Bender, M. A.
   Borenstein, Elhanan
   Stamatoyannopoulos, John A.
TI Conservation of trans-acting circuitry during mammalian regulatory evolution
SO NATURE
LA English
DT Article
ID transcription factor-binding; protein-dna interactions; human genome; networks; dynamics; database; motifs; identification; mechanisms; similarity
AB The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis-versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining similar to 8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is similar to 95% similar with that derived from human TF footprints. However, only similar to 20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.
C1 [Stergachis, Andrew B.; Neph, Shane; Sandstrom, Richard; Haugen, Eric; Reynolds, Alex P.; Canfield, Theresa; Stelhing-Sun, Sandra; Lee, Kristen; Thurman, Robert E.; Vong, Shinny; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Giste, Erika; Dunn, Douglas; Vierstra, Jeff; Hansen, R. Scott; Johnson, Audra K.; Sabo, Peter J.; Kaul, Rajinder; Borenstein, Elhanan; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Zhang, Miaohua; Byron, Rachel; Groudine, Mark] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Hansen, R. Scott; Kaul, Rajinder; Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Wilken, Matthew S.; Reh, Thomas A.] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA.
   [Treuting, Piper M.] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
   [Groudine, Mark] Univ Washington, Div Radiat Oncol, Seattle, WA 98195 USA.
   [Bender, M. A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Borenstein, Elhanan] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98102 USA.
   [Borenstein, Elhanan] Santa Fe Inst, Santa Fe, NM 87501 USA.
C3 University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; 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; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; The Santa Fe Institute
RP Stamatoyannopoulos, JA (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM jstam@uw.edu
FU NIH [U54HG004592, U54HG007010, U01ES01156, RC2HG005654, R37 DK44746]; NIDDK [FDK095678A]; National Eye Institute [R01EY021482] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER
NR 40
TC 173
Z9 218
U1 0
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 NOV 20
PY 2014
VL 515
IS 7527
BP 365
EP +
DI 10.1038/nature13972
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600035
PM 25409825
DA 2026-03-09
ER

PT J
AU Hussein, SMI
   Puri, MC
   Tonge, PD
   Benevento, M
   Corso, AJ
   Clancy, JL
   Mosbergen, R
   Li, M
   Lee, DS
   Cloonan, N
   Wood, DLA
   Munoz, J
   Middleton, R
   Korn, O
   Patel, HR
   White, CA
   Shin, JY
   Gauthier, ME
   Le Cao, KA
   Kim, JI
   Mar, JC
   Shakiba, N
   Ritchie, W
   Rasko, JEJ
   Grimmond, SM
   Zandstra, PW
   Wells, CA
   Preiss, T
   Seo, JS
   Heck, AJR
   Rogers, IM
   Nagy, A
AF Hussein, Samer M. I.
   Puri, Mira C.
   Tonge, Peter D.
   Benevento, Marco
   Corso, Andrew J.
   Clancy, Jennifer L.
   Mosbergen, Rowland
   Li, Mira
   Lee, Dong-Sung
   Cloonan, Nicole
   Wood, David L. A.
   Munoz, Javier
   Middleton, Robert
   Korn, Othmar
   Patel, Hardip R.
   White, Carl A.
   Shin, Jong-Yeon
   Gauthier, Maely E.
   Le Cao, Kim-Anh
   Kim, Jong-Il
   Mar, Jessica C.
   Shakiba, Nika
   Ritchie, William
   Rasko, John E. J.
   Grimmond, Sean M.
   Zandstra, Peter W.
   Wells, Christine A.
   Preiss, Thomas
   Seo, Jeong-Sun
   Heck, Albert J. R.
   Rogers, Ian M.
   Nagy, Andras
TI Genome-wide characterization of the routes to pluripotency
SO NATURE
LA English
DT Article
ID embryonic stem-cells; differential expression analysis; gene-expression; noncoding rnas; ips cells; functional-property; somatic-cells; chromatin; methylation; reveals
AB Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and - independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.
C1 [Hussein, Samer M. I.; Puri, Mira C.; Tonge, Peter D.; Corso, Andrew J.; Li, Mira; Rogers, Ian M.; Nagy, Andras] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
   [Puri, Mira C.] Univ Toronto, Dept Med Biophys, Toronto, ON M5T 3H7, Canada.
   [Benevento, Marco; Munoz, Javier; Heck, Albert J. R.] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
   [Benevento, Marco; Munoz, Javier; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands.
   [Benevento, Marco; Munoz, Javier; Heck, Albert J. R.] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands.
   [Corso, Andrew J.] Univ Toronto, Inst Med Sci, Toronto, ON M5T 3H7, Canada.
   [Clancy, Jennifer L.; Patel, Hardip R.; Preiss, Thomas] Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, Canberra, ACT 2601, Australia.
   [Mosbergen, Rowland; Korn, Othmar; Wells, Christine A.] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia.
   [Lee, Dong-Sung; Shin, Jong-Yeon; Kim, Jong-Il; Seo, Jeong-Sun] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea.
   [Lee, Dong-Sung] Seoul Natl Univ, Coll Med, Dept Biomed Sci & Biochem, Seoul 110799, South Korea.
   [Cloonan, Nicole; Wood, David L. A.; Gauthier, Maely E.; Le Cao, Kim-Anh; Grimmond, Sean M.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia.
   [Middleton, Robert; Ritchie, William; Rasko, John E. J.] Centenary Inst, Gene & Stem Cell Therapy Program, Camperdown, NSW 2050, Australia.
   [Middleton, Robert; Ritchie, William; Rasko, John E. J.] Centenary Inst, Bioinformat Lab, Camperdown, NSW 2050, Australia.
   [Middleton, Robert; Ritchie, William; Rasko, John E. J.] 31 Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
   [Patel, Hardip R.] Australian Natl Univ, John Curtin Sch Med Res, Genome Discovery Unit, Canberra, ACT 2601, Australia.
   [White, Carl A.; Shakiba, Nika; Zandstra, Peter W.] Univ Toronto, Inst Biomat & Biomed Engn IBBME, Toronto, ON M5S 3G9, Canada.
   [White, Carl A.; Zandstra, Peter W.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res CCBR, Toronto, ON M5S 3E1, Canada.
   [Shin, Jong-Yeon] Macrogen Inc, Life Sci Inst, Seoul 153781, South Korea.
   [Mar, Jessica C.] Yeshiva Univ, Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
   [Rasko, John E. J.] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
   [Wells, Christine A.] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8TA, Lanark, Scotland.
   [Preiss, Thomas] Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia.
   [Rogers, Ian M.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
   [Rogers, Ian M.; Nagy, Andras] Univ Toronto, Dept Obstet & Gynaecol, Toronto, ON M5S 1E2, Canada.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Utrecht University; Utrecht University; University of Toronto; Australian National University; John Curtin School of Medical Research; University of Queensland; Seoul National University (SNU); Seoul National University (SNU); University of Queensland; University of Sydney; Centenary Institute; University of Sydney; Centenary Institute; University of Sydney; Australian National University; John Curtin School of Medical Research; University of Toronto; University of Toronto; Macrogen, Inc.; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; NSW Health; Royal Prince Alfred Hospital; University of Sydney; University of Glasgow; Victor Chang Cardiac Research Institute; University of Toronto; University of Toronto
RP Nagy, A (corresponding author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
EM nagy@lunenfeld.ca
FU Ontario Research Fund Global Leadership Round in Genomics and Life Sciences grants [GL2-01-028]; Canadian stem cell network [9/5254 (TR3)]; Canadian Institutes of Health Research [CIHR MOP102575]; Korean Ministry of Knowledge Economy [10037410]; SNUCM Research Fund [0411-20100074]; Macrogen Inc. [MGR03-11, MGR03-12]; Australian Research Council [DP1300101928, SR110001002]; National Health and Medical Research Council of Australia [1024852]; Cancer Council of NSW; National Health & Medical Research Council [571156, 1061906]; Cure the Future Tour de Cure; Wound Management Innovation CRC (under the Australian Government's Cooperative Research Centres Program); Netherlands Proteomics Centre; European Community's Seventh Framework Programme (FP7) by the PRIME-XS project [262067]; McEwen Centre of Regenerative Medicine; National Health and Medical Research Council (NHMRC) [571156, 1061906] Funding Source: National Health and Medical Research Council (NHMRC); National Health and Medical Research Council of Australia [1061906] Funding Source: NHMRC
NR 59
TC 164
Z9 198
U1 0
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 DEC 11
PY 2014
VL 516
IS 7530
BP 198
EP +
DI 10.1038/nature14046
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500035
PM 25503233
DA 2026-03-09
ER

PT J
AU Viros, A
   Sanchez-Laorden, B
   Pedersen, M
   Furney, SJ
   Rae, J
   Hogan, K
   Ejiama, S
   Girotti, MR
   Cook, M
   Dhomen, N
   Marais, R
AF Viros, Amaya
   Sanchez-Laorden, Berta
   Pedersen, Malin
   Furney, Simon J.
   Rae, Joel
   Hogan, Kate
   Ejiama, Sarah
   Girotti, Maria Romina
   Cook, Martin
   Dhomen, Nathalie
   Marais, Richard
TI Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53
SO NATURE
LA English
DT Article
ID melanocytic nevi; sequencing data; p53 gain; mutations; mice; sunscreen; cancer; expression; prevention; exposure
AB Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear(1,2). The most common somatic mutation in melanoma is a V600E substitution in BRAF, which is an early event(3). To investigate how UVR accelerates oncogenic BRAF-driven melanomagenesis, we used a BRAF(V600E) mouse model. In mice expressing BRAF(V600E) in their melanocytes, a single dose of UVR that mimicked mild sunburn in humans induced clonal expansion of the melanocytes, and repeated doses of UVR increased melanoma burden. Here we show that sunscreen (UVA superior, UVB sun protection factor (SPF) 50) delayed the onset of UVR-driven melanoma, but only provided partial protection. The UVR-exposed tumours showed increased numbers of single nucleotide variants and we observed mutations (H39Y, S124F, R245C, R270C, C272G) in the Trp53 tumour suppressor in approximately 40% of cases. TP53 is an accepted UVR target in human non-melanoma skin cancer, but is not thought to have a major role in melanoma(4). However, we show that, in mice, mutant Trp53 accelerated BRAF(V600E)-driven melanomagenesis, and that TP53 mutations are linked to evidence of UVR-induced DNA damage inhuman melanoma. Thus, we provide mechanistic insight into epidemiological data linking UVR to acquired naevi in humans(5). Furthermore, we identify TP53/Trp53 as a UVR-target gene that cooperates with BRAF(V600E) to induce melanoma, providing molecular insight into how UVR accelerates melanomagenesis. Our study validates public health campaigns that promote sunscreen protection for individuals at risk of melanoma.
C1 [Viros, Amaya; Sanchez-Laorden, Berta; Furney, Simon J.; Hogan, Kate; Ejiama, Sarah; Girotti, Maria Romina; Cook, Martin; Marais, Richard] Univ Manchester, Canc Res UK Manchester Inst, Mol Oncol Grp, Manchester M20 4BX, Lancs, England.
   [Pedersen, Malin; Rae, Joel; Dhomen, Nathalie; Marais, Richard] Inst Canc Res, Signal Transduct Team, London SW3 6JB, England.
   [Cook, Martin] Royal Surrey Cty Hosp, Guildford GU2 7XX, Surrey, England.
C3 University of Manchester; Cancer Research UK; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; Royal Surrey County Hospital
RP Marais, R (corresponding author), Univ Manchester, Canc Res UK Manchester Inst, Mol Oncol Grp, Wilmslow Rd, Manchester M20 4BX, Lancs, England.
EM richard.marais@cruk.manchester.ac.uk
FU Cancer Research UK [C107/A10433, C5759/A12328, A13540, A17240]; Wenner-Gren Foundations; Stockholm; Teggerstiftelsen; FEBS Long-Term Fellowship; Cancer Research UK [19279, 17240] Funding Source: researchfish
NR 38
TC 182
Z9 232
U1 2
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 JUL 24
PY 2014
VL 511
IS 7510
BP 478
EP +
DI 10.1038/nature13298
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700049
PM 24919155
DA 2026-03-09
ER

PT J
AU Herbst, RS
   Soria, JC
   Kowanetz, M
   Fine, GD
   Hamid, O
   Gordon, MS
   Sosman, JA
   McDermott, DF
   Powderly, JD
   Gettinger, SN
   Kohrt, HEK
   Horn, L
   Lawrence, DP
   Rost, S
   Leabman, M
   Xiao, YY
   Mokatrin, A
   Koeppen, H
   Hegde, PS
   Mellman, I
   Chen, DS
   Hodi, FS
AF Herbst, Roy S.
   Soria, Jean-Charles
   Kowanetz, Marcin
   Fine, Gregg D.
   Hamid, Omid
   Gordon, Michael S.
   Sosman, Jeffery A.
   McDermott, David F.
   Powderly, John D.
   Gettinger, Scott N.
   Kohrt, Holbrook E. K.
   Horn, Leora
   Lawrence, Donald P.
   Rost, Sandra
   Leabman, Maya
   Xiao, Yuanyuan
   Mokatrin, Ahmad
   Koeppen, Hartmut
   Hegde, Priti S.
   Mellman, Ira
   Chen, Daniel S.
   Hodi, F. Stephen
TI Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
SO NATURE
LA English
DT Article
ID t-cells; in-vivo; safety; tumors; pd-1; melanoma; criteria; pathway; disease; b7-h1
AB The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression. These changes distinguish cancer cells from their normal counterparts, allowing tumours to be recognized as foreign by the immune system(1-4). However, tumours are rarely rejected spontaneously, reflecting their ability to maintain an immunosuppressive microenvironmen(5). Programmed death-ligand 1 (PD-Li; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an important part in blocking the 'cancer immunity cycle' by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are negative regulators of T-lymphocyte activation. Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and restricts tumour cell killing(6-10). The PD -LI-PD -1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections(11). Blocking PD-L1 should therefore enhance anticancer immunity, but little is known about predictive factors of efficacy. This study was designed to evaluate the safety, activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A. Here we show that across multiple cancer types, responses (as evaluated by Response Evaluation Criteria in Solid Tumours, version 1.1) were observed in patients with tumours expressing high levels of PD-L1, especially when PD-L1 was expressed by tumour-infiltrating immune cells. Furthermore, responses were associated with T-helper type 1 (T(H)1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens. Together, these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is re-invigorated on antibody treatment.
C1 [Herbst, Roy S.; Gettinger, Scott N.] Yale Univ, Sch Med, Yale Comprehens Canc Ctr, New Haven, CT 06520 USA.
   [Soria, Jean-Charles] Gustave Roussy South Paris Univ, F-94805 Villejuif, France.
   [Kowanetz, Marcin; Fine, Gregg D.; Rost, Sandra; Leabman, Maya; Xiao, Yuanyuan; Mokatrin, Ahmad; Koeppen, Hartmut; Hegde, Priti S.; Mellman, Ira; Chen, Daniel S.] Genentech Inc, San Francisco, CA 94080 USA.
   [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA 90025 USA.
   [Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ 85258 USA.
   [Sosman, Jeffery A.; Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
   [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Powderly, John D.] Carolina BioOncol Inst, Huntersville, NC 28078 USA.
   [Kohrt, Holbrook E. K.] Stanford Univ, Stanford, CA 94305 USA.
   [Lawrence, Donald P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA.
C3 Yale University; Roche Holding; Roche Holding USA; Genentech; Angeles Clinic & Research Institute; Vanderbilt University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Stanford University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Herbst, RS (corresponding author), Yale Univ, Sch Med, Yale Comprehens Canc Ctr, 333 Cedar St,WWW221, New Haven, CT 06520 USA.
EM roy.herbst@yale.edu
FU NCI [1R01CA155196, P30 CA 016359]; National Cancer Institute [P30CA016359] Funding Source: NIH RePORTER
CR Akbari O, 2010, MUCOSAL IMMUNOL, V3, P81, DOI 10.1038/mi.2009.112
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NR 31
TC 4385
Z9 5035
U1 3
U2 654
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 563
EP +
DI 10.1038/nature14011
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600053
PM 25428504
DA 2026-03-09
ER

PT J
AU Hu, SW
   Shima, T
   Hou, ZM
AF Hu, Shaowei
   Shima, Takanori
   Hou, Zhaomin
TI Carbon-carbon bond cleavage and rearrangement of benzene by a trinuclear titanium hydride
SO NATURE
LA English
DT Article
ID rare-earth; hydrogenation; hydroisomerization; cyclopentadiene; contraction; catalysts; insertion; clusters; monoxide; arene
AB The cleavage of carbon-carbon ( C-C) bonds by transition metals is of great interest, especially as this transformation can be used to produce fuels and other industrially important chemicals from natural resources such as petroleum and biomass. Carbon-carbon bonds are quite stable and are consequently unreactive under many reaction conditions. In the industrial naphtha hydrocracking process, the aromatic carbon skeleton of benzene can be transformed to methylcyclopentane and acyclic saturated hydrocarbons through C-C bond cleavage and rearrangement on the surfaces of solid catalysts(1-6). However, these chemical transformations usually require high temperatures and are fairly non-selective. Microorganisms can degrade aromatic compounds under ambient conditions, but the mechanistic details are not known and are difficult to mimic(7). Several transition metal complexes have been reported to cleave C-C bonds in a selective fashion in special circumstances, such as relief of ring strain, formation of an aromatic system, chelation-assisted cyclometallation and beta-carbon elimination(8-15). However, the cleavage of benzene by a transition metal complex has not been reported(16-19). Here we report the C-C bond cleavage and rearrangement of benzene by a trinuclear titanium poly-hydride complex. The benzene ring is transformed sequentially to a methylcyclopentenyl and a 2-methylpentenyl species through the cleavage of the aromatic carbon skeleton at the multi-titanium sites. Our results suggest that multinuclear titanium hydrides could serve as a unique platform for the activation of aromatic molecules, and may facilitate the design of new catalysts for the transformation of inactive aromatics.
C1 [Hu, Shaowei; Shima, Takanori; Hou, Zhaomin] RIKEN Ctr Sustainable Resource Sci, Adv Catalysis Res Grp, Wako, Saitama 3510198, Japan.
   [Shima, Takanori; Hou, Zhaomin] RIKEN, Organometall Chem Lab, Wako, Saitama 3510198, Japan.
C3 RIKEN; RIKEN
RP Hou, ZM (corresponding author), RIKEN Ctr Sustainable Resource Sci, Adv Catalysis Res Grp, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM houz@riken.jp
FU JSPS [26810041, 26410082, 26220802]; RIKEN; Grants-in-Aid for Scientific Research [26810041, 26220802, 26410082] Funding Source: KAKEN
NR 30
TC 140
Z9 157
U1 3
U2 289
PU NATURE PUBLISHING 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 28
PY 2014
VL 512
IS 7515
BP 413
EP 415
DI 10.1038/nature13624
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600029
PM 25164752
DA 2026-03-09
ER

PT J
AU Auyeung, E
   Li, TING
   Senesi, AJ
   Schmucker, AL
   Pals, BC
   de la Cruz, MO
   Mirkin, CA
AF Auyeung, Evelyn
   Li, Ting I. N. G.
   Senesi, Andrew J.
   Schmucker, Abrin L.
   Pals, Bridget C.
   de la Cruz, Monica Olvera
   Mirkin, Chad A.
TI DNA-mediated nanoparticle crystallization into Wulff polyhedra
SO NATURE
LA English
DT Article
ID superlattices; evolution; growth; shape; size
AB Crystallization is a fundamental and ubiquitous process much studied over the centuries. But although the crystallization of atoms is fairly well understood(1,2), it remains challenging to predict reliably the outcome of molecular crystallization processes that are complicated by various molecular interactions and solvent involvement. This difficulty also applies to nanoparticles: high-quality three-dimensional crystals(3-6) are mostly produced using drying and sedimentation techniques that are often impossible to rationalize and control to give a desired crystal symmetry, lattice spacing and habit (crystal shape). In principle, DNA-mediated assembly of nanoparticles offers an ideal opportunity for studying nanoparticle crystallization(7-17): a well-defined set of rules have been developed to target desired lattice symmetries and lattice constants(8,9,18), and the occurrence of features such as grain boundaries and twinning in DNA superlattices and traditional crystals comprised of molecular or atomic building blocks suggests that similar principles govern their crystallization. But the presence of charged biomolecules, interparticle spacings of tens of nanometres, and the realization so far of only polycrystalline DNA-interconnected nanoparticle superlattices, all suggest that DNA-guided crystallization may differ from traditional crystal growth. Here we show that very slow cooling, over several days, of solutions of complementary-DNA-modified nanoparticles through the melting temperature of the system gives the thermodynamic product with a specific and uniform crystal habit. We find that our nanoparticle assemblies have the Wulff equilibrium crystal structure that is predicted from theoretical considerations and molecular dynamics simulations, thus establishing that DNA hybridization can direct nanoparticle assembly along a pathway that mimics atomic crystallization.
C1 [Auyeung, Evelyn; Li, Ting I. N. G.; de la Cruz, Monica Olvera; Mirkin, Chad A.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Auyeung, Evelyn; Li, Ting I. N. G.; Senesi, Andrew J.; Schmucker, Abrin L.; Pals, Bridget C.; de la Cruz, Monica Olvera; Mirkin, Chad A.] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA.
   [Senesi, Andrew J.; Schmucker, Abrin L.; de la Cruz, Monica Olvera; Mirkin, Chad A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
C3 Northwestern University; Northwestern University; Northwestern University
RP Mirkin, CA (corresponding author), Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
EM chadnano@northwestern.edu
FU Air Force Office of Scientific Research (AFOSR) Multidisciplinary University Research Initiative (MURI) [FA9550-11-1-0275]; National Science Foundation Materials Research Science and Engineering Center at the Materials Research Center of Northwestern University [DMR-1121262]; Non-equilibrium Energy Research Center (NERC), an Energy Frontier Research Center; Department of Energy (DoE), Office of Science, Office of Basic Energy Sciences [DE-SC0000989]; National Defense Science and Engineering Graduate (NDSEG) Fellowship [32 CFR 168a]; Ryan Fellowship from Northwestern University; DoE [DE-AC02-06CH11357]; US Department of Defense National Security Science and Engineering Faculty Fellowship [FA9550-10-1-0167]; Division Of Materials Research; Direct For Mathematical & Physical Scien [1121262] Funding Source: National Science Foundation
NR 28
TC 386
Z9 476
U1 2
U2 600
PU NATURE PUBLISHING 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 2
PY 2014
VL 505
IS 7481
BP 73
EP 77
DI 10.1038/nature12739
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300026
PM 24284632
DA 2026-03-09
ER

PT J
AU Kafsack, BFC
   Rovira-Graells, N
   Clark, TG
   Bancells, C
   Crowley, VM
   Campino, SG
   Williams, AE
   Drought, LG
   Kwiatkowski, DP
   Baker, DA
   Cortés, A
   Llinás, M
AF Kafsack, Bjoern F. C.
   Rovira-Graells, Nuria
   Clark, Taane G.
   Bancells, Cristina
   Crowley, Valerie M.
   Campino, Susana G.
   Williams, April E.
   Drought, Laura G.
   Kwiatkowski, Dominic P.
   Baker, David A.
   Cortes, Alfred
   Llinas, Manuel
TI A transcriptional switch underlies commitment to sexual development in malaria parasites
SO NATURE
LA English
DT Article
ID plasmodium-falciparum gametocytes; protein; genes; expression; transmission; region
AB The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal(1). Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci(2,3) prone to spontaneous activation(4). Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.
C1 [Kafsack, Bjoern F. C.; Crowley, Valerie M.; Llinas, Manuel] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Rovira-Graells, Nuria; Bancells, Cristina; Cortes, Alfred] Hosp Clin Univ Barcelona, CRESIB, Barcelona Ctr Int Hlth Res, Barcelona 08036, Catalonia, Spain.
   [Rovira-Graells, Nuria; Crowley, Valerie M.; Cortes, Alfred] IRB, Barcelona 08028, Catalonia, Spain.
   [Clark, Taane G.; Drought, Laura G.; Baker, David A.] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1E 7HT, England.
   [Clark, Taane G.] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
   [Campino, Susana G.; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Williams, April E.; Llinas, Manuel] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Kwiatkowski, Dominic P.] Wellcome Trust Sanger Ctr Human Genet, Oxford OX37BN, England.
   [Cortes, Alfred] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain.
C3 Princeton University; ISGlobal; CRESIB; University of Barcelona; Hospital Clinic de Barcelona; Barcelona Institute of Science & Technology; Institute for Research in Biomedicine - IRB Barcelona; University of London; London School of Hygiene & Tropical Medicine; University of London; London School of Hygiene & Tropical Medicine; Wellcome Trust Sanger Institute; Princeton University; University of Oxford; Wellcome Centre for Human Genetics; ICREA
RP Llinás, M (corresponding author), Penn State Univ, Dept Mol Biol, State Coll, PA 16802 USA.
EM manuel@psu.edu
FU National Institutes of Health (NIH) [R01 AI076276]; Centre for Quantitative Biology [P50GM071508]; Howard Hughes Medical Institute fellowship of the Damon Runyon Cancer Research Foundation; Wellcome Trust [094752, 098051, 090532/Z/09/Z]; European Commission [223044]; Biotechnology and Biological Sciences Research Council CASE PhD studentship; Spanish Ministry of Science and Innovation [SAF2010-20111]; IRB Barcelona; Medical Research Council UK [J005398, G0600230]; Catalan Government fellowship [2011-BP-B 00060]; ICREA Funding Source: Custom; MRC [G0600230, G0600718] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [971922] Funding Source: researchfish; Medical Research Council [G0600230, G0600718] Funding Source: researchfish; National Institute of General Medical Sciences [T32GM007388] Funding Source: NIH RePORTER
NR 40
TC 384
Z9 462
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 13
PY 2014
VL 507
IS 7491
BP 248
EP +
DI 10.1038/nature12920
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800042
PM 24572369
DA 2026-03-09
ER

PT J
AU Duss, O
   Michel, E
   Yulikov, M
   Schubert, M
   Jeschke, G
   Allain, FHT
AF Duss, Olivier
   Michel, Erich
   Yulikov, Maxim
   Schubert, Mario
   Jeschke, Gunnar
   Allain, Frederic H. -T.
TI Structural basis of the non-coding RNA RsmZ acting as a protein sponge
SO NATURE
LA English
DT Article
ID pseudomonas-fluorescens cha0; escherichia-coli; regulatory rnas; recognition; sensitivity; aeruginosa; biocontrol; principles; efficient; sequence
AB MicroRNA and protein sequestration by non-coding RNAs (ncRNAs) has recently generated much interest. In the bacterial Csr/Rsm system, which is considered to be the most general global post-transcriptional regulatory system responsible for bacterial virulence, ncRNAs such as CsrB or RsmZ activate translation initiation by sequestering homodimeric CsrA-type proteins from the ribosome-binding site of a subset of messenger RNAs. However, the mechanism of ncRNA-mediated protein sequestration is not understood at the molecular level. Here we show for Pseudomonas fluorescens that RsmE protein dimers assemble sequentially, specifically and cooperatively onto the ncRNA RsmZ within a narrow affinity range. This assembly yields two different native ribonucleoprotein structures. Using a powerful combination of nuclear magnetic resonance and electron paramagnetic resonance spectroscopy we elucidate these 70-kilodalton solution structures, thereby revealing the molecular mechanism of the sequestration process and how RsmE binding protects the ncRNA from RNase E degradation. Overall, our findings suggest that RsmZ is well-tuned to sequester, store and release RsmE and therefore can be viewed as an ideal protein 'sponge'.
C1 [Duss, Olivier; Michel, Erich; Schubert, Mario; Allain, Frederic H. -T.] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
   [Yulikov, Maxim; Jeschke, Gunnar] ETH, Phys Chem Lab, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Allain, FHT (corresponding author), ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
EM allain@mol.biol.ethz.ch
FU Swiss National Science Foundation (SNF) [3100A0-118118, 31003ab-133134, 31003A-149921]; SNF-NCCR structural biology Iso-lab; Swiss National Science Foundation (SNF) [31003AB_133134, 31003A_149921] Funding Source: Swiss National Science Foundation (SNF)
NR 51
TC 166
Z9 184
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 MAY 29
PY 2014
VL 509
IS 7502
BP 588
EP +
DI 10.1038/nature13271
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100042
PM 24828038
DA 2026-03-09
ER

PT J
AU Ritsma, L
   Ellenbroek, SIJ
   Zomer, A
   Snippert, HJ
   de Sauvage, FJ
   Simons, BD
   Clevers, H
   van Rheenen, J
AF Ritsma, Laila
   Ellenbroek, Saskia I. J.
   Zomer, Anoek
   Snippert, Hugo J.
   de Sauvage, Frederic J.
   Simons, Benjamin D.
   Clevers, Hans
   van Rheenen, Jacco
TI Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging
SO NATURE
LA English
DT Article
ID self-renewal; bmi1; differentiation; competition; mechanisms; marker; niche; lrig1; lgr5
AB The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt(1). In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region(1-6). Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells(7-9). However, the short-term behaviour of individual Lgr5(+) cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5-Confetti mice. Wefind that Lgr5(+) cells in the upper part of the niche (termed 'border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed 'central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5(+) cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.
C1 [Ritsma, Laila; Ellenbroek, Saskia I. J.; Zomer, Anoek; Clevers, Hans; van Rheenen, Jacco] Hubrecht Inst KNAW, Canc Genom Netherlands, NL-3584 CT Utrecht, Netherlands.
   [Ritsma, Laila; Ellenbroek, Saskia I. J.; Zomer, Anoek; Clevers, Hans; van Rheenen, Jacco] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Snippert, Hugo J.] Univ Med Ctr Utrecht, NL-3584 CG Utrecht, Netherlands.
   [de Sauvage, Frederic J.] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Simons, Benjamin D.] Univ Cambridge, Dept Phys, Cavevdish Lab, Cambridge CB3 0HE, England.
   [Simons, Benjamin D.] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Simons, Benjamin D.] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1QN, England.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; Roche Holding; Roche Holding USA; Genentech; University of Cambridge; University of Cambridge; University of Cambridge
RP van Rheenen, J (corresponding author), Hubrecht Inst KNAW, Canc Genom Netherlands, NL-3584 CT Utrecht, Netherlands.
EM h.clevers@hubrecht.eu; j.vanrheenen@hubrecht.eu
FU Dutch Organization of Scientific Research (NWO) [91710330, 175.010.2007.00, 834.11.002]; Dutch Cancer Society (KWF) [HUBR 2009-4621]; Association for International Cancer Research (AICR) [13-0297]; Wellcome Trust [098357/Z/12/Z]; Wellcome Trust [098357/Z/12/Z] Funding Source: researchfish
NR 30
TC 401
Z9 466
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 MAR 20
PY 2014
VL 507
IS 7492
BP 362
EP +
DI 10.1038/nature12972
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000035
PM 24531760
DA 2026-03-09
ER

PT J
AU Weber, ME
   Clark, PU
   Kuhn, G
   Timmermann, A
   Sprenk, D
   Gladstone, R
   Zhang, X
   Lohmann, G
   Menviel, L
   Chikamoto, MO
   Friedrich, T
   Ohlwein, C
AF Weber, M. E.
   Clark, P. U.
   Kuhn, G.
   Timmermann, A.
   Sprenk, D.
   Gladstone, R.
   Zhang, X.
   Lohmann, G.
   Menviel, L.
   Chikamoto, M. O.
   Friedrich, T.
   Ohlwein, C.
TI Millennial-scale variability in Antarctic ice-sheet discharge during the last deglaciation
SO NATURE
LA English
DT Article
ID pine island glacier; southern-ocean; weddell sea; scotia sea; radiocarbon constraints; circumpolar current; retreat; core; chronology; maximum
AB Our understanding of the deglacial evolution of the Antarctic Ice Sheet (AIS) following the Last Glacial Maximum(26,000-19,000 years ago)(1) is based largely on a few well-dated but temporally and geographically restricted terrestrial and shallow-marine sequences(2-4). This sparseness limits our understanding of the dominant feedbacks between the AIS, Southern Hemisphere climate and global sea level. Marine records of iceberg-rafted debris (IBRD) provide a nearly continuous signal of ice-sheet dynamics and variability. IBRD records from the North Atlantic Ocean have been widely used to reconstruct variability in Northern Hemisphere ice sheets(5), but comparable records from the Southern Ocean of the AIS are lacking because of the low resolution and large dating uncertainties in existing sediment cores. Here we present two well-dated, high-resolution IBRD records that capture a spatially integrated signal of AIS variability during the last deglaciation. We document eight events of increased iceberg flux from various parts of the AIS between 20,000 and 9,000 years ago, in marked contrast to previous scenarios which identified the main AIS retreat as occurring after meltwater pulse 1A(3,6-8) and continuing into the late Holocene epoch. The highest IBRD flux occurred 14,600 years ago, providing the first direct evidence for an Antarctic contribution to meltwater pulse 1A. Climate model simulations with AIS freshwater forcing identify a positive feedback between poleward transport of Circumpolar Deep Water, subsurface warming and AIS melt, suggesting that small perturbations to the ice sheet can be substantially enhanced, providing a possible mechanism for rapid sea-level rise.
C1 [Weber, M. E.; Sprenk, D.] Univ Cologne, Inst Geol & Mineral, D-50935 Cologne, Germany.
   [Clark, P. U.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Kuhn, G.; Zhang, X.; Lohmann, G.] Alfred Wegener Inst Helmholtz Zentrum Polar & Mee, D-27568 Bremerhaven, Germany.
   [Timmermann, A.; Chikamoto, M. O.; Friedrich, T.] Univ Hawaii Manoa, Int Pacific Res Ctr, Sch Ocean & Earth Sci & Technol, Honolulu, HI 96822 USA.
   [Gladstone, R.] Univ Lapland, Arctic Ctr, Rovaniemi 96101, Finland.
   [Menviel, L.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Menviel, L.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Ohlwein, C.] Univ Bonn, Hans Ertel Ctr Weather Res, Climate Monitoring Branch, Inst Meteorol, D-53121 Bonn, Germany.
C3 University of Cologne; Oregon State University; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Hawaii System; University of Hawaii Manoa; University of Lapland; University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; University of New South Wales Sydney; University of Bonn
RP Weber, ME (corresponding author), Univ Cologne, Inst Geol & Mineral, Zuelpicher Str 49a, D-50935 Cologne, Germany.
EM michael.weber@uni-koeln.de
FU Deutsche Forschungsgemeinschaft (DFG) [We2039/7-1, Ri525/17-1, Ku683/9-1]; University of Cologne; US NSF Antarctic Glaciology Program [ANT-1043517, ANT-1341311]; US NSF Paleoclimatology Program; Japan Agency for Marine-Earth Science and Technology; Helmholtz funding through the Polar Regions and Coasts in the changing Earth System (PACES) programme; Directorate For Geosciences [1010869] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [1043517] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1010869] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1341311] Funding Source: National Science Foundation
NR 81
TC 177
Z9 206
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 JUN 5
PY 2014
VL 510
IS 7503
BP 134
EP +
DI 10.1038/nature13397
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900043
PM 24870232
DA 2026-03-09
ER

PT J
AU Dannappel, M
   Vlantis, K
   Kumari, S
   Polykratis, A
   Kim, C
   Wachsmuth, L
   Eftychi, C
   Lin, J
   Corona, T
   Hermance, N
   Zelic, M
   Kirsch, P
   Basic, M
   Bleich, A
   Kelliher, M
   Pasparakis, M
AF Dannappel, Marius
   Vlantis, Katerina
   Kumari, Snehlata
   Polykratis, Apostolos
   Kim, Chun
   Wachsmuth, Laurens
   Eftychi, Christina
   Lin, Juan
   Corona, Teresa
   Hermance, Nicole
   Zelic, Matija
   Kirsch, Petra
   Basic, Marijana
   Bleich, Andre
   Kelliher, Michelle
   Pasparakis, Manolis
TI RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
SO NATURE
LA English
DT Article
ID necrosis-factor receptor; kappa-b activation; in-vivo; cell; mice; kinase; deletion; keratinocytes; inflammation; deficient
AB Necroptosis has emerged as an important pathway of programmed cell death in embryonic development, tissue homeostasis, immunity and inflammation(1-8). RIPK1 is implicated in inflammatory and cell death signalling(9-13) and its kinase activity is believed to drive RIPK3-mediated necroptosis(14,15). Here we show that kinase-independent scaffolding RIPK1 functions regulate homeostasis and prevent inflammation in barrier tissues by inhibiting epithelial cell apoptosis and necroptosis. Intestinal epithelial cell (IEC)-specific RIPK1 knockout caused IEC apoptosis, villus atrophy, loss of goblet and Paneth cells and premature death in mice. This pathology developed independently of the microbiota and of MyD88 signalling but was partly rescued by TNFR1 (also known as TNFRSF1A) deficiency. Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature death of mice with IEC-specific RIPK1 knockout. However, mice lacking both RIPK1 and FADD in IECs displayed RIPK3-dependent IEC necroptosis, Paneth cell loss and focal erosive inflammatory lesions in the colon. Moreover, a RIPK1 kinase inactive knock-in delayed but did not prevent inflammation caused by FADD deficiency in IECs or keratinocytes, showing that RIPK3-dependent necroptosis of FADD-deficient epithelial cells only partly requires RIPK1 kinase activity. Epidermis-specific RIPK1 knockout triggered keratinocyte apoptosis and necroptosis and caused severe skin inflammation that was prevented by RIPK3 but not FADD deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated necroptosis in keratinocytes in vivo and identified necroptosis as a more potent trigger of inflammation compared with apoptosis. Therefore, RIPK1 is a master regulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin.
C1 [Dannappel, Marius; Vlantis, Katerina; Kumari, Snehlata; Polykratis, Apostolos; Kim, Chun; Wachsmuth, Laurens; Eftychi, Christina; Lin, Juan; Corona, Teresa; Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50931 Cologne, Germany.
   [Dannappel, Marius; Vlantis, Katerina; Kumari, Snehlata; Polykratis, Apostolos; Kim, Chun; Wachsmuth, Laurens; Eftychi, Christina; Lin, Juan; Corona, Teresa; Pasparakis, Manolis] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
   [Hermance, Nicole; Zelic, Matija; Kelliher, Michelle] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
   [Kirsch, Petra] Univ Ulm, Tierforschungszentrum, D-89081 Ulm, Germany.
   [Basic, Marijana; Bleich, Andre] Hannover Med Sch, Inst Lab Anim Sci, D-30625 Hannover, Germany.
C3 University of Cologne; University of Cologne; University of Massachusetts System; University of Massachusetts Worcester; Ulm University; Hannover Medical School
RP Pasparakis, M (corresponding author), Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50931 Cologne, Germany.
EM pasparakis@uni-koeln.de
FU European Research Council [2012-ADG_20120314]; German Research Council (DFG) [SFB670, SFB829, SPP1656]; European Commission [223404, 223151]; Deutsche Krebshilfe; Else Kroner-Fresenius-Stiftung; Helmholtz Alliance (PCCC); National Institute of Allergy and Infectious Diseases division of the National Institutes of Health [RO1AI075118]; National Institute of Allergy and Infectious Diseases [R01AI075118, T32AI095213] Funding Source: NIH RePORTER
NR 47
TC 469
Z9 511
U1 2
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 SEP 4
PY 2014
VL 513
IS 7516
BP 90
EP +
DI 10.1038/nature13608
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800036
PM 25132550
DA 2026-03-09
ER

PT J
AU Lui, JH
   Nowakowski, TJ
   Pollen, AA
   Javaherian, A
   Kriegstein, AR
   Oldham, MC
AF Lui, Jan H.
   Nowakowski, Tomasz J.
   Pollen, Alex A.
   Javaherian, Ashkan
   Kriegstein, Arnold R.
   Oldham, Michael C.
TI Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex
SO NATURE
LA English
DT Article
ID receptor-beta; evolution; transcriptome; gene; brain; zones
AB Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential(1,2) of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche(3-5) during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG inhuman, but not mouse, corticogenesis. We also show that the expression domain of PDGFR beta, the cognate receptor(6,7) for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD-PDGFR beta signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFR beta in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFR beta signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.
C1 [Lui, Jan H.; Nowakowski, Tomasz J.; Pollen, Alex A.; Javaherian, Ashkan; Kriegstein, Arnold R.; Oldham, Michael C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Lui, Jan H.; Nowakowski, Tomasz J.; Pollen, Alex A.; Javaherian, Ashkan; Kriegstein, Arnold R.; Oldham, Michael C.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Oldham, MC (corresponding author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
EM kriegsteina@stemcell.ucsf.edu; oldhamm@stemcell.ucsf.edu
FU NIH, NINDS; Bernard Osher Foundation, a California Institute for Regenerative Medicine Predoctoral Fellowship [TG2-01153]; Damon Runyon Foundation Postdoctoral Fellowship [DRG-2013]; University of California San Francisco Program for Breakthrough Biomedical Research - Sandler Foundation
NR 29
TC 134
Z9 153
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 NOV 13
PY 2014
VL 515
IS 7526
BP 264
EP U258
DI 10.1038/nature13973
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400050
PM 25391964
DA 2026-03-09
ER

PT J
AU Pickard, JM
   Maurice, CF
   Kinnebrew, MA
   Abt, MC
   Schenten, D
   Golovkina, TV
   Bogatyrev, SR
   Ismagilov, RF
   Pamer, EG
   Turnbaugh, PJ
   Chervonsky, AV
AF Pickard, Joseph M.
   Maurice, Corinne F.
   Kinnebrew, Melissa A.
   Abt, Michael C.
   Schenten, Dominik
   Golovkina, Tatyana V.
   Bogatyrev, Said R.
   Ismagilov, Rustem F.
   Pamer, Eric G.
   Turnbaugh, Peter J.
   Chervonsky, Alexander V.
TI Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness
SO NATURE
LA English
DT Article
ID chain fatty-acids; differential expression; gene-expression; microbiota; fucose; infection; anorexia; mice; metabolism; mucins
AB Systemic infection induces conserved physiological responses that include both resistance and 'tolerance of infection' mechanisms(1). Temporary anorexia associated with an infection is often beneficial(2,3), reallocating energy from food foraging towards resistance to infection(4) or depriving pathogens of nutrients(5). However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections)(6). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid alpha(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin(IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress.
C1 [Pickard, Joseph M.; Chervonsky, Alexander V.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   [Pickard, Joseph M.; Chervonsky, Alexander V.] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA.
   [Maurice, Corinne F.; Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Kinnebrew, Melissa A.; Abt, Michael C.; Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Schenten, Dominik] Univ Arizona, Tucson, AZ 85721 USA.
   [Golovkina, Tatyana V.] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
   [Bogatyrev, Said R.; Ismagilov, Rustem F.] CALTECH, Pasadena, CA 91125 USA.
C3 University of Chicago; University of Chicago; Harvard University; Memorial Sloan Kettering Cancer Center; University of Arizona; University of Chicago; California Institute of Technology
RP Chervonsky, AV (corresponding author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM achervon@bsd.uchicago.edu
FU National Institutes of Health [P50 GM068763, AI96706, AI42135, T32 AI065382]; Harvard Bauer Fellows Program; National Science Foundation [EFRI-1137089]; Digestive Disease Research Core Center [DK42086]; Kenneth Rainin Foundation; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007090] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK042086] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER; Directorate For Engineering; Emerging Frontiers & Multidisciplinary Activities [1137089] Funding Source: National Science Foundation
NR 54
TC 434
Z9 527
U1 1
U2 184
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 30
PY 2014
VL 514
IS 7524
BP 638
EP +
DI 10.1038/nature13823
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500051
PM 25274297
DA 2026-03-09
ER

PT J
AU Sharma, P
   Ward, A
   Gibaud, T
   Hagan, MF
   Dogic, Z
AF Sharma, Prerna
   Ward, Andrew
   Gibaud, T.
   Hagan, Michael F.
   Dogic, Zvonimir
TI Hierarchical organization of chiral rafts in colloidal membranes
SO NATURE
LA English
DT Article
ID lipid rafts; nucleation; morphology; curvature; particles; crystals; kinetics; clusters; domains; tension
AB Liquid-liquid phase separation is ubiquitous in suspensions of nanoparticles, proteins and colloids. It has an important role in gel formation, protein crystallization and perhaps even as an organizing principle in cellular biology(1,2). With a fewnotable exceptions(3,4), liquid-liquid phase separation in bulk proceeds through the continuous coalescence of droplets until the system undergoes complete phase separation. But when colloids, nanoparticles or proteins are confined to interfaces, surfaces or membranes, their interactions differ fundamentally from those mediated by isotropic solvents(5,6), and this results in significantly more complex phase behaviour(7-13). Here we show that liquid-liquid phase separation in monolayer membranes composed of two dissimilar chiral colloidal rods gives rise to thermodynamically stable rafts that constantly exchange monomeric rods with the background reservoir to maintain a self-limited size. We visualize and manipulate rafts to quantify their assembly kinetics and to show that membrane distortions arising from the rods' chirality lead to long-range repulsive raft-raft interactions. Rafts assemble into cluster crystals at high densities, but they can also form bonds to yield higher-order structures. Taken together, our observations demonstrate a robust membrane-based pathway for the assembly of mono-disperse membrane clusters that is complementary to existing methods for colloid assembly in bulk suspensions(14-16). They also reveal that chiral inclusions in membranes can acquire long-range repulsive interactions, which might more generally have a role in stabilizing assemblages of finite size(13,17).
C1 [Sharma, Prerna; Ward, Andrew; Hagan, Michael F.; Dogic, Zvonimir] Brandeis Univ, Dept Phys, Waltham, MA 02454 USA.
   [Gibaud, T.] Univ Lyon 1, CNRS UMR 5672, Ecole Normale Super Lyon, Phys Lab, F-69007 Lyon, France.
C3 Brandeis University; Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP)
RP Dogic, Z (corresponding author), Brandeis Univ, Dept Phys, 415 South St, Waltham, MA 02454 USA.
EM zdogic@brandeis.edu
FU US National Science Foundation [NSF-MRSEC-0820492, NSF-DMR-0955776, NSF-MRI-0923057]; Petroleum Research Fund [ACS-PRF 50558-DNI7]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0955776] Funding Source: National Science Foundation
NR 38
TC 61
Z9 68
U1 3
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 SEP 4
PY 2014
VL 513
IS 7516
BP 77
EP +
DI 10.1038/nature13694
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800033
PM 25186901
DA 2026-03-09
ER

PT J
AU Zu, C
   Wang, WB
   He, L
   Zhang, WG
   Dai, CY
   Wang, F
   Duan, LM
AF Zu, C.
   Wang, W. -B.
   He, L.
   Zhang, W. -G.
   Dai, C. -Y.
   Wang, F.
   Duan, L. -M.
TI Experimental realization of universal geometric quantum gates with solid-state spins
SO NATURE
LA English
DT Article
ID trapped ions; computation; entanglement; diamond; phases
AB Experimental realization of a universal set of quantum logic gates is the central requirement for the implementation of a quantum computer. In an 'all-geometric' approach to quantum computation(1,2), the quantum gates are implemented using Berry phases(3) and their non-Abelian extensions, holonomies(4), from geometric transformation of quantum states in the Hilbert space(5). Apart from its fundamental interest and rich mathematical structure, the geometric approach has some built-innoise-resilience features(1,2,6,7). On the experimental side, geometric phases and holonomies have been observed in thermal ensembles of liquid molecules using nuclear magnetic resonance(8,9); however, such systems are known to be non-scalable for the purposes of quantum computing(10). There are proposals to implement geometric quantum computation in scalable experimental platforms such as trapped ions(11), superconducting quantum bits(12) and quantum dots(13), and a recent experiment has realized geometric single-bit gates in a superconducting system(14). Here we report the experimental realization of a universal set of geometric quantum gates using the solid-state spins of diamond nitrogen-vacancy centres. These diamond defects provide a scalable experimental platform(15-17) with the potential for room-temperature quantum computing(16-19), which has attracted strong interest in recent years(20). Our experiment shows that all-geometric and potentially robust quantum computation can be realized with solid-state spin quantum bits, making use of recent advances in the coherent control of this system(15-20).
C1 [Zu, C.; Wang, W. -B.; He, L.; Zhang, W. -G.; Dai, C. -Y.; Wang, F.; Duan, L. -M.] Tsinghua Univ, IIIS, Ctr Quantum Informat, Beijing 100084, Peoples R China.
   [Duan, L. -M.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
C3 Tsinghua University; University of Michigan System; University of Michigan
RP Duan, LM (corresponding author), Tsinghua Univ, IIIS, Ctr Quantum Informat, Beijing 100084, Peoples R China.
EM lmduan@umich.edu
FU National Basic Research Program of China [2011CBA00302]; Ministry of Education of China; IARPA MUSIQC program; AFOSR; ARO MURI program
NR 30
TC 321
Z9 347
U1 2
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 OCT 2
PY 2014
VL 514
IS 7520
BP 72
EP +
DI 10.1038/nature13729
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800037
PM 25279920
DA 2026-03-09
ER

PT J
AU Hemani, G
   Shakhbazov, K
   Westra, HJ
   Esko, T
   Henders, AK
   Mcrae, AF
   Yang, J
   Gibson, G
   Martin, NG
   Metspalu, A
   Franke, L
   Montgomery, GW
   Visscher, PM
   Powell, JE
AF Hemani, Gibran
   Shakhbazov, Konstantin
   Westra, Harm-Jan
   Esko, Tonu
   Henders, Anjali K.
   McRae, Allan F.
   Yang, Jian
   Gibson, Greg
   Martin, Nicholas G.
   Metspalu, Andres
   Franke, Lude
   Montgomery, Grant W.
   Visscher, Peter M.
   Powell, Joseph E.
TI RETRACTED: Detection and replication of epistasis influencing transcription in humans (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID genome-wide association; genetic-variation; loci; gwas
AB Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits(1) and contributes to their variation(2,3) is a fundamental question in evolution andhuman genetics. Although oftendemonstrated in artificial gene manipulation studies in model organisms(4,5), and some examples have been reported in other species(6), few examples exist for epistasis among natural polymorphisms in human traits(7,8). Its absence from empirical findingsmay simply be due to low incidence in the genetic control of complex traits(2,3), but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues(9). Here we show, using advanced computation(10) and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individualswith 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between commonSNPs influencing the expression of 238 genes (P < 2.91 x 10(-16)). Replication of these interactions in two independent data sets11,12 showed both concordance of direction of epistatic effects (P = 55.5 x 10(-31)) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P < 9.98 x 10(-5). Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions(13) (P=1.8x10(-10)). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype-phenotype maps for each cis-trans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.
C1 [Hemani, Gibran; Shakhbazov, Konstantin; McRae, Allan F.; Yang, Jian; Visscher, Peter M.; Powell, Joseph E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
   [Hemani, Gibran; Shakhbazov, Konstantin; McRae, Allan F.; Visscher, Peter M.; Powell, Joseph E.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4072, Australia.
   [Westra, Harm-Jan; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
   [Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
   [Esko, Tonu] Broad Inst, Cambridge, MA 02142 USA.
   [Esko, Tonu] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
   [Henders, Anjali K.; Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Gibson, Greg] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Gibson, Greg] Georgia Inst Technol, Ctr Integrat Genom, Atlanta, GA 30332 USA.
C3 University of Queensland; Princess Alexandra Hospital; University of Queensland; University of Groningen; University of Tartu; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; QIMR Berghofer Medical Research Institute; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology
RP Hemani, G (corresponding author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
EM g.hemani@uq.edu.au
FU Australian National Health and Medical Research Council (NHMRC) [389892, 496667, 613601, 1010374, 1046880]; Australian Research Council (ARC) [DE130100691]; National Institutes of Health (NIH) [GM057091, GM099568]; Australian National Health and Medical Research Council [389892, 241944, 389875, 389891, 389938, 442915, 442981, 496739, 496688, 552485]; National Institutes of Health [AA07535, AA10248, AA014041, AA13320, AA13321, AA13326, DA12854]; Georgia Institute of Technology Research Foundation; Celiac Disease Consortium [BSIK03009]; Netherlands Organization for Scientific Research [918.66.620, 916.10.135]; Dutch Digestive Disease Foundation [MLDS WO11-30]; Horizon Breakthrough grant from the Netherlands Genomics Initiative [92519031]; Prinses Beatrix Fonds; VSB fonds; Kersten Foundation; Netherlands ALS Foundation; J. R. van Dijk and the Adessium Foundation; European Communitys [259867]; Estonian Government [SF0180142s08]; Center of Excellence in Genomics (EXCEGEN); University of Tartu [SP1GVARENG]; Australian Research Council [DE130100691] Funding Source: Australian Research Council; Medical Research Council [G9815508, MC_PC_15018] Funding Source: researchfish
NR 39
TC 141
Z9 169
U1 0
U2 73
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 10
PY 2014
VL 508
IS 7495
BP 249
EP +
DI 10.1038/nature13005
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900045
PM 24572353
DA 2026-03-09
ER

PT J
AU Romiguier, J
   Gayral, P
   Ballenghien, M
   Bernard, A
   Cahais, V
   Chenuil, A
   Chiari, Y
   Dernat, R
   Duret, L
   Faivre, N
   Loire, E
   Lourenco, JM
   Nabholz, B
   Roux, C
   Tsagkogeorga, G
   Weber, AAT
   Weinert, LA
   Belkhir, K
   Bierne, N
   Glémin, S
   Galtier, N
AF Romiguier, J.
   Gayral, P.
   Ballenghien, M.
   Bernard, A.
   Cahais, V.
   Chenuil, A.
   Chiari, Y.
   Dernat, R.
   Duret, L.
   Faivre, N.
   Loire, E.
   Lourenco, J. M.
   Nabholz, B.
   Roux, C.
   Tsagkogeorga, G.
   Weber, A. A. -T.
   Weinert, L. A.
   Belkhir, K.
   Bierne, N.
   Glemin, S.
   Galtier, N.
TI Comparative population genomics in animals uncovers the determinants of genetic diversity
SO NATURE
LA English
DT Article
ID evolution
AB Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious(1,2). Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.
C1 [Romiguier, J.; Gayral, P.; Ballenghien, M.; Bernard, A.; Cahais, V.; Dernat, R.; Faivre, N.; Loire, E.; Lourenco, J. M.; Nabholz, B.; Roux, C.; Tsagkogeorga, G.; Weinert, L. A.; Belkhir, K.; Bierne, N.; Glemin, S.; Galtier, N.] Univ Montpellier 2, Inst Evolutionary Sci, CNRS, UMR 5554, F-34095 Montpellier, France.
   [Romiguier, J.; Roux, C.] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
   [Gayral, P.] Univ Tours, CNRS, UMR 7261, Inst Rech Biol Insecte, F-37200 Tours, France.
   [Chenuil, A.; Weber, A. A. -T.] Aix Marseille Univ, Inst Mediterraneen Biodivers & Ecol Marine & Cont, CNRS, IRD,UAPV, F-13007 Marseille, France.
   [Chiari, Y.] Univ S Alabama, Dept Biol, Mobile, AL 36688 USA.
   [Duret, L.] Univ Lyon 1, CNRS, UMR 5558, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France.
   [Tsagkogeorga, G.] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Weinert, L. A.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
C3 Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; CNRS - Institute of Ecology & Environment (INEE); University of Lausanne; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Tours; Institut de Recherche pour le Developpement (IRD); Avignon Universite; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; University of South Alabama; VetAgro Sup; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University of London; Queen Mary University London; University of Cambridge
RP Galtier, N (corresponding author), Univ Montpellier 2, Inst Evolutionary Sci, CNRS, UMR 5554, Pl E Bataillon, F-34095 Montpellier, France.
EM nicolas.galtier@univ-montp2.fr
FU European Research Council advanced grant [232971]; European Research Council (ERC) [232971] Funding Source: European Research Council (ERC)
NR 25
TC 446
Z9 502
U1 3
U2 376
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 261
EP U243
DI 10.1038/nature13685
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400049
PM 25141177
DA 2026-03-09
ER

PT J
AU Willerslev, E
   Davison, J
   Moora, M
   Zobel, M
   Coissac, E
   Edwards, ME
   Lorenzen, ED
   Vestergård, M
   Gussarova, G
   Haile, J
   Craine, J
   Gielly, L
   Boessenkool, S
   Epp, LS
   Pearman, PB
   Cheddadi, R
   Murray, D
   Bråthen, KA
   Yoccoz, N
   Binney, H
   Cruaud, C
   Wincker, P
   Goslar, T
   Alsos, IG
   Bellemain, E
   Brysting, AK
   Elven, R
   Sonstebo, JH
   Murton, J
   Sher, A
   Rasmussen, M
   Ronn, R
   Mourier, T
   Cooper, A
   Austin, J
   Möller, P
   Froese, D
   Zazula, G
   Pompanon, F
   Rioux, D
   Niderkorn, V
   Tikhonov, A
   Savvinov, G
   Roberts, RG
   MacPhee, RDE
   Gilbert, MTP
   Kjær, KH
   Orlando, L
   Brochmann, C
   Taberlet, P
AF Willerslev, Eske
   Davison, John
   Moora, Mari
   Zobel, Martin
   Coissac, Eric
   Edwards, Mary E.
   Lorenzen, Eline D.
   Vestergard, Mette
   Gussarova, Galina
   Haile, James
   Craine, Joseph
   Gielly, Ludovic
   Boessenkool, Sanne
   Epp, Laura S.
   Pearman, Peter B.
   Cheddadi, Rachid
   Murray, David
   Brathen, Kari Anne
   Yoccoz, Nigel
   Binney, Heather
   Cruaud, Corinne
   Wincker, Patrick
   Goslar, Tomasz
   Alsos, Inger Greve
   Bellemain, Eva
   Brysting, Anne Krag
   Elven, Reidar
   Sonstebo, Jorn Henrik
   Murton, Julian
   Sher, Andrei
   Rasmussen, Morten
   Ronn, Regin
   Mourier, Tobias
   Cooper, Alan
   Austin, Jeremy
   Moller, Per
   Froese, Duane
   Zazula, Grant
   Pompanon, Franois
   Rioux, Delphine
   Niderkorn, Vincent
   Tikhonov, Alexei
   Savvinov, Grigoriy
   Roberts, Richard G.
   MacPhee, Ross D. E.
   Gilbert, M. Thomas P.
   Kjaer, Kurt H.
   Orlando, Ludovic
   Brochmann, Christian
   Taberlet, Pierre
TI Fifty thousand years of Arctic vegetation and megafaunal diet
SO NATURE
LA English
DT Article
ID species richness estimators; perennially frozen loess; st-michael island; yukon-territory; radiocarbon chronology; mammoth-steppe; dna-sequences; plant; soil; climate
AB Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr BP (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25-15 kyr BP), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr BP, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.
C1 [Willerslev, Eske; Lorenzen, Eline D.; Vestergard, Mette; Haile, James; Rasmussen, Morten; Mourier, Tobias; Gilbert, M. Thomas P.; Kjaer, Kurt H.; Orlando, Ludovic] Univ Copenhagen, Nat Hist Museum, Ctr GeoGenet, DK-1350 Copenhagen K, Denmark.
   [Davison, John; Moora, Mari; Zobel, Martin] Univ Tartu, Inst Ecol & Earth Sci, Dept Bot, EE-51005 Tartu, Estonia.
   [Coissac, Eric; Gielly, Ludovic; Pompanon, Franois; Rioux, Delphine; Taberlet, Pierre] Univ Grenoble 1, UMR 5553, Lab Ecol Alpine LECA, CNRS, F-38041 Grenoble 9, France.
   [Edwards, Mary E.; Binney, Heather] Univ Southampton, Southampton SO17 1BJ, Hants, England.
   [Lorenzen, Eline D.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Gussarova, Galina; Boessenkool, Sanne; Epp, Laura S.; Bellemain, Eva; Elven, Reidar; Sonstebo, Jorn Henrik; Brochmann, Christian] Univ Oslo, Nat Hist Museum, Natl Ctr Biosystemat, NO-0318 Oslo, Norway.
   [Gussarova, Galina] St Petersburg State Univ, Dept Bot, St Petersburg 199034, Russia.
   [Haile, James] Murdoch Univ, Vet & Life Sci Sch, Ancient DNA Lab, Perth, WA 6150, Australia.
   [Craine, Joseph] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
   [Pearman, Peter B.] Swiss Fed Res Inst WSL, Landscape Dynam Unit, CH-8903 Birmensdorf, Switzerland.
   [Cheddadi, Rachid] Univ Montpellier 2, Inst Sci Evolut Montpellier, UMR 5554, F-34095 Montpellier 5, France.
   [Murray, David] Univ Alaska Museum North, Fairbanks, AK 99775 USA.
   [Brathen, Kari Anne; Yoccoz, Nigel] Arctic Univ Norway, Dept Arctic & Marine Biol, NO-9037 Tromso, Norway.
   [Cruaud, Corinne; Wincker, Patrick] CEA, Inst Genom, Genoscope, F-91000 Evry, France.
   [Goslar, Tomasz] Adam Mickiewicz Univ, Fac Phys, PL-61614 Poznan, Poland.
   [Goslar, Tomasz] Poznan Radiocarbon Lab, PL-61612 Poznan, Poland.
   [Alsos, Inger Greve] Tromso Univ Museum, NO-9037 Tromso, Norway.
   [Brysting, Anne Krag] Univ Oslo, Dept Biosci, Ctr Ecol & Evolutionary Synth, NO-0316 Oslo, Norway.
   [Murton, Julian] Univ Sussex, Dept Geog, Permafrost Lab, Brighton BN1 9QJ, E Sussex, England.
   [Sher, Andrei] Russian Acad Sci, Inst Ecol & Evolut, Moscow 119071, Russia.
   [Ronn, Regin] Terr Ecol, Dept Biol, DK-2100 Copenhagen O, Denmark.
   [Cooper, Alan; Austin, Jeremy] Univ Adelaide, Sch Earth & Environm Sci, Australian Ctr Ancient DNA, Adelaide, SA 5005, Australia.
   [Moller, Per] Lund Univ, Dept Geol Quaternary Sci, SE-22362 Lund, Sweden.
   [Froese, Duane] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Zazula, Grant] Govt Yukon, Dept Tourism & Culture, Yukon Palaeontol Program, Whitehorse, YT Y1A 2C6, Canada.
   [Niderkorn, Vincent] INRA, Herbivores UMR1213, F-63122 St Genes Champanelle, France.
   [Tikhonov, Alexei] Russian Acad Sci, Inst Zool, St Petersburg 199034, Russia.
   [Savvinov, Grigoriy] North Eastern Fed Univ, Inst Appl Ecol North, Yakutsk 677000, Russia.
   [Roberts, Richard G.] Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [MacPhee, Ross D. E.] Amer Museum Nat Hist, Div Vertebrate Zool Mammal, New York, NY 10024 USA.
C3 University of Copenhagen; University of Tartu; Tartu University Institute of Ecology & Earth Sciences; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universite Savoie Mont Blanc; University of Southampton; University of California System; University of California Berkeley; University of Oslo; Saint Petersburg State University; Murdoch University; Kansas State University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; UiT The Arctic University of Tromso; CEA; Adam Mickiewicz University; UiT The Arctic University of Tromso; University of Oslo; University of Sussex; Russian Academy of Sciences; Adelaide University; University of Adelaide; Lund University; University of Alberta; VetAgro Sup; INRAE; Russian Academy of Sciences; Zoological Institute of the Russian Academy of Sciences; North-Eastern Federal University in Yakutsk; University of Wollongong; American Museum of Natural History (AMNH)
RP Willerslev, E (corresponding author), Univ Copenhagen, Nat Hist Museum, Ctr GeoGenet, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
EM ewillerslev@snm.ku.dk
FU European Union [GOCE-2006-036866]; Danish National Research Foundation (Centre of Excellence); European Regional Development Fund (Centre of Excellence FIBIR); European Regional Development Fund [IUT 20-28]; Research Council of Norway [191627/V40]; Australian Research Council [DP0558446]; Marie Curie International Outgoing Fellowship [PIOF-GA-2009-253376]; Carlsberg Foundation; Lundbeck Foundation [R109-2012-9995, R24-2008-2527, R155-2013-16338, R70-2010-6286, R38-2008-3048] Funding Source: researchfish; Australian Research Council [DP0558446] Funding Source: Australian Research Council
NR 108
TC 456
Z9 532
U1 7
U2 528
PU NATURE PUBLISHING 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 6
PY 2014
VL 506
IS 7486
BP 47
EP +
DI 10.1038/nature12921
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100028
PM 24499916
DA 2026-03-09
ER

PT J
AU Kumazaki, K
   Chiba, S
   Takemoto, M
   Furukawa, A
   Nishiyama, K
   Sugano, Y
   Mori, T
   Dohmae, N
   Hirata, K
   Nakada-Nakura, Y
   Maturana, AD
   Tanaka, Y
   Mori, H
   Sugita, Y
   Arisaka, F
   Ito, K
   Ishitani, R
   Tsukazaki, T
   Nureki, O
AF Kumazaki, Kaoru
   Chiba, Shinobu
   Takemoto, Mizuki
   Furukawa, Arata
   Nishiyama, Ken-ichi
   Sugano, Yasunori
   Mori, Takaharu
   Dohmae, Naoshi
   Hirata, Kunio
   Nakada-Nakura, Yoshiko
   Maturana, Andres D.
   Tanaka, Yoshiki
   Mori, Hiroyuki
   Sugita, Yuji
   Arisaka, Fumio
   Ito, Koreaki
   Ishitani, Ryuichiro
   Tsukazaki, Tomoya
   Nureki, Osamu
TI Structural basis of Sec-independent membrane protein insertion by YidC
SO NATURE
LA English
DT Article
ID escherichia-coli yidc; molecular-dynamics; subunit; translocation; biogenesis; validation; requires; receptor; features; regions
AB Newly synthesized membrane proteins must be accurately inserted into the membrane, folded and assembled for proper functioning. The protein YidC inserts its substrates into the membrane, thereby facilitating membrane protein assembly in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in mitochondria and chloroplasts, respectively(1,2). In the bacterial cytoplasmic membrane, YidC functions as an independent insertase and a membrane chaperone in cooperation with the translocon SecYEG(3-5). Here we present the crystal structure of YidC from Bacillus halodurans, at 2.4 angstrom resolution. The structure reveals a novel fold, in which five conserved transmembrane helices form a positively charged hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm but closed on the extracellular side. Structure-based in vivo analyses reveal that a conserved arginine residue in the groove is important for the insertion of membrane proteins by YidC. We propose an insertion mechanism for single-spanning membrane proteins, in which the hydrophilic environment generated by the groove recruits the extracellular regions of substrates into the low-dielectric environment of the membrane.
C1 [Kumazaki, Kaoru; Takemoto, Mizuki; Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Kumazaki, Kaoru; Takemoto, Mizuki; Dohmae, Naoshi; Ishitani, Ryuichiro; Nureki, Osamu] RIKEN, Global Res Cluster, Wako, Saitama 3510198, Japan.
   [Chiba, Shinobu; Ito, Koreaki] Kyoto Sangyo Univ, Fac Life Sci, Kita Ku, Kyoto 6038555, Japan.
   [Furukawa, Arata; Sugano, Yasunori; Tanaka, Yoshiki; Tsukazaki, Tomoya] Nara Inst Sci & Technol, Dept Syst Biol, Grad Sch Biol Sci, Nara 6300192, Japan.
   [Nishiyama, Ken-ichi] Iwate Univ, Fac Agr, Cryobiofrontier Res Ctr, Morioka, Iwate 0208550, Japan.
   [Sugano, Yasunori; Mori, Takaharu; Sugita, Yuji] RIKEN, Theoret Mol Sci Lab, Wako, Saitama 3510198, Japan.
   [Hirata, Kunio] RIKEN SPring 8 Ctr, SR Life Sci Instrumentat Unit, Sayo, Hyogo 6795148, Japan.
   [Nakada-Nakura, Yoshiko] Kyoto Univ, Dept Cell Biol, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan.
   [Maturana, Andres D.] Nagoya Univ, Grad Sch Bioagr Sci, Dept Bioengn Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Mori, Hiroyuki] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan.
   [Arisaka, Fumio] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Midori Ku, Yokohama, Kanagawa 2268503, Japan.
   [Tsukazaki, Tomoya] PRESTO, JST, Kawaguchi, Saitama 3320012, Japan.
C3 University of Tokyo; RIKEN; Kyoto Sangyo University; Nara Institute of Science & Technology; Iwate University; RIKEN; RIKEN; Kyoto University; Nagoya University; Kyoto University; Institute of Science Tokyo; Tokyo Institute of Technology; Japan Science & Technology Agency (JST)
RP Nureki, O (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM ttsukaza@bs.naist.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 [20247020, 20523517, 24687016, 24102503, 24121704, 24227004, 24657095, 25291006, 25291009, 25660073]; FIRST; PRESTO; JST; MEXT; Private University Strategic Research Foundation Support Program (MEXT); Nagase Science and Technology Foundation; Astellas Foundation for Research on Metabolic Disorders; Grants-in-Aid for Scientific Research [24657095, 26102532, 20247020, 24687016, 24102503, 22117007, 26102703, 24121704, 26119701, 13J08353, 24117003, 23570190, 26291023, 25660073] Funding Source: KAKEN
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NR 50
TC 183
Z9 214
U1 2
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 MAY 22
PY 2014
VL 509
IS 7501
BP 516
EP +
DI 10.1038/nature13167
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000044
PM 24739968
DA 2026-03-09
ER

PT J
AU Suez, J
   Korem, T
   Zeevi, D
   Zilberman-Schapira, G
   Thaiss, CA
   Maza, O
   Israeli, D
   Zmora, N
   Gilad, S
   Weinberger, A
   Kuperman, Y
   Harmelin, A
   Kolodkin-Gal, I
   Shapiro, H
   Halpern, Z
   Segal, E
   Elinav, E
AF Suez, Jotham
   Korem, Tal
   Zeevi, David
   Zilberman-Schapira, Gili
   Thaiss, Christoph A.
   Maza, Ori
   Israeli, David
   Zmora, Niv
   Gilad, Shlomit
   Weinberger, Adina
   Kuperman, Yael
   Harmelin, Alon
   Kolodkin-Gal, Ilana
   Shapiro, Hagit
   Halpern, Zamir
   Segal, Eran
   Elinav, Eran
TI Artificial sweeteners induce glucose intolerance by altering the gut microbiota
SO NATURE
LA English
DT Article
ID frequency questionnaire ffq; food frequency; in-vivo; diet; aspartame; obesity; health; association; metabolism; metagenome
AB Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.
C1 [Suez, Jotham; Zilberman-Schapira, Gili; Thaiss, Christoph A.; Maza, Ori; Shapiro, Hagit; Elinav, Eran] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Korem, Tal; Zeevi, David; Weinberger, Adina; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Israeli, David] Kfar Shaul Hosp, Jerusalem Ctr Mental Hlth, Day Care Unit, IL-91060 Jerusalem, Israel.
   [Israeli, David] Kfar Shaul Hosp, Jerusalem Ctr Mental Hlth, Lab Imaging & Brain Stimulat, IL-91060 Jerusalem, Israel.
   [Zmora, Niv] Tel Aviv Sourasky Med Ctr, Dept Internal Med, IL-64239 Tel Aviv, Israel.
   [Zmora, Niv; Halpern, Zamir] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Res Ctr Digest Tract & Liver Dis, IL-69978 Tel Aviv, Israel.
   [Zmora, Niv; Halpern, Zamir] Tel Aviv Sourasky Med Ctr, Digest Ctr, IL-64239 Tel Aviv, Israel.
   [Gilad, Shlomit] Weizmann Inst Sci, Nancy & Stephen Grand Israel Natl Ctr Personalize, IL-76100 Rehovot, Israel.
   [Kuperman, Yael; Harmelin, Alon] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel.
   [Kolodkin-Gal, Ilana] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Hebrew University of Jerusalem; Jerusalem Mental Health Center; Hebrew University of Jerusalem; Jerusalem Mental Health Center; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science
RP Segal, E (corresponding author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
EM eran.segal@weizmann.ac.il; eran.elinav@weizmann.ac.il
FU Weizmann Institute management; Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM); Boehringer Ingelheim Fonds PhD Fellowship; Morris Kahn Fellowships for Systems Biology; National Institute of Health (NIH); European Research Council (ERC); Abisch 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; estate of J. Gitlitz; estate of L. Hershkovich; Rising Tide foundation; Minerva Stiftung foundation; European Research Council
NR 40
TC 1269
Z9 1396
U1 43
U2 1339
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2014
VL 514
IS 7521
BP 181
EP +
DI 10.1038/nature13793
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100032
DA 2026-03-09
ER

PT J
AU Fink, AJP
   Croce, KR
   Huang, ZJ
   Abbott, LF
   Jessell, TM
   Azim, E
AF Fink, Andrew J. P.
   Croce, Katherine R.
   Huang, Z. Josh
   Abbott, L. F.
   Jessell, Thomas M.
   Azim, Eiman
TI Presynaptic inhibition of spinal sensory feedback ensures smooth movement
SO NATURE
LA English
DT Article
ID gamma-aminobutyric-acid; cord; neurons; afferent; cells; muscle; cortex; depolarization; transmission; circuits
AB The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits. One specialized set of spinal GABAergic interneurons forms axo-axonic contacts with the central terminals of sensory afferents, exerting presynaptic inhibitory control over sensory-motor transmission. The inability to achieve selective access to the GABAergic neurons responsible for this unorthodox inhibitory mechanism has left unresolved the contribution of presynaptic inhibition to motor behaviour. We used Gad2 as a genetic entry point to manipulate the interneurons that contact sensory terminals, and show that activation of these interneurons in mice elicits the defining physiological characteristics of presynaptic inhibition. Selective genetic ablation of Gad2-expressing interneurons severely perturbs goal-directed reaching movements, uncovering a pronounced and stereotypic forelimb motor oscillation, the core features of which are captured by modelling the consequences of sensory feedback at high gain. Our findings define the neural substrate of a genetically hardwired gain control system crucial for the smooth execution of movement.
C1 [Fink, Andrew J. P.; Croce, Katherine R.; Jessell, Thomas M.; Azim, Eiman] Columbia Univ, Howard Hughes Med Inst, Mortimer B Zuckerman Mind Brain Behav Inst, Kavli Inst Brain Sci,Dept Neurosci, New York, NY 10032 USA.
   [Fink, Andrew J. P.; Croce, Katherine R.; Jessell, Thomas M.; Azim, Eiman] Columbia Univ, Howard Hughes Med Inst, Mortimer B Zuckerman Mind Brain Behav Inst, Kavli Inst Brain Sci,Dept Biochem, New York, NY 10032 USA.
   [Fink, Andrew J. P.; Croce, Katherine R.; Jessell, Thomas M.; Azim, Eiman] Columbia Univ, Howard Hughes Med Inst, Mortimer B Zuckerman Mind Brain Behav Inst, Kavli Inst Brain Sci,Dept Mol Biophys, New York, NY 10032 USA.
   [Huang, Z. Josh] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Abbott, L. F.] Columbia Univ, Ctr Theoret Neurosci, Dept Physiol, New York, NY 10032 USA.
   [Abbott, L. F.] Columbia Univ, Ctr Theoret Neurosci, Dept Neurosci, New York, NY 10032 USA.
C3 Howard Hughes Medical Institute; Columbia University; Columbia University; Howard Hughes Medical Institute; Howard Hughes Medical Institute; Columbia University; Cold Spring Harbor Laboratory; Columbia University; Columbia University
RP Jessell, TM (corresponding author), Columbia Univ, Howard Hughes Med Inst, Mortimer B Zuckerman Mind Brain Behav Inst, Kavli Inst Brain Sci,Dept Neurosci, New York, NY 10032 USA.
EM af2243@columbia.edu; tmj1@columbia.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NICHD NIH HHS [T32 HD007430] Funding Source: Medline; NIMH NIH HHS [R01 MH093338, U01 MH078844, MH093338, MH078844] Funding Source: Medline; NINDS NIH HHS [R01 NS080932, R37 NS033245, NS033245, R01 NS033245] Funding Source: Medline
NR 57
TC 191
Z9 228
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 MAY 1
PY 2014
VL 509
IS 7498
BP 43
EP +
DI 10.1038/nature13276
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100036
PM 24784215
DA 2026-03-09
ER

PT J
AU Huerta-Sánchez, E
   Jin, X
   Asan
   Bianba, Z
   Peter, BM
   Vinckenbosch, N
   Liang, Y
   Yi, X
   He, MZ
   Somel, M
   Ni, PX
   Wang, B
   Ou, XH
   Huasang
   Luosang, JB
   Cuo, ZXP
   Li, K
   Gao, GY
   Yin, Y
   Wang, W
   Zhang, XQ
   Xu, X
   Yang, HM
   Li, YR
   Wang, J
   Wang, J
   Nielsen, R
AF Huerta-Sanchez, Emilia
   Jin, Xin
   Asan
   Bianba, Zhuoma
   Peter, Benjamin M.
   Vinckenbosch, Nicolas
   Liang, Yu
   Yi, Xin
   He, Mingze
   Somel, Mehmet
   Ni, Peixiang
   Wang, Bo
   Ou, Xiaohua
   Huasang
   Luosang, Jiangbai
   Cuo, Zha Xi Ping
   Li, Kui
   Gao, Guoyi
   Yin, Ye
   Wang, Wei
   Zhang, Xiuqing
   Xu, Xun
   Yang, Huanming
   Li, Yingrui
   Wang, Jian
   Wang, Jun
   Nielsen, Rasmus
TI Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA
SO NATURE
LA English
DT Article
ID hemoglobin concentration; positive selection; genome sequence; recombination; samples; pigmentation; pregnancy; ancestry; signals
AB As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau(1-3). A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans(4-10), and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.
C1 [Huerta-Sanchez, Emilia; Jin, Xin; Asan; Liang, Yu; Yi, Xin; He, Mingze; Somel, Mehmet; Ni, Peixiang; Wang, Bo; Ou, Xiaohua; Huasang; Luosang, Jiangbai; Yin, Ye; Wang, Wei; Zhang, Xiuqing; Xu, Xun; Yang, Huanming; Li, Yingrui; Wang, Jian; Wang, Jun; Nielsen, Rasmus] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Huerta-Sanchez, Emilia; Peter, Benjamin M.; Vinckenbosch, Nicolas; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Huerta-Sanchez, Emilia] Univ Calif, Sch Nat Sci, Merced, CA 95343 USA.
   [Jin, Xin] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510006, Guangdong, Peoples R China.
   [Asan; Liang, Yu; Yi, Xin] BGI Tianjin, Binhai Genom Inst, Tianjin 300308, Peoples R China.
   [Asan; Liang, Yu; Yi, Xin] BGI Tianjin, Tianjin Translat Genom Ctr, Tianjin 300308, Peoples R China.
   [Bianba, Zhuoma] Peoples Hosp Lhasa, Lhasa 850000, Peoples R China.
   [He, Mingze] Iowa State Univ, Bioinformat & Computat Biol Program, Ames, IA 50011 USA.
   [Somel, Mehmet] Middle E Tech Univ, Dept Biol Sci, TR-06800 Ankara, Turkey.
   [Cuo, Zha Xi Ping] Second Peoples Hosp Tibet Autonomous Reg, Lhasa 850000, Peoples R China.
   [Li, Kui] Peoples Hosp Tibet Autonomous Reg, Lhasa 850000, Peoples R China.
   [Gao, Guoyi] Hosp XiShuangBanNa Dai Nationalities, Autonomous Jinghong 666100, Yunnan, Peoples R China.
   [Zhang, Xiuqing] BGI Shenzhen, Guangdong Enterprise Key Lab Human Dis Genom, Shenzhen 518083, Peoples R China.
   [Zhang, Xiuqing] BGI Shenzhen, Shenzhen Key Lab Trans Biotechnol, Shenzhen 518083, Peoples R China.
   [Yang, Huanming; Wang, Jun] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21589, Saudi Arabia.
   [Yang, Huanming; Wang, Jian] James D Watson Inst Genome Sci, Hangzhou 310008, Zhejiang, Peoples R China.
   [Wang, Jun; Nielsen, Rasmus] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China.
   [Wang, Jun] Univ Hong Kong, Dept Med, Hong Kong 999077, Hong Kong, Peoples R China.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
C3 Beijing Genomics Institute (BGI); University of California System; University of California Berkeley; University of California System; University of California Merced; South China University of Technology; Beijing Genomics Institute (BGI); Beijing Genomics Institute (BGI); Iowa State University; Middle East Technical University; Beijing Genomics Institute (BGI); Beijing Genomics Institute (BGI); King Abdulaziz University; University of Copenhagen; Macau University of Science & Technology; University of Hong Kong; University of California System; University of California Berkeley
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM wangjian@genomics.cn; wangj@genomics.cn; rasmus_nielsen@berkeley.edu
FU 973 Program [2011CB809203, 2012CB518201, 2011CB809201, 2011CB809202]; State Key Development Program for Basic Research of China; China National GeneBank-Shenzhen; Shenzhen Key Laboratory of Transomics Biotechnologies [CXB201108250096A]; US NIH [R01HG003229, R01HG003229-08S2]
NR 43
TC 782
Z9 950
U1 11
U2 612
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 14
PY 2014
VL 512
IS 7513
BP 194
EP +
DI 10.1038/nature13408
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700032
PM 25043035
DA 2026-03-09
ER

PT J
AU Carazo, P
   Tan, CKW
   Allen, F
   Wigby, S
   Pizzari, T
AF Carazo, Pau
   Tan, Cedric K. W.
   Allen, Felicity
   Wigby, Stuart
   Pizzari, Tommaso
TI Within-group male relatedness reduces harm to females in Drosophila
SO NATURE
LA English
DT Article
ID sexual conflict; kin selection; competition; peptide; melanogaster; aggression; responses; evolution; exposure; fitness
AB To resolve the mechanisms that switch competition to cooperation is key to understanding biological organization(1). This is particularly relevant for intrasexual competition, which often leads to males harming females(2). Recent theory proposes that kin selection may modulate female harm by relaxing competition among male relatives(3-5). Here we experimentally manipulate the relatedness of groups of male Drosophila melanogaster competing over females to demonstrate that, as expected, within-group relatedness inhibits male competition and female harm. Females exposed to groups of three brothers unrelated to the female had higher lifetime reproductive success and slower reproductive ageing compared to females exposed to groups of three males unrelated to each other. Triplets of brothers also fought less with each other, courted females less intensively and lived longer than triplets of unrelated males. However, associations among brothers may be vulnerable to invasion by minorities of unrelated males: when two brothers were matched with an unrelated male, the unrelated male sired on average twice as many offspring as either brother. These results demonstrate that relatedness can profoundly affect fitness through its modulation of intrasexual competition, as flies plastically adjust sexual behaviour in a manner consistent with kin-selection theory.
C1 [Carazo, Pau; Tan, Cedric K. W.; Allen, Felicity; Wigby, Stuart; Pizzari, Tommaso] Univ Oxford, Dept Zool, Edward Grey Inst, Oxford OX1 3PS, England.
C3 University of Oxford
RP Pizzari, T (corresponding author), Univ Oxford, Dept Zool, Edward Grey Inst, S Parks Rd, Oxford OX1 3PS, England.
EM tommaso.pizzari@zoo.ox.ac.uk
FU Marie Curie fellowship [PIEF-GA-2010-273010]; Wellcome Trust VIP award; NERC; Leverhulme Trust; BBSRC [BB/K014544/1] Funding Source: UKRI; NERC [NE/H008047/1, NE/J018937/1, NE/D003865/1, NE/D002788/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K014544/1] Funding Source: researchfish; Natural Environment Research Council [NE/J018937/1, NE/D002788/1, NE/C507196/1, NE/D003865/1, NE/H008047/1] Funding Source: researchfish
NR 43
TC 67
Z9 73
U1 0
U2 97
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 30
PY 2014
VL 505
IS 7485
BP 672
EP +
DI 10.1038/nature12949
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000039
PM 24463521
DA 2026-03-09
ER

PT J
AU Yamashita, A
   Morioka, M
   Kishi, H
   Kimura, T
   Yahara, Y
   Okada, M
   Fujita, K
   Sawai, H
   Ikegawa, S
   Tsumaki, N
AF Yamashita, Akihiro
   Morioka, Miho
   Kishi, Hiromi
   Kimura, Takeshi
   Yahara, Yasuhito
   Okada, Minoru
   Fujita, Kaori
   Sawai, Hideaki
   Ikegawa, Shiro
   Tsumaki, Noriyuki
TI Statin treatment rescues FGFR3 skeletal dysplasia phenotypes
SO NATURE
LA English
DT Article
ID growth-factor receptor-3; achondroplasia; mutations; apoptosis; mice; activation; expression; cartilage; dwarfism; peptide
AB Gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3) result in skeletal dysplasias, such as thanatophoric dysplasia and achondroplasia (ACH). The lack of disease models using human cells has hampered the identification of a clinically effective treatment for these diseases. Here we show that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia. We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs. Treatment of ACH model mice with statin led to a significant recovery of bone growth. These results suggest that statins could represent a medical treatment for infants and children with TD1 and ACH.
C1 [Yamashita, Akihiro; Morioka, Miho; Kishi, Hiromi; Kimura, Takeshi; Yahara, Yasuhito; Okada, Minoru; Fujita, Kaori; Tsumaki, Noriyuki] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Cell Induct & Regulat Field, Kyoto 6068507, Japan.
   [Kimura, Takeshi] Osaka Univ, Grad Sch Med, Dept Pediat, Suita, Osaka 5650871, Japan.
   [Sawai, Hideaki] Hyogo Coll Med, Dept Obstet & Gynecol, Nishinomiya, Hyogo 6638501, Japan.
   [Ikegawa, Shiro] RIKEN, Ctr Integrated Med Sci, Lab Bone & Joint Dis, Tokyo 1088639, Japan.
   [Tsumaki, Noriyuki] Japan Sci & Technol Agcy, CREST, Tokyo 1020075, Japan.
C3 Kyoto University; University of Osaka; Hyogo Medical University; RIKEN; Japan Science & Technology Agency (JST)
RP Tsumaki, N (corresponding author), Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Cell Induct & Regulat Field, Kyoto 6068507, Japan.
EM ntsumaki@cira.kyoto-u.ac.jp
FU Japan Science Technology Agency (JST), CREST; Research Center Network for Realization of Regenerative Medicine; MEXT [24890101, 26861716, 24390354]; Grants-in-Aid for Scientific Research [24890101, 26861716, 24390354] Funding Source: KAKEN
NR 35
TC 159
Z9 189
U1 0
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 SEP 25
PY 2014
VL 513
IS 7519
BP 507
EP +
DI 10.1038/nature13775
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800031
PM 25231866
DA 2026-03-09
ER

PT J
AU Zirnsak, M
   Steinmetz, NA
   Noudoost, B
   Xu, KZ
   Moore, T
AF Zirnsak, Marc
   Steinmetz, Nicholas A.
   Noudoost, Behrad
   Xu, Kitty Z.
   Moore, Tirin
TI Visual space is compressed in prefrontal cortex before eye movements
SO NATURE
LA English
DT Article
ID peri-saccadic perception; macaque area v4; spatial attention; receptive-fields; frontal-cortex; bottom-up; neurons; signals; search; target
AB We experience the visual world through a series of saccadic eye movements, each one shifting our gaze to bring objects of interest to the fovea for further processing. Although such movements lead to frequent and substantial displacements of the retinal image, these displacements go unnoticed. It is widely assumed that a primary mechanism underlying this apparent stability is an anticipatory shifting of visual receptive fields (RFs) from their presaccadic to their post-saccadic locations before movement onset(1). Evidence of this predictive 'remapping' of RFs has been particularly apparent within brain structures involved in gaze control(2-4). However, critically absent among that evidence are detailed measurements of visual RFs before movement onset. Here we show that during saccade preparation, rather than remap, RFs of neurons in a prefrontal gaze control area massively converge towards the saccadic target. We mapped the visual RFs of prefrontal neurons during stable fixation and immediately before the onset of eye movements, using multi-electrode recordings in monkeys. Following movements from an initial fixation point to a target, RFs remained stationary in retinocentric space. However, in the period immediately before movement onset, RFs shifted by as much as 18 degrees of visual angle, and converged towards the target location. This convergence resulted in a threefold increase in the proportion of RFs responding to stimuli near the target region. In addition, like in human observers(5,6), the population of prefrontal neurons grossly mislocalized presaccadic stimuli as being closer to the target. Our results show that RF shifts do not predict the retinal displacements due to saccades, but instead reflect the overriding perception of target space during eye movements.
C1 [Zirnsak, Marc; Steinmetz, Nicholas A.; Noudoost, Behrad; Xu, Kitty Z.; Moore, Tirin] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
   [Zirnsak, Marc; Moore, Tirin] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute
RP Zirnsak, M (corresponding author), Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
EM mzirnsak@stanford.edu
FU National Institutes of Health [EY014924]; Howard Hughes Medical Institute; National Eye Institute [R01EY014924] Funding Source: NIH RePORTER; National Institute of Mental Health; National Institute on Aging; National Institute of General Medical Sciences [T32MH020016] Funding Source: NIH RePORTER
NR 36
TC 165
Z9 191
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 MAR 27
PY 2014
VL 507
IS 7493
BP 504
EP +
DI 10.1038/nature13149
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000042
PM 24670771
DA 2026-03-09
ER

PT J
AU Kiuchi, T
   Koga, H
   Kawamoto, M
   Shoji, K
   Sakai, H
   Arai, Y
   Ishihara, G
   Kawaoka, S
   Sugano, S
   Shimada, T
   Suzuki, Y
   Suzuki, MG
   Katsuma, S
AF Kiuchi, Takashi
   Koga, Hikaru
   Kawamoto, Munetaka
   Shoji, Keisuke
   Sakai, Hiroki
   Arai, Yuji
   Ishihara, Genki
   Kawaoka, Shinpei
   Sugano, Sumio
   Shimada, Toru
   Suzuki, Yutaka
   Suzuki, Masataka G.
   Katsuma, Susumu
TI A single female-specific piRNA is the primary determiner of sex in the silkworm
SO NATURE
LA English
DT Article
ID w-chromosome; bombyx-mori; rna; expression; system; gene; identification; translocation; amplification; transposons
AB The silkworm Bombyx mori uses a WZ sex determination system that is analogous to the one found in birds and some reptiles. In this system, males have two Z sex chromosomes, whereas females have Z and W sex chromosomes. The silkworm W chromosome has a dominant role in female determination(1,2), suggesting the existence of a dominant feminizing gene in this chromosome. However, the W chromosomeis almost fully occupied by transposable element sequences(3-5), and no functional protein-coding gene has been identified so far. Female-enriched PIWI-interacting RNAs (piRNAs) are the only known transcripts that are produced from the sex-determining region of the W chromosome(6), but the function(s) of these piRNAs are unknown. Here we show that a W-chromosome-derived, female-specific piRNA is the feminizing factor of B. mori. This piRNA is produced from a piRNA precursor which we named Fem. Fem sequences were arranged in tandem in the sex-determining region of the W chromosome. Inhibition of Fem-derived piRNA-mediated signalling in female embryos led to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the downstream end of the sex differentiation cascade(7,8). A target gene of Fem-derived piRNA was identified on the Z chromosome of B. mori. This gene, which we named Masc, encoded a CCCH-type zinc finger protein. We show that the silencing of Masc messenger RNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos, and that Masc protein controls both dosage compensation and masculinization in male embryos. Our study characterizes a single small RNA that is responsible for primary sex determination in the WZ sex determination system.
C1 [Kiuchi, Takashi; Koga, Hikaru; Kawamoto, Munetaka; Shoji, Keisuke; Arai, Yuji; Ishihara, Genki; Kawaoka, Shinpei; Shimada, Toru; Katsuma, Susumu] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Agr & Environm Biol, Bunkyo Ku, Tokyo 1138657, Japan.
   [Sakai, Hiroki; Suzuki, Masataka G.] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Kashiwa, Chiba 2778562, Japan.
   [Sugano, Sumio; Suzuki, Yutaka] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Minato Ku, Tokyo 1088639, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo
RP Katsuma, S (corresponding author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Agr & Environm Biol, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan.
EM katsuma@ss.ab.a.u-tokyo.ac.jp
FU Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry;  [22115502];  [22128004]; Grants-in-Aid for Scientific Research [22128004, 26292172] Funding Source: KAKEN
NR 37
TC 410
Z9 473
U1 12
U2 269
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2014
VL 509
IS 7502
BP 633
EP +
DI 10.1038/nature13315
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100051
PM 24828047
DA 2026-03-09
ER

PT J
AU Liu, Y
   Samuel, BS
   Breen, PC
   Ruvkun, G
AF Liu, Ying
   Samuel, Buck S.
   Breen, Peter C.
   Ruvkun, Gary
TI Caenorhabditis elegans pathways that surveil and defend mitochondria
SO NATURE
LA English
DT Article
ID unfolded protein response; c-elegans; ceramide synthase; apoptosis; activation; longevity; stress; upr
AB Mitochondrial function is challenged by toxic by-products of metabolism as well as by pathogen attack(1,2). Caenorhabditis elegans normally responds to mitochondrial dysfunction with activation of mitochondrial-repair, drug-detoxification and pathogen-response pathways(1-7). Here, from a genome-wide RNA interference (RNAi) screen, we identified 45 C. elegans genes that are required to upregulate detoxification, pathogen-response and mitochondrial-repair pathways after inhibition of mitochondrial function by drug-induced or genetic disruption. Animals defective in ceramide biosynthesis are deficient in mitochondrial surveillance, and addition of particular ceramides can rescue the surveillance defects. Ceramide can also rescue the mitochondrial surveillance defects of other gene inactivations, mapping these gene activities upstream of ceramide. Inhibition of the mevalonate pathway, either by RNAi or statin drugs, also disrupts mitochondrial surveillance. Growth of C. elegans with a significant fraction of bacterial species from their natural habitat causes mitochondrial dysfunction. Other bacterial species inhibit C. elegans defence responses to a mitochondrial toxin, revealing bacterial countermeasures to animal defence.
C1 [Liu, Ying; Samuel, Buck S.; Breen, Peter C.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Liu, Ying; Samuel, Buck S.; Breen, Peter C.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Ruvkun, G (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU Helen Hay Whitney research fellowship; Charles King Trust postdoctoral fellowship; National Institutes of Health [NIH AG043184-16]; National Institute on Aging [R01AG043184] Funding Source: NIH RePORTER
CR Benedetti C, 2006, GENETICS, V174, P229, DOI 10.1534/genetics.106.061580
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NR 24
TC 258
Z9 301
U1 2
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 APR 17
PY 2014
VL 508
IS 7496
BP 406
EP +
DI 10.1038/nature13204
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000054
PM 24695221
DA 2026-03-09
ER

PT J
AU Gill, PG
   Purnell, MA
   Crumpton, N
   Brown, KR
   Gostling, NJ
   Stampanoni, M
   Rayfield, EJ
AF Gill, Pamela G.
   Purnell, Mark A.
   Crumpton, Nick
   Brown, Kate Robson
   Gostling, Neil J.
   Stampanoni, M.
   Rayfield, Emily J.
TI Dietary specializations and diversity in feeding ecology of the earliest stem mammals
SO NATURE
LA English
DT Article
ID microwear texture analysis; finite-element-analysis; dental microwear; bite force; evolution; behavior; hardness; bats; diversification; discrimination
AB The origin and radiation of mammals are key events in the history of life, with fossils placing the origin at 220 million years ago, in the Late Triassic period(1). The earliest mammals, representing the first 50 million years of their evolution and including the most basal taxa, are widely considered to be generalized insectivores(1,2). This implies that the first phase of the mammalian radiation-associated with the appearance in the fossil record of important innovations such as heterodont dentition, diphyodonty and the dentary-squamosal jaw joint(1,3)-was decoupled from ecomorphological diversification(2,4). Finds of exceptionally complete specimens of later Mesozoic mammals have revealed greater ecomorphological diversity than previously suspected, including adaptations for swimming, burrowing, digging and even gliding(2,5,6), but such well-preserved fossils of earlier mammals do not exist(1), and robust analysis of their ecomorphological diversity has previously been lacking. Here we present the results of an integrated analysis, using synchrotron X-ray tomography and analyses of biomechanics, finite element models and tooth microwear textures. We find significant differences in function and dietary ecology between two of the earliest mammalia form taxa, Morganucodon and Kuehneotherium-taxa that are central to the debate on mammalian evolution. Morganucodon possessed comparatively more forceful and robust jaws and consumed 'harder' prey, comparable to extant small bodied mammals that eat considerable amounts of coleopterans. Kuehneotherium ingested a diet comparable to extant mixed feeders and specialists on 'soft' prey such as lepidopterans. Our results reveal previously hidden trophic specialization at the base of the mammalian radiation; hence even the earliest mammalia forms were beginning to diversify-morphologically, functionally and ecologically. In contrast to the prevailing view(2,4), this pattern suggests that lineage splitting during the earliest stages of mammalian evolution was associated with ecomorphological specialization and niche partitioning.
C1 [Gill, Pamela G.; Crumpton, Nick; Gostling, Neil J.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Purnell, Mark A.] Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
   [Brown, Kate Robson] Univ Bristol, Dept Archaeol & Anthropol, Bristol BS8 1UU, Avon, England.
   [Stampanoni, M.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Stampanoni, M.] Univ Zurich, Inst Biomed Engn, CH-8092 Zurich, Switzerland.
   [Stampanoni, M.] Swiss Fed Inst Technol, CH-8092 Zurich, Switzerland.
   [Rayfield, Emily J.] Univ Bristol, Sch Earth Sci, Bristol BS8 1TQ, Avon, England.
C3 University of Bristol; University of Leicester; University of Bristol; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Bristol
RP Gill, PG (corresponding author), Univ Bristol, Sch Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM pam.gill@bristol.ac.uk; e.rayfield@bristol.ac.uk
FU Natural Environment Research Council [NE/E010431/1, NE/K01496X/1]; European Commission [RII3-CT-2004-506008];  [NE/G018189/1]; NERC [NE/K01496X/1, NE/E010431/1, NE/G018189/1] Funding Source: UKRI; Natural Environment Research Council [NE/E010431/1, NE/G018189/1, NE/K01496X/1] Funding Source: researchfish
NR 63
TC 146
Z9 162
U1 5
U2 190
PU NATURE PUBLISHING 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 21
PY 2014
VL 512
IS 7514
BP 303
EP +
DI 10.1038/nature13622
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200033
PM 25143112
DA 2026-03-09
ER

PT J
AU Asangani, IA
   Dommeti, VL
   Wang, XJ
   Malik, R
   Cieslik, M
   Yang, RD
   Escara-Wilke, J
   Wilder-Romans, K
   Dhanireddy, S
   Engelke, C
   Iyer, MK
   Jing, XJ
   Wu, YM
   Cao, XH
   Qin, ZHS
   Wang, SM
   Feng, FY
   Chinnaiyan, AM
AF Asangani, Irfan A.
   Dommeti, Vijaya L.
   Wang, Xiaoju
   Malik, Rohit
   Cieslik, Marcin
   Yang, Rendong
   Escara-Wilke, June
   Wilder-Romans, Kari
   Dhanireddy, Sudheer
   Engelke, Carl
   Iyer, Mathew K.
   Jing, Xiaojun
   Wu, Yi-Mi
   Cao, Xuhong
   Qin, Zhaohui S.
   Wang, Shaomeng
   Feng, Felix Y.
   Chinnaiyan, Arul M.
TI Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer
SO NATURE
LA English
DT Article
ID selective-inhibition; increased survival; chip-seq; p-tefb; brd4; antiandrogen; recruitment; abiraterone; gene; transcription
AB Men who develop metastatic castration-resistant prostate cancer(CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated and rogen receptor (AR) signalling(1-3). Despite the success of recently approved therapies targeting AR signalling, such as abiraterone(4-6) and second generation anti-androgens including MDV3100 (also known as enzalutamide) 7,8, durable responses are limited, presumably owing to acquired resistance. Recently, JQ1 and I-BET762 two selective small-molecule inhibitors that target the amino-terminal bromodomains of BRD4, have been shown to exhibit anti-proliferative effects in a range of malignancies(9-12). Here we show that AR-signalling-competent human CRPC cell lines are preferentially sensitive to bromodomain and extraterminal (BET) inhibition. BRD4 physically interacts with the N-terminal domain of AR and can bedisrupted by JQ1(refs 11, 13). Like the direct AR antagonist MDV3100, JQ1 disrupted AR recruitment to target gene loci. By contrast with MDV3100, JQ1 functions downstream of AR, and more potently abrogated BRD4 localization to AR target loci and AR-mediated gene transcription, including induction of the TMPRSS2-ERG gene fusion and its oncogenic activity. In vivo, BET bromodomain inhibition was more efficacious than direct AR antagonism in CRPC xenograft mouse models. Taken together, these studies provide a novel epigenetic approach for the concerted blockade of oncogenic drivers in advanced prostate cancer.
C1 [Asangani, Irfan A.; Dommeti, Vijaya L.; Wang, Xiaoju; Malik, Rohit; Cieslik, Marcin; Escara-Wilke, June; Dhanireddy, Sudheer; Engelke, Carl; Iyer, Mathew K.; Jing, Xiaojun; Wu, Yi-Mi; Cao, Xuhong; Feng, Felix Y.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
   [Asangani, Irfan A.; Wang, Xiaoju; Malik, Rohit; Wu, Yi-Mi; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Yang, Rendong; Qin, Zhaohui S.] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30329 USA.
   [Wilder-Romans, Kari; Feng, Felix Y.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
   [Cao, Xuhong; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
   [Wang, Shaomeng] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Wang, Shaomeng] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Wang, Shaomeng] Univ Michigan, Sch Med, Dept Med Chem, Ann Arbor, MI 48109 USA.
   [Wang, Shaomeng; Feng, Felix Y.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA.
   [Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Emory University; University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Chinnaiyan, AM (corresponding author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
EM arul@umich.edu
FU Movember-Prostate Cancer Foundation Challenge Award; Early Detection Research Network [UO1 CA111275]; NCI Prostate SPORE [P50CA69568]; Doris Duke Charitable Foundation; American Cancer Society; A. Alfred-Taubman Institute; PCF Young Investigator Award; National Institute of General Medical Sciences [T32GM007863] Funding Source: NIH RePORTER
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NR 42
TC 798
Z9 958
U1 2
U2 217
PU NATURE PUBLISHING 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 12
PY 2014
VL 510
IS 7504
BP 278
EP +
DI 10.1038/nature13229
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400052
PM 24759320
DA 2026-03-09
ER

PT J
AU Krzeszinski, JY
   Wei, W
   Huynh, H
   Jin, ZX
   Wang, XD
   Chang, TC
   Xie, XJ
   He, L
   Mangala, LS
   Lopez-Berestein, G
   Sood, AK
   Mendell, JT
   Wan, YH
AF Krzeszinski, Jing Y.
   Wei, Wei
   HoangDinh Huynh
   Jin, Zixue
   Wang, Xunde
   Chang, Tsung-Cheng
   Xie, Xian-Jin
   He, Lin
   Mangala, Lingegowda S.
   Lopez-Berestein, Gabriel
   Sood, Anil K.
   Mendell, Joshua T.
   Wan, Yihong
TI RETRACTED: miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2 (Retracted article. See vol. 582, pg. 134, 2020)
SO NATURE
LA English
DT Article; Retracted Publication
ID micrornas; receptor; differentiation; repression; mouse
AB Bone-resorbing osteoclasts significantly contribute to osteoporosis and bone metastases of cancer(1-3). MicroRNAs play important roles in physiology and disease(4,5), and present tremendous therapeutic potential(6). Nonetheless, how microRNAs regulate skeletal biology is underexplored. Here we identify miR-34a as a novel and critical suppressor of osteoclastogenesis, bone resorption and the bone metastatic niche. miR-34a is downregulated during osteoclast differentiation. Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass. Conversely, miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass. Consequently, ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment. Mechanistically, we identify transforming growth factor-beta-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic. Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation. Together, using mouse genetic, pharmacological and disease models, we reveal miR-34a as a key osteoclast suppressor and a potential therapeutic strategy to confer skeletal protection and ameliorate bone metastasis of cancers.
C1 [Krzeszinski, Jing Y.; Wei, Wei; HoangDinh Huynh; Jin, Zixue; Wang, Xunde; Wan, Yihong] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Chang, Tsung-Cheng; Mendell, Joshua T.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Xie, Xian-Jin; Mendell, Joshua T.; Wan, Yihong] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA.
   [Xie, Xian-Jin] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [He, Lin] Univ Calif Berkeley, Mol & Cell Biol Dept, Div Cellular & Dev Biol, Berkeley, CA 94705 USA.
   [Mangala, Lingegowda S.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA.
   [Mangala, Lingegowda S.; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA.
   [Lopez-Berestein, Gabriel] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
   [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 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; University of Texas System; University of Texas Southwestern Medical Center; University of California System; University of California Berkeley; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
RP Wan, YH (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
EM yihong.wan@utsouthwestern.edu
FU CPRIT [RP130145, R1008]; DOD [BC122877]; National Institutes of Health [R01 DK089113, R01 CA120185, P01 CA134292, U54 CA151668, UH2 TR000943, R01 CA139067]; Welch Foundation [I-1751]; University of Texas Southwestern Endowed Scholar Startup Fund; Harold C. Simmons Cancer Center through an NCI Cancer Center Support Grant [1P30 CA142543]; Department of Radiology; National Institutes of Health American Recovery and Reinvestment Act stimulus funds [1S10RR02564801]; National Cancer Institute [R01CA139067, P30CA142543] Funding Source: NIH RePORTER
NR 31
TC 282
Z9 325
U1 0
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 AUG 28
PY 2014
VL 512
IS 7515
BP 431
EP U460
DI 10.1038/nature13375
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600034
PM 25043055
DA 2026-03-09
ER

PT J
AU Ransom, SM
   Stairs, IH
   Archibald, AM
   Hessels, JWT
   Kaplan, DL
   van Kerkwijk, MH
   Boyles, J
   Deller, AT
   Chatterjee, S
   Schechtman-Rook, A
   Berndsen, A
   Lynch, RS
   Lorimer, DR
   Karako-Argaman, C
   Kaspi, VM
   Kondratiev, VI
   McLaughlin, MA
   van Leeuwen, J
   Rosen, R
   Roberts, MSE
   Stovall, K
AF Ransom, S. M.
   Stairs, I. H.
   Archibald, A. M.
   Hessels, J. W. T.
   Kaplan, D. L.
   van Kerkwijk, M. H.
   Boyles, J.
   Deller, A. T.
   Chatterjee, S.
   Schechtman-Rook, A.
   Berndsen, A.
   Lynch, R. S.
   Lorimer, D. R.
   Karako-Argaman, C.
   Kaspi, V. M.
   Kondratiev, V. I.
   McLaughlin, M. A.
   van Leeuwen, J.
   Rosen, R.
   Roberts, M. S. E.
   Stovall, K.
TI A millisecond pulsar in a stellar triple system
SO NATURE
LA English
DT Article
ID planetary system; binary evolution; data release; discovery; b1620-26
AB Gravitationally bound three-body systems have been studied for hundreds of years(1,2) and are common in our Galaxy(3,4). They show complex orbital interactions, which can constrain the compositions, masses and interior structures of the bodies(5) and test theories of gravity(6), if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, PSR B1620-26 (refs 7, 8; with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multiwavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar (1.4378(13)M-circle dot, where M-circle dot is the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15)M-circle dot and 0.4101(3)M-circle dot), as well as the inclinations of the orbits (both about 39.2 degrees). The unexpectedly coplanar and nearly circular orbits indicate a complex and exotic evolutionary past that differs from those of known stellar systems. The gravitational field of the outer white dwarf strongly accelerates the inner binary containing the neutron star, and the system will thus provide an ideal laboratory in which to test the strong equivalence principle of general relativity.
C1 [Ransom, S. M.; Rosen, R.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Stairs, I. H.; Berndsen, A.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Archibald, A. M.; Hessels, J. W. T.; Deller, A. T.; Kondratiev, V. I.; van Leeuwen, J.] Netherlands Inst Radio Astron ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Archibald, A. M.; Lynch, R. S.; Karako-Argaman, C.; Kaspi, V. M.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Hessels, J. W. T.; van Leeuwen, J.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 XH Amsterdam, Netherlands.
   [Kaplan, D. L.] Univ Wisconsin, Dept Phys, Milwaukee, WI 53201 USA.
   [Kaplan, D. L.; Schechtman-Rook, A.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [van Kerkwijk, M. H.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Boyles, J.; Lorimer, D. R.; McLaughlin, M. A.; Rosen, R.] W Virginia Univ, Dept Phys & Astron, Morgantown, WV 26506 USA.
   [Boyles, J.] Western Kentucky Univ, Dept Phys & Astron, Bowling Green, KY 42101 USA.
   [Chatterjee, S.] Cornell Univ, Ctr Radiophys & Space Res, Ithaca, NY 14853 USA.
   [Kondratiev, V. I.] PN Lebedev Phys Inst, Ctr Astro Space, Moscow 119991, Russia.
   [Roberts, M. S. E.] Eureka Sci Inc, Oakland, CA 94602 USA.
   [Roberts, M. S. E.] New York Univ Abu Dhabi, Dept Phys, Abu Dhabi, U Arab Emirates.
   [Stovall, K.] Univ Texas Brownsville, Dept Phys & Astron, Brownsville, TX 78520 USA.
   [Stovall, K.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
C3 National Radio Astronomy Observatory (NRAO); University of British Columbia; McGill University; University of Amsterdam; University of Wisconsin System; University of Wisconsin Milwaukee; University of Wisconsin System; University of Wisconsin Madison; University of Toronto; West Virginia University; Western Kentucky University; Cornell University; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute; Eureka Scientific; New York University; New York University Abu Dhabi; University of Texas System; University of Texas Rio Grande Valley; University of New Mexico
RP Ransom, SM (corresponding author), Natl Radio Astron Observ, 520 Edgemont Rd, Charlottesville, VA 22903 USA.
EM sransom@nrao.edu
FU NASA; NSERC; NWO; WV EPSCoR; CRAQ/FQRNT; CIFAR; Canada Research Chairs Program; Lorne Trottier Chair; Office Of Internatl Science &Engineering; Office Of The Director [0968296] Funding Source: National Science Foundation
NR 46
TC 191
Z9 217
U1 0
U2 15
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 23
PY 2014
VL 505
IS 7484
BP 520
EP +
DI 10.1038/nature12917
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000033
PM 24390352
DA 2026-03-09
ER

PT J
AU Zhou, XM
   Levin, EJ
   Pan, YP
   McCoy, JG
   Sharma, R
   Kloss, B
   Bruni, R
   Quick, M
   Zhou, M
AF Zhou, Xiaoming
   Levin, Elena J.
   Pan, Yaping
   McCoy, Jason G.
   Sharma, Ruchika
   Kloss, Brian
   Bruni, Renato
   Quick, Matthias
   Zhou, Ming
TI Structural basis of the alternating-access mechanism in a bile acid transporter
SO NATURE
LA English
DT Article
ID crystal-structure; bacterial homolog; structure refinement; expression cloning; sodium symporter; outward-open; substrate; proteins; family; cholesterol
AB Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat-soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion(1). In humans, there are two Na+-dependent bile acid transporters involved in enterohepatic recirculation, the Na+-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium-dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum(2). In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolaemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption(3,4). However, a lack of three-dimensional structures of bile acid transporters hampers our ability to understand the molecular mechanisms of substrate selectivity and transport, and to interpret the wealth of existing functional data(2,5-8). The crystal structure of an ASBT homologue from Neisseria meningitidis (ASBT(NM)) in detergent was reported recently(9), showing the protein in an inward-open conformation bound to two Na+ and a taurocholic acid. However, the structural changes that bring bile acid and Na+ across the membrane are difficult to infer from a single structure. To understand the structural changes associated with the coupled transport of Na+ and bile acids, here we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBT(Yf)) in a lipid environment, which reveal that a large rigid-body rotation of a substrate-binding domain gives the conserved 'crossover' region, where two discontinuous helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications for the location and orientation of the bile acid during transport, as well as for the translocation pathway for Na+.
C1 [Zhou, Xiaoming; Levin, Elena J.; Pan, Yaping; McCoy, Jason G.; Zhou, Ming] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Zhou, Xiaoming; Sharma, Ruchika; Zhou, Ming] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Kloss, Brian; Bruni, Renato] New York Consortium Membrane Prot Struct, New York, NY 10027 USA.
   [Quick, Matthias] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Quick, Matthias] Columbia Univ, Ctr Mol Recognit, New York, NY 10032 USA.
   [Quick, Matthias] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
   [Zhou, Ming] Chinese Acad Sci, Kunming Inst Zool, Ion Channel Res & Drug Dev Ctr, Kunming 650223, Peoples R China.
C3 Baylor College of Medicine; Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS
RP Zhou, M (corresponding author), Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
EM mq2102@columbia.edu; mzhou@bcm.edu
FU US National Institutes of Health [R01DK088057, R01GM098878, U54GM095315, U54GM087519]; American Heart Association [12EIA8850017]; Cancer Prevention and Research Institute of Texas [R12MZ]; American Heart Association (AHA) [12EIA8850017] Funding Source: American Heart Association (AHA)
NR 40
TC 129
Z9 158
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 JAN 23
PY 2014
VL 505
IS 7484
BP 569
EP 573
DI 10.1038/nature12811
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000044
PM 24317697
DA 2026-03-09
ER

PT J
AU Krause, DW
   Hoffmann, S
   Wible, JR
   Kirk, EC
   Schultz, JA
   von Koenigswald, W
   Groenke, JR
   Rossie, JB
   O'Connor, PM
   Seiffert, ER
   Dumont, ER
   Holloway, WL
   Rogers, RR
   Rahantarisoa, LJ
   Kemp, AD
   Andriamialison, H
AF Krause, David W.
   Hoffmann, Simone
   Wible, John R.
   Kirk, E. Christopher
   Schultz, Julia A.
   von Koenigswald, Wighart
   Groenke, Joseph R.
   Rossie, James B.
   O'Connor, Patrick M.
   Seiffert, Erik R.
   Dumont, Elizabeth R.
   Holloway, Waymon L.
   Rogers, Raymond R.
   Rahantarisoa, Lydia J.
   Kemp, Addison D.
   Andriamialison, Haingoson
TI First cranial remains of a gondwanatherian mammal reveal remarkable mosaicism
SO NATURE
LA English
DT Article
ID south-america; eye size; predatory dinosaur; activity pattern; visual-acuity; madagascar; multituberculate; primates; paleocene; evolution
AB Previously known only from isolated teeth and lower jaw fragments recovered from the Cretaceous and Palaeogene of the Southern Hemisphere, the Gondwanatheria constitute the most poorly known of all major maminaliaform radiations. Here we report the discovery of the first skull material of a gondwanatberian, a complete and well-preserved cranium from Upper Cretaceous strata in Madagascar car that we assign to a new genus and species. Phylogenetc analysis strongly supports its placement within Gondwanatheria, which are recognized a monophyletic and closely related to multituber-culates an evolutionarily success clade of Mesozoic mammals known almost exclusively from the Northern Hemisphere. The new taxon is the largest known mammaliaform from the Mesozoic of Gondwana. Its craniofacial anatomy reveals that it was herbivorous, a us in, large-eyed. of and agile, with well-developed high-frequency hearing and a keen sense of smell. The cranium exhibits primitive and derived features, the disparity of which is extreme and probably reflective of a long evolutionary history in geographic isolation.
C1 [Krause, David W.; Hoffmann, Simone; Groenke, Joseph R.; Seiffert, Erik R.] SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Wible, John R.] Carnegie Museum Nat Hist, Sect Mammals, Pittsburgh, PA 15206 USA.
   [Kirk, E. Christopher; Kemp, Addison D.] Univ Texas Austin, Dept Anthropol, Austin, TX 78712 USA.
   [Schultz, Julia A.; von Koenigswald, Wighart] Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, D-53115 Bonn, Germany.
   [Rossie, James B.] SUNY Stony Brook, Dept Anthropol, Stony Brook, NY 11794 USA.
   [O'Connor, Patrick M.; Holloway, Waymon L.] Ohio Univ, Heritage Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA.
   [O'Connor, Patrick M.; Holloway, Waymon L.] Ohio Univ, Ohio Ctr Ecol & Evolutionary Studies, Athens, OH 45701 USA.
   [Dumont, Elizabeth R.] Univ Massachusetts, Dept Biol, Morrill Sci Ctr 221, Amherst, MA 01003 USA.
   [Rogers, Raymond R.] Macalester Coll, Dept Geol, St Paul, MN 55105 USA.
   [Rahantarisoa, Lydia J.] Univ Antananarivo, Dept Geol, Antananarivo 101, Madagascar.
   [Andriamialison, Haingoson] Univ Antananarivo, Dept Paleontol, Antananarivo 101, Madagascar.
C3 State University of New York (SUNY) System; Stony Brook University; University of Texas System; University of Texas Austin; University of Bonn; State University of New York (SUNY) System; Stony Brook University; University System of Ohio; Ohio University; University System of Ohio; Ohio University; University of Massachusetts System; University of Massachusetts Amherst; Macalester College; University Antananarivo; University Antananarivo
RP Krause, DW (corresponding author), SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
EM David.Krause@stonybrook.edu
FU National Geographic Society [8597-09]; National Science Foundation [EAR-0446488, EAR-1123642]; Direct For Biological Sciences; Division Of Environmental Biology [0946430] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1123642] Funding Source: National Science Foundation
NR 50
TC 99
Z9 112
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 NOV 27
PY 2014
VL 515
IS 7528
BP 512
EP +
DI 10.1038/nature13922
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600044
PM 25383528
DA 2026-03-09
ER

PT J
AU Gupta, S
   Chai, J
   Cheng, J
   D'Mello, R
   Chance, MR
   Fu, D
AF Gupta, Sayan
   Chai, Jin
   Cheng, Jie
   D'Mello, Rhijuta
   Chance, Mark R.
   Fu, Dax
TI Visualizing the kinetic power stroke that drives proton-coupled zinc(II) transport
SO NATURE
LA English
DT Article
ID mass-spectrometry; metal-binding; yiip; specificity; selectivity; mechanism; dynamics; vesicles; family; fief
AB The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of Escherichia coli. Its transport site receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux(1,2). This membrane protein is a well characterized member3- 7 of the family of cation diffusion facilitators that occurs at all phylogenetic levels(8-10). Here we show, using X-ray-mediated hydroxyl radical labelling of YiiP and mass spectrometry, that Zn( II) binding triggers a highly localized, all-or-nothing change of water accessibility to the transport site and an adjacent hydrophobic gate. Milli-secondtime-resolved dynamics reveal a concerted and reciprocal pattern of accessibility changes along a trans membrane helix, suggesting a rigid-body helical re-orientation linked to Zn( II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport site enables a stationary proton gradient to facilitate the conversion of zinc-binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights intoaproton-coupled active-transport reaction.
C1 [Gupta, Sayan; Cheng, Jie; D'Mello, Rhijuta] Case Western Reserve Univ, Ctr Synchrotron Biosci, Cleveland, OH 44109 USA.
   [Gupta, Sayan; D'Mello, Rhijuta; Chance, Mark R.] Case Western Reserve Univ, Ctr Prote & Bioinformat, Cleveland, OH 44109 USA.
   [Chai, Jin; Fu, Dax] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
   [Cheng, Jie; Fu, Dax] Johns Hopkins Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
C3 University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; United States Department of Energy (DOE); Brookhaven National Laboratory; Johns Hopkins University; Johns Hopkins Medicine
RP Fu, D (corresponding author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
EM mrc16@case.edu; dfu3@jhmi.edu
FU National Institutes of Health [R01GM065137]; Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the US Department of Energy (DOE) [DE-AC02-98CH10886]; Physical Biosciences Program, Office of Basic Energy Sciences of the DOE; National Institute for Biomedical Imaging and Bioengineering [P30-EB-09998, R01-EB-09688]; DOE [DE-AC02-98CH10886]
NR 27
TC 130
Z9 141
U1 0
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 AUG 7
PY 2014
VL 512
IS 7512
BP 101
EP +
DI 10.1038/nature13382
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000040
PM 25043033
DA 2026-03-09
ER

PT J
AU Harjunmaa, E
   Seidel, K
   Häkkinen, T
   Renvoisé, E
   Corfe, IJ
   Kallonen, A
   Zhang, ZQ
   Evans, AR
   Mikkola, ML
   Salazar-Ciudad, I
   Klein, OD
   Jernvall, J
AF Harjunmaa, Enni
   Seidel, Kerstin
   Hakkinen, Teemu
   Renvoise, Elodie
   Corfe, Ian J.
   Kallonen, Aki
   Zhang, Zhao-Qun
   Evans, Alistair R.
   Mikkola, Marja L.
   Salazar-Ciudad, Isaac
   Klein, Ophir D.
   Jernvall, Jukka
TI Replaying evolutionary transitions from the dental fossil record
SO NATURE
LA English
DT Article
ID mammalian teeth; patterns; ectodysplasin; molecules; radiation; dynamics; genes; model; trees
AB The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological characters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the developmental underpinnings of character inter-dependence remain obscure because experiments frequently do not provide detailed resolution of morphological characters. Here we show experimentally and computationally how gradual modification of development differentially affects characters in the mouse dentition. We found that intermediate phenotypes could be produced by gradually adding ectodysplas in A (EDA) protein in culture to tooth explants carrying a null mutation in the tooth-patterning gene Eda. By identifying development-based character inter-dependencies, we show how to predict morphological patterns of teeth among mammalian species. Finally, in vivo inhibition of sonic hedgehog signalling in Eda null teeth enabled us to reproduce characters deep in the rodent ancestry. Taken together, evolutionarily informative transitions can be experimentally reproduced, thereby providing development-based expectations for character-state transitions used in evolutionary studies.
C1 [Harjunmaa, Enni; Hakkinen, Teemu; Renvoise, Elodie; Corfe, Ian J.; Mikkola, Marja L.; Salazar-Ciudad, Isaac; Jernvall, Jukka] Univ Helsinki, Inst Biotechnol, Dev Biol Program, FIN-00014 Helsinki, Finland.
   [Seidel, Kerstin; Klein, Ophir D.] Univ Calif San Francisco, Program Craniofacial & Mesenchymal Biol, San Francisco, CA 94114 USA.
   [Seidel, Kerstin; Klein, Ophir D.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94114 USA.
   [Kallonen, Aki] Univ Helsinki, Dept Phys, Div Mat Phys, FIN-00014 Helsinki, Finland.
   [Zhang, Zhao-Qun] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Evans, Alistair R.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [Evans, Alistair R.] Museum Victoria, Melbourne, Vic 3001, Australia.
   [Salazar-Ciudad, Isaac] Univ Autonoma Barcelona, Dept Genet & Microbiol, Genom Bioinformat & Evolut Group, Cerdanyola Del Valles 08193, Spain.
   [Klein, Ophir D.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94114 USA.
   [Klein, Ophir D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94114 USA.
C3 University of Helsinki; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Helsinki; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Monash University; Museum Victoria; Autonomous University of Barcelona; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Jernvall, J (corresponding author), Univ Helsinki, Inst Biotechnol, Dev Biol Program, POB 56, FIN-00014 Helsinki, Finland.
EM ophir.klein@ucsf.edu; jernvall@fastmail.fm
FU Academy of Finland; NIH/NIDCR [R01-DE021420]; NIH [DP2-OD007191]; Australian Research Council; MST [2012CB821904]
NR 43
TC 97
Z9 111
U1 0
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 AUG 7
PY 2014
VL 512
IS 7512
BP 44
EP +
DI 10.1038/nature13613
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000027
PM 25079326
DA 2026-03-09
ER

PT J
AU Kohout, AL
   Williams, MJM
   Dean, SM
   Meylan, MH
AF Kohout, A. L.
   Williams, M. J. M.
   Dean, S. M.
   Meylan, M. H.
TI Storm-induced sea-ice breakup and the implications for ice extent
SO NATURE
LA English
DT Article
ID ocean waves; attenuation; trends; zone; climate
AB The propagation of large, storm-generated waves through sea ice has so far not been measured, limiting our understanding of how ocean waves break sea ice. Without improved knowledge of ice breakup, we are unable to understand recent changes, or predict future changes, in Arctic and Antarctic sea ice. Here we show that storm-generated ocean waves propagating through Antarctic sea ice are able to transport enough energy to break sea ice hundreds of kilometres from the ice edge. Our results, which are based on concurrent observations at multiple locations, establish that large waves break sea ice much farther from the ice edge than would be predicted by the commonly assumed exponential decay(1-3). We observed the wave height decay to be almost linear for large waves-those with a significant wave height greater than three metres-and to be exponential only for small waves. This implies a more prominent role for large ocean waves in sea-ice breakup and retreat than previously thought. We examine the wider relevance of this by comparing observed Antarctic sea-ice edge positions with changes in modelled significant wave heights for the Southern Ocean between 1997 and 2009, and find that the retreat and expansion of the sea-ice edge correlate with mean significant wave height increases and decreases, respectively. This includes capturing the spatial variability in sea-ice trends found in the Ross and Amundsen-Bellingshausen seas. Climate models fail to capture recent changes in sea ice in both polar regions(4,5). Our results suggest that the incorporation of explicit or parameterized interactions between ocean waves and sea ice may resolve this problem.
C1 [Kohout, A. L.] Natl Inst Water & Atmospher Res, Christchurch 8011, New Zealand.
   [Williams, M. J. M.; Dean, S. M.] Natl Inst Water & Atmospher Res, Wellington 6021, New Zealand.
   [Meylan, M. H.] Univ Newcastle, Newcastle, NSW 2308, Australia.
C3 Earth Sciences New Zealand; National Institute of Water & Atmospheric Research (NIWA) - New Zealand; Earth Sciences New Zealand; National Institute of Water & Atmospheric Research (NIWA) - New Zealand; University of Newcastle
RP Kohout, AL (corresponding author), Natl Inst Water & Atmospher Res, Christchurch 8011, New Zealand.
EM alison.kohout@niwa.co.nz
FU New Zealand Foundation of Research Science and Technology; Marsden Fund Council; NIWA, under National Climate Centre Climate Systems programme; Antarctic Climate and Ecosystems Cooperative Research Centre; Australian Antarctic Science project [4073]; Grants-in-Aid for Scientific Research [24510001] Funding Source: KAKEN
NR 34
TC 247
Z9 277
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 MAY 29
PY 2014
VL 509
IS 7502
BP 604
EP +
DI 10.1038/nature13262
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100046
PM 24870546
DA 2026-03-09
ER

PT J
AU Lee, JJ
   Schmitt, FT
   Moore, RG
   Johnston, S
   Cui, YT
   Li, W
   Yi, M
   Liu, ZK
   Hashimoto, M
   Zhang, Y
   Lu, DH
   Devereaux, TP
   Lee, DH
   Shen, ZX
AF Lee, J. J.
   Schmitt, F. T.
   Moore, R. G.
   Johnston, S.
   Cui, Y. -T.
   Li, W.
   Yi, M.
   Liu, Z. K.
   Hashimoto, M.
   Zhang, Y.
   Lu, D. H.
   Devereaux, T. P.
   Lee, D. -H.
   Shen, Z. -X.
TI Interfacial mode coupling as the origin of the enhancement of Tc in FeSe films on SrTiO3
SO NATURE
LA English
DT Article
ID high-temperature superconductivity; photoemission
AB Films of iron selenide (FeSe) one unit cell thick grown on strontium titanate (SrTiO3 or STO) substrates have recently shown(1-4) superconducting energy gaps opening at temperatures close to the boiling point of liquid nitrogen (77 kelvin), which is a record for the iron-based superconductors. The gap opening temperature usually sets the superconducting transition temperature T-c, as the gap signals the formation of Cooper pairs, the bound electron states responsible for superconductivity. To understand why Cooper pairs form at such high temperatures, we examine the role of the SrTiO3 substrate. Here we report high-resolution angle-resolved photoemission spectroscopy results that reveal an unexpected characteristic of the single-unit-cell FeSe/SrTiO3 system: shake-off bands suggesting the presence of bosonic modes, most probably oxygen optical phonons in SrTiO3 (refs 5-7), which couple to the FeSe electrons with only a small momentum transfer. Such interfacial coupling assists superconductivity in most channels, including those mediated by spin fluctuations(8-14). Our calculations suggest that this coupling is responsible for raising the superconducting gap opening temperature in single-unit-cell FeSe/SrTiO3.
C1 [Lee, J. J.; Schmitt, F. T.; Moore, R. G.; Cui, Y. -T.; Li, W.; Yi, M.; Liu, Z. K.; Zhang, Y.; Devereaux, T. P.; Shen, Z. -X.] SLAC Natl Accelerator Lab, Stanford Inst Mat & Energy Sci, Menlo Pk, CA 94025 USA.
   [Lee, J. J.; Yi, M.; Liu, Z. K.; Shen, Z. -X.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Lee, J. J.; Yi, M.; Liu, Z. K.; Shen, Z. -X.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Lee, J. J.; Yi, M.; Liu, Z. K.; Shen, Z. -X.] Stanford Univ, Geballe Lab Adv Mat, Stanford, CA 94305 USA.
   [Johnston, S.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Johnston, S.] Univ British Columbia, Quantum Matter Inst, Vancouver, BC V6T 1Z4, Canada.
   [Johnston, S.] Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
   [Hashimoto, M.; Lu, D. H.] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
   [Zhang, Y.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Lee, D. -H.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Lee, D. -H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; Stanford University; Stanford University; University of British Columbia; University of British Columbia; University of Tennessee System; University of Tennessee Knoxville; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; 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
RP Shen, ZX (corresponding author), SLAC Natl Accelerator Lab, Stanford Inst Mat & Energy Sci, Menlo Pk, CA 94025 USA.
EM zxshen@stanford.edu
FU US Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division; Department of Energy, Office of Basic Energy Sciences, Division of Materials Science, under the Quantum Material programme [DE-AC02-05CH11231]
NR 27
TC 617
Z9 700
U1 7
U2 564
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 245
EP U207
DI 10.1038/nature13894
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400045
PM 25391962
DA 2026-03-09
ER

PT J
AU Bellott, DW
   Hughes, JF
   Skaletsky, H
   Brown, LG
   Pyntikova, T
   Cho, TJ
   Koutseva, N
   Zaghlul, S
   Graves, T
   Rock, S
   Kremitzki, C
   Fulton, RS
   Dugan, S
   Ding, Y
   Morton, D
   Khan, Z
   Lewis, L
   Buhay, C
   Wang, QY
   Watt, J
   Holder, M
   Lee, S
   Nazareth, L
   Rozen, S
   Muzny, DM
   Warren, WC
   Gibbs, RA
   Wilson, RK
   Page, DC
AF Bellott, Daniel W.
   Hughes, Jennifer F.
   Skaletsky, Helen
   Brown, Laura G.
   Pyntikova, Tatyana
   Cho, Ting-Jan
   Koutseva, Natalia
   Zaghlul, Sara
   Graves, Tina
   Rock, Susie
   Kremitzki, Colin
   Fulton, Robert S.
   Dugan, Shannon
   Ding, Yan
   Morton, Donna
   Khan, Ziad
   Lewis, Lora
   Buhay, Christian
   Wang, Qiaoyan
   Watt, Jennifer
   Holder, Michael
   Lee, Sandy
   Nazareth, Lynne
   Rozen, Steve
   Muzny, Donna M.
   Warren, Wesley C.
   Gibbs, Richard A.
   Wilson, Richard K.
   Page, David C.
TI Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
SO NATURE
LA English
DT Article
ID sex-determining region; x-chromosm; short arm; embryonic-development; gene conversion; 2 daughters; inactivation; phenotype; evolution; sequence
AB The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.
C1 [Bellott, Daniel W.; Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Zaghlul, Sara; Rozen, Steve; Page, David C.] MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA.
   [Bellott, Daniel W.; Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Zaghlul, Sara; Rozen, Steve; Page, David C.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Graves, Tina; Rock, Susie; Kremitzki, Colin; Fulton, Robert S.; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Dugan, Shannon; Ding, Yan; Morton, Donna; Khan, Ziad; Lewis, Lora; Buhay, Christian; Wang, Qiaoyan; Watt, Jennifer; Holder, Michael; Lee, Sandy; Nazareth, Lynne; Muzny, Donna M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Washington University (WUSTL); Baylor College of Medicine
RP Bellott, DW (corresponding author), MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA.
EM bellott@wi.mit.edu
FU National Institutes of Health; Howard Hughes Medical Institute
NR 69
TC 508
Z9 571
U1 1
U2 139
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 24
PY 2014
VL 508
IS 7497
BP 494
EP +
DI 10.1038/nature13206
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600030
PM 24759411
DA 2026-03-09
ER

PT J
AU McBride, CS
   Baier, F
   Omondi, AB
   Spitzer, SA
   Lutomiah, J
   Sang, R
   Ignell, R
   Vosshall, LB
AF McBride, Carolyn S.
   Baier, Felix
   Omondi, Aman B.
   Spitzer, Sarabeth A.
   Lutomiah, Joel
   Sang, Rosemary
   Ignell, Rickard
   Vosshall, Leslie B.
TI Evolution of mosquito preference for humans linked to an odorant receptor
SO NATURE
LA English
DT Article
ID aegypti l diptera; aedes-aegypti; volatile compounds; genome annotation; malaria mosquito; host location; alters odor; identification; alignment; behavior
AB Female mosquitoes are major vectors of human disease and the most dangerous are those that preferentially bite humans. A 'domestic' form of the mosquito Aedes aegypti has evolved to specialize in biting humans and is the main worldwide vector of dengue, yellow fever, and chikungunya viruses. The domestic form coexists with an ancestral, 'forest' form that prefers to bite non-human animals and is found along the coast of Kenya. We collected the two forms, established laboratory colonies, and document striking divergence in preference for human versus non-human animal odour. We further show that the evolution of preference for human odour in domestic mosquitoes is tightly linked to increases in the expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found recognizes a compound present at high levels inhuman odour. Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialize on humans.
C1 [McBride, Carolyn S.; Baier, Felix; Spitzer, Sarabeth A.; Vosshall, Leslie B.] Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
   [McBride, Carolyn S.; Vosshall, Leslie B.] Howard Hughes Med Inst, New York, NY 10065 USA.
   [Omondi, Aman B.; Ignell, Rickard] Swedish Univ Agr Sci, Dept Plant Protect Biol, Unit Chem Ecol, S-23053 Alnarp, Sweden.
   [Lutomiah, Joel; Sang, Rosemary] Kenya Govt Med Res Ctr, Ctr Virus Res, Nairobi, Kenya.
C3 Rockefeller University; Howard Hughes Medical Institute; Swedish University of Agricultural Sciences; Kenya Medical Research Institute
RP Vosshall, LB (corresponding author), Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
EM Leslie.Vosshall@rockefeller.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative; National Institutes of Health grants: K99 award from NIDCD [DC012069]; NIAID Vectorbase DBP [HHSN272200900039C]; CTSA award from NCATS [5UL1TR000043]; Swedish Research Council and SLU: Insect Chemical Ecology and Evolution (IC-E3)
NR 69
TC 371
Z9 458
U1 2
U2 292
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2014
VL 515
IS 7526
BP 222
EP U151
DI 10.1038/nature13964
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400040
PM 25391959
DA 2026-03-09
ER

PT J
AU Jo, KN
   Woo, KS
   Yi, S
   Yang, DY
   Lim, HS
   Wang, YJ
   Cheng, H
   Edwards, RL
AF Jo, Kyoung-nam
   Woo, Kyung Sik
   Yi, Sangheon
   Yang, Dong Yoon
   Lim, Hyoun Soo
   Wang, Yongjin
   Cheng, Hai
   Edwards, R. Lawrence
TI Mid-latitude interhemispheric hydrologic seesaw over the past 550,000 years
SO NATURE
LA English
DT Article
ID millennial-scale; korean peninsula; asian monsoon; speleothem growth; climate; record; vegetation; region; cave; precipitation
AB An interhemispheric hydrologic seesaw-in which latitudinal migrations of the Intertropical Convergence Zone (ITCZ) produce simultaneous wetting (increased precipitation) in one hemisphere and drying in the other-has been discovered in some tropical and subtropical regions(1-3). For instance, Chinese and Brazilian subtropical speleothem (cave formations such as stalactites and stalagmites) records show opposite trends in time series of oxygen isotopes (a proxy for precipitation variability) at millennial to orbital timescales(2,3), suggesting that hydrologic cycles were antiphased in the northerly versus southerly subtropics. This tropical to subtropical hydrologic phenomenon is likely to be an initial and important climatic response to orbital forcing(3). The impacts of such an interhemispheric hydrologic seesaw on higher-latitude regions and the global climate system, however, are unknown. Here we show that the antiphasing seen in the tropical records is also present in both hemispheres of the mid-latitude western Pacific Ocean. Our results are based on a new 550,000-year record of the growth frequency of speleothems from the Korean peninsula, which we compare to Southern Hemisphere equivalents(4). The Korean data are discontinuous and derived from 24 separate speleothems, but still allow the identification of periods of peak speleothem growth and, thus, precipitation. The clear hemispheric antiphasing indicates that the sphere of influence of the interhemispheric hydrologic seesaw over the past 550,000 years extended at least to the mid-latitudes, such as northeast Asia, and that orbital-timescale ITCZshifts can have serious effects on temperate climate systems. Furthermore, our result implies that insolationdriven ITCZ dynamics may provoke water vapour and vegetation feedbacks in northern mid-latitude regions and could have regulated global climate conditions throughout the late Quaternary ice age cycles.
C1 [Jo, Kyoung-nam; Yi, Sangheon; Yang, Dong Yoon] Korea Inst Geosci & Mineral Resources, Taejon 305350, South Korea.
   [Woo, Kyung Sik] Kangwon Natl Univ, Dept Geol, Gangwondo 200701, South Korea.
   [Lim, Hyoun Soo] Pusan Natl Univ, Dept Geol Sci, Pusan 609735, South Korea.
   [Wang, Yongjin] Nanjing Normal Univ, Coll Geog Sci, Nanjing 210097, Peoples R China.
   [Cheng, Hai] Xi An Jiao Tong Univ, Inst Global Environm Change, Xian 710049, Peoples R China.
   [Cheng, Hai; Edwards, R. Lawrence] Univ Minnesota, Dept Geol & Geophys, Minneapolis, MN 55455 USA.
C3 Korea Institute of Geoscience & Mineral Resources (KIGAM); Kangwon National University; Pusan National University; Nanjing Normal University; Xi'an Jiaotong University; University of Minnesota System; University of Minnesota Twin Cities
RP Woo, KS (corresponding author), Korea Inst Geosci & Mineral Resources, Taejon 305350, South Korea.
EM wooks@kangwon.ac.kr
FU Ministry of Oceans and Fisheries, Korea; Basic Research Project of KIGAM [GP2009-005, NSFC 41230524, NBRP 2013CB955902]; US NSF [1103403, 1337693]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1103403] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1337693] Funding Source: National Science Foundation
NR 58
TC 69
Z9 78
U1 2
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 APR 17
PY 2014
VL 508
IS 7496
BP 378
EP +
DI 10.1038/nature13076
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000048
PM 24695222
DA 2026-03-09
ER

PT J
AU Motch, C
   Pakull, MW
   Soria, R
   Grisé, F
   Pietrzynski, G
AF Motch, C.
   Pakull, M. W.
   Soria, R.
   Grise, F.
   Pietrzynski, G.
TI A mass of less than 15 solar masses for the black hole in an ultraluminous X-ray source
SO NATURE
LA English
DT Article
ID galaxy ngc 7793; b-supergiants; accretion disc; stellar; emission; hercules-x-1; parameters; evolution; binary; spectra
AB Most ultraluminous X-ray sources(1) have a typical set of properties not seen in Galactic stellar-mass black holes. They have luminosities of more than 3 x 10(39) ergs per second, unusually soft X-ray components (with a typical temperature of less than about 0.3 kiloelectronvolts) and a characteristic downturn(2,3) in their spectra above about 5 kiloelectronvolts. Such puzzling properties have been interpreted either as evidence of intermediate-mass black holes(4,5) or as emission from stellar-mass black holes accreting above their Eddington limit(6,7), analogous to some Galactic black holes at peak luminosity(8,9). Recently, a very soft X-ray spectrum was observed in a rare and transient stellar-mass black hole(10). Here we report that the X-ray source P13 in the galaxy NGC 7793(11) is in a binary system with a period of about 64 days and exhibits all three canonical properties of ultraluminous sources. By modelling the strong optical and ultraviolet modulations arising from X-ray heating of the B9Ia donor star, we constrain the black hole mass to be less than 15 solar masses. Our results demonstrate that in P13, soft thermal emission and spectral curvature are indeed signatures of supercritical accretion. By analogy, ultraluminous X-ray sources with similar X-ray spectra and luminosities of up to a few times 10(40) ergs per second can be explained by supercritical accretion onto massive stellar-mass black holes.
C1 [Motch, C.; Pakull, M. W.; Grise, F.] Univ Strasbourg, CNRS, Observ Astron Strasbourg, UMR 7550, F-67000 Strasbourg, France.
   [Soria, R.] Curtin Univ, Int Ctr Radio Astron Res, Perth, WA 6845, Australia.
   [Grise, F.] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
   [Grise, F.] Univ La Laguna, Dept Astrofis, E-38206 Tenerife, Spain.
   [Grise, F.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
   [Pietrzynski, G.] Univ Concepcion, Dept Astron, Concepcion, Octava Region, Chile.
   [Pietrzynski, G.] Univ Warsaw Observ, PL-00478 Warsaw, Poland.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Curtin University; University of Western Australia; Instituto de Astrofisica de Canarias; Universidad de la Laguna; University of Iowa; Universidad de Concepcion; University of Warsaw; Warsaw University Observatory
RP Motch, C (corresponding author), Univ Strasbourg, CNRS, Observ Astron Strasbourg, UMR 7550, 11 Rue Univ, F-67000 Strasbourg, France.
EM christian.motch@unistra.fr
FU Australian Research Council [DP120102393]; CNES (CNRS/INSU/CNES) [92532]; Spanish Ministry of Science and Innovation (MICINN) [AYA 2010-18080]; Ideas Plus programme of the Polish Ministry of Science; ESO telescopes at the La Silla Paranal Observatory [084.D-0881, 087.D-0602]; ESA member states; NASA
NR 30
TC 203
Z9 210
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 OCT 9
PY 2014
VL 514
IS 7521
BP 198
EP +
DI 10.1038/nature13730
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100035
PM 25297432
DA 2026-03-09
ER

PT J
AU Tilman, D
   Clark, M
AF Tilman, David
   Clark, Michael
TI Global diets link environmental sustainability and human health
SO NATURE
LA English
DT Article
ID mediterranean diet; nutrition transition; meat consumption; vegetarian diets; adventist health; cancer incidence; heart-disease; land-use; mortality; survival
AB Diets link environmental and human health. Rising incomes and urbanization are driving a global dietary transition in which traditional diets are replaced by diets higher in refined sugars, refined fats, oils and meats. By 2050 these dietary trends, if unchecked, would be a major contributor to an estimated 80 per cent increase in global agricultural greenhouse gas emissions from food production and to global land clearing. Moreover, these dietary shifts are greatly increasing the incidence of type II diabetes, coronary heart disease and other chronic non-communicable diseases that lower global life expectancies. Alternative diets that offer substantial health benefits could, if widely adopted, reduce global agricultural greenhouse gas emissions, reduce land clearing and resultant species extinctions, and help prevent such diet-related chronic non-communicable diseases. The implementation of dietary solutions to the tightly linked diet-environment-health trilemma is a global challenge, and opportunity, of great environmental and public health importance.
C1 [Tilman, David; Clark, Michael] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Tilman, David] Univ Calif Santa Barbara, Bren Sch Environm Sci & Management, Santa Barbara, CA 93106 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California Santa Barbara
RP Tilman, D (corresponding author), Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
EM tilman@umn.edu
FU LTER programme of the US National Science Foundation; University of Minnesota Foundation
NR 74
TC 2408
Z9 2809
U1 34
U2 1795
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2014
VL 515
IS 7528
BP 518
EP +
DI 10.1038/nature13959
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600045
PM 25383533
DA 2026-03-09
ER

PT J
AU Moura-Alves, P
   Faé, K
   Houthuys, E
   Dorhoi, A
   Kreuchwig, A
   Furkert, J
   Barison, N
   Diehl, A
   Munder, A
   Constant, P
   Skrahina, T
   Guhlich-Bornhof, U
   Klemm, M
   Koehler, AB
   Bandermann, S
   Goosmann, C
   Mollenkopf, HJ
   Hurwitz, R
   Brinkmann, V
   Fillatreau, S
   Daffe, M
   Tümmler, B
   Kolbe, M
   Oschkinat, H
   Krause, G
   Kaufmann, SHE
AF Moura-Alves, Pedro
   Fae, Kellen
   Houthuys, Erica
   Dorhoi, Anca
   Kreuchwig, Annika
   Furkert, Jens
   Barison, Nicola
   Diehl, Anne
   Munder, Antje
   Constant, Patricia
   Skrahina, Tatsiana
   Guhlich-Bornhof, Ute
   Klemm, Marion
   Koehler, Anne-Britta
   Bandermann, Silke
   Goosmann, Christian
   Mollenkopf, Hans-Joachim
   Hurwitz, Robert
   Brinkmann, Volker
   Fillatreau, Simon
   Daffe, Mamadou
   Tuemmler, Burkhard
   Kolbe, Michael
   Oschkinat, Hartmut
   Krause, Gerd
   Kaufmann, Stefan H. E.
TI AhR sensing of bacterial pigments regulates antibacterial defence
SO NATURE
LA English
DT Article
ID aryl-hydrocarbon receptor; ligand-binding domain; pseudomonas-aeruginosa; gene battery; pyocyanin; activation; expression; toxicity; differentiation; identification
AB The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns.
C1 [Moura-Alves, Pedro; Fae, Kellen; Houthuys, Erica; Dorhoi, Anca; Skrahina, Tatsiana; Guhlich-Bornhof, Ute; Klemm, Marion; Koehler, Anne-Britta; Bandermann, Silke; Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany.
   [Kreuchwig, Annika; Furkert, Jens; Diehl, Anne; Oschkinat, Hartmut; Krause, Gerd] Leibniz Inst Mol Pharmacol FMP, D-13125 Berlin, Germany.
   [Barison, Nicola; Kolbe, Michael] Max Planck Inst Infect Biol, D-10117 Berlin, Germany.
   [Munder, Antje; Tuemmler, Burkhard] Hannover Med Sch, Clin Res Grp, Clin Pediat Pneumol Allergol & Neonatol, D-30625 Hannover, Germany.
   [Constant, Patricia; Daffe, Mamadou] CNRS, IPBS, F-31077 Toulouse 04, France.
   [Constant, Patricia; Daffe, Mamadou] Univ Toulouse 3, F-31077 Toulouse 04, France.
   [Goosmann, Christian; Brinkmann, Volker] Max Planck Inst Infect Biol, Dept Immunol, Microscopy Core Facil, D-10117 Berlin, Germany.
   [Mollenkopf, Hans-Joachim] Max Planck Inst Infect Biol, Dept Immunol, Microarray Core Facil, D-10117 Berlin, Germany.
   [Hurwitz, Robert] Max Planck Inst Infect Biol, Prot Purificat Core Facil, D-10117 Berlin, Germany.
   [Fillatreau, Simon] German Rheumatism Res Ctr Berlin DRFZ, D-10117 Berlin, Germany.
C3 Max Planck Society; Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Max Planck Society; Hannover Medical School; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Max Planck Society; Max Planck Society; Max Planck Society; Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ)
RP Kaufmann, SHE (corresponding author), Max Planck Inst Infect Biol, Dept Immunol, Charitepl 1, D-10117 Berlin, Germany.
EM kaufmann@mpiib-berlin.mpg.de
FU European Union [Health-F3-2009-241745, Health-F4-2008-223451]
NR 67
TC 306
Z9 374
U1 2
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 AUG 28
PY 2014
VL 512
IS 7515
BP 387
EP U332
DI 10.1038/nature13684
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600024
PM 25119038
DA 2026-03-09
ER

PT J
AU Prindle, A
   Selimkhanov, J
   Li, H
   Razinkov, I
   Tsimring, LS
   Hasty, J
AF Prindle, Arthur
   Selimkhanov, Jangir
   Li, Howard
   Razinkov, Ivan
   Tsimring, Lev S.
   Hasty, Jeff
TI Rapid and tunable post-translational coupling of genetic circuits
SO NATURE
LA English
DT Article
ID protein; logic; ultrasensitivity; degradation; proteolysis; sigma(s); biology; rssb
AB One promise of synthetic biology is the creation of genetic circuitry that enables the execution of logical programming in living cells. Such 'wet programming'is positioned to transform a wide and diverse swathe of biotechnology ranging from therapeutics and diagnostics to water treatment strategies. Although progress in the development of a library of genetic modules continues apace(1-4), a major challenge for their integration into larger circuits is the generation of sufficiently fast and precise communication between modules(5,6). Anattractive approach is to integrate engineered circuits with host processes that facilitate robust cellular signalling(7). In this context, recent studies have demonstrated that bacterial protein degradation can trigger a precise response to stress by overloading a limited supply of intracellular proteases(8-10). Here we use protease competition to engineer rapid and tunable coupling of genetic circuits across multiple spatial and temporal scales. We characterize coupling delay times that are more than an order of magnitude faster than standard transcription factor- based coupling methods (less than 1 min compared with 2040 min) and demonstrate tunability through manipulation of the linker between the protein and its degradation tag. We use this mechanism as a platform to couple genetic clocks at the intracellular and colony level, then synchronize the multi-colony dynamics to reduce variability in both clocks. We show how the coupled clock network can be used to encode independent environmental inputs into a single time series output, thus enabling frequency multiplexing (information transmitted on a common channel by distinct frequencies) in a genetic circuit context. Our results establish a general framework for the rapid and tunable coupling of genetic circuits through the use of native `queueing' processes such as competitive protein degradation.
C1 [Prindle, Arthur; Selimkhanov, Jangir; Li, Howard; Razinkov, Ivan; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Tsimring, Lev S.; Hasty, Jeff] Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA.
   [Hasty, Jeff] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
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
RP Hasty, J (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM hasty@bioeng.ucsd.edu
FU National Science Foundation [MCB-1121748]; San Diego Center for Systems Biology (NIH) [P50 GM085764]; US Department of Defense National Defense Science and Engineering Graduate Fellowship; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1121748] Funding Source: National Science Foundation
NR 30
TC 136
Z9 165
U1 2
U2 126
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 17
PY 2014
VL 508
IS 7496
BP 387
EP +
DI 10.1038/nature13238
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000050
PM 24717442
DA 2026-03-09
ER

PT J
AU Kim, MS
   Pinto, SM
   Getnet, D
   Nirujogi, RS
   Manda, SS
   Chaerkady, R
   Madugundu, AK
   Kelkar, DS
   Isserlin, R
   Jain, S
   Thomas, JK
   Muthusamy, B
   Leal-Rojas, P
   Kumar, P
   Sahasrabuddhe, NA
   Balakrishnan, L
   Advani, J
   George, B
   Renuse, S
   Selvan, LDN
   Patil, AH
   Nanjappa, V
   Radhakrishnan, A
   Prasad, S
   Subbannayya, T
   Raju, R
   Kumar, M
   Sreenivasamurthy, SK
   Marimuthu, A
   Sathe, GJ
   Chavan, S
   Datta, KK
   Subbannayya, Y
   Sahu, A
   Yelamanchi, SD
   Jayaram, S
   Rajagopalan, P
   Sharma, J
   Murthy, KR
   Syed, N
   Goel, R
   Khan, AA
   Ahmad, S
   Dey, G
   Mudgal, K
   Chatterjee, A
   Huang, TC
   Zhong, J
   Wu, XY
   Shaw, PG
   Freed, D
   Zahari, MS
   Mukherjee, KK
   Shankar, S
   Mahadevan, A
   Lam, H
   Mitchell, CJ
   Shankar, SK
   Satishchandra, P
   Schroeder, JT
   Sirdeshmukh, R
   Maitra, A
   Leach, SD
   Drake, CG
   Halushka, MK
   Prasad, TSK
   Hruban, RH
   Kerr, CL
   Bader, GD
   Iacobuzio-Donahue, CA
   Gowda, H
   Pandey, A
AF Kim, Min-Sik
   Pinto, Sneha M.
   Getnet, Derese
   Nirujogi, Raja Sekhar
   Manda, Srikanth S.
   Chaerkady, Raghothama
   Madugundu, Anil K.
   Kelkar, Dhanashree S.
   Isserlin, Ruth
   Jain, Shobhit
   Thomas, Joji K.
   Muthusamy, Babylakshmi
   Leal-Rojas, Pamela
   Kumar, Praveen
   Sahasrabuddhe, Nandini A.
   Balakrishnan, Lavanya
   Advani, Jayshree
   George, Bijesh
   Renuse, Santosh
   Selvan, Lakshmi Dhevi N.
   Patil, Arun H.
   Nanjappa, Vishalakshi
   Radhakrishnan, Aneesha
   Prasad, Samarjeet
   Subbannayya, Tejaswini
   Raju, Rajesh
   Kumar, Manish
   Sreenivasamurthy, Sreelakshmi K.
   Marimuthu, Arivusudar
   Sathe, Gajanan J.
   Chavan, Sandip
   Datta, Keshava K.
   Subbannayya, Yashwanth
   Sahu, Apeksha
   Yelamanchi, Soujanya D.
   Jayaram, Savita
   Rajagopalan, Pavithra
   Sharma, Jyoti
   Murthy, Krishna R.
   Syed, Nazia
   Goel, Renu
   Khan, Aafaque A.
   Ahmad, Sartaj
   Dey, Gourav
   Mudgal, Keshav
   Chatterjee, Aditi
   Huang, Tai-Chung
   Zhong, Jun
   Wu, Xinyan
   Shaw, Patrick G.
   Freed, Donald
   Zahari, Muhammad S.
   Mukherjee, Kanchan K.
   Shankar, Subramanian
   Mahadevan, Anita
   Lam, Henry
   Mitchell, Christopher J.
   Shankar, Susarla Krishna
   Satishchandra, Parthasarathy
   Schroeder, John T.
   Sirdeshmukh, Ravi
   Maitra, Anirban
   Leach, Steven D.
   Drake, Charles G.
   Halushka, Marc K.
   Prasad, T. S. Keshava
   Hruban, Ralph H.
   Kerr, Candace L.
   Bader, Gary D.
   Iacobuzio-Donahue, Christine A.
   Gowda, Harsha
   Pandey, Akhilesh
TI A draft map of the human proteome
SO NATURE
LA English
DT Article
ID identification; knowledge; proteins; database; project; tandem
AB The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue ( available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.
C1 [Kim, Min-Sik; Getnet, Derese; Chaerkady, Raghothama; Leal-Rojas, Pamela; Prasad, Samarjeet; Huang, Tai-Chung; Zhong, Jun; Wu, Xinyan; Shaw, Patrick G.; Freed, Donald; Mitchell, Christopher J.; Leach, Steven D.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Kim, Min-Sik; Chaerkady, Raghothama; Wu, Xinyan; Zahari, Muhammad S.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
   [Pinto, Sneha M.; Nirujogi, Raja Sekhar; Manda, Srikanth S.; Madugundu, Anil K.; Kelkar, Dhanashree S.; Thomas, Joji K.; Muthusamy, Babylakshmi; Kumar, Praveen; Sahasrabuddhe, Nandini A.; Balakrishnan, Lavanya; Advani, Jayshree; George, Bijesh; Renuse, Santosh; Selvan, Lakshmi Dhevi N.; Patil, Arun H.; Nanjappa, Vishalakshi; Radhakrishnan, Aneesha; Subbannayya, Tejaswini; Raju, Rajesh; Kumar, Manish; Sreenivasamurthy, Sreelakshmi K.; Marimuthu, Arivusudar; Sathe, Gajanan J.; Chavan, Sandip; Datta, Keshava K.; Subbannayya, Yashwanth; Sahu, Apeksha; Yelamanchi, Soujanya D.; Jayaram, Savita; Rajagopalan, Pavithra; Sharma, Jyoti; Murthy, Krishna R.; Syed, Nazia; Goel, Renu; Khan, Aafaque A.; Ahmad, Sartaj; Dey, Gourav; Chatterjee, Aditi; Sirdeshmukh, Ravi; Prasad, T. S. Keshava; Gowda, Harsha; Pandey, Akhilesh] Inst Bioinformat, Bangalore 560066, Karnataka, India.
   [Getnet, Derese; Pandey, Akhilesh] Adrienne Helis Malvin Med Res Fdn, New Orleans, LA 70130 USA.
   [Isserlin, Ruth; Jain, Shobhit; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Leal-Rojas, Pamela] Univ La Frontera, Dept Pathol, Ctr Genet & Immunol Studies Sci & Technol Bioreso, Temuco 4811230, Chile.
   [Mudgal, Keshav] Univ London Imperial Coll Sci Technol & Med, Sch Med, London SW7 2AZ, England.
   [Mukherjee, Kanchan K.] Postgrad Inst Med Educ & Res, Dept Neurosurg, Chandigarh 160012, India.
   [Shankar, Subramanian] Armed Forces Med Coll, Dept Internal Med, Pune 411040, Maharashtra, India.
   [Mahadevan, Anita; Shankar, Susarla Krishna] Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India.
   [Mahadevan, Anita; Shankar, Susarla Krishna] Natl Inst Mental Hlth & Neurosci, Neurobiol Res Ctr, Bangalore 560029, Karnataka, India.
   [Lam, Henry] Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Hong Kong, Hong Kong, Peoples R China.
   [Lam, Henry] Hong Kong Univ Sci & Technol, Div Biomed Engn, Hong Kong, Hong Kong, Peoples R China.
   [Satishchandra, Parthasarathy] Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India.
   [Schroeder, John T.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA.
   [Maitra, Anirban; Halushka, Marc K.; Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.; Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Sch Med, Baltimore, MD 21231 USA.
   [Maitra, Anirban; Drake, Charles G.; Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA.
   [Leach, Steven D.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21231 USA.
   [Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Immunol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Drake, Charles G.] Johns Hopkins Univ, Sch Med, Dept Urol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Kerr, Candace L.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA.
   [Pandey, Akhilesh] Diana Helis Henry Med Res Fdn, New Orleans, LA 70130 USA.
C3 Johns Hopkins University; Johns Hopkins University; University of Toronto; Universidad de La Frontera; Imperial College London; Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh; Armed Forces Medical College; National Institute of Mental Health & Neurosciences - India; National Institute of Mental Health & Neurosciences - India; Hong Kong University of Science & Technology; Hong Kong University of Science & Technology; National Institute of Mental Health & Neurosciences - India; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University
RP Gowda, H (corresponding author), Inst Bioinformat, Bangalore 560066, Karnataka, India.
EM harsha@ibioinformatics.org; pandey@jhmi.edu
FU NIH [U54GM103520]; NCI's Clinical Proteomic Tumor Analysis Consortium initiative [U24CA160036]; National Heart, Lung and Blood Institute [HHSN268201000032C]; Sol Goldman Pancreatic Cancer Research Center; National Resource for Network Biology [P41GM103504]; DBT Program Support on Neuroproteomics [BT/01/COE/08/05]; NIMHANS; Council of Scientific and Industrial Research; University Grants Commission; Department of Science and Technology, Government of India; National Institute of General Medical Sciences [P41GM103504, T32GM007814] Funding Source: NIH RePORTER
NR 44
TC 1724
Z9 2010
U1 3
U2 598
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2014
VL 509
IS 7502
BP 575
EP +
DI 10.1038/nature13302
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100040
PM 24870542
DA 2026-03-09
ER

PT J
AU Baringhaus, J
   Ruan, M
   Edler, F
   Tejeda, A
   Sicot, M
   Taleb-Ibrahimi, A
   Li, AP
   Jiang, ZG
   Conrad, EH
   Berger, C
   Tegenkamp, C
   de Heer, WA
AF Baringhaus, Jens
   Ruan, Ming
   Edler, Frederik
   Tejeda, Antonio
   Sicot, Muriel
   Taleb-Ibrahimi, Amina
   Li, An-Ping
   Jiang, Zhigang
   Conrad, Edward H.
   Berger, Claire
   Tegenkamp, Christoph
   de Heer, Walt A.
TI Exceptional ballistic transport in epitaxial graphene nanoribbons
SO NATURE
LA English
DT Article
ID quantum; confinement
AB Graphene nanoribbons will be essential components in future graphene nanoelectronics(1). However, in typical nanoribbons produced from lithographically patterned exfoliated graphene, the charge carriers travel only about ten nanometres between scattering events, resulting in minimum sheet resistances of about one kilohm per square(2-5). Here we show that 40-nanometre-wide graphene nanoribbons epitaxially grown on silicon carbide(6,7) are single-channel room-temperature ballistic conductors on a length scale greater than ten micrometres, which is similar to the performance of metallic carbon nanotubes. This is equivalent to sheet resistances below 1 ohm per square, surpassing theoretical predictions for perfect graphene(8) by at least an order of magnitude. In neutral graphene ribbons, we show that transport is dominated by two modes. One is ballistic and temperature independent; the other is thermally activated. Transport is protected from back-scattering, possibly reflecting ground-state properties of neutral graphene. At room temperature, the resistance of both modes is found to increase abruptly at a particular length-the ballistic mode at 16 micrometres and the other at 160 nanometres. Our epitaxial graphene nanoribbons will be important not only in fundamental science, but also-because they can be readily produced in thousands-in advanced nanoelectronics, which can make use of their room-temperature ballistic transport properties.
C1 [Baringhaus, Jens; Edler, Frederik; Tegenkamp, Christoph] Leibniz Univ Hannover, Inst Festkorperphys, D-30167 Hannover, Germany.
   [Ruan, Ming; Jiang, Zhigang; Conrad, Edward H.; Berger, Claire; de Heer, Walt A.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Tejeda, Antonio; Sicot, Muriel] Univ Lorraine, UMR CNRS 7198, Inst Jean Lamour, F-54506 Vandoeuvre Les Nancy, France.
   [Tejeda, Antonio; Taleb-Ibrahimi, Amina] UR1 CNRS Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France.
   [Li, An-Ping] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
   [Berger, Claire] CNRS UJF INP, Inst Neel, F-38042 Grenoble 6, France.
C3 Leibniz University Hannover; University System of Georgia; Georgia Institute of Technology; Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); United States Department of Energy (DOE); Oak Ridge National Laboratory; Center for Nanophase Materials Sciences; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP de Heer, WA (corresponding author), Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
EM walt.deheer@physics.gatech.edu
FU German Research Foundation [1459]; AFOSR; NSF [MRSEC - DMR 0820382]; W. M. Keck Foundation; Partner University Fund; Scientific User Facilities Division, BES of the DOE
NR 30
TC 512
Z9 600
U1 4
U2 633
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 20
PY 2014
VL 506
IS 7488
BP 349
EP 354
DI 10.1038/nature12952
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800037
PM 24499819
DA 2026-03-09
ER

PT J
AU Ranade, SS
   Woo, SH
   Dubin, AE
   Moshourab, RA
   Wetzel, C
   Petrus, M
   Mathur, J
   Bégay, V
   Coste, B
   Mainquist, J
   Wilson, AJ
   Francisco, AG
   Reddy, K
   Qiu, ZZ
   Wood, JN
   Lewin, GR
   Patapoutian, A
AF Ranade, Sanjeev S.
   Woo, Seung-Hyun
   Dubin, Adrienne E.
   Moshourab, Rabih A.
   Wetzel, Christiane
   Petrus, Matt
   Mathur, Jayanti
   Begay, Valerie
   Coste, Bertrand
   Mainquist, James
   Wilson, A. J.
   Francisco, Allain G.
   Reddy, Kritika
   Qiu, Zhaozhu
   Wood, John N.
   Lewin, Gary R.
   Patapoutian, Ardem
TI Piezo2 is the major transducer of mechanical forces for touch sensation in mice
SO NATURE
LA English
DT Article
ID regulated anion channel; merkel cells; sensory neurons; mechanosensitive currents; essential component; ion channels; mouse; nociception; protein; contributes
AB The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals(1). It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive(2). Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes(3,4). It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron(4-6); however, major aspects of touch sensation remain intact without Merkel cell activity(4,7). Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
C1 [Ranade, Sanjeev S.; Woo, Seung-Hyun; Dubin, Adrienne E.; Coste, Bertrand; Francisco, Allain G.; Reddy, Kritika; Qiu, Zhaozhu; Patapoutian, Ardem] Scripps Res Inst, Dorris Neurosci Ctr, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Moshourab, Rabih A.; Wetzel, Christiane; Begay, Valerie; Lewin, Gary R.] Max Delbruck Ctr Mol Med, Dept Neurosci, D-13092 Berlin, Germany.
   [Moshourab, Rabih A.] Univ Med Berlin, Klin Anasthesiol Schwerpunkt Operat Intens Med, Virchow Klinikum Charite, D-13353 Berlin, Germany.
   [Petrus, Matt; Mathur, Jayanti; Mainquist, James; Wilson, A. J.; Qiu, Zhaozhu] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
   [Wood, John N.] UCL, Mol Nocicept Grp, Wolfson Inst Biomed Res, London WC1E 6BT, England.
C3 Scripps Research Institute; Howard Hughes Medical Institute; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Novartis; Novartis USA; University of London; University College London
RP Patapoutian, A (corresponding author), Scripps Res Inst, Dorris Neurosci Ctr, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
EM ardem@scripps.edu
FU California Institute of Regenerative Medicine; Max Delbruck Center (MDC); European Research Council [294678]; Deutsche Forschungsgemeinshaft [SFB958]; NIH [R01 DE022358]; European Research Council (ERC) [294678] Funding Source: European Research Council (ERC); Biotechnology and Biological Sciences Research Council [BB/F000227/1] Funding Source: researchfish; Medical Research Council [G0901905] Funding Source: researchfish; Versus Arthritis [20200] Funding Source: researchfish; Wellcome Trust [101054/Z/13/Z] Funding Source: researchfish; BBSRC [BB/F000227/1] Funding Source: UKRI; MRC [G0901905] Funding Source: UKRI
NR 35
TC 692
Z9 825
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 DEC 4
PY 2014
VL 516
IS 7529
BP 121
EP U330
DI 10.1038/nature13980
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800052
PM 25471886
DA 2026-03-09
ER

PT J
AU Pascoli, V
   Terrier, J
   Espallergues, J
   Valjent, E
   O'Connor, EC
   Lüscher, C
AF Pascoli, Vincent
   Terrier, Jean
   Espallergues, Julie
   Valjent, Emmanuel
   O'Connor, Eoin Cornelius
   Luescher, Christian
TI Contrasting forms of cocaine-evoked plasticity control components of relapse
SO NATURE
LA English
DT Article
ID accumbens-projection neurons; long-term depression; nucleus-accumbens; synaptic plasticity; ampa receptors; addiction; mechanisms; dopamine; incubation; reward
AB Nucleus accumbens neurons serve to integrate information from cortical and limbic regions to direct behaviour. Addictive drugs are proposed to hijack this system, enabling drug-associated cues to trigger relapse to drug seeking. However, the connections affected and proof of causality remain to be established. Here we use a mouse model of delayed cue-associated cocaine seeking with ex vivo electrophysiology in optogenetically delineated circuits. We find that seeking correlates with rectifying AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor transmission and a reduced AMPA/NMDA (N-methyl-D-aspartate) ratio at medial prefrontal cortex (mPFC) to nucleus accumbens shell D1-receptor medium-sized spiny neurons (D1R-MSNs). In contrast, the AMPA/NMDA ratio increases at ventral hippocampus to D1R-MSNs. Optogenetic reversal of cocaine-evoked plasticity at both inputs abolishes seeking, whereas selective reversal at mPFC or ventral hippocampus synapses impairs response discrimination or reduces response vigour during seeking, respectively. Taken together, we describe how information integration in the nucleus accumbens is commandeered by cocaine at discrete synapses to allow relapse. Our approach holds promise for identifying synaptic causalities in other behavioural disorders.
C1 [Pascoli, Vincent; Terrier, Jean; O'Connor, Eoin Cornelius; Luescher, Christian] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Espallergues, Julie; Valjent, Emmanuel] CNRS, INSERM, U661, F-34094 Montpellier, France.
   [Espallergues, Julie; Valjent, Emmanuel] CNRS, Inst Genom Fonct, UMR 5203, F-34094 Montpellier, France.
   [Espallergues, Julie; Valjent, Emmanuel] Univ Montpellier I, UMR 5203, F-34094 Montpellier, France.
   [Espallergues, Julie; Valjent, Emmanuel] Univ Montpellier 2, UMR 5203, F-34094 Montpellier, France.
   [Luescher, Christian] Univ Hosp Geneva, Dept Clin Neurosci, Clin Neurol, CH-1211 Geneva, Switzerland.
C3 University of Geneva; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); 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; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); University of Geneva
RP Lüscher, C (corresponding author), Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
EM christian.luscher@unige.ch
FU Swiss National Science Foundation; National Center of Competence in Research (NCCR) 'SYNAPSY - The Synaptic Bases of Mental Diseases' of the Swiss National Science Foundation; European Research Council advanced grant (MeSSI); MD-PhD grant of the Swiss Confederation; Avenir grant (Inserm); Agence Nationale de la Recherche
NR 50
TC 323
Z9 380
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 MAY 22
PY 2014
VL 509
IS 7501
BP 459
EP +
DI 10.1038/nature13257
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000032
PM 24848058
DA 2026-03-09
ER

PT J
AU Cooper, KL
   Sears, KE
   Uygur, A
   Maier, J
   Baczkowski, KS
   Brosnahan, M
   Antczak, D
   Skidmore, JA
   Tabin, CJ
AF Cooper, Kimberly L.
   Sears, Karen E.
   Uygur, Aysu
   Maier, Jennifer
   Baczkowski, Karl-Stephan
   Brosnahan, Margaret
   Antczak, Doug
   Skidmore, Julian A.
   Tabin, Clifford J.
TI Patterning and post-patterning modes of evolutionary digit loss in mammals
SO NATURE
LA English
DT Article
ID apical ectodermal ridge; programmed cell-death; limb development; vertebrate limb; developmental basis; reduction; hedgehog; bud; hemiergis; number
AB A reduction in the number of digits has evolved many times in tetrapods, particularly in cursorial mammals that travel over deserts and plains, yet the underlying developmental mechanisms have remained elusive. Here we show that digit loss can occur both during early limbpatterning and at later post-patterning stages of chondrogenesis. In the 'odd-toed' jerboa (Dipus sagitta) and horse and the 'even-toed' camel, extensive cell death sculpts the tissue around the remaining toes. In contrast, digit loss inthepig is orchestrated by earlier limb patterning mechanisms including downregulation of Ptch1 expression but no increase in cell death. Together these data demonstrate remarkable plasticity in the mechanisms of vertebrate limb evolution and shed light on the complexity of morphological convergence, particularly within the artiodactyl lineage.
C1 [Cooper, Kimberly L.; Uygur, Aysu; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sears, Karen E.; Maier, Jennifer] Univ Illinois, Dept Anim Biol, Urbana, IL 61801 USA.
   [Baczkowski, Karl-Stephan] Ecole Normale Super Lyon, F-69007 Lyon, France.
   [Brosnahan, Margaret; Antczak, Doug] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
   [Skidmore, Julian A.] Camel Reprod Ctr, Dubai, U Arab Emirates.
C3 Harvard University; Harvard Medical School; University of Illinois System; University of Illinois Urbana-Champaign; Ecole Normale Superieure de Lyon (ENS de LYON); Cornell University
RP Cooper, KL (corresponding author), Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
EM kcooper@ucsd.edu; ksears@life.illinois.edu
FU NIH [R37HD032443]; NSF IOS grant [1257873]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1257873] Funding Source: National Science Foundation
NR 36
TC 120
Z9 145
U1 4
U2 119
PU NATURE PUBLISHING 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 3
PY 2014
VL 511
IS 7507
BP 41
EP U537
DI 10.1038/nature13496
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400031
PM 24990742
DA 2026-03-09
ER

PT J
AU Sun, T
   Wang, KL
   Iinuma, T
   Hino, R
   He, JH
   Fujimoto, H
   Kido, M
   Osada, Y
   Miura, S
   Ohta, Y
   Hu, Y
AF Sun, Tianhaozhe
   Wang, Kelin
   Iinuma, Takeshi
   Hino, Ryota
   He, Jiangheng
   Fujimoto, Hiromi
   Kido, Motoyuki
   Osada, Yukihito
   Miura, Satoshi
   Ohta, Yusaku
   Hu, Yan
TI Prevalence of viscoelastic relaxation after the 2011 Tohoku-oki earthquake
SO NATURE
LA English
DT Article
ID lithosphere-asthenosphere boundary; postseismic deformation; arc; displacement; friction; sumatra; zone; melt
AB After a large subduction earthquake, crustal deformation continues to occur, with a complex pattern of evolution(1). This postseismic deformation is due primarily to viscoelastic relaxation of stresses induced by the earthquake rupture and continuing slip (afterslip) or relocking of different parts of the fault(2-6). When postseismic geodetic observations are used to study Earth's rheology and fault behaviour, it is commonly assumed that short-term (a few years) deformation near the rupture zone is caused mainly by afterslip, and that viscoelasticity is important only for longer-term deformation(6,7). However, it is difficult to test the validity of this assumption against conventional geodetic data. Here we show that new seafloor GPS(Global Positioning System) observations immediately after the great Tohoku-oki earthquake provide unambiguous evidence for the dominant role of viscoelastic relaxation in short-term postseismic deformation. These data reveal fast landward motion of the trench area, opposing the seaward motion of GPS siteson land. Using numerical models of transient viscoelastic mantle rheology, we demonstrate that the landward motion is a consequence of relaxation of stresses induced by the asymmetric rupture of the thrust earthquake, a process previously unknown because of the lack of near-field observations. Our findings indicate that previous models assuming an elastic Earth will have substantially overestimated afterslip downdip of the rupture zone, and underestimated afterslip updip of the rupture zone; our knowledge of fault friction based on these estimates therefore needs to be revised.
C1 [Sun, Tianhaozhe; Wang, Kelin] Univ Victoria, Sch Earth & Ocean Sci, Victoria, BC V8P 5C2, Canada.
   [Sun, Tianhaozhe; He, Jiangheng] Nat Resources Canada, Geol Survey Canada, Pacific Geosci Ctr, Sidney, BC V8L 4B2, Canada.
   [Iinuma, Takeshi; Fujimoto, Hiromi; Kido, Motoyuki; Osada, Yukihito] Tohoku Univ, Int Res Inst Disaster Sci, Sendai, Miyagi 9800845, Japan.
   [Miura, Satoshi; Ohta, Yusaku] Tohoku Univ, Grad Sch Sci, Res Ctr Predict Earthquakes & Volcan Erupt, Sendai, Miyagi 9808578, Japan.
   [Hu, Yan] Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
   [Hu, Yan] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 University of Victoria; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; Tohoku University; Tohoku University; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Wang, KL (corresponding author), Univ Victoria, Sch Earth & Ocean Sci, Victoria, BC V8P 5C2, Canada.
EM kwang@nrcan.gc.ca
FU Geological Survey of Canada; Natural Sciences and Engineering Research Council of Canada through University of Victoria; University of Victoria; Howard E. Petch Scholarship; Ministry of Education, Culture, Sports, Science and Technology of Japan under Earthquake and Volcano Hazards Observation and Research Program; Grants-in-Aid for Scientific Research [23253003, 26109007, 26000002] Funding Source: KAKEN
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   Fujimoto H, 2014, MONOGRAPHS ENVIRON., V0, P0
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   Japan Coast Guard & Tohoku University, 2013, REP COORD COMM EARTH, V90, P3
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NR 46
TC 252
Z9 283
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 OCT 2
PY 2014
VL 514
IS 7520
BP 84
EP +
DI 10.1038/nature13778
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800040
PM 25231864
DA 2026-03-09
ER

PT J
AU Lo, JCL
   Gui, JH
   Yabe, YK
   Pan, CM
   Baran, PS
AF Lo, Julian C.
   Gui, Jinghan
   Yabe, Yuki
   Pan, Chung-Mao
   Baran, Phil S.
TI Functionalized olefin cross-coupling to construct carbon-carbon bonds
SO NATURE
LA English
DT Article
ID conjugate addition; unactivated olefins; tertiary alcohols; hydrogenation; reagents; esters; phenylsilane; chemistry; mechanism; radicals
AB Carbon-carbon (C-C) bonds form the backbone of many important molecules, including polymers, dyes and pharmaceutical agents. The development of new methods to create these essential connections in a rapid and practical fashion has been the focus of numerous organic chemists. This endeavour relies heavily on the ability to form C-C bonds in the presence of sensitive functional groups and congested structural environments. Here we report a chemical transformation that allows the facile construction of highly substituted and uniquely functionalized C-C bonds. Using a simple iron catalyst, an inexpensive silane and a benign solvent under ambient atmosphere, heteroatom-substituted olefins are easily reacted with electron-deficient olefins to create molecular architectures that were previously difficult or impossible to access. More than 60 examples are presented with a wide array of substrates, demonstrating the chemoselectivity and mildness of this simple reaction.
C1 [Lo, Julian C.; Gui, Jinghan; Yabe, Yuki; Pan, Chung-Mao; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Baran, PS (corresponding author), Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM pbaran@scripps.edu
FU NIH/NIGMS [GM-097444]; National Science Foundation; Shanghai Institute of Organic Chemistry; Zhejiang Medicine Co.; Pharmaron; Japan Society for the Promotion of Science
NR 47
TC 400
Z9 461
U1 7
U2 361
PU NATURE PUBLISHING 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 18
PY 2014
VL 516
IS 7531
BP 343
EP 348
DI 10.1038/nature14006
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800036
PM 25519131
DA 2026-03-09
ER

PT J
AU Mizuguchi, T
   Fudenberg, G
   Mehta, S
   Belton, JM
   Taneja, N
   Folco, HD
   FitzGerald, P
   Dekker, J
   Mirny, L
   Barrowman, J
   Grewal, SIS
AF Mizuguchi, Takeshi
   Fudenberg, Geoffrey
   Mehta, Sameet
   Belton, Jon-Matthew
   Taneja, Nitika
   Folco, Hernan Diego
   FitzGerald, Peter
   Dekker, Job
   Mirny, Leonid
   Barrowman, Jemima
   Grewal, Shiv I. S.
TI Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe
SO NATURE
LA English
DT Article
ID fission yeast chromosm; gene-expression; saccharomyces-cerevisiae; chromatin interactions; drosophila genome; hi-c; organization; centromeres; principles; domains
AB Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions(1-7). How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis(8) to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes(9). Our analyses of wild-type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form 'globules'. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains(9-11), is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fibre compaction at centromeres and promotes prominent inter-arm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra-and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions.
C1 [Mizuguchi, Takeshi; Mehta, Sameet; Taneja, Nitika; Folco, Hernan Diego; Barrowman, Jemima; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
   [Fudenberg, Geoffrey; Mirny, Leonid] Harvard Univ, Grad Program Biophys, Boston, MA 02115 USA.
   [Fudenberg, Geoffrey; Mirny, Leonid] MIT, Dept Phys, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
   [Belton, Jon-Matthew; Dekker, Job] Univ Massachusetts, Sch Med, Program Syst Biol, Worcester, MA 01605 USA.
   [FitzGerald, Peter] NCI, Genome Anal Unit, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Harvard University; Massachusetts Institute of Technology (MIT); University of Massachusetts System; University of Massachusetts Worcester; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Grewal, SIS (corresponding author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU National Institutes of Health, National Cancer Institute; NHGRI [HG003143]; NCI Physical Sciences-Oncology Center at MIT [U54CA143874]; National Cancer Institute [ZIABC011208, ZIABC010523] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER
NR 35
TC 208
Z9 253
U1 1
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 DEC 18
PY 2014
VL 516
IS 7531
BP 432
EP +
DI 10.1038/nature13833
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800055
PM 25307058
DA 2026-03-09
ER

PT J
AU Riol-Blanco, L
   Ordovas-Montanes, J
   Perro, M
   Naval, E
   Thiriot, A
   Alvarez, D
   Paust, S
   Wood, JN
   von Andrian, UH
AF Riol-Blanco, Lorena
   Ordovas-Montanes, Jose
   Perro, Mario
   Naval, Elena
   Thiriot, Aude
   Alvarez, David
   Paust, Silke
   Wood, John N.
   von Andrian, Ulrich H.
TI Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation
SO NATURE
LA English
DT Article
ID delta t-cells; peripheral lymphoid organs; dendritic cells; plaque-formation; nervous-system; receptor; mice; identification; monocytes; cytokine
AB The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbours specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17-producing gamma delta T (gamma delta T17) cells, the aberrant activation of which by IL-23 can provoke psoriasis-like inflammation(1-4). The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibres. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear(5,6). We exposed the skin of mice to imiquimod, which induces IL-23-dependent psoriasis-like inflammation(7,8). Hereweshowthat a subset of sensory neurons expressing the ion channels TRPV1 and Na(v)1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors(9-11), DDCs failed to produce IL-23 in imiquimod-exposed skin. Consequently, the local production of IL-23-dependent inflammatory cytokines by dermal gamma delta T17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communicationwithDDCs and restored the inflammatory response(12). These findings indicate that TRPV1(+)Na(v)1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway andcontrol cutaneousimmune responses.
C1 [Riol-Blanco, Lorena; Ordovas-Montanes, Jose; Perro, Mario; Naval, Elena; Thiriot, Aude; Alvarez, David; Paust, Silke; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
   [Wood, John N.] UCL, Inst Biomed Res, London WC1E 6BT, England.
C3 Harvard University; Harvard Medical School; University of London; University College London
RP von Andrian, UH (corresponding author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
EM uva@hms.harvard.edu
FU National Institutes of Health (NIH) [AI069259, AI078897, AI095261, AI111595]; NIH [5F31AR063546-02]; Human Frontiers Science Program; Charles A. King Trust; National Psoriasis Foundation; BBSRC [BB/F000227/1] Funding Source: UKRI; MRC [G0901905] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F000227/1] Funding Source: researchfish; Medical Research Council [G0901905] Funding Source: researchfish; Wellcome Trust [101054/Z/13/Z] Funding Source: researchfish
NR 36
TC 455
Z9 519
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 JUN 5
PY 2014
VL 510
IS 7503
BP 157
EP +
DI 10.1038/nature13199
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900048
PM 24759321
DA 2026-03-09
ER

PT J
AU Reich, S
   Guilligay, D
   Pflug, A
   Malet, H
   Berger, I
   Crépin, T
   Hart, D
   Lunardi, T
   Nanao, M
   Ruigrok, RWH
   Cusack, S
AF Reich, Stefan
   Guilligay, Delphine
   Pflug, Alexander
   Malet, Helene
   Berger, Imre
   Crepin, Thibaut
   Hart, Darren
   Lunardi, Thomas
   Nanao, Max
   Ruigrok, Rob W. H.
   Cusack, Stephen
TI Structural insight into cap-snatching and RNA synthesis by influenza polymerase
SO NATURE
LA English
DT Article
ID virus virion rna; p-proteins; in-vitro; endonuclease; mechanism; subunit; complex; binding; transcription; initiation
AB Influenza virus polymerase uses a capped primer, derived by 'cap-snatching' from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in situ rotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into the active initiation and elongation states.
C1 [Reich, Stefan; Guilligay, Delphine; Pflug, Alexander; Malet, Helene; Berger, Imre; Hart, Darren; Lunardi, Thomas; Nanao, Max; Cusack, Stephen] European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France.
   [Reich, Stefan; Guilligay, Delphine; Pflug, Alexander; Malet, Helene; Berger, Imre; Crepin, Thibaut; Hart, Darren; Lunardi, Thomas; Nanao, Max; Ruigrok, Rob W. H.; Cusack, Stephen] Univ Grenoble Alpes, Ctr Natl Rech Sci, EMBL Unit Virus Host Cell Interact, F-38042 Grenoble 9, France.
C3 European Molecular Biology Laboratory (EMBL); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS)
RP Cusack, S (corresponding author), European Mol Biol Lab, Grenoble Outstn, 71 Ave Martyrs,CS 90181, F-38042 Grenoble 9, France.
EM cusack@embl.fr
FU ERC V-RNA [322586]; EU FLU-PHARM [259751]; Roche; European Research Council (ERC) [322586] Funding Source: European Research Council (ERC)
NR 54
TC 374
Z9 428
U1 1
U2 104
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 361
EP +
DI 10.1038/nature14009
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800039
PM 25409151
DA 2026-03-09
ER

PT J
AU Kang, D
   Pikhitsa, PV
   Choi, YW
   Lee, C
   Shin, SS
   Piao, LF
   Park, B
   Suh, KY
   Kim, TI
   Choi, M
AF Kang, Daeshik
   Pikhitsa, Peter V.
   Choi, Yong Whan
   Lee, Chanseok
   Shin, Sung Soo
   Piao, Linfeng
   Park, Byeonghak
   Suh, Kahp-Yang
   Kim, Tae-il
   Choi, Mansoo
TI Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system
SO NATURE
LA English
DT Article
ID artificial skin; electronics; transistors; matrix; fracture; films
AB Recently developed flexible mechanosensors based on inorganic silicon(1-3), organic semiconductors(4-6), carbon nanotubes(7), graphene platelets(8), pressure-sensitive rubber(9) and self-powered devices(10,11) are highly sensitive and can be applied to humanskin. However, the development of a multifunctional sensor satisfying the requirements of ultra-high mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints(12). Here we demonstrate that sensors based on nanoscale crack junctions and inspired by the geometry of a spider's slit organ can attain ultrahigh sensitivity and serve multiple purposes. The sensors are sensitive to strain (with a gauge factor of over 2,000 in the 0-2 per cent strain range) and vibration (with the ability to detect amplitudes of approximately 10 nanometres). The device is reversible, reproducible, durable and mechanically flexible, and can thus be easily mounted on human skin as an electronic multipixel array. The ultrahigh mechanosensitivity is attributed to the disconnection-reconnection process undergone by the zip-like nanoscale crack junctions under strain or vibration. The proposed theoretical model is consistent with experimental data that we report here. We also demonstrate that sensors based on nanoscale crack junctions are applicable to highly selective speech pattern recognition and the detection of physiological signals. The nanoscale crack junction-based sensory system could be useful in diverse applications requiring ultrahigh displacement sensitivity.
C1 [Kang, Daeshik; Pikhitsa, Peter V.; Choi, Yong Whan; Lee, Chanseok; Shin, Sung Soo; Piao, Linfeng; Suh, Kahp-Yang; Choi, Mansoo] Seoul Natl Univ, Dept Mech & Aerosp Engn, Global Frontier Ctr Multiscale Energy Syst, Seoul 151742, South Korea.
   [Kang, Daeshik; Suh, Kahp-Yang; Choi, Mansoo] Seoul Natl Univ, Div WCU Multiscale Mech Design, Dept Mech & Aerosp Engn, Seoul 151742, South Korea.
   [Park, Byeonghak; Kim, Tae-il] Inst Basic Sci IBS, Ctr Neurosci Imaging Res CNIR, Suwon 440746, South Korea.
   [Park, Byeonghak; Kim, Tae-il] Sungkyunkwan Univ SKKU, Sch Chem Engn, Suwon 440746, South Korea.
   [Suh, Kahp-Yang] Seoul Natl Univ, Interdisciplinary Program Bioengn, Seoul 151742, South Korea.
C3 Seoul National University (SNU); Seoul National University (SNU); Institute for Basic Science - Korea (IBS); Sungkyunkwan University (SKKU); Seoul National University (SNU)
RP Choi, M (corresponding author), Seoul Natl Univ, Dept Mech & Aerosp Engn, Global Frontier Ctr Multiscale Energy Syst, Seoul 151742, South Korea.
EM taeilkim@skku.edu; mchoi@snu.ac.kr
FU Global Frontier R&D Program of the Center for Multiscale Energy Systems - National Research Foundation of Korea under the Ministry of Science, ICT and Future Planning [2011-0031561, 2011-0031577, IBS-R015-D1, NRF-2013-R1A1A1061403]; Basic Science Research Program - National Research Foundation of Korea under the Ministry of Science, ICT and Future Planning [IBS-R015-D1, NRF-2013-R1A1A1061403, 2009-0083540]
NR 24
TC 1414
Z9 1530
U1 68
U2 2178
PU NATURE PUBLISHING 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 11
PY 2014
VL 516
IS 7530
BP 222
EP 226
DI 10.1038/nature14002
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500039
PM 25503234
DA 2026-03-09
ER

PT J
AU Fromer, M
   Pocklington, AJ
   Kavanagh, DH
   Williams, HJ
   Dwyer, S
   Gormley, P
   Georgieva, L
   Rees, E
   Palta, P
   Ruderfer, DM
   Carrera, N
   Humphreys, I
   Johnson, JS
   Roussos, P
   Barker, DD
   Banks, E
   Milanova, V
   Grant, SG
   Hannon, E
   Rose, SA
   Chambert, K
   Mahajan, M
   Scolnick, EM
   Moran, JL
   Kirov, G
   Palotie, A
   McCarroll, SA
   Holmans, P
   Sklar, P
   Owen, MJ
   Purcell, SM
   O'Donovan, MC
AF Fromer, Menachem
   Pocklington, Andrew J.
   Kavanagh, David H.
   Williams, Hywel J.
   Dwyer, Sarah
   Gormley, Padhraig
   Georgieva, Lyudmila
   Rees, Elliott
   Palta, Priit
   Ruderfer, Douglas M.
   Carrera, Noa
   Humphreys, Isla
   Johnson, Jessica S.
   Roussos, Panos
   Barker, Douglas D.
   Banks, Eric
   Milanova, Vihra
   Grant, Seth G.
   Hannon, Eilis
   Rose, Samuel A.
   Chambert, Kimberly
   Mahajan, Milind
   Scolnick, Edward M.
   Moran, Jennifer L.
   Kirov, George
   Palotie, Aarno
   McCarroll, Steven A.
   Holmans, Peter
   Sklar, Pamela
   Owen, Michael J.
   Purcell, Shaun M.
   O'Donovan, Michael C.
TI De novo mutations in schizophrenia implicate synaptic networks
SO NATURE
LA English
DT Article
ID autism spectrum disorders; copy-number variants; intellectual disability; disease; gene; plasticity; mechanisms; complexity; patterns; rates
AB Inherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Here we show that small de novo mutations, affecting one ora few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes. Mutations are additionally enriched in proteins that interact with these complexes to modulate synaptic strength, namely proteins regulating actin filament dynamics and those whose messenger RNAs are targets of fragile X mental retardation protein (FMRP). Genes affected by mutations in schizophrenia overlap those mutated in autism and intellectual disability, as do mutation-enriched synaptic pathways. Aligning our findings with a parallel case-control study, we demonstrate reproducible insights into aetiological mechanisms for schizophrenia and reveal pathophysiology shared with other neurodevelopmental disorders.
C1 [Fromer, Menachem; Ruderfer, Douglas M.; Johnson, Jessica S.; Roussos, Panos; Mahajan, Milind; Sklar, Pamela; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA.
   [Fromer, Menachem; Ruderfer, Douglas M.; Johnson, Jessica S.; Roussos, Panos; Mahajan, Milind; Sklar, Pamela; Purcell, Shaun M.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
   [Fromer, Menachem; Barker, Douglas D.; Rose, Samuel A.; Chambert, Kimberly; Scolnick, Edward M.; Moran, Jennifer L.; McCarroll, Steven A.; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Pocklington, Andrew J.; Kavanagh, David H.; Williams, Hywel J.; Dwyer, Sarah; Georgieva, Lyudmila; Rees, Elliott; Ruderfer, Douglas M.; Carrera, Noa; Humphreys, Isla; Hannon, Eilis; Kirov, George; Holmans, Peter; Owen, Michael J.; O'Donovan, Michael C.] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales.
   [Gormley, Padhraig; Palta, Priit; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Gormley, Padhraig; Banks, Eric; Palotie, Aarno; McCarroll, Steven A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Palta, Priit] Univ Tartu, Inst Mol & Cell Biol, Dept Bioinformat, EE-51010 Tartu, Estonia.
   [Palta, Priit; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland.
   [Milanova, Vihra] Med Univ, Dept Psychiat, Sofia 1431, Bulgaria.
   [Grant, Seth G.] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland.
   [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
   [Purcell, Shaun M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cardiff University; Wellcome Trust Sanger Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Tartu; University of Helsinki; Medical University Sofia; University of Edinburgh; Harvard University; Harvard Medical School; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Owen, MJ (corresponding author), Cardiff Univ, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales.
EM owenmj@cardiff.ac.uk
FU Medical Research Council (MRC) Centre [G0800509, G0801418]; European Community [HEALTH-F2-2010-241909]; NIMH [2 P50 MH066392-05A1]; Friedman Brain Institute; Institute for Genomics and Multiscale Biology; National Institutes of Health [R01HG005827, R01MH099126, R01MH071681]; Fidelity Foundations; Sylvan Herman Foundation; Stanley Medical Research Institute; Wellcome Trust [WT089062, WT098051]; European Commission [261123]; Medical Research Council [MR/L010305/1, G0802238, G0801418, G0800509, G0801418B] Funding Source: researchfish; MRC [G0801418, G0802238, G0800509] Funding Source: UKRI
NR 43
TC 1256
Z9 1444
U1 1
U2 179
PU NATURE PUBLISHING 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 13
PY 2014
VL 506
IS 7487
BP 179
EP +
DI 10.1038/nature12929
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700029
PM 24463507
DA 2026-03-09
ER

PT J
AU Chouchani, ET
   Pell, VR
   Gaude, E
   Aksentijevic, D
   Sundier, SY
   Robb, EL
   Logan, A
   Nadtochiy, SM
   Ord, ENJ
   Smith, AC
   Eyassu, F
   Shirley, R
   Hu, CH
   Dare, AJ
   James, AM
   Rogatti, S
   Hartley, RC
   Eaton, S
   Costa, ASH
   Brookes, PS
   Davidson, SM
   Duchen, MR
   Saeb-Parsy, K
   Shattock, MJ
   Robinson, AJ
   Work, LM
   Frezza, C
   Krieg, T
   Murphy, MP
AF Chouchani, Edward T.
   Pell, Victoria R.
   Gaude, Edoardo
   Aksentijevic, Dunja
   Sundier, Stephanie Y.
   Robb, Ellen L.
   Logan, Angela
   Nadtochiy, Sergiy M.
   Ord, Emily N. J.
   Smith, Anthony C.
   Eyassu, Filmon
   Shirley, Rachel
   Hu, Chou-Hui
   Dare, Anna J.
   James, Andrew M.
   Rogatti, Sebastian
   Hartley, Richard C.
   Eaton, Simon
   Costa, Ana S. H.
   Brookes, Paul S.
   Davidson, Sean M.
   Duchen, Michael R.
   Saeb-Parsy, Kourosh
   Shattock, Michael J.
   Robinson, Alan J.
   Work, Lorraine M.
   Frezza, Christian
   Krieg, Thomas
   Murphy, Michael P.
TI Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS
SO NATURE
LA English
DT Article
ID purine nucleotide cycle; complex-i; superoxide-production; hypoxia-ischemia; mechanism; cardioprotection; dehydrogenase; consequences; inhibition; protection
AB Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS)(1-5). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion(1,3). Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies.
C1 [Chouchani, Edward T.; Robb, Ellen L.; Logan, Angela; Smith, Anthony C.; Eyassu, Filmon; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Robinson, Alan J.; Murphy, Michael P.] MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
   [Chouchani, Edward T.; Pell, Victoria R.; Hu, Chou-Hui; Krieg, Thomas] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England.
   [Gaude, Edoardo; Costa, Ana S. H.; Frezza, Christian] Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge CB2 0XZ, England.
   [Aksentijevic, Dunja; Shattock, Michael J.] Kings Coll London, Rayne Inst, British Heart Fdn Ctr Res Excellence, St Thomas Hosp, London SE1 7EH, England.
   [Sundier, Stephanie Y.; Duchen, Michael R.] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England.
   [Sundier, Stephanie Y.; Duchen, Michael R.] UCL, UCL Consortium Mitochondrial Biol, London WC1E 6BT, England.
   [Nadtochiy, Sergiy M.; Brookes, Paul S.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA.
   [Ord, Emily N. J.; Shirley, Rachel; Work, Lorraine M.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
   [Hartley, Richard C.] Univ Glasgow, Sch Chem, Glasgow G12 8QQ, Lanark, Scotland.
   [Eaton, Simon] UCL Inst Child Hlth, Unit Paediat Surg, London WC1N 1EH, England.
   [Davidson, Sean M.] UCL, Hatter Cardiovasc Inst, London WC1E 6HX, England.
   [Saeb-Parsy, Kourosh] Addenbrookes Hosp, Univ Dept Surg, Cambridge CB2 0QQ, England.
   [Saeb-Parsy, Kourosh] Addenbrookes Hosp, Cambridge NIHR Biomed Res Ctr, Cambridge CB2 0QQ, England.
C3 Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; University of London; University College London; University of London; University College London; University of Rochester; University of Glasgow; University of Glasgow; University of London; University College London; University of London; University College London; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge
RP Frezza, C (corresponding author), Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Box 197, Cambridge CB2 0XZ, England.
EM CF366@mrc-cu.cam.ac.uk; tk382@medschl.cam.ac.uk; mpm@mrc-mbu.cam.ac.uk
FU Medical Research Council (UK); Canadian Institutes of Health Research; Gates Cambridge Trust; British Heart Foundation; National Heart Lung and Blood Institute [R01HL071158] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/I012923/1] Funding Source: researchfish; British Heart Foundation [PG/07/126/24223, PG/12/42/29655, RG/12/4/29426] Funding Source: researchfish; Medical Research Council [MC_U105663142, MC_UU_12022/6, 1095363, MC_UP_1101/3, MC_U105674181, G1100562] Funding Source: researchfish; BBSRC [BB/I012923/1] Funding Source: UKRI; MRC [MC_U105663142, G1100562, MC_UP_1101/3, MC_U105674181, MC_UU_12022/6] Funding Source: UKRI
NR 50
TC 2289
Z9 2549
U1 4
U2 535
PU NATURE PUBLISHING 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 20
PY 2014
VL 515
IS 7527
BP 431
EP +
DI 10.1038/nature13909
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600050
PM 25383517
DA 2026-03-09
ER

PT J
AU Bagci, T
   Simonsen, A
   Schmid, S
   Villanueva, LG
   Zeuthen, E
   Appel, J
   Taylor, JM
   Sorensen, A
   Usami, K
   Schliesser, A
   Polzik, ES
AF Bagci, T.
   Simonsen, A.
   Schmid, S.
   Villanueva, L. G.
   Zeuthen, E.
   Appel, J.
   Taylor, J. M.
   Sorensen, A.
   Usami, K.
   Schliesser, A.
   Polzik, E. S.
TI Optical detection of radio waves through a nanomechanical transducer
SO NATURE
LA English
DT Article
ID cavity optomechanics; microwave; resonator; state
AB Low-loss transmission and sensitive recovery of weak radio-frequency and microwave signals is a ubiquitous challenge, crucial in radio astronomy, medical imaging, navigation, and classical and quantum communication. Efficient up-conversion of radio-frequency signals to an optical carrier would enable their transmission through optical fibres instead of through copper wires, drastically reducing losses, and would give access to the set of established quantum optical techniques that are routinely used in quantum-limited signal detection. Research in cavity optomechanics(1,2) has shown that nanomechanical oscillators can couple strongly to either microwave(3-5) or optical fields(6,7). Here we demonstrate a room-temperature optoelectromechanical transducer with both these functionalities, following a recent proposal(8) using a high-quality nanomembrane. A voltage bias of less than 10 V is sufficient to induce strong coupling(4,6,7) between the voltage fluctuations in a radio-frequency resonance circuit and the membrane's displacement, which is simultaneously coupled to light reflected off its surface. The radio-frequency signals are detected as an optical phase shift with quantum-limited sensitivity. The corresponding half-wave voltage is in the microvolt range, orders of magnitude less than that of standard optical modulators. The noise of the transducer-beyond the measured 800 pV Hz(-1/2) Johnson noise of the resonant circuit-consists of the quantum noise of light and thermal fluctuations of the membrane, dominating the noise floor in potential applications in radio astronomy and nuclear magnetic imaging. Each of these contributions is inferred to be 60 pV Hz(-1/2) when balanced by choosing an electromechanical cooperativity of similar to 150 with an optical power of 1 mW. The noise temperature of the membrane is 300 K divided by the cooperativity. For the highest observed cooperativity of 6,800, this leads to a projected noise temperature of 40 mK and a sensitivity limit of 5 pV Hz(-1/2). Our approach to all-optical, ultralow-noise detection of classical electronic signals sets the stage for coherent up-conversion of low-frequency quantum signals to the optical domain(8-11).
C1 [Bagci, T.; Simonsen, A.; Zeuthen, E.; Appel, J.; Sorensen, A.; Usami, K.; Schliesser, A.; Polzik, E. S.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Schmid, S.; Villanueva, L. G.] Tech Univ Denmark, DTU Nanotech, Dept Micro & Nanotechnol, DK-2800 Lyngby, Denmark.
   [Taylor, J. M.] NIST, Joint Quantum Inst, College Pk, MD 20742 USA.
C3 University of Copenhagen; Niels Bohr Institute; Technical University of Denmark; National Institute of Standards & Technology (NIST) - USA
RP Polzik, ES (corresponding author), Univ Copenhagen, Niels Bohr Inst, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
EM albert.schliesser@nbi.dk; polzik@nbi.dk
FU DARPA project QUASAR; European Union Seventh Framework Program through SIQS [600645]; European Union Seventh Framework Program through iQUOEMS [323924]; ERC grant QIOS [306576]; ERC grant INTERFACE [291038]; European Research Council (ERC) [291038] Funding Source: European Research Council (ERC)
NR 30
TC 394
Z9 450
U1 3
U2 289
PU NATURE PUBLISHING 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 6
PY 2014
VL 507
IS 7490
BP 81
EP 85
DI 10.1038/nature13029
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400046
PM 24598636
DA 2026-03-09
ER

PT J
AU Venkatesh, B
   Lee, AP
   Ravi, V
   Maurya, AK
   Lian, MM
   Swann, JB
   Ohta, Y
   Flajnik, MF
   Sutoh, Y
   Kasahara, M
   Hoon, S
   Gangu, V
   Roy, SW
   Irimia, M
   Korzh, V
   Kondrychyn, I
   Lim, ZW
   Tay, BH
   Tohari, S
   Kong, KW
   Ho, SF
   Lorente-Galdos, B
   Quilez, J
   Marques-Bonet, T
   Raney, BJ
   Ingham, PW
   Tay, A
   Hillier, LW
   Minx, P
   Boehm, T
   Wilson, RK
   Brenner, S
   Warren, WC
AF Venkatesh, Byrappa
   Lee, Alison P.
   Ravi, Vydianathan
   Maurya, Ashish K.
   Lian, Michelle M.
   Swann, Jeremy B.
   Ohta, Yuko
   Flajnik, Martin F.
   Sutoh, Yoichi
   Kasahara, Masanori
   Hoon, Shawn
   Gangu, Vamshidhar
   Roy, Scott W.
   Irimia, Manuel
   Korzh, Vladimir
   Kondrychyn, Igor
   Lim, Zhi Wei
   Tay, Boon-Hui
   Tohari, Sumanty
   Kong, Kiat Whye
   Ho, Shufen
   Lorente-Galdos, Belen
   Quilez, Javier
   Marques-Bonet, Tomas
   Raney, Brian J.
   Ingham, Philip W.
   Tay, Alice
   Hillier, LaDeana W.
   Minx, Patrick
   Boehm, Thomas
   Wilson, Richard K.
   Brenner, Sydney
   Warren, Wesley C.
TI Elephant shark genome provides unique insights into gnathostome evolution
SO NATURE
LA English
DT Article
ID cartilaginous fish; metabolic-rate; vertebrates; origin; repertoire; phylogeny; receptors; sequence; immunity; lamprey
AB The emergence of jawed vertebrates (gnathostomes) fromjawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii). We find that the C. milii genome is the slowest evolving of all known vertebrates, including the ` living fossil' coelacanth, and features extensive synteny conservation with tetrapod genomes, making it a goodmodel for comparative analyses of gnathostome genomes. Our functional studies suggest that the lack of genes encoding secreted calcium-binding phosphoproteins in cartilaginous fishes explains the absence of bone in their endoskeleton. Furthermore, the adaptive immune system of cartilaginous fishes is unusual: it lacks the canonical CD4 co-receptor and most transcription factors, cytokines and cytokine receptors related to the CD4 lineage, despite the presence of polymorphic major histocompatibility complex class II molecules. It thus presents a new model for understanding the origin of adaptive immunity.
C1 [Venkatesh, Byrappa; Lee, Alison P.; Ravi, Vydianathan; Lian, Michelle M.; Lim, Zhi Wei; Tay, Boon-Hui; Tohari, Sumanty; Tay, Alice; Brenner, Sydney] ASTAR, Inst Mol & Cell Biol, Comparat Genom Lab, Biopolis, Singapore 138673, Singapore.
   [Venkatesh, Byrappa] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 119228, Singapore.
   [Maurya, Ashish K.; Ingham, Philip W.] ASTAR, Inst Mol & Cell Biol, Dev & Biomed Genet Lab, Biopolis, Singapore 138673, Singapore.
   [Swann, Jeremy B.; Boehm, Thomas] Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
   [Ohta, Yuko; Flajnik, Martin F.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Sutoh, Yoichi; Kasahara, Masanori] Hokkaido Univ, Grad Sch Med, Dept Pathol, Sapporo, Hokkaido 0608638, Japan.
   [Hoon, Shawn; Gangu, Vamshidhar; Kong, Kiat Whye; Ho, Shufen] ASTAR, Inst Biomed Sci, Mol Engn Lab, Biopolis, Singapore 138673, Singapore.
   [Roy, Scott W.] San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA.
   [Irimia, Manuel] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Irimia, Manuel] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Korzh, Vladimir; Kondrychyn, Igor] ASTAR, Inst Mol & Cell Biol, Fish Dev Biol Lab, Biopolis, Singapore 138673, Singapore.
   [Lorente-Galdos, Belen; Quilez, Javier; Marques-Bonet, Tomas] Inst Biol Evolut UPF CSIC, PRBB, Barcelona 08003, Spain.
   [Lorente-Galdos, Belen; Quilez, Javier; Marques-Bonet, Tomas] ICREA, Barcelona 08010, Catalonia, Spain.
   [Raney, Brian J.] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Hillier, LaDeana W.; Minx, Patrick; Wilson, Richard K.; Warren, Wesley C.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Max Planck Society; University System of Maryland; University of Maryland Baltimore; Hokkaido University; Agency for Science Technology & Research (A*STAR); California State University System; San Francisco State University; University of Toronto; University of Toronto; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Pompeu Fabra University; Barcelona Biomedical Research Park; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); ICREA; University of California System; University of California Santa Cruz; Washington University (WUSTL)
RP Venkatesh, B (corresponding author), ASTAR, Inst Mol & Cell Biol, Comparat Genom Lab, Biopolis, Singapore 138673, Singapore.
EM mcbbv@imcb.a-star.edu.sg; wwarren@genome.wustl.edu
FU National Human Genome Research Institute, USA; Biomedical Research Council of A*STAR, Singapore; A*STAR Computational Resource Centre; Max Planck Society; NIH [RR006603, AI27877]; Ministry of Education, Culture, Sports, Science and Technology, Japan; Human Frontiers Science Program Organization; ERC [260372]; MICINN (Spain) [BFU2011-28549]; ICREA Funding Source: Custom; National Human Genome Research Institute [U41HG002371] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [24111001] Funding Source: KAKEN; European Research Council (ERC) [260372] Funding Source: European Research Council (ERC)
NR 37
TC 564
Z9 635
U1 3
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 JAN 9
PY 2014
VL 505
IS 7482
BP 174
EP 179
DI 10.1038/nature12826
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500030
PM 24402279
DA 2026-03-09
ER

PT J
AU Thacker, D
   Mohibullah, N
   Zhu, X
   Keeney, S
AF Thacker, Drew
   Mohibullah, Neeman
   Zhu, Xuan
   Keeney, Scott
TI Homologue engagement controls meiotic DNA break number and distribution
SO NATURE
LA English
DT Article
ID double-strand breaks; synaptonemal complex-formation; saccharomyces-cerevisiae; crossing-over; muts homolog; zmm proteins; recombination; meiosis; pachytene; mutants
AB Meiotic recombination promotes genetic diversification as well as pairing and segregation of homologous chromosomes, but the double-strand breaks (DSBs) that initiate recombination are dangerous lesions that can cause mutation or meiotic failure. How cells control DSBs to balance between beneficial and deleterious outcomes is not well understood. Here we test the hypothesis that DSB control involves a network of intersecting negative regulatory circuits. Using multiple complementary methods, we show that DSBs form in greater numbers in Saccharomyces cerevisiae cells lacking ZMM proteins, a suite of recombination-promoting factors traditionally regarded as acting strictly downstream of DSB formation. ZMM-dependent DSB control is genetically distinct from a pathway tying break formation to meiotic progression through the Ndt80 transcription factor. These counterintuitive findings suggest that homologous chromosomes that have successfully engaged one another stop making breaks. Genome-wide DSB maps uncover distinct responses by different subchromosomal domains to the ZMM mutation zip3 (also known as cst9), and show that Zip3 is required for the previously unexplained tendency of DSB density to vary with chromosome size. Thus, feedback tied to ZMM function contributes in unexpected ways to spatial patterning of recombination.
C1 [Thacker, Drew; Mohibullah, Neeman; Zhu, Xuan; Keeney, Scott] Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10065 USA.
   [Thacker, Drew; Zhu, Xuan; Keeney, Scott] Cornell Univ, Weill Grad Sch Med Sci, New York, NY 10065 USA.
   [Mohibullah, Neeman; Keeney, Scott] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center
RP Keeney, S (corresponding author), Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10065 USA.
EM s-keeney@ski.mskcc.org
FU National Institutes of Health [R01 GM058673]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 54
TC 151
Z9 175
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 JUN 12
PY 2014
VL 510
IS 7504
BP 241
EP +
DI 10.1038/nature13120
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400044
PM 24717437
DA 2026-03-09
ER

PT J
AU Hatsukade, B
   Ohta, K
   Endo, A
   Nakanishi, K
   Tamura, Y
   Hashimoto, T
   Kohno, K
AF Hatsukade, B.
   Ohta, K.
   Endo, A.
   Nakanishi, K.
   Tamura, Y.
   Hashimoto, T.
   Kohno, K.
TI Two γ-ray bursts from dusty regions with little molecular gas
SO NATURE
LA English
DT Article
ID high-metallicity host; star-formation; conversion factor; galaxy; co; redshift; afterglow; constraints; dependence; grb-051022
AB Long-duration gamma-ray bursts are associated with the explosions of massive stars(1) and are accordingly expected to reside in star-forming regions with molecular gas (the fuel for star formation). Previous searches for carbon monoxide (CO), a tracer of molecular gas, in burst host galaxies did not detect any emission(2-4). Molecules have been detected as absorption in the spectra of gamma-ray burst afterglows, and the molecular gas is similar to the translucent or diffuse molecular clouds of the Milky Way(5,6). Absorption lines probe the interstellar medium only along the line of sight, so it is not clear whether the molecular gas represents the general properties of the regions where the bursts occur. Here we report spatially resolved observations of CO line emission and millimetre-wavelength continuum emission in two galaxies hosting gamma-ray bursts. The bursts happened in regions rich in dust, but not particularly rich in molecular gas. The ratio of molecular gas to dust (<9-14) is significantly lower than in star-forming regions of the Milky Way and nearby star-forming galaxies, suggesting that much of the dense gas where stars form has been dissipated by other massive stars.
C1 [Hatsukade, B.; Nakanishi, K.; Hashimoto, T.] Natl Astron Observ Japan, Mitaka, Tokyo 1818588, Japan.
   [Ohta, K.] Kyoto Univ, Dept Astron, Kyoto 6068502, Japan.
   [Endo, A.] Delft Univ Technol, Kavli Inst NanoSci, Fac Sci Appl, NL-2628 CJ Delft, Netherlands.
   [Nakanishi, K.] Joint ALMA Observ, Santiago 7630355, Chile.
   [Nakanishi, K.] Grad Univ Adv Studies SOKENDAI, Mitaka, Tokyo 1818588, Japan.
   [Tamura, Y.; Kohno, K.] Univ Tokyo, Inst Astron, Mitaka, Tokyo 1810015, Japan.
   [Kohno, K.] Univ Tokyo, Res Ctr Early Universe, Bunkyo Ku, Tokyo 1130033, Japan.
C3 National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Kyoto University; Delft University of Technology; Graduate University for Advanced Studies - Japan; University of Tokyo; University of Tokyo
RP Hatsukade, B (corresponding author), Natl Astron Observ Japan, 2-21-1 Osawa, Mitaka, Tokyo 1818588, Japan.
EM bunyo.hatsukade@nao.ac.jp
FU Japan Society for the Promotion of Science (JSPS) [24540230, 25103503]; NWO (Veni grant) [639.041.023]; Grants-in-Aid for Scientific Research [25247019, 24103003, 24540230, 25103503] Funding Source: KAKEN
NR 51
TC 34
Z9 35
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 12
PY 2014
VL 510
IS 7504
BP 247
EP +
DI 10.1038/nature13325
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400045
PM 24919918
DA 2026-03-09
ER

PT J
AU Dotera, T
   Oshiro, T
   Ziherl, P
AF Dotera, T.
   Oshiro, T.
   Ziherl, P.
TI Mosaic two-lengthscale quasicrystals
SO NATURE
LA English
DT Article
ID phases; 12-fold; model
AB Over the past decade, quasicrystalline order(1) has been observed in many soft-matter systems: in dendritic micelles(2), in star(3) and tetrablock(4) terpolymer melts and in diblock copolymer(5) and surfactant micelles(6). The formation of quasicrystals(7-9) from such a broad range of 'soft' macromolecular micelles suggests that they assemble by a generic mechanism rather than being dependent on the specific chemistry of each system. Indeed, micellar softness has been postulated(7) and shown to lead to quasicrystalline order(10). Here we theoretically explore this link by studying two-dimensional hard disks decorated with step-like square-shoulder repulsion that mimics, for example, the soft alkyl shell around the aromatic core in dendritic micelles(2). We find a family of quasicrystals with 10-, 12-, 18- and 24-fold bond orientational order which originate from mosaics of equilateral and isosceles triangles formed by particles arranged core-to-core and shoulder-to-shoulder. The pair interaction responsible for these phases highlights the role of local packing geometry in generating quasicrystallinity in soft matter, complementing the principles that lead to quasicrystal formation in hard tetrahedra(11,12). Based on simple interparticle potentials, quasicrystalline mosaics may well find use in diverse applications ranging from improved image reproduction(13) to advanced photonic materials(14).
C1 [Dotera, T.; Oshiro, T.] Kinki Univ, Dept Phys, Higashiosaka, Osaka 5778502, Japan.
   [Ziherl, P.] Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia.
   [Ziherl, P.] Jozef Stefan Inst, SI-1000 Ljubljana, Slovenia.
C3 Kindai University (Kinki University); University of Ljubljana; Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute
RP Dotera, T (corresponding author), Kinki Univ, Dept Phys, 3-4-1 Kowakae, Higashiosaka, Osaka 5778502, Japan.
EM dotera@phys.kindai.ac.jp
FU Japan Society for the Promotion of Science [22540375]; Slovenian Research Agency [P1-0055]; Marie-Curie Initial Training Network COMPLOIDS under FP7-PEOPLE-ITN [234810]; Grants-in-Aid for Scientific Research [22540375] Funding Source: KAKEN
NR 30
TC 195
Z9 221
U1 1
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 FEB 13
PY 2014
VL 506
IS 7487
BP 208
EP 211
DI 10.1038/nature12938
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700035
PM 24487618
DA 2026-03-09
ER

PT J
AU Sifré, D
   Gardés, E
   Massuyeau, M
   Hashim, L
   Hier-Majumder, S
   Gaillard, F
AF Sifre, David
   Gardes, Emmanuel
   Massuyeau, Malcolm
   Hashim, Leila
   Hier-Majumder, Saswata
   Gaillard, Fabrice
TI Electrical conductivity during incipient melting in the oceanic low-velocity zone
SO NATURE
LA English
DT Article
ID mantle; carbon; lithosphere; extraction; boundary; rocks; water; 14-degrees-n; constraints; olivine
AB The low-viscosity layer in the upper mantle, the asthenosphere, is a requirement for plate tectonics(1). The seismic low velocities and the high electrical conductivities of the asthenosphere are attributed either to subsolidus, water-related defects in olivine minerals(2-4) or to a few volume per cent of partial melt(5-8), but these two interpretations have two shortcomings. First, the amount of water stored in olivine is not expected to be higher than 50 parts per million owing to partitioning with other mantle phases(9) (including pargasite amphibole at moderate temperatures(10)) and partial melting at high temperatures(9). Second, elevated melt volume fractions are impeded by the temperatures prevailing in the asthenosphere, which are too low, and by the melt mobility, which is high and can lead to gravitational segregation(11,12). Here we determine the electrical conductivity of carbon-dioxide-rich and water-rich melts, typically produced at the onset of mantle melting. Electrical conductivity increases modestly with moderate amounts of water and carbon dioxide, but it increases drastically once the carbon dioxide content exceeds six weight per cent in the melt. Incipient melts, long-expected to prevail in the asthenosphere(10,13-15), can therefore produce high electrical conductivities there. Taking into account variable degrees of depletion of the mantle in water and carbon dioxide, and their effect on the petrology of incipient melting, we calculated conductivity profiles across the asthenosphere for various tectonic plate ages. Several electrical discontinuities are predicted and match geophysical observations in a consistent petrological and geochemical framework. In moderately aged plates (more than five million years old), incipient melts probably trigger both the seismic low velocities and the high electrical conductivities in the upper part of the asthenosphere, whereas in young plates(4), where seamount volcanism occurs(6), a higher degree of melting is expected.
C1 [Sifre, David; Gardes, Emmanuel; Massuyeau, Malcolm; Hashim, Leila; Hier-Majumder, Saswata; Gaillard, Fabrice] Univ Orleans, ISTO, UMR 7327, F-45071 Orleans, France.
   [Sifre, David; Gardes, Emmanuel; Massuyeau, Malcolm; Hashim, Leila; Hier-Majumder, Saswata; Gaillard, Fabrice] CNRS, ISTO, UMR 7327, F-45071 Orleans, France.
   [Sifre, David; Gardes, Emmanuel; Massuyeau, Malcolm; Hashim, Leila; Hier-Majumder, Saswata; Gaillard, Fabrice] Bur Rech Geol & Minieres, ISTO, UMR 7327, F-45060 Orleans, France.
   [Gardes, Emmanuel] Univ Caen Basse Normandie, CNRS, Ctr Rech Ions Mat & Photon,UMR 6252, Commissariat Energie Atom,Ecole Natl Super Ingeni, F-14070 Caen, France.
   [Hier-Majumder, Saswata] Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
   [Hier-Majumder, Saswata] Univ Maryland, Ctr Sci Computat & Appl Math Modeling, College Pk, MD 20742 USA.
   [Hier-Majumder, Saswata] Royal Holloway Univ London, Dept Earth Sci, Egham TW20 0EX, Surrey, England.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Bureau de Recherches Geologiques et Minieres (BRGM); Universite de Orleans; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Bureau de Recherches Geologiques et Minieres (BRGM); Universite de Orleans; Bureau de Recherches Geologiques et Minieres (BRGM); Centre National de la Recherche Scientifique (CNRS); Universite de Orleans; CNRS - National Institute for Earth Sciences & Astronomy (INSU); CEA; Centre National de la Recherche Scientifique (CNRS); Universite de Caen Normandie; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CNRS - Institute of Physics (INP); University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University of London; Royal Holloway University London
RP Gaillard, F (corresponding author), Univ Orleans, ISTO, UMR 7327, F-45071 Orleans, France.
EM fabrice.gaillard@cnrs-orleans.fr
FU European Research Council (ERC) [279790]; French agency for research (ANR) [2010 BLAN62101]; US NSF [EAR1215800]; University of Orleans; Directorate For Geosciences; Division Of Earth Sciences [1215800] Funding Source: National Science Foundation
NR 55
TC 178
Z9 201
U1 2
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 MAY 1
PY 2014
VL 509
IS 7498
BP 81
EP +
DI 10.1038/nature13245
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100043
PM 24784219
DA 2026-03-09
ER

PT J
AU Portugal, SJ
   Hubel, TY
   Fritz, J
   Heese, S
   Trobe, D
   Voelkl, B
   Hailes, S
   Wilson, AM
   Usherwood, JR
AF Portugal, Steven J.
   Hubel, Tatjana Y.
   Fritz, Johannes
   Heese, Stefanie
   Trobe, Daniela
   Voelkl, Bernhard
   Hailes, Stephen
   Wilson, Alan M.
   Usherwood, James R.
TI Upwash exploitation and downwash avoidance by flap phasing in ibis formation flight
SO NATURE
LA English
DT Article
ID energy savings; birds; dynamics; geese; kinematics; leadership; efficiency; behavior; pairs; bat
AB Many species travel in highly organized groups(1-3). The most quoted function of these configurations is to reduce energy expenditure and enhance locomotor performance of individuals in the assemblage(4-11). The distinctive V formation of bird flocks has long intrigued researchers and continues to attract both scientific and popular attention(4,7,9-14). The well-held belief is that such aggregations give an energetic benefit for those birds that are flying behind and to one side of another bird through using the regions of upwash generated by the wings of the preceding bird(4,7,9-11), although a definitive account of the aerodynamic implications of these formations has remained elusive. Here we show that individuals of northern bald ibises (Geronticus eremita) flying in a V flock position themselves in aerodynamically optimum positions, in that they agree with theoretical aerodynamic predictions. Furthermore, we demonstrate that birds show wingtip path coherence when flying in V positions, flapping spatially in phase and thus enabling upwash capture to be maximized throughout the entire flap cycle. In contrast, when birds fly immediately behind another bird-in a streamwise position-there is no wingtip path coherence; the wing-beats are in spatial anti-phase. This could potentially reduce the adverse effects of downwash for the following bird. These aerodynamic accomplishments were previously not thought possible for birds because of the complex flight dynamics and sensory feedback that would be required to perform such a feat(12,14). We conclude that the intricate mechanisms involved in V formation flight indicate awareness of the spatial wake structures of nearby flock-mates, and remarkable ability either to sense or predict it. We suggest that birds in V formation have phasing strategies to cope with the dynamic wakes produced by flapping wings.
C1 [Portugal, Steven J.; Hubel, Tatjana Y.; Hailes, Stephen; Wilson, Alan M.; Usherwood, James R.] Univ London, Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
   [Fritz, Johannes; Heese, Stefanie; Trobe, Daniela; Voelkl, Bernhard] Waldrappteam, A-6162 Mutters, Austria.
   [Voelkl, Bernhard] Humboldt Univ, Inst Theoret Biol, D-10115 Berlin, Germany.
   [Hailes, Stephen] UCL, Dept Comp Sci, London WC1E 6BT, England.
C3 University of London; University of London Royal Veterinary College; Humboldt University of Berlin; University of London; University College London
RP Portugal, SJ (corresponding author), Univ London, Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
EM SPortugal@rvc.ac.uk
FU Engineering and Physical Sciences Research Council [EP/H013016/1]; Biotechnology and Biological Sciences Research Council [BB/J018007/1]; Wellcome Trust [095061/Z/10/Z]; Wellcome Trust [095061/Z/10/Z] Funding Source: Wellcome Trust; BBSRC [BB/J018007/1] Funding Source: UKRI; EPSRC [EP/H013016/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/J018007/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/H013016/1] Funding Source: researchfish
NR 42
TC 281
Z9 330
U1 1
U2 137
PU NATURE PUBLISHING 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 16
PY 2014
VL 505
IS 7483
BP 399
EP +
DI 10.1038/nature12939
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800042
PM 24429637
DA 2026-03-09
ER

PT J
AU Gillis, KM
   Snow, JE
   Klaus, A
   Abe, N
   Adriao, AB
   Akizawa, N
   Ceuleneer, G
   Cheadle, MJ
   Faak, K
   Falloon, TJ
   Friedman, SA
   Godard, M
   Guerin, G
   Harigane, Y
   Horst, AJ
   Hoshide, T
   Ildefonse, B
   Jean, MM
   John, BE
   Koepke, J
   Machi, S
   Maeda, J
   Marks, NE
   McCaig, AM
   Meyer, R
   Morris, A
   Nozaka, T
   Python, M
   Saha, A
   Wintsch, RP
AF Gillis, Kathryn M.
   Snow, Jonathan E.
   Klaus, Adam
   Abe, Natsue
   Adriao, Alden B.
   Akizawa, Norikatsu
   Ceuleneer, Georges
   Cheadle, Michael J.
   Faak, Kathrin
   Falloon, Trevor J.
   Friedman, Sarah A.
   Godard, Marguerite
   Guerin, Gilles
   Harigane, Yumiko
   Horst, Andrew J.
   Hoshide, Takashi
   Ildefonse, Benoit
   Jean, Marlon M.
   John, Barbara E.
   Koepke, Juergen
   Machi, Sumiaki
   Maeda, Jinichiro
   Marks, Naomi E.
   McCaig, Andrew M.
   Meyer, Romain
   Morris, Antony
   Nozaka, Toshio
   Python, Marie
   Saha, Abhishek
   Wintsch, Robert P.
TI Primitive layered gabbros from fast-spreading lower oceanic crust
SO NATURE
LA English
DT Article
ID east pacific rise; midocean ridge basalts; hess deep rift; liquid equilibria; magma chambers; upper-mantle; melt; model; flow; differentiation
AB Three-quarters of the oceanic crust formed at fast-spreading ridges is composed of plutonic rocks whose mineral assemblages, textures and compositions record the history of melt transport and crystallization between the mantle and the sea floor. Despite the importance of these rocks, sampling them in situ is extremely challenging owing to the overlying dykes and lavas. This means that models for understanding the formation of the lower crust are based largely on geophysical studies(1) and ancient analogues (ophiolites)(2-5) that did not form at typical mid-ocean ridges. Here we describe cored intervals of primitive, modally layered gabbroic rocks from the lower plutonic crust formed at a fast-spreading ridge, sampled by the Integrated Ocean Drilling Program at the Hess Deep rift. Centimetre-scale, modally layered rocks, some of which have a strong layering-parallel foliation, confirm a long-held belief that such rocks are a key constituent of the lower oceanic crust formed at fast-spreading ridges(3,6). Geochemical analysis of these primitive lower plutonic rocks-in combination with previous geochemical data for shallow-level plutonic rocks, sheeted dykes and lavas-provides the most completely constrained estimate of the bulk composition of fast-spreading oceanic crust so far. Simple crystallization models using this bulk crustal composition as the parental melt accurately predict the bulk composition of both the lavas and the plutonic rocks. However, the recovered plutonic rocks show early crystallization of orthopyroxene, which is not predicted by current models of melt extraction from the mantle(7) and mid-ocean-ridge basalt differentiation(8,9). The simplest explanation of this observation is that compositionally diverse melts are extracted from the mantle and partly crystallize before mixing to produce the more homogeneous magmas that erupt.
C1 [Gillis, Kathryn M.; Faak, Kathrin] Univ Victoria, Sch Earth & Ocean Sci, Victoria, BC V8W 2Y2, Canada.
   [Snow, Jonathan E.] Univ Houston, Houston, TX 77204 USA.
   [Klaus, Adam] Texas A&M Univ, Integrated Ocean Drilling Program, US Implementing Org, College Stn, TX 77845 USA.
   [Abe, Natsue] Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Yokosuka, Kanagawa 2370061, Japan.
   [Adriao, Alden B.] Univ Fed Rio Grande do Sul, Inst Geosci, BR-91501970 Porto Alegre, RS, Brazil.
   [Akizawa, Norikatsu; Machi, Sumiaki] Kanazawa Univ, Dept Earth Sci, Kanazawa, Ishikawa 9201192, Japan.
   [Ceuleneer, Georges] Univ Toulouse 3, CNRS, UMS 831, Observ Midipyrenees, F-31400 Toulouse, France.
   [Cheadle, Michael J.; John, Barbara E.] Univ Wyoming, Dept 3006, Dept Geol & Geophys, Laramie, WY 82071 USA.
   [Faak, Kathrin] Ruhr Univ Bochum, Inst Geol Mineral & Geophys, D-44780 Bochum, Germany.
   [Falloon, Trevor J.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas, Australia.
   [Falloon, Trevor J.] Univ Tasmania, Sch Earth Sci, Hobart, Tas, Australia.
   [Friedman, Sarah A.] So Illinois Univ, Dept Geol, Carbondale, IL 62901 USA.
   [Godard, Marguerite; Ildefonse, Benoit] Univ Montpellier 2, CNRS UMR5243, Geosci Montpellier, CC 60, F-34095 Montpellier 5, France.
   [Guerin, Gilles] Columbia Univ, Lamont Doherty Earth Observ, Borehole Res Grp, Palisades, NY USA.
   [Harigane, Yumiko] Geol Survey Japan, Natl Inst Adv Ind Sci & Technol, Inst Geol & Geoinformat, Tsukuba, Ibaraki 3058567, Japan.
   [Horst, Andrew J.] Oberlin Coll, Dept Geol, Oberlin, OH 44074 USA.
   [Hoshide, Takashi] Tohoku Univ, Grad Sch Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan.
   [Jean, Marlon M.] No Illinois Univ, Dept Geol & Environm, De Kalb, IL 60115 USA.
   [Koepke, Juergen] Leibniz Univ Hannover, Inst Mineral, D-30167 Hannover, Germany.
   [Maeda, Jinichiro; Python, Marie] Hokkaido Univ, Dept Nat Hist Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan.
   [Marks, Naomi E.] Lawrence Livermore Natl Lab, Chem & Mat Sci Dept, Livermore, CA 94551 USA.
   [McCaig, Andrew M.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Meyer, Romain] Univ Bergen, Ctr Geobiol, N-5007 Bergen, Norway.
   [Meyer, Romain] Univ Bergen, Dept Earth Sci, N-5007 Bergen, Norway.
   [Morris, Antony] Univ Plymouth, Sch Geog Earth & Environm Sci, Plymouth PL4 8AA, Devon, England.
   [Nozaka, Toshio] Okayama Univ, Dept Earth Sci, Okayama 7008530, Japan.
   [Saha, Abhishek] Univ Calcutta, Dept Geol, Kolkata 700019, India.
   [Wintsch, Robert P.] Indiana Univ, Dept Geol Sci, Bloomington, IN 47405 USA.
C3 University of Victoria; University of Houston System; University of Houston; Texas A&M University System; Texas A&M University College Station; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Universidade Federal do Rio Grande do Sul; Kanazawa University; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of Wyoming; Ruhr University Bochum; University of Tasmania; University of Tasmania; Southern Illinois University System; Southern Illinois University; Universite de Montpellier; Columbia University; National Institute of Advanced Industrial Science & Technology (AIST); University System of Ohio; Oberlin College; Tohoku University; Northern Illinois University; Leibniz University Hannover; Hokkaido University; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Leeds; University of Bergen; University of Bergen; University of Plymouth; Okayama University; University of Calcutta; Indiana University System; Indiana University Bloomington
RP Gillis, KM (corresponding author), Univ Victoria, Sch Earth & Ocean Sci, POB 1700 Stn CSC, Victoria, BC V8W 2Y2, Canada.
EM kgillis@uvic.ca
FU Grants-in-Aid for Scientific Research [11J04217, 25400515] Funding Source: KAKEN; NERC [NE/K011057/1, NE/K011030/1, NE/C509023/1] Funding Source: UKRI; Natural Environment Research Council [NE/K011057/1, NE/K011030/1, NE/C509023/1] Funding Source: researchfish
NR 45
TC 112
Z9 130
U1 0
U2 132
PU NATURE PUBLISHING 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 9
PY 2014
VL 505
IS 7482
BP 204
EP +
DI 10.1038/nature12778
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500036
PM 24291793
DA 2026-03-09
ER

PT J
AU Bloom, BJ
   Nicholson, TL
   Williams, JR
   Campbell, SL
   Bishof, M
   Zhang, X
   Zhang, W
   Bromley, SL
   Ye, J
AF Bloom, B. J.
   Nicholson, T. L.
   Williams, J. R.
   Campbell, S. L.
   Bishof, M.
   Zhang, X.
   Zhang, W.
   Bromley, S. L.
   Ye, J.
TI An optical lattice clock with accuracy and stability at the 10-18 level
SO NATURE
LA English
DT Article
ID quantum; frequency; metrology; shift
AB Progress in atomic, optical and quantum science(1,2) has led to rapid improvements in atomic clocks. At the same time, atomic clock research has helped to advance the frontiers of science, affecting both fundamental and applied research. The ability to control quantum states of individual atoms and photons is central to quantum information science and precision measurement, and optical clocks based on single ions have achieved the lowest systematic uncertainty of any frequency standard(3-5). Although many-atom lattice clocks have shown advantages in measurement precision over trapped-ion clocks(6,7), their accuracy has remained 16 times worse(8-10). Here we demonstrate a many-atom system that achieves an accuracy of 6.4x10(-18), which is not only better than a single-ion-based clock, but also reduces the required measurement time by two orders of magnitude. By systematically evaluating all known sources of uncertainty, including in situ monitoring of the blackbody radiation environment, we improve the accuracy of optical lattice clocks by a factor of 22. This single clock has simultaneously achieved the best known performance in the key characteristics necessary for consideration as a primary standard-stability and accuracy. More stable and accurate atomic clocks will benefit a wide range of fields, such as the realization and distribution of SI units(11), the search for time variation of fundamental constants(12), clock-based geodesy(13) and other precision tests of the fundamental laws of nature. This work also connects to the development of quantum sensors and many-body quantum state engineering(14) (such as spin squeezing) to advance measurement precision beyond the standard quantum limit.
C1 [Bloom, B. J.; Nicholson, T. L.; Williams, J. R.; Campbell, S. L.; Bishof, M.; Zhang, X.; Zhang, W.; Bromley, S. L.; Ye, J.] NIST, JILA, Boulder, CO 80309 USA.
   [Bloom, B. J.; Nicholson, T. L.; Williams, J. R.; Campbell, S. L.; Bishof, M.; Zhang, X.; Zhang, W.; Bromley, S. L.; Ye, J.] Univ Colorado, Boulder, CO 80309 USA.
   [Bloom, B. J.; Nicholson, T. L.; Williams, J. R.; Campbell, S. L.; Bishof, M.; Zhang, X.; Zhang, W.; Bromley, S. L.; Ye, J.] Univ Colorado, Dept Phys, Boulder, CO 80309 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
RP Ye, J (corresponding author), NIST, JILA, Boulder, CO 80309 USA.
EM ye@jila.colorado.edu
FU National Institute of Standards and Technology; Defense Advanced Research Projects Agency's QuASAR Program; NSF PFC; National Defense Science and Engineering Graduate fellowship programme; NSF; Division Of Physics; Direct For Mathematical & Physical Scien [1125844] Funding Source: National Science Foundation
NR 38
TC 901
Z9 1077
U1 2
U2 393
PU NATURE PUBLISHING 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 6
PY 2014
VL 506
IS 7486
BP 71
EP +
DI 10.1038/nature12941
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100033
PM 24463513
DA 2026-03-09
ER

PT J
AU Chen, L
   Xiao, S
   Pang, K
   Zhou, CM
   Yuan, XL
AF Chen, Lei
   Xiao, Shuhai
   Pang, Ke
   Zhou, Chuanming
   Yuan, Xunlai
TI Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils
SO NATURE
LA English
DT Article
ID neoproterozoic doushantuo formation; origin; wengan; algae; microfossils; evolution; guizhou; china
AB Phosphorites of the Ediacaran Doushantuo Formation (similar to 600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern(1,2). These fossils have been variously interpreted as sulphur-oxidizing bacteria(3), unicellular protists(4), mesomycetozoean-like holozoans(5), green algae akin to Volvox(6,7), and blastula embryos of early metazoans(1,2,8-10) or bilaterian animals(11,12). However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.
C1 [Chen, Lei; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Jiangsu, Peoples R China.
   [Chen, Lei; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, Key Lab Econ Stratig & Palaeogeog, Nanjing 210008, Jiangsu, Peoples R China.
   [Chen, Lei; Pang, Ke] Univ Chinese Acad Sci, Coll Earth Sci, Beijing 100049, Peoples R China.
   [Xiao, Shuhai] Virginia Tech, Dept Geosci, Blacksburg, VA 24061 USA.
   [Yuan, Xunlai] NW Univ Xian, Dept Geol, Xian 710069, Peoples R China.
C3 Chinese Academy of Sciences; Chinese Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Virginia Polytechnic Institute & State University; Northwest University Xi'an
RP Xiao, S (corresponding author), Virginia Tech, Dept Geosci, Blacksburg, VA 24061 USA.
EM xiao@vt.edu; xlyuan@nigpas.ac.cn
FU Ministry of Science and Technology of China; National Natural Science Foundation of China; Chinese Academy of Sciences; US National Science Foundation
NR 36
TC 84
Z9 109
U1 0
U2 103
PU NATURE PUBLISHING 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 11
PY 2014
VL 516
IS 7530
BP 238
EP +
DI 10.1038/nature13766
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500043
PM 25252979
DA 2026-03-09
ER

PT J
AU Noubade, R
   Wong, K
   Ota, N
   Rutz, S
   Eidenschenk, C
   Valdez, PA
   Ding, JB
   Peng, I
   Sebrell, A
   Caplazi, P
   DeVoss, J
   Soriano, RH
   Sai, T
   Lu, RZ
   Modrusan, Z
   Hackney, J
   Ouyang, WJ
AF Noubade, Rajkumar
   Wong, Kit
   Ota, Naruhisa
   Rutz, Sascha
   Eidenschenk, Celine
   Valdez, Patricia A.
   Ding, Jiabing
   Peng, Ivan
   Sebrell, Andrew
   Caplazi, Patrick
   DeVoss, Jason
   Soriano, Robert H.
   Sai, Tao
   Lu, Rongze
   Modrusan, Zora
   Hackney, Jason
   Ouyang, Wenjun
TI NRROS negatively regulates reactive oxygen species during host defence and autoimmunity
SO NATURE
LA English
DT Article
ID chronic granulomatous-disease; neutrophil nadph oxidase; plasma-membrane; lysosomal membrane; macrophages; encephalomyelitis; phosphorylation; activation; expression; apoptosis
AB Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease(1,2). Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interactswith nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS prodution-one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage.
C1 [Noubade, Rajkumar; Wong, Kit; Ota, Naruhisa; Rutz, Sascha; Eidenschenk, Celine; Valdez, Patricia A.; Ding, Jiabing; Peng, Ivan; DeVoss, Jason; Lu, Rongze; Ouyang, Wenjun] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
   [Sebrell, Andrew; Sai, Tao] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
   [Caplazi, Patrick] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Soriano, Robert H.; Modrusan, Zora] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Hackney, Jason] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA
RP Ouyang, WJ (corresponding author), Genentech Inc, Dept Immunol, 1 DNA Way, San Francisco, CA 94080 USA.
EM ouyang.wenjun@gene.com
NR 38
TC 206
Z9 239
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 MAY 8
PY 2014
VL 509
IS 7499
BP 235
EP +
DI 10.1038/nature13152
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300041
PM 24739962
DA 2026-03-09
ER

PT J
AU Singh, DP
   Saudemont, B
   Guglielmi, G
   Arnaiz, O
   Goût, JF
   Prajer, M
   Potekhin, A
   Przybòs, E
   Aubusson-Fleury, A
   Bhullar, S
   Bouhouche, K
   Lhuillier-Akakpo, M
   Tanty, V
   Blugeon, C
   Alberti, A
   Labadie, K
   Aury, JM
   Sperling, L
   Duharcourt, S
   Meyer, E
AF Singh, Deepankar Pratap
   Saudemont, Baptiste
   Guglielmi, Gerard
   Arnaiz, Olivier
   Gout, Jean-Francois
   Prajer, Malgorzata
   Potekhin, Alexey
   Przybos, Ewa
   Aubusson-Fleury, Anne
   Bhullar, Simran
   Bouhouche, Khaled
   Lhuillier-Akakpo, Maoussi
   Tanty, Veronique
   Blugeon, Corinne
   Alberti, Adriana
   Labadie, Karine
   Aury, Jean-Marc
   Sperling, Linda
   Duharcourt, Sandra
   Meyer, Eric
TI Genome-defence small RNAs exapted for epigenetic mating-type inheritance
SO NATURE
LA English
DT Article
ID programmed dna elimination; paramecium-tetraurelia; developmental excision; sex determination; genetic-analysis; sequence; differentiation; rearrangements; proteins; expression
AB In the ciliate Paramecium, transposable elements and their single-copy remnants are deleted during the development of somatic macronuclei from germline micronuclei, at each sexual generation. Deletions are targeted by scnRNAs, small RNAs produced from the germ line during meiosis that first scan the maternal macronuclear genome to identify missing sequences, and then allow the zygotic macronucleus to reproduce the same deletions. Here we show that this process accounts for the maternal inheritance of mating types in Paramecium tetraurelia, a long-standing problem in epigenetics. Mating type E depends on expression of the transmembrane protein mtA, and the default type O is determined during development by scnRNA-dependent excision of the mtA promoter. In the sibling species Paramecium septaurelia, mating type O is determined by coding-sequence deletions in a different gene, mtB, which is specifically required for mtA expression. These independently evolved mechanisms suggest frequent exaptation of the scnRNA pathway to regulate cellular genes and mediate transgene-rational epigenetic inheritance of essential phenotypic polymorphisms.
C1 [Singh, Deepankar Pratap; Saudemont, Baptiste; Guglielmi, Gerard; Bhullar, Simran; Bouhouche, Khaled; Tanty, Veronique; Blugeon, Corinne; Meyer, Eric] Ecole Normale Super, Inst Biol, ENS, IBENS, F-75005 Paris, France.
   [Singh, Deepankar Pratap; Saudemont, Baptiste; Guglielmi, Gerard; Bhullar, Simran; Bouhouche, Khaled; Tanty, Veronique; Blugeon, Corinne; Meyer, Eric] INSERM, U1024, F-75005 Paris, France.
   [Singh, Deepankar Pratap; Saudemont, Baptiste; Guglielmi, Gerard; Bhullar, Simran; Bouhouche, Khaled; Tanty, Veronique; Blugeon, Corinne; Meyer, Eric] CNRS, UMR 8197, F-75005 Paris, France.
   [Singh, Deepankar Pratap; Saudemont, Baptiste; Lhuillier-Akakpo, Maoussi] UPMC Univ, Sorbonne Univ, IFD, F-75252 Paris 05, France.
   [Arnaiz, Olivier; Aubusson-Fleury, Anne] Ctr Genet Molec, CNRS, UMR 8197, F-91198 Gif Sur Yvette, France.
   [Arnaiz, Olivier; Aubusson-Fleury, Anne] Univ Paris Sud, Dept Biol, F-91405 Orsay 05, France.
   [Gout, Jean-Francois] Univ Lyon, UMR5558, CNRS, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France.
   [Prajer, Malgorzata; Przybos, Ewa] Polish Acad Sci, Inst Systemat & Evolut Anim, PL-31016 Krakow, Poland.
   [Potekhin, Alexey] St Petersburg State Univ, Dept Microbiol, Fac Biol, St Petersburg 199034, Russia.
   [Lhuillier-Akakpo, Maoussi; Duharcourt, Sandra] Univ Paris Diderot, Sorbonne Paris Cite, CNRS, Inst Jacques Monod,UMR 7592, F-75205 Paris, France.
   [Alberti, Adriana; Labadie, Karine; Aury, Jean-Marc] CEA, IG, Genoscope, F-91057 Evry, France.
C3 Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; VetAgro Sup; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite Lyon 1; Polish Academy of Sciences; Institute of Systematics & Evolution of Animals of the Polish Academy of Sciences; Saint Petersburg State University; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA
RP Meyer, E (corresponding author), Ecole Normale Super, Inst Biol, ENS, IBENS, F-75005 Paris, France.
EM emeyer@biologie.ens.fr
FU 'Investissements d'Avenir' program, Paris Sciences et Lettres* Research University [ANR-10-LABX-54 MEMO LIFE/ANR-11-IDEX-0001-02]; 'Equipe FRM' grant; CNRS ATIP-Avenir; National Science Foundation [MCB-1050161]; Erasmus Mundus program; Ligue Nationale Contre le Cancer; Ministere de l'Enseignement Superieur et de la Recherche; Fondation de la Recherche Medicale; CNRS;  [ANR-08-BLAN-0233];  [ANR-12-BSV6-0017];  [ANR-2010-BLAN-1603];  [RFBR 13-04-01683a]
NR 64
TC 80
Z9 85
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 MAY 22
PY 2014
VL 509
IS 7501
BP 447
EP +
DI 10.1038/nature13318
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000030
PM 24805235
DA 2026-03-09
ER

PT J
AU Sherwood, SC
   Bony, S
   Dufresne, JL
AF Sherwood, Steven C.
   Bony, Sandrine
   Dufresne, Jean-Louis
TI Spread in model climate sensitivity traced to atmospheric convective mixing
SO NATURE
LA English
DT Article
ID general-circulation; feedbacks; future; clouds; simulations; cmip5
AB Equilibrium climate sensitivity refers to the ultimate change in global mean temperature in response to a change in external forcing. Despite decades of research attempting to narrow uncertainties, equilibrium climate sensitivity estimates from climate models still span roughly 1.5 to 5 degrees Celsius for a doubling of atmospheric carbon dioxide concentration, precluding accurate projections of future climate. The spread arises largely from differences in the feedback from low clouds, for reasons not yet understood. Here we show that differences in the simulated strength of convective mixing between the lower and middle tropical troposphere explain about half of the variance in climate sensitivity estimated by 43 climate models. The apparent mechanism is that such mixing dehydrates the low-cloud layer at a rate that increases as the climate warms, and this rate of increase depends on the initial mixing strength, linking the mixing to cloud feedback. The mixing inferred from observations appears to be sufficiently strong to imply a climate sensitivity of more than 3 degrees for a doubling of carbon dioxide. This is significantly higher than the currently accepted lower bound of 1.5 degrees, thereby constraining model projections towards relatively severe future warming.
C1 [Sherwood, Steven C.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Sherwood, Steven C.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Bony, Sandrine; Dufresne, Jean-Louis] Univ Paris 06, CNRS, Meteorol Dynam Lab, F-75252 Paris, France.
   [Bony, Sandrine; Dufresne, Jean-Louis] Univ Paris 06, CNRS, Inst Pierre Simon Laplace LMD IPSL, F-75252 Paris, France.
C3 University of New South Wales Sydney; University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; Sorbonne Universite; Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Institut Polytechnique de Paris; Ecole Nationale des Ponts et Chaussees; Sorbonne Universite
RP Sherwood, SC (corresponding author), Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
EM s.sherwood@unsw.edu.au
FU FP7-ENV-2009-1 European project EUCLIPSE [244067]
NR 35
TC 597
Z9 680
U1 0
U2 206
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 2
PY 2014
VL 505
IS 7481
BP 37
EP +
DI 10.1038/nature12829
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300019
PM 24380952
DA 2026-03-09
ER

PT J
AU Sun, JL
   Ramos, A
   Chapman, B
   Johnnidis, JB
   Le, L
   Ho, YJ
   Klein, A
   Hofmann, O
   Camargo, FD
AF Sun, Jianlong
   Ramos, Azucena
   Chapman, Brad
   Johnnidis, Jonathan B.
   Le, Linda
   Ho, Yu-Jui
   Klein, Allon
   Hofmann, Oliver
   Camargo, Fernando D.
TI Clonal dynamics of native haematopoiesis
SO NATURE
LA English
DT Article
ID stem-cells; in-vivo; lifelong hematopoiesis; self-renewal; bone-marrow; mice; integration; differentiation; progenitors; homeostasis
AB It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear. Here we have established a novel experimental model in mice where cells can be uniquely and genetically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs following transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived progenitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease.
C1 [Sun, Jianlong; Ramos, Azucena; Le, Linda; Camargo, Fernando D.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
   [Sun, Jianlong; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Sun, Jianlong; Camargo, Fernando D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Chapman, Brad; Hofmann, Oliver] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Johnnidis, Jonathan B.] Univ Penn, Dept Immunol, Philadelphia, PA 19104 USA.
   [Ho, Yu-Jui] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Klein, Allon] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University; Harvard University; Harvard T.H. Chan School of Public Health; University of Pennsylvania; Cold Spring Harbor Laboratory; Harvard University; Harvard Medical School
RP Camargo, FD (corresponding author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM Camargo@fas.harvard.edu
FU NIH [P30 DK049216, DP2OD006472]; Harvard Stem Cell Institute
NR 33
TC 634
Z9 781
U1 0
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 OCT 16
PY 2014
VL 514
IS 7522
BP 322
EP +
DI 10.1038/nature13824
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600042
PM 25296256
DA 2026-03-09
ER

PT J
AU Sasaki, E
   Zhang, X
   Sun, HG
   Lu, MYJ
   Liu, TL
   Ou, A
   Li, JY
   Chen, YH
   Ealick, SE
   Liu, HW
AF Sasaki, Eita
   Zhang, Xuan
   Sun, He G.
   Lu, Mei-Yeh Jade
   Liu, Tsung-lin
   Ou, Albert
   Li, Jeng-yi
   Chen, Yu-hsiang
   Ealick, Steven E.
   Liu, Hung-wen
TI Co-opting sulphur-carrier proteins from primary metabolic pathways for 2-thiosugar biosynthesis
SO NATURE
LA English
DT Article
ID molybdenum cofactor; sugar biosynthesis; crystal-structure; thiolation; mechanism; sequence; genes; mocs3
AB Sulphur is an essential element for life and is ubiquitous in living systems(1,2). Yet how the sulphur atom is incorporated into many sulphur-containing secondary metabolites is poorly understood. For bond formation between carbon and sulphur in primary metabolites, the major ionic sulphur sources are the persulphide and thiocarboxylate groups on sulphur-carrier (donor) proteins(3,4). Each group is post-translationally generated through the action of a specific activating enzyme. In all reported bacterial cases, the gene encoding the enzyme that catalyses the carbon-sulphur bond formation reaction and that encoding the cognate sulphur-carrier protein exist in the same gene cluster(5). To study the production of the 2-thiosugar moiety in BE-7585A, an antibiotic from Amycolatopsis orientalis, we identified a putative 2-thioglucose synthase, BexX, whose protein sequence and mode of action seem similar to those of ThiG, the enzyme that catalyses thiazole formation in thiamine biosynthesis(6,7). However, no gene encoding a sulphur-carrier protein could be located in the BE-7585A cluster. Subsequent genome sequencing uncovered a few genes encoding sulphur-carrier proteins that are probably involved in the biosynthesis of primary metabolites but only one activating enzyme gene in the A. orientalis genome. Further experiments showed that this activating enzyme can adenylate each of these sulphur carrier proteins and probably also catalyses the subsequent thiolation, through its rhodanese domain. A proper combination of these sulphur-delivery systems is effective for BexX-catalysed2-thioglucose production. The ability of BexX to selectively distinguish sulphur-carrier proteins is given a structural basis using X-ray crystallography. This study is, to our knowledge, the first complete characterization of thiosugar formation in nature and also demonstrates the receptor promiscuity of the A. orientalis sulphur-delivery system. Our results also show that co-opting the sulphur-delivery machinery of primary metabolism for the biosynthesis of sulphur-containing natural products is probably a general strategy found in nature.
C1 [Sasaki, Eita; Liu, Hung-wen] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
   [Zhang, Xuan; Ealick, Steven E.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Sun, He G.; Liu, Hung-wen] Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA.
   [Lu, Mei-Yeh Jade; Li, Jeng-yi; Chen, Yu-hsiang] Acad Sinica, Biodivers Res Ctr, Taipei 115, Taiwan.
   [Lu, Mei-Yeh Jade; Liu, Tsung-lin; Ou, Albert] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
   [Liu, Tsung-lin] Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Tainan 701, Taiwan.
C3 University of Texas System; University of Texas Austin; Cornell University; University of Texas System; University of Texas Austin; Academia Sinica - Taiwan; Academia Sinica - Taiwan; National Cheng Kung University
RP Liu, HW (corresponding author), Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
EM h.w.liu@mail.utexas.edu
FU Academia Sinica; National Institutes of Health (NIH) [GM035906, DK67081]; Welch Foundation [F-1511]; National Institute of General Medical Sciences, NIH [GM103403]; National Institute of General Medical Sciences [R01GM035906] Funding Source: NIH RePORTER
NR 45
TC 54
Z9 64
U1 0
U2 93
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 19
PY 2014
VL 510
IS 7505
BP 427
EP +
DI 10.1038/nature13256
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200041
PM 24814342
DA 2026-03-09
ER

PT J
AU Wilson, ML
   Boesch, C
   Fruth, B
   Furuichi, T
   Gilby, IC
   Hashimoto, C
   Hobaiter, CL
   Hohmann, G
   Itoh, N
   Koops, K
   Lloyd, JN
   Matsuzawa, T
   Mitani, JC
   Mjungu, DC
   Morgan, D
   Muller, MN
   Mundry, R
   Nakamura, M
   Pruetz, J
   Pusey, AE
   Riedel, J
   Sanz, C
   Schel, AM
   Simmons, N
   Waller, M
   Watts, DP
   White, F
   Wittig, RM
   Zuberbühler, K
   Wrangham, RW
AF Wilson, Michael L.
   Boesch, Christophe
   Fruth, Barbara
   Furuichi, Takeshi
   Gilby, Ian C.
   Hashimoto, Chie
   Hobaiter, Catherine L.
   Hohmann, Gottfried
   Itoh, Noriko
   Koops, Kathelijne
   Lloyd, Julia N.
   Matsuzawa, Tetsuro
   Mitani, John C.
   Mjungu, Deus C.
   Morgan, David
   Muller, Martin N.
   Mundry, Roger
   Nakamura, Michio
   Pruetz, Jill
   Pusey, Anne E.
   Riedel, Julia
   Sanz, Crickette
   Schel, Anne M.
   Simmons, Nicole
   Waller, Michel
   Watts, David P.
   White, Frances
   Wittig, Roman M.
   Zuberbuehler, Klaus
   Wrangham, Richard W.
TI Lethal aggression in Pan is better explained by adaptive strategies than human impacts
SO NATURE
LA English
DT Article
ID kibale-national-park; male chimpanzees; intragroup infanticide; intergroup aggression; wild chimpanzees; cannibalism; violence; ngogo; evolution; death
AB Observations of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) provide valuable comparative data for understanding the significance of conspecific killing. Two kinds of hypothesis have been proposed. Lethal violence is sometimes concluded to be the result of adaptive strategies, such that killers ultimately gain fitness benefits by increasing their access to resources such as food or mates(1-5). Alternatively, it could be a non-adaptive result of human impacts, such as habitat change or food provisioning(6-9). To discriminate between these hypotheses we compiled information from 18 chimpanzee communities and 4 bonobo communities studied over five decades. Our data include 152 killings (n = 58 observed, 41 inferred, and 53 suspected killings) by chimpanzees in 15 communities and one suspected killing by bonobos. We found that males were the most frequent attackers (92% of participants) and victims (73%); most killings (66%) involved intercommunity attacks; and attackers greatly outnumbered their victims (median 8:1 ratio). Variation in killing rates was unrelated to measures of human impacts. Our results are compatible with previously proposed adaptive explanations for killing by chimpanzees, whereas the human impact hypothesis is not supported.
C1 [Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Humphrey Ctr 395, Minneapolis, MN 55455 USA.
   [Wilson, Michael L.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Boesch, Christophe; Hohmann, Gottfried; Riedel, Julia; Wittig, Roman M.] Max Planck Inst Evolutionare Anthropol, Dept Primatol, D-04103 Leipzig, Germany.
   [Fruth, Barbara] Univ Munich, Div Neurobiol, D-81377 Munich, Germany.
   [Fruth, Barbara] Royal Zool Soc Antwerp, Ctr Res & Conservat, Antwerp, Belgium.
   [Furuichi, Takeshi; Hashimoto, Chie; Matsuzawa, Tetsuro] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 4848506, Japan.
   [Gilby, Ian C.; Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA.
   [Gilby, Ian C.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
   [Hobaiter, Catherine L.; Zuberbuehler, Klaus] Univ St Andrews, Sch Psychol & Neurosci, St Andrews KY16 9JP, Fife, Scotland.
   [Itoh, Noriko; Nakamura, Michio] Kyoto Univ, Wildlife Res Ctr, Sakyo Ku, Kyoto, Japan.
   [Koops, Kathelijne] Univ Cambridge, Dept Archaeol & Anthropol, Div Biol Anthropol, Cambridge CB2 1QH, England.
   [Lloyd, Julia N.; Simmons, Nicole] Makerere Univ, Dept Zool, Kampala, Uganda.
   [Matsuzawa, Tetsuro] Japan Monkey Ctr, Inuyama, Aichi 4840081, Japan.
   [Mitani, John C.] Univ Michigan, Dept Anthropol, Ann Arbor, MI 48109 USA.
   [Mjungu, Deus C.] Jane Goodall Inst Tanzania, Gombe Stream Res Ctr, Kigoma, Tanzania.
   [Morgan, David] Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL 60614 USA.
   [Muller, Martin N.] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA.
   [Mundry, Roger] Max Planck Inst Evolutionare Anthropol, D-04103 Leipzig, Germany.
   [Pruetz, Jill] Iowa State Univ, Dept Anthropol, Ames, IA 50011 USA.
   [Sanz, Crickette] Washington Univ, Dept Anthropol, St Louis, MO 63130 USA.
   [Schel, Anne M.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
   [Waller, Michel; White, Frances] Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA.
   [Watts, David P.] Yale Univ, Dept Anthropol, New Haven, CT 06511 USA.
   [Zuberbuehler, Klaus] Univ Neuchatel, Inst Biol, CH-2000 Neuchatel, Switzerland.
   [Wrangham, Richard W.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Max Planck Society; University of Munich; Kyoto University; Duke University; Arizona State University; Arizona State University-Tempe; University of St Andrews; Kyoto University; University of Cambridge; Makerere University; Kyoto University; University of Michigan System; University of Michigan; University of New Mexico; Max Planck Society; Iowa State University; Washington University (WUSTL); University of York - UK; University of Oregon; Yale University; University of Neuchatel; Harvard University
RP Wilson, ML (corresponding author), Univ Minnesota, Dept Anthropol, Humphrey Ctr 395, 301 19th Ave South, Minneapolis, MN 55455 USA.
EM wilso198@umn.edu
FU National Science Foundation [BCS-0648481, LTREB-1052693]; National Institutes of Health [R01 AI 058715]; Grants-in-Aid for Scientific Research [24000001, 25304019, 26257408] Funding Source: KAKEN; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1052693] Funding Source: National Science Foundation
NR 64
TC 328
Z9 379
U1 2
U2 246
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2014
VL 513
IS 7518
BP 414
EP +
DI 10.1038/nature13727
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900059
PM 25230664
DA 2026-03-09
ER

PT J
AU Li, CY
   de Grijs, R
   Deng, LC
AF Li, Chengyuan
   de Grijs, Richard
   Deng, Licai
TI The exclusion of a significant range of ages in a massive star cluster
SO NATURE
LA English
DT Article
ID large-magellanic-cloud; double main-sequence; multiple stellar populations; color-magnitude diagrams; globular-clusters; formation history; omega-centauri; ngc 1818; parameters; rotation
AB Stars spend most of their lifetimes on the main sequence in the Hertzsprung-Russell diagram. The extended main-sequence turn-off regions-containing stars leaving the main sequence after having spent all of the hydrogen in their cores-found in massive (more than a few tens of thousands of solar masses), intermediate-age (about one to three billion years old) star clusters1-8 are usually interpreted as evidence of internal age spreads of more than 300 million years(2,4,5), although young clusters are thought to quickly lose any remaining star-forming fuel following a period of rapid gas expulsion on timescales of order 10(7) years(9,10). Here we report, on the basis of a combination of high-resolution imaging observations and theoretical modelling, that the stars beyond the main sequence in the two-billion-year-old cluster NGC 1651, characterized by a mass of about 1.7 x 10(5) solar masses(3), can be explained only by a single-age stellar population, even though the cluster has a clearly extended main-sequence turn-off region. The most plausible explanation for the existence of such extended regions invokes a population of rapidly rotating stars, although the secondary effects of the prolonged stellar lifetimes associated with such a stellar population mixture are as yet poorly understood. From preliminary analysis of previously obtained data, we find that similar morphologies are apparent in the Hertzsprung-Russell diagrams of at least five additional intermediate-age star clusters(2,3,5,11), suggesting that an extended main-sequence turn-off region does not necessarily imply the presence of a significant internal age dispersion.
C1 [Li, Chengyuan; de Grijs, Richard] Peking Univ, Kavli Inst Astron & Astrophys, Beijing 100871, Peoples R China.
   [Li, Chengyuan; de Grijs, Richard] Peking Univ, Dept Astron, Beijing 100871, Peoples R China.
   [Li, Chengyuan; Deng, Licai] Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, Beijing 100012, Peoples R China.
C3 Peking University; Peking University; Chinese Academy of Sciences; National Astronomical Observatory, CAS
RP Li, CY (corresponding author), Peking Univ, Kavli Inst Astron & Astrophys, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.
EM joshuali@pku.edu.cn
FU National Natural Science Foundation of China [11073001, 11373010, 11473037]
NR 38
TC 59
Z9 61
U1 0
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 DEC 18
PY 2014
VL 516
IS 7531
BP 367
EP +
DI 10.1038/nature13969
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800040
PM 25519133
DA 2026-03-09
ER

PT J
AU Reiserer, A
   Kalb, N
   Rempe, G
   Ritter, S
AF Reiserer, Andreas
   Kalb, Norbert
   Rempe, Gerhard
   Ritter, Stephan
TI A quantum gate between a flying optical photon and a single trapped atom
SO NATURE
LA English
DT Article
ID phase-shifts; communication
AB The steady increase in control over individual quantum systems supports the promotion of a quantum technology that could provide functionalities beyond those of any classical device. Two particularly promising applications have been explored during the past decade: photon-based quantum communication, which guarantees unbreakable encryption(1) but which still has to be scaled to high rates over large distances, and quantum computation, which will fundamentally enhance computability(2) if it can be scaled to a large number of quantum bits (qubits). It was realized early on that a hybrid system of light qubits and matter qubits(3) could solve the scalability problem of each field-that of communication by use of quantum repeaters4, and that of computation by use of an optical interconnect between smaller quantum processors(5,6). To this end, the development of a robust two-qubit gate that allows the linking of distant computational nodes is "a pressing challenge"(6). Here we demonstrate such a quantum gate between the spin state of a single trapped atom and the polarization state of an optical photon contained in a faint laser pulse. The gate mechanism presented(7,8) is deterministic and robust, and is expected to be applicable to almost any matter qubit. It is based on reflection of the photonic qubit from a cavity that provides strong light-matter coupling. To demonstrate its versatility, we use the quantum gate to create atom-photon, atom-photon-photon and photon-photon entangled states from separable input states. We expect our experiment to enable various applications, including the generation of atomic(9) and photonic(10) cluster states and Schrodinger-cat states(11), deterministic photonic Bell-state measurements(12), scalable quantum computation(7) and quantum communication using a redundant quantum parity code(13).
C1 [Reiserer, Andreas; Kalb, Norbert; Rempe, Gerhard; Ritter, Stephan] Max Planck Inst Quanten Opt, D-85748 Garching, Germany.
C3 Max Planck Society
RP Rempe, G (corresponding author), Max Planck Inst Quanten Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM gerhard.rempe@mpq.mpg.de
FU European Union; Bundesministerium fur Bildung und Forschung [IKT 2020]
NR 30
TC 331
Z9 402
U1 1
U2 179
PU NATURE PUBLISHING 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 10
PY 2014
VL 508
IS 7495
BP 237
EP +
DI 10.1038/nature13177
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900042
PM 24717512
DA 2026-03-09
ER

PT J
AU Schatz, H
   Gupta, S
   Möller, P
   Beard, M
   Brown, EF
   Deibel, AT
   Gasques, LR
   Hix, WR
   Keek, L
   Lau, R
   Steiner, AW
   Wiescher, M
AF Schatz, H.
   Gupta, S.
   Moeller, P.
   Beard, M.
   Brown, E. F.
   Deibel, A. T.
   Gasques, L. R.
   Hix, W. R.
   Keek, L.
   Lau, R.
   Steiner, A. W.
   Wiescher, M.
TI Strong neutrino cooling by cycles of electron capture and β- decay in neutron star crusts
SO NATURE
LA English
DT Article
ID x-ray-bursts; inner crust; models; ignition; ocean
AB The temperature in the crust of an accreting neutron star, which comprises its outermost kilometre, is set by heating from nuclear reactions at large densities(1-4), neutrino cooling(5,6) and heat transport from the interior(7-11). The heated crust has been thought to affect observable phenomena at shallower depths, such as thermonuclear bursts in the accreted envelope(10,11). Here we report that cycles of electron capture and its inverse, beta(-) decay, involving neutron-rich nuclei at a typical depth of about 150 metres, cool the outer neutron star crust by emitting neutrinos while also thermally decoupling the surface layers from the deeper crust. This 'Urca' mechanism(12) has been studied in the context of white dwarfs(13) and type Ia supernovae(14,15), but hitherto was not considered in neutron stars, because previous models(1,2) computed the crust reactions using a zero-temperature approximation and assumed that only a single nuclear species was present at any given depth. The thermal decoupling means that X-ray bursts and other surface phenomena are largely independent of the strength of deep crustal heating. The unexpectedly short recurrence times, of the order of years, observed for very energetic thermonuclear superbursts(16) are therefore not an indicator of a hot crust, but may point instead to an unknown local heating mechanism near the neutron star surface.
C1 [Schatz, H.; Brown, E. F.; Keek, L.; Lau, R.] Michigan State Univ, Natl Superconducting Cyclotron Lab, E Lansing, MI 48824 USA.
   [Schatz, H.; Moeller, P.; Beard, M.; Brown, E. F.; Deibel, A. T.; Keek, L.; Lau, R.; Steiner, A. W.; Wiescher, M.] Univ Notre Dame, Joint Inst Nucl Astrophys, Notre Dame, IN 46556 USA.
   [Schatz, H.; Brown, E. F.; Deibel, A. T.; Keek, L.; Lau, R.] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Gupta, S.] Indian Inst Technol Ropar, Rupnagar Ropar 140001, Punjab, India.
   [Moeller, P.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA.
   [Beard, M.; Wiescher, M.] Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA.
   [Gasques, L. R.] Univ Sao Paulo, Inst Fis, Dept Fis Nucl, BR-05315970 Sao Paulo, Brazil.
   [Hix, W. R.] Oak Ridge Natl Lab, Div Phys, Oak Ridge, TN 37831 USA.
   [Hix, W. R.] Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
   [Steiner, A. W.] Univ Washington, Inst Nucl Theory, Seattle, WA 98195 USA.
C3 Michigan State University; University of Notre Dame; Michigan State University; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Ropar; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Notre Dame; Universidade de Sao Paulo; United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Tennessee System; University of Tennessee Knoxville; University of Washington; University of Washington Seattle
RP Schatz, H (corresponding author), Michigan State Univ, Natl Superconducting Cyclotron Lab, 640 South Shaw Lane, E Lansing, MI 48824 USA.
EM schatz@nscl.msu.edu
FU NSF [PHY 08-22648, PHY 06-06007, AST 11-09176]; INT DOE [DE-FG02-00ER41132]; National Nuclear Security Administration of the US Department of Energy at Los Alamos National Laboratory [DE-AC52-06NA25396]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109176] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1068192] Funding Source: National Science Foundation
NR 29
TC 108
Z9 120
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 JAN 2
PY 2014
VL 505
IS 7481
BP 62
EP +
DI 10.1038/nature12757
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300023
PM 24291788
DA 2026-03-09
ER

PT J
AU Araya, CL
   Kawli, T
   Kundaje, A
   Jiang, LX
   Wu, BJ
   Vafeados, D
   Terrell, R
   Weissdepp, P
   Gevirtzman, L
   Mace, D
   Niu, W
   Boyle, AP
   Xie, D
   Ma, LJ
   Murray, JI
   Reinke, V
   Waterston, RH
   Snyder, M
AF Araya, Carlos L.
   Kawli, Trupti
   Kundaje, Anshul
   Jiang, Lixia
   Wu, Beijing
   Vafeados, Dionne
   Terrell, Robert
   Weissdepp, Peter
   Gevirtzman, Louis
   Mace, Daniel
   Niu, Wei
   Boyle, Alan P.
   Xie, Dan
   Ma, Lijia
   Murray, John I.
   Reinke, Valerie
   Waterston, Robert H.
   Snyder, Michael
TI Regulatory analysis of the C. elegans genome with spatiotemporal resolution
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; gene-expression; cell lineage; chip-seq; transcription factors; factor colocalization; binding; morphogenesis; similarity; homolog
AB Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatio-temporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.
C1 [Araya, Carlos L.; Kawli, Trupti; Jiang, Lixia; Wu, Beijing; Boyle, Alan P.; Xie, Dan; Snyder, Michael] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Kundaje, Anshul] MIT, Dept Comp Sci, Cambridge, MA 02139 USA.
   [Vafeados, Dionne; Terrell, Robert; Weissdepp, Peter; Gevirtzman, Louis; Mace, Daniel; Waterston, Robert H.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Niu, Wei; Reinke, Valerie] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Ma, Lijia] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
   [Murray, John I.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
C3 Stanford University; Massachusetts Institute of Technology (MIT); University of Washington; University of Washington Seattle; Yale University; University of Chicago; University of Pennsylvania
RP Snyder, M (corresponding author), Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
EM watersto@u.washington.edu; mpsnyder@stanford.edu
FU NHGRI as part of the modENCODE project [U01 HG004267]
NR 49
TC 88
Z9 110
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 AUG 28
PY 2014
VL 512
IS 7515
BP 400
EP U363
DI 10.1038/nature13497
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600026
PM 25164749
DA 2026-03-09
ER

PT J
AU Lee, JM
   Wagner, M
   Xiao, R
   Kim, KH
   Feng, D
   Lazar, MA
   Moore, DD
AF Lee, Jae Man
   Wagner, Martin
   Xiao, Rui
   Kim, Kang Ho
   Feng, Dan
   Lazar, Mitchell A.
   Moore, David D.
TI Nutrient-sensing nuclear receptors coordinate autophagy
SO NATURE
LA English
DT Article
ID farnesoid-x-receptor; negative feedback-regulation; activated receptor; bile-acid; targeted disruption; fatty-acids; identification; mtor; ampk; metabolism
AB Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis(1-3). Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-alpha (PPAR alpha) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively(4,5). Here we show that both PPARa and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPARa reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARa knockout (Ppara(-/-), also known as Nr1c1(-/-) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARa and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.
C1 [Lee, Jae Man; Wagner, Martin; Xiao, Rui; Kim, Kang Ho; Moore, David D.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Feng, Dan; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19014 USA.
   [Feng, Dan; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19014 USA.
C3 Baylor College of Medicine; University of Pennsylvania; University of Pennsylvania
RP Moore, DD (corresponding author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
EM moore@bcm.edu
FU Alkek Foundation; Robert R.P. Doherty Jr-Welch Chair in Science [R01 DK49780, DK43806];  [U54 HD-07495-39];  [P30 DX56338-05A2];  [P39 CA125123-04];  [S10RR027783-01A1]; National Cancer Institute [P30CA125123] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056338, R01DK049780, P30DK019525, R01DK043806] Funding Source: NIH RePORTER
NR 46
TC 429
Z9 491
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 DEC 4
PY 2014
VL 516
IS 7529
BP 112
EP U291
DI 10.1038/nature13961
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800050
PM 25383539
DA 2026-03-09
ER

PT J
AU Whitney, JB
   Hill, AL
   Sanisetty, S
   Penaloza-MacMaster, P
   Liu, JY
   Shetty, M
   Parenteau, L
   Cabral, C
   Shields, J
   Blackmore, S
   Smith, JY
   Brinkman, AL
   Peter, LE
   Mathew, SI
   Smith, KM
   Borducchi, EN
   Rosenbloom, DIS
   Lewis, MG
   Hattersley, J
   Li, B
   Hesselgesser, J
   Geleziunas, R
   Robb, ML
   Kim, JH
   Michael, NL
   Barouch, DH
AF Whitney, James B.
   Hill, Alison L.
   Sanisetty, Srisowmya
   Penaloza-MacMaster, Pablo
   Liu, Jinyan
   Shetty, Mayuri
   Parenteau, Lily
   Cabral, Crystal
   Shields, Jennifer
   Blackmore, Stephen
   Smith, Jeffrey Y.
   Brinkman, Amanda L.
   Peter, Lauren E.
   Mathew, Sheeba I.
   Smith, Kaitlin M.
   Borducchi, Erica N.
   Rosenbloom, Daniel I. S.
   Lewis, Mark G.
   Hattersley, Jillian
   Li, Bei
   Hesselgesser, Joseph
   Geleziunas, Romas
   Robb, Merlin L.
   Kim, Jerome H.
   Michael, Nelson L.
   Barouch, Dan H.
TI Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys
SO NATURE
LA English
DT Article
ID antiretroviral therapy; latent reservoir; hiv-1 infection; replication; vaccine; prevention; initiation; dynamics; depends; assay
AB The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies(1-5). However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early anti-retroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIVMAC251 infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.
C1 [Whitney, James B.; Sanisetty, Srisowmya; Penaloza-MacMaster, Pablo; Liu, Jinyan; Shetty, Mayuri; Parenteau, Lily; Cabral, Crystal; Shields, Jennifer; Blackmore, Stephen; Smith, Jeffrey Y.; Brinkman, Amanda L.; Peter, Lauren E.; Mathew, Sheeba I.; Smith, Kaitlin M.; Borducchi, Erica N.; Barouch, Dan H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
   [Whitney, James B.; Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
   [Hill, Alison L.; Rosenbloom, Daniel I. S.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Lewis, Mark G.] Bioqual, Rockville, MD 20852 USA.
   [Hattersley, Jillian; Li, Bei; Hesselgesser, Joseph; Geleziunas, Romas] Gilead Sci Inc, Foster City, CA 94404 USA.
   [Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; 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; Walter Reed Army Institute of Research (WRAIR); United States Department of Defense; United States Army
RP Barouch, DH (corresponding author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
FU US Army Medical Research and Material Command; US Military HIV Research Program; Henry M. Jackson Foundation for the Advancement of Military Medicine [W81XWH-07-2-0067, W81XWH-11-2-0174]; NIH [AI060354, AI078526, AI084794, AI095985, AI096040, AI100645]; Ragon Institute of MGH, MIT and Harvard; National Institute of Allergy and Infectious Diseases [T32AI007245] Funding Source: NIH RePORTER; National Institute on Minority Health and Health Disparities; National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Nursing Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Cancer Institute; National Heart Lung and Blood Institute; National Institute of Dental and Craniofacial Research [P30AI060354] Funding Source: NIH RePORTER
NR 28
TC 504
Z9 649
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 AUG 7
PY 2014
VL 512
IS 7512
BP 74
EP +
DI 10.1038/nature13594
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000034
PM 25042999
DA 2026-03-09
ER

PT J
AU Jones, OR
   Scheuerlein, A
   Salguero-Gómez, R
   Camarda, CG
   Schaible, R
   Casper, BB
   Dahlgren, JP
   Ehrlén, J
   García, MB
   Menges, ES
   Quintana-Ascencio, PF
   Caswell, H
   Baudisch, A
   Vaupel, JW
AF Jones, Owen R.
   Scheuerlein, Alexander
   Salguero-Gomez, Roberto
   Camarda, Carlo Giovanni
   Schaible, Ralf
   Casper, Brenda B.
   Dahlgren, Johan P.
   Ehrlen, Johan
   Garcia, Maria B.
   Menges, Eric S.
   Quintana-Ascencio, Pedro F.
   Caswell, Hal
   Baudisch, Annette
   Vaupel, James W.
TI Diversity of ageing across the tree of life
SO NATURE
LA English
DT Article
ID senescence; mortality; age; reproduction; history; longevity; selection; evolution; models; stage
AB Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long-and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.
C1 [Jones, Owen R.; Dahlgren, Johan P.; Vaupel, James W.] Max Planck Odense Ctr Biodemog Aging, DK-5230 Odense M, Denmark.
   [Jones, Owen R.; Dahlgren, Johan P.; Caswell, Hal] Univ Southern Denmark, Dept Biol, DK-5230 Odense M, Denmark.
   [Scheuerlein, Alexander; Salguero-Gomez, Roberto; Schaible, Ralf; Caswell, Hal; Baudisch, Annette; Vaupel, James W.] Max Planck Inst Demog Res, D-18057 Rostock, Germany.
   [Salguero-Gomez, Roberto] Univ Queensland, Ctr Biodivers & Conservat Sci, Sch Biol Sci, Brisbane, Qld 4072, Australia.
   [Camarda, Carlo Giovanni] Inst Natl Etud Demog, F-75980 Paris 20, France.
   [Casper, Brenda B.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Ehrlen, Johan] Stockholm Univ, Dept Ecol Environm & Plant Sci, S-10691 Stockholm, Sweden.
   [Garcia, Maria B.] CSIC, Pyrenean Inst Ecol, Zaragoza 50059, Spain.
   [Menges, Eric S.] Archbold Biol Stn, Venus, FL 33960 USA.
   [Quintana-Ascencio, Pedro F.] Univ Cent Florida, Dept Biol, Orlando, FL 32816 USA.
   [Caswell, Hal] Woods Hole Oceanog Inst, Biol Dept MS 34, Woods Hole, MA 02543 USA.
   [Caswell, Hal] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, NL-1090 GE Amsterdam, Netherlands.
   [Vaupel, James W.] Duke Univ, Duke Populat Res Inst, Durham, NC 27705 USA.
C3 University of Southern Denmark; Max Planck Society; University of Queensland; University of Pennsylvania; Stockholm University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Pirenaico de Ecologia (IPE); State University System of Florida; University of Central Florida; Woods Hole Oceanographic Institution; University of Amsterdam; Duke University
RP Jones, OR (corresponding author), Max Planck Odense Ctr Biodemog Aging, Campusvej 55, DK-5230 Odense M, Denmark.
EM jones@biology.sdu.dk
FU NIH [PO1 AG-031719]; Alexander von Humboldt Foundation; European Research Council [322989]; ARC [DP110100727]; Max Planck Society; NERC [NE/G004854/1] Funding Source: UKRI; Natural Environment Research Council [NE/G004854/1] Funding Source: researchfish
NR 49
TC 693
Z9 766
U1 4
U2 483
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 9
PY 2014
VL 505
IS 7482
BP 169
EP +
DI 10.1038/nature12789
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500029
PM 24317695
DA 2026-03-09
ER

PT J
AU Barrett, KT
   Metrano, AJ
   Rablen, PR
   Miller, SJ
AF Barrett, Kimberly T.
   Metrano, Anthony J.
   Rablen, Paul R.
   Miller, Scott J.
TI Spontaneous transfer of chirality in an atropisomerically enriched two-axis system
SO NATURE
LA English
DT Article
ID tertiary aromatic amides; kinetic resolution; axial chirality; drug discovery; rotation; enantiomerization; barriers; equilibration; separation; catalysis
AB One of the most well-recognized stereogenic elements in a chiral molecule is an sp(3)-hybridized carbon atom that is connected to four different substituents. Axes of chirality can also exist about bonds with hindered barriers of rotation; molecules containing such axes are known as atropisomers(1). Understanding the dynamics of these systems can be useful, for example, in the design of single-atropisomer drugs(2) or molecular switches and motors(3). For molecules that exhibit a single axis of chirality, rotation about that axis leads to racemization as the system reaches equilibrium. Here we report a two-axis system for which an enantioselective reaction produces four stereoisomers (two enantiomeric pairs): following a catalytic asymmetric transformation, we observe a kinetically controlled product distribution that is perturbed from the system's equilibrium position. As the system undergoes isomerization, one of the diastereomeric pairs drifts spontaneously to a higher enantiomeric ratio. In a compensatory manner, the enantiomeric ratio of the other diastereomeric pair decreases. These observations are made for a class of unsymmetrical amides that exhibits two asymmetric axes-one axis is defined through a benzamide substructure, and the other axis is associated with differentially N,N-disubstituted amides. The stereodynamics of these substrates provides an opportunity to observe a curious interplay of kinetics and thermodynamics intrinsic to a system of stereoisomers that is constrained to a situation of partial equilibrium.
C1 [Barrett, Kimberly T.; Metrano, Anthony J.; Miller, Scott J.] Yale Univ, Dept Chem, New Haven, CT 06520 USA.
   [Rablen, Paul R.] Swarthmore Coll, Dept Chem & Biochem, Swarthmore, PA 19081 USA.
C3 Yale University; Swarthmore College
RP Miller, SJ (corresponding author), Yale Univ, Dept Chem, POB 208107, New Haven, CT 06520 USA.
EM scott.miller@yale.edu
FU National Institute of General Medical Sciences of the NIH [GM-068649]; National Science Foundation; Yale University Faculty of Arts and Sciences High Performance Computing Center; National Science Foundation [CNS 08-21132]
NR 29
TC 157
Z9 174
U1 1
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 MAY 1
PY 2014
VL 509
IS 7498
BP 71
EP 75
DI 10.1038/nature13189
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100041
PM 24747399
DA 2026-03-09
ER

PT J
AU Bhatnagar, S
   Gazin, C
   Chamberlain, L
   Ou, JH
   Zhu, XC
   Tushir, JS
   Virbasius, CM
   Lin, L
   Zhu, LHJ
   Wajapeyee, N
   Green, MR
AF Bhatnagar, Sanchita
   Gazin, Claude
   Chamberlain, Lynn
   Ou, Jianhong
   Zhu, Xiaochun
   Tushir, Jogender S.
   Virbasius, Ching-Man
   Lin, Ling
   Zhu, Lihua J.
   Wajapeyee, Narendra
   Green, Michael R.
TI TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein
SO NATURE
LA English
DT Article
ID polycomb group proteins; chip-chip data; gene-expression; transcription activation; 17q23 amplicon; complex; chromatin; ubiquitylation; bioconductor; methylation
AB The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to similar to 40% of breast cancers(1). TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases(2), but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression(3). We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B)(3,4) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP) -chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1)(3-5), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC I are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRCI and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.
C1 [Bhatnagar, Sanchita; Chamberlain, Lynn; Zhu, Xiaochun; Virbasius, Ching-Man; Lin, Ling; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
   [Bhatnagar, Sanchita; Chamberlain, Lynn; Ou, Jianhong; Zhu, Xiaochun; Virbasius, Ching-Man; Lin, Ling; Zhu, Lihua J.; Green, Michael R.] Univ Massachusetts, Sch Med, Programs Gene Funct & Express & Mol Med, Worcester, MA 01605 USA.
   [Gazin, Claude] CEA DSV iRCM LEFG, Genopole G2, F-91057 Evry, France.
   [Gazin, Claude] Univ Paris Diderot, F-91057 Evry, France.
   [Tushir, Jogender S.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
   [Zhu, Lihua J.] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA.
   [Wajapeyee, Narendra] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
C3 Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; Universite Paris Cite; Boehringer Ingelheim; University of Massachusetts System; University of Massachusetts Worcester; Yale University
RP Green, MR (corresponding author), Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
EM michael.green@umassmed.edu
FU National Lung Cancer Partnership/Uniting Against Lung Cancer; Melanoma Research Alliance; International Association for the Study of Lung Cancer; CEA-DSV; ATIGE Genopole; Centre National de la Recherche Scientifique (CNRS); National Institutes of Health [R01GM033977]
NR 42
TC 153
Z9 181
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 DEC 4
PY 2014
VL 516
IS 7529
BP 116
EP U313
DI 10.1038/nature13955
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800051
PM 25470042
DA 2026-03-09
ER

PT J
AU Cordier, P
   Demouchy, S
   Beausir, B
   Taupin, V
   Barou, F
   Fressengeas, C
AF Cordier, Patrick
   Demouchy, Sylvie
   Beausir, Benoit
   Taupin, Vincent
   Barou, Fabrice
   Fressengeas, Claude
TI Disclinations provide the missing mechanism for deforming olivine-rich rocks in the mantle
SO NATURE
LA English
DT Article
ID elastoplastic theory; grain-boundary; deformation; dislocation; creep; constraints; orientation; diffusion; strength
AB Mantle flow involves large strains of polymineral aggregates. The strongly anisotropic plastic response of each individual grain in the aggregate results from the interactions between neighbouring grains and the continuity of material displacement across the grain boundaries. Orthorhombic olivine, which is the dominant mineral phase of the Earth's upper mantle, does not exhibit enough slip systems to accommodate a general deformation state by intracrystalline slip without inducing damage. Here we show that a more general description of the deformation process that includes the motion of rotational defects referred to as disclinations can solve the olivine deformation paradox. We use high-resolution electron backscattering diffraction (EBSD) maps of deformed olivine aggregates to resolve the disclinations. The disclinations are found to decorate grain boundaries in olivine samples deformed experimentally and in nature. We present a disclination-based model of a high-angle tilt boundary in olivine, which demonstrates that an applied shear induces grain-boundary migration through disclination motion. This new approach clarifies grain-boundary-mediated plasticity in polycrystalline aggregates. By providing the missing mechanism for describing plastic flow in olivine, this work will permit multiscale modelling of the rheology of the upper mantle, from the atomic scale to the scale of the flow.
C1 [Cordier, Patrick] CNRS, UMR 8207, Unite Mat & Transformat, F-59650 Villeneuve Dascq, France.
   [Cordier, Patrick] Univ Lille 1, F-59650 Villeneuve Dascq, France.
   [Demouchy, Sylvie; Barou, Fabrice] CNRS, UMR 5342, Geosci Montpellier, F-34095 Montpellier, France.
   [Demouchy, Sylvie; Barou, Fabrice] Univ Montpellier 2, F-34095 Montpellier, France.
   [Beausir, Benoit; Taupin, Vincent; Fressengeas, Claude] CNRS, UMR 7239, Lab Etud Microstruct & Mecan Mat, F-57045 Metz, France.
   [Beausir, Benoit; Taupin, Vincent; Fressengeas, Claude] Univ Lorraine, F-57045 Metz, France.
C3 Universite de Lille; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite de Lille; Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; Universite de Montpellier; Arts et Metiers Institute of Technology; Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universite de Lorraine
RP Cordier, P (corresponding author), CNRS, UMR 8207, Unite Mat & Transformat, F-59650 Villeneuve Dascq, France.
EM patrick.cordier@univ-lille1.fr
FU European Research Council under the Seventh Framework Programme (FP7-ERC) [290424-RheoMan]; Marie Curie fellowship [FP7-PEOPLE-20074-3-IRG, 230748-PoEM]; Agence Nationale de la Recherche [ANR-11-JS09-007-01]
NR 34
TC 94
Z9 103
U1 2
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 6
PY 2014
VL 507
IS 7490
BP 51
EP +
DI 10.1038/nature13043
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400040
PM 24572356
DA 2026-03-09
ER

PT J
AU Willis, NA
   Chandramouly, G
   Huang, B
   Kwok, A
   Follonier, C
   Deng, CX
   Scully, R
AF Willis, Nicholas A.
   Chandramouly, Gurushankar
   Huang, Bin
   Kwok, Amy
   Follonier, Cindy
   Deng, Chuxia
   Scully, Ralph
TI BRCA1 controls homologous recombination at Tus/Ter-stalled mammalian replication forks
SO NATURE
LA English
DT Article
ID sister-chromatid recombination; tract gene conversion; dna-damage response; repair; orip; maintenance; termination; initiation; resolution; arrest
AB Replication fork stalling can promote genomic instability, predisposing to cancer and other diseases(1-3). Stalled replication forks may be processed by sister chromatid recombination (SCR), generating error-free or error-prone homologous recombination (HR) outcomes(4-8). In mammalian cells, a long-standing hypothesis proposes that the major hereditary breast/ovarian cancer predisposition gene products, BRCA1 and BRCA2, control HR/SCR at stalled replication forks(9). Although BRCA1 and BRCA2 affect replication fork processing(10-12), direct evidence that BRCA gene products regulate homologous recombination at stalled chromosomal replication forks is lacking, due to a dearth of tools for studying this process. Here we report that the Escherichia coli Tus/Ter complex(13-16) can be engineered to induce site-specific replication fork stalling and chromosomal HR/SCR in mouse cells. Tus/Ter-induced homologous recombination entails processing of bidirectionally arrested forks. We find that the Brca1 carboxy (C)-terminal tandem BRCT repeat and regions of Brca1 encoded by exon 11-two Brca1 elements implicated in tumour suppression-control Tus/Ter-induced homologous recombination. Inactivation of either Brca1 or Brca2 increases the absolute frequency of 'long-tract' gene conversions at Tus/Ter-stalled forks, an outcome not observed in response to a site-specific endonuclease-mediated chromosomal double-strand break. Therefore, homologous recombination at stalled forks is regulated differently from homologous recombination at double-strand breaks arising independently of a replication fork. We propose that aberrant long-tract homologous recombination at stalled replication forks contributes to genomic instability and breast/ovarian cancer predisposition in BRCA mutant cells.
C1 [Willis, Nicholas A.; Chandramouly, Gurushankar; Huang, Bin; Kwok, Amy; Scully, Ralph] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Willis, Nicholas A.; Chandramouly, Gurushankar; Huang, Bin; Kwok, Amy; Scully, Ralph] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Follonier, Cindy] Princeton Univ, Lewis Thomas Lab 101, Princeton, NJ 08544 USA.
   [Deng, Chuxia] NIDDK, NIH, Bethesda, MD 20814 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Princeton University; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Scully, R (corresponding author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
EM rscully@bidmc.harvard.edu
FU NIH [R01CA095175, R01GM073894, R21CA144017, R37GM26938]; NIH/NCI [5T32CA081156]; ACS [PF-12-248-01-DMC]; National Cancer Institute [R01CA095175] Funding Source: NIH RePORTER
NR 33
TC 126
Z9 152
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 JUN 26
PY 2014
VL 510
IS 7506
BP 556
EP +
DI 10.1038/nature13295
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300051
PM 24776801
DA 2026-03-09
ER

PT J
AU Magda, GZ
   Jin, XZ
   Hagymási, I
   Vancsó, P
   Osváth, Z
   Nemes-Incze, P
   Hwang, CY
   Biró, LP
   Tapasztó, L
AF Magda, Gabor Zsolt
   Jin, Xiaozhan
   Hagymasi, Imre
   Vancso, Peter
   Osvath, Zoltan
   Nemes-Incze, Peter
   Hwang, Chanyong
   Biro, Laszlo P.
   Tapaszto, Levente
TI Room-temperature magnetic order on zigzag edges of narrow graphene nanoribbons
SO NATURE
LA English
DT Article
ID augmented-wave method; point-defects; ferromagnetism; state; spin
AB The possibility that non-magnetic materials such as carbon could exhibit a novel type of s-p electron magnetism has attracted much attention over the years, not least because such magnetic order is predicted to be stable at high temperatures(1). It has been demonstrated that atomic-scale structural defects of graphene can host unpaired spins(2,3), but it remains unclear under what conditions long-range magnetic order can emerge from such defect-bound magnetic moments. Here we propose that, in contrast to random defect distributions, atomic-scale engineering of graphene edges with specific crystallographic orientation-comprising edge atoms from only one sub-lattice of the bipartite graphene lattice-can give rise to a robust magnetic order. We use a nanofabrication technique(4) based on scanning tunnelling microscopy to define graphene nanoribbons with nanometre precision and well-defined crystallographic edge orientations. Although so-called 'armchair' ribbons display quantum confinement gaps, ribbons with the 'zigzag' edge structure that are narrower than 7 nanometres exhibit an electronic bandgap of about 0.2-0.3 electronvolts, which can be identified as a signature of interaction-induced spin ordering along their edges. Moreover, upon increasing the ribbon width, a semiconductor-to-metal transition is revealed, indicating the switching of the magnetic coupling between opposite ribbon edges from the antiferromagnetic to the ferromagnetic configuration. We found that the magnetic order on graphene edges of controlled zigzag orientation can be stable even at room temperature, raising hopes of graphene-based spintronic devices operating under ambient conditions.
C1 [Magda, Gabor Zsolt; Vancso, Peter; Osvath, Zoltan; Nemes-Incze, Peter; Biro, Laszlo P.; Tapaszto, Levente] 2D Nanoelect Lendulet Res Grp, Inst Tech Phys & Mat Sci, Nanotechnol Dept, Res Ctr Nat Sci, H-1121 Budapest, Hungary.
   [Jin, Xiaozhan; Hwang, Chanyong] Korea Res Inst Stand & Sci, Ctr Nanometrol, Taejon 305340, South Korea.
   [Hagymasi, Imre] Strongly Correlated Syst Lendulet Res Grp, Inst Solid State Phys & Opt, Wigner Res Ctr Phys, H-1121 Budapest, Hungary.
   [Hagymasi, Imre] Univ Szeged, Dept Theoret Phys, H-6720 Szeged, Hungary.
C3 HUN-REN; HUN-REN Research Centre for Natural Sciences; Institute of Technical Physics & Materials Science - HAS; Korea Research Institute of Standards & Science (KRISS); HUN-REN; HUN-REN Wigner Research Centre for Physics; Institute for Solid State Physics & Optics - HAS; Szeged University
RP Tapasztó, L (corresponding author), 2D Nanoelect Lendulet Res Grp, Inst Tech Phys & Mat Sci, Nanotechnol Dept, Res Ctr Nat Sci, H-1121 Budapest, Hungary.
EM tapaszto@mfa.kfki.hu
FU OTKA [K108753, K101599, K100908]; Bolyai Fellowship; Nano.Material Technology Development Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [2012M3A7B4049888]; European Union; State of Hungary; European Social Fund [TAMOP-4.2.4.A/2-11/1-2012-0001]; National Excellence Program
NR 35
TC 715
Z9 780
U1 11
U2 670
PU NATURE PUBLISHING 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 30
PY 2014
VL 514
IS 7524
BP 608
EP +
DI 10.1038/nature13831
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500044
PM 25355361
DA 2026-03-09
ER

PT J
AU Li, B
   Qiu, B
   Lee, DSM
   Walton, ZE
   Ochocki, JD
   Mathew, LK
   Mancuso, A
   Gade, TPF
   Keith, B
   Nissim, I
   Simon, MC
AF Li, Bo
   Qiu, Bo
   Lee, David S. M.
   Walton, Zandra E.
   Ochocki, Joshua D.
   Mathew, Lijoy K.
   Mancuso, Anthony
   Gade, Terence P. F.
   Keith, Brian
   Nissim, Itzhak
   Simon, M. Celeste
TI Fructose-1,6-bisphosphatase opposes renal carcinoma progression
SO NATURE
LA English
DT Article
ID cell carcinoma; identification; metabolism; inactivation; disease
AB Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer(1), is characterized by elevated glycogen levels and fat deposition(2). These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs)3 secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours(4). However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation(5), suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1 -associated protein-1, among others)(6-9), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1)(10) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients". Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin(12), thereby inhibiting a potential Warburg effect(13,14). Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalyticactivity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours(6,7,15).
C1 [Li, Bo; Qiu, Bo; Lee, David S. M.; Walton, Zandra E.; Ochocki, Joshua D.; Mathew, Lijoy K.; Mancuso, Anthony; Keith, Brian; Simon, M. Celeste] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Lee, David S. M.; Mathew, Lijoy K.; Simon, M. Celeste] Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
   [Walton, Zandra E.; Mancuso, Anthony; Keith, Brian] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA.
   [Mancuso, Anthony; Gade, Terence P. F.] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA.
   [Nissim, Itzhak] Univ Penn, Dept Pediat,Biochem & Biophys, Philadelphia, PA 19104 USA.
   [Nissim, Itzhak] Childrens Hosp Philadelphia, Div Child Dev & Metab Dis, Philadelphia, PA 19104 USA.
   [Simon, M. Celeste] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Howard Hughes Medical Institute; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania
RP Simon, MC (corresponding author), Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
EM celeste2@mail.med.upenn.edu
FU Howard Hughes Medical Institute, NIH Grant [CA104838, DK053761]; National Cancer Institute [P30CA016520] Funding Source: NIH RePORTER
NR 30
TC 439
Z9 494
U1 0
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 SEP 11
PY 2014
VL 513
IS 7517
BP 251
EP +
DI 10.1038/nature13557
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800054
PM 25043030
DA 2026-03-09
ER

PT J
AU Young, AF
   Sanchez-Yamagishi, JD
   Hunt, B
   Choi, SH
   Watanabe, K
   Taniguchi, T
   Ashoori, RC
   Jarillo-Herrero, P
AF Young, A. F.
   Sanchez-Yamagishi, J. D.
   Hunt, B.
   Choi, S. H.
   Watanabe, K.
   Taniguchi, T.
   Ashoori, R. C.
   Jarillo-Herrero, P.
TI Tunable symmetry breaking and helical edge transport in a graphene quantum spin Hall state
SO NATURE
LA English
DT Article
ID topological insulators
AB Low-dimensional electronic systems have traditionally been obtained by electrostatically confining electrons, either in heterostructures or in intrinsically nanoscale materials such as single molecules, nanowires and graphene. Recently, a new method has emerged with the recognition that symmetry-protected topological (SPT) phases(1,2), which occur in systems with an energy gap to quasiparticle excitations (such as insulators or superconductors), can host robust surface states that remain gapless as long as the relevant global symmetry remains unbroken. The nature of the charge carriers in SPT surface states is intimately tied to the symmetry of the bulk, resulting in one- and two-dimensional electronic systems with novel properties. For example, time reversal symmetry endows the massless charge carriers on the surface of a three-dimensional topological insulator with helicity, fixing the orientation of their spin relative to their momentum(3,4). Weakly breaking this symmetry generates a gap on the surface(5), resulting in charge carriers with finite effective mass and exotic spin textures(6). Analogous manipulations have yet to be demonstrated in two-dimensional topological insulators, where the primary example of a SPT phase is the quantum spin Hall state(7,8). Here we demonstrate experimentally that charge-neutral monolayer graphene has a quantum spin Hall state(9,10) when it is subjected to a very large magnetic field angled with respect to the graphene plane. In contrast to time-reversal-symmetric systems(7), this state is protected by a symmetry of planar spin rotations that emerges as electron spins in a half-filled Landau level are polarized by the large magnetic field. The properties of the resulting helical edge states can be modulated by balancing the applied field against an intrinsic antiferromagnetic instability(11-13), which tends to spontaneously break the spin-rotation symmetry. In the resulting canted antiferromagnetic state, we observe transport signatures of gapped edge states, which constitute a new kind of one- dimensional electronic system with a tunable bandgap and an associated spin texture(14).
C1 [Young, A. F.; Sanchez-Yamagishi, J. D.; Hunt, B.; Choi, S. H.; Ashoori, R. C.; Jarillo-Herrero, P.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Watanabe, K.; Taniguchi, T.] Natl Inst Mat Sci, Adv Mat Lab, Tsukuba, Ibaraki 3050044, Japan.
C3 Massachusetts Institute of Technology (MIT); National Institute for Materials Science
RP Young, AF (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM afy@mit.edu; jdsy@mit.edu; benhunt@mit.edu
FU BES Program of the Office of Science of the US DOE [FG02-08ER46514]; Gordon and Betty Moore Foundation [GBMF2931]; US DOE, BES Office, Division of Materials Sciences and Engineering [DE-SC0001819]; NSF [DMR-0845287, DMR-0819762, ECS-0335765, DMR-0654118]; ONR GATE MURI; Pappalardo Fellowship in Physics; Gordon and Betty Moore Foundation (GBMF) [GBMF2931] Funding Source: Gordon and Betty Moore Foundation (GBMF); Grants-in-Aid for Scientific Research [23246116] Funding Source: KAKEN; Division Of Materials Research; Direct For Mathematical & Physical Scien [0845287] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0001819] Funding Source: U.S. Department of Energy (DOE)
NR 36
TC 262
Z9 310
U1 2
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 23
PY 2014
VL 505
IS 7484
BP 528
EP +
DI 10.1038/nature12800
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000035
PM 24362569
DA 2026-03-09
ER

PT J
AU Tseng, YY
   Moriarity, BS
   Gong, WM
   Akiyama, R
   Tiwari, A
   Kawakami, H
   Ronning, P
   Reuland, B
   Guenther, K
   Beadnell, TC
   Essig, J
   Otto, GM
   O'Sullivan, MG
   Largaespada, DA
   Schwertfeger, KL
   Marahrens, Y
   Kawakami, Y
   Bagchi, A
AF Tseng, Yuen-Yi
   Moriarity, Branden S.
   Gong, Wuming
   Akiyama, Ryutaro
   Tiwari, Ashutosh
   Kawakami, Hiroko
   Ronning, Peter
   Reuland, Brian
   Guenther, Kacey
   Beadnell, Thomas C.
   Essig, Jaclyn
   Otto, George M.
   O'Sullivan, M. Gerard
   Largaespada, David A.
   Schwertfeger, Kathryn L.
   Marahrens, York
   Kawakami, Yasuhiko
   Bagchi, Anindya
TI PVT1 dependence in cancer with MYC copy-number increase
SO NATURE
LA English
DT Article
ID comparative genomic hybridization; breast-cancer; c-myc; transcription factors; mammary-gland; chromosome 8q; cell-lines; expression; amplification; mice
AB 'Gain' of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers(1-13) and is associated with poor prognosis(7,10,14). The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent 'gene desert' of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.
C1 [Tseng, Yuen-Yi; Gong, Wuming; Akiyama, Ryutaro; Kawakami, Hiroko; Ronning, Peter; Reuland, Brian; Guenther, Kacey; Essig, Jaclyn; Largaespada, David A.; Marahrens, York; Kawakami, Yasuhiko; Bagchi, Anindya] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Moriarity, Branden S.; Gong, Wuming; Tiwari, Ashutosh; Otto, George M.; O'Sullivan, M. Gerard; Largaespada, David A.; Schwertfeger, Kathryn L.; Bagchi, Anindya] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Akiyama, Ryutaro; Kawakami, Hiroko; Kawakami, Yasuhiko] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA.
   [Beadnell, Thomas C.; Schwertfeger, Kathryn L.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 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; University of Minnesota System; University of Minnesota Twin Cities
RP Bagchi, A (corresponding author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
EM bagch005@umn.edu
FU Masonic Cancer Center Laboratory; Institute of Prostate and Urologic Cancer, University of Minnesota; American Cancer Society [118198-IRG-58-001-52-IRG92]; Indo-US fellowship from the Indo-US Science and Technology Forum; National Cancer Institute [P30CA077598] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR064195] Funding Source: NIH RePORTER
NR 37
TC 618
Z9 698
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 AUG 7
PY 2014
VL 512
IS 7512
BP 82
EP +
DI 10.1038/nature13311
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000036
PM 25043044
DA 2026-03-09
ER

PT J
AU Del Toro-De León, G
   García-Aguilar, M
   Gillmor, CS
AF Del Toro-De Leon, Gerardo
   Garcia-Aguilar, Marcelina
   Stewart Gillmor, C.
TI Non-equivalent contributions of maternal and paternal genomes to early plant embryogenesis
SO NATURE
LA English
DT Article
ID to-zygotic transition; seed development; arabidopsis hybrids; embryo development; gene-expression; methylation; activation; endosperm; maize
AB Zygotic genome activation in metazoans typically occurs several hours to a day after fertilization, and thus maternal RNAs and proteins drive early animal embryo development(1). In plants, despite several molecular studies of post-fertilization transcriptional activation, the timing of zygotic genome activation remains a matter of debate. For example, two recent reports that used different hybrid ecotype combinations for RNA sequence profiling of early Arabidopsis embryo transcriptomes came to divergent conclusions. One identified paternal contributions that varied by gene, but with overall maternal dominance(2), while the other found that the maternal and paternal genomes are transcriptionally equivalent(3). Here we assess paternal gene activation functionally in an isogenic background, by performing a large-scale genetic analysis of 49 EMBRYO DEFECTIVE genes and testing the ability of wild-type paternal alleles to complement phenotypes conditioned by mutant maternal alleles. Our results demonstrate that wild-type paternal alleles for nine of these genes are completely functional 2 days after pollination, with the remaining 40 genes showing partial activity beginning at 2, 3 or 5 days after pollination. Using our functional assay, we also demonstrate that different hybrid combinations exhibit significant variation in paternal allele activation, reconciling the apparently contradictory results of previous transcriptional studies(2,3). The variation in timing of gene function that we observe confirms that paternal genome activation does not occur in one early discrete step, provides large-scale functional evidence that maternal and paternal genomes make non-equivalent contributions to early plant embryogenesis, and uncovers an unexpectedly profound effect of hybrid genetic backgrounds on paternal gene activity.
C1 [Del Toro-De Leon, Gerardo; Garcia-Aguilar, Marcelina; Stewart Gillmor, C.] Inst Politecn Nacl CINVESTAV IPN, Ctr Invest & Estudios Avanzados, Unidad Genom Avanzada, Lab Nacl Genom Biodiversidad Langebio, Irapuato 36821, Guanajuato, Mexico.
C3 CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional
RP Gillmor, CS (corresponding author), Inst Politecn Nacl CINVESTAV IPN, Ctr Invest & Estudios Avanzados, Unidad Genom Avanzada, Lab Nacl Genom Biodiversidad Langebio, Irapuato 36821, Guanajuato, Mexico.
EM sgillmor@langebio.cinvestav.mx
FU CONACyT [300802, 152333]; CINVESTAV
NR 26
TC 76
Z9 84
U1 1
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 30
PY 2014
VL 514
IS 7524
BP 624
EP +
DI 10.1038/nature13620
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500048
PM 25209660
DA 2026-03-09
ER

PT J
AU Deane, RP
   Paragi, Z
   Jarvis, MJ
   Coriat, M
   Bernardi, G
   Fender, RP
   Frey, S
   Heywood, I
   Klöckner, HR
   Grainge, K
   Rumsey, C
AF Deane, R. P.
   Paragi, Z.
   Jarvis, M. J.
   Coriat, M.
   Bernardi, G.
   Fender, R. P.
   Frey, S.
   Heywood, I.
   Kloeckner, H-R
   Grainge, K.
   Rumsey, C.
TI A close-pair binary in a distant triple supermassive black hole system
SO NATURE
LA English
DT Article
ID active galactic nucleus; radio-sources; minor merger; galaxy; discovery; jets; scale; sky; evolution; quasars
AB Galaxies are believed to evolve through merging(1), which should lead to some hosting multiple supermassive black holes(2-4). There are four known triple black hole systems(5-8), with the closest black hole pair being 2.4 kiloparsecs apart (the third component in this system is at 3 kiloparsecs)(7), which is far from the gravitational sphere of influence (about 100 parsecs for a black hole with mass one billion times that of the Sun). Previous searches for compact black hole systems concluded that they were rare(9), with the tightest binary system having a separation of 7 parsecs (ref. 10). Here we report observations of a triple black hole system at redshift z = 0.39, with the closest pair separated by about 140 parsecs and significantly more distant from Earth than any other known binary of comparable orbital separation. The effect of the tight pair is to introduce a rotationally symmetric helical modulation on the structure of the large-scale radio jets, which provides a useful way to search for other tight pairs without needing extremely high resolution observations. As we found this tight pair after searching only six galaxies, we conclude that tight pairs are more common than hitherto believed, which is an important observational constraint for low-frequency gravitational wave experiments(11,12).
C1 [Deane, R. P.; Coriat, M.] Univ Cape Town, Dept Astron, Astrophys Cosmol & Grav Ctr, ZA-7701 Cape Town, South Africa.
   [Deane, R. P.; Coriat, M.; Bernardi, G.] Sq Kilometre Array South Africa, ZA-7405 Cape Town, South Africa.
   [Paragi, Z.] Joint Inst VLBI Europe, NL-7990 AA Dwingeloo, Netherlands.
   [Jarvis, M. J.; Fender, R. P.] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
   [Jarvis, M. J.] Univ Western Cape, Dept Phys, ZA-7535 Bellville, South Africa.
   [Bernardi, G.; Heywood, I.] Rhodes Univ, Dept Phys & Elect, Ctr Radio Astron Tech & Technol, ZA-6140 Grahamstown, South Africa.
   [Bernardi, G.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Frey, S.] Inst Geodesy Cartog & Remote Sensing, Satellite Geodet Observ, H-1592 Budapest, Hungary.
   [Heywood, I.] CSIRO Astron & Space Sci, Australia Telescope Natl Facil, Epping, NSW 1710, Australia.
   [Kloeckner, H-R] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Grainge, K.] Univ Manchester, Sch Phys & Astron, Jodrell Bank Ctr Astrophys, Manchester, Lancs, England.
   [Rumsey, C.] Univ Cambridge, Cavendish Lab, Astrophys Grp, Cambridge CB3 0HE, England.
C3 University of Cape Town; SKA South Africa; University of Oxford; University of the Western Cape; Rhodes University; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility; CSIRO Astronomy & Space; Max Planck Society; University of Manchester; Jodrell Bank Centre for Astrophysics; University of Cambridge
RP Deane, RP (corresponding author), Univ Cape Town, Dept Astron, Astrophys Cosmol & Grav Ctr, ZA-7701 Cape Town, South Africa.
EM roger.deane@ast.uct.ac.za
FU European Union [RI-261525 NEXPReS]; South African SKA Project (SKA SA); Hungarian Scientific Research Fund [OTKA 104539]; International Space Science Institute; Science and Technology Facilities Council [ST/L000768/1, ST/J001600/1] Funding Source: researchfish; STFC [ST/J001600/1, ST/L000768/1] Funding Source: UKRI
NR 45
TC 105
Z9 122
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 JUL 3
PY 2014
VL 511
IS 7507
BP 57
EP U578
DI 10.1038/nature13454
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400034
PM 24990745
DA 2026-03-09
ER

PT J
AU Bellini, G
   Benziger, J
   Bick, D
   Bonfini, G
   Bravo, D
   Caccianiga, B
   Cadonati, L
   Calaprice, F
   Caminata, A
   Cavalcante, P
   Chavarria, A
   Chepurnov, A
   D'Angelo, D
   Davini, S
   Derbin, A
   Empl, A
   Etenko, A
   Fomenke, K
   Franco, D
   Gabriele, F
   Galbiati, C
   Gazzana, S
   Ghiano, C
   Giammarchi, M
   Göger-Neff, M
   Goretti, A
   Gromov, M
   Hagner, C
   Hungerford, E
   Ianni, A
   Ianni, A
   Kobychev, V
   Korablev, D
   Korga, G
   Kryn, D
   Laubenstein, M
   Lehnert, B
   Lewke, T
   Litvinovich, E
   Lombardi, F
   Lombardi, P
   Ludhova, L
   Lukyanchenko, G
   Machulin, I
   Manecki, S
   Maneschg, W
   Marcocci, S
   Meindl, Q
   Meroni, E
   Meyer, M
   Miramonti, L
   Misiaszek, M
   Montuschi, M
   Mosteiro, P
   Muratova, V
   Oberauer, L
   Obolensky, M
   Ortica, F
   Otis, K
   Pallavicini, M
   Papp, L
   Perasso, L
   Pocar, A
   Ranucci, G
   Razeto, A
   Re, A
   Romani, A
   Rossi, N
   Saldanha, R
   Salvo, C
   Schönert, S
   Simgen, H
   Skorokhvatov, M
   Smirnov, O
   Sotnikov, A
   Sukhotin, S
   Suvorov, Y
   Tartaglia, R
   Testera, G
   Vignaud, D
   Vogelaar, RB
   von Feilitzsch, F
   Wang, H
   Winter, J
   Wojcik, M
   Wright, A
   Wurm, M
   Zaimidoroga, O
   Zavatarelli, S
   Zuber, K
   Zuzel, G
AF Bellini, G.
   Benziger, J.
   Bick, D.
   Bonfini, G.
   Bravo, D.
   Caccianiga, B.
   Cadonati, L.
   Calaprice, F.
   Caminata, A.
   Cavalcante, P.
   Chavarria, A.
   Chepurnov, A.
   D'Angelo, D.
   Davini, S.
   Derbin, A.
   Empl, A.
   Etenko, A.
   Fomenke, K.
   Franco, D.
   Gabriele, F.
   Galbiati, C.
   Gazzana, S.
   Ghiano, C.
   Giammarchi, M.
   Goeger-Neff, M.
   Goretti, A.
   Gromov, M.
   Hagner, C.
   Hungerford, E.
   Ianni, Aldo
   Ianni, Andrea
   Kobychev, V.
   Korablev, D.
   Korga, G.
   Kryn, D.
   Laubenstein, M.
   Lehnert, B.
   Lewke, T.
   Litvinovich, E.
   Lombardi, F.
   Lombardi, P.
   Ludhova, L.
   Lukyanchenko, G.
   Machulin, I.
   Manecki, S.
   Maneschg, W.
   Marcocci, S.
   Meindl, Q.
   Meroni, E.
   Meyer, M.
   Miramonti, L.
   Misiaszek, M.
   Montuschi, M.
   Mosteiro, P.
   Muratova, V.
   Oberauer, L.
   Obolensky, M.
   Ortica, F.
   Otis, K.
   Pallavicini, M.
   Papp, L.
   Perasso, L.
   Pocar, A.
   Ranucci, G.
   Razeto, A.
   Re, A.
   Romani, A.
   Rossi, N.
   Saldanha, R.
   Salvo, C.
   Schoenert, S.
   Simgen, H.
   Skorokhvatov, M.
   Smirnov, O.
   Sotnikov, A.
   Sukhotin, S.
   Suvorov, Y.
   Tartaglia, R.
   Testera, G.
   Vignaud, D.
   Vogelaar, R. B.
   von Feilitzsch, F.
   Wang, H.
   Winter, J.
   Wojcik, M.
   Wright, A.
   Wurm, M.
   Zaimidoroga, O.
   Zavatarelli, S.
   Zuber, K.
   Zuzel, G.
TI Neutrinos from the primary proton-proton fusion process in the Sun
SO NATURE
LA English
DT Article
ID solar neutrinos; models; oscillations; abundance; chain; pp
AB In the core of the Sun, energy is released through sequences of nuclear reactions that convert hydrogen into helium. The primary reaction is thought to be the fusion of two protons with the emission of a low-energy neutrino. These These so-called pp neutrinos constitute nearly the entirety of the solar neutrino flux, vastly outnumbering those emitted in the reactions that follow. Although solar neutrinos from secondary processes have been observed, proving the nuclear origin of the Sun's energy and contributing to the discovery of neutrino oscillations, those from proton-proton fusion have hitherto eluded direct detection. Here we report spectral observations of pp neutrinos, demonstrating that about 99 per cent of the Power of the Sun, 3.84 x 10(33) ergs per second, is generated by the proton-proton fusion process.
C1 [Bellini, G.; Caccianiga, B.; D'Angelo, D.; Giammarchi, M.; Lombardi, P.; Ludhova, L.; Meroni, E.; Miramonti, L.; Ranucci, G.; Re, A.] Univ Milan, Dipartimento Fis, I-20133 Milan, Italy.
   [Bellini, G.; Caccianiga, B.; D'Angelo, D.; Giammarchi, M.; Lombardi, P.; Ludhova, L.; Meroni, E.; Miramonti, L.; Ranucci, G.; Re, A.] Ist Nazl Fis Nucl, I-20133 Milan, Italy.
   [Benziger, J.] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA.
   [Bick, D.; Hagner, C.; Meyer, M.] Univ Hamburg, Inst Expt Phys, D-22761 Hamburg, Germany.
   [Bonfini, G.; Cavalcante, P.; Chavarria, A.; Fomenke, K.; Gabriele, F.; Gazzana, S.; Ianni, Aldo; Laubenstein, M.; Lombardi, F.; Montuschi, M.; Razeto, A.; Rossi, N.; Suvorov, Y.; Tartaglia, R.] Ist Nazl Fis Nucl, Lab Nazl Gran Sasso, I-67100 Assergi, Italy.
   [Bravo, D.; Manecki, S.; Papp, L.; Vogelaar, R. B.] Virginia Polytech Inst & State Univ, Dept Phys, Blacksburg, VA 24061 USA.
   [Cadonati, L.; Otis, K.; Pocar, A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
   [Calaprice, F.; Chavarria, A.; Galbiati, C.; Goretti, A.; Ianni, Andrea; Mosteiro, P.; Saldanha, R.; Wright, A.] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Calaprice, F.; Marcocci, S.] Ist Nazl Fis Nucl, Gran Sasso Sci Inst, I-67100 Laquila, Italy.
   [Caminata, A.; Ghiano, C.; Marcocci, S.; Pallavicini, M.; Perasso, L.; Salvo, C.; Testera, G.; Zavatarelli, S.] Univ Genoa, Dipartimento Fis, I-16146 Genoa, Italy.
   [Caminata, A.; Ghiano, C.; Marcocci, S.; Pallavicini, M.; Perasso, L.; Salvo, C.; Testera, G.; Zavatarelli, S.] Ist Nazl Fis Nucl, I-16146 Genoa, Italy.
   [Chepurnov, A.; Gromov, M.] Moscow MV Lomonosov State Univ, Skobeltsyn Inst Nucl Phys, Moscow 119234, Russia.
   [Davini, S.; Empl, A.; Hungerford, E.; Korga, G.] Univ Houston, Dept Phys, Houston, TX 77204 USA.
   [Derbin, A.; Muratova, V.] St Petersburg Nucl Phys Inst, Gatchina 188350, Russia.
   [Etenko, A.; Litvinovich, E.; Lukyanchenko, G.; Machulin, I.; Skorokhvatov, M.; Sukhotin, S.; Suvorov, Y.] NRC Kurchatov Inst, Moscow 123182, Russia.
   [Etenko, A.; Litvinovich, E.; Machulin, I.] Natl Res Nucl Univ MEPhl, Moscow Engn Phys Inst, Moscow 115409, Russia.
   [Fomenke, K.; Korablev, D.; Smirnov, O.; Sotnikov, A.; Zaimidoroga, O.] Joint Inst Nucl Res, Dubna 141980, Russia.
   [Franco, D.; Kryn, D.; Obolensky, M.; Vignaud, D.] Univ Paris Diderot, APC, CNRS CEA Irfu IN2P3, Observ Paris,Sorbonne Paris Cite, F-75205 Paris 13, France.
   [Goeger-Neff, M.; Lewke, T.; Meindl, Q.; Oberauer, L.; Papp, L.; Schoenert, S.; von Feilitzsch, F.] Tech Univ Munich, Dept Phys, D-85748 Garching, Germany.
   [Goeger-Neff, M.; Lewke, T.; Meindl, Q.; Oberauer, L.; Papp, L.; Schoenert, S.; von Feilitzsch, F.] Tech Univ Munich, Excellence Cluster Universe, D-85748 Garching, Germany.
   [Kobychev, V.] Kiev Inst Nucl Res, UA-03680 Kiev, Ukraine.
   [Lehnert, B.; Zuber, K.] Tech Univ Dresden, Dept Phys, D-01062 Dresden, Germany.
   [Maneschg, W.; Simgen, H.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Misiaszek, M.; Wojcik, M.; Zuzel, G.] Jagiellonian Univ, M Smoluchowski Inst Phys, PL-30059 Krakow, Poland.
   [Ortica, F.; Romani, A.] Univ Perugia, Dipartimento Chim Biol & Biotecnol, I-06123 Perugia, Italy.
   [Suvorov, Y.; Wang, H.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Winter, J.; Wurm, M.] Johannes Gutenberg Univ Mainz, Inst Phys, D-55122 Mainz, Germany.
C3 University of Milan; Istituto Nazionale di Fisica Nucleare (INFN); Princeton University; University of Hamburg; Gran Sasso Science Institute (GSSI); Istituto Nazionale di Fisica Nucleare (INFN); Virginia Polytechnic Institute & State University; University of Massachusetts System; University of Massachusetts Amherst; Princeton University; Istituto Nazionale di Fisica Nucleare (INFN); Gran Sasso Science Institute (GSSI); University of Genoa; Istituto Nazionale di Fisica Nucleare (INFN); Lomonosov Moscow State University; University of Houston System; University of Houston; National Research Centre - Kurchatov Institute; Petersburg Nuclear Physics Institute; National Research Centre - Kurchatov Institute; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Joint Institute for Nuclear Research - Russia; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite PSL; Observatoire de Paris; CEA; Universite Paris Cite; Technical University of Munich; Technical University of Munich; University of Munich; National Academy of Sciences Ukraine; Institute for Nuclear Research of NASU; Technische Universitat Dresden; Max Planck Society; Jagiellonian University; University of Perugia; University of California System; University of California Los Angeles; Johannes Gutenberg University of Mainz
RP Smirnov, O (corresponding author), Joint Inst Nucl Res, Dubna 141980, Russia.
EM borex-spokeperson@lngs.infn.it
FU INFN (Italy); NSF (USA); BMBF (Germany); DFG (Germany); MPG (Germany); JINR; RFBR (Russia); RSC (Russia); NRC Kurchatov Institute (Russia); NCN (Poland); Laboratori Nazionali del Gran Sasso (Italy); Direct For Mathematical & Physical Scien; Division Of Physics [1413031] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1102798, 1103987] Funding Source: National Science Foundation
NR 41
TC 248
Z9 283
U1 1
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 AUG 28
PY 2014
VL 512
IS 7515
BP 383
EP U313
DI 10.1038/nature13702
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600023
PM 25164748
DA 2026-03-09
ER

PT J
AU Hammerschmidt, K
   Rose, CJ
   Kerr, B
   Rainey, PB
AF Hammerschmidt, Katrin
   Rose, Caroline J.
   Kerr, Benjamin
   Rainey, Paul B.
TI Life cycles, fitness decoupling and the evolution of multicellularity
SO NATURE
LA English
DT Article
ID pseudomonas-fluorescens; experimental populations; adaptive divergence; cooperation; selection; individuality; construction; competition; transition; conflict
AB Cooperation is central to the emergence of multicellular life; however, the means by which the earliest collectives (groups of cells) maintained integrity in the face of destructive cheating types is unclear. One idea posits cheats as a primitive germ line in a life cycle that facilitates collective reproduction. Here we describe an experiment in which simple cooperating lineages of bacteria were propagated under a selective regime that rewarded collective-level persistence. Collectives reproduced via life cycles that either embraced, or purged, cheating types. When embraced, the life cycle alternated between phenotypic states. Selection fostered inception of a developmental switch that underpinned the emergence of collectives whose fitness, during the course of evolution, became decoupled from the fitness of constituent cells. Such development and decoupling did not occur when groups reproduced via a cheat-purging regime. Our findings capture key events in the evolution of Darwinian individuality during the transition from single cells to multicellularity.
C1 [Hammerschmidt, Katrin; Rose, Caroline J.; Rainey, Paul B.] Massey Univ, New Zealand Inst Adv Study, Auckland 0745, New Zealand.
   [Hammerschmidt, Katrin; Rose, Caroline J.; Rainey, Paul B.] Massey Univ, Allan Wilson Ctr Mol Ecol & Evolut, Auckland 0745, New Zealand.
   [Kerr, Benjamin] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
   [Kerr, Benjamin] Univ Washington, BEACON Ctr Study Evolut Act, Seattle, WA 98195 USA.
   [Rainey, Paul B.] Max Planck Inst Evolutionary Biol, D-24306 Plon, Germany.
C3 Massey University; Massey University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Max Planck Society
RP Rainey, PB (corresponding author), Massey Univ, New Zealand Inst Adv Study, Auckland 0745, New Zealand.
EM p.b.rainey@massey.ac.nz
FU French State; Ile-de-France; Marsden Fund Council; Foundational Questions in Evolutionary Biology Fund [RFP-12-20]; National Science Foundation [DBI-0939454]; NSF CAREER Award [DEB0952825]; Direct For Biological Sciences; Division Of Environmental Biology [0952825] Funding Source: National Science Foundation
NR 47
TC 143
Z9 161
U1 1
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 NOV 6
PY 2014
VL 515
IS 7525
BP 75
EP +
DI 10.1038/nature13884
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500031
PM 25373677
DA 2026-03-09
ER

PT J
AU Shipony, Z
   Mukamel, Z
   Cohen, NM
   Landan, G
   Chomsky, E
   Zeliger, SR
   Fried, YC
   Ainbinder, E
   Friedman, N
   Tanay, A
AF Shipony, Zohar
   Mukamel, Zohar
   Cohen, Netta Mendelson
   Landan, Gilad
   Chomsky, Elad
   Zeliger, Shlomit Reich
   Fried, Yael Chagit
   Ainbinder, Elena
   Friedman, Nir
   Tanay, Amos
TI Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells
SO NATURE
LA English
DT Article
ID dna methylation patterns; stem-cells; genome; plasticity; chromatin; elements; domains; regions
AB Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory(1-4) that can be written during embryonic development(5,6) and then guide cell-type-specific gene expression(7). Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly(8) and to near perfection(9) after induced pluripotency.
C1 [Shipony, Zohar; Mukamel, Zohar; Cohen, Netta Mendelson; Landan, Gilad; Chomsky, Elad; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Shipony, Zohar; Mukamel, Zohar; Cohen, Netta Mendelson; Landan, Gilad; Chomsky, Elad; Tanay, Amos] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Chomsky, Elad] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Zeliger, Shlomit Reich; Friedman, Nir] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Fried, Yael Chagit; Ainbinder, Elena] Weizmann Inst Sci, Dept Biol Sci, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science
RP Tanay, A (corresponding author), Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
EM amos.tanay@weizmann.ac.il
FU European Research Council (EVOEPIC); EU BLUEPRINT project; Israel Science Foundation [1050/12]; Israel Ministry of Science; Helen and Martin Kimmel Award
NR 36
TC 120
Z9 156
U1 1
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 SEP 4
PY 2014
VL 513
IS 7516
BP 115
EP +
DI 10.1038/nature13458
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800041
PM 25043040
DA 2026-03-09
ER

PT J
AU Raghavan, M
   Skoglund, P
   Graf, KE
   Metspalu, M
   Albrechtsen, A
   Moltke, I
   Rasmussen, S
   Stafford, TW
   Orlando, L
   Metspalu, E
   Karmin, M
   Tambets, K
   Rootsi, S
   Mägi, R
   Campos, PF
   Balanovska, E
   Balanovsky, O
   Khusnutdinova, E
   Litvinov, S
   Osipova, LP
   Fedorova, SA
   Voevoda, MI
   DeGiorgio, M
   Sicheritz-Ponten, T
   Brunak, S
   Demeshchenko, S
   Kivisild, T
   Villems, R
   Nielsen, R
   Jakobsson, M
   Willerslev, E
AF Raghavan, Maanasa
   Skoglund, Pontus
   Graf, Kelly E.
   Metspalu, Mait
   Albrechtsen, Anders
   Moltke, Ida
   Rasmussen, Simon
   Stafford, Thomas W., Jr.
   Orlando, Ludovic
   Metspalu, Ene
   Karmin, Monika
   Tambets, Kristiina
   Rootsi, Siiri
   Maegi, Reedik
   Campos, Paula F.
   Balanovska, Elena
   Balanovsky, Oleg
   Khusnutdinova, Elza
   Litvinov, Sergey
   Osipova, Ludmila P.
   Fedorova, Sardana A.
   Voevoda, Mikhail I.
   DeGiorgio, Michael
   Sicheritz-Ponten, Thomas
   Brunak, Soren
   Demeshchenko, Svetlana
   Kivisild, Toomas
   Villems, Richard
   Nielsen, Rasmus
   Jakobsson, Mattias
   Willerslev, Eske
TI Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans
SO NATURE
LA English
DT Article
ID mitochondrial-dna; hunter-gatherers; genetic history; ancient; radiocarbon; sequence; origins; diversity; accuracy; cave
AB The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians(1-3), there is no consensus with regard to which specific Old World populations they are closest to(4-8). Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia(9), to an average depth of 1x. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers(10-12), and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages(5). Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians(2,13). Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago(14), revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.
C1 [Raghavan, Maanasa; Stafford, Thomas W., Jr.; Orlando, Ludovic; Campos, Paula F.; Willerslev, Eske] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen, Denmark.
   [Skoglund, Pontus; Jakobsson, Mattias] Uppsala Univ, Dept Evolutionary Biol, S-75236 Uppsala, Sweden.
   [Graf, Kelly E.] Texas A&M Univ, Ctr Study Amer 1, College Stn, TX 77845 USA.
   [Metspalu, Mait; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Litvinov, Sergey; Kivisild, Toomas; Villems, Richard] Estonian Bioctr, Evolutionary Biol Grp, EE-51010 Tartu, Estonia.
   [Metspalu, Mait; DeGiorgio, Michael; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Metspalu, Mait; Metspalu, Ene; Karmin, Monika; Villems, Richard] Univ Tartu, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Albrechtsen, Anders; Moltke, Ida] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
   [Moltke, Ida] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Rasmussen, Simon] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Stafford, Thomas W., Jr.] Univ Aarhus, Dept Phys & Astron, AMS Dating Ctr 14C, DK-8000 Aarhus, Denmark.
   [Maegi, Reedik] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
   [Balanovska, Elena; Balanovsky, Oleg] Russian Acad Med Sci, Res Ctr Med Genet, Moscow 115479, Russia.
   [Balanovsky, Oleg] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia.
   [Khusnutdinova, Elza; Litvinov, Sergey] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450054, Bashkorostan, Russia.
   [Khusnutdinova, Elza] Bashkir State Univ, Biol Dept, Ufa 450054, Bashkorostan, Russia.
   [Osipova, Ludmila P.; Voevoda, Mikhail I.] Russian Acad Sci, Siberian Branch, Ctr Brain Neurobiol & Neurogenet, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Fedorova, Sardana A.] Russian Acad Med Sci, Yakut Res Ctr Complex Med Problems, Dept Mol Genet, Sakha 677010, Yakutia, Russia.
   [Fedorova, Sardana A.] North Eastern Fed Univ, Sakha 677010, Yakutia, Russia.
   [Voevoda, Mikhail I.] North Eastern Fed Univ, Sakha 677010, Yakutia, Russia.
   [Sicheritz-Ponten, Thomas; Brunak, Soren] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark.
   [Demeshchenko, Svetlana] State Hermitage Museum, St Petersburg 190000, Russia.
   [Kivisild, Toomas] Univ Cambridge, Dept Biol Anthropol, Cambridge CB2 1QH, England.
   [Villems, Richard] Estonian Acad Sci, EE-10130 Tallinn, Estonia.
   [Jakobsson, Mattias] Uppsala Univ, Sci Life Lab, S-75236 Uppsala, Sweden.
C3 University of Copenhagen; Uppsala University; Texas A&M University System; Texas A&M University College Station; Estonian Biocentre; University of California System; University of California Berkeley; University of Tartu; University of Copenhagen; University of Chicago; Technical University of Denmark; Aarhus University; University of Tartu; Research Centre for Medical Genetics; Russian Academy of Medical Sciences; Russian Academy of Sciences; Vavilov Institute of General Genetics; Institute of Biochemistry & Genetics of Ufa Science Centre of the RAS; Russian Academy of Sciences; Ufa University of Science & Technology; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; Russian Academy of Medical Sciences; North-Eastern Federal University in Yakutsk; North-Eastern Federal University in Yakutsk; Technical University of Denmark; State Hermitage Museum; University of Cambridge; Estonian Academy of Sciences; Uppsala University
RP Willerslev, E (corresponding author), Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, Oster Voldgade 5-7, DK-1350 Copenhagen, Denmark.
EM ewillerslev@snm.ku.dk
FU Danish National Research Foundation; Lundbeck Foundation; Arctic Social Sciences Program, National Science Foundation [PLR-1003725]; European Regional Development Fund (European Union) through the Centre of Excellence in Genomics to Estonian Biocentre; University of Tartu and Estonian Basic Research grant [SF0270177As08]; Estonian Science Foundation [8973]; Baltic-American Freedom Foundation Research Scholarship program; Government of Russian Federation [14.B25.31.0033]; US National Science Foundation [DBI-1103639]; Swedish National Infrastructure for Computing (SNIC-UPPMAX) [b2012063]; Lundbeck Foundation [R24-2008-2527, R38-2008-3048, R70-2010-6286, R155-2013-16338, R109-2012-9995] Funding Source: researchfish; Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish; Villum Fonden [00007171] Funding Source: researchfish
NR 65
TC 552
Z9 629
U1 2
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 JAN 2
PY 2014
VL 505
IS 7481
BP 87
EP +
DI 10.1038/nature12736
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300029
PM 24256729
DA 2026-03-09
ER

PT J
AU Liu, XD
   Chen, X
   Zhong, B
   Wang, AB
   Wang, XH
   Chu, FL
   Nurieva, RI
   Yan, XW
   Chen, P
   van der Flier, LG
   Nakatsukasa, H
   Neelapu, SS
   Chen, WJ
   Clevers, H
   Tian, Q
   Qi, H
   Wei, L
   Dong, C
AF Liu, Xindong
   Chen, Xin
   Zhong, Bo
   Wang, Aibo
   Wang, Xiaohu
   Chu, Fuliang
   Nurieva, Roza I.
   Yan, Xiaowei
   Chen, Ping
   van der Flier, Laurens G.
   Nakatsukasa, Hiroko
   Neelapu, Sattva S.
   Chen, Wanjun
   Clevers, Hans
   Tian, Qiang
   Qi, Hai
   Wei, Lai
   Dong, Chen
TI Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development
SO NATURE
LA English
DT Article
ID b-cells; c-maf; differentiation; expression; bcl6; regulators; stat5; il-21; fate; gene
AB In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (T-FH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres(1,2). Although Bcl6 has been shown to be essential in T-FH-cell function, it may not regulate the initial migration of T cells(3) or the induction of the T-FH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation(4). Here we show that expression of achaete-scute homologue 2 (Ascl2)-a basic helix-loop-helix (bHLH) transcription factor(5)-is ;selectively upregulated in T-FH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and T-FH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates T-FH-related genes whereas it inhibits expression of T-helper cell 1 (T(H)1) and T(H)17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4(+) T cells, results in impaired T-FH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances T-FH-cell generation. Thus, Ascl2 directly initiates T-FH-cell development.
C1 [Liu, Xindong; Chen, Xin; Wang, Aibo; Wang, Xiaohu; Qi, Hai; Dong, Chen] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Liu, Xindong; Zhong, Bo; Wang, Aibo; Wang, Xiaohu; Nurieva, Roza I.; Dong, Chen] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA.
   [Chu, Fuliang; Neelapu, Sattva S.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77054 USA.
   [Yan, Xiaowei; Tian, Qiang] Inst Syst Biol, Seattle, WA 98103 USA.
   [Chen, Ping] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [van der Flier, Laurens G.; Clevers, Hans] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
   [van der Flier, Laurens G.; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Nakatsukasa, Hiroko; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
   [Wei, Lai] Sun Yat Sen Univ, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
C3 Tsinghua University; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Institute for Systems Biology (ISB); National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI); Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); Sun Yat Sen University
RP Dong, C (corresponding author), Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
EM xindongliu@hotmail.com; cdonglab@hotmail.com
FU National Institutes of Health (NIH) [AI106654]; NIDCR; NIH Lymphoma SPORE; MD Anderson Cancer Center; Chinese Ministry of Science and Technology '973' program [2014CB542501, 2012CB910402]; National Natural Science Foundation of China [81361120397]; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER; National Institute of Dental and Craniofacial Research [ZIADE000101] Funding Source: NIH RePORTER
NR 30
TC 287
Z9 341
U1 0
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 MAR 27
PY 2014
VL 507
IS 7493
BP 513
EP +
DI 10.1038/nature12910
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000044
PM 24463518
DA 2026-03-09
ER

PT J
AU Gogala, M
   Becker, T
   Beatrix, B
   Armache, JP
   Barrio-Garcia, C
   Berninghausen, O
   Beckmann, R
AF Gogala, Marko
   Becker, Thomas
   Beatrix, Birgitta
   Armache, Jean-Paul
   Barrio-Garcia, Clara
   Berninghausen, Otto
   Beckmann, Roland
TI Structures of the Sec61 complex engaged in nascent peptide translocation or membrane insertion
SO NATURE
LA English
DT Article
ID protein-conducting channel; cryo-em structure; endoplasmic-reticulum; electron-microscopy; transmembrane segments; human cytomegalovirus; plug domain; recognition; ribosome; integration
AB The biogenesis of secretory as well as transmembrane proteins requires the activity of the universally conserved protein-conducting channel (PCC), the Sec61 complex (SecY complex in bacteria)(1). In eukaryotic cells the PCC is located in the membrane of the endoplasmic reticulum where it can bind to translating ribosomes for co-translational protein transport. The Sec complex consists of three subunits (Sec61 alpha, beta and gamma) and provides an aqueous environment for the translocation of hydrophilic peptides as well as a lateral opening in the Sec61a subunit that has been proposed to act as a gate for the membrane partitioning of hydrophobic domains(2). A plug helix and a so-called pore ring are believed to seal the PCC against ion flow and are proposed to rearrange for accommodation of translocating peptides(2,3). Several crystal and cryo-electron microscopy structures revealed different conformations of closed and partially open Sec61 and SecY complexes(2,4-8). However, in none of these samples has the translocation state been unambiguously defined biochemically. Here we present cryo-electron microscopy structures of ribosome-bound Sec61 complexes engaged in translocation or membrane insertion of nascent peptides. Our data show that a hydrophilic peptide can translocate through the Sec complex with an essentially closed lateral gate and an only slightly rearranged central channel. Membrane insertion of a hydrophobic domain seems to occur with the Sec complex opening the proposed lateral gate while rearranging the plug to maintain an ion permeability barrier. Taken together, we provide a structural model for the basic activities of the Sec61 complex as a protein-conducting channel.
C1 [Gogala, Marko; Becker, Thomas; Beatrix, Birgitta; Armache, Jean-Paul; Barrio-Garcia, Clara; Berninghausen, Otto; Beckmann, Roland] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Gogala, Marko; Becker, Thomas; Beatrix, Birgitta; Armache, Jean-Paul; Barrio-Garcia, Clara; Berninghausen, Otto; Beckmann, Roland] Univ Munich, Dept Biochem, Ctr integrated Prot Sci Munich, D-81377 Munich, Germany.
C3 University of Munich; University of Munich
RP Beckmann, R (corresponding author), Univ Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM beckmann@lmb.uni-muenchen.de
FU German Research Council [SFB594, SFB646, GRK1721]; Center for Integrated Protein Science; European Research Council
NR 45
TC 176
Z9 208
U1 1
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 FEB 6
PY 2014
VL 506
IS 7486
BP 107
EP +
DI 10.1038/nature12950
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100041
PM 24499919
DA 2026-03-09
ER

PT J
AU Mahieu, E
   Chipperfield, MP
   Notholt, J
   Reddmann, T
   Anderson, J
   Bernath, PF
   Blumenstock, T
   Coffey, MT
   Dhomse, SS
   Feng, W
   Franco, B
   Froidevaux, L
   Griffith, DWT
   Hannigan, JW
   Hase, F
   Hossaini, R
   Jones, NB
   Morino, I
   Murata, I
   Nakajima, H
   Palm, M
   Paton-Walsh, C
   Russell, JM
   Schneider, M
   Servais, C
   Smale, D
   Walker, KA
AF Mahieu, E.
   Chipperfield, M. P.
   Notholt, J.
   Reddmann, T.
   Anderson, J.
   Bernath, P. F.
   Blumenstock, T.
   Coffey, M. T.
   Dhomse, S. S.
   Feng, W.
   Franco, B.
   Froidevaux, L.
   Griffith, D. W. T.
   Hannigan, J. W.
   Hase, F.
   Hossaini, R.
   Jones, N. B.
   Morino, I.
   Murata, I.
   Nakajima, H.
   Palm, M.
   Paton-Walsh, C.
   Russell, J. M., III
   Schneider, M.
   Servais, C.
   Smale, D.
   Walker, K. A.
TI Recent Northern Hemisphere stratospheric HCl increase due to atmospheric circulation changes
SO NATURE
LA English
DT Article
ID inorganic chlorine; ozone; evolution; system; air; age
AB The abundance of chlorine in the Earth's atmosphere increased considerably during the 1970s to 1990s, following large emissions of anthropogenic long-lived chlorine-containing source gases, notably the chlorofluorocarbons. The chemical inertness of chlorofluorocarbons allows their transport and mixing throughout the troposphere on a global scale(1), before they reach the stratosphere where they release chlorine atoms that cause ozone depletion(2). The large ozone loss over Antarctica(3) was the key observation that stimulated the definition and signing in 1987 of the Montreal Protocol, an international treaty establishing a schedule to reduce the production of the major chlorine-and bromine-containing halocarbons. Owing to its implementation, the near-surface total chlorine concentration showed a maximum in 1993, followed by a decrease of half a per cent to one per cent per year(4), in line with expectations. Remote-sensing data have revealed a peak in stratospheric chlorine after 1996(5), then a decrease of close to one per cent per year(6,7), in agreement with the surface observations of the chlorine source gases and model calculations(7). Here we present ground-based and satellite data that show a recent and significant increase, at the 2 sigma level, in hydrogen chloride (HCl), the main stratospheric chlorine reservoir, starting around 2007 in the lower stratosphere of the Northern Hemisphere, in contrast with the ongoing monotonic decrease of near-surface source gases. Using model simulations, we attribute this trend anomaly to a slow down in the Northern Hemisphere atmospheric circulation, occurring over several consecutive years, transporting more aged air to the lower stratosphere, and characterized by a larger relative conversion of source gases to HCl. This short-term dynamical variability will also affect other stratospheric tracers and needs to be accounted for when studying the evolution of the stratospheric ozone layer.
C1 [Mahieu, E.; Franco, B.; Servais, C.] Univ Liege, Inst Astrophys & Geophys, B-4000 Liege, Belgium.
   [Chipperfield, M. P.; Dhomse, S. S.; Feng, W.; Hossaini, R.] Univ Leeds, Sch Earth & Environm, Natl Ctr Atmospher Sci, Leeds LS2 9JT, W Yorkshire, England.
   [Notholt, J.; Palm, M.] Univ Bremen, Dept Phys, D-28334 Bremen, Germany.
   [Reddmann, T.; Blumenstock, T.; Hase, F.; Schneider, M.] Karlsruhe Inst Technol KIT, Inst Meteorol & Climate Res IMK ASF, D-76021 Karlsruhe, Germany.
   [Anderson, J.; Russell, J. M., III] Hampton Univ, Dept Atmospher & Planetary Sci, Hampton, VA 23668 USA.
   [Bernath, P. F.] Old Dominion Univ, Dept Chem & Biochem, Norfolk, VA 23529 USA.
   [Bernath, P. F.] Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England.
   [Bernath, P. F.; Walker, K. A.] Univ Waterloo, Dept Chem, Waterloo, ON N2L 3G1, Canada.
   [Coffey, M. T.; Hannigan, J. W.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Froidevaux, L.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Griffith, D. W. T.; Jones, N. B.; Paton-Walsh, C.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia.
   [Morino, I.; Nakajima, H.] Natl Inst Environm Studies NIES, Tsukuba, Ibaraki 3058506, Japan.
   [Murata, I.] Tohoku Univ, Grad Sch Environm Studies, Sendai, Miyagi 9808578, Japan.
   [Smale, D.] Natl Inst Water & Atmospher Res NIWA, Lauder 9352, New Zealand.
   [Walker, K. A.] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
C3 University of Liege; University of Leeds; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC National Centre for Atmospheric Science; University of Bremen; Helmholtz Association; Karlsruhe Institute of Technology; Hampton University; Old Dominion University; University of York - UK; University of Waterloo; National Center Atmospheric Research (NCAR) - USA; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Wollongong; National Institute for Environmental Studies - Japan; Tohoku University; Earth Sciences New Zealand; National Institute of Water & Atmospheric Research (NIWA) - New Zealand; University of Toronto
RP Mahieu, E (corresponding author), Univ Liege, Inst Astrophys & Geophys, B-4000 Liege, Belgium.
EM emmanuel.mahieu@ulg.ac.be
FU Belgian Science Policy Office (BELSPO), Brussels; Fonds de la Recherche Scientifique-FNRS, Brussels; MeteoSwiss (Global Atmospheric Watch); Federation Wallonie-Bruxelles; International Foundation High Altitude Research Stations Jungfraujoch and Gornergrat (HFSJG, Bern); NASA MEASURE's GOZCARDS programme; National Oceanic and Atmospheric Administration's Educational Partnership Program Cooperative Remote Sensing Science and Technology Center (NOAA EPP CREST); Canadian Space Agency; National Science Foundation; National Aeronautics and Space Administration (NASA); NSF Office of Polar Programs; Danish Meteorological Institute; Australian Research Council [DP110101948]; New Zealand's Ministry of Business, Innovation and Employment; Natural Environment Research Council [NE/J02449X/1, ncas10009, nceo020005] Funding Source: researchfish; NERC [NE/J02449X/1, nceo020005] Funding Source: UKRI
NR 21
TC 100
Z9 108
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 NOV 6
PY 2014
VL 515
IS 7525
BP 104
EP 107
DI 10.1038/nature13857
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500038
PM 25373680
DA 2026-03-09
ER

PT J
AU Churazov, E
   Sunyaev, R
   Isern, J
   Knödlseder, J
   Jean, P
   Lebrun, F
   Chugai, N
   Grebenev, S
   Bravo, E
   Sazonov, S
   Renaud, M
AF Churazov, E.
   Sunyaev, R.
   Isern, J.
   Knoedlseder, J.
   Jean, P.
   Lebrun, F.
   Chugai, N.
   Grebenev, S.
   Bravo, E.
   Sazonov, S.
   Renaud, M.
TI Cobalt-56 γ-ray emission lines from the type Ia supernova 2014J
SO NATURE
LA English
DT Article
ID positron-annihilation spectrum; sn 2014j; models; region; constraints; progenitor; discovery; binary; spi
AB A type Ia supernova is thought to be a thermonuclear explosion of either a single carbon-oxygen white dwarf or a pair of merging white dwarfs. The explosion fuses a large amount of radioactive Ni-56 (refs 1-3). After the explosion, the decay chain from Ni-56 to Co-56 to Fe-56 generates gamma-ray photons, which are reprocessed in the expanding ejecta and give rise to powerful optical emission. Here we report the detection of Co-56 lines at energies of 847 and 1,238 kiloelectronvolts and a gamma-ray continuum in the 200-400 kiloelectronvolt band from the type Ia supernova 2014J in the nearby galaxy M82. The line fluxes suggest that about 0.6 +/- 0.1 solar masses of radioactive Ni-56 were synthesized during the explosion. The line broadening gives a characteristic mass-weighted ejecta expansion velocity of 10,000 +/- 3,000 kilometres per second. The observed gamma-ray properties are in broad agreement with the canonical model of an explosion of a white dwarf just massive enough to be unstable to gravitational collapse, but do not exclude merger scenarios that fuse comparable amounts of Ni-56.
C1 [Churazov, E.; Sunyaev, R.; Grebenev, S.; Sazonov, S.] Space Res Inst IKI, Profsouznaya 84-32, Moscow 117997, Russia.
   [Churazov, E.; Sunyaev, R.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Isern, J.] Inst Space Sci ICE CSIC IEEC, Bellaterra 08193, Spain.
   [Knoedlseder, J.; Jean, P.] Univ Toulouse, UPS OMP, IRAP, Toulouse, France.
   [Knoedlseder, J.; Jean, P.] CNRS, IRAP, F-31028 Toulouse 4, France.
   [Lebrun, F.] Univ Paris Diderot, APC, CNRS IN2P3, Observ Paris,Sorbonne Paris Cite, F-75205 Paris 13, France.
   [Chugai, N.] Russian Acad Sci, Inst Astron, Moscow 119017, Russia.
   [Bravo, E.] Univ Politecn Cataluna, ETSAV, Sant Cugat Del Valles 08173, Spain.
   [Sazonov, S.] Moscow Inst Phys & Technol, Dolgoprudnyi 141700, Russia.
   [Renaud, M.] Univ Montpellier 2, LUPM, CNRS IN2P3, CC 72, F-34095 Montpellier 5, France.
C3 Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Max Planck Society; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); 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); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite PSL; Observatoire de Paris; CEA; Universite Paris Cite; Institute of Astronomy of the Russian Academy of Sciences; Russian Academy of Sciences; Universitat Politecnica de Catalunya; Moscow Institute of Physics & Technology; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3)
RP Churazov, E (corresponding author), Space Res Inst IKI, Profsouznaya 84-32, Moscow 117997, Russia.
EM churazov@mpa-garching.mpg.de
FU ESA; Russian Scientific Foundation [14-22-00271]; MINECO-FEDER; Generalitat de Catalunya; CNES; Russian Science Foundation [14-22-00271] Funding Source: Russian Science Foundation
NR 42
TC 136
Z9 145
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 AUG 28
PY 2014
VL 512
IS 7515
BP 406
EP +
DI 10.1038/nature13672
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600027
PM 25164750
DA 2026-03-09
ER

PT J
AU Zhu, SY
   Rezvani, M
   Harbell, J
   Mattis, AN
   Wolfe, AR
   Benet, LZ
   Willenbring, H
   Ding, S
AF Zhu, Saiyong
   Rezvani, Milad
   Harbell, Jack
   Mattis, Aras N.
   Wolfe, Alan R.
   Benet, Leslie Z.
   Willenbring, Holger
   Ding, Sheng
TI Mouse liver repopulation with hepatocytes generated from human fibroblasts
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; nuclear receptors; defined factors; in-vivo; expression; mice; transplantation; conversion; induction; differentiation
AB Human induced pluripotent stem cells (iPSCs) have the capability of revolutionizing research and therapy of liver diseases by providing a source of hepatocytes for autologous cell therapy and disease modelling. However, despite progress in advancing the differentiation of iPSCs into hepatocytes (iPSC-Heps) in vitro(1-3), cells that replicate the ability of human primary adult hepatocytes (aHeps) to proliferate extensively in vivo have not been reported. This deficiency has hampered efforts to recreate human liver diseases in mice, and has cast doubt on the potential of iPSC-Heps for liver cell therapy. The reason is that extensive post-transplant expansion is needed to establish and sustain a therapeutically effective liver cell mass in patients, a lesson learned from clinical trials of aHep transplantation(4). Here, as a solution to this problem, we report the generation of human fibroblast-derived hepatocytes that can repopulate mouse livers. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs but cut short reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) state from which endoderm progenitor cells and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. For this purpose we identified small molecules that aided endoderm and hepatocyte differentiation without compromising proliferation. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps proliferated extensively and acquired levels of hepatocyte function similar to those of aHeps. Unfractionated iMPC-Heps did not form tumours, most probably because they never entered a pluripotent state. Our results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy.
C1 [Zhu, Saiyong; Ding, Sheng] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Rezvani, Milad; Mattis, Aras N.; Willenbring, Holger] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Harbell, Jack; Willenbring, Holger] Univ Calif San Francisco, Div Transplantat, Dept Surg, San Francisco, CA 94143 USA.
   [Mattis, Aras N.; Willenbring, Holger] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94110 USA.
   [Mattis, Aras N.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Wolfe, Alan R.; Benet, Leslie Z.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
   [Ding, Sheng] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; 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 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 Willenbring, H (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, 35 Med Ctr Way, San Francisco, CA 94143 USA.
EM willenbringh@stemcell.ucsf.edu; sheng.ding@gladstone.ucsf.edu
FU California Institute for Regenerative Medicine (CIRM) [RN2-00950]; National Institutes of Health (NIH) [P30 DK26743]; CIRM [TG2-01160, TG2-01153]; NIH; Gladstone Institutes; German Academic Exchange Service; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK026743] Funding Source: NIH RePORTER
NR 37
TC 205
Z9 249
U1 0
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 APR 3
PY 2014
VL 508
IS 7494
BP 93
EP 97
DI 10.1038/nature13020
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900049
PM 24572354
DA 2026-03-09
ER

PT J
AU Potenski, CJ
   Niu, HY
   Sung, P
   Klein, HL
AF Potenski, Catherine J.
   Niu, Hengyao
   Sung, Patrick
   Klein, Hannah L.
TI Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms
SO NATURE
LA English
DT Article
ID rad51 presynaptic filament; saccharomyces-cerevisiae; mismatch repair; srs2 helicase; anti-recombinase; topoisomerase-i; dna; yeast; protein; signals
AB Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to prevent spurious recombination events(1-6) and unwind trinucleotide sequences that are prone to hairpin formation(7). Here we document a new, unexpected genome maintenance role of Srs2 in the suppression of mutations arising from mis-insertion of ribonucleoside monophosphates during DNA replication. In cells lacking RNase H2, Srs2 unwinds DNA from the 5' side of a nick generated by DNA topoisomerase I-8 at a ribonucleoside monophosphate residue. In addition, Srs2 interacts with and enhances the activity of the nuclease Exo1, to generate a DNA gap in preparation for repair. Srs2-Exo1 thus functions in a new pathway of nick processing-gap filling that mediates tolerance of ribonucleoside monophosphates in the genome. Our results have implications for understanding the basis of Aicardi-Goutieres syndrome, which stems from inactivation of the human RNase H2 complex(9).
C1 [Potenski, Catherine J.; Klein, Hannah L.] NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA.
   [Niu, Hengyao; Sung, Patrick] Yale Univ, Sch Med, New Haven, CT 06520 USA.
C3 New York University; Yale University
RP Sung, P (corresponding author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA.
EM patrick.sung@yale.edu; Hannah.Klein@nyumc.org
FU National Institutes of Health [RO1GM053738, RO1ES007061, K99ES021441]; National Institute of Environmental Health Sciences [R01ES007061] Funding Source: NIH RePORTER
NR 26
TC 71
Z9 78
U1 0
U2 21
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 251
EP +
DI 10.1038/nature13292
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800050
PM 24896181
DA 2026-03-09
ER

PT J
AU Sousa-Victor, P
   Gutarra, S
   García-Prat, L
   Rodriguez-Ubreva, J
   Ortet, L
   Ruiz-Bonilla, V
   Jardí, M
   Ballestar, E
   González, S
   Serrano, AL
   Perdiguero, E
   Muñoz-Cánoves, P
AF Sousa-Victor, Pedro
   Gutarra, Susana
   Garcia-Prat, Laura
   Rodriguez-Ubreva, Javier
   Ortet, Laura
   Ruiz-Bonilla, Vanessa
   Jardi, Merce
   Ballestar, Esteban
   Gonzalez, Susana
   Serrano, Antonio L.
   Perdiguero, Eusebio
   Munoz-Canoves, Pura
TI Geriatric muscle stem cells switch reversible quiescence into senescence
SO NATURE
LA English
DT Article
ID duchenne muscular-dystrophy; skeletal-muscle; cellular senescence; satellite cells; p16(ink4a); mechanisms; myogenesis; sarcopenia; chromatin; bmi-1
AB Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16(INK4a) (also called Cdkn2a). On injury, these cells fail to activate and expand, undergoing accelerated entry into a full senescence state (geroconversion), even in a youthful environment. p16(INK4a) silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Our results demonstrate that maintenance of quiescence in adult life depends on the active repression of senescence pathways. As p16(INK4a) is dysregulated in human geriatric satellite cells, these findings provide the basis for stem-cell rejuvenation in sarcopenic muscles.
C1 [Sousa-Victor, Pedro; Gutarra, Susana; Garcia-Prat, Laura; Ortet, Laura; Ruiz-Bonilla, Vanessa; Jardi, Merce; Serrano, Antonio L.; Perdiguero, Eusebio; Munoz-Canoves, Pura] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Cell Biol Grp, CIBER Neurodegenerat Dis, E-08003 Barcelona, Spain.
   [Rodriguez-Ubreva, Javier; Ballestar, Esteban] Bellvitge Biomed Res Inst, Canc Epigenet & Biol Programme, Chromatin & Dis Grp, E-08907 Barcelona, Spain.
   [Gonzalez, Susana] Ctr Nacl Invest Cardiovasc, Stem Cell Aging Grp, E-28029 Madrid, Spain.
   [Munoz-Canoves, Pura] Inst Catalana Recerca & Estudis Avancats, E-08010 Barcelona, Spain.
C3 Pompeu Fabra University; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro Nacional de Investigaciones Cardiovasculares (CNIC); ICREA
RP Muñoz-Cánoves, P (corresponding author), Pompeu Fabra Univ, Dept Expt & Hlth Sci, Cell Biol Grp, CIBER Neurodegenerat Dis, E-08003 Barcelona, Spain.
EM eusebio.perdiguero@upf.edu; pura.munoz@upf.edu
FU MINECO-Spain [SAF2012-38547, FIS-PS09/01267, FIS-PI13/025, PLE2009-0124]; AFM; MDA; E-Rare; Fundacio Marato TV3; DuchennePP-NL; EU; Fundacao para a Ciencia e a Tecnologia (Portugal); Programa de Formacion de Personal Investigador (Spain); ICREA Funding Source: Custom
NR 50
TC 758
Z9 899
U1 9
U2 181
PU NATURE PUBLISHING 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 20
PY 2014
VL 506
IS 7488
BP 316
EP +
DI 10.1038/nature13013
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800031
PM 24522534
DA 2026-03-09
ER

PT J
AU Tavora, B
   Reynolds, LE
   Batista, S
   Demircioglu, F
   Fernandez, I
   Lechertier, T
   Lees, DM
   Wong, PP
   Alexopoulou, A
   Elia, G
   Clear, A
   Ledoux, A
   Hunter, J
   Perkins, N
   Gribben, JG
   Hodivala-Dilke, KM
AF Tavora, Bernardo
   Reynolds, Louise E.
   Batista, Silvia
   Demircioglu, Fevzi
   Fernandez, Isabelle
   Lechertier, Tanguy
   Lees, Delphine M.
   Wong, Ping-Pui
   Alexopoulou, Annika
   Elia, George
   Clear, Andrew
   Ledoux, Adeline
   Hunter, Jill
   Perkins, Neil
   Gribben, John G.
   Hodivala-Dilke, Kairbaan M.
TI Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy
SO NATURE
LA English
DT Article
ID focal adhesion kinase; nf-kappa-b; cancer-cells; resistance; microenvironment; inflammation; activation; angiogenesis; metastasis; expression
AB Chemoresistance is a serious limitation of cancer treatment(1). Until recently, almost all the work done to study this limitation has been restricted to tumour cells(2). Here we identify a novel molecular mechanism by which endothelial cells regulate chemosensitivity. We establish that specific targeting of focal adhesion kinase (FAK; also known as PTK2) in endothelial cells is sufficient to induce tumour-cell sensitization to DNA-damaging therapies and thus inhibit tumour growth in mice. The clinical relevance of this work is supported by our observations that low blood vessel FAK expression is associated with complete remission in human lymphoma. Our study shows that deletion of FAK in endothelial cells has no apparent effect on blood vessel function per se, but induces increased apoptosis and decreased proliferation within perivascular tumour-cell compartments of doxorubicin-and radiotherapy-treated mice. Mechanistically, we demonstrate that endothelial-cell FAK is required for DNA-damage induced NF-kappa B activation in vivo and in vitro, and the production of cytokines from endothelial cells. Moreover, loss of endothelial-cell FAK reduces DNA-damage-induced cytokine production, thus enhancing chemosensitization of tumour cells to DNA-damaging therapies in vitro and in vivo. Overall, our data identify endothelial-cell FAK as a regulator of tumour chemosensitivity. Furthermore, we anticipate that this proof-of-principle data will be a starting point for the development of new possible strategies to regulate chemosensitization by targeting endothelial-cell FAK specifically.
C1 [Tavora, Bernardo; Reynolds, Louise E.; Batista, Silvia; Demircioglu, Fevzi; Fernandez, Isabelle; Lechertier, Tanguy; Lees, Delphine M.; Wong, Ping-Pui; Alexopoulou, Annika; Hodivala-Dilke, Kairbaan M.] Queen Mary Univ London, CR UK Ctr Excellence, Barts Canc Inst, Adhes & Angiogenesis Lab,Ctr Tumour Biol, London EC1M 6BQ, England.
   [Elia, George] Queen Mary Univ London, CR UK Ctr Excellence, Barts Canc Inst, London EC1M 6BQ, England.
   [Clear, Andrew; Gribben, John G.] Queen Mary Univ London, CR UK Ctr Excellence, Barts Canc Inst, Ctr Haematooncol, London EC1M 6BQ, England.
   [Ledoux, Adeline; Hunter, Jill; Perkins, Neil] Newcastle Univ, Sch Med, Inst Cell & Mol Biosci ICaMB, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
C3 University of London; Queen Mary University London; University of London; Queen Mary University London; University of London; Queen Mary University London; Newcastle University - UK
RP Hodivala-Dilke, KM (corresponding author), Queen Mary Univ London, CR UK Ctr Excellence, Barts Canc Inst, Adhes & Angiogenesis Lab,Ctr Tumour Biol, London EC1M 6BQ, England.
EM K.Hodivala-Dilke@qmul.ac.uk
FU CR-UK [C9218/A12007, C1443/A9215]; AICR [12-1068]; Medical Research Council [G0901609]; National Cancer Institute [P01 CA95426]; Leukemia Lymphoma Research [11022]; MRC [G0901609] Funding Source: UKRI; Cancer Research UK [12007] Funding Source: researchfish; Medical Research Council [G0901609, 1365527] Funding Source: researchfish
CR Acharyya S, 2012, CELL, V150, P165, DOI 10.1016/j.cell.2012.04.042
   Ben-Neriah Y, 2011, NAT IMMUNOL, V12, P715, DOI 10.1038/ni.2060
   DeVita VT, 2001, CANCER PRINCIPLES AND PRACTICE OF ONCOLOGY, V6th, P0
   DiDonato JA, 2012, IMMUNOL REV, V246, P379, DOI 10.1111/j.1600-065X.2012.01099.x
   FISHER RI, 1993, NEW ENGL J MED, V328, P1002, DOI 10.1056/NEJM199304083281404
   Funakoshi-Tago M, 2003, J BIOL CHEM, V278, P29359, DOI 10.1074/jbc.M213115200
   Gilbert LA, 2010, CELL, V143, P355, DOI 10.1016/j.cell.2010.09.043
   Hagemeister FB, 2002, CANCER CHEMOTH PHARM, V49, PS13, DOI 10.1007/s00280-002-0447-1
   Hambardzumyan D, 2008, GENE DEV, V22, P436, DOI 10.1101/gad.1627008
   Lim ST, 2012, J CELL BIOL, V197, P907, DOI 10.1083/jcb.201109067
   Lu J, 2013, CANCER CELL, V23, P171, DOI 10.1016/j.ccr.2012.12.021
   May T, 2005, J BIOTECHNOL, V120, P99, DOI 10.1016/j.jbiotec.2005.03.027
   McLean GW, 2004, GENE DEV, V18, P2998, DOI 10.1101/gad.316304
   Mitra SK, 2006, CURR OPIN CELL BIOL, V18, P516, DOI 10.1016/j.ceb.2006.08.011
   Nakamura J, 2008, BIOCHEM BIOPH RES CO, V374, P699, DOI 10.1016/j.bbrc.2008.07.123
   Nakasone ES, 2012, CANCER CELL, V21, P488, DOI 10.1016/j.ccr.2012.02.017
   Perkins ND, 2012, NAT REV CANCER, V12, P121, DOI 10.1038/nrc3204
   Petzold T, 2009, AM J PHYSIOL-CELL PH, V297, PC814, DOI 10.1152/ajpcell.00226.2009
   Pikarsky E, 2004, NATURE, V431, P461, DOI 10.1038/nature02924
   Reynolds LE, 2006, METH MOLEC MED, V120, P503
   Rocha S, 2003, MOL CELL, V12, P15, DOI 10.1016/S1097-2765(03)00223-5
   Rottenberg S, 2008, DRUG RESIST UPDATE, V11, P51, DOI 10.1016/j.drup.2007.11.002
   Shibue T, 2009, P NATL ACAD SCI USA, V106, P10290, DOI 10.1073/pnas.0904227106
   Stokes JB, 2011, MOL CANCER THER, V10, P2135, DOI 10.1158/1535-7163.MCT-11-0261
   Straussman R, 2012, NATURE, V487, P500, DOI 10.1038/nature11183
   Sun Y, 2012, NAT MED, V18, P1359, DOI 10.1038/nm.2890
   Tavora B, 2010, EMBO MOL MED, V2, P516, DOI 10.1002/emmm.201000106
   Tseng WP, 2010, J CELL PHYSIOL, V223, P389, DOI 10.1002/jcp.22047
   Wilson TR, 2012, NATURE, V487, P505, DOI 10.1038/nature11249
   Zhang HFM, 2006, AM J PHYSIOL-CELL PH, V290, PC1310, DOI 10.1152/ajpcell.00450.2005
NR 30
TC 142
Z9 158
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 OCT 2
PY 2014
VL 514
IS 7520
BP 112
EP +
DI 10.1038/nature13541
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800046
PM 25079333
DA 2026-03-09
ER

PT J
AU Westphalen, K
   Gusarova, GA
   Islam, MN
   Subramanian, M
   Cohen, TS
   Prince, AS
   Bhattacharya, J
AF Westphalen, Kristin
   Gusarova, Galina A.
   Islam, Mohammad N.
   Subramanian, Manikandan
   Cohen, Taylor S.
   Prince, Alice S.
   Bhattacharya, Jahar
TI Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity
SO NATURE
LA English
DT Article
ID dendritic cells; lung; activation; atherosclerosis; determines; secretion; protects; injury
AB The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens(1). Bacterial constituents ligate Toll-like receptors (TLRs) on AMs(2), causing AMs to secrete proinflammatory cytokines(3) that activate alveolar epithelial receptors(4), leading to recruitment of neutrophils that engulf pathogens(5,6). Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.
C1 [Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Bhattacharya, Jahar] Columbia Univ, Dept Med, Med Ctr, Lung Biol Lab,Div Pulm Allergy & Crit Care, New York, NY 10032 USA.
   [Subramanian, Manikandan] Columbia Univ, Med Ctr, Div Mol Med, Dept Med, New York, NY 10032 USA.
   [Cohen, Taylor S.; Prince, Alice S.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
   [Bhattacharya, Jahar] Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University
RP Bhattacharya, J (corresponding author), Columbia Univ, Dept Med, Med Ctr, Lung Biol Lab,Div Pulm Allergy & Crit Care, New York, NY 10032 USA.
EM jb39@columbia.edu
FU US National Institutes of Health [HL78645, HL57556, HL64896, HL73989]; Parker B. Francis Fellowships
NR 31
TC 369
Z9 449
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 FEB 27
PY 2014
VL 506
IS 7489
BP 503
EP +
DI 10.1038/nature12902
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100041
PM 24463523
DA 2026-03-09
ER

PT J
AU Oh, SW
   Harris, JA
   Ng, L
   Winslow, B
   Cain, N
   Mihalas, S
   Wang, QX
   Lau, C
   Kuan, L
   Henry, AM
   Mortrud, MT
   Ouellette, B
   Nguyen, TN
   Sorensen, SA
   Slaughterbeck, CR
   Wakeman, W
   Li, Y
   Feng, D
   Ho, A
   Nicholas, E
   Hirokawa, KE
   Bohn, P
   Joines, KM
   Peng, HC
   Hawrylycz, MJ
   Phillips, JW
   Hohmann, JG
   Wohnoutka, P
   Koch, C
   Bernard, A
   Dang, C
   Jones, AR
   Zeng, HK
   Gerfen, CR
AF Oh, Seung Wook
   Harris, Julie A.
   Ng, Lydia
   Winslow, Brent
   Cain, Nicholas
   Mihalas, Stefan
   Wang, Quanxin
   Lau, Chris
   Kuan, Leonard
   Henry, Alex M.
   Mortrud, Marty T.
   Ouellette, Benjamin
   Nguyen, Thuc Nghi
   Sorensen, Staci A.
   Slaughterbeck, Clifford R.
   Wakeman, Wayne
   Li, Yang
   Feng, David
   Ho, Anh
   Nicholas, Eric
   Hirokawa, Karla E.
   Bohn, Phillip
   Joines, Kevin M.
   Peng, Hanchuan
   Hawrylycz, Michael J.
   Phillips, John W.
   Hohmann, John G.
   Wohnoutka, Paul
   Koch, Christof
   Bernard, Amy
   Dang, Chinh
   Jones, Allan R.
   Zeng, Hongkui
   Gerfen, Charles R.
TI A mesoscale connectome of the mouse brain
SO NATURE
LA English
DT Article
ID medial prefrontal cortex; phaseolus-vulgaris-leukoagglutinin; parafascicular thalamic nucleus; efferent projections; thalamocortical projections; barrel cortex; afferent connections; perirhinal cortex; limbic cortex; corticothalamic projections
AB Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
C1 [Oh, Seung Wook; Harris, Julie A.; Ng, Lydia; Winslow, Brent; Cain, Nicholas; Mihalas, Stefan; Wang, Quanxin; Lau, Chris; Kuan, Leonard; Henry, Alex M.; Mortrud, Marty T.; Ouellette, Benjamin; Nguyen, Thuc Nghi; Sorensen, Staci A.; Slaughterbeck, Clifford R.; Wakeman, Wayne; Li, Yang; Feng, David; Ho, Anh; Nicholas, Eric; Hirokawa, Karla E.; Bohn, Phillip; Joines, Kevin M.; Peng, Hanchuan; Hawrylycz, Michael J.; Phillips, John W.; Hohmann, John G.; Wohnoutka, Paul; Koch, Christof; Bernard, Amy; Dang, Chinh; Jones, Allan R.; Zeng, Hongkui] Allen Inst Brain Sci, Seattle, WA 98103 USA.
   [Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
C3 Allen Institute for Brain Science; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
RP Zeng, HK (corresponding author), Allen Inst Brain Sci, Seattle, WA 98103 USA.
FU Allen Institute for Brain Science; National Institute of Mental Health [ZIAMH002497] Funding Source: NIH RePORTER
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NR 127
TC 1832
Z9 2154
U1 12
U2 333
PU NATURE PUBLISHING 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 10
PY 2014
VL 508
IS 7495
BP 207
EP +
DI 10.1038/nature13186
PG 28
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900037
PM 24695228
DA 2026-03-09
ER

PT J
AU Wen, ZX
   Nguyen, HN
   Guo, ZY
   Lalli, MA
   Wang, XY
   Su, YJ
   Kim, NS
   Yoon, KJ
   Shin, J
   Zhang, C
   Makri, G
   Nauen, D
   Yu, HM
   Guzman, E
   Chiang, CH
   Yoritomo, N
   Kaibuchi, K
   Zou, JZ
   Christian, KM
   Cheng, LZ
   Ross, CA
   Margolis, RL
   Chen, G
   Kosik, KS
   Song, HJ
   Ming, GL
AF Wen, Zhexing
   Ha Nam Nguyen
   Guo, Ziyuan
   Lalli, Matthew A.
   Wang, Xinyuan
   Su, Yijing
   Kim, Nam-Shik
   Yoon, Ki-Jun
   Shin, Jaehoon
   Zhang, Ce
   Makri, Georgia
   Nauen, David
   Yu, Huimei
   Guzman, Elmer
   Chiang, Cheng-Hsuan
   Yoritomo, Nadine
   Kaibuchi, Kozo
   Zou, Jizhong
   Christian, Kimberly M.
   Cheng, Linzhao
   Ross, Christopher A.
   Margolis, Russell L.
   Chen, Gong
   Kosik, Kenneth S.
   Song, Hongjun
   Ming, Guo-li
TI Synaptic dysregulation in a human iPS cell model of mental disorders
SO NATURE
LA English
DT Article
ID de-novo mutations; stem-cells; schizophrenia; gene; disease; quantification; integration; proteins
AB Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders(1), and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia(2). Although this hypothesis has gained indirect support from human post-mortem brain analyses' and genetic studies(5-10), little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes(11). Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia! (DISCI) co-segregated with major psychiatric disorders' and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISCI causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISCI depletes wild-type DISCI protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders.
C1 [Wen, Zhexing; Ha Nam Nguyen; Wang, Xinyuan; Su, Yijing; Kim, Nam-Shik; Yoon, Ki-Jun; Shin, Jaehoon; Zhang, Ce; Makri, Georgia; Nauen, David; Yu, Huimei; Chiang, Cheng-Hsuan; Zou, Jizhong; Christian, Kimberly M.; Cheng, Linzhao; Song, Hongjun; Ming, Guo-li] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
   [Wen, Zhexing; Su, Yijing; Kim, Nam-Shik; Yoon, Ki-Jun; Zhang, Ce; Makri, Georgia; Yu, Huimei; Chiang, Cheng-Hsuan; Christian, Kimberly M.; Song, Hongjun; Ming, Guo-li] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
   [Ha Nam Nguyen; Shin, Jaehoon; Ross, Christopher A.; Margolis, Russell L.; Song, Hongjun; Ming, Guo-li] Johns Hopkins Univ, Sch Med, Grad Program Cellular & Mol Med, Baltimore, MD 21205 USA.
   [Guo, Ziyuan; Chen, Gong] Penn State Univ, Huck Inst Life Sci, Dept Biol, University Pk, PA 16802 USA.
   [Lalli, Matthew A.; Guzman, Elmer; Kosik, Kenneth S.] Univ Calif Santa Barbara, Biomol Sci & Engn Program, Dept Mol Cellular & Dev Biol, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Wang, Xinyuan] Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China.
   [Nauen, David] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Chiang, Cheng-Hsuan; Ross, Christopher A.; Margolis, Russell L.; Song, Hongjun; Ming, Guo-li] Johns Hopkins Univ, Sch Med, Solomon Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Yoritomo, Nadine; Ross, Christopher A.; Margolis, Russell L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Kaibuchi, Kozo] Nagoya Univ, Grad Sch Med, Showa Ku, Dept Cell Pharmacol, Nagoya, Aichi 4668550, Japan.
   [Zou, Jizhong; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of California System; University of California Santa Barbara; Fudan University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Nagoya University; Johns Hopkins University
RP Ming, GL (corresponding author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
EM gming1@jhmi.edu
FU NIH [MH087874, N5047344, NS048271, AG045656, MH102978]; IMHRO; SFARI; NARSAD; MSCRF; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
NR 40
TC 424
Z9 501
U1 0
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 NOV 20
PY 2014
VL 515
IS 7527
BP 414
EP +
DI 10.1038/nature13716
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600046
PM 25132547
DA 2026-03-09
ER

PT J
AU Kir, S
   White, JP
   Kleiner, S
   Kazak, L
   Cohen, P
   Baracos, VE
   Spiegelman, BM
AF Kir, Serkan
   White, James P.
   Kleiner, Sandra
   Kazak, Lawrence
   Cohen, Paul
   Baracos, Vickie E.
   Spiegelman, Bruce M.
TI Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia
SO NATURE
LA English
DT Article
ID hormone-related protein; skeletal-muscle; monoclonal-antibody; nude-mice; mechanisms; cell; thermogenesis; activation; survival
AB Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat(1-6). How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.
C1 [Kir, Serkan; White, James P.; Kleiner, Sandra; Kazak, Lawrence; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Baracos, Vickie E.] Univ Alberta, Div Palliat Care Med, Dept Oncol, Edmonton, AB T6G 1Z2, Canada.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; University of Alberta
RP Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU American Cancer Society [PF-13-385-01-TBE]; National Institutes of Health [DK31405]
NR 24
TC 532
Z9 597
U1 0
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 SEP 4
PY 2014
VL 513
IS 7516
BP 100
EP +
DI 10.1038/nature13528
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800038
PM 25043053
DA 2026-03-09
ER

PT J
AU Endo, M
   Shimizu, H
   Nohales, MA
   Araki, T
   Kay, SA
AF Endo, Motomu
   Shimizu, Hanako
   Nohales, Maria A.
   Araki, Takashi
   Kay, Steve A.
TI Tissue-specific clocks in Arabidopsis show asymmetric coupling
SO NATURE
LA English
DT Article
ID circadian clock; expression; promoter; network; roles; time
AB Many organisms rely on a circadian clock system to adapt to daily and seasonal environmental changes. The mammalian circadian clock consists of a central clock in the suprachiasmatic nucleus that has tightly coupled neurons and synchronizes other clocks in peripheral tissues(1,2). Plants also have a circadian clock, but plant circadian clock function has long been assumed to be uncoupled(3). Only a few studies have been able to show weak, local coupling among cells'. Here, by implementing two novel techniques, we have performed a comprehensive tissue-specific analysis of leaf tissues, and show that the vasculature and mesophyll clocks asymmetrically regulate each other in Arabidopsis. The circadian clock in the vasculature has characteristics distinct from other tissues, cycles robustly without environmental cues, and affects circadian clock regulation in other tissues. Furthermore, we found that vasculature-enriched genes that are rhythmically expressed are preferentially expressed in the evening, whereas rhythmic mesophyll-enriched genes tend to be expressed in the morning. Our results set the stage for a deeper understanding of how the vasculature circadian clock in plants regulates key physiological responses such as flowering time.
C1 [Endo, Motomu; Shimizu, Hanako; Araki, Takashi] Kyoto Univ, Grad Sch Biostudies, Div Integrated Life Sci, Sakyo Ku, Kyoto 6068501, Japan.
   [Endo, Motomu] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Nohales, Maria A.; Kay, Steve A.] Univ So Calif Mol & Computat Biol, Dept Biol, Dana & David Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA.
C3 Kyoto University; Japan Science & Technology Agency (JST)
RP Endo, M (corresponding author), Kyoto Univ, Grad Sch Biostudies, Div Integrated Life Sci, Sakyo Ku, Kyoto 6068501, Japan.
EM moendo@lif.kyoto-u.ac.jp
FU HFSP long-term Fellowship [LT00017/2008-L]; JST PRESTO [11103346]; JSPS KAKENHI [22770036, 25650097]; Sumitomo Foundation; Nakatani Foundation; National Institutes of Health (NIH) [R01 GM056006, GM067837];  [19060012];  [19060016]; Grants-in-Aid for Scientific Research [22770036, 25113005, 25650097] Funding Source: KAKEN
NR 36
TC 213
Z9 252
U1 2
U2 141
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2014
VL 515
IS 7527
BP 419
EP +
DI 10.1038/nature13919
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600047
PM 25363766
DA 2026-03-09
ER

PT J
AU Geach, JE
   Hickox, RC
   Diamond-Stanic, AM
   Krips, M
   Rudnick, GH
   Tremonti, CA
   Sell, PH
   Coils, AL
   Moustakas, J
AF Geach, J. E.
   Hickox, R. C.
   Diamond-Stanic, A. M.
   Krips, M.
   Rudnick, G. H.
   Tremonti, C. A.
   Sell, P. H.
   Coils, A. L.
   Moustakas, J.
TI Stellar feedback as the origin of an extended molecular outflow in a starburst galaxy
SO NATURE
LA English
DT Article
ID active galactic nuclei; high-velocity outflows; star-formation; radiation pressure; agn feedback; black-holes; emission; constraints; evolution; mechanism
AB Recent observations have revealed that starburst galaxies can drive molecular gas outflows through stellar radiation pressure(1,2). Molecular gas is the phase of the interstellar medium from which stars form, so these outflows curtail stellar mass growth in galaxies. Previously known outflows, however, involve small fractions of the total molecular gas content and have typical scales of less than a kilopar-sec(1,2). In at least some cases, input from active galactic nuclei is dynamically important(2,3), so pure stellar feedback (the momentum return into the interstellar medium) has been considered incapable of rapidly terminating star formation on galactic scales. Molecular gas has been detected outside the galactic plane of the archetypal starburst galaxy M82 (refs 4 and 5), but so far there has been no evidence that starbursts can propel substantial quantities of cold molecular gas to the same galactocentric radius (about 10 kiloparsecs) as the warmer gas that has been traced by metal ion absorbers in the circumgalactic medium(6,7). Here we report observations of molecular gas in a compact (effective radius 100 parsecs) massive starburst galaxy at redshift 0.7, which is known to drive a fast outflow of ionized gas(8). We find that 35 per cent of the total molecular gas extends approximately 10 kiloparsecs, and one-third of this extended gas has a velocity of up to 1,000 kilometres per second. The kinetic energy associated with this high-velocity component is consistent with the momentum flux available from stellar radiation pressure(9-12). This demonstrates that nuclear bursts of star formation are capable of ejecting large amounts of cold gas from the central regions of galaxies, thereby strongly affecting their evolution by truncating star formation and redistributing matter(13,14).
C1 [Geach, J. E.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Hickox, R. C.] Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA.
   [Diamond-Stanic, A. M.; Tremonti, C. A.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [Krips, M.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Rudnick, G. H.] Univ Kansas, Dept Phys & Astron, Lawrence, KS 66045 USA.
   [Rudnick, G. H.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Sell, P. H.] Texas Tech Univ, Dept Phys, Lubbock, TX 79409 USA.
   [Coils, A. L.] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
   [Moustakas, J.] Siena Coll, Dept Phys & Astron, New York, NY 12211 USA.
C3 University of Hertfordshire; Dartmouth College; University of Wisconsin System; University of Wisconsin Madison; University of Kansas; Max Planck Society; Texas Tech University System; Texas Tech University; University of California System; University of California San Diego
RP Geach, JE (corresponding author), Univ Hertfordshire, Ctr Astrophys Res, Coll Lane, Hatfield AL10 9AB, Herts, England.
EM j.geach@herts.ac.uk
FU Royal Society; Grainger Foundation; Alexander von Humboldt Foundation; NSF CAREER grant [AST-1055081]; INSU/CNRS (France); MPG (Germany); IGN (Spain); W. M. Keck Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1211358] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1055081] Funding Source: National Science Foundation
NR 40
TC 67
Z9 78
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 DEC 4
PY 2014
VL 516
IS 7529
BP 68
EP U384
DI 10.1038/nature14012
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800039
PM 25471881
DA 2026-03-09
ER

PT J
AU Sherwood, OA
   Guilderson, TP
   Batista, FC
   Schiff, JT
   McCarthy, MD
AF Sherwood, Owen A.
   Guilderson, Thomas P.
   Batista, Fabian C.
   Schiff, John T.
   McCarthy, Matthew D.
TI Increasing subtropical North Pacific Ocean nitrogen fixation since the Little Ice Age
SO NATURE
LA English
DT Article
ID isotopic composition; station aloha; amino-acids; variability; sea; radiocarbon; circulation; patterns; biogeochemistry; denitrification
AB The North Pacific subtropical gyre (NPSG) plays a major part in the export of carbon and other nutrients to the deep ocean(1). Primary production in the NPSG has increased in recent decades despite a reduction in nutrient supply to surface waters(2,3). It is thought that this apparent paradox can be explained by a shift in plankton community structure from mostly eukaryotes to mostly nitrogen-fixing prokaryotes(2-4). It remains uncertain, however, whether the plankton community domain shift can be linked to cyclical climate variability or a long-term global warming trend(5). Here we analyse records of bulk and amino-acid-specific N-15/N-14 isotopic ratios (delta N-15) preserved in the skeletons of long-lived deep-sea proteinaceous corals collected from the Hawaiian archipelago; these isotopic records serve as a proxy for the source of nitrogen-supported export production through time. We find that the recent increase in nitrogen fixation is the continuation of a much larger, centennial-scale trend. After a millennium of relatively minor fluctuation, delta N-15 decreases between 1850 and the present. The total shift in delta N-15 of -2 per mil over this period is comparable to the total change in global mean sedimentary delta N-15 across the Pleistocene-Holocene transition, but it is happening an order of magnitude faster(6). We use a steady-state model and find that the isotopic mass balance between nitrate and nitrogen fixation implies a 17 to 27 per cent increase in nitrogen fixation over this time period. A comparison with independent records(7,8) suggests that the increase in nitrogen fixation might be linked to Northern Hemisphere climate change since the end of the Little Ice Age.
C1 [Sherwood, Owen A.; Guilderson, Thomas P.; Batista, Fabian C.; Schiff, John T.; McCarthy, Matthew D.] Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
   [Guilderson, Thomas P.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Guilderson, Thomas P.] Univ Calif Santa Cruz, Inst Marine Sci, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California Santa Cruz
RP Sherwood, OA (corresponding author), Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
EM owen.sherwood@colorado.edu
FU NOAA/NURP; National Geographic Society [7717-04]; US Department of Energy [DE-AC52-07NA27344]; NSF [OCE 1061689]; Directorate For Geosciences [1260164] Funding Source: National Science Foundation; Division Of Ocean Sciences [1260164] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1061689] Funding Source: National Science Foundation
NR 47
TC 86
Z9 106
U1 1
U2 156
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 2
PY 2014
VL 505
IS 7481
BP 78
EP +
DI 10.1038/nature12784
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300027
PM 24336216
DA 2026-03-09
ER

PT J
AU Czuczman, MA
   Fattouh, R
   van Rijn, JM
   Canadien, V
   Osborne, S
   Muise, AM
   Kuchroo, VK
   Higgins, DE
   Brumell, JH
AF Czuczman, Mark A.
   Fattouh, Ramzi
   van Rijn, Jorik M.
   Canadien, Veronica
   Osborne, Suzanne
   Muise, Aleixo M.
   Kuchroo, Vijay K.
   Higgins, Darren E.
   Brumell, John H.
TI Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread
SO NATURE
LA English
DT Article
ID plasma-membrane; host-cells; phospholipases-c; infection; clearance; survival; roles; actin; mice
AB Efferocytosis, the process by which dying or dead cells are removed by phagocytosis, has an important role in development, tissue homeostasis and innate immunity(1). Efferocytosis is mediated, in part, by receptors that bind to exofacial phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes, can exploit efferocytosis to promote cell-to-cell spread during infection. These bacteria can escape the phagosome in host cells by using the poreforming toxin listeriolysin O (LLO) and two phospholipase C enzymes(2). Expression of the cell surface protein ActA allows L. monocytogenes to activate host actin regulatory factors and undergo actin-based motility in the cytosol, eventually leading to formation of actin-rich protrusions at the cell surface. Here we show that protrusion formation is associated with plasma membrane damage due to LLO's poreforming activity. LLO also promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial PS. The PS-binding receptor TIM-4 (encoded by the Timd4 gene) contributes to efficient cell-to-cell spread by L. monocytogenes in macrophages in vitro and growth of these bacteria is impaired in Timd4(-/-) mice. Thus, L. monocytogenes promotes its dissemination in a host by exploiting efferocytosis. Our results indicate that PS-targeted therapeutics may be useful in the fight against infections by L. monocytogenes and other bacteria that use similar strategies of cell-to-cell spread during infection.
C1 [Czuczman, Mark A.; Fattouh, Ramzi; Canadien, Veronica; Osborne, Suzanne; Muise, Aleixo M.; Brumell, John H.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 0A4, Canada.
   [Czuczman, Mark A.; Brumell, John H.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [van Rijn, Jorik M.] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
   [van Rijn, Jorik M.] Univ Med Ctr Utrecht, Inst Biomembranes, NL-3584 CX Utrecht, Netherlands.
   [Muise, Aleixo M.] Hosp Sick Children, Dept Paediat, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G 1X8, Canada.
   [Muise, Aleixo M.; Brumell, John H.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
   [Muise, Aleixo M.; Brumell, John H.] Hosp Sick Children, Sickkids IBD Ctr, Toronto, ON M5G 1X8, Canada.
   [Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Higgins, Darren E.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Brumell, JH (corresponding author), Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 0A4, Canada.
EM john.brumell@sickkids.ca
FU Canadian Foundation for Innovation; Ontario Innovation Trust; Canadian Institutes of Health Research; Canadian Association of Gastroenterology; Crohn's and Colitis Foundation of Canada; Research Training Committee at the Hospital for Sick Children; Arthritis Society of Canada [RG11/013]; US Public Health Service grant from the National Institutes of Health [AI053669]
NR 39
TC 121
Z9 156
U1 2
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 8
PY 2014
VL 509
IS 7499
BP 230
EP +
DI 10.1038/nature13168
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300040
PM 24739967
DA 2026-03-09
ER

PT J
AU Northcott, PA
   Lee, C
   Zichner, T
   Stütz, AM
   Erkek, S
   Kawauchi, D
   Shih, DJH
   Hovestadt, V
   Zapatka, M
   Sturm, D
   Jones, DTW
   Kool, M
   Remke, M
   Cavalli, FMG
   Zuyderduyn, S
   Bader, GD
   VandenBerg, S
   Esparza, LA
   Ryzhova, M
   Wang, W
   Wittmann, A
   Stark, S
   Sieber, L
   Seker-Cin, H
   Linke, L
   Kratochwil, F
   Jäger, N
   Buchhalter, I
   Imbusch, CD
   Zipprich, G
   Raeder, B
   Schmidt, S
   Diessl, N
   Wolf, S
   Wiemann, S
   Brors, B
   Lawerenz, C
   Eils, J
   Warnatz, HJ
   Risch, T
   Yaspo, ML
   Weber, UD
   Bartholomae, CC
   von Kalle, C
   Turányi, E
   Hauser, P
   Sanden, E
   Darabi, A
   Siesjö, P
   Sterba, J
   Zitterbart, K
   Sumerauer, D
   van Sluis, P
   Versteeg, R
   Volckmann, R
   Koster, J
   Schuhmann, MU
   Ebinger, M
   Grimes, HL
   Robinson, GW
   Gajjar, A
   Mynarek, M
   von Hoff, K
   Rutkowski, S
   Pietsch, T
   Scheurlen, W
   Felsberg, J
   Reifenberger, G
   Kulozik, AE
   von Deimling, A
   Witt, O
   Eils, R
   Gilbertson, RJ
   Korshunov, A
   Taylor, MD
   Lichter, P
   Korbel, JO
   Wechsler-Reya, RJ
   Pfister, SM
AF Northcott, Paul A.
   Lee, Catherine
   Zichner, Thomas
   Stuetz, Adrian M.
   Erkek, Serap
   Kawauchi, Daisuke
   Shih, David J. H.
   Hovestadt, Volker
   Zapatka, Marc
   Sturm, Dominik
   Jones, David T. W.
   Kool, Marcel
   Remke, Marc
   Cavalli, Florence M. G.
   Zuyderduyn, Scott
   Bader, Gary D.
   VandenBerg, Scott
   Esparza, Lourdes Adriana
   Ryzhova, Marina
   Wang, Wei
   Wittmann, Andrea
   Stark, Sebastian
   Sieber, Laura
   Seker-Cin, Huriye
   Linke, Linda
   Kratochwil, Fabian
   Jaeger, Natalie
   Buchhalter, Ivo
   Imbusch, Charles D.
   Zipprich, Gideon
   Raeder, Benjamin
   Schmidt, Sabine
   Diessl, Nicolle
   Wolf, Stephan
   Wiemann, Stefan
   Brors, Benedikt
   Lawerenz, Chris
   Eils, Juergen
   Warnatz, Hans-Joerg
   Risch, Thomas
   Yaspo, Marie-Laure
   Weber, Ursula D.
   Bartholomae, Cynthia C.
   von Kalle, Christof
   Turanyi, Eszter
   Hauser, Peter
   Sanden, Emma
   Darabi, Anna
   Siesjoe, Peter
   Sterba, Jaroslav
   Zitterbart, Karel
   Sumerauer, David
   van Sluis, Peter
   Versteeg, Rogier
   Volckmann, Richard
   Koster, Jan
   Schuhmann, Martin U.
   Ebinger, Martin
   Grimes, H. Leighton
   Robinson, Giles W.
   Gajjar, Amar
   Mynarek, Martin
   von Hoff, Katja
   Rutkowski, Stefan
   Pietsch, Torsten
   Scheurlen, Wolfram
   Felsberg, Joerg
   Reifenberger, Guido
   Kulozik, Andreas E.
   von Deimling, Andreas
   Witt, Olaf
   Eils, Roland
   Gilbertson, Richard J.
   Korshunov, Andrey
   Taylor, Michael D.
   Lichter, Peter
   Korbel, Jan O.
   Wechsler-Reya, Robert J.
   Pfister, Stefan M.
TI Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma
SO NATURE
LA English
DT Article
ID finger protein gfi-1; super-enhancers; cell identity; genome; gene; myc; mutations; subgroup; model; pim-1
AB Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
C1 [Northcott, Paul A.; Erkek, Serap; Kawauchi, Daisuke; Sturm, Dominik; Jones, David T. W.; Kool, Marcel; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Lee, Catherine] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Lee, Catherine; Esparza, Lourdes Adriana; Wechsler-Reya, Robert J.] Sanford Burnham Med Res Inst, Tumor Initiat & Maintenance Program, La Jolla, CA 92037 USA.
   [Zichner, Thomas; Stuetz, Adrian M.; Erkek, Serap; Raeder, Benjamin; Korbel, Jan O.] European Mol Biol Lab EMBL, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Shih, David J. H.; Remke, Marc; Cavalli, Florence M. G.; Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada.
   [Hovestadt, Volker; Zapatka, Marc; Wang, Wei; Weber, Ursula D.; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Zuyderduyn, Scott; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [VandenBerg, Scott] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
   [Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow 125047, Russia.
   [Jaeger, Natalie; Buchhalter, Ivo; Brors, Benedikt; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Imbusch, Charles D.; Zipprich, Gideon; Lawerenz, Chris; Eils, Juergen] German Canc Res Ctr, Data Management Facil, D-69120 Heidelberg, Germany.
   [Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan] German Canc Res Ctr, Genom & Prote Core Facil, D-69120 Heidelberg, Germany.
   [Warnatz, Hans-Joerg; Risch, Thomas; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany.
   [Bartholomae, Cynthia C.; von Kalle, Christof] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany.
   [Bartholomae, Cynthia C.; von Kalle, Christof] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany.
   [von Kalle, Christof; Eils, Roland; Lichter, Peter] Heidelberg Ctr Personalised Oncol DKFZ HIPO, D-69120 Heidelberg, Germany.
   [Turanyi, Eszter] Semmelweis Univ SE, Dept Pathol & Expt Canc Res 1, H-1094 Budapest, Hungary.
   [Hauser, Peter] Semmelweis Univ, Dept Pediat 2, H-1094 Budapest, Hungary.
   [Sanden, Emma; Darabi, Anna; Siesjoe, Peter] Lund Univ, Div Neurosurg, Glioma Immunotherapy Grp, S-22100 Lund, Sweden.
   [Sanden, Emma; Darabi, Anna; Siesjoe, Peter] Lund Univ, Dept Clin Sci, S-22100 Lund, Sweden.
   [Sterba, Jaroslav; Zitterbart, Karel] Masaryk Univ, Dept Pediat Oncol, Brno 61300, Czech Republic.
   [Sterba, Jaroslav; Zitterbart, Karel] Univ Hosp, Brno 61300, Czech Republic.
   [Sumerauer, David] Charles Univ Prague, Dept Pediat Hematol & Oncol, Fac Med 2, Prague 15006, Czech Republic.
   [Sumerauer, David] Univ Hosp Motol, Prague 15006, Czech Republic.
   [van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan] Univ Amsterdam, AMC, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands.
   [Schuhmann, Martin U.; Ebinger, Martin] Tubingen Univ Hosp, Dept Neurosurg, D-72076 Tubingen, Germany.
   [Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Program Hematol Malignancies, Program Canc Pathol, Div Immunobiol,Div Expt Hematol & Pathol,Canc & B, Cincinnati, OH 45229 USA.
   [Robinson, Giles W.; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Robinson, Giles W.; Gajjar, Amar; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   Univ Med Ctr Hamburg Eppendorf, Dept Paediat Haematol & Oncol, D-20246 Hamburg, Germany.
   [Pietsch, Torsten] Univ Bonn, Dept Neuropathol, D-53105 Bonn, Germany.
   [Scheurlen, Wolfram] Nurnberg Childrens Hosp, Cnopfsche Kinderklin, D-90419 Nurnberg, Germany.
   [Felsberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany.
   [Kulozik, Andreas E.; Witt, Olaf; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
   [von Deimling, Andreas; Korshunov, Andrey] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
   [Korbel, Jan O.] European Bioinformat Inst EMBL EBI, EMBL, Saffron Walden CB10 1SD, Essex, England.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); University of California System; University of California San Diego; Sanford Burnham Prebys Medical Discovery Institute; European Molecular Biology Laboratory (EMBL); University of Toronto; Hospital for Sick Children (SickKids); Helmholtz Association; German Cancer Research Center (DKFZ); University of Toronto; University of California System; University of California San Diego; Russian Academy of Medical Sciences; N.N.Burdenko National Medical Research Center of Neurosurgery; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Max Planck Society; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Semmelweis University; Semmelweis University; Lund University; Lund University; Masaryk University; University Hospital Brno; Motol University Hospital; Charles University Prague; Motol University Hospital; University of Amsterdam; Academic Medical Center Amsterdam; Eberhard Karls University of Tubingen; TUBINGEN UNIVERSITY CHILDRENS HOSPITAL; Eberhard Karls University Hospital; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Bonn; Heinrich Heine University Dusseldorf; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; University of Toronto; Hospital for Sick Children (SickKids); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute
RP Northcott, PA (corresponding author), German Canc Res Ctr, Div Pediat Neurooncol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM m.macleod@dkfz-heidelberg.de; korbel@embl.de; rwreya@sanfordburnham.org; s.pfister@dkfz-heidelberg.de
FU PedBrain Tumor Project - German Cancer Aid [109252]; German Federal Ministry of Education and Research (BMBF) [01KU1201A, MedSys 0315416C, NGFNplus 01GS0883]; German Cancer Research Center-Heidelberg Center for Personalized Oncology (DKFZ-HIPO); EMBL International PhD Programme; Dutch Cancer Foundation KWF [2010-4713]; Dutch Cancer Foundation KIKA; US National Institutes of Health, National Center for Research Resources [P41 GM103504]; CancerSys grant MYC-NET (German Federal Ministry of Education and Research, BMBF) [0316076A]; European Commission [Health-F2-2010-260791]; Helmholtz Alliance PCCC [HA-305]; Hertie Foundation; DKFZ; California Institute for Regenerative Medicine [CIRM LA1-01747]; National Cancer Institute [5P30CA030199, R01 CA159859]; CureSearch for Children's Cancer Foundation; National Cancer Institute [P30CA030199, R01CA159859, P01CA096832] Funding Source: NIH RePORTER; National Center for Advancing Translational Sciences [UL1TR001425] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103504] Funding Source: NIH RePORTER
NR 46
TC 511
Z9 621
U1 1
U2 88
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 24
PY 2014
VL 511
IS 7510
BP 428
EP +
DI 10.1038/nature13379
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700038
PM 25043047
DA 2026-03-09
ER

PT J
AU Cortez, D
   Marin, R
   Toledo-Flores, D
   Froidevaux, L
   Liechti, A
   Waters, PD
   Grützner, F
   Kaessmann, H
AF Cortez, Diego
   Marin, Ray
   Toledo-Flores, Deborah
   Froidevaux, Laure
   Liechti, Angelica
   Waters, Paul D.
   Gruetzner, Frank
   Kaessmann, Henrik
TI Origins and functional evolution of Y chromosomes across mammals
SO NATURE
LA English
DT Article
ID sex-determining region; determining gene; w-chromosome; dna-sequence; long arm; mouse; identification; platypus; expression; alignment
AB Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome originations in mammals and birds (the outgroup). The original placental and marsupial (therian) Y, containing the sex-determining gene SRY, emerged in the therian ancestor approximately 180 million years ago, in parallel with the first of five monotreme Y chromosomes, carrying the probable sex-determining gene AMH. The avian W chromosome arose approximately 140 million years ago in the bird ancestor. The small Y/W gene repertoires, enriched in regulatory functions, were rapidly defined following stratification (recombination arrest) and erosion events and have remained considerably stable. Despite expression decreases in therians, Y/W genes show notable conservation of proto-sex chromosome expression patterns, although various Y genes evolved testis-specificities through differential regulatory decay. Thus, although some genes evolved novel functions through spatial/temporal expression shifts, most Y genes probably endured, at least initially, because of dosage constraints.
C1 [Cortez, Diego; Marin, Ray; Froidevaux, Laure; Liechti, Angelica; Kaessmann, Henrik] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Cortez, Diego; Marin, Ray; Kaessmann, Henrik] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Toledo-Flores, Deborah; Gruetzner, Frank] Univ Adelaide, Robinson Res Inst, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia.
   [Waters, Paul D.] UNSW Australia, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia.
C3 University of Lausanne; Swiss Institute of Bioinformatics; Robinson Research Institute; Adelaide University; University of Adelaide; University of New South Wales Sydney
RP Cortez, D (corresponding author), Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
EM diegoclaudio.cortezquezada@unil.ch; henrik.kaessmann@unil.ch
FU Mexican National Council for Science and Technology (CONACyT); ARC; European Research Council [242597]; Swiss National Science Foundation [130287]; European Research Council (ERC) [242597] Funding Source: European Research Council (ERC)
NR 92
TC 392
Z9 458
U1 4
U2 198
PU NATURE PUBLISHING 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 24
PY 2014
VL 508
IS 7497
BP 488
EP +
DI 10.1038/nature13151
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600029
PM 24759410
DA 2026-03-09
ER

PT J
AU Du, DJ
   Wang, Z
   James, NR
   Voss, JE
   Klimont, E
   Ohene-Agyei, T
   Venter, H
   Chiu, W
   Luisi, BF
AF Du, Dijun
   Wang, Zhao
   James, Nathan R.
   Voss, Jarrod E.
   Klimont, Ewa
   Ohene-Agyei, Thelma
   Venter, Henrietta
   Chiu, Wah
   Luisi, Ben F.
TI Structure of the AcrAB-TolC multidrug efflux pump
SO NATURE
LA English
DT Article
ID cryo-em structure; crystal-structure; membrane protein; system; channel; crystallography; refinement; component; software; complex
AB The capacity of numerous bacterial species to tolerate antibiotics and other toxic compounds arises in part from the activity of energy-dependent transporters. In Gram-negative bacteria, many of these transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component(1-7). A model system for such a pump is the acridine resistance complex of Escherichia Coli(1). This pump assembly comprises the outer-membrane channel TolC, the secondary transporter AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport vectorially a diverse array of compounds with little chemical similarity, thus conferring resistance to a broad spectrum of antibiotics. Homologous complexes are found in many Gram-negative species, including in animal and plant pathogens. Crystal structures are available for the individual components of the pump(2-7) and have provided insights into substrate recognition, energy coupling and the transduction of conformational changes associated with the transport process. However, how the subunits are organized in the pump, their stoichiometry and the details of their interactions are not known. Here we present the pseudo-atomic structure of a complete multidrug efflux pump in complex with a modulatory protein partner(8) from E. Coli. The model defines the quaternary organization of the pump, identifies key domain interactions, and suggests a cooperative process for channel assembly and opening. These findings illuminate the basis for drug resistance in numerous pathogenic bacterial species.
C1 [Du, Dijun; James, Nathan R.; Voss, Jarrod E.; Klimont, Ewa; Luisi, Ben F.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
   [Wang, Zhao; Chiu, Wah] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
   [Ohene-Agyei, Thelma] Dept Pharmacol, Cambridge CB2 1PD, England.
   [Venter, Henrietta] Univ S Australia, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Adelaide, SA 5000, Australia.
C3 University of Cambridge; Baylor College of Medicine; Adelaide University; University of South Australia
RP Luisi, BF (corresponding author), Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1GA, England.
EM dd339@cam.ac.uk; bfl20@cam.ac.uk
FU Wellcome Trust; Human Frontier Science Program; National Institutes of Health [P41GM103832]; Herschel Smith scholarship; Cambridge Trust scholarship; Adam Glinsman award; Faculty for the Future Fellowship from the Schlumberger Foundation
NR 52
TC 496
Z9 592
U1 2
U2 280
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 512
EP +
DI 10.1038/nature13205
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000043
PM 24747401
DA 2026-03-09
ER

PT J
AU Xu, XLL
   Singh, HP
   Wang, L
   Qi, DL
   Poulos, BK
   Abramson, DH
   Jhanwar, SC
   Cobrinik, D
AF Xu, Xiaoliang L.
   Singh, Hardeep P.
   Wang, Lu
   Qi, Dong-Lai
   Poulos, Bradford K.
   Abramson, David H.
   Jhanwar, Suresh C.
   Cobrinik, David
TI Rb suppresses human cone-precursor-derived retinoblastoma tumours
SO NATURE
LA English
DT Article
ID genomic instability; expression; cells; gene; identification; proteins; retina
AB Retinoblastoma is a childhood retinal tumour that initiates in response to biallelic RB1 inactivation and loss of functional retinoblastoma (Rb) protein. Although Rb has diverse tumour-suppressor functions and is inactivated in many cancers(1-5), germline RB1 mutations predispose to retinoblastoma far more strongly than to other malignancies(6). This tropism suggests that retinal cell-type-specific circuitry sensitizes to Rb loss, yet the nature of the circuitry and the cell type in which it operates have beenunclear(7,8). Here we show that post-mitotic human cone precursors are uniquely sensitive to Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN and MDM2. Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation. Moreover, Rb-depleted cone precursors formed tumours in orthotopic xenografts with histological features and protein expression typical of human retinoblastoma. These findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. More generally, they demonstrate that cell-type-specific circuitry can collaborate with an initiating oncogenic mutation to enable tumorigenesis.
C1 [Xu, Xiaoliang L.; Wang, Lu; Jhanwar, Suresh C.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Xu, Xiaoliang L.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, New York, NY 10021 USA.
   [Singh, Hardeep P.; Qi, Dong-Lai; Cobrinik, David] Childrens Hosp Los Angeles, Div Ophthalmol, Dept Surg, Vis Ctr, Los Angeles, CA 90027 USA.
   [Singh, Hardeep P.; Qi, Dong-Lai; Cobrinik, David] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA.
   [Poulos, Bradford K.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
   [Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA.
   [Jhanwar, Suresh C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Cobrinik, David] Univ So Calif, Keck Sch Med, Dept Ophthalmol, USC Eye Inst, Los Angeles, CA 90033 USA.
   [Cobrinik, David] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Children's Hospital Los Angeles; Children's Hospital Los Angeles; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Southern California; University of Southern California
RP Jhanwar, SC (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
EM jhanwars@mskcc.org; dcobrinik@chla.usc.edu
FU Gerber Foundation; Fund for Ophthalmic Knowledge; Research and Development Funds of the MSKCC Department of Pathology; Larry & Celia Moh Foundation; National Institutes of Health [1R01CA137124]; National Cancer Institute [R01CA137124] Funding Source: NIH RePORTER
NR 32
TC 187
Z9 221
U1 1
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 OCT 16
PY 2014
VL 514
IS 7522
BP 385
EP +
DI 10.1038/nature13813
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600056
PM 25252974
DA 2026-03-09
ER

PT J
AU Schumacher, T
   Bunse, L
   Pusch, S
   Sahm, F
   Wiestler, B
   Quandt, J
   Menn, O
   Osswald, M
   Oezen, I
   Ott, M
   Keil, M
   Balss, J
   Rauschenbach, K
   Grabowska, AK
   Vogler, I
   Diekmann, J
   Trautwein, N
   Eichmüller, SB
   Okun, J
   Stevanovic, S
   Riemer, AB
   Sahin, U
   Friese, MA
   Beckhove, P
   von Deimling, A
   Wick, W
   Platten, M
AF Schumacher, Theresa
   Bunse, Lukas
   Pusch, Stefan
   Sahm, Felix
   Wiestler, Benedikt
   Quandt, Jasmin
   Menn, Oliver
   Osswald, Matthias
   Oezen, Iris
   Ott, Martina
   Keil, Melanie
   Balss, Joerg
   Rauschenbach, Katharina
   Grabowska, Agnieszka K.
   Vogler, Isabel
   Diekmann, Jan
   Trautwein, Nico
   Eichmueller, Stefan B.
   Okun, Juergen
   Stevanovic, Stefan
   Riemer, Angelika B.
   Sahin, Ugur
   Friese, Manuel A.
   Beckhove, Philipp
   von Deimling, Andreas
   Wick, Wolfgang
   Platten, Michael
TI A vaccine targeting mutant IDH1 induces antitumour immunity
SO NATURE
LA English
DT Article
ID brain-tumors; mutations; cells; differentiation; phenotype; melanoma; gliomas; mice
AB Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas(1-3) and other types of tumour(4-6). They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG)(7,8), genomic hypermethylation9-11, genetic instability and malignant transformation(12). More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells(13,14). Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable formutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses. CD41 TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restrictedmutation-specific antitumourimmune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+)T-cell-dependent manner. As IDH1(R132H) is present in all tumour cells of these slow-growing gliomas(15), a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.
C1 [Schumacher, Theresa; Bunse, Lukas; Wiestler, Benedikt; Menn, Oliver; Osswald, Matthias; Oezen, Iris; Ott, Martina; Keil, Melanie; Rauschenbach, Katharina; Wick, Wolfgang; Platten, Michael] Univ Heidelberg Hosp, Dept Neurooncol, D-69120 Heidelberg, Germany.
   [Schumacher, Theresa; Bunse, Lukas; Wiestler, Benedikt; Menn, Oliver; Osswald, Matthias; Oezen, Iris; Ott, Martina; Keil, Melanie; Rauschenbach, Katharina; Wick, Wolfgang; Platten, Michael] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
   [Schumacher, Theresa; Bunse, Lukas; Oezen, Iris; Ott, Martina; Keil, Melanie; Balss, Joerg; Rauschenbach, Katharina; Platten, Michael] German Canc Res Ctr, German Canc Consortium DKTK Clin Cooperat Unit Ne, D-69120 Heidelberg, Germany.
   [Pusch, Stefan; Sahm, Felix; von Deimling, Andreas] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Pusch, Stefan; Sahm, Felix; von Deimling, Andreas] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
   [Pusch, Stefan; Sahm, Felix; Balss, Joerg; von Deimling, Andreas] German Canc Res Ctr, German Canc Consortium DKTK Clin Cooperat Unit Ne, D-69120 Heidelberg, Germany.
   [Wiestler, Benedikt; Osswald, Matthias; Wick, Wolfgang] German Canc Res Ctr, German Canc Consortium DKTK Clin Cooperat Unit Ne, D-69120 Heidelberg, Germany.
   [Quandt, Jasmin; Eichmueller, Stefan B.; Beckhove, Philipp] German Canc Res Ctr, Dept Translat Immunol, D-69120 Heidelberg, Germany.
   [Grabowska, Agnieszka K.; Riemer, Angelika B.] German Canc Res Ctr, Dept Immunotherapy & Prevent Grp, D-69120 Heidelberg, Germany.
   [Vogler, Isabel] Ribological GmbH, D-55131 Mainz, Germany.
   [Diekmann, Jan; Sahin, Ugur] Translat Oncol, D-55131 Mainz, Germany.
   [Trautwein, Nico; Stevanovic, Stefan] Univ Tubingen, Dept Immunol, D-72076 Tubingen, Germany.
   [Okun, Juergen] Univ Childrens Hosp, Metab Ctr Heidelberg, D-69120 Heidelberg, Germany.
   [Friese, Manuel A.] Univ Med Ctr, Ctr Mol Neurobiol, D-20251 Hamburg, Germany.
C3 Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Eberhard Karls University of Tubingen; Ruprecht Karls University Heidelberg; University of Hamburg; University Medical Center Hamburg-Eppendorf
RP Platten, M (corresponding author), Univ Heidelberg Hosp, Dept Neurooncol, D-69120 Heidelberg, Germany.
EM m.platten@dkfz.de
FU DKFZ Light Microscopy and Genomics and Proteomics Facilities; NIH; Interdisciplinary Research Program of the National Center for Tumor Diseases Heidelberg [IFP III/2]; Wilhelm Sander Foundation [2012.118.1]; Helmholtz Foundation [VH-NG-306]; Andreas Zimprich Foundation; German Research Foundation [SFB938]; Helmholtz International Graduate School; Heinrich F. C. Behr Foundation; Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology MD/PhD program, University Heidelberg; University Hospital Heidelberg
NR 26
TC 569
Z9 652
U1 5
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 AUG 21
PY 2014
VL 512
IS 7514
BP 324
EP +
DI 10.1038/nature13387
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200038
PM 25043048
DA 2026-03-09
ER

PT J
AU Dias, C
   Feng, J
   Sun, HS
   Shao, NY
   Mazei-Robison, MS
   Damez-Werno, D
   Scobie, K
   Bagot, R
   LaBonté, B
   Ribeiro, E
   Liu, XC
   Kennedy, P
   Vialou, V
   Ferguson, D
   Peña, C
   Calipari, ES
   Koo, JW
   Mouzon, E
   Ghose, S
   Tamminga, C
   Neve, R
   Shen, L
   Nestler, EJ
AF Dias, Caroline
   Feng, Jian
   Sun, Haosheng
   Shao, Ning yi
   Mazei-Robison, Michelle S.
   Damez-Werno, Diane
   Scobie, Kimberly
   Bagot, Rosemary
   LaBonte, Benoit
   Ribeiro, Efrain
   Liu, XiaoChuan
   Kennedy, Pamela
   Vialou, Vincent
   Ferguson, Deveroux
   Pena, Catherine
   Calipari, Erin S.
   Koo, Ja Wook
   Mouzon, Ezekiell
   Ghose, Subroto
   Tamminga, Carol
   Neve, Rachael
   Shen, Li
   Nestler, Eric J.
TI β-catenin mediates stress resilience through Dicer1/microRNA regulation
SO NATURE
LA English
DT Article
ID nucleus-accumbens; distinct roles; social defeat; synthase kinase-3; striatal neurons; transcription; pathway; reward; bdnf; identification
AB beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis-as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin fromnucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. Wethus present a foundation for the development of novel therapeutic targets to promote stress resilience.
C1 [Dias, Caroline; Feng, Jian; Sun, Haosheng; Shao, Ning yi; Mazei-Robison, Michelle S.; Damez-Werno, Diane; Scobie, Kimberly; Bagot, Rosemary; LaBonte, Benoit; Ribeiro, Efrain; Liu, XiaoChuan; Kennedy, Pamela; Vialou, Vincent; Ferguson, Deveroux; Pena, Catherine; Calipari, Erin S.; Koo, Ja Wook; Mouzon, Ezekiell; Shen, Li; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA.
   [Dias, Caroline; Feng, Jian; Sun, Haosheng; Shao, Ning yi; Mazei-Robison, Michelle S.; Damez-Werno, Diane; Scobie, Kimberly; Bagot, Rosemary; LaBonte, Benoit; Ribeiro, Efrain; Liu, XiaoChuan; Kennedy, Pamela; Vialou, Vincent; Ferguson, Deveroux; Pena, Catherine; Calipari, Erin S.; Koo, Ja Wook; Mouzon, Ezekiell; Shen, Li; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
   [Ghose, Subroto; Tamminga, Carol] Univ Texas Southwestern, Dept Psychiat, Dallas, TX 75390 USA.
   [Neve, Rachael] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Texas System; University of Texas Southwestern Medical Center; Massachusetts Institute of Technology (MIT)
RP Shen, L (corresponding author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA.
EM li.shen@mssm.edu; eric.nestler@mssm.edu
FU National Institute of Mental Health; Hope for Depression Research Foundation (HDRF); National Institute of Mental Health [P50MH096890] Funding Source: NIH RePORTER
NR 51
TC 203
Z9 241
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 DEC 4
PY 2014
VL 516
IS 7529
BP 51
EP U86
DI 10.1038/nature13976
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800036
PM 25383518
DA 2026-03-09
ER

PT J
AU Koyano, F
   Okatsu, K
   Kosako, H
   Tamura, Y
   Go, E
   Kimura, M
   Kimura, Y
   Tsuchiya, H
   Yoshihara, H
   Hirokawa, T
   Endo, T
   Fon, EA
   Trempe, JF
   Saeki, Y
   Tanaka, K
   Matsuda, N
AF Koyano, Fumika
   Okatsu, Kei
   Kosako, Hidetaka
   Tamura, Yasushi
   Go, Etsu
   Kimura, Mayumi
   Kimura, Yoko
   Tsuchiya, Hikaru
   Yoshihara, Hidehito
   Hirokawa, Takatsugu
   Endo, Toshiya
   Fon, Edward A.
   Trempe, Jean-Francois
   Saeki, Yasushi
   Tanaka, Keiji
   Matsuda, Noriyuki
TI Ubiquitin is phosphorylated by PINK1 to activate parkin
SO NATURE
LA English
DT Article
ID mitochondrial translocation; mechanisms; drosophila-pink1; recruitment; dysfunction; mutations; defects; complex; domain
AB PINK1 (PTEN induced putative kinase 1) and PARKIN (also known as PARK2) have been identified as the causal genes responsible for hereditary recessive early-onset Parkinsonism(1,2). PINK1 is a Ser/Thr kinase that specifically accumulates on depolarized mitochondria, whereas parkin is an E3 ubiquitin ligase that catalyses ubiquitin transfer to mitochondrial substrates(3-5). PINK1 acts as an upstream factor for parkin(6,7) and is essential both for the activation of latent E3 parkin activity(8) and for recruiting parkin onto depolarized mitochondria(8-12). Recently, mechanistic insights into mitochondrial quality control mediated by PINK1 and parkin have been revealed(3-5), and PINK1-dependent phosphorylation of parkin has been reported(13-15). However, the requirement of PINK1 for parkin activation was not bypassed by phosphomimetic parkin mutation(15), and how PINK1 accelerates the E3 activity of parkin on damaged mitochondria is still obscure. Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential. Unexpectedly, phosphomimetic ubiquitin bypassed PINK1-dependent activation of a phosphomimetic parkin mutant in cells. Furthermore, phosphomimetic ubiquitin accelerates discharge of the thioester conjugate formed by UBCH7 (also known as UBE2L3) and ubiquitin (UBCH7 ubiquitin) in the presence of parkin in vitro, indicating that it acts allosterically. The phosphorylation-dependent interaction between ubiquitin and parkin suggests that phosphorylated ubiquitin unlocks autoinhibition of the catalytic cysteine. Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator.
C1 [Koyano, Fumika; Okatsu, Kei; Go, Etsu; Kimura, Mayumi; Kimura, Yoko; Tsuchiya, Hikaru; Yoshihara, Hidehito; Saeki, Yasushi; Tanaka, Keiji; Matsuda, Noriyuki] Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 1568506, Japan.
   [Koyano, Fumika; Okatsu, Kei] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba 2778561, Japan.
   [Kosako, Hidetaka] Univ Tokushima, Div Cell Signaling, Fujii Mem Inst Med Sci, Tokushima 7708503, Japan.
   [Tamura, Yasushi] Nagoya Univ, Res Ctr Mat Sci, Nagoya, Aichi 4648602, Japan.
   [Kimura, Yoko] Shizuoka Univ, Grad Sch Agr, Shizuoka 4228529, Japan.
   [Hirokawa, Takatsugu] Natl Inst Adv Ind Sci & Technol, Mol Profiling Res Ctr Drug Discovery, Koto Ku, Tokyo 1350064, Japan.
   [Endo, Toshiya] Nagoya Univ, Grad Sch Sci, JST CREST Dept Chem, Chikusa Ku, Nagoya, Aichi 4648602, Japan.
   [Endo, Toshiya] Kyoto Sangyo Univ, JST CREST Fac Life Sci, Kita Ku, Kyoto 6038555, Japan.
   [Fon, Edward A.] McGill Univ, McGill Parkinson Program, Dept Neurol & Neurosurg, Montreal Neurol Inst & Hosp, Montreal, PQ H3A 2B4, Canada.
   [Trempe, Jean-Francois] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada.
   [Matsuda, Noriyuki] Tokyo Metropolitan Inst Med Sci, Prot Metab Project, Setagaya Ku, Tokyo 1568506, Japan.
C3 Tokyo Metropolitan Institute of Medical Science; University of Tokyo; Tokushima University; Nagoya University; Shizuoka University; National Institute of Advanced Industrial Science & Technology (AIST); Nagoya University; Kyoto Sangyo University; McGill University; McGill University; Tokyo Metropolitan Institute of Medical Science
RP Matsuda, N (corresponding author), Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 1568506, Japan.
EM tanaka-kj@igakuken.or.jp; matsuda-nr@igakuken.or.jp
FU JSPS KAKENHI [23687018, 23-6061, 21000012, 24657072, 22227003]; MEXT KAKENHI [24111557, 25112522, 24112008]; Tomizawa Jun-ichi and Keiko Fund; JST CREST; Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT; McGill University; GRASP from the FRSQ; CIHR; FRSQ; Takeda Science Foundation; Grants-in-Aid for Scientific Research [26000014, 24657072, 26440101, 26650042, 23570231, 24112008, 26440070, 25112522, 26111729, 22227003, 21000012, 23687018, 24111557, 25870311] Funding Source: KAKEN
NR 30
TC 1216
Z9 1426
U1 3
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 JUN 5
PY 2014
VL 510
IS 7503
BP 162
EP +
DI 10.1038/nature13392
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900049
PM 24784582
DA 2026-03-09
ER

PT J
AU O'Gorman, PA
AF O'Gorman, Paul A.
TI Contrasting responses of mean and extreme snowfall to climate change
SO NATURE
LA English
DT Article
ID precipitation extremes; heavy precipitation; trends; temperature; probability; snowstorms; events
AB Snowfall is an important element of the climate system, and one that is expected to change in a warming climate(1-4). Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts(5-7). Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures(3,4). The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall overmany Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as -9 degrees C, compared to -14 degrees C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain-snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.
C1 MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP O'Gorman, PA (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM pog@mit.edu
FU NSF [AGS-1148594]; NASA ROSES [09-IDS09-0049]
NR 42
TC 194
Z9 224
U1 5
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 AUG 28
PY 2014
VL 512
IS 7515
BP 416
EP U401
DI 10.1038/nature13625
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600030
PM 25164753
DA 2026-03-09
ER

PT J
AU Brohawn, SG
   Campbell, EB
   MacKinnon, R
AF Brohawn, Stephen G.
   Campbell, Ernest B.
   MacKinnon, Roderick
TI Physical mechanism for gating and mechano sensitivity of the human TRAAK K+ channel
SO NATURE
LA English
DT Article
ID mechanosensitive channels; crystal-structure; lipid-bilayer; trek-1; pore; membrane; protein; model; mscl
AB Activation of mechanosensitive ion channels by physical force underlies many physiological processes including the sensation of touch, hearing and pain(1-5). TRAAK (also known as KCNK4) ion channels are neuronally expressed members of the two-pore domain K+ (K2P) channel family and are mechano sensitive'. They are involved in controlling mechanical and temperature nociception in mice'. Mechanosensitivity of TRAAK is mediated directly through the lipid bilayer it is a membrane-tension-gated channel'. However, the molecular mechanism of TRAAK channel gating and mechanosensitivity is unknown. Here we present crystal structures of TRAAK in conductive and non-conductive conformations defined by the presence of permeant ions along the conduction pathway. In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Awide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of a transmembrane helix (TM4) about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM 3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures reveals a biophysical explanation for TRAAK mechanosensitivity an expansion in cross-sectional area up to 2.7 nm(2) in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation. Our results show how tension of the lipid bilayer can be harnessed to control gating and mechanosensitivity of a eukaryotic ion channel.
C1 [Brohawn, Stephen G.; Campbell, Ernest B.; MacKinnon, Roderick] Rockefeller Univ, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA.
   [Brohawn, Stephen G.; Campbell, Ernest B.; MacKinnon, Roderick] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University; Howard Hughes Medical Institute
RP MacKinnon, R (corresponding author), Rockefeller Univ, Lab Mol Neurobiol & Biophys, 1230 York Ave, New York, NY 10065 USA.
EM mackinn@rockefeller.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 40
TC 263
Z9 296
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 DEC 4
PY 2014
VL 516
IS 7529
BP 126
EP U345
DI 10.1038/nature14013
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800053
PM 25471887
DA 2026-03-09
ER

PT J
AU Mack, SC
   Witt, H
   Piro, RM
   Gu, L
   Zuyderduyn, S
   Stütz, AM
   Wang, X
   Gallo, M
   Garzia, L
   Zayne, K
   Zhang, X
   Ramaswamy, V
   Jäger, N
   Jones, DTW
   Sill, M
   Pugh, TJ
   Ryzhova, M
   Wani, KM
   Shih, DJH
   Head, R
   Remke, M
   Bailey, SD
   Zichner, T
   Faria, CC
   Barszczyk, M
   Stark, S
   Seker-Cin, H
   Hutter, S
   Johann, P
   Bender, S
   Hovestadt, V
   Tzaridis, T
   Dubuc, AM
   Northcott, PA
   Peacock, J
   Bertrand, KC
   Agnihotri, S
   Cavalli, FMG
   Clarke, I
   Nethery-Brokx, K
   Creasy, CL
   Verma, SK
   Koster, J
   Wu, X
   Yao, Y
   Milde, T
   Sin-Chan, P
   Zuccaro, J
   Lau, L
   Pereira, S
   Castelo-Branco, P
   Hirst, M
   Marra, MA
   Roberts, SS
   Fults, D
   Massimi, L
   Cho, YJ
   Van Meter, T
   Grajkowska, W
   Lach, B
   Kulozik, AE
   von Deimling, A
   Witt, O
   Scherer, SW
   Fan, X
   Muraszko, KM
   Kool, M
   Pomeroy, SL
   Gupta, N
   Phillips, J
   Huang, A
   Tabori, U
   Hawkins, C
   Malkin, D
   Kongkham, PN
   Weiss, WA
   Jabado, N
   Rutka, JT
   Bouffet, E
   Korbel, JO
   Lupien, M
   Aldape, KD
   Bader, GD
   Eils, R
   Lichter, P
   Dirks, PB
   Pfister, SM
   Korshunov, A
   Taylor, MD
AF Mack, S. C.
   Witt, H.
   Piro, R. M.
   Gu, L.
   Zuyderduyn, S.
   Stuetz, A. M.
   Wang, X.
   Gallo, M.
   Garzia, L.
   Zayne, K.
   Zhang, X.
   Ramaswamy, V.
   Jaeger, N.
   Jones, D. T. W.
   Sill, M.
   Pugh, T. J.
   Ryzhova, M.
   Wani, K. M.
   Shih, D. J. H.
   Head, R.
   Remke, M.
   Bailey, S. D.
   Zichner, T.
   Faria, C. C.
   Barszczyk, M.
   Stark, S.
   Seker-Cin, H.
   Hutter, S.
   Johann, P.
   Bender, S.
   Hovestadt, V.
   Tzaridis, T.
   Dubuc, A. M.
   Northcott, P. A.
   Peacock, J.
   Bertrand, K. C.
   Agnihotri, S.
   Cavalli, F. M. G.
   Clarke, I.
   Nethery-Brokx, K.
   Creasy, C. L.
   Verma, S. K.
   Koster, J.
   Wu, X.
   Yao, Y.
   Milde, T.
   Sin-Chan, P.
   Zuccaro, J.
   Lau, L.
   Pereira, S.
   Castelo-Branco, P.
   Hirst, M.
   Marra, M. A.
   Roberts, S. S.
   Fults, D.
   Massimi, L.
   Cho, Y. J.
   Van Meter, T.
   Grajkowska, W.
   Lach, B.
   Kulozik, A. E.
   von Deimling, A.
   Witt, O.
   Scherer, S. W.
   Fan, X.
   Muraszko, K. M.
   Kool, M.
   Pomeroy, S. L.
   Gupta, N.
   Phillips, J.
   Huang, A.
   Tabori, U.
   Hawkins, C.
   Malkin, D.
   Kongkham, P. N.
   Weiss, W. A.
   Jabado, N.
   Rutka, J. T.
   Bouffet, E.
   Korbel, J. O.
   Lupien, M.
   Aldape, K. D.
   Bader, G. D.
   Eils, R.
   Lichter, P.
   Dirks, P. B.
   Pfister, S. M.
   Korshunov, A.
   Taylor, M. D.
TI Epigenomic alterations define lethal CIMP-positive ependymomas of infancy
SO NATURE
LA English
DT Article
ID island methylator phenotype; gene-expression signature; driver mutations; genomic complexity; distinct subgroups; cancer; landscape; strategy; subtype
AB Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
C1 [Mack, S. C.; Wang, X.; Gallo, M.; Garzia, L.; Zayne, K.; Ramaswamy, V.; Shih, D. J. H.; Head, R.; Remke, M.; Faria, C. C.; Barszczyk, M.; Dubuc, A. M.; Peacock, J.; Bertrand, K. C.; Agnihotri, S.; Cavalli, F. M. G.; Clarke, I.; Nethery-Brokx, K.; Wu, X.; Yao, Y.; Sin-Chan, P.; Zuccaro, J.; Lau, L.; Pereira, S.; Castelo-Branco, P.; Scherer, S. W.; Huang, A.; Tabori, U.; Hawkins, C.; Kongkham, P. N.; Rutka, J. T.; Dirks, P. B.; Taylor, M. D.] Hosp Sick Children, Dev & Stem Cell Biol Program, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1L7, Canada.
   [Mack, S. C.; Wang, X.; Ramaswamy, V.; Shih, D. J. H.; Remke, M.; Barszczyk, M.; Dubuc, A. M.; Peacock, J.; Bertrand, K. C.; Yao, Y.; Hawkins, C.; Kongkham, P. N.; Rutka, J. T.; Dirks, P. B.; Taylor, M. D.] Univ Toronto, Toronto, ON M5S 1A8, Canada.
   [Mack, S. C.; Kongkham, P. N.; Rutka, J. T.; Dirks, P. B.; Taylor, M. D.] Univ Toronto, Div Neurosurg, Toronto, ON M5S 1A8, Canada.
   [Witt, H.; Jones, D. T. W.; Ryzhova, M.; Stark, S.; Seker-Cin, H.; Hutter, S.; Johann, P.; Bender, S.; Tzaridis, T.; Northcott, P. A.; Kool, M.; Pfister, S. M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Witt, H.; Milde, T.; Kulozik, A. E.; Witt, O.; Pfister, S. M.] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
   [Witt, H.; Piro, R. M.; Gu, L.; Stuetz, A. M.; Jaeger, N.; Jones, D. T. W.; Sill, M.; Ryzhova, M.; Zichner, T.; Stark, S.; Seker-Cin, H.; Hutter, S.; Johann, P.; Bender, S.; Hovestadt, V.; Tzaridis, T.; Northcott, P. A.; Milde, T.; Kulozik, A. E.; von Deimling, A.; Witt, O.; Kool, M.; Eils, R.; Lichter, P.; Pfister, S. M.; Korshunov, A.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
   [Piro, R. M.; Hovestadt, V.; Lichter, P.] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Gu, L.; Jaeger, N.; Eils, R.] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Zuyderduyn, S.; Bader, G. D.] Univ Toronto, Donnelly Ctr, Banting & Best Dept Med Res, Dept Mol Genet, Toronto, ON M4N 1X8, Canada.
   [Stuetz, A. M.; Zichner, T.; Korbel, J. O.] European Mol Biol, Genome Biol, D-69117 Heidelberg, Germany.
   [Zhang, X.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Genet, Lebanon, NH 03756 USA.
   [Sill, M.] German Canc Res Ctr, Div Bioinformat, D-69120 Heidelberg, Germany.
   [Pugh, T. J.; Pomeroy, S. L.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol,MIT, Boston, MA 02115 USA.
   [Wani, K. M.; Aldape, K. D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Bailey, S. D.; Lupien, M.] Univ Hlth Network, Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
   [Bailey, S. D.; Lupien, M.] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada.
   [Creasy, C. L.; Verma, S. K.] GlaxoSmithKline, Canc Epigenet Discovery Performance Unit, Collegeville, PA 19426 USA.
   [Koster, J.] Acad Med Ctr, Dept Oncogen, NL-1105 Amsterdam, Netherlands.
   [Milde, T.; Witt, O.] German Canc Res Ctr, CCU Pediat Oncol, D-69120 Heidelberg, Germany.
   [Hirst, M.] Univ British Columbia, Dept Microbiol & Immunol, Ctr High Throughput Biol, Vancouver, BC V6T 1Z4, Canada.
   [Hirst, M.; Marra, M. A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Marra, M. A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
   [Roberts, S. S.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
   [Roberts, S. S.] Uniformed Serv Univ Hlth Sci, Natl Capital Consortium, Bethesda, MD 20814 USA.
   [Fults, D.] Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT 84132 USA.
   [Massimi, L.] Univ Cattolica Sacro Cuore, Sch Med, Gemelli Hosp, I-00168 Rome, Italy.
   [Cho, Y. J.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [Van Meter, T.] Virginia Commonwealth, Dept Pediat, Richmond, VA 23298 USA.
   [Grajkowska, W.] Univ Warsaw, Dept Pathol, Childrens Mem Hlth Inst, PL-04730 Warsaw, Poland.
   [Lach, B.] McMaster Univ, Hamilton Gen Hosp, Div Anat Pathol, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada.
   [von Deimling, A.] Heidelberg Univ, Inst Pathol, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Fan, X.; Korshunov, A.] Univ Michigan Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Fan, X.; Muraszko, K. M.] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI 48109 USA.
   [Gupta, N.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
   [Phillips, J.; Weiss, W. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
   [Phillips, J.; Weiss, W. A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
   [Phillips, J.; Weiss, W. A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94158 USA.
   [Huang, A.; Tabori, U.; Bouffet, E.] Hosp Sick Children, Dept Neurooncol, Toronto, ON M5G 1X8, Canada.
   [Malkin, D.] Hosp Sick Children, Dept Haematol & Oncol, Toronto, ON M5G 1X8, Canada.
   [Jabado, N.] McGill Univ, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada.
   [Jabado, N.] McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada.
   [Jabado, N.] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3Z 2Z3, Canada.
   [Lupien, M.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada.
   [Dirks, P. B.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Korshunov, A.] German Canc Res Ctr, CCU Neuropathol, D-69120 Heidelberg, Germany.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); University of Toronto; Dartmouth Cancer Center; Dartmouth College; Helmholtz Association; German Cancer Research Center (DKFZ); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; University of Texas System; UTMD Anderson Cancer Center; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Ontario Institute for Cancer Research; University of Toronto; GlaxoSmithKline; Glaxosmithkline USA; Helmholtz Association; German Cancer Research Center (DKFZ); University of British Columbia; British Columbia Cancer Agency; University of British Columbia; Uniformed Services University of the Health Sciences - USA; Uniformed Services University of the Health Sciences - USA; Utah System of Higher Education; University of Utah; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Stanford University; Virginia Commonwealth University; University of Warsaw; Children's Memorial Health Institute; McMaster University; McMaster University Hospital; Ruprecht Karls University Heidelberg; University of Michigan System; University of Michigan; 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 California System; University of California San Francisco; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); McGill University; McGill University; McGill University; University of Toronto; University of Toronto; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Korshunov, A (corresponding author), German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
EM Andrey.Korshunov@med.uni-heidelberg.de; mdtaylor@sickkids.ca
FU Canadian Institutes of Health Research (CIHR); Garron Family Chair in Childhood Cancer Research; Cure Search Foundation; Younger Foundation; National Institutes of Health [R01CA148699, R01CA159859]; Pediatric Brain Tumor Foundation; Canadian Cancer Society; Terry Fox Research Institute; Brainchild; CIHR; Ontario Institute for Cancer Research through the Government of Ontario; Cure Search for Children's Cancer; PedBrain Tumor Project; German Cancer Aid [109252]; German Federal Ministry of Education and Research (BMBF) [01KU1201A, MedSys 0315416C, NGFNplus 01GS0883]; Sander Foundation; DKTK (Molecular Diagnostics of Pediatric Malignancies); National Cancer Institute [P30CA016672, R01CA159859, P50CA097257] Funding Source: NIH RePORTER
NR 49
TC 471
Z9 533
U1 0
U2 76
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 27
PY 2014
VL 506
IS 7489
BP 445
EP +
DI 10.1038/nature13108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100029
PM 24553142
DA 2026-03-09
ER

PT J
AU Ntziachristos, P
   Tsirigos, A
   Welstead, GG
   Trimarchi, T
   Bakogianni, S
   Xu, LY
   Loizou, E
   Holmfeldt, L
   Strikoudis, A
   King, B
   Mullenders, J
   Becksfort, J
   Nedjic, J
   Paietta, E
   Tallman, MS
   Rowe, JM
   Tonon, G
   Satoh, T
   Kruidenier, L
   Prinjha, R
   Akira, S
   Van Vlierberghe, P
   Ferrando, AA
   Jaenisch, R
   Mullighan, CG
   Aifantis, I
AF Ntziachristos, Panagiotis
   Tsirigos, Aristotelis
   Welstead, G. Grant
   Trimarchi, Thomas
   Bakogianni, Sofia
   Xu, Luyao
   Loizou, Evangelia
   Holmfeldt, Linda
   Strikoudis, Alexandros
   King, Bryan
   Mullenders, Jasper
   Becksfort, Jared
   Nedjic, Jelena
   Paietta, Elisabeth
   Tallman, Martin S.
   Rowe, Jacob M.
   Tonon, Giovanni
   Satoh, Takashi
   Kruidenier, Laurens
   Prinjha, Rab
   Akira, Shizuo
   Van Vlierberghe, Pieter
   Ferrando, Adolfo A.
   Jaenisch, Rudolf
   Mullighan, Charles G.
   Aifantis, Iannis
TI Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia
SO NATURE
LA English
DT Article
ID initiating cell-activity; acute myeloid-leukemia; h3k27 demethylase; expression profiles; jmjd3 contributes; stem-cell; utx; mutations; activation; genome
AB T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders(1), and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified(2,3); however, epigenetic drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL(4). Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, we found that UTX functions as a tumour suppressor and is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting JMJD3 activity. These findings show that two proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating haematopoietic malignancies with a new category of epigenetic inhibitors.
C1 [Ntziachristos, Panagiotis; Tsirigos, Aristotelis; Trimarchi, Thomas; Bakogianni, Sofia; Loizou, Evangelia; Strikoudis, Alexandros; King, Bryan; Mullenders, Jasper; Nedjic, Jelena; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Ntziachristos, Panagiotis; Tsirigos, Aristotelis; Trimarchi, Thomas; Bakogianni, Sofia; Loizou, Evangelia; Strikoudis, Alexandros; King, Bryan; Mullenders, Jasper; Nedjic, Jelena; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Ntziachristos, Panagiotis; Trimarchi, Thomas; Bakogianni, Sofia; Loizou, Evangelia; Strikoudis, Alexandros; King, Bryan; Mullenders, Jasper; Nedjic, Jelena; Aifantis, Iannis] NYU, Sch Med, NYU Canc Inst, New York, NY 10016 USA.
   [Ntziachristos, Panagiotis; Trimarchi, Thomas; Bakogianni, Sofia; Loizou, Evangelia; Strikoudis, Alexandros; King, Bryan; Mullenders, Jasper; Nedjic, Jelena; Aifantis, Iannis] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Stem Cell Biol, New York, NY 10016 USA.
   [Tsirigos, Aristotelis] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA.
   [Welstead, G. Grant; Jaenisch, Rudolf] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Welstead, G. Grant; Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Xu, Luyao; Van Vlierberghe, Pieter; Ferrando, Adolfo A.] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
   [Holmfeldt, Linda; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Becksfort, Jared] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
   [Paietta, Elisabeth] Montefiore Med Ctr North, Bronx, NY 10467 USA.
   [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Rowe, Jacob M.] Technion Israel Inst Technol, IL-31096 Haifa, Israel.
   [Rowe, Jacob M.] Shaare Zedek Med Ctr, IL-9103102 Jerusalem, Israel.
   [Tonon, Giovanni] Ist Sci San Raffaele, IRCCS, Div Mol Oncol, Funct Genom Canc Unit, I-20132 Milan, Italy.
   [Satoh, Takashi; Akira, Shizuo] Osaka Univ, WPI IFReC, Lab Host Def, Suita, Osaka 5650871, Japan.
   [Satoh, Takashi; Akira, Shizuo] Osaka Univ, RIMD, Dept Host Def, Suita, Osaka 5650871, Japan.
   [Kruidenier, Laurens; Prinjha, Rab] GlaxoSmithKline R&D, Med Res Ctr, Immunoinflammat Therapy Area, Epinova DPU, Stevenage SG1 2NY, Herts, England.
   [Van Vlierberghe, Pieter] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
   [Ferrando, Adolfo A.] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA.
   [Ferrando, Adolfo A.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
C3 Howard Hughes Medical Institute; New York University; New York University; New York University; New York University; New York University; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Columbia University; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Montefiore Medical Center; Memorial Sloan Kettering Cancer Center; Technion Israel Institute of Technology; Hebrew University of Jerusalem; Shaare Zedek Medical Center; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Osaka; University of Osaka; GlaxoSmithKline; Glaxosmithkline United Kingdom; Ghent University; Ghent University Hospital; Columbia University; Columbia University
RP Tsirigos, A (corresponding author), NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
EM Aristotelis.Tsirigos@nyumc.org; charles.mullighan@stjude.org
FU National Institutes of Health (NIH)/National Cancer Institute (NCI) grant [P30 CA016087-30]; NIH/NCI [5P30CA16087-31, K99CA188293]; NIH [1R01CA133379, 1R01CA105129, 1R01CA149655, 5R01CA173636, 5R01CA169784, 5 T32 CA009161-37, R37-HD04502, R01CA120196]; Damon Runyon Cancer Research Foundation; NYU Cell and Molecular Biology Training Program; Lady Tata Memorial Trust for leukaemia; American Society of Hematology; Research Foundation Flanders; Odysseus type II grant; NCI [U24 CA114737, U10 CA21115]; Stand Up To Cancer Innovative Research Award; William Lawrence and Blanche Hughes Foundation; Leukemia & Lymphoma Society; Ralph S. French Charitable Foundation Trust; Chemotherapy Foundation; V Foundation for Cancer Research; St. Baldrick's Foundation; ECOG tumour bank; National Cancer Institute [U10CA180820, P30CA016087, R01CA173636, P30CA014051, P30CA021765] Funding Source: NIH RePORTER
NR 47
TC 302
Z9 350
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 OCT 23
PY 2014
VL 514
IS 7523
BP 513
EP +
DI 10.1038/nature13605
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900045
PM 25132549
DA 2026-03-09
ER

PT J
AU Zhang, YN
   Nicholatos, J
   Dreier, JR
   Ricoult, SJH
   Widenmaier, SB
   Hotamisligil, GS
   Kwiatkowski, DJ
   Manning, BD
AF Zhang, Yinan
   Nicholatos, Justin
   Dreier, John R.
   Ricoult, Stephane J. H.
   Widenmaier, Scott B.
   Hotamisligil, Goekhan S.
   Kwiatkowski, David J.
   Manning, Brendan D.
TI Coordinated regulation of protein synthesis and degradation by mTORC1
SO NATURE
LA English
DT Article
ID activation; homeostasis; autophagy; srebp-1a; pathway; complex; target; genes
AB Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. Mechanistic target of rapamycin complex 1 (mTORC1) promotes nutrient-consuming anabolic processes, such as protein synthesis(1). Here we show that as well as increasing protein synthesis, mTORC1 activation in mouse and human cells also promotes an increased capacity for protein degradation. Cells with activated mTORC1 exhibited elevated levels of intact and active proteasomes through a global increase in the expression of genes encoding proteasome subunits. The increase in proteasome gene expression, cellular proteasome content, and rates of protein turnover downstream of mTORC1 were all dependent on induction of the transcription factor nuclear factor erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1). Genetic activation of mTORC1 through loss of the tuberous sclerosis complex tumour suppressors, TSC1 or TSC2, or physiological activation of mTORC1 in response to growth factors or feeding resulted in increased NRF1 expression in cells and tissues. We find that this NRF1-dependent elevation in proteasome levels serves to increase the intracellular pool of amino acids, which thereby influences rates of new protein synthesis. Therefore, mTORC1 signalling increases the efficiency of proteasome-mediated protein degradation for both quality control and as a mechanism to supply substrate for sustained protein synthesis.
C1 [Zhang, Yinan; Nicholatos, Justin; Ricoult, Stephane J. H.; Widenmaier, Scott B.; Hotamisligil, Goekhan S.; Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
   [Dreier, John R.; Kwiatkowski, David J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Translat Med Div,Dept Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Manning, BD (corresponding author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM bmanning@hsph.harvard.edu
FU Department of Defense Tuberous Sclerosis Complex Research Program [W81XWH-10-1-0861]; National Institutes of Health [CA122617, CA120964]; Ellison Medical Foundation; National Science Foundation [DGE-1144152]; Canadian Institutes of Health Research; National Cancer Institute [P01CA120964] Funding Source: NIH RePORTER
NR 27
TC 265
Z9 333
U1 0
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 SEP 18
PY 2014
VL 513
IS 7518
BP 440
EP +
DI 10.1038/nature13492
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900065
PM 25043031
DA 2026-03-09
ER

PT J
AU Yan, C
   Liu, D
   Li, L
   Wempe, MF
   Guin, S
   Khanna, M
   Meier, J
   Hoffman, B
   Owens, C
   Wysoczynski, CL
   Nitz, MD
   Knabe, WE
   Ahmed, M
   Brautigan, DL
   Paschal, BM
   Schwartz, MA
   Jones, DNM
   Ross, D
   Meroueh, SO
   Theodorescu, D
AF Yan, Chao
   Liu, Degang
   Li, Liwei
   Wempe, Michael F.
   Guin, Sunny
   Khanna, May
   Meier, Jeremy
   Hoffman, Brenton
   Owens, Charles
   Wysoczynski, Christina L.
   Nitz, Matthew D.
   Knabe, William E.
   Ahmed, Mansoor
   Brautigan, David L.
   Paschal, Bryce M.
   Schwartz, Martin A.
   Jones, David N. M.
   Ross, David
   Meroueh, Samy O.
   Theodorescu, Dan
TI Discovery and characterization of small molecules that target the GTPase Ral
SO NATURE
LA English
DT Article
ID activation; protein; effectors; reveals; pathway; bind; raia; sec5
AB The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis(1). Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and H-1-N-15 transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers.
C1 [Yan, Chao; Guin, Sunny; Owens, Charles; Theodorescu, Dan] Univ Colorado, Dept Surg, Aurora, CO 80045 USA.
   [Liu, Degang; Li, Liwei; Khanna, May; Knabe, William E.; Meroueh, Samy O.] Indiana Univ Sch Med, Dept Biochem, Indianapolis, IN 46202 USA.
   [Wempe, Michael F.; Ross, David] Univ Colorado, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
   [Meier, Jeremy; Hoffman, Brenton; Schwartz, Martin A.] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Wysoczynski, Christina L.; Jones, David N. M.; Theodorescu, Dan] Univ Colorado, Dept Pharmacol, Aurora, CO 80045 USA.
   [Nitz, Matthew D.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
   [Ahmed, Mansoor] Yale Univ, Dept Cardiol, New Haven, CT 06511 USA.
   [Ahmed, Mansoor; Schwartz, Martin A.] Yale Univ, Dept Cell Biol, New Haven, CT 06511 USA.
   [Paschal, Bryce M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
   [Meroueh, Samy O.] Indiana Univ Purdue Univ, Dept Chem & Chem Biol, Indianapolis, IN 46202 USA.
   [Theodorescu, Dan] Univ Colorado, Ctr Comprehens Canc, Aurora, CO 80045 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical Campus; Indiana University System; Indiana University Bloomington; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Virginia; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Virginia; Yale University; Yale University; University of Virginia; Purdue University System; Purdue University; Purdue University in Indianapolis; University of Colorado System; University of Colorado Anschutz Medical Campus
RP Theodorescu, D (corresponding author), Univ Colorado, Dept Surg, Aurora, CO 80045 USA.
EM dan.theodorescu@ucdenver.edu
FU NIH [CA091846, CA075115, CA104106, GM47214]; IUPUI Research Scholar Grant Foundation; American Cancer Society; Colorado Clinical and Translational Sciences Institute from the National Center for Research Resources, NIH [UL1TR001082]; National Cancer Institute [P30CA044579, R01CA075115, P30CA046934] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007635] Funding Source: NIH RePORTER
NR 34
TC 124
Z9 170
U1 3
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 NOV 20
PY 2014
VL 515
IS 7527
BP 443
EP +
DI 10.1038/nature13713
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600053
PM 25219851
DA 2026-03-09
ER

PT J
AU Gambino, F
   Pagès, S
   Kehayas, V
   Baptista, D
   Tatti, R
   Carleton, A
   Holtmaat, A
AF Gambino, Frederic
   Pages, Stephane
   Kehayas, Vassilis
   Baptista, Daniela
   Tatti, Roberta
   Carleton, Alan
   Holtmaat, Anthony
TI Sensory-evoked LTP driven by dendritic plateau potentials in vivo
SO NATURE
LA English
DT Article
ID long-term potentiation; rat barrel cortex; dependent plasticity; neural activity; nmda; spike; responses; neurons; depolarization; organization
AB Long-term synaptic potentiation (LTP) is thought to be a key process in cortical synaptic network plasticity and memory formation(1). Hebbian forms of LTPdependon strong postsynaptic depolarization, which in many models is generated by action potentials that propagate back from the soma into dendrites(2,3). However, local dendritic depolarization has been shown to mediate these forms of LTP as well(1,4,5). As pyramidal cells in supragranular layers of the somatosensory cortex spike infrequently(6-8), it is unclear which of the two mechanisms prevails for those cellsin vivo. Using whole-cell recordings in the mouse somatosensory cortexin vivo, we demonstrate that rhythmic sensory whisker stimulation efficiently induces synaptic LTP in layer 2/3 (L2/3) pyramidal cells in the absence of somatic spikes. The induction of LTP depended on the occurrence of NMDAR(N-methyl-D-aspartate receptor)-mediated long-lasting depolarizations, which bear similarities to dendritic plateau potentials(9-13). In addition, we show that whisker stimuli recruit synaptic networks that originate from the posteromedial complex of the thalamus (POm). Photostimulation of channelrhodopsin-2 expressing POm neurons generated NMDAR mediated plateau potentials, whereas the inhibition of POm activity during rhythmic whisker stimulation suppressed the generation of those potentials and prevented whisker-evoked LTP. Taken together, our data provide evidence for sensory-driven synaptic LTP in vivo, in the absence of somatic spiking. Instead, LTP is mediated by plateau potentials that are generated through the cooperative activity of lemniscal and paralemniscal synaptic circuitry(14-16).
C1 [Gambino, Frederic; Pages, Stephane; Kehayas, Vassilis; Baptista, Daniela; Tatti, Roberta; Carleton, Alan; Holtmaat, Anthony] Univ Geneva, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Gambino, Frederic; Pages, Stephane; Kehayas, Vassilis; Baptista, Daniela; Tatti, Roberta; Carleton, Alan; Holtmaat, Anthony] Univ Geneva, CMU, Ctr Neurosci, CH-1211 Geneva, Switzerland.
   [Kehayas, Vassilis; Tatti, Roberta] Leman Neurosci Doctoral Sch, CH-1211 Geneva, Switzerland.
C3 University of Geneva; University of Geneva
RP Holtmaat, A (corresponding author), Univ Geneva, Dept Basic Neurosci, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland.
EM anthony.holtmaat@unige.ch
FU Swiss National Science Foundation [31003A_120685, 31003A_135631, CRSI33_127289, 31003A_153410]; National Centre of Competence in Research (NCCR) SYNAPSY - Swiss National Science Foundation [51AU40_125759]; International Foundation for Research on Paraplegia; Hans Wilsdorf Foundation; SyMBaD (EU FP7-PEOPLE-ITN Marie Curie) [238608]; Swiss National Science Foundation (SNF) [CRSI33_127289, 31003A_153410, 31003A_120685, 31003A_135631] Funding Source: Swiss National Science Foundation (SNF)
NR 41
TC 193
Z9 224
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 NOV 6
PY 2014
VL 515
IS 7525
BP 116
EP +
DI 10.1038/nature13664
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500041
PM 25174710
DA 2026-03-09
ER

PT J
AU Choi, SH
   Kim, YH
   Hebisch, M
   Sliwinski, C
   Lee, S
   D'Avanzo, C
   Chen, HC
   Hooli, B
   Asselin, C
   Muffat, J
   Klee, JB
   Zhang, C
   Wainger, BJ
   Peitz, M
   Kovacs, DM
   Woolf, CJ
   Wagner, SL
   Tanzi, RE
   Kim, DY
AF Choi, Se Hoon
   Kim, Young Hye
   Hebisch, Matthias
   Sliwinski, Christopher
   Lee, Seungkyu
   D'Avanzo, Carla
   Chen, Hechao
   Hooli, Basavaraj
   Asselin, Caroline
   Muffat, Julien
   Klee, Justin B.
   Zhang, Can
   Wainger, Brian J.
   Peitz, Michael
   Kovacs, Dora M.
   Woolf, Clifford J.
   Wagner, Steven L.
   Tanzi, Rudolph E.
   Kim, Doo Yeon
TI A three-dimensional human neural cell culture model of Alzheimer's disease
SO NATURE
LA English
DT Article
ID transgenic mouse models; amyloid hypothesis; a-beta; tau; pathology; ipscs
AB Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-beta plaques and neurofibrillary tangles(1). The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-beta peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau(2,3). However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-beta-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology(4,5). Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-beta species and phosphorylated tau but did not demonstrate amyloid-beta plaquesor neurofibrillary tangles(6-11). Here we report that FAD mutations in beta-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-beta, including amyloid-beta plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloidb beta generation with beta- or gamma-secretase inhibitors not only decreased amyloid-beta pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-beta-mediated tau phosphorylation. We have successfully recapitulated amyloid-beta and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.
C1 [Choi, Se Hoon; Kim, Young Hye; Hebisch, Matthias; Sliwinski, Christopher; D'Avanzo, Carla; Chen, Hechao; Hooli, Basavaraj; Asselin, Caroline; Klee, Justin B.; Zhang, Can; Kovacs, Dora M.; Tanzi, Rudolph E.; Kim, Doo Yeon] Harvard Univ, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Genet & Aging Res Unit,Med Sch, Charlestown, MA 02129 USA.
   [Kim, Young Hye] Korea Basic Sci Inst, Div Mass Spectrometry Res, Cheongju 363883, Chungbuk, South Korea.
   [Hebisch, Matthias; Peitz, Michael] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany.
   [Hebisch, Matthias; Peitz, Michael] Hertie Fdn, D-53127 Bonn, Germany.
   [Lee, Seungkyu; Wainger, Brian J.; Woolf, Clifford J.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Lee, Seungkyu; Wainger, Brian J.; Woolf, Clifford J.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Muffat, Julien] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Wagner, Steven L.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Korea Basic Science Institute (KBSI); University of Bonn; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Whitehead Institute; University of California System; University of California San Diego
RP Kim, DY (corresponding author), Harvard Univ, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Genet & Aging Res Unit,Med Sch, Charlestown, MA 02129 USA.
EM tanzi@helix.mgh.harvard.edu; dkim@helix.mgh.harvard.edu
FU Cure Alzheimer's fund; national Institute of Health grants [5P01AG15379, 5R37MH060009]; NIH/NINDS [P30NS04776]; IBDG Grant [DK43351]; BADERC Award [DK57521]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01NS045860] Funding Source: NIH RePORTER; National Institute on Aging [P01AG015379] Funding Source: NIH RePORTER
NR 30
TC 912
Z9 1091
U1 3
U2 550
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 274
EP U293
DI 10.1038/nature13800
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400052
PM 25307057
DA 2026-03-09
ER

PT J
AU Pallotta, M
   Schnurbusch, T
   Hayes, J
   Hay, A
   Baumann, U
   Paull, J
   Langridge, P
   Sutton, T
AF Pallotta, Margaret
   Schnurbusch, Thorsten
   Hayes, Julie
   Hay, Alison
   Baumann, Ute
   Paull, Jeff
   Langridge, Peter
   Sutton, Tim
TI Molecular basis of adaptation to high soil boron in wheat landraces and elite cultivars
SO NATURE
LA English
DT Article
ID triticum-aestivum l.; toxicity tolerance; aegilops-tauschii; draft genome; barley; genes; identification; expression; evolution; software
AB Environmental constraints severely restrict crop yields inmost production environments, and expanding the use of variation will underpin future progress in breeding. In semi-arid environments boron toxicity constrains productivity, and genetic improvement is the only effective strategy for addressing the problem(1). Wheat breeders have sought and used available genetic diversity from landraces to maintain yield in these environments; however, the identity of the genes at the major tolerance loci was unknown. Here we describe the identification of near-identical, root-specific boron transporter genes underlying the two major-effect quantitative trait loci for boron tolerance in wheat, Bo1 and Bo4 (ref. 2). We show that tolerance to a high concentration of boron is associated with multiple genomic changes including tetraploid introgression, dispersed gene duplication, and variation in gene structure and transcript level. An allelic series was identified from a panel of bread and durum wheat cultivars and landraces originating from diverse agronomic zones. Our results demonstrate that, during selection, breeders have matched functionally different boron tolerance alleles to specific environments. The characterization of boron tolerance in wheat illustrates the power of the new wheat genomic resources to define key adaptive processes that have underpinned crop improvement.
C1 [Pallotta, Margaret; Schnurbusch, Thorsten; Hayes, Julie; Hay, Alison; Baumann, Ute; Langridge, Peter; Sutton, Tim] Univ Adelaide, Sch Agr Food & Wine, Australian Ctr Plant Funct Genom, Urrbrae, SA 5064, Australia.
   [Schnurbusch, Thorsten] Leibniz Inst Plant Genet & Crop Plant Res IPK, Genebank Dept, D-06466 Gatersleben, Germany.
   [Paull, Jeff] Univ Adelaide, Sch Agr Food & Wine, Urrbrae, SA 5064, Australia.
C3 Australian Centre for Plant Functional Genomics; Adelaide University; University of Adelaide; Leibniz Institut fur Pflanzengenetik und Kulturpflanzenforschung; Adelaide University; University of Adelaide
RP Sutton, T (corresponding author), Univ Adelaide, Sch Agr Food & Wine, Australian Ctr Plant Funct Genom, Waite Campus, Urrbrae, SA 5064, Australia.
EM tim.sutton@acpfg.com.au
FU Australian Research Council; Grains Research and Development Corporation; South Australian Government
NR 40
TC 85
Z9 88
U1 2
U2 141
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 2
PY 2014
VL 514
IS 7520
BP 88
EP +
DI 10.1038/nature13538
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800041
PM 25043042
DA 2026-03-09
ER

PT J
AU Popow, J
   Jurkin, J
   Schleiffer, A
   Martinez, J
AF Popow, Johannes
   Jurkin, Jennifer
   Schleiffer, Alexander
   Martinez, Javier
TI Analysis of orthologous groups reveals archease and DDX1 as tRNA splicing factors
SO NATURE
LA English
DT Article
ID 3,5-phosphodiester linkage; m(5)c methyltransferase; substrate-specificity; junction phosphate; sequence alignment; virus-replication; cell extract; ligase; proteins; complex
AB RNA ligases have essential roles in many cellular processes in eukaryotes, archaea and bacteria, including in RNA repair(1,2) and stress-induced splicing of messenger RNA(3). In archaea and eukaryotes, RNA ligases also have a role in transfer RNA splicing to generate functional tRNAs required for protein synthesis(4-7). We recently identified the human tRNA splicing ligase, a multimeric protein complex with RTCB (also known as HSPC117, C22orf28, FAAP and D10Wsu52e) as the essential subunit(8). The functions of the additional complex components ASW (also known as C2orf49), CGI-99 (also known as C14orf166), FAM98B and the DEAD-box helicase DDX1 in the context of RNA ligation have remained unclear. Taking advantage of clusters of eukaryotic orthologous groups, here we find that archease (ARCH; also known as ZBTB8OS), a protein of unknown function, is required for full activity of the human tRNA ligase complex and, in cooperation with DDX1, facilitates the formation of an RTCB-guanylate intermediate central to mammalian RNA ligation. Our findings define a role for DDX1 in the context of the human tRNA ligase complex and suggest that the widespread co-occurrence of archease and RtcB proteins implies evolutionary conservation of their functional interplay.
C1 [Popow, Johannes; Jurkin, Jennifer; Martinez, Javier] Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Popow, Johannes] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Schleiffer, Alexander] Res Inst Mol Pathol IMP, IMP IMBA Bioinformat Core Facil, A-1030 Vienna, Austria.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); European Molecular Biology Laboratory (EMBL); Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Martinez, J (corresponding author), Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
EM javier.martinez@imba.oeaw.ac.at
FU Fonds zur Forderung der wissenschaftlichen Forschung [P24687]; GEN-AU 3 research programme [820982]; Institute of Molecular Biotechnology of the Austrian Academy of Sciences; Austrian Science Fund (FWF) [W1207, P24687] Funding Source: Austrian Science Fund (FWF); Austrian Science Fund (FWF) [P 24687] Funding Source: researchfish
NR 36
TC 98
Z9 122
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 JUL 3
PY 2014
VL 511
IS 7507
BP 104
EP U508
DI 10.1038/nature13284
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400045
PM 24870230
DA 2026-03-09
ER

PT J
AU Nakada, D
   Oguro, H
   Levi, BP
   Ryan, N
   Kitano, A
   Saitoh, Y
   Takeichi, M
   Wendt, GR
   Morrison, SJ
AF Nakada, Daisuke
   Oguro, Hideyuki
   Levi, Boaz P.
   Ryan, Nicole
   Kitano, Ayumi
   Saitoh, Yusuke
   Takeichi, Makiko
   Wendt, George R.
   Morrison, Sean J.
TI Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy
SO NATURE
LA English
DT Article
ID receptor-alpha; bone-marrow; expression; progenitors; division; mice
AB Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones(1-6). An important question is whether stem cells also exhibit sex differences in physiological function and hormonal regulation in tissues that do not show sex-specific morphological differences. The terminal differentiation and function of some haematopoietic cells are regulated by sex hormones(7-10), but haematopoietic stem-cell function is thought to be similar in both sexes. Here we show that mouse haematopoietic stem cells exhibit sex differences in cell-cycle regulation by oestrogen. Haematopoietic stem cells in female mice divide significantly more frequently than in male mice. This difference depends on the ovaries but not the testes. Administration of oestradiol, a hormone produced mainly in the ovaries, increased haematopoietic stem-cell division in males and females. Oestrogen levels increased during pregnancy, increasing haematopoietic stem-cell division, haematopoietic stem-cell frequency, cellularity, and erythropoiesis in the spleen. Haematopoietic stem cells expressed high levels of oestrogen receptor-alpha (ER alpha). Conditional deletion of ER alpha from haematopoietic stem cells reduced haematopoietic stem-cell division in female, but not male, mice and attenuated the increases in haematopoietic stem-cell division, haematopoietic stem-cell frequency, and erythropoiesis during pregnancy. Oestrogen/ER alpha signalling promotes haematopoietic stem-cell self-renewal, expanding splenic haematopoietic stem cells and erythropoiesis during pregnancy.
C1 [Nakada, Daisuke; Ryan, Nicole; Kitano, Ayumi; Saitoh, Yusuke; Takeichi, Makiko] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Nakada, Daisuke] Baylor Coll Med, Stem Cells & Regenerat Med Ctr, Houston, TX 77030 USA.
   [Nakada, Daisuke] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
   [Oguro, Hideyuki; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dept Pediat, Dallas, TX 75390 USA.
   [Oguro, Hideyuki; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dallas, TX 75390 USA.
   [Levi, Boaz P.; Wendt, George R.] Univ Michigan, Ctr Stem Cell Biol, Inst Life Sci, Ann Arbor, MI 48109 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; 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 Michigan System; University of Michigan
RP Nakada, D (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM nakada@bcm.edu; Sean.Morrison@utsouthwestern.edu
FU Cancer Prevention and Research Institute of Texas; National Heart Lung and Blood Institute [HL097760]; Irvington Institute-Cancer Research Institute/Edmond J. Safra Memorial Fellowship; National Institutes of Health (NCRR) [S10RR024574, NIAID AI036211, NCI P30CA125123]; National Cancer Institute [P30CA125123] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008014] Funding Source: NIH RePORTER
NR 38
TC 320
Z9 377
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 JAN 23
PY 2014
VL 505
IS 7484
BP 555
EP +
DI 10.1038/nature12932
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000041
PM 24451543
DA 2026-03-09
ER

PT J
AU Wang, GJ
   Zhou, MF
   Goettel, JT
   Schrobilgen, GJ
   Su, J
   Li, J
   Schlöder, T
   Riedel, S
AF Wang, Guanjun
   Zhou, Mingfei
   Goettel, James T.
   Schrobilgen, Gary J.
   Su, Jing
   Li, Jun
   Schloeder, Tobias
   Riedel, Sebastian
TI Identification of an iridium-containing compound with a formal oxidation state of IX
SO NATURE
LA English
DT Article
ID basis-sets; infrared-spectra; spectroscopy; ion; energy; chemistry; molecule
AB One of the most important classifications in chemistry and within the periodic table is the concept of formal oxidation states(1-4). The preparation and characterization of compounds containing elements with unusual oxidation states is of great interest to chemists(5). The highest experimentally known formal oxidation state of any chemical element is at present VIII2-4, although higher oxidation states have been postulated(6,7). Compounds with oxidation state VIII include several xenon compounds(8) (for example XeO4 and XeO3F2) and the well-characterized species RuO4 and OsO4 (refs 2-4). Iridium, which has nine valence electrons, is predicted to have the greatest chance of being oxidized beyond the VIII oxidation state(1). In recent matrix-isolation experiments, the IrO4 molecule was characterized as an isolated molecule in rare-gas matrices(9). The valence electron configuration of iridium in IrO4 is 5d(1), with a formal oxidation state of VIII. Removal of the remaining d electron from IrO4 would lead to the iridium tetroxide cation ([IrO4](+)), which was recently predicted to be stable(10) and in which iridium is in a formal oxidation state of IX. There has been some speculation about the formation of [IrO4](+) species(11,12), but these experimental observations have not been structurally confirmed. Here we report the formation of [IrO4](+) and its identification by infrared photodissociation spectroscopy. Quantum-chemical calculations were carried out at the highest level of theory that is available today, and predict that the iridium tetroxide cation, with a T-d-symmetrical structure and a d(0) electron configuration, is the most stable of all possible [IrO4](+) isomers.
C1 [Wang, Guanjun; Zhou, Mingfei] Fudan Univ, Collaborat Innovat Ctr Chem Energy Mat, Shanghai Key Lab Mol Catalysts & Innovat Mat, Dept Chem, Shanghai 200433, Peoples R China.
   [Goettel, James T.; Schrobilgen, Gary J.] McMaster Univ, Dept Chem, Hamilton, ON L8S 4M1, Canada.
   [Su, Jing; Li, Jun] Tsinghua Univ, Dept Chem, Minist Educ, Beijing 100084, Peoples R China.
   [Su, Jing; Li, Jun] Tsinghua Univ, Key Lab Organ Optoelect & Mol Engn, Minist Educ, Beijing 100084, Peoples R China.
   [Schloeder, Tobias; Riedel, Sebastian] Univ Freiburg, Inst Anorgan & Analyt Chem, D-79104 Freiburg, Germany.
   [Riedel, Sebastian] Free Univ Berlin, Inst Chem & Biochem Anorgan Chem, D-14195 Berlin, Germany.
C3 Fudan University; McMaster University; Tsinghua University; Tsinghua University; University of Freiburg; Free University of Berlin
RP Zhou, MF (corresponding author), Fudan Univ, Collaborat Innovat Ctr Chem Energy Mat, Shanghai Key Lab Mol Catalysts & Innovat Mat, Dept Chem, Shanghai 200433, Peoples R China.
EM mfzhou@fudan.edu.cn; schrobil@mcmaster.ca; sriedel@psichem.de
FU Ministry of Science and Technology of China [2013CB834603, 2012YQ220113-3]; National Natural Science Foundation of China [21173053, 21433005, 91026003]; Committee of Science and Technology of Shanghai [13XD1400800]; Fonds der Chemischen Industrie; GRK [1582]; Natural Sciences and Engineering Research Council of Canada
NR 41
TC 163
Z9 183
U1 6
U2 380
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2014
VL 514
IS 7523
BP 475
EP +
DI 10.1038/nature13795
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900036
PM 25341786
DA 2026-03-09
ER

PT J
AU Parker, JL
   Newstead, S
AF Parker, Joanne L.
   Newstead, Simon
TI Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1
SO NATURE
LA English
DT Article
ID peptide transporters; crystal-structure; protein; mechanism; arabidopsis; system; chl1; overexpression; reconstitution; optimization
AB The NRT1/PTR family of proton-coupled transporters are responsible for nitrogen assimilation in eukaryotes and bacteria through the uptake of peptides. However, in most plant species members of this family have evolved to transport nitrate as well as additional secondary metabolites and hormones. In response to falling nitrate levels, NRT1.1 is phosphorylated on an intracellular threonine that switches the transporter from a low-affinity to high-affinity state. Here we present both the apo and nitrate-bound crystal structures of Arabidopsis thaliana NRT1.1, which together with in vitro binding and transport data identify a key role for His 356 in nitrate binding. Our data support a model whereby phosphorylation increases structural flexibility and in turn the rate of transport. Comparison with peptide transporters further reveal show the NRT1/PTR family has evolved to recognize diverse nitrogenous ligands, while maintaining elements of a conserved coupling mechanism within this superfamily of nutrient transporters.
C1 [Parker, Joanne L.; Newstead, Simon] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [Newstead, Simon] Rutherford Appleton Lab, Didcot OX11 0FA, Oxon, England.
C3 University of Oxford; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory
RP Parker, JL (corresponding author), Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
EM joanne.parker@bioch.ox.ac.uk; simon.newstead@bioch.ox.ac.uk
FU Medical Research Council (MRC) [G0900399]; Royal Society [RG110211, IE111401]; MRC [G0900399] Funding Source: UKRI; Medical Research Council [G0900399] Funding Source: researchfish; Wellcome Trust [102890/Z/13/Z] Funding Source: researchfish
NR 57
TC 320
Z9 372
U1 4
U2 309
PU NATURE PUBLISHING 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 6
PY 2014
VL 507
IS 7490
BP 68
EP +
DI 10.1038/nature13116
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400043
PM 24572366
DA 2026-03-09
ER

PT J
AU Sturm, S
   Köhler, F
   Zatorski, J
   Wagner, A
   Harman, Z
   Werth, G
   Quint, W
   Keitel, CH
   Blaum, K
AF Sturm, S.
   Koehler, F.
   Zatorski, J.
   Wagner, A.
   Harman, Z.
   Werth, G.
   Quint, W.
   Keitel, C. H.
   Blaum, K.
TI High-precision measurement of the atomic mass of the electron
SO NATURE
LA English
DT Article
ID magnetic-moment; ion
AB The quest for the value of the electron's atomic mass has been the subject of continuing efforts over the past few decades(1-4). Among the seemingly fundamental constants that parameterize the Standard Model of physics(5) and which are thus responsible for its predictive power, the electron mass m(e) is prominent, being responsible for the structure and properties of atoms and molecules. It is closely linked to other fundamental constants, such as the Rydberg constant R-infinity and the fine-structure constant alpha (ref. 6). However, the low mass of the electron considerably complicates its precise determination. Here we combine a very precise measurement of the magnetic moment of a single electron bound to a carbon nucleus with a state-of-the-art calculation in the framework of bound-state quantum electrodynamics. The precision of the resulting value for the atomic mass of the electron surpasses the current literature value of the Committee on Data for Science and Technology (CODATA(6)) by a factor of 13. This result lays the foundation for future fundamental physics experiments(7,8) and precision tests of the Standard Model(9-11).
C1 [Sturm, S.; Koehler, F.; Zatorski, J.; Wagner, A.; Harman, Z.; Keitel, C. H.; Blaum, K.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Koehler, F.; Quint, W.] GSI Helmholtzzentrum Schwerionenforschung, D-64291 Darmstadt, Germany.
   [Harman, Z.] ExtreMe Matter Inst EMMI, D-64291 Darmstadt, Germany.
   [Werth, G.] Johannes Gutenberg Univ Mainz, Inst Phys, D-55128 Mainz, Germany.
C3 Max Planck Society; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Johannes Gutenberg University of Mainz
RP Sturm, S (corresponding author), Max Planck Inst Kernphys, Saupfercheckweg 1, D-69117 Heidelberg, Germany.
EM sven.sturm@mpi-hd.mpg.de
FU Max Planck Society; EU (ERC) [290870]; IMPRS-QD; GSI; Helmholtz Alliance [HA216/EMMI]; European Research Council (ERC) [290870] Funding Source: European Research Council (ERC)
NR 27
TC 269
Z9 301
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 FEB 27
PY 2014
VL 506
IS 7489
BP 467
EP 470
DI 10.1038/nature13026
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100033
PM 24553144
DA 2026-03-09
ER

PT J
AU Harms, MJ
   Thornton, JW
AF Harms, Michael J.
   Thornton, Joseph W.
TI Historical contingency and its biophysical basis in glucocorticoid receptor evolution
SO NATURE
LA English
DT Article
ID molecular-dynamics; key innovation; force-field; protein; mutations; charmm; sites
AB Understanding how chance historical events shape evolutionary processes is a central goal of evolutionary biology(1-7). Direct insights into the extent and causes of evolutionary contingency have been limited to experimental systems(7-9), because it is difficult to know what happened in the deep past and to characterize other paths that evolution could have followed. Here we combine ancestral protein reconstruction, directed evolution and biophysical analysis to explore alternative 'might-have-been' trajectories during the ancient evolution of a novel protein function. We previously found that the evolution of cortisol specificity in the ancestral glucocorticoid receptor (GR) was contingent on permissive substitutions, which had no apparent effect on receptor function but were necessary for GR to tolerate the large-effect mutations that caused the shift in specificity(6). Here we show that alternative mutations that could have permitted the historical function-switching substitutions are extremely rare in the ensemble of genotypes accessible to the ancestral GR. In a library of thousands of variants of the ancestral protein, we recovered historical permissive substitutions but no alternative permissive genotypes. Using biophysical analysis, we found that permissive mutations must satisfy at least three physical requirements-they must stabilize specific local elements of the protein structure, maintain the correct energetic balance between functional conformations, and be compatible with the ancestral and derived structures-thus revealing why permissive mutations are rare. These findings demonstrate that GR evolution depended strongly on improbable, non-deterministic events, and this contingency arose from intrinsic biophysical properties of the protein.
C1 [Harms, Michael J.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA.
   [Harms, Michael J.] Univ Oregon, Dept Chem & Biochem, Eugene, OR 97403 USA.
   [Harms, Michael J.; Thornton, Joseph W.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Harms, Michael J.; Thornton, Joseph W.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Thornton, Joseph W.] Univ Oregon, Inst Ecol & Evolut, Eugene, OR 97403 USA.
C3 University of Oregon; University of Oregon; University of Chicago; University of Chicago; University of Oregon
RP Thornton, JW (corresponding author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
EM joet1@uchicago.edu
FU National Institutes of Health (NIH) [F32-GM090650, NIH R01-GM081592, R01-GM104397]; NSF [IOB-0546906]; Howard Hughes Medical Institute Early Career Scientist award
NR 48
TC 116
Z9 152
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 AUG 14
PY 2014
VL 512
IS 7513
BP 203
EP +
DI 10.1038/nature13410
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700034
PM 24930765
DA 2026-03-09
ER

PT J
AU Audet, P
   Bürgmann, R
AF Audet, Pascal
   Buergmann, Roland
TI Possible control of subduction zone slow-earthquake periodicity by silica enrichment
SO NATURE
LA English
DT Article
ID non-volcanic tremor; new-zealand; northern cascadia; episodic tremor; southern mexico; km depth; slip; quartz; velocity; crustal
AB Seismic and geodetic observations in subduction zone forearcs indicate that slow earthquakes, including episodic tremor and slip, recur at intervals of less than six months to more than two years(1,2). In Cascadia, slow slip is segmented along strike(3) and tremor data show a gradation from large, infrequent slip episodes to small, frequent slip events with increasing depth of the plate interface(4). Observations(5-7) and models(8,9) of slow slip and tremor require the presence of near-lithostatic pore-fluid pressures in slow-earthquake source regions; however, direct evidence of factors controlling the variability in recurrence times is elusive. Here we compile seismic data from subduction zone forearcs exhibiting recurring slow earthquakes and show that the average ratio of compressional (P)-wave velocity to shear (S)-wave velocity (v(P)/v(S)) of the overlying forearc crust ranges between 1.6 and 2.0 and is linearly related to the average recurrence time of slow earthquakes. In northern Cascadia, forearc v(P)/v(S) values decrease with increasing depth of the plate interface and with decreasing tremor-episode recurrence intervals. Low v(P)/v(S) values require a large addition of quartz in a mostly mafic forearc environment(10,11). We propose that silica enrichment varying from 5 per cent to 15 per cent by volume from slab-derived fluids and upward mineralization in quartz veins(12) can explain the range of observed v(P)/v(S) values as well as the downdip decrease in v(P)/v(S). The solubility of silica depends on temperature(13), and deposition prevails near the base of the forearc crust(11). We further propose that the strong temperature dependence of healing and permeability reduction in silica-rich fault gouge via dissolution-precipitation creep(14) can explain the reduction in tremor recurrence time with progressive silica enrichment. Lower gouge permeability at higher temperatures leads to faster fluid overpressure development and low effective fault-normal stress, and therefore shorter recurrence times. Our results also agree with numerical models of slip stabilization under fault zone dilatancy strengthening(15) caused by decreasing fluid pressure as pore space increases. This implies that temperature-dependent silica deposition, permeability reduction and fluid overpressure development control dilatancy and slow-earthquake behaviour.
C1 [Audet, Pascal] Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
   [Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Buergmann, Roland] Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
C3 University of Ottawa; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Audet, P (corresponding author), Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
EM pascal.audet@uottawa.ca
FU Natural Science and Engineering Research Council (Canada); Miller Institute for Basic Research in Science (University of California, Berkeley)
NR 41
TC 184
Z9 207
U1 1
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 JUN 19
PY 2014
VL 510
IS 7505
BP 389
EP +
DI 10.1038/nature13391
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200033
PM 24943955
DA 2026-03-09
ER

PT J
AU Lingaraju, GM
   Bunker, RD
   Cavadini, S
   Hess, D
   Hassiepen, U
   Renatus, M
   Fischer, ES
   Thomä, NH
AF Lingaraju, Gondichatnahalli M.
   Bunker, Richard D.
   Cavadini, Simone
   Hess, Daniel
   Hassiepen, Ulrich
   Renatus, Martin
   Fischer, Eric S.
   Thomae, Nicolas H.
TI Crystal structure of the human COP9 signalosome
SO NATURE
LA English
DT Article
ID pci domain; nedd8 modification; arabidopsis cop9; architecture; complex; initiation; subunit; protein; model; activation
AB Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin-RINGE3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn2+-dependent isopeptidase that is inactive in isolation. Here we present the crystal structure of the entire similar to 350-kDa human CSN holoenzyme at 3.8 angstrom resolution, detailing the molecular architecture of the complex. CSN has two organizational centres: a horseshoe-shaped ring created by its six proteasome lid-CSN-initiation factor 3 (PCI) domain proteins, and a large bundle formed by the carboxy-terminal a-helices of every subunit. CSN5 and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase.
C1 [Lingaraju, Gondichatnahalli M.; Bunker, Richard D.; Cavadini, Simone; Hess, Daniel; Fischer, Eric S.; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Lingaraju, Gondichatnahalli M.; Bunker, Richard D.; Cavadini, Simone; Fischer, Eric S.; Thomae, Nicolas H.] Univ Basel, CH-4003 Basel, Switzerland.
   [Hassiepen, Ulrich; Renatus, Martin] Novartis Pharma AG, Inst Biomed Res, CH-4056 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Novartis; Universita della Svizzera Italiana
RP Thomä, NH (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM nicolas.thoma@fmi.ch
FU Novartis Research Foundation; Swiss National Science Foundation [31003A_144020]; European Research Council (MoBa-CS) [260481]; Novartis (NIBR); Swiss National Science Foundation (SNF) [31003A_144020] Funding Source: Swiss National Science Foundation (SNF); European Research Council (ERC) [260481] Funding Source: European Research Council (ERC)
NR 72
TC 183
Z9 213
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 AUG 14
PY 2014
VL 512
IS 7513
BP 161
EP +
DI 10.1038/nature13566
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700024
PM 25043011
DA 2026-03-09
ER

PT J
AU Ryan, KK
   Tremaroli, V
   Clemmensen, C
   Kovatcheva-Datchary, P
   Myronovych, A
   Karns, R
   Wilson-Pérez, HE
   Sandoval, DA
   Kohli, R
   Bäckhed, F
   Seeley, RJ
AF Ryan, Karen K.
   Tremaroli, Valentina
   Clemmensen, Christoffer
   Kovatcheva-Datchary, Petia
   Myronovych, Andriy
   Karns, Rebekah
   Wilson-Perez, Hilary E.
   Sandoval, Darleen A.
   Kohli, Rohit
   Backhed, Fredrik
   Seeley, Randy J.
TI FXR is a molecular target for the effects of vertical sleeve gastrectomy
SO NATURE
LA English
DT Article
ID farnesoid-x-receptor; y gastric bypass; bile-acid metabolism; human gut microbiota; insulin-sensitivity; weight-loss; bariatric surgery; high-fat; glucose-homeostasis; improves glucose
AB Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.
C1 [Ryan, Karen K.; Clemmensen, Christoffer; Wilson-Perez, Hilary E.; Sandoval, Darleen A.; Seeley, Randy J.] Univ Cincinnati, Div Endocrinol Diabet & Metab, Dept Internal Med, Cincinnati, OH 45237 USA.
   [Tremaroli, Valentina; Kovatcheva-Datchary, Petia; Backhed, Fredrik] Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, S-41345 Gothenburg, Sweden.
   [Tremaroli, Valentina; Kovatcheva-Datchary, Petia; Backhed, Fredrik] Univ Gothenburg, Sahlgrenska Ctr Cardiovasc & Metab Res, S-41345 Gothenburg, Sweden.
   [Clemmensen, Christoffer] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark.
   [Myronovych, Andriy; Kohli, Rohit] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol Hepatol & Nutr, Dept Pediat, Cincinnati, OH 45229 USA.
   [Karns, Rebekah] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
   [Backhed, Fredrik] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Receptol & Enteroendocrinol, Fac Hlth Sci, DK-2200 Copenhagen, Denmark.
C3 University System of Ohio; University of Cincinnati; University of Gothenburg; University of Gothenburg; University of Copenhagen; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Novo Nordisk Foundation; University of Copenhagen
RP Seeley, RJ (corresponding author), Univ Cincinnati, Div Endocrinol Diabet & Metab, Dept Internal Med, Cincinnati, OH 45237 USA.
EM randy.seeley@uc.edu
FU UNIK Food Fitness and Pharma for Health and Disease research programme; Torsten Soderberg foundation; NovoNordisk foundation; Ethicon Endo-Surgery; NIH [DK082173, HL111319, DK093848]; NIH (Bioinformatics Core of the Digestive Disease Research Core Center in Cincinnati) [DK078392]; Novo Nordisk Fonden [NNF13OC0008163] Funding Source: researchfish; National Center for Advancing Translational Sciences [UL1TR001425] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK078392] Funding Source: NIH RePORTER
NR 54
TC 762
Z9 879
U1 2
U2 145
PU NATURE PUBLISHING 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 8
PY 2014
VL 509
IS 7499
BP 183
EP +
DI 10.1038/nature13135
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300030
PM 24670636
DA 2026-03-09
ER

PT J
AU Schulz, MD
   Atay, Ç
   Heringer, J
   Romrig, FK
   Schwitalla, S
   Aydin, B
   Ziegler, PK
   Varga, J
   Reindl, W
   Pommerenke, C
   Salinas-Riester, G
   Böck, A
   Alpert, C
   Blaut, M
   Polson, SC
   Brandl, L
   Kirchner, T
   Greten, FR
   Polson, SW
   Arkan, MC
AF Schulz, Manon D.
   Atay, Cigdem
   Heringer, Jessica
   Romrig, Franziska K.
   Schwitalla, Sarah
   Aydin, Begum
   Ziegler, Paul K.
   Varga, Julia
   Reindl, Wolfgang
   Pommerenke, Claudia
   Salinas-Riester, Gabriela
   Boeck, Andreas
   Alpert, Carl
   Blaut, Michael
   Polson, Sara C.
   Brandl, Lydia
   Kirchner, Thomas
   Greten, Florian R.
   Polson, Shawn W.
   Arkan, Melek C.
TI High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity
SO NATURE
LA English
DT Article
ID microbial ecology; gut; innate; inflammation; metabolism; interface; sequences; cells
AB Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known risk factors for gastrointestinal cancers(1). There is substantial evidence suggesting that diet markedly affects the composition of the intestinal microbiota(2). Moreover, there is now unequivocal evidence linking dysbiosis to cancer development(3). However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-ras(G12Dint), mice independently of obesity. HFD consumption, in conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed K-ras(G12Dint) mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal tumours to healthy adult K-ras(G12Dint) mice was sufficient to transmit disease in the absence of an HFD. Furthermore, treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest that tumorigenesis is transmissible among genetically predisposed individuals.
C1 [Schulz, Manon D.; Atay, Cigdem; Heringer, Jessica; Romrig, Franziska K.; Schwitalla, Sarah; Arkan, Melek C.] Tech Univ Munich, Inst Mol Immunol, Klinikum Rechts Isar, D-81675 Munich, Germany.
   [Aydin, Begum] Bogazici Univ, Dept Mol Biol & Genet, TR-34342 Istanbul, Turkey.
   [Ziegler, Paul K.; Varga, Julia; Greten, Florian R.] Georg Speyer Haus, Inst Tumor Biol & Expt Therapy, D-60596 Frankfurt, Germany.
   [Ziegler, Paul K.; Varga, Julia; Kirchner, Thomas; Greten, Florian R.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
   [Ziegler, Paul K.; Varga, Julia; Kirchner, Thomas; Greten, Florian R.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Reindl, Wolfgang] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Internal Med 2, D-68167 Mannheim, Germany.
   [Pommerenke, Claudia; Salinas-Riester, Gabriela] Univ Med Ctr Gottingen, Microarray & Deep Sequencing Core Facil, D-37077 Gottingen, Germany.
   [Boeck, Andreas] Tech Univ Munich, Inst Math Stat, D-81675 Munich, Germany.
   [Alpert, Carl; Blaut, Michael] German Inst Human Nutr Potsdam Rehbrucke, Dept Gastrointestinal Microbiol, D-14558 Nuthetal, Germany.
   [Polson, Sara C.; Polson, Shawn W.] Univ Delaware, Delaware Biotechnol Inst, Ctr Bioinformat & Computat Biol, Newark, DE 19711 USA.
   [Brandl, Lydia; Kirchner, Thomas] Univ Munich, Inst Pathol, D-80337 Munich, Germany.
C3 Technical University of Munich; Bogazici University; Octapharma; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; University of Gottingen; University of Gottingen Hospital; Technical University of Munich; Leibniz Association; Deutsches Institut fur Ernahrungsforschung Potsdam-Rehbrucke (DIfE); University of Delaware; University of Munich
RP Arkan, MC (corresponding author), Tech Univ Munich, Inst Mol Immunol, Klinikum Rechts Isar, D-81675 Munich, Germany.
EM canan.arkan@lrz.tum.de
FU LOEWE Center for Cell and Gene Therapy Frankfurt (CGT) [III L 4-518/17.004]; Georg-Speyer-Haus; Deutsche Forschungsgemeinschaft (DFG) [Gr1916/5-1]; Deutsche Krebshilfe [108872, 107977]; ERC [ROSCAN-281967]; US National Institutes of Health National Institute of General Medical Sciences [8 P20 GM103446-12]; US National Science Foundation EPSCoR [EPS-081425]; DFG [AR710/2-1]; National Institute of General Medical Sciences [P20GM103446] Funding Source: NIH RePORTER; Academy of Finland (AKA) [107977] Funding Source: Academy of Finland (AKA)
NR 37
TC 368
Z9 440
U1 2
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 OCT 23
PY 2014
VL 514
IS 7523
BP 508
EP +
DI 10.1038/nature13398
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900044
PM 25174708
DA 2026-03-09
ER

PT J
AU Sakai, N
   Sakai, T
   Hirota, T
   Watanabe, Y
   Ceccarelli, C
   Kahane, C
   Bottinelli, S
   Caux, E
   Demyk, K
   Vastel, C
   Coutens, A
   Taquet, V
   Ohashi, N
   Takakuwa, S
   Yen, HW
   Aikawa, Y
   Yamamoto, S
AF Sakai, Nami
   Sakai, Takeshi
   Hirota, Tomoya
   Watanabe, Yoshimasa
   Ceccarelli, Cecilia
   Kahane, Claudine
   Bottinelli, Sandrine
   Caux, Emmanuel
   Demyk, Karine
   Vastel, Charlotte
   Coutens, Audrey
   Taquet, Vianney
   Ohashi, Nagayoshi
   Takakuwa, Shigehisa
   Yen, Hsi-Wei
   Aikawa, Yuri
   Yamamoto, Satoshi
TI Change in the chemical composition of infalling gas forming a disk around a protostar
SO NATURE
LA English
DT Article
ID carbon-chain molecules; prestellar; mass; emission; shocks; phase; core
AB IRAS 04368+2557 is a solar-type (low-mass) protostar embedded in a protostellar core (L1527) in the Taurus molecular cloud(1,2), which is only 140 parsecs away from Earth, making it the closest large star-forming region. The protostellar envelope has a flattened shape with a diameter of a thousand astronomical units (1 AU is the distance from Earth to the Sun), and is infalling and rotating(3-5). It also has a protostellar disk with a radius of 90 AU (ref. 6), from which a planetary system is expected to form(7,8). The interstellar gas, mainly consisting of hydrogen molecules, undergoes a change in density of about three orders of magnitude as it collapses from the envelope into the disk, while being heated from 10 kelvin to over 100 kelvin in the mid-plane, but it has hitherto not been possible to explore changes in chemical composition associated with this collapse. Here we report that the unsaturated hydrocarbon molecule cyclic-C3H2 resides in the infalling rotating envelope, whereas sulphur monoxide (SO) is enhanced in the transition zone at the radius of the centrifugal barrier (100 +/- 20 AU), which is the radius at which the kinetic energy of the infalling gas is converted to rotational energy. Such a drastic change in chemistry at the centrifugal barrier was not anticipated, but is probably caused by the discontinuous infalling motion at the centrifugal barrier and local heating processes there.
C1 [Sakai, Nami; Watanabe, Yoshimasa; Yamamoto, Satoshi] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130033, Japan.
   [Sakai, Takeshi] Univ Electrocommun, Dept Commun Engn & Informat, Chofu, Tokyo 1828585, Japan.
   [Hirota, Tomoya] Natl Astron Observ Japan, Mitaka, Tokyo 1818588, Japan.
   [Ceccarelli, Cecilia; Kahane, Claudine] Inst Planetol & Astrophys Grenoble, F-38041 Grenoble 9, France.
   [Bottinelli, Sandrine; Caux, Emmanuel; Demyk, Karine; Vastel, Charlotte] Univ Toulouse 3, Observ Midi Pyrenees, Univ Toulouse, IRAP, F-31062 Toulouse, France.
   [Bottinelli, Sandrine; Caux, Emmanuel; Demyk, Karine; Vastel, Charlotte] CNRS, IRAP, F-31028 Toulouse 4, France.
   [Coutens, Audrey] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Osterbro, Denmark.
   [Coutens, Audrey] Univ Copenhagen, Ctr Star & Planet Format, DK-1350 Copenhagen K, Denmark.
   [Coutens, Audrey] Univ Copenhagen, Nat Hist Museum Denmark, DK-1350 Copenhagen K, Denmark.
   [Taquet, Vianney] NASA, Goddard Space Flight Ctr, Astrochem Lab, Greenbelt, MD 20771 USA.
   [Ohashi, Nagayoshi; Yen, Hsi-Wei] Acad Sinica, Inst Astron & Astrophys, Taipei 10617, Taiwan.
   [Ohashi, Nagayoshi] Natl Astron Observ Japan, Subaru Telescope, Hilo, HI 96720 USA.
   [Takakuwa, Shigehisa; Yen, Hsi-Wei] Natl Taiwan Univ, Inst Astrophys, Taipei 10617, Taiwan.
   [Aikawa, Yuri] Kobe Univ, Dept Earth & Planetary Sci, Kobe, Hyogo 6578501, Japan.
C3 University of Tokyo; University of Electro-Communications - Japan; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); 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); University of Copenhagen; Niels Bohr Institute; University of Copenhagen; University of Copenhagen; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Academia Sinica - Taiwan; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); National Taiwan University; Kobe University
RP Sakai, N (corresponding author), Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130033, Japan.
EM nami@taurus.phys.s.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technologies of Japan [21224002, 25400223, 25108005, 24684011]; JSPS; MAEE under the Japan-France integrated action programme (SAKURA); French Agence Nationale pour la Recherche (ANR) project FORCOMS [ANR-08-BLAN-0225]; Partenariats Hubert Curien (PHC) Programme SAKURA [25765VC]; Grants-in-Aid for Scientific Research [21224002, 24684011, 23540266, 23103004, 25108004, 25108005] Funding Source: KAKEN
NR 28
TC 226
Z9 241
U1 0
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 6
PY 2014
VL 507
IS 7490
BP 78
EP +
DI 10.1038/nature13000
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400045
PM 24522533
DA 2026-03-09
ER

PT J
AU Luksza, M
   Lässig, M
AF Luksza, Marta
   Laessig, Michael
TI A predictive fitness model for influenza
SO NATURE
LA English
DT Article
ID evolutionary dynamics; linked glycosylation; beneficial mutations; clonal interference; seasonal influenza; receptor-binding; antigenic sites; a h3n2; hemagglutinin; selection
AB The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.
C1 [Luksza, Marta; Laessig, Michael] Univ Cologne, Inst Theoret Phys, D-50937 Cologne, Germany.
   [Luksza, Marta] Columbia Univ, Fairchild Ctr 607D, New York, NY 10027 USA.
C3 University of Cologne; Columbia University
RP Lässig, M (corresponding author), Univ Cologne, Inst Theoret Phys, Zulpicher Str 77, D-50937 Cologne, Germany.
FU Deutsche Forschungsgemeinschaft [SFB 680]; German Federal Ministry of Education and Research [0315893-Sybacol]; National Science Foundation [PHY05-51164]
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NR 58
TC 303
Z9 377
U1 1
U2 112
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2014
VL 507
IS 7490
BP 57
EP +
DI 10.1038/nature13087
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400041
PM 24572367
DA 2026-03-09
ER

PT J
AU Burov, E
   Gerya, T
AF Burov, Evgueni
   Gerya, Taras
TI Asymmetric three-dimensional topography over mantle plumes
SO NATURE
LA English
DT Article
ID dynamic topography; flood basalts; continental lithosphere; surface-topography; temperature; instability; transition; convection; rheology; africa
AB The role of mantle-lithosphere interactions in shaping surface topography has long been debated(1-3). In general(3,4), it is supposed that mantle plumes and vertical mantle flows result in axisymmetric, long-wavelength topography, which strongly differs from the generally asymmetric short-wavelength topography created by intraplate tectonic forces. However, identification of mantle-induced topography is difficult(3), especially in the continents(5). It can be argued therefore that complex brittle-ductile rheology and stratification of the continental lithosphere result in short-wavelength modulation and localization of deformation induced by mantle flow(6). This deformation should also be affected by far-field stresses and, hence, interplay with the 'tectonic' topography (for example, in the 'active/passive' rifting scenario(7,8)). Testing these ideas requires fully coupled three-dimensional numerical modelling of mantle-lithosphere interactions, which so far has not been possible owing to the conceptual and technical limitations of earlier approaches. Here we present new, ultra-high-resolution, three-dimensional numerical experiments on topography over mantle plumes, incorporating a weakly pre-stressed (ultra-slow spreading), rheologically realistic lithosphere. The results show complex surface evolution, which is very different from the smooth, radially symmetric patterns usually assumed as the canonical surface signature of mantle upwellings(9). In particular, the topography exhibits strongly asymmetric, small-scale, three-dimensional features, which include narrow and wide rifts, flexural flank uplifts and fault structures. This suggests a dominant role for continental rheological structure and intra-plate stresses in controlling dynamic topography, mantle-lithosphere interactions, and continental break-up processes above mantle plumes.
C1 [Burov, Evgueni] Univ Paris 06, Sorbonne Univ, UMR 7193, Inst Sci Terre Paris ISTeP, F-75005 Paris, France.
   [Burov, Evgueni] CNRS, UMR 7193, Inst Sci Terre Paris ISTeP, F-75005 Paris, France.
   [Gerya, Taras] ETH, CH-8092 Zurich, Switzerland.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Burov, E (corresponding author), Univ Paris 06, Sorbonne Univ, UMR 7193, Inst Sci Terre Paris ISTeP, F-75005 Paris, France.
EM evgenii.burov@upmc.fr
FU Advanced ERC grant RHEOLITH; INSU-CNRS; UPMC Invited Professor grant; ETH Invited Professor grant
NR 45
TC 176
Z9 193
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 SEP 4
PY 2014
VL 513
IS 7516
BP 85
EP +
DI 10.1038/nature13703
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800035
PM 25186903
DA 2026-03-09
ER

PT J
AU Johnston, DT
   Gill, BC
   Masterson, A
   Beirne, E
   Casciotti, KL
   Knapp, AN
   Berelson, W
AF Johnston, D. T.
   Gill, B. C.
   Masterson, A.
   Beirne, E.
   Casciotti, K. L.
   Knapp, A. N.
   Berelson, W.
TI Placing an upper limit on cryptic marine sulphur cycling
SO NATURE
LA English
DT Article
ID bacterial sulfate reduction; oxygen isotopic composition; pore-water sulfate; organic-matter; deep biosphere; stable sulfur; fractionation; nitrate; denitrification; rates
AB A quantitative understanding of sources and sinks of fixed nitrogen in low-oxygen waters is required to explain the role of oxygen-minimum zones (OMZs) in controlling the fixed nitrogen inventory of the global ocean. Apparent imbalances in geochemical nitrogen budgets(1) have spurred numerous studies to measure the contributions of heterotrophic and autotrophic N-2-producing metabolisms(denitrification and anaerobic ammonia oxidation, respectively)(2,3). Recently, 'cryptic' sulphur cycling was proposed as a partial solution to the fundamental biogeochemical problem of closing marine fixed-nitrogen budgets in intensely oxygen-deficient regions(4). The degree to which the cryptic sulphur cycle can fuel a loss of fixed nitrogen in the modern ocean requires the quantification of sulphur recycling in OMZ settings. Here we provide a new constraint for OMZ sulphate reduction based on isotopic profiles of oxygen (O-18/O-16) and sulphur (S-33/S-32, S-34/S-32) in seawater sulphate through oxygenated open-ocean and OMZ-bearing water columns. When coupled with observations and models of sulphate isotope dynamics and data-constrained model estimates of OMZ water-mass residence time, we find that previous estimates for sulphur-driven remineralization and loss of fixed nitrogen from the oceans are near the upper limit for what is possible given in situ sulphate isotope data.
C1 [Johnston, D. T.; Masterson, A.; Beirne, E.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Gill, B. C.] Virginia Tech Univ, Dept Geosci, Blacksburg, VA 24061 USA.
   [Casciotti, K. L.] Stanford Univ, Dept Environm Earth Syst Sci, Stanford, CA 94305 USA.
   [Knapp, A. N.] Florida State Univ, Dept Earth Ocean & Atmospher Sci, Tallahassee, FL 32306 USA.
   [Berelson, W.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
C3 Harvard University; Virginia Polytechnic Institute & State University; Stanford University; State University System of Florida; Florida State University; University of Southern California
RP Johnston, DT (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
EM johnston@eps.harvard.edu
FU National Science Foundation (NSF) Division of Ocean Sciences; Harvard University; Agouron Institute; NSF EAR-I/F; NSF/OCE [1140404, 0850905]; Division Of Ocean Sciences; Directorate For Geosciences [0850905, 1140404] Funding Source: National Science Foundation
NR 55
TC 91
Z9 106
U1 2
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 SEP 25
PY 2014
VL 513
IS 7519
BP 530
EP +
DI 10.1038/nature13698
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800036
PM 25209667
DA 2026-03-09
ER

PT J
AU Nguyen, C
   Haushalter, RW
   Lee, DJ
   Markwick, PRL
   Bruegger, J
   Caldara-Festin, G
   Finzel, K
   Jackson, DR
   Ishikawa, F
   O'Dowd, B
   McCammon, JA
   Opella, SJ
   Tsai, SC
   Burkart, MD
AF Chi Nguyen
   Haushalter, Robert W.
   Lee, D. John
   Markwick, Phineus R. L.
   Bruegger, Joel
   Caldara-Festin, Grace
   Finzel, Kara
   Jackson, David R.
   Ishikawa, Fumihiro
   O'Dowd, Bing
   McCammon, J. Andrew
   Opella, Stanley J.
   Tsai, Shiou-Chuan
   Burkart, Michael D.
TI Trapping the dynamic acyl carrier protein in fatty acid biosynthesis
SO NATURE
LA English
DT Article
ID escherichia-coli; structural insights; synthase; complex; dehydratase; reveal; crystallization; inhibition; binding; domain
AB Acyl carrier protein (ACP) transports the growing fatty acid chain between enzymatic domains of fatty acid synthase (FAS) during biosynthesis(1). Because FAS enzymes operate on ACP-bound acyl groups, ACP must stabilize and transport the growing lipid chain(2). ACPs have a central role in transporting starting materials and intermediates throughout the fatty acid biosynthetic pathway(3-5). The transient nature of ACP-enzyme interactions impose major obstacles to obtaining high-resolution structural information about fatty acid biosynthesis, and a new strategy is required to study protein-protein interactions effectively. Here we describe the application of a mechanism-based probe that allows active site-selective covalent crosslinking of AcpP to FabA, the Escherichia coli ACP and fatty acid 3-hydroxyacyl-ACP dehydratase, respectively. We report the 1.9 angstrom crystal structure of the crosslinked AcpP-FabA complex as a homodimer in which AcpP exhibits two different conformations, representing probable snapshots of ACP in action: the 4'-phosphopantetheine group of AcpP first binds an arginine-rich groove of FabA, then an AcpP helical conformational change locks AcpP and FabA in place. Residues at the interface of AcpP and FabA are identified and validated by solution nuclear magnetic resonance techniques, including chemical shift perturbations and residual dipolar coupling measurements. These not only support our interpretation of the crystal structures but also provide an animated view of ACP in action during fatty acid dehydration. These techniques, in combination with molecular dynamics simulations, show for the first time that FabA extrudes the sequestered acyl chain from the ACP binding pocket before dehydration by repositioning helix III. Extensive sequence conservation among carrier proteins suggests that the mechanistic insights gleaned from our studies may be broadly applicable to fatty acid, polyketide and non-ribosomal biosynthesis. Here the foundation is laid for defining the dynamic action of carrier-protein activity in primary and secondary metabolism, providing insight into pathways that can have major roles in the treatment of cancer, obesity and infectious disease.
C1 [Chi Nguyen; Bruegger, Joel; Caldara-Festin, Grace; Jackson, David R.; Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
   [Chi Nguyen; Bruegger, Joel; Caldara-Festin, Grace; Jackson, David R.; Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
   [Chi Nguyen; Bruegger, Joel; Caldara-Festin, Grace; Jackson, David R.; Tsai, Shiou-Chuan] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA.
   [Haushalter, Robert W.; Lee, D. John; Markwick, Phineus R. L.; Finzel, Kara; Ishikawa, Fumihiro; O'Dowd, Bing; McCammon, J. Andrew; Opella, Stanley J.; Burkart, Michael D.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Markwick, Phineus R. L.] San Diego Supercomp Ctr, La Jolla, CA 92093 USA.
   [Markwick, Phineus R. L.; McCammon, J. Andrew] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 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; University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Burkart, MD (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM sctsai@uci.edu; mburkart@ucsd.edu
FU Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; NSF; NIH; HHMI; Advanced Light Source; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231];  [GM100305];  [GM095970]; Grants-in-Aid for Scientific Research [24810015] Funding Source: KAKEN; National Institute of General Medical Sciences [R01GM095970] Funding Source: NIH RePORTER; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1020765] Funding Source: National Science Foundation
NR 30
TC 218
Z9 284
U1 2
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 16
PY 2014
VL 505
IS 7483
BP 427
EP 431
DI 10.1038/nature12810
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800048
PM 24362570
DA 2026-03-09
ER

PT J
AU Walz, S
   Lorenzin, F
   Morton, J
   Wiese, KE
   von Eyss, B
   Herold, S
   Rycak, L
   Dumay-Odelot, H
   Karim, S
   Bartkuhn, M
   Roels, F
   Wüstefeld, T
   Fischer, M
   Teichmann, M
   Zender, L
   Wei, CL
   Sansom, O
   Wolf, E
   Eilers, M
AF Walz, Susanne
   Lorenzin, Francesca
   Morton, Jennifer
   Wiese, Katrin E.
   von Eyss, Bjoern
   Herold, Steffi
   Rycak, Lukas
   Dumay-Odelot, Helene
   Karim, Saadia
   Bartkuhn, Marek
   Roels, Frederik
   Wuestefeld, Torsten
   Fischer, Matthias
   Teichmann, Martin
   Zender, Lars
   Wei, Chia-Lin
   Sansom, Owen
   Wolf, Elmar
   Eilers, Martin
TI Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles
SO NATURE
LA English
DT Article
ID c-myc; transcription; promoter; binding; genome; dna; association; integration; induction; cells
AB In mammalian cells, the MYC oncoprotein binds to thousands of promoters(1-4). During mitogenic stimulation of primary lymphocytes, MYC promotes an increase in the expression of virtually all genes(1). In contrast, MYC-driven tumour cells differ from normal cells in the expression of specific sets of up-and downregulated genes that have considerable prognostic value(5-7). To understand this discrepancy, we studied the consequences of inducible expression and depletion of MYC in human cells and murine tumour models. Changes in MYC levels activate and repress specific sets of direct target genes that are characteristic of MYC-transformed tumour cells. Three factors account for this specificity. First, the magnitude of response parallels the change in occupancy by MYC at each promoter. Functionally distinct classes of target genes differ in the E-box sequence bound by MYC, suggesting that different cellular responses to physiological and oncogenic MYC levels are controlled by promoter affinity. Second, MYC both positively and negatively affects transcription initiation independent of its effect on transcriptional elongation(8). Third, complex formation with MIZ1 (also known as ZBTB17)(9) mediates repression of multiple target genes by MYC and the ratio of MYC and MIZ1 bound to each promoter correlates with the direction of response.
C1 [Walz, Susanne; Lorenzin, Francesca; Wiese, Katrin E.; von Eyss, Bjoern; Herold, Steffi; Wolf, Elmar; Eilers, Martin] Univ Wurzburg, Bioctr, Theodor Boveri Inst, D-97074 Wurzburg, Germany.
   [Morton, Jennifer; Karim, Saadia; Sansom, Owen] CRUK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland.
   [Rycak, Lukas] Inst Mol Biol & Tumor Res IMT, D-35033 Marburg, Germany.
   [Dumay-Odelot, Helene; Teichmann, Martin] Univ Bordeaux, IECB, ARNA Lab, Equipe Labellisee Canc, F-33600 Pessac, France.
   [Bartkuhn, Marek] Univ Giessen, Inst Genet, D-35390 Giessen, Germany.
   [Roels, Frederik; Fischer, Matthias] Univ Cologne, Univ Childrens Hosp Cologne, D-50924 Cologne, Germany.
   [Roels, Frederik; Fischer, Matthias] Univ Cologne, Cologne Ctr Mol Med CMMC, D-50924 Cologne, Germany.
   [Wuestefeld, Torsten; Zender, Lars] Univ Tubingen Hosp, Div Translat Gastrointestinal Oncol, Dept Internal Med 1, D-72076 Tubingen, Germany.
   [Zender, Lars] German Canc Res Ctr, German Ctr Translat Canc Res DKTK, Translat Gastrointestinal Oncol Grp, D-69121 Heidelberg, Germany.
   [Wei, Chia-Lin] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Wolf, Elmar] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, D-97080 Wurzburg, Germany.
   [Eilers, Martin] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97080 Wurzburg, Germany.
C3 University of Wurzburg; Beatson Institute; Universite de Bordeaux; Justus Liebig University Giessen; University of Cologne; University of Cologne; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Helmholtz Association; German Cancer Research Center (DKFZ); United States Department of Energy (DOE); University of Wurzburg; German Research Foundation (DFG); University of Wurzburg
RP Eilers, M (corresponding author), Univ Wurzburg, Bioctr, Theodor Boveri Inst, Hubland, D-97074 Wurzburg, Germany.
EM elmar.wolf@biozentrum.uni-wuerzburg.de; martin.eilers@biozentrum.uni-wuerzburg.de
FU Deutsche Forschungsgemeinschaft (DFG) [222/5-3, 222/12-1]; graduate college 1048 ("Molecular basis of organ development in vertebrates''); DFG Research Center for Experimental Biomedicine; Institut National Du Cancer (INCa); Ligue National Contre le Cancer (Equipe Labellisee); Cancer Research UK core grant; European Research Council investigator grant, "Coloncan''; Cancer Research UK [12481] Funding Source: researchfish
NR 38
TC 399
Z9 482
U1 0
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 JUL 24
PY 2014
VL 511
IS 7510
BP 483
EP +
DI 10.1038/nature13473
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700050
PM 25043018
DA 2026-03-09
ER

PT J
AU Bonapace, L
   Coissieux, MM
   Wyckoff, J
   Mertz, KD
   Varga, Z
   Junt, T
   Bentires-Alj, M
AF Bonapace, Laura
   Coissieux, Marie-May
   Wyckoff, Jeffrey
   Mertz, Kirsten D.
   Varga, Zsuzsanna
   Junt, Tobias
   Bentires-Alj, Mohamed
TI Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis
SO NATURE
LA English
DT Article
ID chemoattractant protein-1; carcinoma cells; expression; interleukin-6; monocytes; growth
AB Secretion of C-C chemokine ligand 2 (CCL2) by mammary tumours recruits CCR2-expressing inflammatory monocytes to primary tumours and metastatic sites, and CCL2 neutralization in mice inhibits metastasis-1 by retaining monocytes in the bone marrow. Here we report a paradoxical effect of CCL2 in four syngeneic mouse models of metastatic breast cancer. Surprisingly, interruption of CCL2 inhibition leads to an overshoot of metastases and accelerates death. This is the result of monocyte release from the bone marrow and enhancement of cancer cell mobilization from the primary tumour, as well as blood vessel formation and increased proliferation of metastatic cells in the lungs in an interleukin (IL)-6- and vascular endothelial growth factor (VEGF)-A-dependent manner. Notably, inhibition of CCL2 and IL-6 markedly reduced metastases and increased survival of the animals. CCL2 has been implicated in various neoplasias and adopted as a therapeutic target(1-3). However, our results call for caution when considering anti-CCL2 agents as monotherapy in metastatic disease and highlight the tumour microenvironment as a critical determinant of successful anti-metastatic therapy.
C1 [Bonapace, Laura; Coissieux, Marie-May; Wyckoff, Jeffrey; Bentires-Alj, Mohamed] Friedrich Miescher Inst Biomed Res FMI, CH-4058 Basel, Switzerland.
   [Bonapace, Laura; Junt, Tobias] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
   [Mertz, Kirsten D.; Varga, Zsuzsanna] Univ Zurich Hosp, Dept Pathol, CH-8006 Zurich, Switzerland.
   [Mertz, Kirsten D.] Cantonal Hosp Baselland, Inst Pathol Liestal, CH-4410 Liestal, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research; Novartis; University of Zurich; University Zurich Hospital; Kantonsspital Baselland
RP Bonapace, L (corresponding author), Friedrich Miescher Inst Biomed Res FMI, CH-4058 Basel, Switzerland.
EM bentires@fmi.ch
FU Novartis Research Foundation; European Research Council [243211-PTPsBDC]; Swiss Cancer League; Swiss National Foundation; Krebsliga Beider Basel; FP7 Marie Curie Fellowship; Medical Research Council [MR/K011014/1] Funding Source: researchfish; MRC [MR/K011014/1] Funding Source: UKRI
NR 30
TC 584
Z9 682
U1 0
U2 181
PU NATURE PUBLISHING 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 6
PY 2014
VL 515
IS 7525
BP 
EP 
DI 10.1038/nature13862
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB3RG
UT WOS:000349545400001
PM 25337873
DA 2026-03-09
ER

PT J
AU Acevedo, A
   Brodsky, L
   Andino, R
AF Acevedo, Ashley
   Brodsky, Leonid
   Andino, Raul
TI Mutational and fitness landscapes of an RNA virus revealed through population sequencing
SO NATURE
LA English
DT Article
ID nucleotide substitutions; substrate recognition; protein; polymerase; attenuation; dna
AB RNA viruses exist as genetically diverse populations(1). It is thought that diversity and genetic structure of viral populations determine the rapid adaptation observed in RNA viruses(2) and hence their pathogenesis(3). However, our understanding of the mechanisms underlying virus evolution has been limited by the inability to accurately describe the genetic structure of virus populations. Next-generation sequencing technologies generate data of sufficient depth to characterize virus populations, but are limited in their utility because most variants are present at very low frequencies and are thus indistinguishable from next-generation sequencing errors. Here we present an approach that reduces next-generation sequencing errors and allows the description of virus populations with unprecedented accuracy. Using this approach, we define the mutation rates of poliovirus and uncover the mutation landscape of the population. Furthermore, by monitoring changes in variant frequencies on serially passaged populations, we determined fitness values for thousands of mutations across the viral genome. Mapping of these fitness values onto three-dimensional structures of viral proteins offers a powerful approach for exploring structure-function relationships and potentially uncovering new functions. To our knowledge, our study provides the first single-nucleotide fitness landscape of an evolving RNA virus and establishes a general experimental platform for studying the genetic changes underlying the evolution of virus populations.
C1 [Acevedo, Ashley; Andino, Raul] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94122 USA.
   [Brodsky, Leonid] Univ Haifa, Tauber Bioinformat Res Ctr, IL-31905 Haifa, Israel.
   [Brodsky, Leonid] Univ Haifa, Dept Evolutionary & Environm Biol, IL-31905 Haifa, Israel.
C3 University of California System; University of California San Francisco; University of Haifa; University of Haifa
RP Andino, R (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94122 USA.
EM raul.andino@ucsf.edu
FU National Science Foundation; NIAID [AI091575, AI36178, AI40085]; DARPA Prophecy
NR 39
TC 288
Z9 343
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 JAN 30
PY 2014
VL 505
IS 7485
BP 686
EP +
DI 10.1038/nature12861
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000042
PM 24284629
DA 2026-03-09
ER

PT J
AU Bershteyn, M
   Hayashi, Y
   Desachy, G
   Hsiao, EC
   Sami, S
   Tsang, KM
   Weiss, LA
   Kriegstein, AR
   Yamanaka, S
   Wynshaw-Boris, A
AF Bershteyn, Marina
   Hayashi, Yohei
   Desachy, Guillaume
   Hsiao, Edward C.
   Sami, Salma
   Tsang, Kathryn M.
   Weiss, Lauren A.
   Kriegstein, Arnold R.
   Yamanaka, Shinya
   Wynshaw-Boris, Anthony
TI Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID preimplantation genetic diagnosis; uniparental disomy; mitotic behavior; dieker-syndrome; somatic-cells; human embryos; association; instability; mechanisms
AB Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation(1,2). Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions(2). Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate(3-9). The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs)(10-12) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of 'chromosome therapy'(13) to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.
C1 [Bershteyn, Marina; Wynshaw-Boris, Anthony] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Bershteyn, Marina; Wynshaw-Boris, Anthony] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Bershteyn, Marina; Kriegstein, Arnold R.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Hayashi, Yohei; Sami, Salma; Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Hayashi, Yohei; Sami, Salma; Yamanaka, Shinya] Roddenberry Ctr Stem Cell Biol & Med Gladstone, San Francisco, CA 94158 USA.
   [Desachy, Guillaume; Tsang, Kathryn M.; Weiss, Lauren A.] Univ Calif San Francisco, Inst Human Genet, Dept Psychiat, San Francisco, CA 94143 USA.
   [Hsiao, Edward C.] Univ Calif San Francisco, Div Endocrinol & Metab, San Francisco, CA 94143 USA.
   [Hsiao, Edward C.] Univ Calif San Francisco, Inst Human Genet, Dept Med, San Francisco, CA 94143 USA.
   [Yamanaka, Shinya] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   [Yamanaka, Shinya] Kyoto Univ, Dept Reprogramming Sci, Ctr iPS Cell Res & Applicat, Kyoto 6068507, Japan.
   [Wynshaw-Boris, Anthony] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 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; University of California System; University of California San Francisco; The J David Gladstone Institutes; 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 California System; University of California San Francisco; Kyoto University; University System of Ohio; Case Western Reserve University
RP Wynshaw-Boris, A (corresponding author), Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
EM syamanaka@gladstone.ucsf.edu; ajw168@case.edu
FU NIH/NIGMS [GM007085-32]; California Institute for Regenerative Medicine [TG2-01153]; Uehara Memorial Foundation; USCF's Program for Breakthrough Biomedical Research; NIAMS/NIH [K08 AR056299]; UCSF Department of Medicine; NHLBI/NIH [UO1HL098179]; MEXT (Japan); JSPS (Japan); JSPS; NIBIO (Japan); L. K. Whittier Foundation; Roddenberry Foundation; National Center for Research Resources [RR18928]
NR 38
TC 73
Z9 82
U1 0
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 MAR 6
PY 2014
VL 507
IS 7490
BP 99
EP +
DI 10.1038/nature12923
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400050
PM 24413397
DA 2026-03-09
ER

PT J
AU Doitsh, G
   Galloway, NLK
   Geng, X
   Yang, ZY
   Monroe, KM
   Zepeda, O
   Hunt, PW
   Hatano, H
   Sowinski, S
   Muñoz-Arias, I
   Greene, WC
AF Doitsh, Gilad
   Galloway, Nicole L. K.
   Geng, Xin
   Yang, Zhiyuan
   Monroe, Kathryn M.
   Zepeda, Orlando
   Hunt, Peter W.
   Hatano, Hiroyu
   Sowinski, Stefanie
   Munoz-Arias, Isa
   Greene, Warner C.
TI Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; ex-vivo; dendritic cells; lymphoid-tissue; apoptosis; activation; inhibitors; maturation; il-1-beta; monocytes
AB The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1 beta, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.
C1 [Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Sowinski, Stefanie; Munoz-Arias, Isa; Greene, Warner C.] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
   [Hunt, Peter W.; Hatano, Hiroyu; Greene, Warner C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Greene, Warner C.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Greene, WC (corresponding author), Gladstone Inst Virol & Immunol, 1650 Owens St, San Francisco, CA 94158 USA.
EM wgreene@gladstone.ucsf.edu
FU NIH/NIAID [R21AI102782, 1DP1036502, U19 AI0961133]; UCSF/Robert John Sabo Trust Award; A. P. Giannini Foundation Postdoctoral Research Fellowship; NIH [P30 AI027763]; National Heart Lung and Blood Institute; National Institute on Aging; National Institute of Allergy and Infectious Diseases; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases [P30AI027763] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI060537] Funding Source: NIH RePORTER; National Institute on Drug Abuse; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Nursing Research [P30AI027763] Funding Source: NIH RePORTER
NR 69
TC 922
Z9 1188
U1 3
U2 316
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 23
PY 2014
VL 505
IS 7484
BP 509
EP +
DI 10.1038/nature12940
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000031
PM 24356306
DA 2026-03-09
ER

PT J
AU Khan, AG
   Whidby, J
   Miller, MT
   Scarborough, H
   Zatorski, AV
   Cygan, A
   Price, AA
   Yost, SA
   Bohannon, CD
   Jacob, J
   Grakoui, A
   Marcotrigiano, J
AF Khan, Abdul Ghafoor
   Whidby, Jillian
   Miller, Matthew T.
   Scarborough, Hannah
   Zatorski, Alexandra V.
   Cygan, Alicja
   Price, Aryn A.
   Yost, Samantha A.
   Bohannon, Caitlin D.
   Jacob, Joshy
   Grakoui, Arash
   Marcotrigiano, Joseph
TI Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2
SO NATURE
LA English
DT Article
ID e2; scattering; protein; fusion; neutralization; involvement; expression; resolution; region-1; sequence
AB Hepatitis C virus (HCV) is a significant public health concern with approximately 160 million people infected worldwide(1). HCV infection often results in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. No vaccine is available and current therapies are effective against some, but not all, genotypes. HCV is an enveloped virus with two surface glycoproteins (E1 and E2). E2 binds to the host cell through interactions with scavenger receptor class B type I (SR-BI) and CD81, and serves as a target for neutralizing antibodies(2-4). Little is known about the molecular mechanism that mediates cell entry and membrane fusion, although E2 is predicted to be a class II viral fusion protein. Here we describe the structure of the E2 core domain in complex with an antigen-binding fragment (Fab) at 2.4 angstrom resolution. The E2 core has a compact, globular domain structure, consisting mostly of beta-strands and random coil with two small alpha-helices. The strands are arranged in two, perpendicular sheets (A and B), which are held together by an extensive hydrophobic core and disulphide bonds. Sheet A has an IgG-like fold that is commonly found in viral and cellular proteins, whereas sheet B represents a novel fold. Solution-based studies demonstrate that the full-length E2 ectodomain has a similar globular architecture and does not undergo significant conformational or oligomeric rearrangements on exposure to low pH. Thus, the IgG-like fold is the only feature that E2 shares with class II membrane fusion proteins. These results provide unprecedented insights into HCV entry and will assist in developing an HCV vaccine and new inhibitors.
C1 [Khan, Abdul Ghafoor; Whidby, Jillian; Miller, Matthew T.; Zatorski, Alexandra V.; Cygan, Alicja; Yost, Samantha A.; Marcotrigiano, Joseph] Rutgers State Univ, Dept Chem & Chem Biol, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
   [Scarborough, Hannah; Price, Aryn A.; Bohannon, Caitlin D.; Jacob, Joshy; Grakoui, Arash] Emory Univ, Div Microbiol & Immunol, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA.
   [Grakoui, Arash] Emory Univ, Div Infect Dis, Dept Med, Sch Med, Atlanta, GA 30322 USA.
C3 Rutgers University System; Rutgers University New Brunswick; Emory University; Emory University
RP Marcotrigiano, J (corresponding author), Rutgers State Univ, Dept Chem & Chem Biol, Ctr Adv Biotechnol & Med, 679 Hoes Lane West, Piscataway, NJ 08854 USA.
EM arash.grakoui@emory.edu; jmarco@cabm.rutgers.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886]; Yerkes Research Center Base Grant [RR-00165]; NIH [P50 GM103368, R01 AI080659, AI070101, DK083356]; New Jersey Commission on Cancer Research [DFHS13CRP001]; NIH Office of the Director [P51OD011132] Funding Source: NIH RePORTER
NR 43
TC 235
Z9 254
U1 0
U2 77
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 15
PY 2014
VL 509
IS 7500
BP 381
EP +
DI 10.1038/nature13117
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200043
PM 24553139
DA 2026-03-09
ER

PT J
AU Sanchez-Valencia, JR
   Dienel, T
   Gröning, O
   Shorubalko, I
   Mueller, A
   Jansen, M
   Amsharov, K
   Ruffieux, P
   Fasel, R
AF Sanchez-Valencia, Juan Ramon
   Dienel, Thomas
   Groening, Oliver
   Shorubalko, Ivan
   Mueller, Andreas
   Jansen, Martin
   Amsharov, Konstantin
   Ruffieux, Pascal
   Fasel, Roman
TI Controlled synthesis of single-chirality carbon nanotubes
SO NATURE
LA English
DT Article
ID surface-catalyzed cyclodehydrogenation; cap precursor molecules; growth-mechanism; aromatic precursors; fullerenes; separation; nanorings; modes; metal
AB Over the past two decades, single-walled carbon nanotubes (SWCNTs) have received much attention because their extraordinary properties are promising for numerous applications(1,2). Many of these properties depend sensitively on SWCNT structure, which is characterized by the chiral index (n,m) that denotes the length and orientation of the circumferential vector in the hexagonal carbon lattice. Electronic properties are particularly strongly affected, with subtle structural changes switching tubes from metallic to semiconducting with various band-gaps. Monodisperse 'single-chirality' (that is, with a single (n, m) index) SWCNTs are thus needed to fully exploit their technological potential(1,2). Controlled synthesis through catalyst engineering(3-6), end-cap engineering(7) or cloning strategies(8,9), and also tube sorting based on chromatography(10,11), density-gradient centrifugation, electrophoresis and other techniques(12), have delivered SWCNT samples with narrow distributions of tube diameter and a large fraction of a predetermined tube type. But an effective pathway to truly monodisperse SWCNTs remains elusive. The use of template molecules to unambiguously dictate the diameter and chirality of the resulting nanotube(8,13-16) holds great promise in this regard, but has hitherto had only limited practical success(7,17,18). Here we show that this bottom-up strategy can produce targeted nanotubes: we convert molecular precursors into ultrashort singly capped (6,6) 'armchair' nanotube seeds using surface-catalysed cyclodehydrogenation on a platinum (111) surface, and then elongate these during a subsequent growth phase to produce single-chirality and essentially defect-free SWCNTs with lengths up to a few hundred nanometres. We expect that our on-surface synthesis approach will provide a route to nanotube-based materials with highly optimized properties for applications such as light detectors, photovoltaics, field-effect transistors and sensors(2).
C1 [Sanchez-Valencia, Juan Ramon; Dienel, Thomas; Groening, Oliver; Ruffieux, Pascal; Fasel, Roman] Empa, Swiss Fed Labs Mat Sci & Technol, Nanotech Surfaces Lab, CH-8600 Dubendorf, Switzerland.
   [Shorubalko, Ivan] Empa, Swiss Fed Labs Mat Sci & Technol, Lab Reliabil Sci & Technol, CH-8600 Dubendorf, Switzerland.
   [Mueller, Andreas; Jansen, Martin; Amsharov, Konstantin] Max Planck Inst Solid State Res, D-70569 Stuttgart, 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); Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); Max Planck Society; University of Bern
RP Fasel, R (corresponding author), Empa, Swiss Fed Labs Mat Sci & Technol, Nanotech Surfaces Lab, CH-8600 Dubendorf, Switzerland.
EM konstantin.amsharov@fau.de; roman.fasel@empa.ch
FU Swiss National Science Foundation; State Secretariat for Education, Research and Innovation via the COST Action [MP0901]; Deutsche Forschungsgemeinschaft
NR 30
TC 508
Z9 577
U1 9
U2 1028
PU NATURE PUBLISHING 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 7
PY 2014
VL 512
IS 7512
BP 61
EP +
DI 10.1038/nature13607
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000031
PM 25100481
DA 2026-03-09
ER

PT J
AU Cantalupo, S
   Arrigoni-Battaia, F
   Prochaska, JX
   Hennawi, JF
   Madau, P
AF Cantalupo, Sebastiano
   Arrigoni-Battaia, Fabrizio
   Prochaska, J. Xavier
   Hennawi, Joseph F.
   Madau, Piero
TI A cosmic web filament revealed in Lyman-α emission around a luminous high-redshift quasar
SO NATURE
LA English
DT Article
ID adaptive mesh refinement; emitting galaxy; x-ray; radio; emitters; spectroscopy; evolution; discovery; nebula; forest
AB Simulations of structure formation in the Universe predict that galaxies are embedded in a 'cosmic web'(1), where most baryons reside as rarefied and highly ionized gas(2). This material has been studied for decades in absorption against background sources(3), but the sparseness of these inherently one-dimensional probes preclude direct constraints on the three-dimensional morphology of the underlying web. Here we report observations of a cosmic web filament in Lyman-alpha emission, discovered during a survey for cosmic gas fluorescently illuminated by bright quasars(4,5) at redshift z approximate to 2.3. With a linear projected size of approximately 460 physical kiloparsecs, the Lyman-alpha emission surrounding the radio-quiet quasar UM287 extends well beyond the virial radius of any plausible associated dark-matter halo and therefore traces intergalactic gas. The estimated cold gas mass of the filament from the observed emission-about 10(12.0 +/- 0.5)/C-1/2 solar masses, where C is the gas clumping factor-is more than ten times larger than what is typically found in cosmological simulations(5,6), suggesting that a population of intergalactic gas clumps with subkiloparsec sizes may be missing in current numerical models.
C1 [Cantalupo, Sebastiano; Prochaska, J. Xavier; Madau, Piero] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Cantalupo, Sebastiano; Prochaska, J. Xavier] Univ Calif Santa Cruz, Univ Calif Observ, Lick Observ, Santa Cruz, CA 95064 USA.
   [Arrigoni-Battaia, Fabrizio; Prochaska, J. Xavier; Hennawi, Joseph F.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Max Planck Society
RP Cantalupo, S (corresponding author), Univ Calif Santa Cruz, Dept Astron & Astrophys, 1156 High St, Santa Cruz, CA 95064 USA.
EM cantal@ucolick.org
FU National Science Foundation (NSF) [AST-1010004, OIA-1124453]; NASA [NNX12AF87G]; W.M. Keck Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1229745, 1010004] Funding Source: National Science Foundation; Office of Integrative Activities; Office Of The Director [1124453] Funding Source: National Science Foundation
NR 46
TC 341
Z9 373
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 FEB 6
PY 2014
VL 506
IS 7486
BP 63
EP +
DI 10.1038/nature12898
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100031
PM 24463517
DA 2026-03-09
ER

PT J
AU Torres, MA
   West, AJ
   Li, GJ
AF Torres, Mark A.
   West, A. Joshua
   Li, Gaojun
TI Sulphide oxidation and carbonate dissolution as a source of CO2 over geological timescales
SO NATURE
LA English
DT Article
ID mackenzie river-basin; organic-carbon; isotope fractionation; weathering processes; atmospheric oxygen; global carbon; mass-balance; ocean; evolution; seawater
AB The observed stability of Earth's climate over millions of years is thought to depend on the rate of carbon dioxide (CO2) release from the solid Earth being balanced by the rate of CO2 consumption by silicate weathering(1). During the Cenozoic era, spanning approximately the past 66 million years, the concurrent increases in the marine isotopic ratios of strontium, osmium and lithium(2-4) suggest that extensive uplift of mountain ranges may have stimulated CO2 consumption by silicate weathering(5), but reconstructions of sea-floor spreading(6) do not indicate a corresponding increase in CO2 inputs from volcanic degassing. The resulting imbalance would have depleted the atmosphere of all CO2 within a few million years(7). As a result, reconciling Cenozoic isotopic records with the need for mass balance in the long-term carbon cycle has been a major and unresolved challenge in geochemistry and Earth history. Here we show that enhanced sulphide oxidation coupled to carbonate dissolution can provide a transient source of CO2 to Earth's atmosphere that is relevant over geological timescales. Like drawdown by means of silicate weathering, this source is probably enhanced by tectonic uplift, and so may have contributed to the relative stability of the partial pressure of atmospheric CO2 during the Cenozoic. A variety of other hypotheses(8-10) have been put forward to explain the 'Cenozoic isotope-weathering paradox', and the evolution of the carbon cycle probably depended on multiple processes. However, an important role for sulphide oxidation coupled to carbonate dissolution is consistent with records of radiogenic isotopes2,3, atmospheric CO2 partial pressure(11,12) and the evolution of the Cenozoic sulphur cycle, and could be accounted for by geologically reasonable changes in the global dioxygen cycle, suggesting that this CO2 source should be considered a potentially important but as yet generally unrecognized component of the long-term carbon cycle.
C1 Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
   [Li, Gaojun] Nanjing Univ, Dept Earth Sci, MOE Key Lab Surficial Geochem, Nanjing 210046, Jiangsu, Peoples R China.
C3 University of Southern California; Nanjing University
RP Li, GJ (corresponding author), Nanjing Univ, Dept Earth Sci, MOE Key Lab Surficial Geochem, Nanjing 210046, Jiangsu, Peoples R China.
EM marktorr@usc.edu; joshwest@usc.edu; ligaojun@nju.edu.cn
FU USC College Fellowship; C-DEBI Graduate Fellowship; NSF [NSF-EAR/GLD-1053504, EAR/GLTG-1227192]; National Natural Science Foundation of China [41173105, 41102103, 41321062]; Division Of Earth Sciences; Directorate For Geosciences [1227192] Funding Source: National Science Foundation
NR 46
TC 286
Z9 343
U1 5
U2 307
PU NATURE PUBLISHING 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 20
PY 2014
VL 507
IS 7492
BP 346
EP +
DI 10.1038/nature13030
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000031
PM 24646998
DA 2026-03-09
ER

PT J
AU Takala, H
   Björling, A
   Berntsson, O
   Lehtivuori, H
   Niebling, S
   Hoernke, M
   Kosheleva, I
   Henning, R
   Menzel, A
   Ihalainen, JA
   Westenhoff, S
AF Takala, Heikki
   Bjorling, Alexander
   Berntsson, Oskar
   Lehtivuori, Heli
   Niebling, Stephan
   Hoernke, Maria
   Kosheleva, Irina
   Henning, Robert
   Menzel, Andreas
   Ihalainen, Janne A.
   Westenhoff, Sebastian
TI Signal amplification and transduction in phytochrome photosensors
SO NATURE
LA English
DT Article
ID structural dynamics; crystal-structure; bacteriophytochrome; photoconversion; reveals; protein; similarity; kinases; binding; domain
AB Sensory proteins must relay structural signals from the sensory site over large distances to regulatory output domains. Phytochromes are a major family of red-light-sensing kinases that control diverse cellular functions in plants, bacteria and fungi(1-9). Bacterial phytochromes consist of a photosensory core and a carboxy-terminal regulatory domain(10,11). Structures of photosensory cores are reported in the resting state(12-18) and conformational responses to light activation have been proposed in the vicinity of the chromophore(19-23). However, the structure of the signalling state and the mechanism of downstream signal relay through the photosensory core remain elusive. Here we report crystal and solution structures of the resting and activated states of the photosensory core of the bacteriophytochrome from Deinococcus radiodurans. The structures show an open and closed form of the dimeric protein for the activated and resting states, respectively. This nanometre-scale rearrangement is controlled by refolding of an evolutionarily conserved 'tongue', which is in contact with the chromophore. The findings reveal an unusual mechanism in which atomic-scale conformational changes around the chromophore are first amplified into ana angstrom-scale distance change in the tongue, and further grow into a nanometre-scale conformational signal. The structural mechanism is a blueprint for understanding how phytochromes connect to the cellular signalling network.
C1 [Takala, Heikki; Lehtivuori, Heli; Ihalainen, Janne A.] Univ Jyvaskyla, Dept Biol & Environm Sci, Nanosci Ctr, Jyvaskyla 40014, Finland.
   [Takala, Heikki; Bjorling, Alexander; Berntsson, Oskar; Niebling, Stephan; Hoernke, Maria; Westenhoff, Sebastian] Univ Gothenburg, Dept Chem & Mol Biol, S-40530 Gothenburg, Sweden.
   [Kosheleva, Irina; Henning, Robert] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
   [Menzel, Andreas] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
C3 University of Jyvaskyla; University of Gothenburg; University of Chicago; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute
RP Ihalainen, JA (corresponding author), Univ Jyvaskyla, Dept Biol & Environm Sci, Nanosci Ctr, Jyvaskyla 40014, Finland.
EM janne.ihalainen@jyu.fi; westenho@chem.gu.se
FU European Community [312284 CALIPSO]; National Institutes of Health, National Institute of General Medical Sciences [1R24GM111072]; Foundation of Strategic Research, Sweden; Swedish Research Council [279944]; European Research Council [279944]; Finnish Academy [138063]; Finnish Cultural Foundation [0131067]; Academy of Finland (AKA) [138063] Funding Source: Academy of Finland (AKA); European Research Council (ERC) [279944] Funding Source: European Research Council (ERC)
NR 35
TC 319
Z9 358
U1 1
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 8
PY 2014
VL 509
IS 7499
BP 245
EP +
DI 10.1038/nature13310
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300043
PM 24776794
DA 2026-03-09
ER

PT J
AU Levander, A
   Bezada, MJ
   Niu, F
   Humphreys, ED
   Palomeras, I
   Thurner, SM
   Masy, J
   Schmitz, M
   Gallart, J
   Carbonell, R
   Miller, MS
AF Levander, A.
   Bezada, M. J.
   Niu, F.
   Humphreys, E. D.
   Palomeras, I.
   Thurner, S. M.
   Masy, J.
   Schmitz, M.
   Gallart, J.
   Carbonell, R.
   Miller, M. S.
TI Subduction-driven recycling of continental margin lithosphere
SO NATURE
LA English
DT Article
ID gulf-of-mexico; tectonic evolution; atlas mountains; alboran region; moroccan atlas; south-america; beneath; delamination; constraints; tomography
AB Whereas subduction recycling of oceanic lithosphere is one of the central themes of plate tectonics, the recycling of continental lithosphere appears to be far more complicated and less well understood(1). Delamination and convective downwelling are two widely recognized processes invoked to explain the removal of lithospheric mantle under or adjacent to orogenic belts(2-5). Here we relate oceanic plate subduction to removal of adjacent continental lithosphere in certain plate tectonic settings. We have developed teleseismic body wave images from dense broadband seismic experiments that show higher than expected volumes of anomalously fast mantle associated with the subducted Atlantic slab under northeastern South America and the Alboran slab beneath the Gibraltar arc region(6,7); the anomalies are under, and are aligned with, the continental margins at depths greater than 200 kilometres. Rayleigh wave analysis(8,9) finds that the lithospheric mantle under the continental margins is significantly thinner than expected, and that thin lithosphere extends from the orogens adjacent to the subduction zones inland to the edges of nearby cratonic cores. Taking these data together, here we describe a process that can lead to the loss of continental lithosphere adjacent to a subduction zone. Subducting oceanic plates can viscously entrain and remove the bottom of the continental thermal boundary layer lithosphere from adjacent continental margins. This drives surface tectonics and pre-conditions the margins for further deformation by creating topography along the lithosphere-asthenosphere boundary. This can lead to development of secondary downwellings under the continental interior, probably under both South America and the Gibraltar arc(8,10), and to delamination of the entire lithospheric mantle, as around the Gibraltar arc(11). This process reconciles numerous, sometimes mutually exclusive, geodynamic models proposed to explain the complex oceanic-continental tectonics of these subduction zones(12-17).
C1 [Levander, A.; Niu, F.; Palomeras, I.; Thurner, S. M.; Masy, J.] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Bezada, M. J.; Humphreys, E. D.] Univ Oregon, Dept Geol Sci, Eugene, OR 97043 USA.
   [Bezada, M. J.] Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
   [Niu, F.] Univ Petr, State Key Lab Petr Resources & Prospecting, Beijing 102249, Peoples R China.
   [Niu, F.] Univ Petr, Unconvent Nat Gas Inst, Beijing 102249, Peoples R China.
   [Schmitz, M.] Fdn Venezolana Invest Sismol, Caracas 1073, Venezuela.
   [Gallart, J.; Carbonell, R.] CSIC, Inst Ciencias Terra Jaume Almera, E-08028 Barcelona, Spain.
   [Miller, M. S.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
C3 Rice University; University of Oregon; University of Minnesota System; University of Minnesota Twin Cities; China University of Petroleum; China University of Petroleum; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Geociencias Barcelona (GEO3BCN); University of Southern California
RP Levander, A (corresponding author), Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
EM alan@rice.edu
FU US National Science Foundation [EAR 0003572, 0607801, 0808939, EAR 0808931, EAR 0809023, 1054638]; Venezuelan National Fund for Science, Technology and Innovation grant [G-2002000478]; PDVSA-INTEVEP-FUNVISIS [2004-141]; Spanish Ministry of Science and Innovation [CSD2006-00041, CGL2009-09727, CGL2010-15146]; A. v. Humboldt Foundation Research Prize; Directorate For Geosciences; Division Of Earth Sciences [0808939, 1054638, 0809023] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0808931, 0607801] Funding Source: National Science Foundation
NR 38
TC 67
Z9 72
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 NOV 13
PY 2014
VL 515
IS 7526
BP 253
EP U219
DI 10.1038/nature13878
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400047
PM 25391963
DA 2026-03-09
ER

PT J
AU Song, YM
   Li, L
   Ou, YW
   Gao, ZB
   Li, EM
   Li, XC
   Zhang, WM
   Wang, JQ
   Xu, LY
   Zhou, Y
   Ma, XJ
   Liu, LY
   Zhao, ZT
   Huang, XL
   Fan, J
   Dong, LJ
   Chen, G
   Ma, LY
   Yang, J
   Chen, LY
   He, MH
   Li, M
   Zhuang, XH
   Huang, K
   Qiu, KL
   Yin, GL
   Guo, GW
   Feng, Q
   Chen, PS
   Wu, ZY
   Wu, JY
   Ma, L
   Zhao, JY
   Luo, LH
   Fu, M
   Xu, BN
   Chen, B
   Li, YR
   Tong, T
   Wang, MR
   Liu, ZH
   Lin, DX
   Zhang, XQ
   Yang, HM
   Wang, J
   Zhan, QM
AF Song, Yongmei
   Li, Lin
   Ou, Yunwei
   Gao, Zhibo
   Li, Enmin
   Li, Xiangchun
   Zhang, Weimin
   Wang, Jiaqian
   Xu, Liyan
   Zhou, Yong
   Ma, Xiaojuan
   Liu, Lingyan
   Zhao, Zitong
   Huang, Xuanlin
   Fan, Jing
   Dong, Lijia
   Chen, Gang
   Ma, Liying
   Yang, Jie
   Chen, Longyun
   He, Minghui
   Li, Miao
   Zhuang, Xuehan
   Huang, Kai
   Qiu, Kunlong
   Yin, Guangliang
   Guo, Guangwu
   Feng, Qiang
   Chen, Peishan
   Wu, Zhiyong
   Wu, Jianyi
   Ma, Ling
   Zhao, Jinyang
   Luo, Longhai
   Fu, Ming
   Xu, Bainan
   Chen, Bo
   Li, Yingrui
   Tong, Tong
   Wang, Mingrong
   Liu, Zhihua
   Lin, Dongxin
   Zhang, Xiuqing
   Yang, Huanming
   Wang, Jun
   Zhan, Qimin
TI Identification of genomic alterations in oesophageal squamous cell cancer
SO NATURE
LA English
DT Article
ID circular binary segmentation; somatic mutation; adenocarcinoma; immortalization; aberrations; patterns; exome
AB Oesophageal cancer is one of the most aggressive cancers and is the sixth leading cause of cancer death worldwide(1). Approximately 70% of global oesophageal cancer cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the histopathological form in the vast majority of cases (>90%)(2,3). Currently, there are limited clinical approaches for the early diagnosis and treatment of ESCC, resulting in a 10% five-year survival rate for patients. However, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of the International Cancer Genome Consortium research project. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and whole-exome sequencing, were subjected to array comparative genomic hybridization analysis. We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B). Notably, FAM135B is identified as a novel cancer-implicated gene as assayed for its ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA encoded in the amplified 11q13.3-13.4 region, is characterized as a novel oncogene, and functional assays demonstrate that MIR548K enhances malignant phenotypes of ESCC cells. Moreover, we have found that several important histone regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP and EP300) are frequently altered in ESCC. Pathway assessment reveals that somatic aberrations are mainly involved in the Wnt, cell cycle and Notch pathways. Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking. This study has explored novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC.
C1 [Song, Yongmei; Ou, Yunwei; Zhang, Weimin; Ma, Xiaojuan; Liu, Lingyan; Zhao, Zitong; Fan, Jing; Dong, Lijia; Ma, Liying; Ma, Ling; Fu, Ming; Tong, Tong; Wang, Mingrong; Liu, Zhihua; Lin, Dongxin; Zhan, Qimin] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Canc Hosp, Beijing 100021, Peoples R China.
   [Song, Yongmei; Ou, Yunwei; Zhang, Weimin; Ma, Xiaojuan; Liu, Lingyan; Zhao, Zitong; Fan, Jing; Dong, Lijia; Ma, Liying; Ma, Ling; Fu, Ming; Tong, Tong; Wang, Mingrong; Liu, Zhihua; Lin, Dongxin; Zhan, Qimin] Peking Union Med Coll, Beijing 100021, Peoples R China.
   [Li, Lin; Gao, Zhibo; Li, Xiangchun; Wang, Jiaqian; Zhou, Yong; Huang, Xuanlin; Chen, Gang; Yang, Jie; Chen, Longyun; He, Minghui; Li, Miao; Zhuang, Xuehan; Huang, Kai; Qiu, Kunlong; Yin, Guangliang; Guo, Guangwu; Feng, Qiang; Chen, Peishan; Zhao, Jinyang; Luo, Longhai; Li, Yingrui; Zhang, Xiuqing; Yang, Huanming; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
   [Ou, Yunwei; Xu, Bainan] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, Beijing 100853, Peoples R China.
   [Li, Enmin; Wu, Jianyi] Shantou Univ, Coll Med, Dept Biochem & Mol Biol, Key Lab Mol Biol High Canc Incidence Coastal Chao, Shantou 515041, Guangdong, Peoples R China.
   [Xu, Liyan; Chen, Bo] Shantou Univ, Coll Med, Inst Oncol Pathol, Shantou 515041, Guangdong, Peoples R China.
   [Wu, Zhiyong] Sun Yat Sen Univ, Affiliated Shantou Hosp, Shantou Cent Hosp, Dept Tumor Surg, Shantou 515041, Guangdong, Peoples R China.
C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Beijing Genomics Institute (BGI); Chinese People's Liberation Army General Hospital; Shantou University; Shantou University; Sun Yat Sen University
RP Zhan, QM (corresponding author), Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Canc Hosp, Beijing 100021, Peoples R China.
EM zhanqimin@pumc.edu.cn
FU National High Technology Research and Development Program of China (863 program) [2012AA02A209, 2012AA02A503]; National Natural Science Foundation Fund [81021061]; Guangdong Innovative Research Team Program [2009010016]; National Natural Science Foundation of China [U0932001]; National Key Basic Research Program of China (973 program) [2011CB911004, 2009CB521801, 2012CB526608]
NR 37
TC 921
Z9 1030
U1 1
U2 404
PU NATURE PUBLISHING 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 1
PY 2014
VL 509
IS 7498
BP 91
EP +
DI 10.1038/nature13176
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100045
PM 24670651
DA 2026-03-09
ER

PT J
AU Wang, X
   Lu, ZK
   Gomez, A
   Hon, GC
   Yue, YN
   Han, DL
   Fu, Y
   Parisien, M
   Dai, Q
   Jia, GF
   Ren, B
   Pan, T
   He, C
AF Wang, Xiao
   Lu, Zhike
   Gomez, Adrian
   Hon, Gary C.
   Yue, Yanan
   Han, Dali
   Fu, Ye
   Parisien, Marc
   Dai, Qing
   Jia, Guifang
   Ren, Bing
   Pan, Tao
   He, Chuan
TI N6-methyladenosine-dependent regulation of messenger RNA stability
SO NATURE
LA English
DT Article
ID binding protein; sites; domain; n6-methyladenosine; translation; methylation; sequences; granules; decay; gene
AB N-6-methyladenosine (m(6)A) is the most prevalent internal (non-cap) modification present in the messenger RNA of all higher eukaryotes(1,2). Although essential to cell viability and development(3-5), the exact role of m(6)A modification remains to be determined. The recent discovery of two m(6)A demethylases in mammalian cells highlighted the importance of m(6)A in basic biological functions and disease(6-8). Here we show that m(6)A is selectively recognized by the human YTH domain family 2 (YTHDF2) 'reader' protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m(6)A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies(9). The carboxy-terminal domain of YTHDF2 selectively binds to m(6)A-containing mRNA, whereas the amino-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m(6)A modification is recognized by selectively binding proteins to affect the translation status and lifetime of mRNA.
C1 [Wang, Xiao; Lu, Zhike; Gomez, Adrian; Yue, Yanan; Han, Dali; Fu, Ye; Dai, Qing; Jia, Guifang; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Wang, Xiao; Lu, Zhike; Gomez, Adrian; Yue, Yanan; Han, Dali; Fu, Ye; Parisien, Marc; Dai, Qing; Jia, Guifang; Pan, Tao; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
   [Hon, Gary C.; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Cellular & Mol Med,UCSD Moores Canc Ctr, La Jolla, CA 92093 USA.
   [Hon, Gary C.; Ren, Bing] Univ Calif San Diego, Sch Med, Inst Genome Med, La Jolla, CA 92093 USA.
   [Parisien, Marc; Pan, Tao] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Jia, Guifang] Peking Univ, Dept Chem Biol, Beijing 100871, Peoples R China.
   [Jia, Guifang] Peking Univ, Synthet & Funct Biomol Ctr, Coll Chem & Mol Engn, Beijing 100871, Peoples R China.
C3 University of Chicago; University of Chicago; University of California System; University of California San Diego; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of Chicago; Peking University; Peking University
RP He, C (corresponding author), Univ Chicago, Dept Chem, 929 East 57th St, Chicago, IL 60637 USA.
EM chuanhe@uchicago.edu
FU National Institutes of Health [GM071440]; EUREKA [GM088599]; National Science Foundation [CHE-1048528]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1048528] Funding Source: National Science Foundation
NR 41
TC 3649
Z9 4060
U1 20
U2 672
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 2
PY 2014
VL 505
IS 7481
BP 117
EP +
DI 10.1038/nature12730
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300035
PM 24284625
DA 2026-03-09
ER

PT J
AU Andrews-Hanna, JC
   Besserer, J
   Head, JW
   Howett, CJA
   Kiefer, WS
   Lucey, PJ
   McGovern, PJ
   Melosh, HJ
   Neumann, GA
   Phillips, RJ
   Schenk, PM
   Smith, DE
   Solomon, SC
   Zuber, MT
AF Andrews-Hanna, Jeffrey C.
   Besserer, Jonathan
   Head, James W., III
   Howett, Carly J. A.
   Kiefer, Walter S.
   Lucey, Paul J.
   McGovern, Patrick J.
   Melosh, H. Jay
   Neumann, Gregory A.
   Phillips, Roger J.
   Schenk, Paul M.
   Smith, David E.
   Solomon, Sean C.
   Zuber, Maria T.
TI Structure and evolution of the lunar Procellarum region as revealed by GRAIL gravity data
SO NATURE
LA English
DT Article
ID south-pole; mare basalts; origin; moon; enceladus; interior; model; constraints; tectonics; volcanism
AB The Procellarum region is a broad area on the nearside of the Moon that is characterized by low elevations(1), thin crust(2), and high surface concentrations of the heat-producing elements uranium, thorium, and potassium(3,4). The region has been interpreted as an ancient impact basin approximately 3,200 kilometres in diameter(5-7), although supporting evidence at the surface would have been largely obscured as a result of the great antiquity and poor preservation of any diagnostic features. Here we use data from the Gravity Recovery and Interior Laboratory (GRAIL) mission(8) to examine the subsurface structure of Procellarum. The Bouguer gravity anomalies and gravity gradients reveal a pattern of narrow linear anomalies that border Procellarum and are interpreted to be the frozen remnants of lava-filled rifts and the underlying feeder dykes that served as the magma plumbing system for much of the nearside mare volcanism. The discontinuous surface structures that were earlier interpreted as remnants of an impact basin rim are shown in GRAIL data to be a part of this continuous set of border structures in a quasi-rectangular pattern with angular intersections, contrary to the expected circular or elliptical shape of an impact basin(9). The spatial pattern of magmatic-tectonic structures bounding Procellarum is consistent with their formation in response to thermal stresses produced by the differential cooling of the province relative to its surroundings, coupled with magmatic activity driven by the greater-than-average heat flux in the region.
C1 [Andrews-Hanna, Jeffrey C.] Colorado Sch Mines, Dept Geophys, Golden, CO 80401 USA.
   [Andrews-Hanna, Jeffrey C.] Colorado Sch Mines, Ctr Space Resources, Golden, CO 80401 USA.
   [Besserer, Jonathan] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Head, James W., III] Brown Univ, Dept Earth Environm & Planetary Sci, Providence, RI 02912 USA.
   [Howett, Carly J. A.; Phillips, Roger J.] SW Res Inst, Planetary Sci Directorate, Boulder, CO 80302 USA.
   [Kiefer, Walter S.; McGovern, Patrick J.; Schenk, Paul M.] Lunar & Planetary Inst, Houston, TX 77058 USA.
   [Lucey, Paul J.] Univ Hawaii, Hawaii Inst Geophys & Planetol, Honolulu, HI 96822 USA.
   [Melosh, H. Jay] Purdue Univ, Dept Earth Atmospher & Planetary Sci, W Lafayette, IN 47907 USA.
   [Neumann, Gregory A.] NASA, Goddard Space Flight Ctr, Solar Syst Explorat Div, Greenbelt, MD 20771 USA.
   [Smith, David E.; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Solomon, Sean C.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
   [Solomon, Sean C.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Colorado School of Mines; Colorado School of Mines; University of California System; University of California Santa Cruz; Brown University; University of Hawaii System; Purdue University System; Purdue University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Massachusetts Institute of Technology (MIT); Carnegie Institution for Science; Columbia University
RP Andrews-Hanna, JC (corresponding author), Colorado Sch Mines, Dept Geophys, Golden, CO 80401 USA.
EM jcahanna@mines.edu
FU NASA's GRAIL Guest Scientist Program [NNX12AL20G]; NASA [43760, NNX12AL20G] Funding Source: Federal RePORTER
NR 72
TC 102
Z9 115
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 OCT 2
PY 2014
VL 514
IS 7520
BP 68
EP +
DI 10.1038/nature13697
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800036
PM 25279919
DA 2026-03-09
ER

PT J
AU Obokata, H
   Sasai, Y
   Niwa, H
   Kadota, M
   Andrabi, M
   Takata, N
   Tokoro, M
   Terashita, Y
   Yonemura, S
   Vacanti, CA
   Wakayama, T
AF Obokata, Haruko
   Sasai, Yoshiki
   Niwa, Hitoshi
   Kadota, Mitsutaka
   Andrabi, Munazah
   Takata, Nozomu
   Tokoro, Mikiko
   Terashita, Yukari
   Yonemura, Shigenobu
   Vacanti, Charles A.
   Wakayama, Teruhiko
TI RETRACTED: Bidirectional developmental potential in reprogrammed cells with acquired pluripotency (Retracted article. See vol. 511, pg. 112, 2014)
SO NATURE
LA English
DT Article; Retracted Publication
ID embryonic stem-cells; ground-state; self-renewal; expression; mice
AB We recently discovered an unexpected phenomenon of somatic cell reprogramming into pluripotent cells by exposure to sublethal stimuli, which we call stimulus-triggered acquisition of pluripotency (STAP)(1). This reprogramming does not require nuclear transfer(2,3) or genetic manipulation(4). Here we report that reprogrammed STAP cells, unlike embryonic stem (ES) cells, can contribute to both embryonic and placental tissues, as seen in a blastocyst injection assay. Mouse STAP cells lose the ability to contribute to the placenta as well as trophoblast marker expression on converting into ES-like stem cells by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF). In contrast, when cultured with Fgf4, STAP cells give rise to proliferative stem cells with enhanced trophoblastic characteristics. Notably, unlike conventional trophoblast stem cells, the Fgf4-induced stem cells from STAP cells contribute to both embryonic and placental tissues in vivo and transform into ES-like cells when cultured with LIF-containing medium. Taken together, the developmental potential of STAP cells, shown by chimaera formation and in vitro cell conversion, indicates that they represent a unique state of pluripotency.
C1 [Obokata, Haruko; Terashita, Yukari] RIKEN Ctr Dev Biol, Lab Cellular Reprogramming, Kobe, Hyogo 6500047, Japan.
   [Obokata, Haruko; Tokoro, Mikiko; Terashita, Yukari; Wakayama, Teruhiko] RIKEN Ctr Dev Biol, Lab Genom Reprogramming, Kobe, Hyogo 6500047, Japan.
   [Obokata, Haruko; Vacanti, Charles A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Tissue Engn & Regenerat Med, Boston, MA 02115 USA.
   [Sasai, Yoshiki; Takata, Nozomu] RIKEN Ctr Dev Biol, Lab Organogenesis & Neurogenesis, Kobe, Hyogo 6500047, Japan.
   [Niwa, Hitoshi] RIKEN Ctr Dev Biol, Lab Pluripotent Stem Cell Studies, Kobe, Hyogo 6500047, Japan.
   [Kadota, Mitsutaka; Andrabi, Munazah] RIKEN Ctr Dev Biol, Genome Resource & Anal Unit, Kobe, Hyogo 6500047, Japan.
   [Yonemura, Shigenobu] RIKEN Ctr Dev Biol, Electron Microscopy Lab, Kobe, Hyogo 6500047, Japan.
   [Wakayama, Teruhiko] Univ Yamanashi, Fac Life & Environm Sci, Yamanashi 4008510, Japan.
C3 RIKEN; RIKEN; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; RIKEN; RIKEN; RIKEN; RIKEN; University of Yamanashi
RP Obokata, H (corresponding author), RIKEN Ctr Dev Biol, Lab Cellular Reprogramming, Kobe, Hyogo 6500047, Japan.
EM obokata@cdb.riken.jp; yoshikisasai@cdb.riken.jp; teru@cdb.riken.jp
FU RIKEN; Network Project for Realization of Regenerative Medicine; Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women's Hospital;  [20062015]
NR 23
TC 83
Z9 111
U1 1
U2 413
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 30
PY 2014
VL 505
IS 7485
BP 676
EP +
DI 10.1038/nature12969
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000040
PM 24476891
DA 2026-03-09
ER

PT J
AU Matusek, T
   Wendler, F
   Polès, S
   Pizette, S
   D'Angelo, G
   Fürthauer, M
   Thérond, PP
AF Matusek, Tamas
   Wendler, Franz
   Poles, Sophie
   Pizette, Sandrine
   D'Angelo, Gisela
   Fuerthauer, Maximilian
   Therond, Pascal P.
TI The ESCRT machinery regulates the secretion and long-range activity of Hedgehog
SO NATURE
LA English
DT Article
ID cholesterol modification; extracellular vesicles; drosophila epithelia; sonic hedgehog; protein; trafficking; membrane; release; vps25; microvesicles
AB The conserved family of Hedgehog (Hh) proteins acts as short- and long-range secreted morphogens, controlling tissue patterning and differentiation during embryonic development(1). Mature Hh carries hydrophobic palmitic acid and cholesterol modifications essential for its extracellular spreading(2). Various extracellular transportation mechanisms for Hh have been suggested, but the pathways actually used for Hh secretion and transport in vivo remain unclear. Here we show that Hh secretion in Drosophila wing imaginal discs is dependent on the endosomal sorting complex required for transport (ESCRT)(3). In vivo the reduction of ESCRT activity in cells producing Hh leads to a retention of Hh at the external cell surface. Furthermore, we show that ESCRT activity in Hh-producing cells is required for long-range signalling. We also provide evidence that pools of Hh and ESCRT proteins are secreted together into the extracellular space in vivo and can subsequently be detected together at the surface of receiving cells. These findings uncover a new function for ESCRT proteins in controlling morphogen activity and reveal a new mechanism for the transport of secreted Hh across the tissue by extracellular vesicles, which is necessary for long-range target induction.
C1 [Matusek, Tamas; Wendler, Franz; Poles, Sophie; Pizette, Sandrine; D'Angelo, Gisela; Fuerthauer, Maximilian; Therond, Pascal P.] Univ Nice Sophia Antipolis, IBV, UMR 7277, F-06100 Nice, France.
   [Matusek, Tamas; Wendler, Franz; Poles, Sophie; Pizette, Sandrine; D'Angelo, Gisela; Fuerthauer, Maximilian; Therond, Pascal P.] CNRS, IBV, UMR 7277, F-06100 Nice, France.
   [Matusek, Tamas; Wendler, Franz; Poles, Sophie; Pizette, Sandrine; D'Angelo, Gisela; Fuerthauer, Maximilian; Therond, Pascal P.] INSERM, IBV, U1091, F-06100 Nice, France.
C3 Universite Cote d'Azur; Institut National de la Sante et de la Recherche Medicale (Inserm); 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); Universite Cote d'Azur; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Cote d'Azur
RP Thérond, PP (corresponding author), Univ Nice Sophia Antipolis, IBV, UMR 7277, F-06100 Nice, France.
EM therond@unice.fr
FU French Government (National Research Agency, ANR) through the "Investments for the Future" LABEX SIGNALIFE [ANR-11-LABX-0028-01]; Fondation pour la Recherche Medicale [DEQ20110421324]; Fondation Association pour la Recherche Contre le Cancer (ARC); Ligue Nationale Contre le Cancer; ATIP/Avenir; ARC; Human Frontier Science Program
NR 33
TC 136
Z9 159
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 DEC 4
PY 2014
VL 516
IS 7529
BP 99
EP U240
DI 10.1038/nature13847
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800047
PM 25471885
DA 2026-03-09
ER

PT J
AU Rouskin, S
   Zubradt, M
   Washietl, S
   Kellis, M
   Weissman, JS
AF Rouskin, Silvi
   Zubradt, Meghan
   Washietl, Stefan
   Kellis, Manolis
   Weissman, Jonathan S.
TI Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo
SO NATURE
LA English
DT Article
ID secondary structure; dimethyl sulfate; protein response; web server; translation; prediction; ribosome; yeast; thermosensor; degradation
AB RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA's ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational(1,2) and experimental(3-8) efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo(5). Indeed, the presence of RNA-binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single-nucleotide precision. This method is based on in vivo modification with dimethyl sulphate (DMS), which reacts with unpaired adenine and cytosine residues(9), followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known messenger RNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome(10). Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast shows that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding whereby the structure formed is the most thermodynamically favourable, thermodynamics have an incomplete role in determining mRNA structure in vivo.
C1 [Rouskin, Silvi; Zubradt, Meghan; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, Calif Inst Quantitat Biol,Ctr RNA Syst Biol, San Francisco, CA 94158 USA.
   [Washietl, Stefan; Kellis, Manolis] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Washietl, Stefan; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Washietl, Stefan; Kellis, Manolis] Broad Inst, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Francisco; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Weissman, JS (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, Calif Inst Quantitat Biol,Ctr RNA Syst Biol, San Francisco, CA 94158 USA.
EM weissman@cmp.ucsf.edu
FU Center for RNA Systems Biology; Howard Hughes Medical Institute; National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0644282] Funding Source: National Science Foundation
NR 40
TC 672
Z9 838
U1 1
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 JAN 30
PY 2014
VL 505
IS 7485
BP 701
EP +
DI 10.1038/nature12894
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000045
PM 24336214
DA 2026-03-09
ER

PT J
AU Wu, Z
   Autry, AE
   Bergan, JF
   Watabe-Uchida, M
   Dulac, CG
AF Wu, Zheng
   Autry, Anita E.
   Bergan, Joseph F.
   Watabe-Uchida, Mitsuko
   Dulac, Catherine G.
TI Galanin neurons in the medial preoptic area govern parental behaviour
SO NATURE
LA English
DT Article
ID maternal-behavior; sexual-behavior; male-aggression; male-mice; vomeronasal; nucleus; infanticide; expression; organization; receptor
AB Mice display robust, stereotyped behaviours towards pups: virgin males typically attack pups, whereas virgin females and sexually experienced males and females display parental care. Here we show that virgin males genetically impaired in vomeronasal sensing do not attack pups and are parental. Furthermore, we uncover a subset of galanin-expressing neurons in the medial preoptic area (MPOA) that are specifically activated during male and female parenting, and a different subpopulation that is activated during mating. Genetic ablation of MPOA galanin neurons results in marked impairment of parental responses in males and females and affects male mating. Optogenetic activation of these neurons in virgin males suppresses inter-male and pup-directed aggression and induces pup grooming. Thus, MPOA galanin neurons emerge as an essential regulatory node of male and female parenting behaviour and other social responses. These results provide an entry point to a circuit-level dissection of parental behaviour and its modulation by social experience.
C1 [Wu, Zheng; Autry, Anita E.; Bergan, Joseph F.; Dulac, Catherine G.] Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [Watabe-Uchida, Mitsuko] Harvard Univ, Dept Mol & Cellular Biol, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University
RP Dulac, CG (corresponding author), Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Ctr Brain Sci, Cambridge, MA 02138 USA.
EM dulac@fas.harvard.edu
FU Howard Hughes Medical Institute; National Institute of Health (NIDCD)
NR 55
TC 442
Z9 525
U1 1
U2 119
PU NATURE PUBLISHING 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 15
PY 2014
VL 509
IS 7500
BP 325
EP +
DI 10.1038/nature13307
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200031
PM 24828191
DA 2026-03-09
ER

PT J
AU Haeusler, AR
   Donnelly, CJ
   Periz, G
   Simko, EAJ
   Shaw, PG
   Kim, MS
   Maragakis, NJ
   Troncoso, JC
   Pandey, A
   Sattler, R
   Rothstein, JD
   Wang, J
AF Haeusler, Aaron R.
   Donnelly, Christopher J.
   Periz, Goran
   Simko, Eric A. J.
   Shaw, Patrick G.
   Kim, Min-Sik
   Maragakis, Nicholas J.
   Troncoso, Juan C.
   Pandey, Akhilesh
   Sattler, Rita
   Rothstein, Jeffrey D.
   Wang, Jiou
TI C9orf72 nucleotide repeat structures initiate molecular cascades of disease
SO NATURE
LA English
DT Article
ID amyotrophic-lateral-sclerosis; rna g-quadruplex; frontotemporal dementia; hexanucleotide repeat; ggggcc repeat; dna repeats; expansion; protein; als; acids
AB A hexanucleotide repeat expansion (HRE), (GGGGCC)(n), inC9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA-DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformation-dependent manner. Specifically, nucleolin, an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases.
C1 [Haeusler, Aaron R.; Periz, Goran; Simko, Eric A. J.; Wang, Jiou] Johns Hopkins Univ, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA.
   [Haeusler, Aaron R.; Periz, Goran; Simko, Eric A. J.; Rothstein, Jeffrey D.; Wang, Jiou] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA.
   [Donnelly, Christopher J.; Maragakis, Nicholas J.; Sattler, Rita; Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
   [Donnelly, Christopher J.; Sattler, Rita; Rothstein, Jeffrey D.] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD 21205 USA.
   [Shaw, Patrick G.; Kim, Min-Sik; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Troncoso, Juan C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
RP Wang, J (corresponding author), Johns Hopkins Univ, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA.
EM jiouw@jhmi.edu
FU National Institutes of Health [NS07432, NS085207]; Robert Packard Center for ALS Research at Johns Hopkins; Muscular Dystrophy Association; Target ALS; ALS Association; Johns Hopkins Alzheimer's Disease Research Center NIH [P50AG05146]; National Cancer Institute [5T32CA009110-36]; Maryland Stem Cell Research Fund; Judith & Jean Pape Adams Charitable Foundation; Samuel I. Newhouse Foundation; National Cancer Institute [T32CA009110] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01NS074324] Funding Source: NIH RePORTER
NR 46
TC 758
Z9 912
U1 0
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 MAR 13
PY 2014
VL 507
IS 7491
BP 195
EP +
DI 10.1038/nature13124
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800031
PM 24598541
DA 2026-03-09
ER

PT J
AU Mayer-Barber, KD
   Andrade, BB
   Oland, SD
   Amaral, EP
   Barber, DL
   Gonzales, J
   Derrick, SC
   Shi, RR
   Kumar, NP
   Wei, W
   Yuan, X
   Zhang, GL
   Cai, Y
   Babu, S
   Catalfamo, M
   Salazar, AM
   Via, LE
   Barry, CE
   Sher, A
AF Mayer-Barber, Katrin D.
   Andrade, Bruno B.
   Oland, Sandra D.
   Amaral, Eduardo P.
   Barber, Daniel L.
   Gonzales, Jacqueline
   Derrick, Steven C.
   Shi, Ruiru
   Kumar, Nathella Pavan
   Wei, Wang
   Yuan, Xing
   Zhang, Guolong
   Cai, Ying
   Babu, Subash
   Catalfamo, Marta
   Salazar, Andres M.
   Via, Laura E.
   Barry, Clifton E., III
   Sher, Alan
TI Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk
SO NATURE
LA English
DT Article
ID necrosis-factor-alpha; mycobacterium-tuberculosis; induction; susceptibility; inflammation; infection; immunity; innate
AB Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent(1). Despite chemotherapy, the global tuberculosis epidemic has intensified because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria(2-5). Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality(6). The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target(7). Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.
C1 [Mayer-Barber, Katrin D.; Andrade, Bruno B.; Oland, Sandra D.; Amaral, Eduardo P.; Sher, Alan] NIAID, Immunobiol Sect, LPD, NIH, Bethesda, MD 20892 USA.
   [Amaral, Eduardo P.] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo, Brazil.
   [Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, LPD, NIH, Bethesda, MD 20892 USA.
   [Gonzales, Jacqueline; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Derrick, Steven C.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
   [Shi, Ruiru; Wei, Wang; Yuan, Xing] Henan Chest Hosp, Zhengzhou 450003, Peoples R China.
   [Kumar, Nathella Pavan; Babu, Subash] Int Ctr Excellence Res, NIH, Madras 600031, Tamil Nadu, India.
   [Kumar, Nathella Pavan] NIRT, Madras 600031, Tamil Nadu, India.
   [Zhang, Guolong] SinoUS Int Res Ctr TB, Zhengzhou 450003, Peoples R China.
   [Zhang, Guolong] Henan Publ Hlth Ctr, Zhengzhou 450003, Peoples R China.
   [Babu, Subash] NIAID, Helminth Immunol Sect, LPD, NIH, Bethesda, MD 20892 USA.
   [Catalfamo, Marta] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Salazar, Andres M.] Oncovir Inc, Washington, DC 20008 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Universidade de Sao Paulo; Institute Biomed Science, University Sao Paulo; 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); US Food & Drug Administration (FDA); Center for Biologics Evaluation & Research (CBER); Indian Council of Medical Research (ICMR); ICMR - National Institute for Research in Tuberculosis (NIRT); 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)
RP Mayer-Barber, KD (corresponding author), NIAID, Immunobiol Sect, LPD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mayerk@niaid.nih.gov
FU NIAID Intramural Research program; Concept Acceleration Program-Award from DMID, NIAID; National Institute of Allergy and Infectious Diseases [ZIAAI001044, ZIAAI000734, ZIAAI001171, ZIAAI001065, ZIAAI001081] Funding Source: NIH RePORTER
NR 32
TC 620
Z9 725
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 JUL 3
PY 2014
VL 511
IS 7507
BP 99
EP U491
DI 10.1038/nature13489
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400044
PM 24990750
DA 2026-03-09
ER

PT J
AU Averill, C
   Turner, BL
   Finzi, AC
AF Averill, Colin
   Turner, Benjamin L.
   Finzi, Adrien C.
TI Mycorrhiza-mediated competition between plants and decomposers drives soil carbon storage
SO NATURE
LA English
DT Article
ID organic-carbon; microbial efficiency; nitrogen limitation; sensitivity; ecosystems; matter
AB Soil contains more carbon than the atmosphere and vegetation combined(1). Understanding the mechanisms controlling the accumulation and stability of soil carbon is critical to predicting the Earth's future climate(2,3). Recent studies suggest that decomposition of soil organic matter is often limited by nitrogen availability to microbes(4-6) and that plants, via their fungal symbionts, compete directly with free-living decomposers for nitrogen(6,7). Ectomycorrhizal and ericoid mycorrhizal (EEM) fungi produce nitrogen-degrading enzymes, allowing them greater access to organic nitrogen sources than arbuscular mycorrhizal (AM) fungi(8-10). This leads to the theoretical prediction that soil carbon storage is greater in ecosystems dominated by EEM fungi than in those dominated by AM fungi(11). Using global data sets, we show that soil in ecosystems dominated by EEM-associated plants contains 70% more carbon per unit nitrogen than soil in ecosystems dominated by AM-associated plants. The effect of mycorrhizal type on soil carbon is independent of, and of far larger consequence than, the effects of net primary production, temperature, precipitation and soil clay content. Hence the effect of mycorrhizal type on soil carbon content holds at the global scale. This finding links the functional traits of mycorrhizal fungi to carbon storage at ecosystem-to-global scales, suggesting that plant-decomposer competition for nutrients exerts a fundamental control over the terrestrial carbon cycle.
C1 [Averill, Colin] Univ Texas Austin, Dept Integrat Biol, Grad Program Ecol Evolut & Behav, Austin, TX 78712 USA.
   [Turner, Benjamin L.] Smithsonian Trop Res Inst, Balboa, Ancon, Panama.
   [Finzi, Adrien C.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
C3 University of Texas System; University of Texas Austin; Smithsonian Institution; Smithsonian Tropical Research Institute; Boston University
RP Averill, C (corresponding author), Univ Texas Austin, Dept Integrat Biol, Grad Program Ecol Evolut & Behav, Austin, TX 78712 USA.
EM colin.averill@utexas.edu
FU Center for Tropical Forest Science (CTFS); Smithsonian Institution Geo-observatories (SIGEO); University of Texas at Austin; National Science Foundation [DGE-1110007]; NSF [DEB 07-43564]; DOE [10-DOE-1053, DE-SC0006916]; U.S. Department of Energy (DOE) [DE-SC0006916] Funding Source: U.S. Department of Energy (DOE)
NR 40
TC 820
Z9 972
U1 53
U2 1921
PU NATURE PUBLISHING 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 23
PY 2014
VL 505
IS 7484
BP 543
EP +
DI 10.1038/nature12901
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000038
PM 24402225
DA 2026-03-09
ER

PT J
AU Bhatia, V
   Barroso, SI
   García-Rubio, ML
   Tumini, E
   Herrera-Moyano, E
   Aguilera, A
AF Bhatia, Vaibhav
   Barroso, Sonia I.
   Garcia-Rubio, Maria L.
   Tumini, Emanuela
   Herrera-Moyano, Emilia
   Aguilera, Andres
TI BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2
SO NATURE
LA English
DT Article
ID replication fork progression; fanconi-anemia; transcription elongation; genomic instability; in-vitro; complex; impairment; stability; genes; recombination
AB Genome instability is central to ageing, cancer and other diseases. It is not only proteins involved in DNA replication or the DNA damage response (DDR) that are important for maintaining genome integrity: from yeast to higher eukaryotes, mutations in genes involved in pre-mRNA splicing and in the biogenesis and export of messenger ribonudeoprotein (mRNP) also induce DNA damage and genome instability. This instability is frequently mediated by R-loops formed by DNA-RNA hybrids and a displaced single-stranded DNA(1). Here we show that the human TREX-2 complex, which is involved in mRNP biogenesis and export, prevents genome instability as determined by the accumulation of gamma-H2AX (Ser-139 phosphorylated histone H2AX) and 53BP1 foci and single-cell electrophoresis in cells depleted of the TREX-2 subunits PCID2, GANP and DSSI. We show that the BRCA2 repair factor, which binds to DSS1, also associates with PCID2 in the cell. The use of an enhanced green fluorescent protein-tagged hybrid-binding domain of RNase HI and the S9.6 antibody did not detect R-loops in TREX-2-depleted cells, but did detect the accumulation of R-loops in BRCA2-depleted cells. The results indicate that R-loops are frequently formed in cells and that BRCA2 is required for their processing. This link between BRCA2 and RNA-mediated genome instability indicates that R-loops may be a chief source of replication stress and cancer-associated instability.
C1 [Bhatia, Vaibhav; Barroso, Sonia I.; Garcia-Rubio, Maria L.; Tumini, Emanuela; Herrera-Moyano, Emilia; Aguilera, Andres] Univ Seville, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Seville 41092, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Pablo de Olavide; University of Sevilla; CSIC - Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER)
RP Aguilera, A (corresponding author), Univ Seville, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Ave Amer Vespucio S-N, Seville 41092, Spain.
EM aguilo@us.es
FU Spanish Ministry of Economy and Competitiveness [C5D2007-00015, BFU2010-16372]; Junta de Andalucia [CVI4567]; European Union (FEDER)
NR 33
TC 422
Z9 509
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 17
PY 2014
VL 511
IS 7509
BP 362
EP +
DI 10.1038/nature13374
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200039
PM 24896180
DA 2026-03-09
ER

PT J
AU Sternberg, SH
   Redding, S
   Jinek, M
   Greene, EC
   Doudna, JA
AF Sternberg, Samuel H.
   Redding, Sy
   Jinek, Martin
   Greene, Eric C.
   Doudna, Jennifer A.
TI DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
SO NATURE
LA English
DT Article
ID immune-system; targeted mutagenesis; gene-expression; seed sequence; specificity; activation; mechanism; transcription; recognition; prokaryotes
AB The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.
C1 [Sternberg, Samuel H.; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Redding, Sy] Columbia Univ, Dept Chem, New York, NY 10032 USA.
   [Jinek, Martin; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Greene, Eric C.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Greene, Eric C.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; Columbia University; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Columbia University; Howard Hughes Medical Institute; Columbia University; 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 Doudna, JA (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM ecg2108@columbia.edu; doudna@berkeley.edu
FU National Science Foundation [MCB-1154511, MCB-1244557]; National Defense Science & Engineering Graduate Research Fellowship programs; National Institutes of Health [GM074739]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1154511] Funding Source: National Science Foundation; National Institute of General Medical Sciences [T32GM066698] Funding Source: NIH RePORTER
NR 48
TC 1403
Z9 2060
U1 16
U2 754
PU NATURE PUBLISHING 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 6
PY 2014
VL 507
IS 7490
BP 62
EP +
DI 10.1038/nature13011
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400042
PM 24476820
DA 2026-03-09
ER

PT J
AU Zhao, HT
   Sheng, G
   Wang, JY
   Wang, M
   Bunkoczi, G
   Gong, WM
   Wei, ZY
   Wang, YL
AF Zhao, Hongtu
   Sheng, Gang
   Wang, Jiuyu
   Wang, Min
   Bunkoczi, Gabor
   Gong, Weimin
   Wei, Zhiyi
   Wang, Yanli
TI Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli
SO NATURE
LA English
DT Article
ID in-vitro reconstitution; crispr-cas systems; target recognition; antiviral defense; seed sequence; dna; interference; prokaryotes; degradation; crystallography
AB Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (Cas) proteins form the CRISPR/Cas system to defend against foreign nucleic acids of bacterial and archaeal origin(1-9). In the I-E subtype CRISPR/Cas system, eleven subunits from five Cas proteins (CasA(1)B(2)C(6)D(1)E(1)) assemble along a CRISPR RNA (crRNA) to form the Cascade complex(10-13). Here we report on the 3.05 angstrom crystal structure of the 405-kilodalton Escherichia coli Cascade complex that provides molecular details beyond those available from earlier lower-resolution cryo-electron microscopy structures. The bound 61-nucleotide crRNA spans the entire 11-protein subunit-containing complex, where it interacts with all six CasC subunits (named CasC1-6), with its 5 ' and 3 ' terminal repeats anchored by CasD and CasE, respectively. The crRNA spacer region is positioned along a continuous groove on the concave surface generated by the aligned CasC1-6 subunits. The five long beta-hairpins that project from individual CasC2-6 subunits extend across the crRNA, with each beta-hairpin inserting into the gap between the last stacked base and its adjacent splayed counterpart, and positioned within the groove of the preceding CasC subunit. Therefore, instead of continuously stacking, the crRNA spacer region is divided into five equal fragments, with each fragment containing five stacked bases flanked by one flipped-out base. Each of those crRNA spacer fragments interacts with CasC in a similar fashion. Furthermore, our structure explains why the seed sequence, with its outward directed bases, has a critical role in target DNA recognition. Inconclusion, our structure of the Cascade complex provides novel molecular details of protein-protein and protein-RNA alignments and interactions required for generation of a complex mediating RNA-guided immune surveillance.
C1 [Zhao, Hongtu; Sheng, Gang; Wang, Jiuyu; Wang, Min; Gong, Weimin; Wang, Yanli] Chinese Acad Sci, Inst Biophys, Lab RNA Biol, Beijing 100101, Peoples R China.
   [Zhao, Hongtu] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
   [Bunkoczi, Gabor] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Wei, Zhiyi] South Univ Sci & Technol China, Dept Biol, Shenzhen 518055, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Biophysics, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Southern University of Science & Technology
RP Wang, YL (corresponding author), Chinese Acad Sci, Inst Biophys, Lab RNA Biol, Beijing 100101, Peoples R China.
EM wei.zy@sustc.edu.cn; ylwang@ibp.ac.cn
FU Chinese Ministry of Science and Technology [2014CB910102, 2011CBA01105]; Natural Science Foundation of China [31222014, 31170705]; Strategic Priority Research program of the Chinese Academy of Sciences [XDB08010203]; South University of Science and Technology of China; Shenzhen Government
NR 39
TC 144
Z9 180
U1 4
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 NOV 6
PY 2014
VL 515
IS 7525
BP 147
EP +
DI 10.1038/nature13733
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500047
PM 25118175
DA 2026-03-09
ER

PT J
AU Deng, D
   Xu, C
   Sun, PC
   Wu, JP
   Yan, CY
   Hu, MX
   Yan, N
AF Deng, Dong
   Xu, Chao
   Sun, Pengcheng
   Wu, Jianping
   Yan, Chuangye
   Hu, Mingxu
   Yan, Nieng
TI Crystal structure of the human glucose transporter GLUT1
SO NATURE
LA English
DT Article
ID blood-brain-barrier; deficiency syndrome; mutations; epilepsy; onset; expression; proteins; spectrum; model
AB The glucose transporter GLUT1 catalyses facilitative diffusion of glucose into erythrocytes and is responsible for glucose supply to the brain and other organs. Dysfunctional mutations may lead to GLUT1 deficiency syndrome, whereas overexpression of GLUT1 is a prognostic indicator for cancer. Despite decades of investigation, the structure of GLUT1 remains unknown. Here we report the crystal structure of human GLUT1 at 3.2 angstrom resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides an insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homologue XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.
C1 [Deng, Dong; Xu, Chao; Sun, Pengcheng; Wu, Jianping; Yan, Chuangye; Hu, Mingxu; Yan, Nieng] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Deng, Dong; Xu, Chao; Sun, Pengcheng; Wu, Jianping; Yan, Chuangye; Hu, Mingxu; Yan, Nieng] Tsinghua Univ, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Deng, Dong; Xu, Chao; Sun, Pengcheng; Wu, Jianping; Yan, Chuangye; Hu, Mingxu; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Deng, Dong; Xu, Chao; Wu, Jianping; Hu, Mingxu; Yan, Nieng] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
RP Yan, N (corresponding author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2011CB910501]; National Natural Science Foundation of China [31321062-20131319400, 31125009, 91017011]; Tsinghua-Peking Center for Life Sciences; Howard Hughes Medical Institute
NR 60
TC 630
Z9 747
U1 19
U2 722
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2014
VL 510
IS 7503
BP 121
EP +
DI 10.1038/nature13306
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900040
PM 24847886
DA 2026-03-09
ER

PT J
AU Jullien, T
   Roulleau, P
   Roche, B
   Cavanna, A
   Jin, Y
   Glattli, DC
AF Jullien, T.
   Roulleau, P.
   Roche, B.
   Cavanna, A.
   Jin, Y.
   Glattli, D. C.
TI Quantum tomography of an electron
SO NATURE
LA English
DT Article
ID states; light; qubit
AB The complete knowledge of a quantum state allows the prediction of the probability of all possible measurement outcomes, a crucial step in quantum mechanics. It can be provided by tomographic methods(1) which have been applied to atomic(2,3), molecular(4), spin(5,6) and photonic states. For optical(7-9) or microwave(10-13) photons, standard tomography is obtained by mixing the unknown state with a large-amplitude coherent photon field. However, for fermions such as electrons in condensed matter, this approach is not applicable because fermionic fields are limited to small amplitudes (at most one particle per state), and so far no determination of an electron wavefunction has been made. Recent proposals involving quantum conductors suggest that the wavefunction can be obtained by measuring the time-dependent current of electronic wave interferometers(14) or the current noise of electronic Hanbury-Brown/Twiss interferometers(15-17). Here we show that such measurements are possible despite the extreme noise sensitivity required, and present the reconstructed wavefunction quasi-probability, or Wigner distribution function(17), of single electrons injected into a ballistic conductor. Many identical electrons are prepared in well-controlled quantum states called levitons(18) by repeatedly applying Lorentzian voltage pulses to a contact on the conductor(19-21). After passing through an electron beam splitter, the levitons are mixed with a weak-amplitude fermionic field formed by a coherent superposition of electron-hole pairs generated by a small alternating current with a frequency that is a multiple of the voltage pulse frequency(16). Antibunching of the electrons and holes with the levitons at the beam splitter changes the leviton partition statistics, and the noise variations provide the energy density matrix elements of the levitons. This demonstration of quantum tomography makes the developing field of electron quantum optics with ballistic conductors a new test-bed for quantum information with fermions(20,22-24). These results may find direct application in probing the entanglement of electron flying quantum bits(25), electron decoherence(17) and electron interactions. They could also be applied to cold fermionic (or spin-1/2) atoms(26).
C1 [Jullien, T.; Roulleau, P.; Roche, B.; Glattli, D. C.] CEA Saclay, CNRS, URA 2464, Serv Phys Etat Condense,IRAMIS DSM, F-91191 Gif Sur Yvette, France.
   [Cavanna, A.; Jin, Y.] CNRS, Lab Photon & Nanostruct, F-91460 Marcoussis, France.
C3 Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS)
RP Glattli, DC (corresponding author), CEA Saclay, CNRS, URA 2464, Serv Phys Etat Condense,IRAMIS DSM, F-91191 Gif Sur Yvette, France.
EM christian.glattli@cea.fr
FU ERC [228273 MeQuaNo]
NR 31
TC 185
Z9 189
U1 0
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 30
PY 2014
VL 514
IS 7524
BP 603
EP 607
DI 10.1038/nature13821
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500043
PM 25355360
DA 2026-03-09
ER

PT J
AU Liu, YJ
   Xu, H
   Kong, WJ
   Shang, M
   Dai, HX
   Yu, JQ
AF Liu, Yue-Jin
   Xu, Hui
   Kong, Wei-Jun
   Shang, Ming
   Dai, Hui-Xiong
   Yu, Jin-Quan
TI Overcoming the limitations of directed C-H functionalizations of heterocycles
SO NATURE
LA English
DT Article
ID ortho-metalation; bonds; arylation; activation; pyridine
AB In directed C-H activation reactions, any nitrogen or sulphur atoms present in heterocyclic substrates will coordinate strongly with metal catalysts. This coordination, which can lead to catalyst poisoning or C-H functionalization at an undesired position, limits the application of C-H activation reactions in heterocycle-based drug discovery(1-5), in which regard they have attracted much interest from pharmaceutical companies(3-5). Here we report a robust and synthetically useful method that overcomes the complications associated with performing C-H functionalization reactions on heterocycles. Our approach employs a simple N-methoxy amide group, which serves as both a directing group and an anionic ligand that promotes the in situ generation of the reactive PdX2 (X = ArCONOMe) species from a Pd(0) source using air as the sole oxidant. In this way, the PdX2 species is localized near the target C-H bond, avoiding interference from any nitrogen or sulphur atoms present in the heterocyclic substrates. This reaction overrides the conventional positional selectivity patterns observed with substrates containing strongly coordinating heteroatoms, including nitrogen, sulphur and phosphorus. Thus, this operationally simple aerobic reaction demonstrates that it is possible to bypass a fundamental limitation that has long plagued applications of directed C-H activation in medicinal chemistry.
C1 [Liu, Yue-Jin; Xu, Hui; Kong, Wei-Jun; Shang, Ming; Dai, Hui-Xiong; Yu, Jin-Quan] Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, Shanghai 200032, Peoples R China.
   [Yu, Jin-Quan] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; Scripps Research Institute
RP Dai, HX (corresponding author), Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China.
EM hxdai@sioc.ac.cn; yu200@scripps.edu
FU Shanghai Institute of Organic Chemistry; Chinese Academy of Sciences; CAS/SAFEA International Partnership Program for Creative Research Teams; National Natural Science Foundation of China [NSFC-21121062]; Recruitment Program of Global Experts; Scripps Research Institute; NIH (NIGMS) [1R01 GM102265]; National Institute of General Medical Sciences [R01GM102265] Funding Source: NIH RePORTER
NR 30
TC 306
Z9 325
U1 3
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 20
PY 2014
VL 515
IS 7527
BP 389
EP 393
DI 10.1038/nature13885
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600040
PM 25383516
DA 2026-03-09
ER

PT J
AU Denger, K
   Weiss, M
   Felux, AK
   Schneider, A
   Mayer, C
   Spiteller, D
   Huhn, T
   Cook, AM
   Schleheck, D
AF Denger, Karin
   Weiss, Michael
   Felux, Ann-Katrin
   Schneider, Alexander
   Mayer, Christoph
   Spiteller, Dieter
   Huhn, Thomas
   Cook, Alasdair M.
   Schleheck, David
TI Sulphoglycolysis in Escherichia coli K-12 closes a gap in the biogeochemical sulphur cycle
SO NATURE
LA English
DT Article
ID complete degradation; bacteria; sulfoquinovose; pathway; biosynthesis; synthase; enzymes
AB Sulphoquinovose (SQ, 6-deoxy-6-sulphoglucose) has been known for 50 years as the polar headgroup of the plant sulpholipid(1,2) in the photosynthetic membranes of all higher plants, mosses, ferns, algae and most photosynthetic bacteria(3). It is also found in some non-photosynthetic bacteria(4), and SQ is part of the surface layer of some Archaea(5). The estimated annual production of SQ(4) is 10,000,000,000 tonnes (10 petagrams), thus it comprises a major portion of the organo-sulphur in nature, where SQ is degraded by bacteria(6,7). However, despite evidence for at least three different degradative pathways in bacteria(6-8), no enzymic reaction or gene in any pathway has been defined, although a sulphoglycolytic pathway has been proposed(7). Here we show that Escherichia coli K-12, the most widely studied prokaryotic model organism, performs sulphoglycolysis, in addition to standard glycolysis. SQ is catabolised through four newly discovered reactions that we established using purified, heterologously expressed enzymes: SQ isomerase, 6-deoxy-6-sulphofructose (SF) kinase, 6-deoxy-6-sulphofructose-1-phosphate (SFP) aldolase, and 3-sulpholactaldehyde (SLA) reductase. The enzymes are encoded in a ten-gene cluster, which probably also encodes regulation, transport and degradation of the whole sulpholipid; the gene cluster is present in almost all (>91%) available E. coli genomes, and is wide-spread in Enterobacteriaceae. The pathway yields dihydroxyacetone phosphate (DHAP), which powers energy conservation and growth of E. coli, and the sulphonate product 2,3-dihydroxypropane-1-sulphonate (DHPS), which is excreted. DHPS is mineralized by other bacteria, thus closing the sulphur cycle within a bacterial community.
C1 [Denger, Karin; Spiteller, Dieter; Cook, Alasdair M.; Schleheck, David] Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
   [Weiss, Michael; Felux, Ann-Katrin] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78457 Constance, Germany.
   [Schneider, Alexander; Mayer, Christoph] Univ Tubingen, Interfac Inst Microbiol & Infect Med, D-72076 Tubingen, Germany.
   [Huhn, Thomas] Univ Konstanz, Dept Chem, D-78457 Constance, Germany.
C3 University of Konstanz; University of Konstanz; Eberhard Karls University of Tubingen; University of Konstanz
RP Cook, AM (corresponding author), Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
EM alasdair.cook@uni-konstanz.de; david.schleheck@uni-konstanz.de
FU Konstanz Research School Chemical Biology (KoRS-CB); German Research Foundation (DFG) [MA2436/4, SFB766/A15]; Baden-Wurttemberg Stiftung [P-BWS-Glyko11]; DFG [SCHL 1936/1-1]; University of Konstanz; Konstanz Young Scholar Fund
NR 28
TC 107
Z9 122
U1 2
U2 81
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2014
VL 507
IS 7490
BP 114
EP +
DI 10.1038/nature12947
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400053
PM 24463506
DA 2026-03-09
ER

PT J
AU Smith, RF
   Eggert, JH
   Jeanloz, R
   Duffy, TS
   Braun, DG
   Patterson, JR
   Rudd, RE
   Biener, J
   Lazicki, AE
   Hamza, AV
   Wang, J
   Braun, T
   Benedict, LX
   Celliers, PM
   Collins, GW
AF Smith, R. F.
   Eggert, J. H.
   Jeanloz, R.
   Duffy, T. S.
   Braun, D. G.
   Patterson, J. R.
   Rudd, R. E.
   Biener, J.
   Lazicki, A. E.
   Hamza, A. V.
   Wang, J.
   Braun, T.
   Benedict, L. X.
   Celliers, P. M.
   Collins, G. W.
TI Ramp compression of diamond to five terapascals
SO NATURE
LA English
DT Article
ID mass-radius relationships; ductile porous materials; laser-shock compression; equation-of-state; high-pressure; isentropic compression; solid exoplanets; interior; hydrogen; models
AB The recent discovery of more than a thousand planets outside our Solar System(1,2), together with the significant push to achieve inertially confined fusion in the laboratory(3), has prompted a renewed interest in how dense matter behaves at millions to billions of atmospheres of pressure. The theoretical description of such electron-degenerate matter has matured since the early quantum statistical model of Thomas and Fermi(4-10), and now suggests that new complexities can emerge at pressures where core electrons (not only valence electrons) influence the structure and bonding of matter(11). Recent developments in shock-free dynamic (ramp) compression now allow laboratory access to this dense matter regime. Here we describe ramp-compression measurements for diamond, achieving 3.7-fold compression at a peak pressure of 5 terapascals (equivalent to 50 million atmospheres). These equation-of-state data can now be compared to first-principles density functional calculations(12) and theories long used to describe matter present in the interiors of giant planets, in stars, and in inertial-confinement fusion experiments. Our data also provide new constraints on mass-radius relationships for carbon-rich planets.
C1 [Smith, R. F.; Eggert, J. H.; Braun, D. G.; Patterson, J. R.; Rudd, R. E.; Biener, J.; Lazicki, A. E.; Hamza, A. V.; Braun, T.; Benedict, L. X.; Celliers, P. M.; Collins, G. W.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Jeanloz, R.; Wang, J.] Univ Calif Berkeley, Dept Earth & Planetary Sci, Dept Astron, Berkeley, CA 94720 USA.
   [Jeanloz, R.; Wang, J.] Univ Calif Berkeley, Miller Inst Basic Res Sci, Berkeley, CA 94720 USA.
   [Duffy, T. S.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
C3 United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Princeton University
RP Collins, GW (corresponding author), Lawrence Livermore Natl Lab, POB 808, Livermore, CA 94550 USA.
EM collins7@llnl.gov
FU US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Department of Energy; University of California; Miller Institute for Basic Research in Science
NR 49
TC 212
Z9 260
U1 3
U2 182
PU NATURE PUBLISHING 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 17
PY 2014
VL 511
IS 7509
BP 330
EP +
DI 10.1038/nature13526
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200031
PM 25030170
DA 2026-03-09
ER

PT J
AU Finnegan, NJ
   Schumer, R
   Finnegan, S
AF Finnegan, Noah J.
   Schumer, Rina
   Finnegan, Seth
TI A signature of transience in bedrock river incision rates over timescales of 104-107 years
SO NATURE
LA English
DT Article
ID cosmogenic al-26; tibetan-plateau; strath terraces; stream incision; climate-change; yellow-river; fore-arc; erosion; canyon; uplift
AB Measured rates of river incision into bedrock are commonly interpreted as proxies for rates of rock uplift (see refs 1 and 2, for example) and indices of the strength of climatic forcing of erosion over time (see refs 3 and 4, for example). This approach implicitly assumes that river incision rates are in equilibrium with external forcings over a wide range of timescales. Here we directly test this assumption by examining the temporal scaling of bedrock river incision from 155 independent measurements of river incision compiled from 14 sites. Of these sites, 11 exhibit a negative power-law dependence of bedrock river incision rate on measurement interval, a relationship that is apparent over timescales of 10(4)-10(7) years and is independent of tectonic and geomorphic setting. Thus, like rates of sediment accumulation(5), rates of river incision into bedrock exhibit non-steady-state behaviour even over very long measurement intervals. Non-steady-state behaviour can be explained by episodic hiatuses in river incision triggered by alluvial deposition, if such hiatuses have a heavy-tailed length distribution(6). Regardless of its cause, the dependence of incision rate on measurement interval complicates efforts to infer tectonic or climatic forcing from changes in rates of river incision over time or from comparison of rates computed over different timescales.
C1 [Finnegan, Noah J.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Schumer, Rina] Desert Res Inst, Div Hydrol Sci, Reno, NV 89512 USA.
   [Finnegan, Seth] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Santa Cruz; Nevada System of Higher Education (NSHE); Desert Research Institute NSHE; University of California System; University of California Berkeley
RP Finnegan, NJ (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
EM nfinnega@ucsc.edu
FU National Science Foundation [EAR-1049889]; Division Of Earth Sciences; Directorate For Geosciences [1242458] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1049889] Funding Source: National Science Foundation
NR 39
TC 150
Z9 181
U1 1
U2 88
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 16
PY 2014
VL 505
IS 7483
BP 391
EP +
DI 10.1038/nature12913
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800040
PM 24429636
DA 2026-03-09
ER

PT J
AU Tschopp, P
   Sherratt, E
   Sanger, TJ
   Groner, AC
   Aspiras, AC
   Hu, JK
   Pourquié, O
   Gros, J
   Tabin, CJ
AF Tschopp, Patrick
   Sherratt, Emma
   Sanger, Thomas J.
   Groner, Anna C.
   Aspiras, Ariel C.
   Hu, Jimmy K.
   Pourquie, Olivier
   Gros, Jerome
   Tabin, Clifford J.
TI A relative shift in cloacal location repositions external genitalia in amniote evolution
SO NATURE
LA English
DT Article
ID gene-expression; mesenchymal transition; vertebrate embryos; homology; package; limb; ontology; program; biology; tissue
AB The move of vertebrates to a terrestrial lifestyle required major adaptations in their locomotory apparatus and reproductive organs. While the fin-to-limb transition has received considerable attention(1,2), little is known about the developmental and evolutionary origins of external genitalia. Similarities in gene expression have been interpreted as a potential evolutionary link between the limb and genitals(3-6); however, no underlying developmental mechanism has been identified. We re-examined this question using micro-computed tomography, lineage tracing in three amniote clades, and RNA-sequencing-based transcriptional profiling. Here we show that the developmental origin of external genitalia has shifted through evolution, and in some taxa limbs and genitals share a common primordium. In squamates, the genitalia develop directly from the budding hindlimbs, or the remnants thereof, whereas in mice the genital tubercle originates from the ventral and tail bud mesenchyme. The recruitment of different cell populations for genital outgrowth follows a change in the relative position of the cloaca, the genitalia organizing centre. Ectopic grafting of the cloaca demonstrates the conserved ability of different mesenchymal cells to respond to these genitalia-inducing signals. Our results support a limb-like developmental origin of external genitalia as the ancestral condition. Moreover, they suggest that a change in the relative position of the cloacal signalling centre during evolution has led to an altered developmental route for external genitalia in mammals, while preserving parts of the ancestral limb molecular circuitry owing to a common evolutionary origin.
C1 [Tschopp, Patrick; Aspiras, Ariel C.; Hu, Jimmy K.; Pourquie, Olivier; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sherratt, Emma; Sanger, Thomas J.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Groner, Anna C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Pourquie, Olivier] IGBMC, F-67400 Illkirch Graffenstaden, France.
   [Pourquie, Olivier] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Gros, Jerome] Inst Pasteur, Dev & Stem Cell Biol Dept, F-75724 Paris 15, France.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Institut National de la Sante et de la Recherche Medicale (Inserm); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
RP Tabin, CJ (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM jgros@pasteur.fr; tabin@genetics.med.harvard.edu
FU National Science Foundation [ECS-0335765]; Swiss National Science Foundation; EMBO; Human Frontiers Science Program; National Institutes of Health [R37-HD032443]
NR 48
TC 64
Z9 80
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 DEC 18
PY 2014
VL 516
IS 7531
BP 391
EP +
DI 10.1038/nature13819
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800046
PM 25383527
DA 2026-03-09
ER

PT J
AU Licht, A
   van Cappelle, M
   Abels, HA
   Ladant, JB
   Trabucho-Alexandre, J
   France-Lanord, C
   Donnadieu, Y
   Vandenberghe, J
   Rigaudier, T
   Lécuyer, C
   Terry, D
   Adriaens, R
   Boura, A
   Guo, Z
   Soe, AN
   Quade, J
   Dupont-Nivet, G
   Jaeger, JJ
AF Licht, A.
   van Cappelle, M.
   Abels, H. A.
   Ladant, J. -B.
   Trabucho-Alexandre, J.
   France-Lanord, C.
   Donnadieu, Y.
   Vandenberghe, J.
   Rigaudier, T.
   Lecuyer, C.
   Terry, D., Jr.
   Adriaens, R.
   Boura, A.
   Guo, Z.
   Soe, Aung Naing
   Quade, J.
   Dupont-Nivet, G.
   Jaeger, J. -J.
TI Asian monsoons in a late Eocene greenhouse world
SO NATURE
LA English
DT Article
ID late middle eocene; grain-size; isotope compositions; pondaung formation; stable-isotopes; climate; oxygen; china; reconstructions; sensitivity
AB The strong present-day Asian monsoons are thought to have originated between 25 and 22 million years (Myr) ago, driven by Tibetan-Himalayan uplift. However, the existence of older Asian monsoons and their response to enhanced greenhouse conditions such as those in the Eocene period (55-34Myrago) are unknown because of the paucity of well-dated records. Here we show late Eocene climate records revealing marked monsoon-like patterns in rainfall and wind south and north of the Tibetan-Himalayan orogen. This is indicated by low oxygen isotope values with strong seasonality in gastropod shells and mammal teeth from Myanmar, and by aeolian dust deposition in northwest China. Our climate simulations support modern-like Eocene monsoonal rainfall and show that a reinforced hydrological cycle responding to enhanced greenhouse conditions counterbalanced the negative effect of lower Tibetan relief on precipitation. These strong monsoons later weakened with the global shift to icehouse conditions 34 Myr ago.
C1 [Licht, A.; Jaeger, J. -J.] Univ Poitiers, CNRS, Inst Paleoprimatol Paleontol Humaine Evolut & Pal, UMR 7262, F-86000 Poitiers, France.
   [Licht, A.; France-Lanord, C.; Rigaudier, T.] Univ Lorraine, CNRS, Ctr Rech Petrograph & Geochim, UMR 7358, F-54501 Vandoeuvre Les Nancy, France.
   [Licht, A.; Quade, J.] Univ Arizona, Dept Geosci, Tucson, AZ 85721 USA.
   [van Cappelle, M.; Abels, H. A.; Dupont-Nivet, G.] Univ Utrecht, Dept Earth Sci, NL-3584 CD Utrecht, Netherlands.
   [van Cappelle, M.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Abels, H. A.; Adriaens, R.] Katholieke Univ Leuven, Dept Earth & Environm Sci, B-3001 Louvain, Belgium.
   [Ladant, J. -B.; Donnadieu, Y.] CNRS, Lab Sci Climat & Environm, UMR 8212, F-91198 Gif Sur Yvette, France.
   [Trabucho-Alexandre, J.] Univ Durham, Dept Earth Sci, Durham DH1 3LE, England.
   [Vandenberghe, J.] Vrije Univ, Dept Earth Sci, NL-1081 HV Amsterdam, Netherlands.
   [Lecuyer, C.] Univ Lyon, CNRS, Inst Univ France, Lab Geol Lyon,UMR 5276, F-69622 Lyon, France.
   [Terry, D., Jr.] Temple Univ, Dept Earth & Environm Sci, Philadelphia, PA 19122 USA.
   [Boura, A.] UPMC, MNHN, CNRS, Ctr Rech Paleodiversite & Paleoenvironm, F-75005 Paris, France.
   [Guo, Z.; Dupont-Nivet, G.] Peking Univ, Key Lab Orogen Belts & Crustal Evolut, Beijing 100871, Peoples R China.
   [Soe, Aung Naing] Def Serv Acad, Dept Geol, Pyin Oo Lwin, Myanmar.
   [Dupont-Nivet, G.] Univ Rennes, CNRS, UMR 6118, F-35042 Rennes, France.
   [Dupont-Nivet, G.] Univ Potsdam, Inst Earth & Environm Sci, D-14476 Potsdam, Germany.
C3 Universite de Poitiers; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Lorraine; University of Arizona; Utrecht University; Imperial College London; KU Leuven; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Durham University; Vrije Universiteit Amsterdam; Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Lyon 1; Institut Universitaire de France; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Peking University; Universite de Rennes; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Potsdam
RP Licht, A (corresponding author), Univ Poitiers, CNRS, Inst Paleoprimatol Paleontol Humaine Evolut & Pal, UMR 7262, F-86000 Poitiers, France.
EM alicht@email.arizona.edu
FU University of Poitiers; Netherlands Organisation for Scientific Research (NWO-ALW); Marie Curie CIG [294282]; Ministry of Culture of the Republic of the Union of Myanmar; French ministry of Foreign Affairs; French ministry of Higher Education and Research; Alexander von Humboldt Foundation; Chinese Ministry of Education; National Natural Science Foundation of China (NSFC); Fyssen Foundation;  [ANR-09-BLAN-0238-02]; Academy of Finland (AKA) [294282] Funding Source: Academy of Finland (AKA)
NR 49
TC 420
Z9 492
U1 2
U2 293
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 501
EP +
DI 10.1038/nature13704
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800030
PM 25219854
DA 2026-03-09
ER

PT J
AU Cogan, GB
   Thesen, T
   Carlson, C
   Doyle, W
   Devinsky, O
   Pesaran, B
AF Cogan, Gregory B.
   Thesen, Thomas
   Carlson, Chad
   Doyle, Werner
   Devinsky, Orrin
   Pesaran, Bijan
TI Sensory-motor transformations for speech occur bilaterally
SO NATURE
LA English
DT Article
ID brain; integration; perception; language
AB Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output(1-4). A kind of 'parity' is essential, as both perception-and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere(5,6). Although various theories have been proposed to unite perception and production(2,7), the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area)(8,9). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system(10). Although recent evidence indicates that speech perception occurs bilaterally(11-13), prevailing models maintain that the speech sensory-motor system is left lateralized(11,14-18) and facilitates the transformation from sensory-based auditory representations to motor-based production representations(11,15,16). However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging(16,19). Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception-and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.
C1 [Cogan, Gregory B.; Pesaran, Bijan] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Thesen, Thomas; Carlson, Chad; Devinsky, Orrin] NYU, Sch Med, Dept Neurol, New York, NY 10016 USA.
   [Doyle, Werner; Devinsky, Orrin] NYU, Sch Med, Dept Neurosurg, New York, NY 10016 USA.
C3 New York University; New York University; New York University
RP Pesaran, B (corresponding author), NYU, Ctr Neural Sci, New York, NY 10003 USA.
EM bijan@nyu.edu
FU NIDCD [R03-DC010475]; Burroughs Wellcome Fund; NYSTAR; McKnight Scholar Award; Sloan Research Fellowship
NR 36
TC 181
Z9 209
U1 0
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 MAR 6
PY 2014
VL 507
IS 7490
BP 94
EP +
DI 10.1038/nature12935
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400049
PM 24429520
DA 2026-03-09
ER

PT J
AU Buffett, B
AF Buffett, Bruce
TI Geomagnetic fluctuations reveal stable stratification at the top of the Earth's core
SO NATURE
LA English
DT Article
ID magnetic-field; mantle boundary; torsional oscillations; secular variation; motions
AB Modern observations of the geomagnetic field reveal fluctuations(1-3) with a dominant period of about 60 years. These fluctuations are probably a result of waves in the liquid core(4), although the precise nature of the waves is uncertain. Common suggestions include a type of magnetic wave, known as a torsional oscillation(5), but recent studies(6) favour periods that are too short to account for a 60-year fluctuation. Another possibility involves MAC waves(7), which arise from the interplay between magnetic, Archimedes and Coriolis forces. Waves with a suitable period can emerge when the top of the core is stably stratified. Here I show that MAC waves provide a good description of time-dependent zonal flow at the top of the core(8), as inferred from geomagnetic secular variation(9). The same wave motion can also account for unexplained fluctuations in the dipole field(10). Both of these independent predictions require a 140-kilometre-thick stratified layer with a buoyancy frequency comparable to the Earth's rotation rate. Such a stratified layer could have a thermal origin(11,12), implying a core heat flow of about 13 terawatts. Alternatively, the layer could result from chemical stratification(13,14). In either case, the existence of a stratified layer at the top of the core obscures the nature of flow deeper in the core, where the magnetic field is continually regenerated.
C1 Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Buffett, B (corresponding author), Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
EM bbuffett@berkeley.edu
FU US National Science Foundation [EAR-1045277]
NR 32
TC 148
Z9 158
U1 0
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 MAR 27
PY 2014
VL 507
IS 7493
BP 484
EP +
DI 10.1038/nature13122
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000037
PM 24670768
DA 2026-03-09
ER

PT J
AU Zhang, ZS
   Ramstein, G
   Schuster, M
   Li, C
   Contoux, C
   Yan, Q
AF Zhang, Zhongshi
   Ramstein, Gilles
   Schuster, Mathieu
   Li, Camille
   Contoux, Camille
   Yan, Qing
TI Aridification of the Sahara desert caused by Tethys Sea shrinkage during the Late Miocene
SO NATURE
LA English
DT Article
ID climate-change; african; evolution; monsoon; simulations; feedbacks; plateau; uplift; model; age
AB It is widely believed that the Sahara desert is no more than similar to 2-3-million years (Myr) old(1), with geological evidence showing a remarkable aridification of north Africa at the onset of the Quaternary ice ages(2-4). Before that time, north African aridity was mainly controlled by the African summer monsoon (ASM)(5-8), which oscillated with Earth's orbital precession cycles. Afterwards, the Northern Hemisphere glaciation added an ice volume forcing on the ASM, which additionally oscillated with glacial-interglacial cycles(2). These findings led to the idea that the Sahara desert came into existence when the Northern Hemisphere glaciated similar to 2-3 Myr ago. The later discovery, however, of aeolian dune deposits similar to 7 Myr old(9) suggested a much older age, although this interpretation is hotly challenged(1) and there is no clear mechanism for aridification around this time. Here we use climate model simulations to identify the Tortonian stage (similar to 7-11 Myr ago) of the Late Miocene epoch as the pivotal period for triggering north African aridity and creating the Sahara desert. Through a set of experiments with the Norwegian Earth System Model(10) and the Community Atmosphere Model(11), we demonstrate that the African summer monsoon was drastically weakened by the Tethys Sea shrinkage during the Tortonian, allowing arid, desert conditions to expand across north Africa. Not only did the Tethys shrinkage alter the mean climate of the region, it also enhanced the sensitivity of the African monsoon to orbital forcing, which subsequently became the major driver of Sahara extent fluctuations. These important climatic changes probably caused the shifts in Asian and African flora and fauna observed during the same period(4,12-14), with possible links to the emergence of early hominins in north Africa(15,16).
C1 [Zhang, Zhongshi; Contoux, Camille] Uni Res Climate, Bjerknes Ctr Climate Res, N-5007 Bergen, Norway.
   [Zhang, Zhongshi; Yan, Qing] Chinese Acad Sci, Inst Atmospher Phys, Nansen Zhu Int Res Ctr, Beijing 100029, Peoples R China.
   [Ramstein, Gilles] CE Saclay, CEA CNRS UVSQ, Lab Sci Climat & Environm IPSL, UMR8212, F-91191 Gif Sur Yvette, France.
   [Schuster, Mathieu] CNRS, Ecole & Observ Sci Terre, Inst Phys Globe Strasbourg UMR 7516, F-67084 Strasbourg, France.
   [Schuster, Mathieu] Univ Strasbourg, F-67084 Strasbourg, France.
   [Li, Camille] Univ Bergen, Inst Geophys, Bjerknes Ctr Climate Res, N-5007 Bergen, Norway.
C3 Bjerknes Centre for Climate Research; Chinese Academy of Sciences; Institute of Atmospheric Physics, CAS; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); CEA; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Bjerknes Centre for Climate Research; University of Bergen
RP Zhang, ZS (corresponding author), Uni Res Climate, Bjerknes Ctr Climate Res, Allegaten 70, N-5007 Bergen, Norway.
EM zhongshi.zhang@uni.no
FU Chinese Academy of Sciences [XDA05080803]; National 973 Program of China [2010CB950102]; Earth System Modelling (ESM) project - Statoil, Norway; Dynamics of Past Warm Climates (DYNAWARM) project - Centre for Climate Dynamics (SKD) at the Bjerknes Centre; Aurora mobility program France-Norway - Research Council of Norway
NR 53
TC 232
Z9 279
U1 5
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 18
PY 2014
VL 513
IS 7518
BP 401
EP +
DI 10.1038/nature13705
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900056
PM 25230661
DA 2026-03-09
ER

PT J
AU Karhu, K
   Auffret, MD
   Dungait, JAJ
   Hopkins, DW
   Prosser, JI
   Singh, BK
   Subke, JA
   Wookey, PA
   Ågren, GI
   Sebastià, MT
   Gouriveau, F
   Bergkvist, G
   Meir, P
   Nottingham, AT
   Salinas, N
   Hartley, IP
AF Karhu, Kristiina
   Auffret, Marc D.
   Dungait, Jennifer A. J.
   Hopkins, David W.
   Prosser, James I.
   Singh, Brajesh K.
   Subke, Jens-Arne
   Wookey, Philip A.
   Agren, Goran I.
   Sebastia, Maria-Teresa
   Gouriveau, Fabrice
   Bergkvist, Goran
   Meir, Patrick
   Nottingham, Andrew T.
   Salinas, Norma
   Hartley, Iain P.
TI Temperature sensitivity of soil respiration rates enhanced by microbial community response
SO NATURE
LA English
DT Article
ID thermal-acclimation; carbon; adaptation; decomposition; feedbacks
AB Soils store about four times as much carbon as plant biomass(1), and soil microbial respiration releases about 60 petagrams of carbon per year to the atmosphere as carbon dioxide(2). Short-term experiments have shown that soil microbial respiration increases exponentially with temperature(3). This information has been incorporated into soil carbon and Earth-system models, which suggest that warming-induced increases in carbon dioxide release from soils represent an important positive feedback loop that could influence twenty-first-century climate change(4). The magnitude of this feedback remains uncertain, however, not least because the response of soil microbial communities to changing temperatures has the potential to either decrease(5-7) or increase(8,9) warming-induced carbon losses substantially. Here we collect soils from different ecosystems along a climate gradient from the Arctic to the Amazon and investigate how microbial community-level responses control the temperature sensitivity of soil respiration. We find that the microbial community-level response more often enhances than reduces the mid-to long-term (90 days) temperature sensitivity of respiration. Furthermore, the strongest enhancing responses were observed in soils with high carbon-to-nitrogen ratios and in soils from cold climatic regions. After 90 days, microbial community responses increased the temperature sensitivity of respiration in high-latitude soils by a factor of 1.4 compared to the instantaneous temperature response. This suggests that the substantial carbon stores in Arctic and boreal soils could be more vulnerable to climate warming than currently predicted.
C1 [Karhu, Kristiina; Hartley, Iain P.] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4RJ, Devon, England.
   [Auffret, Marc D.; Prosser, James I.] Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen AB24 3UU, Scotland.
   [Dungait, Jennifer A. J.] Rothamsted Res North Wyke, Okehampton EX20 2SB, Devon, England.
   [Hopkins, David W.] Royal Agr Univ, Sch Agr Food & Environm, Cirencester GL7 6JS, Glos, England.
   [Singh, Brajesh K.] Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2751, Australia.
   [Subke, Jens-Arne] Univ Stirling, Sch Nat Sci Biol & Environm Sci, Stirling FK9 4LA, Scotland.
   [Wookey, Philip A.] Heriot Watt Univ, Sch Life Sci, Edinburgh EH14 4AS, Midlothian, Scotland.
   [Agren, Goran I.] Swedish Univ Agr Sci SLU, Dept Ecol, S-75007 Uppsala, Sweden.
   [Sebastia, Maria-Teresa; Gouriveau, Fabrice] Forest Sci Ctr Catalonia CTFC, Lab Funct Ecol & Global Change, Solsona 25280, Spain.
   [Sebastia, Maria-Teresa] Univ Lleida, Sch Agrifood & Forestry Sci & Engn, Dept Hort Bot & Landscaping, Lleida 25198, Spain.
   [Bergkvist, Goran] Swedish Univ Agr Sci SLU, Dept Crop Prod Ecol, S-75007 Uppsala, Sweden.
   [Meir, Patrick; Nottingham, Andrew T.] Univ Edinburgh, Sch Geosci, Edinburgh EH8 9XP, Midlothian, Scotland.
   [Meir, Patrick] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia.
   [Salinas, Norma] Pontificia Univ Catolica Peru, Secc Quim, Lima 32, Peru.
C3 University of Exeter; University of Aberdeen; Royal Agricultural University; Western Sydney University; University of Stirling; Heriot Watt University; Swedish University of Agricultural Sciences; Centre Tecnologic Forestal de Catalunya (CTFC); Universitat de Lleida; Swedish University of Agricultural Sciences; University of Edinburgh; Australian National University; Pontificia Universidad Catolica del Peru
RP Karhu, K (corresponding author), Univ Helsinki, Dept Forest Sci, FIN-00014 Helsinki, Finland.
EM kristiina.karhu@helsinki.fi
FU Natural Environment Research Council (NERC) [NE/H022333/1]; Academy of Finland; ARC [FT110100457, DP130104841]; NERC [NE/G018278/1]; Grain Research and Development Corporation; BBSRC [BBS/E/C/00005214, BBS/E/C/00005196] Funding Source: UKRI; NERC [NE/H022333/1, NE/H023550/1, NE/G018278/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/C/00005214, BBS/E/C/00005196] Funding Source: researchfish; Natural Environment Research Council [NE/H022333/1, NE/G018278/1, NE/H023550/1] Funding Source: researchfish
NR 30
TC 584
Z9 684
U1 22
U2 1617
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2014
VL 513
IS 7516
BP 81
EP +
DI 10.1038/nature13604
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800034
PM 25186902
DA 2026-03-09
ER

PT J
AU Parker, M
   Mohankumar, KM
   Punchihewa, C
   Weinlich, R
   Dalton, JD
   Li, YJ
   Lee, R
   Tatevossian, RG
   Phoenix, TN
   Thiruvenkatam, R
   White, E
   Tang, B
   Orisme, W
   Gupta, K
   Rusch, M
   Chen, X
   Li, YX
   Nagahawhatte, P
   Hedlund, E
   Finkelstein, D
   Wu, G
   Shurtleff, S
   Easton, J
   Boggs, K
   Yergeau, D
   Vadodaria, B
   Mulder, HL
   Becksford, J
   Gupta, P
   Huether, R
   Ma, J
   Song, GC
   Gajjar, A
   Merchant, T
   Boop, F
   Smith, AA
   Ding, L
   Lu, C
   Ochoa, K
   Zhao, D
   Fulton, RS
   Fulton, LL
   Mardis, ER
   Wilson, RK
   Downing, JR
   Green, DR
   Zhang, JH
   Ellison, DW
   Gilbertson, RJ
AF Parker, Matthew
   Mohankumar, Kumarasamypet M.
   Punchihewa, Chandanamali
   Weinlich, Ricardo
   Dalton, James D.
   Li, Yongjin
   Lee, Ryan
   Tatevossian, Ruth G.
   Phoenix, Timothy N.
   Thiruvenkatam, Radhika
   White, Elsie
   Tang, Bo
   Orisme, Wilda
   Gupta, Kirti
   Rusch, Michael
   Chen, Xiang
   Li, Yuxin
   Nagahawhatte, Panduka
   Hedlund, Erin
   Finkelstein, David
   Wu, Gang
   Shurtleff, Sheila
   Easton, John
   Boggs, Kristy
   Yergeau, Donald
   Vadodaria, Bhavin
   Mulder, Heather L.
   Becksford, Jared
   Gupta, Pankaj
   Huether, Robert
   Ma, Jing
   Song, Guangchun
   Gajjar, Amar
   Merchant, Thomas
   Boop, Frederick
   Smith, Amy A.
   Ding, Li
   Lu, Charles
   Ochoa, Kerri
   Zhao, David
   Fulton, Robert S.
   Fulton, Lucinda L.
   Mardis, Elaine R.
   Wilson, Richard K.
   Downing, James R.
   Green, Douglas R.
   Zhang, Jinghui
   Ellison, David W.
   Gilbertson, Richard J.
TI C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma
SO NATURE
LA English
DT Article
ID distinct subgroups; cancer genm; cyclin d1; p65; mutations; phosphorylation; association; subunit; disease; complex
AB Members of the nuclear factor-kappa B (NF-kappa B) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappa B signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappa B activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappa B signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappa B target genes, and rapidly transformed neural stem cells-the cell of origin of ependymoma-to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.
C1 [Parker, Matthew; Dalton, James D.; Li, Yongjin; Tatevossian, Ruth G.; Tang, Bo; Orisme, Wilda; Boggs, Kristy; Yergeau, Donald; Vadodaria, Bhavin; Mulder, Heather L.; Ma, Jing; Song, Guangchun; Gajjar, Amar; Ding, Li; Lu, Charles; Ochoa, Kerri; Zhao, David; Fulton, Robert S.; Fulton, Lucinda L.; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Zhang, Jinghui; Ellison, David W.; Gilbertson, Richard J.] Washington Univ, St Jude Childrens Res Hosp, Pediat Canc Genome Project, Memphis, TN 38105 USA.
   [Parker, Matthew; Li, Yongjin; Rusch, Michael; Chen, Xiang; Li, Yuxin; Nagahawhatte, Panduka; Hedlund, Erin; Finkelstein, David; Wu, Gang; Gupta, Pankaj; Zhao, David; Zhang, Jinghui] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
   [Mohankumar, Kumarasamypet M.; Phoenix, Timothy N.; Thiruvenkatam, Radhika; White, Elsie; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Punchihewa, Chandanamali; Dalton, James D.; Lee, Ryan; Tatevossian, Ruth G.; Tang, Bo; Orisme, Wilda; Gupta, Kirti; Shurtleff, Sheila; Easton, John; Becksford, Jared; Downing, James R.; Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Weinlich, Ricardo; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Li, Yuxin; Huether, Robert] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Gajjar, Amar] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Merchant, Thomas] St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA.
   [Boop, Frederick] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA.
   [Smith, Amy A.] MD Anderson Canc Ctr Orlando, Orlando, FL 32806 USA.
   [Ding, Li; Lu, Charles; Ochoa, Kerri; Fulton, Robert S.; Fulton, Lucinda L.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Ochoa, Kerri; Fulton, Lucinda L.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63108 USA.
   [Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Siteman Canc Ctr, St Louis, MO 63108 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Texas System; UTMD Anderson Cancer Center; Saint Louis University; Washington University (WUSTL); Washington University (WUSTL); Saint Louis University; Saint Louis University; Washington University (WUSTL); Siteman Cancer Center
RP Gilbertson, RJ (corresponding author), Washington Univ, St Jude Childrens Res Hosp, Pediat Canc Genome Project, Memphis, TN 38105 USA.
EM Jinghui.Zhang@stjude.org; David.Ellison@stjude.org; Richard.Gilbertson@stjude.org
FU St. Jude Children's Research Hospital, Washington University Pediatric Cancer Genome Project; National Institutes of Health [R01CA129541, P01CA96832, P30CA021765]; Collaborative Ependymoma Research Network (CERN); American Lebanese Syrian Associated Charities (ALSAC); National Cancer Institute [P01CA096832, P30CA021765] Funding Source: NIH RePORTER
NR 28
TC 504
Z9 573
U1 0
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 FEB 27
PY 2014
VL 506
IS 7489
BP 451
EP +
DI 10.1038/nature13109
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100030
PM 24553141
DA 2026-03-09
ER

PT J
AU Sackton, KL
   Dimova, N
   Zeng, X
   Tian, W
   Zhang, MM
   Sackton, TB
   Meaders, J
   Pfaff, KL
   Sigoillot, F
   Yu, HT
   Luo, XL
   King, RW
AF Sackton, Katharine L.
   Dimova, Nevena
   Zeng, Xing
   Tian, Wei
   Zhang, Mengmeng
   Sackton, Timothy B.
   Meaders, Johnathan
   Pfaff, Kathleen L.
   Sigoillot, Frederic
   Yu, Hongtao
   Luo, Xuelian
   King, Randall W.
TI Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C
SO NATURE
LA English
DT Article
ID anaphase-promoting complex; cell-cycle; degron recognition; substrate-binding; destruction; degradation; activator; cdc20; complex/cyclosome; engagement
AB Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome(1,2). Because blocking mitotic exit is an effective approach for inducing tumour cell death(3,4), the APC/Crepresents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box(D-box)(6-14). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-L-arginine methyl ester, a small molecule that blocks the APC/C-Cdc20 interaction(15,16). This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine.
C1 [Sackton, Katharine L.; Dimova, Nevena; Zeng, Xing; Zhang, Mengmeng; Meaders, Johnathan; Pfaff, Kathleen L.; Sigoillot, Frederic; King, Randall W.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Tian, Wei; Yu, Hongtao; Luo, Xuelian] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Sackton, Timothy B.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Yu, Hongtao] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard Medical School; University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Howard Hughes Medical Institute
RP King, RW (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM randy_king@hms.harvard.edu
FU US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; National Institutes of Health [GM085004, GM066492]; Lynch Foundation
NR 40
TC 218
Z9 249
U1 2
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 OCT 30
PY 2014
VL 514
IS 7524
BP 646
EP +
DI 10.1038/nature13660
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500053
PM 25156254
DA 2026-03-09
ER

PT J
AU Crevillén, P
   Yang, HC
   Cui, X
   Greeff, C
   Trick, M
   Qiu, Q
   Cao, XF
   Dean, C
AF Crevillen, Pedro
   Yang, Hongchun
   Cui, Xia
   Greeff, Christiaan
   Trick, Martin
   Qiu, Qi
   Cao, Xiaofeng
   Dean, Caroline
TI Epigenetic reprogramming that prevents transgenerational inheritance of the vernalized state
SO NATURE
LA English
DT Article
ID flowering-locus-c; gene; flc; expression; methylation; rna; repression; frigida; plant
AB The reprogramming of epigenetic states in gametes and embryos is essential for correct development in plants and mammals(1). In plants, the germ line arises from somatic tissues of the flower, necessitating the erasure of chromatin modifications that have accumulated at specific loci during development or in response to external stimuli. If this process occurs inefficiently, it can lead to epigenetic states being inherited from one generation to the next(2-4). However, inmost cases, accumulated epigenetic modifications are efficiently erased before the next generation. An important example of epigenetic reprogramming in plants is the resetting of the expression of the floral repressor locus FLC in Arabidopsis thaliana. FLC is epigenetically silenced by prolonged cold in a process called vernalization. However, the locus is reactivated before the completion of seed development, ensuring the requirement for vernalization in every generation. In contrast to our detailed understanding of the polycomb-mediated epigenetic silencing induced by vernalization, little is known about the mechanism involved in the reactivation of FLC. Here we show that a hypomorphic mutation in the jumonji-domain-containing protein ELF6 impaired the reactivation of FLC in reproductive tissues, leading to the inheritance of a partially vernalized state. ELF6 has H3K27 me3 demethylase activity, and the mutation reduced this enzymatic activity in planta. Consistent with this, in the next generation of mutant plants, H3K27me3 levels at the FLC locus stayed higher, and FLC expression remained lower, than in the wild type. Our data reveal an ancient role for H3K27 demethylation in the reprogramming of epigenetic states in plant and mammalian embryos(5-7).
C1 [Crevillen, Pedro; Yang, Hongchun; Greeff, Christiaan; Trick, Martin; Dean, Caroline] John Innes Ctr Plant Sci Res, Dept Cell & Dev Biol, Norwich NR4 7UH, Norfolk, England.
   [Cui, Xia; Qiu, Qi; Cao, Xiaofeng] Chinese Acad Sci, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
   [Cui, Xia; Qiu, Qi; Cao, Xiaofeng] Chinese Acad Sci, Inst Genet & Dev Biol, Natl Ctr Plant Gene Res, Beijing 100101, Peoples R China.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Chinese Academy of Sciences; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS
RP Dean, C (corresponding author), John Innes Ctr Plant Sci Res, Dept Cell & Dev Biol, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England.
EM caroline.dean@jic.ac.uk
FU UK Biotechnology and Biological Sciences Research Council [BB/G009562/1, BB/C517633/1]; European Research Council [233039 ENVGENE]; National Basic Research Program of China [2013CB967300, 2011CB915400]; National Natural Science Foundation of China [31271363]; Biotechnology and Biological Sciences Research Council [BB/C517633/1, BBS/E/J/000CA376, BBS/E/J/000CA369, BBS/E/J/00000581, BBS/E/J/000CA447, BB/G009562/1] Funding Source: researchfish; BBSRC [BBS/E/J/000CA447, BBS/E/J/000CA369, BBS/E/J/000CA376, BB/G009562/1] Funding Source: UKRI
NR 36
TC 213
Z9 233
U1 1
U2 159
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 27
PY 2014
VL 515
IS 7528
BP 587
EP +
DI 10.1038/nature13722
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600003
PM 25219852
DA 2026-03-09
ER

PT J
AU Milo, A
   Bess, EN
   Sigman, MS
AF Milo, Anat
   Bess, Elizabeth N.
   Sigman, Matthew S.
TI Interrogating selectivity in catalysis using molecular vibrations
SO NATURE
LA English
DT Article
ID gaussian-basis sets; infrared-spectra; heck arylations; atoms li; parameters
AB The delineation of molecular properties that underlie reactivity and selectivity is at the core of physical organic chemistry(1-5), and this knowledge can be used to inform the design of improved synthetic methods or identify new chemical transformations(6-9). For this reason, the mathematical representation of properties affecting reactivity and selectivity trends, that is, molecular parameters, is paramount. Correlations produced by equating these molecular parameters with experimental outcomes are often defined as free-energy relationships and can be used to evaluate the origin of selectivity and to generate new, experimentally testable hypotheses(6,10-12). The premise behind successful correlations of this type is that a systematically perturbed molecular property affects a transition-state interaction between the catalyst, substrate and any reaction components involved in the determination of selectivity(10,11). Classic physical organic molecular descriptors, such as Hammett(4), Taft(3) or Charton(5) parameters, seek to independently probe isolated electronic or steric effects(3-6,13,14). However, these parameters cannot address simultaneous, non-additive variations to more than one molecular property, which limits their utility. Here we report a parameter system based on the vibrational response of a molecule to infrared radiation that can be used to mathematically model and predict selectivity trends for reactions with interlinked steric and electronic effects at positions of interest. The disclosed parameter system is mechanistically derived and should find broad use in the study of chemical and biological systems.
C1 [Milo, Anat; Bess, Elizabeth N.; Sigman, Matthew S.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Sigman, MS (corresponding author), Univ Utah, Dept Chem, 315 South 1400 E, Salt Lake City, UT 84112 USA.
EM sigman@chem.utah.edu
FU US National Science Foundation [CHE-0749506]; Center for High Performance Computing at the University of Utah; Direct For Mathematical & Physical Scien; Division Of Chemistry [1110599] Funding Source: National Science Foundation
NR 51
TC 136
Z9 169
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 MAR 13
PY 2014
VL 507
IS 7491
BP 210
EP +
DI 10.1038/nature13019
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800034
PM 24622199
DA 2026-03-09
ER

PT J
AU Qiu, XG
   Wong, G
   Audet, J
   Bello, A
   Fernando, L
   Alimonti, JB
   Fausther-Bovendo, H
   Wei, HY
   Aviles, J
   Hiatt, E
   Johnson, A
   Morton, J
   Swope, K
   Bohorov, O
   Bohorova, N
   Goodman, C
   Kim, D
   Pauly, MH
   Velasco, J
   Pettitt, J
   Olinger, GG
   Whaley, K
   Xu, BL
   Strong, JE
   Zeitlin, L
   Kobinger, GP
AF Qiu, Xiangguo
   Wong, Gary
   Audet, Jonathan
   Bello, Alexander
   Fernando, Lisa
   Alimonti, Judie B.
   Fausther-Bovendo, Hugues
   Wei, Haiyan
   Aviles, Jenna
   Hiatt, Ernie
   Johnson, Ashley
   Morton, Josh
   Swope, Kelsi
   Bohorov, Ognian
   Bohorova, Natasha
   Goodman, Charles
   Kim, Do
   Pauly, Michael H.
   Velasco, Jesus
   Pettitt, James
   Olinger, Gene G.
   Whaley, Kevin
   Xu, Bianli
   Strong, James E.
   Zeitlin, Larry
   Kobinger, Gary P.
TI Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
SO NATURE
LA English
DT Article
ID postexposure protection; mediated protection; hemorrhagic-fever; antibody; infection; challenge
AB Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.
C1 [Qiu, Xiangguo; Wong, Gary; Audet, Jonathan; Bello, Alexander; Fernando, Lisa; Alimonti, Judie B.; Fausther-Bovendo, Hugues; Wei, Haiyan; Aviles, Jenna; Strong, James E.; Kobinger, Gary P.] Publ Hlth Agcy Canada, Natl Lab Zoonot Dis & Special Pathogens, Winnipeg, MB R3E 3R2, Canada.
   [Wong, Gary; Audet, Jonathan; Bello, Alexander; Fausther-Bovendo, Hugues; Strong, James E.; Kobinger, Gary P.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada.
   [Wei, Haiyan; Xu, Bianli] Henan Ctr Dis Control & Prevent, Inst Infect Dis, Zhengzhou 450012, Henan, Peoples R China.
   [Hiatt, Ernie; Johnson, Ashley; Morton, Josh; Swope, Kelsi] Kentucky BioProc, Owensboro, KY 42301 USA.
   [Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Kim, Do; Pauly, Michael H.; Velasco, Jesus; Whaley, Kevin; Zeitlin, Larry] Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.
   [Pettitt, James; Olinger, Gene G.] US Army, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
   [Strong, James E.] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3A 1S1, Canada.
   [Kobinger, Gary P.] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada.
   [Kobinger, Gary P.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
C3 Public Health Agency of Canada; University of Manitoba; Henan Provincial center for Disease Prevention & Control; University of Manitoba; University of Manitoba; University of Pennsylvania
RP Zeitlin, L (corresponding author), Mapp Biopharmaceut Inc, San Diego, CA 92121 USA.
EM larry.zeitlin@mappbio.com; gary.kobinger@phac-aspc.gc.ca
FU Defense Threat Reduction Agency (DTRA) [HDTRA1-13-C-0018]; National Institutes of Health [U19AI109762]; Public Health Agency of Canada (PHAC); Canadian Safety and Security Program (CSSP); Canadian Institute for Health Research (CIHR)
NR 33
TC 762
Z9 941
U1 5
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 OCT 2
PY 2014
VL 514
IS 7520
BP 47
EP +
DI 10.1038/nature13777
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800032
PM 25171469
DA 2026-03-09
ER

PT J
AU Albert, JB
   Auty, DJ
   Barbeau, PS
   Beauchamp, E
   Beck, D
   Belov, V
   Benitez-Medina, C
   Bonatt, J
   Breidenbach, M
   Brunner, T
   Burenkov, A
   Cao, GF
   Chambers, C
   Chaves, J
   Cleveland, B
   Coon, M
   Craycraft, A
   Daniels, T
   Danilov, M
   Daugherty, SJ
   Davis, CG
   Davis, J
   Devoe, R
   Delaquis, S
   Didberidze, T
   Dolgolenko, A
   Dolinski, MJ
   Dunford, M
   Fairbank, W
   Farine, J
   Feldmeier, W
   Fierlinger, P
   Fudenberg, D
   Giroux, G
   Gornea, R
   Graham, K
   Gratta, G
   Hall, C
   Herrin, S
   Hughes, M
   Jewell, MJ
   Jiang, XS
   Johnson, A
   Johnson, TN
   Johnston, S
   Karelin, A
   Kaufman, LJ
   Killick, R
   Koffas, T
   Kravitz, S
   Kuchenkov, A
   Kumar, KS
   Leonard, DS
   Leonard, F
   Licciardi, C
   Lin, YH
   MacLellan, R
   Marino, MG
   Mong, B
   Moore, D
   Nelson, R
   Odian, A
   Ostrovskiy, I
   Ouellet, C
   Piepke, A
   Pocar, A
   Prescott, CY
   Rivas, A
   Rowson, PC
   Rozo, MP
   Russell, JJ
   Schubert, A
   Sinclair, D
   Slutsky, S
   Smith, E
   Stekhanov, V
   Tarka, M
   Tolba, T
   Tosi, D
   Twelker, K
   Vogel, P
   Vuilleumier, JL
   Waite, A
   Walton, J
   Walton, T
   Weber, M
   Wen, LJ
   Wichoski, U
   Wright, JD
   Yang, L
   Yen, YR
   Zeldovich, OY
   Zhao, YB
AF Albert, J. B.
   Auty, D. J.
   Barbeau, P. S.
   Beauchamp, E.
   Beck, D.
   Belov, V.
   Benitez-Medina, C.
   Bonatt, J.
   Breidenbach, M.
   Brunner, T.
   Burenkov, A.
   Cao, G. F.
   Chambers, C.
   Chaves, J.
   Cleveland, B.
   Coon, M.
   Craycraft, A.
   Daniels, T.
   Danilov, M.
   Daugherty, S. J.
   Davis, C. G.
   Davis, J.
   Devoe, R.
   Delaquis, S.
   Didberidze, T.
   Dolgolenko, A.
   Dolinski, M. J.
   Dunford, M.
   Fairbank, W., Jr.
   Farine, J.
   Feldmeier, W.
   Fierlinger, P.
   Fudenberg, D.
   Giroux, G.
   Gornea, R.
   Graham, K.
   Gratta, G.
   Hall, C.
   Herrin, S.
   Hughes, M.
   Jewell, M. J.
   Jiang, X. S.
   Johnson, A.
   Johnson, T. N.
   Johnston, S.
   Karelin, A.
   Kaufman, L. J.
   Killick, R.
   Koffas, T.
   Kravitz, S.
   Kuchenkov, A.
   Kumar, K. S.
   Leonard, D. S.
   Leonard, F.
   Licciardi, C.
   Lin, Y. H.
   MacLellan, R.
   Marino, M. G.
   Mong, B.
   Moore, D.
   Nelson, R.
   Odian, A.
   Ostrovskiy, I.
   Ouellet, C.
   Piepke, A.
   Pocar, A.
   Prescott, C. Y.
   Rivas, A.
   Rowson, P. C.
   Rozo, M. P.
   Russell, J. J.
   Schubert, A.
   Sinclair, D.
   Slutsky, S.
   Smith, E.
   Stekhanov, V.
   Tarka, M.
   Tolba, T.
   Tosi, D.
   Twelker, K.
   Vogel, P.
   Vuilleumier, J. -L.
   Waite, A.
   Walton, J.
   Walton, T.
   Weber, M.
   Wen, L. J.
   Wichoski, U.
   Wright, J. D.
   Yang, L.
   Yen, Y. -R.
   Zeldovich, O. Ya.
   Zhao, Y. B.
TI Search for Majorana neutrinos with the first two years of EXO-200 data
SO NATURE
LA English
DT Article
ID decay
AB Many extensions of the standard model of particle physics suggest that neutrinos should be Majorana-type fermions-that is, that neutrinos are their own anti-particles-but this assumption is difficult to confirm. Observation of neutrinoless double-beta decay (0 nu beta beta), a spontaneous transition that may occur in several candidate nuclei, would verify the Majorana nature of the neutrino and constrain the absolute scale of the neutrino mass spectrum. Recent searches carried out with Ge-76 (the GERDA experiment) and Xe-136 (the KamLAND-Zen and EXO (Enriched Xenon Observatory)-200 experiments) have established the lifetime of this decay to be longer than 10(25) years, corresponding to a limit on the neutrino mass of 0.2-0.4 electronvolts. Here we report new results from EXO-200 based on a large Xe-136 exposure that represents an almost fourfold increase from our earlier published data sets. We have improved the detector resolution and revised the data analysis. The half-life sensitivity we obtain is 1.9x10(25) years, an improvement by a factor of 2.7 on previous EXO-200 results. We find no statistically significant evidence for 0 nu beta beta decay and set a half-life limit of 1.1x10(25) years at the 90 per cent confidence level. The high sensitivity holds promise for further running of the EXO-200 detector and future 0 nu beta beta decay searches with an improved Xe-based experiment, nEXO.
C1 [Albert, J. B.; Daugherty, S. J.; Johnson, T. N.; Kaufman, L. J.] Indiana Univ, Dept Phys, Bloomington, IN 47405 USA.
   [Albert, J. B.; Daugherty, S. J.; Johnson, T. N.; Kaufman, L. J.] Indiana Univ, CEEM, Bloomington, IN 47405 USA.
   [Auty, D. J.; Didberidze, T.; Hughes, M.; Piepke, A.] Univ Alabama, Dept Phys & Astron, Tuscaloosa, AL 35487 USA.
   [Barbeau, P. S.] Duke Univ, Dept Phys, Durham, NC 27708 USA.
   [Barbeau, P. S.] Triangle Univ Nucl Lab, Durham, NC 27708 USA.
   [Beauchamp, E.; Cleveland, B.; Farine, J.; Mong, B.; Wichoski, U.] Laurentian Univ, Dept Phys, Sudbury, ON P3E 2C6, Canada.
   [Beck, D.; Coon, M.; Tarka, M.; Walton, J.; Yang, L.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Belov, V.; Burenkov, A.; Danilov, M.; Dolgolenko, A.; Karelin, A.; Kuchenkov, A.; Stekhanov, V.; Zeldovich, O. Ya.] Inst Theoret & Expt Phys, Moscow 117218, Russia.
   [Benitez-Medina, C.; Chambers, C.; Craycraft, A.; Fairbank, W., Jr.; Walton, T.] Colorado State Univ, Dept Phys, Ft Collins, CO 80523 USA.
   [Bonatt, J.; Daniels, T.; Johnston, S.; Kumar, K. S.; Pocar, A.; Wright, J. D.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
   [Bonatt, J.; Brunner, T.; Chaves, J.; Davis, J.; Devoe, R.; Fudenberg, D.; Gratta, G.; Kravitz, S.; Moore, D.; Ostrovskiy, I.; Rivas, A.; Schubert, A.; Tosi, D.; Twelker, K.; Weber, M.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Breidenbach, M.; Herrin, S.; Johnson, A.; MacLellan, R.; Odian, A.; Prescott, C. Y.; Rowson, P. C.; Russell, J. J.; Waite, A.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Cao, G. F.; Jiang, X. S.; Wen, L. J.; Zhao, Y. B.] Inst High Energy Phys, Beijing 100049, Peoples R China.
   [Cleveland, B.] SNOLAB, Sudbury, ON P3Y 1N2, Canada.
   [Davis, C. G.; Hall, C.; Slutsky, S.; Yen, Y. -R.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Delaquis, S.; Giroux, G.; Gornea, R.; Tolba, T.; Vuilleumier, J. -L.] Univ Bern, Albert Einstein Ctr, LHEP, CH-3012 Bern, Switzerland.
   [Dolinski, M. J.; Jewell, M. J.; Lin, Y. H.; Smith, E.; Yen, Y. -R.] Drexel Univ, Dept Phys, Philadelphia, PA 19104 USA.
   [Dunford, M.; Graham, K.; Killick, R.; Koffas, T.; Leonard, F.; Licciardi, C.; Ouellet, C.; Rozo, M. P.; Sinclair, D.] Carleton Univ, Dept Phys, Ottawa, ON K1S 5B6, Canada.
   [Feldmeier, W.; Fierlinger, P.; Marino, M. G.] Tech Univ Munich, Dept Phys, D-85748 Garching, Germany.
   [Feldmeier, W.; Fierlinger, P.; Marino, M. G.] Excellence Cluster Universe, D-85748 Garching, Germany.
   [Leonard, D. S.] Univ Seoul, Dept Phys, Seoul 130743, South Korea.
   [Nelson, R.] Waste Isolat Pilot Plant, Carlsbad, NM 88220 USA.
   [Sinclair, D.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Vogel, P.] CALTECH, Kellogg Lab, Pasadena, CA 91125 USA.
   [Giroux, G.] Queens Univ, Kingston, ON K7L 3N6, Canada.
   [Slutsky, S.] CALTECH, Pasadena, CA 91125 USA.
   [Tosi, D.] Univ Wisconsin, Madison, WI 53706 USA.
C3 Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; University of Alabama System; University of Alabama Tuscaloosa; Duke University; University of North Carolina; University of North Carolina Chapel Hill; Duke University; North Carolina State University; Triangle Universities Nuclear Laboratory; Laurentian University; University of Illinois System; University of Illinois Urbana-Champaign; National Research Centre - Kurchatov Institute; Alikhanov Institute for Theoretical & Experimental Physics; Colorado State University System; Colorado State University Fort Collins; University of Massachusetts System; University of Massachusetts Amherst; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Chinese Academy of Sciences; Institute of High Energy Physics, CAS; University System of Maryland; University of Maryland College Park; University of Bern; Drexel University; Carleton University; Technical University of Munich; University of Munich; University of Seoul; University of British Columbia; California Institute of Technology; Queens University - Canada; California Institute of Technology; University of Wisconsin System; University of Wisconsin Madison
RP Albert, JB (corresponding author), Indiana Univ, Dept Phys, Bloomington, IN 47405 USA.
FU DOE; NSF in the United States; NSERC in Canada; SNF in Switzerland; NRF in Korea; RFBR in Russia [12-02-12145]; DFG Cluster of Excellence 'Universe' in Germany; Office of Science of the US DOE [DE-AC02-05CH11231]; Direct For Mathematical & Physical Scien; Division Of Physics [1205977, 1307362] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1132428] Funding Source: National Science Foundation
NR 33
TC 353
Z9 410
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 JUN 12
PY 2014
VL 510
IS 7504
BP 229
EP 234
DI 10.1038/nature13432
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400042
PM 24896189
DA 2026-03-09
ER

PT J
AU Al Jord, A
   Lemaitre, AI
   Delgehyr, N
   Faucourt, M
   Spassky, N
   Meunier, A
AF Al Jord, Adel
   Lemaitre, Anne-Iris
   Delgehyr, Nathalie
   Faucourt, Marion
   Spassky, Nathalie
   Meunier, Alice
TI Centriole amplification by mother and daughter centrioles differs in multiciliated cells
SO NATURE
LA English
DT Article
ID primary cilium; centrosome; ciliogenesis; biogenesis; tubulin; morphogenesis; epithelium; interacts; cycle; cpap
AB The semi-conservative centrosome duplication in cycling cells gives rise to a centrosome composed of a mother and a newly formed daughter centriole(1). Both centrioles are regarded as equivalent in their ability to form new centrioles and their symmetric duplication is crucial for cell division homeostasis(2,4). Multiciliated cells do not use the archetypal duplication program and instead form more than a hundred centrioles that are required for the growth of motile cilia and the efficient propelling of physiological fluids(5). The majority of these new centrioles are thought to appear de novo, that is, independently from the centrosome, around electron-dense structures called deuterosomes(5,9). Their origin remains unknown. Using live imaging combined with correlative super-resolution light and electron microscopy, we show that all new centrioles derive from the pre-existing progenitor cell centrosome through multiple rounds of procentriole seeding. Moreover, we establish that only the daughter centrosomal centriole contributes to deuterosome formation, and thus to over ninety per cent of the final centriole population. This unexpected centriolar asymmetry grants new perspectives when studying cilia-related diseases and pathological centriole amplification observed in cycling cells and associated with microcephaly and cancer(2-4,10).
C1 [Al Jord, Adel; Lemaitre, Anne-Iris; Delgehyr, Nathalie; Faucourt, Marion; Spassky, Nathalie; Meunier, Alice] Ecole Normale Super, ENS, IBENS, Inst Biol, F-75005 Paris, France.
   [Al Jord, Adel; Lemaitre, Anne-Iris; Delgehyr, Nathalie; Faucourt, Marion; Spassky, Nathalie; Meunier, Alice] INSERM, U1024, F-75005 Paris, France.
   [Al Jord, Adel; Lemaitre, Anne-Iris; Delgehyr, Nathalie; Faucourt, Marion; Spassky, Nathalie; Meunier, Alice] CNRS, UMR 8197, F-75005 Paris, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Spassky, N (corresponding author), Ecole Normale Super, ENS, IBENS, Inst Biol, F-75005 Paris, France.
EM nathalie.spassky@ens.fr; alice.meunier@ens.fr
FU Federation pour la Recherche sur le Cerveau; Region Ile de France DIM NeRF; France-BioImaging; CNRS; ENS; INSERM; FPGG; ANR [ANR-12-BSV4-0006 CILIASTEM, ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL]; ARC [PJA-20131200184]; La ligue contre le cancer-comite de Paris [RS14/75-88]; 'Investissements d'Avenir' program of the French Government; City of Paris; FRM; French Ministry of Higher Education and Research
NR 38
TC 105
Z9 127
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 DEC 4
PY 2014
VL 516
IS 7529
BP 104
EP U259
DI 10.1038/nature13770
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800048
PM 25307055
DA 2026-03-09
ER

PT J
AU Basnet, H
   Su, XB
   Tan, YL
   Meisenhelders, J
   Merkurjev, D
   Ohgi, KA
   Hunters, T
   Pillus, L
   Rosenfeld, MG
AF Basnet, Harihar
   Su, Xue B.
   Tan, Yuliang
   Meisenhelders, Jill
   Merkurjev, Dana
   Ohgi, Kenneth A.
   Hunters, Tony
   Pillus, Lorraine
   Rosenfeld, Michael G.
TI Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation
SO NATURE
LA English
DT Article
ID protein-kinase ck2; rna-polymerase-ii; yeast; ubiquitylation; methylation; mutants; heterochromatin; ubiquitination; transition; expression
AB Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication and DNA damage repair(1). The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2A in yeast or inhibition of CK2 activity impairs transcriptional elongation in yeast as well as in mammalian cells. Genome-wide binding analysis reveals that CK2 alpha, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers. Mutation of Tyr 57 causes a loss of H2B mono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks associated with active transcription. Mechanistically, both CK2 inhibition and the H2A(Y57F) mutation enhance H2B deubiquitination activity of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, suggesting a critical role of this phosphorylation in coordinating the activity of the SAGA complex during transcription. Together, these results identify a new component of regulation in transcriptional elongation based on CK2-dependent tyrosine phosphorylation of the globular domain of H2A.
C1 [Basnet, Harihar; Tan, Yuliang; Merkurjev, Dana; Ohgi, Kenneth A.; Rosenfeld, Michael G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA.
   [Basnet, Harihar] Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Su, Xue B.; Pillus, Lorraine] Univ Calif San Diego, UCSD Moores Canc Ctr, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
   [Merkurjev, Dana] Univ Calif San Diego, Dept Bioengn, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA.
   [Meisenhelders, Jill; Hunters, Tony] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
C3 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; University of California System; University of California San Diego; Salk Institute
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA.
EM lpillus@ucsd.edu; mrosenfeld@ucsd.edu
FU NIH [NS034934, DK039949, DK018477, HL065445, CA173903, GM033279]; UC-CRCC; NCI [CA82683]; National Cancer Institute [P30CA023100] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, T32DK007541, R01DK039949] Funding Source: NIH RePORTER
NR 29
TC 98
Z9 117
U1 1
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 11
PY 2014
VL 516
IS 7530
BP 267
EP +
DI 10.1038/nature13736
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500050
PM 25252977
DA 2026-03-09
ER

PT J
AU Creasey, KM
   Zhai, JX
   Borges, F
   Van Ex, F
   Regulski, M
   Meyers, BC
   Martienssen, RA
AF Creasey, Kate M.
   Zhai, Jixian
   Borges, Filipe
   Van Ex, Frederic
   Regulski, Michael
   Meyers, Blake C.
   Martienssen, Robert A.
TI miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis
SO NATURE
LA English
DT Article
ID dna methylation; small rna; plants; biogenesis; micrornas; targets; demethylation; methylome; endosperm; elements
AB In plants, post-transcriptional gene silencing (PTGS) is mediated by DICER-LIKE 1 (DCL1)-dependent microRNAs (miRNAs), which also trigger 21-nucleotide secondary short interfering RNAs (siRNAs) via RNA-DEPENDENT RNA POLYMERASE 6 (RDR6), DCL4 and ARGONAUTE 1 (AGO1)(1-3), whereas transcriptional gene silencing (TGS) of transposons is mediated by 24-nucleotide heterochromatic (het) siRNAs, RDR2, DCL3 and AGO4 (ref. 4). Transposons can also give rise to abundant 21-nucleotide 'epigenetically activated' small interfering RNAs (easiRNAs) in DECREASED DNA METHYLATION 1 (ddm1) and DNA METHYLTRANSFERASE 1 (met1) mutants, as well as in the vegetative nucleus of pollen grains(5) and in dedifferentiated plant cell cultures(6). Here we show that easiRNAs in Arabidopsis thaliana resemble secondary siRNAs, in that thousands of transposon transcripts are specifically targeted by more than 50 miRNAs for cleavage and processing by RDR6. Loss of RDR6, DCL4 or DCL1 in a ddm1 background results in loss of 21-nucleotide easiRNAs and severe infertility, but 24-nucleotide hetsi-RNAs are partially restored, supporting an antagonistic relationship between PTGS and TGS. Thus miRNA-directed easiRNA biogenesis is a latent mechanism that specifically targets transposon transcripts, but only when they are epigenetically reactivated during reprogramming of the germ line. This ancient recognition mechanism may have been retained both by transposons to evade long-term heterochromatic silencing and by their hosts for genome defence.
C1 [Creasey, Kate M.; Borges, Filipe; Van Ex, Frederic; Regulski, Michael; Martienssen, Robert A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Zhai, Jixian; Meyers, Blake C.] Univ Delaware, Delaware Biotechnol Inst, Newark, DC 19711 USA.
   [Zhai, Jixian; Meyers, Blake C.] Univ Delaware, Dept Plant & Soil Sci, Newark, DC 19711 USA.
   [Martienssen, Robert A.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Cold Spring Harbor, NY 11724 USA.
   [Martienssen, Robert A.] IBENS, Chaire Blaise Pascal, F-75230 Paris, France.
C3 Cold Spring Harbor Laboratory; University of Delaware; University of Delaware; Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Martienssen, RA (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM martiens@cshl.edu
FU DuPont Pioneer; Belgian American Educational Foundation; University of Delaware Graduate fellowship; National Institutes of Health [RO1GM067014]; Howard Hughes Medical Institute; Gordon and Betty Moore Foundation [GBMF3033]; Cancer Center Support Grant [5PP30CA045508]; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER; Gordon and Betty Moore Foundation (GBMF) [GBMF3033] Funding Source: Gordon and Betty Moore Foundation (GBMF)
NR 33
TC 255
Z9 287
U1 1
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 APR 17
PY 2014
VL 508
IS 7496
BP 411
EP +
DI 10.1038/nature13069
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000055
PM 24670663
DA 2026-03-09
ER

PT J
AU Bianchi, E
   Doe, B
   Goulding, D
   Wright, GJ
AF Bianchi, Enrica
   Doe, Brendan
   Goulding, David
   Wright, Gavin J.
TI Juno is the egg Izumo receptor and is essential for mammalian fertilization
SO NATURE
LA English
DT Article
ID regulatory t-cells; membrane block; sperm penetration; plasma-membrane; myoblast fusion; folic-acid; folate; polyspermy; cd9; surface
AB Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.
C1 [Bianchi, Enrica; Wright, Gavin J.] Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge CB10 1SA, England.
   [Doe, Brendan] Wellcome Trust Sanger Inst, Mouse Prod Team, Cambridge CB10 1SA, England.
   [Goulding, David] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 Wellcome Trust Sanger Institute; Wellcome Trust Sanger Institute
RP Wright, GJ (corresponding author), Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge CB10 1SA, England.
EM gw2@sanger.ac.uk
FU Wellcome Trust [098051]
NR 50
TC 469
Z9 549
U1 2
U2 157
PU NATURE PUBLISHING 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 24
PY 2014
VL 508
IS 7497
BP 483
EP +
DI 10.1038/nature13203
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600028
PM 24739963
DA 2026-03-09
ER

PT J
AU Wang, KT
   Sitsel, O
   Meloni, G
   Autzen, HE
   Andersson, M
   Klymchuk, T
   Nielsen, AM
   Rees, DC
   Nissen, P
   Gourdon, P
AF Wang, Kaituo
   Sitsel, Oleg
   Meloni, Gabriele
   Autzen, Henriette Elisabeth
   Andersson, Magnus
   Klymchuk, Tetyana
   Nielsen, Anna Marie
   Rees, Douglas C.
   Nissen, Poul
   Gourdon, Pontus
TI Structure and mechanism of Zn2+-transporting P-type ATPases
SO NATURE
LA English
DT Article
ID molecular-dynamics; crystal-structure; transmembrane transport; cu+ chaperones; metal-binding; calcium-pump; zinc; coordination; sites; znta
AB Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis(1). In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements(2,3). Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2.P-i) of ZntA from Shigella sonnei, determined at 3.2 angstrom and 2.7 angstrom resolution, respectively. The structures reveal a similar fold to Cu+-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn2+ ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2.P-i state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn2+ release as a built-in counter ion, as has been proposed for H+-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between P-IB-type Zn2+-ATPases and P-III-type H+-ATPases and at the same time show structural features of the extracellular release pathway that resemble P-II-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase(4,5) (SERCA) and Na+, K+-ATPase(6). These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.
C1 [Wang, Kaituo; Sitsel, Oleg; Meloni, Gabriele; Autzen, Henriette Elisabeth; Klymchuk, Tetyana; Nielsen, Anna Marie; Nissen, Poul; Gourdon, Pontus] Aarhus Univ, Dept Mol Biol & Genet, Danish Natl Res Fdn, Ctr Membrane Pumps Cells & Dis PUMPkin, DK-8000 Aarhus C, Denmark.
   [Andersson, Magnus] KTH Royal Inst Technol, Dept Theoret Phys, Swedish E Sci Res Ctr, Sci Life Lab, SE-17121 Solna, Sweden.
   [Rees, Douglas C.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Rees, Douglas C.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
C3 Aarhus University; Danmarks Grundforskningsfond; Royal Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology
RP Gourdon, P (corresponding author), Univ Copenhagen, Dept Biomed Sci, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
EM pontus@sund.ku.dk
FU Graduate School of Science and Technology at Aarhus University; Marie Curie International Outgoing Fellowship (European Commission) [252961]; Marie Curie Career Integration Grant [FP7-MC-CIG-618558]; European Research Council [250322 Biomemos]; Lundbeck Foundation; Swedish Research Council [K2013-99X-22251-01-5]; Danscatt program of the Danish Council of Independent Research; BioStruct-X [860]; Lundbeck Foundation [R139-2012-12689] Funding Source: researchfish; Novo Nordisk Fonden [NNF12OC0002082] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [252961] Funding Source: National Health and Medical Research Council (NHMRC)
NR 54
TC 106
Z9 118
U1 0
U2 119
PU NATURE PUBLISHING 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 23
PY 2014
VL 514
IS 7523
BP 518
EP +
DI 10.1038/nature13618
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900046
PM 25132545
DA 2026-03-09
ER

PT J
AU Murayama, Y
   Uhlmann, F
AF Murayama, Yasuto
   Uhlmann, Frank
TI Biochemical reconstitution of topological DNA binding by the cohesin ring
SO NATURE
LA English
DT Article
ID sister-chromatid cohesion; strand-break repair; fission yeast; in-vitro; saccharomyces-cerevisiae; atp hydrolysis; s-phase; complex; condensin; protein
AB Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for faithful chromosome segregation in mitosis. Cohesin also has vital roles in DNA repair and transcriptional regulation. The ring-shaped cohesin complex is thought to encircle sister DNA strands, but its molecular mechanism of action is poorly understood and the biochemical reconstitution of cohesin activity in vitro has remained an unattained goal. Here we reconstitute cohesin loading onto DNA using purified fission yeast cohesin and its loader complex, Mis4(Scc2)-Ssl3(Scc4) (Schizosaccharomyces pombe gene names appear throughout with their more commonly known Saccharomyces cerevisiae counterparts added in superscript). Incubation of cohesin with DNA leads to spontaneous topological loading, but this remains inefficient. The loader contacts cohesin at multiple sites around the ring circumference, including the hitherto enigmatic Psc3(Scc3) subunit, and stimulates cohesin's ATPase, resulting in efficient topological loading. The in vitro reconstitution of cohesin loading onto DNA provides mechanistic insight into the initial steps of the establishment of sister chromatid cohesion and other chromosomal processes mediated by cohesin.
C1 [Murayama, Yasuto; Uhlmann, Frank] Canc Res UK London Res Inst, Chromosome Segregat Lab, London WC2A 3LY, England.
C3 Cancer Research UK
RP Uhlmann, F (corresponding author), Canc Res UK London Res Inst, Chromosome Segregat Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM frank.uhlmann@cancer.org.uk
FU European Research Council; Japanese Society for the Promotion of Science (JSPS); Cancer Research UK [15671] Funding Source: researchfish
NR 45
TC 240
Z9 284
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 JAN 16
PY 2014
VL 505
IS 7483
BP 367
EP +
DI 10.1038/nature12867
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800035
PM 24291789
DA 2026-03-09
ER

PT J
AU Pop, IM
   Geerlings, K
   Catelani, G
   Schoelkopf, RJ
   Glazman, LI
   Devoret, MH
AF Pop, Ioan M.
   Geerlings, Kurtis
   Catelani, Gianluigi
   Schoelkopf, Robert J.
   Glazman, Leonid I.
   Devoret, Michel H.
TI Coherent suppression of electromagnetic dissipation due to superconducting quasiparticles
SO NATURE
LA English
DT Article
ID josephson; fluctuations; dependence; junctions; qubit
AB Owing to the low-loss propagation of electromagnetic signals in superconductors, Josephson junctions constitute ideal building blocks for quantum memories, amplifiers, detectors and high-speed processing units, operating over a wide band of microwave frequencies. Nevertheless, although transport in superconducting wires is perfectly lossless for direct current, transport of radio-frequency signals can be dissipative in the presence of quasiparticle excitations above the superconducting gap(1). Moreover, the exact mechanism of this dissipation in Josephson junctions has never been fully resolved experimentally. In particular, Josephson's key theoretical prediction that quasiparticle dissipation should vanish in transport through a junction when the phase difference across the junction is pi ( ref. 2) has never been observed(3). This subtle effect can be understood as resulting from the destructive interference of two separate dissipative channels involving electron-like and hole-like quasiparticles. Here we report the experimental observation of this quantum coherent suppression of quasiparticle dissipation across a Josephson junction. As the average phase bias across the junction is swept through p, we measure an increase of more than one order of magnitude in the energy relaxation time of a superconducting artificial atom. This striking suppression of dissipation, despite the presence of lossy quasiparticle excitations above the superconducting gap, provides a powerful tool for minimizing decoherence in quantum electronic systems and could be directly exploited in quantum information experiments with superconducting quantum bits.
C1 [Pop, Ioan M.; Geerlings, Kurtis; Catelani, Gianluigi; Schoelkopf, Robert J.; Glazman, Leonid I.; Devoret, Michel H.] Yale Univ, Dept Appl Phys, New Haven, CT 06511 USA.
   [Catelani, Gianluigi] Peter Grunberg Inst PGI 2, Forschungszentrum Julich, D-52425 Julich, Germany.
C3 Yale University; Helmholtz Association; Julich Research Centre
RP Pop, IM (corresponding author), Yale Univ, Dept Appl Phys, 15 Prospect St, New Haven, CT 06511 USA.
EM ioan.pop@yale.edu
FU YINQE; NSF MRSEC DMR [1119826]; IARPA [W911NF-09-1-0369]; ARO [W911NF-09-1-0514]; NSF [DMR-1006060, DMR-0653377]; DOE [DE-FG02-08ER46482]; EU under REA [CIG-618258]
NR 39
TC 234
Z9 304
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 APR 17
PY 2014
VL 508
IS 7496
BP 369
EP +
DI 10.1038/nature13017
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000046
PM 24740067
DA 2026-03-09
ER

PT J
AU Yang, Y
   Torchinsky, MB
   Gobert, M
   Xiong, HZ
   Xu, M
   Linehan, JL
   Alonzo, F
   Ng, C
   Chen, A
   Lin, XY
   Sczesnak, A
   Liao, JJ
   Torres, VJ
   Jenkins, MK
   Lafaille, JJ
   Littman, DR
AF Yang, Yi
   Torchinsky, Miriam B.
   Gobert, Michael
   Xiong, Huizhong
   Xu, Mo
   Linehan, Jonathan L.
   Alonzo, Francis
   Ng, Charles
   Chen, Alessandra
   Lin, Xiyao
   Sczesnak, Andrew
   Liao, Jia-Jun
   Torres, Victor J.
   Jenkins, Marc K.
   Lafaille, Juan J.
   Littman, Dan R.
TI Focused specificity of intestinal TH17 cells towards commensal bacterial antigens
SO NATURE
LA English
DT Article
ID segmented filamentous bacteria; t-cells; microbiota; th17; induction; differentiation; identification; expression; maturation; prediction
AB T-helper-17 (T(H)17) cells have critical roles in mucosal defence and in autoimmune disease pathogenesis(1-3). They are most abundant in the small intestine lamina propria, where their presence requires colonization of mice with microbiota(4-7). Segmented filamentous bacteria (SFB) are sufficient to induce T(H)17 cells and to promote T(H)17-dependent autoimmune disease in animal models(8-14). However, the specificity of T(H)17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T-cell antigen receptor (TCR) repertoire of intestinal T(H)17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4(+) T cells and that most T(H)17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into ROR gamma t-expressing T(H)17 cells, even if SFB-colonized mice also harboured a strong T(H)1 cell inducer, Listeria monocytogenes, in their intestine. The match of T-cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.
C1 [Yang, Yi; Torchinsky, Miriam B.; Gobert, Michael; Xiong, Huizhong; Xu, Mo; Ng, Charles; Chen, Alessandra; Lin, Xiyao; Sczesnak, Andrew; Liao, Jia-Jun; Lafaille, Juan J.; Littman, Dan R.] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY 10016 USA.
   [Linehan, Jonathan L.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
   [Alonzo, Francis; Torres, Victor J.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
   [Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
C3 New York University; University of Minnesota System; University of Minnesota Twin Cities; New York University; Howard Hughes Medical Institute; New York University
RP Littman, DR (corresponding author), NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY 10016 USA.
EM dan.littman@med.nyu.edu
FU National Center for Advancing Translational Sciences [UL1 TR00038]; National Cancer Institute [5P30CA016087-32]; NIH [R01 AI039614]; Arthritis National Research Foundation; Irvington Institute fellowship program of the Cancer Research Institute; National Cancer Institute [P30CA077598, P30CA016087] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI039614] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 36
TC 425
Z9 520
U1 3
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 JUN 5
PY 2014
VL 510
IS 7503
BP 152
EP +
DI 10.1038/nature13279
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900047
PM 24739972
DA 2026-03-09
ER

PT J
AU Tessarz, P
   Santos-Rosa, H
   Robson, S
   Sylvestersen, KB
   Nelson, CJ
   Nielsen, ML
   Kouzarides, T
AF Tessarz, Peter
   Santos-Rosa, Helena
   Robson, Samc.
   Sylvestersen, Kathrine B.
   Nelson, Christopher J.
   Nielsen, Michael L.
   Kouzarides, Tony
TI Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification
SO NATURE
LA English
DT Article
ID nucleolar protein; transcription; fibrillarin; association; complexes; versatile; defects; roles; spt16; yfact
AB Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes(1). Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex(2). Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.
C1 [Tessarz, Peter; Santos-Rosa, Helena; Robson, Samc.; Nelson, Christopher J.; Kouzarides, Tony] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
   [Tessarz, Peter; Santos-Rosa, Helena; Robson, Samc.; Nelson, Christopher J.; Kouzarides, Tony] Univ Cambridge, Dept Pathol, Cambridge CB2 1QN, England.
   [Sylvestersen, Kathrine B.; Nielsen, Michael L.] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Prot Res, Dept Prote, DK-2200 Copenhagen, Denmark.
C3 University of Cambridge; University of Cambridge; University of Copenhagen
RP Kouzarides, T (corresponding author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM t.kouzarides@gurdon.cam.ac.uk
FU Cancer Research UK; Biotechnology and Biological Sciences Research Council [BB/K017438/1]; BBSRC [BB/K017438/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K017438/1] Funding Source: researchfish; Cancer Research UK [17001] Funding Source: researchfish; Cancer Research UK; The Francis Crick Institute [10827] Funding Source: researchfish; Novo Nordisk Fonden [NNF13OC0006477] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Michael Lund Nielsen] Funding Source: researchfish
NR 42
TC 186
Z9 251
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 JAN 23
PY 2014
VL 505
IS 7484
BP 564
EP +
DI 10.1038/nature12819
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000043
PM 24352239
DA 2026-03-09
ER

PT J
AU Nelson, E
   van Dokkum, P
   Franx, M
   Brammer, G
   Momcheva, I
   Schreiber, NF
   da Cunha, E
   Tacconi, L
   Bezanson, R
   Kirkpatrick, A
   Leja, J
   Rix, HW
   Skelton, R
   van der Wel, A
   Whitaker, K
   Wuyts, S
AF Nelson, Erica
   van Dokkum, Pieter
   Franx, Marijn
   Brammer, Gabriel
   Momcheva, Ivelina
   Schreiber, Natascha Foerster
   da Cunha, Elisabete
   Tacconi, Linda
   Bezanson, Rachel
   Kirkpatrick, Allison
   Leja, Joel
   Rix, Hans-Walter
   Skelton, Rosalind
   van der Wel, Arjen
   Whitaker, Katherine
   Wuyts, Stijn
TI A massive galaxy in its core formation phase three billion years after the Big Bang
SO NATURE
LA English
DT Article
ID hubble-space-telescope; star-forming galaxy; extragalactic legacy survey; compact quycent galaxy; high-redshift; submillimeter galaxy; velocity dispersions; metallicity relation; large-sample; red nuggets
AB Most massive galaxies are thought to have formed their dense stellar cores in early cosmic epochs(1-3). Previous studies have found galaxies with high gas velocity dispersions(4) or small apparent sizes(5-7), but so far no objects have been identified with both the stellar structure and the gas dynamics of a forming core. Here we report a candidate core in the process of formation 11 billion years ago, at redshift z = 2.3. This galaxy, GOODS-N-774, has a stellar mass of 100 billion solar masses, a half-light radius of 1.0 kiloparsecs and a star formation rate of 90(-20)(+45) solar masses per year. The star-forming gas has a velocity dispersion of 317 +/- 30 kilometres per second. This is similar to the stellar velocity dispersions of the putative descendants of GOODS-N-774, which are compact quiescent galaxies at z approximate to 2 (refs 8-11) and giant elliptical galaxies in the nearby Universe. Galaxies such as GOODS-N-774 seem to be rare; however, from the star formation rate and size of this galaxy weinfer that many star-forming cores may be heavily obscured, and could be missed in optical and near-infrared surveys.
C1 [Nelson, Erica; van Dokkum, Pieter; Momcheva, Ivelina; Leja, Joel] Yale Univ, Dept Astron, New Haven, CT 06511 USA.
   [Franx, Marijn] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Brammer, Gabriel] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Schreiber, Natascha Foerster; Tacconi, Linda; Wuyts, Stijn] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [da Cunha, Elisabete; Rix, Hans-Walter; van der Wel, Arjen] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Bezanson, Rachel] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Kirkpatrick, Allison] Univ Massachusetts, Dept Astron, Amherst, MA 01002 USA.
   [Skelton, Rosalind] South African Astron Observ, ZA-7935 Cape Town, South Africa.
   [Whitaker, Katherine] NASA, Goddard Space Flight Ctr, Astrophys Sci Div, Greenbelt, MD 20771 USA.
C3 Yale University; Leiden University; Leiden University - Excl LUMC; Space Telescope Science Institute; Max Planck Society; Max Planck Society; University of Arizona; University of Massachusetts System; University of Massachusetts Amherst; National Research Foundation - South Africa; South African Astronomical Observatory; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Nelson, E (corresponding author), Yale Univ, Dept Astron, New Haven, CT 06511 USA.
EM erica.nelson@yale.edu
FU STScI [GO-1277]
NR 46
TC 77
Z9 85
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 SEP 18
PY 2014
VL 513
IS 7518
BP 394
EP +
DI 10.1038/nature13616
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900054
PM 25162527
DA 2026-03-09
ER

PT J
AU Kwiatkowski, N
   Zhang, TH
   Rahl, PB
   Abraham, BJ
   Reddy, J
   Ficarro, SB
   Dastur, A
   Amzallag, A
   Ramaswamy, S
   Tesar, B
   Jenkins, CE
   Hannett, NM
   McMillin, D
   Sanda, T
   Sim, T
   Kim, ND
   Look, T
   Mitsiades, CS
   Weng, AP
   Brown, JR
   Benes, CH
   Marto, JA
   Young, RA
   Gray, NS
AF Kwiatkowski, Nicholas
   Zhang, Tinghu
   Rahl, Peter B.
   Abraham, Brian J.
   Reddy, Jessica
   Ficarro, Scott B.
   Dastur, Anahita
   Amzallag, Arnaud
   Ramaswamy, Sridhar
   Tesar, Bethany
   Jenkins, Catherine E.
   Hannett, Nancy M.
   McMillin, Douglas
   Sanda, Takaomi
   Sim, Taebo
   Kim, Nam Doo
   Look, Thomas
   Mitsiades, Constantine S.
   Weng, Andrew P.
   Brown, Jennifer R.
   Benes, Cyril H.
   Marto, Jarrod A.
   Young, Richard A.
   Gray, Nathanael S.
TI Targeting transcription regulation in cancer with a covalent CDK7 inhibitor
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; activating kinase; super-enhancers; factor tfiih; ctd kinase; phosphorylation; elongation; complex; identification; discovery
AB Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state', but direct pharmacological inhibition of transcription factors has so far proven difficult(2). However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates', including cyclin-dependent kinases (CDKs)(4). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNXI and suggests that sensitivity to THZ I may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNXI in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 Ifinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.
C1 [Kwiatkowski, Nicholas; Zhang, Tinghu; Ficarro, Scott B.; Marto, Jarrod A.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Kwiatkowski, Nicholas; Zhang, Tinghu; Ficarro, Scott B.; Marto, Jarrod A.; Gray, Nathanael S.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA.
   [Kwiatkowski, Nicholas; Rahl, Peter B.; Abraham, Brian J.; Reddy, Jessica; Hannett, Nancy M.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Reddy, Jessica; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA.
   [Dastur, Anahita; Amzallag, Arnaud; Ramaswamy, Sridhar; Benes, Cyril H.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Charlestown, MA 02129 USA.
   [Dastur, Anahita; Amzallag, Arnaud; Ramaswamy, Sridhar; Benes, Cyril H.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Amzallag, Arnaud; Ramaswamy, Sridhar] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Tesar, Bethany; McMillin, Douglas; Mitsiades, Constantine S.; Brown, Jennifer R.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA.
   [Tesar, Bethany; McMillin, Douglas; Mitsiades, Constantine S.; Brown, Jennifer R.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA.
   [Jenkins, Catherine E.; Weng, Andrew P.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
   [Sanda, Takaomi; Look, Thomas] Harvard Univ, Dana Farber Canc Inst, Dept Pediat Oncol, Sch Med, Boston, MA 02215 USA.
   [Sanda, Takaomi] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore.
   [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 136791, South Korea.
   [Sim, Taebo] KU KIST Grad Sch Converging Sci & Technol, Seoul 136713, South Korea.
   [Kim, Nam Doo] Daegu Gyeongbuk Med Innovat Fdn, Taegu 706010, South Korea.
   [Look, Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; British Columbia Cancer Agency; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; National University of Singapore; Korea Institute of Science & Technology (KIST); Korea University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Gray, NS (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM young@wi.mit.edu; nathanael_gray@dfci.harvard.edu
FU National Institutes of Health [R01 CA130876-04, U54 HG006097-02, CA178860-01, P01 N5047572-10, HG002668, CA109901]; American Cancer Society Postdoctoral Fellowship [120272-PF-11-042-01-DMC]; Translational Research Program of the Leukemia Lymphoma Society; American Cancer Society; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008042] Funding Source: NIH RePORTER
NR 30
TC 716
Z9 845
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 30
PY 2014
VL 511
IS 7511
BP 616
EP +
DI 10.1038/nature13393
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300040
PM 25043025
DA 2026-03-09
ER

PT J
AU Han, P
   Li, W
   Lin, CH
   Yang, J
   Shang, C
   Nurnberg, ST
   Jin, KK
   Xu, WH
   Lin, CY
   Lin, CJ
   Xiong, YQ
   Chien, HC
   Zhou, B
   Ashley, E
   Bernstein, D
   Chen, PS
   Chen, HSV
   Quertermous, T
   Chang, CP
AF Han, Pei
   Li, Wei
   Lin, Chiou-Hong
   Yang, Jin
   Shang, Ching
   Nurnberg, Sylvia T.
   Jin, Kevin Kai
   Xu, Weihong
   Lin, Chieh-Yu
   Lin, Chien-Jung
   Xiong, Yiqin
   Chien, Huan-Chieh
   Zhou, Bin
   Ashley, Euan
   Bernstein, Daniel
   Chen, Peng-Sheng
   Chen, Huei-Sheng Vincent
   Quertermous, Thomas
   Chang, Ching-Pin
TI A long noncoding RNA protects the heart from pathological hypertrophy
SO NATURE
LA English
DT Article
ID cardiac-hypertrophy; structural basis; in-vivo; chromatin; transcription; growth; domain; gene; morphogenesis; recognition
AB The role of long noncoding RNA(lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription(1), including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction(2). Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA-chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Myheart, orMhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1-Hdac-Parp chromatin repressor complex(3) to inhib-it Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the prestress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy(3). Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA(Mhrt) and chromatinized-but not naked-DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA chromatin interaction.
C1 [Han, Pei; Li, Wei; Yang, Jin; Chen, Peng-Sheng; Chang, Ching-Pin] Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA.
   [Han, Pei; Li, Wei; Yang, Jin; Chen, Peng-Sheng; Chang, Ching-Pin] Indiana Univ, Sch Med, Div Cardiol, Dept Med, Indianapolis, IN 46202 USA.
   [Han, Pei; Li, Wei; Lin, Chiou-Hong; Shang, Ching; Nurnberg, Sylvia T.; Jin, Kevin Kai; Lin, Chieh-Yu; Lin, Chien-Jung; Xiong, Yiqin; Chien, Huan-Chieh; Ashley, Euan; Quertermous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Div Cardiovasc Med, Stanford, CA 94305 USA.
   [Xu, Weihong] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Stanford, CA 94305 USA.
   [Zhou, Bin] Yeshiva Univ Albert Einstein Coll Med, Dept Genet Pediat & Med Cardiol, Bronx, NY 10461 USA.
   [Bernstein, Daniel] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Chen, Huei-Sheng Vincent] Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, La Jolla, CA 92037 USA.
   [Chang, Ching-Pin] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
   [Chang, Ching-Pin] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
C3 Indiana University System; Indiana University Indianapolis; Indiana University System; Indiana University Indianapolis; Stanford University; Stanford University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Stanford University; Sanford Burnham Prebys Medical Discovery Institute; Indiana University System; Indiana University Indianapolis; Indiana University System; Indiana University Indianapolis
RP Chang, CP (corresponding author), Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA.
EM changcp@iu.edu
FU American Heart Association (AHA) [12EIA8960018]; National Institutes of Health (NIH) [HL118087, HL121197]; March of Dimes Foundation [6-FY11-260]; California Institute of Regenerative Medicine (CIRM) [RN2-00909]; Oak Foundation; Baxter Foundation; Stanford Heart Center Research Program; Indiana University (IU) School of Medicine-IU Health Strategic Research Initiative; IU Physician-Scientist Initiative; AHA; Lucile Packard Children's Foundation; NIH [HL109512, HL105194, HL78931, HL71140, HL116997, HL111770]; CIRM [RB2-01512, RB4-06276]; National Heart Lung and Blood Institute [R01HL121197] Funding Source: NIH RePORTER; American Heart Association (AHA) [12EIA8960018] Funding Source: American Heart Association (AHA)
NR 51
TC 616
Z9 718
U1 3
U2 211
PU NATURE PUBLISHING 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 2
PY 2014
VL 514
IS 7520
BP 102
EP +
DI 10.1038/nature13596
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800044
PM 25119045
DA 2026-03-09
ER

PT J
AU Bald, T
   Quast, T
   Landsberg, J
   Rogava, M
   Glodde, N
   Lopez-Ramos, D
   Kohlmeyer, J
   Riesenberg, S
   van den Boorn-Konijnenberg, D
   Hömig-Hölzel, C
   Reuten, R
   Schadow, B
   Weighardt, H
   Wenzel, D
   Helfrich, I
   Schadendorf, D
   Bloch, W
   Bianchi, ME
   Lugassy, C
   Barnhill, RL
   Koch, M
   Fleischmann, BK
   Förster, I
   Kastenmüller, W
   Kolanus, W
   Hölzel, M
   Gaffal, E
   Tüting, T
AF Bald, Tobias
   Quast, Thomas
   Landsberg, Jennifer
   Rogava, Meri
   Glodde, Nicole
   Lopez-Ramos, Dorys
   Kohlmeyer, Judith
   Riesenberg, Stefanie
   van den Boorn-Konijnenberg, Debby
   Hoemig-Hoelzel, Cornelia
   Reuten, Raphael
   Schadow, Benjamin
   Weighardt, Heike
   Wenzel, Daniela
   Helfrich, Iris
   Schadendorf, Dirk
   Bloch, Wilhelm
   Bianchi, Marco E.
   Lugassy, Claire
   Barnhill, Raymond L.
   Koch, Manuel
   Fleischmann, Bernd K.
   Foerster, Irmgard
   Kastenmueller, Wolfgang
   Kolanus, Waldemar
   Hoelzel, Michael
   Gaffal, Evelyn
   Tueting, Thomas
TI Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma
SO NATURE
LA English
DT Article
ID circulating tumor-cells; malignant-melanoma; cytokine release; angiogenesis; neutrophils; expression; protein; immune; stage; mouse
AB Intermittent intense ultraviolet (UV) exposure represents an important aetiological factor in the development of malignant melanoma(1). The ability of UV radiation to cause tumour-initiating DNA mutations in melanocytes is now firmly established(2), but how the microenvironmental effects of UV radiation(3,4) influence melanoma pathogenesis is not fully understood. Here we report that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model(5) promotes metastatic progression, independent of its tumour-initiating effects. UV irradiation enhanced the expansion of tumour cells along abluminal blood vessel surfaces and increased the number of lung metastases. This effect depended on the recruitment and activation of neutrophils, initiated by the release of high mobility group box 1 (HMGB1) from UV-damaged epidermal keratinocytes and driven by Toll-like receptor 4 (TLR4). The UV-induced neutrophilic inflammatory response stimulated angiogenesis and promoted the ability of melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces. Our results not only reveal how UV irradiation of epidermal keratinocytes is sensed by the innate immune system, but also show that the resulting inflammatory response catalyses reciprocal melanoma-endothelial cell interactions leading to perivascular invasion, a phenomenon originally described as angiotropism in human melanomas by histopathologists(6). Angiotropism represents a hitherto underappreciated mechanism of metastasis(7) that also increases the likelihood of intravasation and haematogenous dissemination. Consistent with our findings, ulcerated primary human melanomas with abundant neutrophils and reactive angiogenesis frequently show angiotropism and a high risk for metastases. Our work indicates that targeting the inflammation-induced phenotypic plasticity of melanoma cells and their association with endothelial cells represent rational strategies to specifically interfere with metastatic progression.
C1 [Bald, Tobias; Landsberg, Jennifer; Rogava, Meri; Glodde, Nicole; Lopez-Ramos, Dorys; Kohlmeyer, Judith; Gaffal, Evelyn; Tueting, Thomas] Univ Bonn, Dept Dermatol & Allergy, Lab Expt Dermatol, D-53115 Bonn, Germany.
   [Quast, Thomas; Schadow, Benjamin; Weighardt, Heike; Foerster, Irmgard; Kolanus, Waldemar] Univ Bonn, Life & Med Sci Inst, D-53115 Bonn, Germany.
   [Riesenberg, Stefanie; van den Boorn-Konijnenberg, Debby; Hoemig-Hoelzel, Cornelia; Hoelzel, Michael] Univ Bonn, Dept Clin Chem & Clin Pharmacol, Unit RNA Biol, D-53105 Bonn, Germany.
   [Reuten, Raphael; Koch, Manuel] Univ Cologne, Inst Dent Res & Oral Musculoskeletal Biol, Fac Med, Ctr Biochem, D-50931 Cologne, Germany.
   [Wenzel, Daniela; Fleischmann, Bernd K.] Univ Bonn, Life & Brain Ctr, Inst Physiol 1, D-53105 Bonn, Germany.
   [Helfrich, Iris; Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, D-45122 Essen, Germany.
   [Bloch, Wilhelm] German Sport Univ Cologne, Inst Cardiovasc Res & Sport Med, Dept Mol & Cellular Sport Med, D-50933 Cologne, Germany.
   [Bianchi, Marco E.] San Raffaele Univ & Sci Inst, Div Genet & Cell Biol, I-20132 Milan, Italy.
   [Lugassy, Claire; Barnhill, Raymond L.] Univ Calif Los Angeles, Med Ctr, Jonsson Comprehens Canc Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   [Kastenmueller, Wolfgang] Univ Bonn, Inst Mol Med & Expt Immunol, D-53105 Bonn, Germany.
C3 University of Bonn; University of Bonn; University of Bonn; University of Cologne; University of Bonn; University of Duisburg Essen; German Sport University Cologne; Vita-Salute San Raffaele University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; UCLA Jonsson Comprehensive Cancer Center; University of Bonn
RP Hölzel, M (corresponding author), Univ Bonn, Dept Clin Chem & Clin Pharmacol, Unit RNA Biol, D-53105 Bonn, Germany.
EM michael.hoelzel@ukb.uni-bonn.de; evelyn.gaffal@ukb.uni-bonn.de; thomas.tueting@ukb.uni-bonn.de
FU Deutsche Krebshilfe P9 in the Melanoma Research Network; DFG [SFB832, SFB704, HO 4281/2-1, SFB829, SFB829 Z2]; BONFOR; NRW junior research group; Jurgen Manchot Stiftung; AIRC
NR 51
TC 513
Z9 589
U1 2
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 MAR 6
PY 2014
VL 507
IS 7490
BP 109
EP +
DI 10.1038/nature13111
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400052
PM 24572365
DA 2026-03-09
ER

PT J
AU Albert, FW
   Treusch, S
   Shockley, AH
   Bloom, JS
   Kruglyak, L
AF Albert, Frank W.
   Treusch, Sebastian
   Shockley, Arthur H.
   Bloom, Joshua S.
   Kruglyak, Leonid
TI Genetics of single-cell protein abundance variation in large yeast populations
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; budding yeast; expression; reveals; transcription; construction; architecture; dissection; evolution; strains
AB Variation among individuals arises in part from differences in DNA sequences, but the genetic basis for variation in most traits, including common diseases, remains only partly understood. Many DNA variants influence phenotypes by altering the expression level of one or several genes. The effects of such variants can be detected as expression quantitative trait loci (eQTL)(1). Traditional eQTL mapping requires large-scale genotype and gene expression data for each individual in the study sample, which limits sample sizes to hundreds of individuals in both humans and model organisms and reduces statistical power(2-6). Consequently, many eQTL are probably missed, especially those with smaller effects(7). Furthermore, most studies use messenger RNA rather than protein abundance as the measure of gene expression. Studies that have used mass-spectrometry proteomics(8-13) reported unexpected differences between eQTL and protein QTL (pQTL) for the same genes(9,10), but these studies have been even more limited in scope. Here we introduce a powerful method for identifying genetic loci that influence protein expression in the yeast Saccharomyces cerevisiae. We measure single-cell protein abundance through the use of green fluorescent protein tags in very large populations of genetically variable cells, and use pooled sequencing to compare allele frequencies across the genome in thousands of individuals with high versus low protein abundance. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci that we detected were clustered in 'hotspots' that influence multiple proteins, and some hotspots were found to influence more than half of the proteins that we examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains.
C1 [Albert, Frank W.; Bloom, Joshua S.; Kruglyak, Leonid] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Albert, Frank W.; Treusch, Sebastian] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Shockley, Arthur H.] Synthet Genom, La Jolla, CA 92037 USA.
   [Bloom, Joshua S.; Kruglyak, Leonid] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Kruglyak, Leonid] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; Princeton University; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of California System; University of California Los Angeles
RP Albert, FW (corresponding author), Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
EM falbert@mednet.ucla.edu; LKruglyak@mednet.ucla.edu
FU National Institutes of Health (NIH) [R01 GM102308]; James S. McDonnell Centennial Fellowship; Howard Hughes Medical Institute; German Science Foundation [AL 1525/1-1]; National Science Foundation; NIH [F32 GM101857-02]; National Institute of General Medical Sciences [R01GM102308] Funding Source: NIH RePORTER
NR 41
TC 96
Z9 119
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 FEB 27
PY 2014
VL 506
IS 7489
BP 494
EP +
DI 10.1038/nature12904
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100039
PM 24402228
DA 2026-03-09
ER

PT J
AU Schwefel, D
   Groom, HCT
   Boucherit, VC
   Christodoulou, E
   Walker, PA
   Stoye, JP
   Bishop, KN
   Taylor, IA
AF Schwefel, David
   Groom, Harriet C. T.
   Boucherit, Virginie C.
   Christodoulou, Evangelos
   Walker, Philip A.
   Stoye, Jonathan P.
   Bishop, Kate N.
   Taylor, Ian A.
TI Structural basis of lentiviral subversion of a cellular protein degradation pathway
SO NATURE
LA English
DT Article
ID restriction factor samhd1; e3 ubiquitin ligase; hiv-1 infection; virus; transduction; architecture; inhibition; nuclear; usurps; cycle
AB Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection ofmyeloid-lineage cells(1,2) as well as resting CD4(+) T cells(3,4) by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function(5,6). In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation(7,8). The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.
C1 [Schwefel, David; Christodoulou, Evangelos; Walker, Philip A.; Taylor, Ian A.] Natl Inst Med Res, MRC, Div Mol Struct, London NW7 1AA, England.
   [Groom, Harriet C. T.; Boucherit, Virginie C.; Stoye, Jonathan P.; Bishop, Kate N.] Natl Inst Med Res, MRC, Div Virol, London NW7 1AA, England.
C3 MRC National Institute for Medical Research; MRC National Institute for Medical Research
RP Taylor, IA (corresponding author), Natl Inst Med Res, MRC, Div Mol Struct, Mill Hill, London NW7 1AA, England.
EM itaylor@nimr.mrc.ac.uk
FU Diamond Light Source for synchrotron access [7707]; UK Medical Research Council [U117565647, U117592729, U117512710]; Wellcome Trust [084955]; EMBO; European Commission [GA-2010-267146]; Medical Research Council [MC_U117512710, MC_U117592729, MC_U117565647] Funding Source: researchfish; MRC [MC_U117512710, MC_U117565647, MC_U117592729] Funding Source: UKRI
NR 42
TC 105
Z9 124
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 9
PY 2014
VL 505
IS 7482
BP 234
EP +
DI 10.1038/nature12815
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500042
PM 24336198
DA 2026-03-09
ER

PT J
AU Hu, S
   Lozada-Hidalgo, M
   Wang, FC
   Mishchenko, A
   Schedin, F
   Nair, RR
   Hill, EW
   Boukhvalov, DW
   Katsnelson, MI
   Dryfe, RAW
   Grigorieva, IV
   Wu, HA
   Geim, AK
AF Hu, S.
   Lozada-Hidalgo, M.
   Wang, F. C.
   Mishchenko, A.
   Schedin, F.
   Nair, R. R.
   Hill, E. W.
   Boukhvalov, D. W.
   Katsnelson, M. I.
   Dryfe, R. A. W.
   Grigorieva, I. V.
   Wu, H. A.
   Geim, A. K.
TI Proton transport through one-atom-thick crystals
SO NATURE
LA English
DT Article
ID graphene oxide membranes; nanoporous graphene; porous graphene; single-layer; water desalination; nafion; conductivity; temperature; permeation; mechanisms
AB Graphene is increasingly explored as a possible platform for developing novel separation technologies(1-19). This interest has arisen because it is a maximally thin membrane that, once perforated with atomic accuracy, may allow ultrafast and highly selective sieving of gases, liquids, dissolved ions and other species of interest(2,9-19). However, a perfect graphene monolayer is impermeable to all atoms and molecules under ambient conditions(1-7): even hydrogen, the smallest of atoms, is expected to take billions of years to penetrate graphene's dense electronic cloud(3-6). Only accelerated atoms possess the kinetic energy required to do this(20,21). The same behaviour might reasonably be expected in the case of other atomically thin crystals(22,23). Here we report transport and mass spectroscopy measurements which establish that monolayers of graphene and hexagonal boron nitride (hBN) are highly permeable to thermal protons under ambient conditions, whereas no proton transport is detected for thicker crystals such as monolayer molybdenum disulphide, bilayer graphene or multilayer hBN. Protons present an intermediate case between electrons (which can tunnel easily through atomically thin barriers(24)) and atoms, yet our measured transport rates are unexpectedly high(4,5) and raise fundamental questions about the details of the transport process. We see the highest room-temperature proton conductivity with monolayer hBN, for which we measure a resistivity to proton flow of about 10 Omega cm(2) and a low activation energy of about 0.3 electronvolts. At higher temperatures, hBN is outperformed by graphene, the resistivity of which is estimated to fall below 10(-3) Omega cm(2) above 250 degrees Celsius. Proton transport can be further enhanced by decorating the graphene and hBN membranes with catalytic metal nanoparticles. The high, selective proton conductivity and stability make one-atom-thick crystals promising candidates for use in many hydrogen-based technologies.
C1 [Hu, S.; Lozada-Hidalgo, M.; Mishchenko, A.; Nair, R. R.; Grigorieva, I. V.; Geim, A. K.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Hu, S.; Schedin, F.; Hill, E. W.; Geim, A. K.] Univ Manchester, Manchester Ctr Mesosci & Nanotechnol, Manchester M13 9PL, Lancs, England.
   [Wang, F. C.; Wu, H. A.] Univ Sci & Technol China, Dept Modern Mech, Key Lab Mech Behav & Design Mat, Chinese Acad Sci, Hefei 230027, Anhui, Peoples R China.
   [Boukhvalov, D. W.; Katsnelson, M. I.] Radboud Univ Nijmegen, Inst Mol & Mat, NL-6525 AJ Nijmegen, Netherlands.
   [Dryfe, R. A. W.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England.
C3 University of Manchester; University of Manchester; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Radboud University Nijmegen; University of Manchester
RP Lozada-Hidalgo, M (corresponding author), Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
EM marcelo.lozadahidalgo@manchester.ac.uk; wuha@ustc.edu.cn
FU European Research Council; Royal Society; Office of Naval Research; Air Force Office of Scientific Research; National Science Foundation of China; Consejo Nacional de Ciencia y Tecnologia (Mexico); EPSRC [EP/K005014/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/K005014/1] Funding Source: researchfish
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NR 45
TC 683
Z9 789
U1 16
U2 1391
PU NATURE PUBLISHING 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 11
PY 2014
VL 516
IS 7530
BP 227
EP +
DI 10.1038/nature14015
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500040
PM 25470058
DA 2026-03-09
ER

PT J
AU Arnegard, ME
   McGee, MD
   Matthews, B
   Marchinko, KB
   Conte, GL
   Kabir, S
   Bedford, N
   Bergek, S
   Chan, YF
   Jones, FC
   Kingsley, DM
   Peichel, CL
   Schluter, D
AF Arnegard, Matthew E.
   McGee, Matthew D.
   Matthews, Blake
   Marchinko, Kerry B.
   Conte, Gina L.
   Kabir, Sahriar
   Bedford, Nicole
   Bergek, Sara
   Chan, Yingguang Frank
   Jones, Felicity C.
   Kingsley, David M.
   Peichel, Catherine L.
   Schluter, Dolph
TI Genetics of ecological divergence during speciation
SO NATURE
LA English
DT Article
ID dependent postmating isolation; adaptive radiation; natural-selection; 3-spined sticklebacks; trophic position; species-pair; habitat use; evolution; adaptation; size
AB Ecological differences often evolve early in speciation as divergent natural selection drives adaptation to distinct ecological niches, leading ultimately to reproductive isolation. Although this process is a major generator of biodiversity, its genetic basis is still poorly understood. Here we investigate the genetic architecture of niche differentiation in a sympatric species pair of threespine stickleback fish by mapping the environment-dependent effects of phenotypic traits on hybrid feeding and performance under semi-natural conditions. We show that multiple, unlinked loci act largely additively to determine position along the major niche axis separating these recently diverged species. We also find that functional mismatch between phenotypic traits reduces the growth of some stickleback hybrids beyond that expected from an intermediate phenotype, suggesting a role for epistasis between the underlying genes. This functional mismatch might lead to hybrid incompatibilities that are analogous to those underlying intrinsic reproductive isolation but depend on the ecological context.
C1 [Arnegard, Matthew E.; Peichel, Catherine L.] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA.
   [Arnegard, Matthew E.; Peichel, Catherine L.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Arnegard, Matthew E.; Marchinko, Kerry B.; Conte, Gina L.; Kabir, Sahriar; Bedford, Nicole; Schluter, Dolph] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Arnegard, Matthew E.; Marchinko, Kerry B.; Conte, Gina L.; Kabir, Sahriar; Bedford, Nicole; Schluter, Dolph] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [McGee, Matthew D.] Univ Calif Davis, Dept Ecol & Evolut, Davis, CA 95616 USA.
   [Matthews, Blake] EAWAG, Ctr Ecol Evolut & Biogeochem, Dept Aquat Ecol, CH-6047 Kastanienbaum, Switzerland.
   [Bergek, Sara] Uppsala Univ, Dept Anim Ecol, Evolutionary Biol Ctr, SE-75236 Uppsala, Sweden.
   [Chan, Yingguang Frank; Jones, Felicity C.; Kingsley, David M.] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA.
   [Chan, Yingguang Frank; Jones, Felicity C.; Kingsley, David M.] Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; University of British Columbia; University of British Columbia; University of California System; University of California Davis; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Uppsala University; Stanford University; Howard Hughes Medical Institute
RP Arnegard, ME (corresponding author), Fred Hutchinson Canc Res Ctr, Human Biol Div, 1100 Fairview Ave North, Seattle, WA 98109 USA.
EM marnegar@fhcrc.org
FU US National Institutes of Health [F32GM086125, R01 GM089733, P50 HG002568]; Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation; National Cancer Institute [P30CA015704] Funding Source: NIH RePORTER
NR 82
TC 245
Z9 289
U1 1
U2 507
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 17
PY 2014
VL 511
IS 7509
BP 307
EP +
DI 10.1038/nature13301
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200027
PM 24909991
DA 2026-03-09
ER

PT J
AU Xue, W
   Chen, SD
   Yin, H
   Tammela, T
   Papagiannakopoulos, T
   Joshi, NS
   Cai, WX
   Yang, GL
   Bronson, R
   Crowley, DG
   Zhang, F
   Anderson, DG
   Sharp, PA
   Jacks, T
AF Xue, Wen
   Chen, Sidi
   Yin, Hao
   Tammela, Tuomas
   Papagiannakopoulos, Thales
   Joshi, Nikhil S.
   Cai, Wenxin
   Yang, Gillian
   Bronson, Roderick
   Crowley, Denise G.
   Zhang, Feng
   Anderson, Daniel G.
   Sharp, Phillip A.
   Jacks, Tyler
TI CRISPR-mediated direct mutation of cancer genes in the mouse liver
SO NATURE
LA English
DT Article
ID one-step generation; p53 restoration; mice; cas9; specificity
AB The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells(1). Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs)(2-4) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology(7,8). Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the beta-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of b-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.
C1 [Xue, Wen; Chen, Sidi; Yin, Hao; Tammela, Tuomas; Papagiannakopoulos, Thales; Joshi, Nikhil S.; Cai, Wenxin; Yang, Gillian; Crowley, Denise G.; Anderson, Daniel G.; Sharp, Phillip A.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
   [Bronson, Roderick] Tufts Univ, Boston, MA 02115 USA.
   [Bronson, Roderick] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Zhang, Feng] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Zhang, Feng] Harvard, Cambridge, MA 02142 USA.
   [Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02142 USA.
   [Anderson, Daniel G.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Anderson, Daniel G.] MIT, Inst Med Engn & Sci, Cambridge, MA 02142 USA.
   [Sharp, Phillip A.; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Tufts University; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Jacks, T (corresponding author), MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
EM tjacks@mit.edu
FU National Institutes of Health [2-PO1-CA42063, RO1-EB000244, RO1-CA115527, RO1-CA132091]; Cancer Center Support (core) grant from the National Cancer Institute [P30-CA14051]; NIH [R01-CA133404]; Casimir-Lambert Fund; NIH Centers for Cancer Nanotechnology Excellence [5-U54-CA151884-04]; Harvard-MIT Center of Cancer Nanotechnology Excellence; American Association for Cancer Research; Leukemia Lymphoma Society;  [1K99CA169512]; National Cancer Institute [P01CA042063, P30CA014051] Funding Source: NIH RePORTER; National Institute of Biomedical Imaging and Bioengineering [R01EB000244] Funding Source: NIH RePORTER
NR 33
TC 626
Z9 780
U1 4
U2 490
PU NATURE PUBLISHING 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 16
PY 2014
VL 514
IS 7522
BP 380
EP +
DI 10.1038/nature13589
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600055
PM 25119044
DA 2026-03-09
ER

PT J
AU Ghavi-Helm, Y
   Klein, FA
   Pakozdi, T
   Ciglar, L
   Noordermeer, D
   Huber, W
   Furlong, EEM
AF Ghavi-Helm, Yad
   Klein, Felix A.
   Pakozdi, Tibor
   Ciglar, Lucia
   Noordermeer, Daan
   Huber, Wolfgang
   Furlong, Eileen E. M.
TI Enhancer loops appear stable during development and are associated with paused polymerase
SO NATURE
LA English
DT Article
ID gene-expression; drosophila-melanogaster; abdominal-b; transcription; organization; binding; range; transformation; conservation; elements
AB Developmental enhancers initiate transcription and are fundamental to our understanding of developmental networks, evolution and disease. Despite their importance, the properties governing enhancer-promoter interactions and their dynamics during embryogenesis remain unclear. At the beta-globin locus, enhancer-promoter interactions appear dynamic and cell-type specific(1,2), whereas at the HoxD locus they are stable and ubiquitous, being present in tissues where the target genes are not expressed(3,4). The extent to which preformed enhancer-promoter conformations exist at other, more typical, loci and how transcription is eventually triggered is unclear. Here we generated a high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis, covering two developmental stages and tissue contexts, at unprecedented resolution. Although local regulatory interactions are common, long-range interactions are highly prevalent within the compact Drosophila genome. Each enhancer contacts multiple enhancers, and promoters with similar expression, suggesting a role in their co-regulation. Notably, most interactions appear unchanged between tissue context and across development, arising before gene activation, and are frequently associated with paused RNA polymerase. Our results indicate that the general topology governing enhancer contacts is conserved from flies to humans and suggest that transcription initiates from preformed enhancer-promoter loops through release of paused polymerase.
C1 [Ghavi-Helm, Yad; Klein, Felix A.; Pakozdi, Tibor; Ciglar, Lucia; Huber, Wolfgang; Furlong, Eileen E. M.] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Noordermeer, Daan] Swiss Fed Inst Technol, Sch Life Sci, CH-1015 Lausanne, Switzerland.
C3 European Molecular Biology Laboratory (EMBL); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+)
RP Furlong, EEM (corresponding author), European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
EM furlong@embl.de
FU DFG [FU 750]; EMBO; EC
NR 55
TC 398
Z9 485
U1 0
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 AUG 7
PY 2014
VL 512
IS 7512
BP 96
EP +
DI 10.1038/nature13417
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000039
PM 25043061
DA 2026-03-09
ER

PT J
AU Krivanek, OL
   Lovejoy, TC
   Dellby, N
   Aoki, T
   Carpenter, RW
   Rez, P
   Soignard, E
   Zhu, JT
   Batson, PE
   Lagos, MJ
   Egerton, RF
   Crozier, PA
AF Krivanek, Ondrej L.
   Lovejoy, Tracy C.
   Dellby, Niklas
   Aoki, Toshihiro
   Carpenter, R. W.
   Rez, Peter
   Soignard, Emmanuel
   Zhu, Jiangtao
   Batson, Philip E.
   Lagos, Maureen J.
   Egerton, Ray F.
   Crozier, Peter A.
TI Vibrational spectroscopy in the electron microscope
SO NATURE
LA English
DT Article
ID energy-loss spectroscopy; aberration; excitations; interfaces; films
AB Vibrational spectroscopies using infrared radiation(1,2), Raman scattering(3), neutrons(4), low-energy electrons(5) and inelastic electron tunnelling(6) are powerful techniques that can analyse bonding arrangements, identify chemical compounds and probe many other important properties of materials. The spatial resolution of these spectroscopies is typically one micrometre or more, although it can reach a few tens of nanometres or even a few a angstroms when enhanced by the presence of a sharp metallic tip(6,7). If vibrational spectroscopy could be combined with the spatial resolution and flexibility of the transmission electron microscope, it would open up the study of vibrational modes in many different types of nanostructures. Unfortunately, the energy resolution of electron energy loss spectroscopy performed in the electron microscope has until now been too poor to allow such a combination. Recent developments that have improved the attainable energy resolution of electron energy loss spectroscopy in a scanning transmission electron microscope to around ten millielectronvolts now allow vibrational spectroscopy to be carried out in the electron microscope. Here we describe the innovations responsible for the progress, and present examples of applications in inorganic and organic materials, including the detection of hydrogen. We also demonstrate that the vibrational signal has both high-and low-spatial-resolution components, that the first component can be used to map vibrational features at nanometre-level resolution, and that the second component can be used for analysis carried out with the beam positioned just outside the sample-that is, for 'aloof' spectroscopy that largely avoids radiation damage.
C1 [Krivanek, Ondrej L.; Lovejoy, Tracy C.; Dellby, Niklas] Nion Co, Kirkland, WA 98033 USA.
   [Krivanek, Ondrej L.; Rez, Peter] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Aoki, Toshihiro; Soignard, Emmanuel; Zhu, Jiangtao] Arizona State Univ, LeRoy Eyring Ctr Solid State Sci, Tempe, AZ 85287 USA.
   [Carpenter, R. W.; Soignard, Emmanuel] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Batson, Philip E.; Lagos, Maureen J.] Rutgers State Univ, Inst Adv Mat Devices & Nanotechnol, Piscataway, NJ 08854 USA.
   [Batson, Philip E.; Lagos, Maureen J.] Rutgers State Univ, Dept Phys, Piscataway, NJ 08854 USA.
   [Batson, Philip E.; Lagos, Maureen J.] Rutgers State Univ, Dept Mat Sci, Piscataway, NJ 08854 USA.
   [Egerton, Ray F.] Univ Alberta, Dept Phys, Edmonton, AB T6G 2E1, Canada.
   [Crozier, Peter A.] Arizona State Univ, Sch Engn Matter Transport & Energy, Tempe, AZ 85287 USA.
C3 Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; University of Alberta; Arizona State University; Arizona State University-Tempe
RP Krivanek, OL (corresponding author), Nion Co, 1102 Eighth St, Kirkland, WA 98033 USA.
EM krivanek@nion.com; crozier@asu.edu
FU National Science Foundation [DMR MRI 0821796, DMR MRI-R2 959905]; Department of Energy [DE-SC0004954, DE-SC0005132, DE-SC0007694]; Natural Sciences and Engineering Council of Canada; UK Engineering and Physical Research Council (capital equipment grant) [EP/J021156/1]; Arizona State University; Rutgers University; Nion Co.; Engineering and Physical Sciences Research Council [EP/J021156/1] Funding Source: researchfish; U.S. Department of Energy (DOE) [DE-SC0005132, DE-SC0004954] Funding Source: U.S. Department of Energy (DOE)
NR 42
TC 514
Z9 702
U1 8
U2 588
PU NATURE PUBLISHING 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 9
PY 2014
VL 514
IS 7521
BP 209
EP +
DI 10.1038/nature13870
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100038
PM 25297434
DA 2026-03-09
ER

PT J
AU Purcell, SM
   Moran, JL
   Fromer, M
   Ruderfer, D
   Solovieff, N
   Roussos, P
   O'Dushlaine, C
   Chambert, K
   Bergen, SE
   Kähler, A
   Duncan, L
   Stahl, E
   Genovese, G
   Fernández, E
   Collins, MO
   Komiyama, NH
   Choudhary, JS
   Magnusson, PKE
   Banks, E
   Shakir, K
   Garimella, K
   Fennell, T
   DePristo, M
   Grant, SGN
   Haggarty, SJ
   Gabriel, S
   Scolnick, EM
   Lander, ES
   Hultman, CM
   Sullivan, PF
   McCarroll, SA
   Sklar, P
AF Purcell, Shaun M.
   Moran, Jennifer L.
   Fromer, Menachem
   Ruderfer, Douglas
   Solovieff, Nadia
   Roussos, Panos
   O'Dushlaine, Colm
   Chambert, Kimberly
   Bergen, Sarah E.
   Kahler, Anna
   Duncan, Laramie
   Stahl, Eli
   Genovese, Giulio
   Fernandez, Esperanza
   Collins, Mark O.
   Komiyama, Noboru H.
   Choudhary, Jyoti S.
   Magnusson, Patrik K. E.
   Banks, Eric
   Shakir, Khalid
   Garimella, Kiran
   Fennell, Tim
   DePristo, Mark
   Grant, Seth G. N.
   Haggarty, Stephen J.
   Gabriel, Stacey
   Scolnick, Edward M.
   Lander, Eric S.
   Hultman, Christina M.
   Sullivan, Patrick F.
   McCarroll, Steven A.
   Sklar, Pamela
TI A polygenic burden of rare disruptive mutations in schizophrenia
SO NATURE
LA English
DT Article
ID de-novo mutations; messenger-rna; postsynaptic density-95; intellectual disability; association analysis; protein; variant; autism; risk; complex
AB Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive mutations distributed across many genes. Particularly enriched gene sets include the voltage-gated calcium ion channel and the signalling complex formed by the activity-regulated cytoskeleton-associated scaffold protein (ARC) of the postsynaptic density, sets previously implicated by genome-wide association and copy-number variation studies. Similar to reports in autism, targets of the fragile X mental retardation protein (FMRP, product of FMR1) are enriched for case mutations. No individual gene-based test achieves significance after correction for multiple testing and we do not detect any alleles of moderately low frequency (approximately 0.5 to 1 per cent) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene-mapping paradigms in neuropsychiatric disease.
C1 [Purcell, Shaun M.; Moran, Jennifer L.; Fromer, Menachem; O'Dushlaine, Colm; Chambert, Kimberly; Bergen, Sarah E.; Duncan, Laramie; Genovese, Giulio; Haggarty, Stephen J.; Scolnick, Edward M.; McCarroll, Steven A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Purcell, Shaun M.; Fromer, Menachem; Ruderfer, Douglas; Roussos, Panos; Stahl, Eli; Sklar, Pamela] Icahn Sch Med Mt Sinai, Div Psychiat Genom, Dept Psychiat, New York, NY 10029 USA.
   [Purcell, Shaun M.; Fromer, Menachem; Ruderfer, Douglas; Roussos, Panos; Stahl, Eli; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
   [Purcell, Shaun M.; Fromer, Menachem; Solovieff, Nadia; Duncan, Laramie; Haggarty, Stephen J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
   [Purcell, Shaun M.; Duncan, Laramie; Banks, Eric; Shakir, Khalid; Garimella, Kiran; Fennell, Tim; DePristo, Mark; Gabriel, Stacey; Lander, Eric S.; McCarroll, Steven A.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA.
   [Bergen, Sarah E.; Kahler, Anna; Magnusson, Patrik K. E.; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Fernandez, Esperanza] Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium.
   [Fernandez, Esperanza] VIB Ctr Biol Dis, B-3000 Louvain, Belgium.
   [Collins, Mark O.; Komiyama, Noboru H.; Choudhary, Jyoti S.] Wellcome Trust Sanger Inst, Prote Mass Spectrometry, Cambridge CB10 1SA, England.
   [Grant, Seth G. N.] Univ Edinburgh, Ctr Clin Brain Sci, Genes Cognit Programme, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Grant, Seth G. N.] Univ Edinburgh, Ctr Neuroregenerat, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
   [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Karolinska Institutet; KU Leuven; Flanders Institute for Biotechnology (VIB); Wellcome Trust Sanger Institute; University of Edinburgh; University of Edinburgh; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Harvard Medical School; Icahn School of Medicine at Mount Sinai
RP Purcell, SM (corresponding author), Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
EM shaun@broadinstitute.org
FU National Institutes of Health (NIH)/National Institute of Mental Health (NIMH) ARRA Grand Opportunity grant [NIMH RC2 MH089905]; Sylvan Herman Foundation; Stanley Center for Psychiatric Research; Stanley Medical Research Institute; NIH/National Human Genome Research Institute (NHGRI) [U54HG003067]; NIH/NIMH [R01 MH095088, R01 MH091115, R01 MH099126, R01 MH077139, R01 MH095034, T32 MH017119]; Tau Consortium; NIH/NHGRI [R01 HG005827]; Friedman Brain Institute at Mount Sinai School of Medicine; Karolinska Institutet, Karolinska University Hospital; Swedish Research Council; ALF from Swedish County Council; Soderstrom Konigska Foundation; Netherlands Scientific Organization [NWO 645-000-003]; Wellcome Trust; Genes to Cognition Program; Medical Research Council; European Union [241995, 242498, 242167]; Institute for Genomics and Multiscale Biology; National Institute of Mental Health [T32MH017119] Funding Source: NIH RePORTER; MRC [G0802238] Funding Source: UKRI; Medical Research Council [G0802238] Funding Source: researchfish
NR 49
TC 1064
Z9 1229
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 FEB 13
PY 2014
VL 506
IS 7487
BP 185
EP +
DI 10.1038/nature12975
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700030
PM 24463508
DA 2026-03-09
ER

PT J
AU Swarts, DC
   Jore, MM
   Westra, ER
   Zhu, YF
   Janssen, JH
   Snijders, AP
   Wang, YL
   Patel, DJ
   Berenguer, J
   Brouns, SJJ
   van der Oost, J
AF Swarts, Daan C.
   Jore, Matthijs M.
   Westra, Edze R.
   Zhu, Yifan
   Janssen, Jorijn H.
   Snijders, Ambrosius P.
   Wang, Yanli
   Patel, Dinshaw J.
   Berenguer, Jose
   Brouns, Stan J. J.
   van der Oost, John
TI DNA-guided DNA interference by a prokaryotic Argonaute
SO NATURE
LA English
DT Article
ID thermophile thermus-thermophilus; structural basis; rna; recognition; eubacteria; sequence
AB RNA interference is widely distributed in eukaryotes and has a variety of functions, including antiviral defence and gene regulation(1,2). All RNA interference pathways use small single-stranded RNA(ssRNA) molecules that guide proteins of the Argonaute (Ago) family to complementary ssRNA targets: RNA-guided RNA interference(1,2). The role of prokaryotic Ago variants has remained elusive, although bioinformatics analysis has suggested their involvement in host defence(3). Here we demonstrate that Ago of the bacterium Thermus thermophilus (TtAgo) acts as a barrier for the uptake and propagation of foreign DNA. In vivo, TtAgo is loaded with 5'-phosphorylated DNA guides, 13-25 nucleotides in length, that are mostly plasmid derived and have a strong bias for a 5'-end deoxycytidine. These small interfering DNAs guide TtAgo to cleave complementary DNA strands. Hence, despite structural homology to its eukaryotic counterparts, TtAgo functions in host defence by DNA-guided DNA interference.
C1 [Swarts, Daan C.; Jore, Matthijs M.; Westra, Edze R.; Zhu, Yifan; Janssen, Jorijn H.; Brouns, Stan J. J.; van der Oost, John] Wageningen Univ, Dept Agrotechnol & Food Sci, Microbiol Lab, NL-6703 HB Wageningen, Netherlands.
   [Snijders, Ambrosius P.] Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
   [Wang, Yanli] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
   [Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Berenguer, Jose] UAM CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain.
C3 Wageningen University & Research; Cancer Research UK; Chinese Academy of Sciences; Institute of Biophysics, CAS; Memorial Sloan Kettering Cancer Center; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM)
RP van der Oost, J (corresponding author), Wageningen Univ, Dept Agrotechnol & Food Sci, Microbiol Lab, Dreijenpl 10, NL-6703 HB Wageningen, Netherlands.
EM john.vanderoost@wur.nl
FU Netherlands Organization of Scientific Research (NWO) ((NWO-TOP) [854.10.003]; Netherlands Organization of Scientific Research (NWO) (NWO Vidi) [864.11.005]; Spanish Ministry of Science and Innovation [BIO2010-18875]; Fundacion Ramon Areces; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
CR Averhoff B, 2009, FEMS MICROBIOL REV, V33, P611, DOI 10.1111/j.1574-6976.2008.00160.x
   Bates AD, 2005, DNA TOPOLOGY, V0, P0
   Cava F, 2008, ENVIRON MICROBIOL, V10, P605, DOI 10.1111/j.1462-2920.2007.01482.x
   Cava F, 2007, MOL MICROBIOL, V64, P630, DOI 10.1111/j.1365-2958.2007.05687.x
   CHARBONNIER F, 1994, J BACTERIOL, V176, P1251, DOI 10.1128/jb.176.5.1251-1259.1994
   COLLIN RG, 1988, FEMS MICROBIOL LETT, V55, P235, DOI 10.1111/j.1574-6968.1988.tb13940.x
   Duguet M, 1993, NUCLEIC ACIDS RES, V21, P463
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   Frank F, 2012, EMBO J, V31, P3588, DOI 10.1038/emboj.2012.204
   Frank F, 2010, NATURE, V465, P818, DOI 10.1038/nature09039
   Gregory ST, 2008, FEMS MICROBIOL LETT, V289, P187, DOI 10.1111/j.1574-6968.2008.01389.x
   Joshua-Tor L, 2011, CSH PERSPECT BIOL, V3, P0, DOI 10.1101/cshperspect.a003772
   Ketting RF, 2010, ADV EXP MED BIOL, V700, P1, DOI 10.1007/978-1-4419-7823-3_1
   KOYAMA Y, 1986, J BACTERIOL, V166, P338, DOI 10.1128/jb.166.1.338-340.1986
   Laptenko O, 2006, EMBO J, V25, P2131, DOI 10.1038/sj.emboj.7601094
   Li H, 2009, BIOINFORMATICS, V25, P1754, DOI 10.1093/bioinformatics/btp324
   Liu JD, 2004, SCIENCE, V305, P1437, DOI 10.1126/science.1102513
   Ma JB, 2005, NATURE, V434, P666, DOI 10.1038/nature03514
   Makarova KS, 2009, BIOL DIRECT, V4, P0, DOI 10.1186/1745-6150-4-29
   Milne I, 2013, BRIEF BIOINFORM, V14, P193, DOI 10.1093/bib/bbs012
   Nakanishi K, 2012, NATURE, V486, P368, DOI 10.1038/nature11211
   Olovnikov I, 2013, MOL CELL, V51, P594, DOI 10.1016/j.molcel.2013.08.014
   Rocha EPC, 2002, TRENDS GENET, V18, P291, DOI 10.1016/S0168-9525(02)02690-2
   Sheng G, 2014, P NATL ACAD SCI USA, V111, P652, DOI 10.1073/pnas.1321032111
   Travers A, 2005, NAT REV MICROBIOL, V3, P157, DOI 10.1038/nrmicro1088
   Uliczka F, 2011, PLOS ONE, V6, P0, DOI 10.1371/journal.pone.0020425
   Wang YL, 2008, NATURE, V456, P209, DOI 10.1038/nature07315
   Wang YL, 2009, NATURE, V461, P754, DOI 10.1038/nature08434
   Wang YL, 2008, NATURE, V456, P921, DOI 10.1038/nature07666
   Westra ER, 2012, MOL CELL, V46, P595, DOI 10.1016/j.molcel.2012.03.018
   Yuan YR, 2005, MOL CELL, V19, P405, DOI 10.1016/j.molcel.2005.07.011
NR 31
TC 391
Z9 621
U1 10
U2 276
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 13
PY 2014
VL 507
IS 7491
BP 258
EP +
DI 10.1038/nature12971
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800044
PM 24531762
DA 2026-03-09
ER

PT J
AU Wang, XH
   Piao, SL
   Ciais, P
   Friedlingstein, P
   Myneni, RB
   Cox, P
   Heimann, M
   Miller, J
   Peng, SS
   Wang, T
   Yang, H
   Chen, AP
AF Wang, Xuhui
   Piao, Shilong
   Ciais, Philippe
   Friedlingstein, Pierre
   Myneni, Ranga B.
   Cox, Peter
   Heimann, Martin
   Miller, John
   Peng, Shushi
   Wang, Tao
   Yang, Hui
   Chen, Anping
TI A two-fold increase of carbon cycle sensitivity to tropical temperature variations
SO NATURE
LA English
DT Article
ID atmospheric co2; tree mortality; climate; drought; land; dioxide; dataset; feedbacks; anomaly; extremes
AB Earth system models project that the tropical land carbon sink will decrease in size in response to an increase in warming and drought during this century, probably causing a positive climate feedback(1,2). But available data(3-5) are too limited at present to test the predicted changes in the tropical carbon balance in response to climate change. Long-term atmospheric carbon dioxide data provide a global record that integrates the interannual variability of the global carbon balance. Multiple lines of evidence(6-8) demonstrate that most of this variability originates in the terrestrial biosphere. In particular, the year-to-year variations in the atmospheric carbon dioxide growth rate (CGR) are thought to be the result of fluctuations in the carbon fluxes of tropical land areas(6,9,10). Recently, the response of CGR to tropical climate interannual variability was used to put a constraint on the sensitivity of tropical land carbon to climate change(10). Here we use the long-term CGR record from Mauna Loa and the South Pole to show that the sensitivity of CGR to tropical temperature interannual variability has increased by a factor of 1.9 +/- 0.3 in the past five decades. We find that this sensitivity was greater when tropical land regions experienced drier conditions. This suggests that the sensitivity of CGR to interannual temperature variations is regulated by moisture conditions, even though the direct correlation between CGR and tropical precipitation is weak(9). We also find that present terrestrial carbon cycle models do not capture the observed enhancement in CGR sensitivity in the past five decades. More realistic model predictions of future carbon cycle and climate feedbacks require a better understanding of the processes driving the response of tropical ecosystems to drought and warming.
C1 [Wang, Xuhui; Piao, Shilong; Ciais, Philippe; Peng, Shushi; Wang, Tao; Yang, Hui] Peking Univ, Sinofrench Inst Earth Syst Sci, Coll Urban & Environm Sci, Beijing 100871, Peoples R China.
   [Piao, Shilong] Chinese Acad Sci, Inst Tibetan Plateau Res, Beijing 100085, Peoples R China.
   [Ciais, Philippe; Wang, Tao] CEA CNRS UVSQ, Lab Sci Climat & Environm, F-91191 Gif Sur Yvette, France.
   [Friedlingstein, Pierre; Cox, Peter] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
   [Myneni, Ranga B.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Heimann, Martin] Max Planck Inst Biogeochem, D-07701 Jena, Germany.
   [Miller, John] NOAA, Global Monitoring Div, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Miller, John] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Chen, Anping] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
C3 Peking University; Chinese Academy of Sciences; Institute of Tibetan Plateau Research, CAS; CEA; Universite Paris Saclay; University of Exeter; Boston University; Max Planck Society; National Oceanic Atmospheric Admin (NOAA) - USA; University of Colorado System; University of Colorado Boulder; Princeton University
RP Piao, SL (corresponding author), Peking Univ, Sinofrench Inst Earth Syst Sci, Coll Urban & Environm Sci, Beijing 100871, Peoples R China.
EM slpiao@pku.edu.cn
FU National Natural Science Foundation of China [41125004]; National Basic Research Program of China [2010CB950601, 2013CB956303]; National Youth Top-notch Talent Support Program in China; NASA Earth Science Division
NR 51
TC 301
Z9 349
U1 6
U2 620
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 13
PY 2014
VL 506
IS 7487
BP 212
EP +
DI 10.1038/nature12915
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700036
PM 24463514
DA 2026-03-09
ER

PT J
AU Ouyang, H
   Xue, YC
   Lin, Y
   Zhang, XH
   Xi, L
   Patel, S
   Cai, HM
   Luo, J
   Zhang, MX
   Zhang, M
   Yang, Y
   Li, G
   Li, HR
   Jiang, W
   Yeh, E
   Lin, J
   Pei, M
   Zhu, J
   Cao, GQ
   Zhang, LF
   Yu, B
   Chen, SC
   Fu, XD
   Liu, YZ
   Zhang, K
AF Ouyang, Hong
   Xue, Yuanchao
   Lin, Ying
   Zhang, Xiaohui
   Xi, Lei
   Patel, Sherrina
   Cai, Huimin
   Luo, Jing
   Zhang, Meixia
   Zhang, Ming
   Yang, Yang
   Li, Gen
   Li, Hairi
   Jiang, Wei
   Yeh, Emily
   Lin, Jonathan
   Pei, Michelle
   Zhu, Jin
   Cao, Guiqun
   Zhang, Liangfang
   Yu, Benjamin
   Chen, Shaochen
   Fu, Xiang-Dong
   Liu, Yizhi
   Zhang, Kang
TI WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis
SO NATURE
LA English
DT Article
ID stem-cells; p63; morphogenesis; pathway; differentiation; expression; keratins; limb; skin
AB The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs)(1,2), and deficiency in LSCs or corneal epithelium-which turns cornea into a non-transparent, keratinized skin-like epithelium-causes corneal surface disease that leads to blindness in millions of people worldwide(3). How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases.
C1 [Ouyang, Hong; Lin, Ying; Xi, Lei; Liu, Yizhi; Zhang, Kang] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
   [Ouyang, Hong; Lin, Ying; Zhang, Xiaohui; Xi, Lei; Patel, Sherrina; Luo, Jing; Yang, Yang; Yeh, Emily; Lin, Jonathan; Pei, Michelle; Zhu, Jin; Zhang, Liangfang; Chen, Shaochen; Fu, Xiang-Dong; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA.
   [Ouyang, Hong; Lin, Ying; Zhang, Xiaohui; Xi, Lei; Patel, Sherrina; Luo, Jing; Yang, Yang; Yeh, Emily; Lin, Jonathan; Pei, Michelle; Zhu, Jin; Zhang, Liangfang; Chen, Shaochen; Fu, Xiang-Dong; Zhang, Kang] Univ Calif San Diego, Biomat & Tissue Engn Ctr, Inst Engn Med, La Jolla, CA 92093 USA.
   [Xue, Yuanchao; Li, Hairi; Fu, Xiang-Dong] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Cai, Huimin; Zhang, Meixia; Zhang, Ming; Li, Gen; Jiang, Wei; Cao, Guiqun; Zhang, Kang] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Mol Med Res Ctr, Chengdu 610041, Sichuan, Peoples R China.
   [Cai, Huimin] Guangzhou KangRui Biol Pharmaceut Technol Co Ltd, Guangzhou 510005, Guangdong, Peoples R China.
   [Zhang, Liangfang; Chen, Shaochen] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA.
   [Yu, Benjamin] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Yu, Benjamin; Fu, Xiang-Dong; Zhang, Kang] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
   [Zhang, Kang] Vet Adm Healthcare Syst, San Diego, CA 92093 USA.
C3 Sun Yat Sen University; 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; Sichuan University; 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 Zhang, K (corresponding author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
EM xdfu@ucsd.edu; yzliu62@yahoo.com; kangzhang@ucsd.edu
FU 973 program [2013CB967504, 2014CB964900]; Project of Fundamental Research Funds [2012KF03]; State Key laboratory of Ophthalmology; NIH [GM049369]; KACST-UCSD Center of Excellence in Nanomedicine; NIH Director's Transformative R01 Program [R01 EY021374]; CIRM
NR 22
TC 210
Z9 240
U1 2
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 JUL 17
PY 2014
VL 511
IS 7509
BP 358
EP +
DI 10.1038/nature13465
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200038
PM 25030175
DA 2026-03-09
ER

PT J
AU Kiviet, DJ
   Nghe, P
   Walker, N
   Boulineau, S
   Sunderlikova, V
   Tans, SJ
AF Kiviet, Daniel J.
   Nghe, Philippe
   Walker, Noreen
   Boulineau, Sarah
   Sunderlikova, Vanda
   Tans, Sander J.
TI Stochasticity of metabolism and growth at the single-cell level
SO NATURE
LA English
DT Article
ID gene-expression noise; escherichia-coli; bacteria; networks
AB Elucidating the role of molecular stochasticity(1) in cellular growth is central to understanding phenotypic heterogeneity(2) and the stability of cellular proliferation(3). The inherent stochasticity of metabolic reaction events(4) should have negligible effect, because of averaging over the many reaction events contributing to growth. Indeed, metabolism and growth are often considered to be constant for fixed conditions(5,6). Stochastic fluctuations in the expression level(1,7-9) of metabolic enzymes could produce variations in the reactions they catalyse. However, whether such molecular fluctuations can affect growth is unclear, given the various stabilizing regulatory mechanisms(10-12), the slow adjustment of key cellular components such as ribosomes(13,14), and the secretion(15) and buffering(16,17) of excess metabolites. Here we use time-lapse microscopy to measure fluctuations in the instantaneous growth rate of single cells of Escherichia coli, and quantify time-resolved cross-correlations with the expression of lac genes and enzymes in central metabolism. We show that expression fluctuations of catabolically active enzymes can propagate and cause growth fluctuations, with transmission depending on the limitation of the enzyme to growth. Conversely, growth fluctuations propagate back to perturb expression. Accordingly, enzymes were found to transmit noise to other unrelated genes via growth. Homeostasis is promoted by a noise-cancelling mechanism that exploits fluctuations in the dilution of proteins by cell-volume expansion. The results indicate that molecular noise is propagated not only by regulatory proteins(18,19) but also by metabolic reactions. They also suggest that cellular metabolism is inherently stochastic, and a generic source of phenotypic heterogeneity.
C1 [Kiviet, Daniel J.; Nghe, Philippe; Walker, Noreen; Boulineau, Sarah; Sunderlikova, Vanda; Tans, Sander J.] FOM Inst AMOLF, NL-1098 XG Amsterdam, Netherlands.
   [Kiviet, Daniel J.] Swiss Fed Inst Technol, Dept Environm Syst Sci, CH-8092 Zurich, Switzerland.
   [Kiviet, Daniel J.] Eawag, Dept Environm Microbiol, CH-8600 Dubendorf, Switzerland.
C3 AMOLF; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG)
RP Tans, SJ (corresponding author), FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
EM kiviet@env.ethz.ch; tans@amolf.nl
FU ETH Zurich Postdoctoral Fellowship
NR 30
TC 307
Z9 342
U1 3
U2 142
PU NATURE PUBLISHING 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 16
PY 2014
VL 514
IS 7522
BP 376
EP +
DI 10.1038/nature13582
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600054
PM 25186725
DA 2026-03-09
ER

PT J
AU Lin, IW
   Sosso, D
   Chen, LQ
   Gase, K
   Kim, SG
   Kessler, D
   Klinkenberg, PM
   Gorder, MK
   Hou, BH
   Qu, XQ
   Carter, CJ
   Baldwin, IT
   Frommer, WB
AF Lin, I. Winnie
   Sosso, Davide
   Chen, Li-Qing
   Gase, Klaus
   Kim, Sang-Gyu
   Kessler, Danny
   Klinkenberg, Peter M.
   Gorder, Molly K.
   Hou, Bi-Huei
   Qu, Xiao-Qing
   Carter, Clay J.
   Baldwin, Ian T.
   Frommer, Wolf B.
TI Nectar secretion requires sucrose phosphate synthases and the sugar transporter SWEET9
SO NATURE
LA English
DT Article
ID differential gene-expression; transformation; generation; selection; proteins; exchange; sequence; flowers; lines
AB Angiosperms developed floral nectaries that reward pollinating insects(1). Although nectar function and composition have been characterized, the mechanism of nectar secretion has remained unclear(2). Here we identify SWEET9 as a nectary-specific sugar transporter in three eudicot species: Arabidopsis thaliana, Brassica rapa (extrastaminal nectaries) and Nicotiana attenuata (gynoecial nectaries). We show that SWEET9 is essential for nectar production and can function as an efflux transporter. We also show that sucrose phosphate synthase genes, encoding key enzymes for sucrose biosynthesis, are highly expressed in nectaries and that their expression is also essential for nectar secretion. Together these data are consistent with a model in which sucrose is synthesized in the nectary parenchyma and subsequently secreted into the extracellular space via SWEET9, where sucrose is hydrolysed by an apoplasmic invertase to produce a mixture of sucrose, glucose and fructose. The recruitment of SWEET9 for sucrose export may have been a key innovation, and could have coincided with the evolution of core eudicots and contributed to the evolution of nectar secretion to reward pollinators.
C1 [Lin, I. Winnie; Sosso, Davide; Frommer, Wolf B.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Lin, I. Winnie; Sosso, Davide; Chen, Li-Qing; Hou, Bi-Huei; Qu, Xiao-Qing; Frommer, Wolf B.] Carnegie Inst Sci, Stanford, CA 94305 USA.
   [Gase, Klaus; Kim, Sang-Gyu; Kessler, Danny; Baldwin, Ian T.] Max Planck Inst Chem Oekol, D-07745 Jena, Germany.
   [Klinkenberg, Peter M.; Gorder, Molly K.; Carter, Clay J.] Univ Minnesota, Dept Biol, Duluth, MN 55812 USA.
   [Qu, Xiao-Qing] China Agr Univ, Key Lab Plant & Soil Interact, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
C3 Stanford University; Carnegie Institution for Science; Max Planck Society; University of Minnesota System; University of Minnesota Duluth; China Agricultural University
RP Frommer, WB (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM wfrommer@stanford.edu
FU Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences at the US Department of Energy [DE-FG02-04ER15542]; Department of Biology, Stanford University; Carnegie; Carnegie Institution; Chinese Scholarship Council [2009635108]; US National Science Foundation [0820730]; European Research Council [293926]; Max Planck Gesellschaft; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0820730] Funding Source: National Science Foundation
NR 47
TC 346
Z9 411
U1 11
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 APR 24
PY 2014
VL 508
IS 7497
BP 1
EP +
DI 10.1038/nature13082
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600041
PM 24670640
DA 2026-03-09
ER

PT J
AU Ojesina, AI
   Lichtenstein, L
   Freeman, SS
   Pedamallu, CS
   Imaz-Rosshandler, I
   Pugh, TJ
   Cherniack, AD
   Ambrogio, L
   Cibulskis, K
   Bertelsen, B
   Romero-Cordoba, S
   Treviño, V
   Vazquez-Santillan, K
   Guadarrama, AS
   Wright, AA
   Rosenberg, MW
   Duke, F
   Kaplan, B
   Wang, R
   Nickerson, E
   Walline, HM
   Lawrence, MS
   Stewart, C
   Carter, SL
   McKenna, A
   Rodriguez-Sanchez, IP
   Espinosa-Castilla, M
   Woie, K
   Bjorge, L
   Wik, E
   Halle, MK
   Hoivik, EA
   Krakstad, C
   Gabiño, NB
   Gómez-Macías, GS
   Valdez-Chapa, LD
   Garza-Rodríguez, ML
   Maytorena, G
   Vazquez, J
   Rodea, C
   Cravioto, A
   Cortes, ML
   Greulich, H
   Crum, CP
   Neuberg, DS
   Hidalgo-Miranda, A
   Escareno, CR
   Akslen, LA
   Carey, TE
   Vintermyr, OK
   Gabriel, SB
   Barrera-Saldaña, HA
   Melendez-Zajgla, J
   Getz, G
   Salvesen, HB
   Meyerson, M
AF Ojesina, Akinyemi I.
   Lichtenstein, Lee
   Freeman, Samuel S.
   Pedamallu, Chandra Sekhar
   Imaz-Rosshandler, Ivan
   Pugh, Trevor J.
   Cherniack, Andrew D.
   Ambrogio, Lauren
   Cibulskis, Kristian
   Bertelsen, Bjorn
   Romero-Cordoba, Sandra
   Trevino, Victor
   Vazquez-Santillan, Karla
   Salido Guadarrama, Alberto
   Wright, Alexi A.
   Rosenberg, Mara W.
   Duke, Fujiko
   Kaplan, Bethany
   Wang, Rui
   Nickerson, Elizabeth
   Walline, Heather M.
   Lawrence, Michael S.
   Stewart, Chip
   Carter, Scott L.
   McKenna, Aaron
   Rodriguez-Sanchez, Iram P.
   Espinosa-Castilla, Magali
   Woie, Kathrine
   Bjorge, Line
   Wik, Elisabeth
   Halle, Mari K.
   Hoivik, Erling A.
   Krakstad, Camilla
   Belem Gabino, Nayeli
   Sofia Gomez-Macias, Gabriela
   Valdez-Chapa, Lezmes D.
   Lourdes Garza-Rodriguez, Maria
   Maytorena, German
   Vazquez, Jorge
   Rodea, Carlos
   Cravioto, Adrian
   Cortes, Maria L.
   Greulich, Heidi
   Crum, Christopher P.
   Neuberg, Donna S.
   Hidalgo-Miranda, Alfredo
   Escareno, Claudia Rangel
   Akslen, Lars A.
   Carey, Thomas E.
   Vintermyr, Olav K.
   Gabriel, Stacey B.
   Barrera-Saldana, Hugo A.
   Melendez-Zajgla, Jorge
   Getz, Gad
   Salvesen, Helga B.
   Meyerson, Matthew
TI Landscape of genomic alterations in cervical carcinomas
SO NATURE
LA English
DT Article
ID somatic mutations; human-papillomavirus; sensitive detection; cancer; discovery; expression; framework; catalog; fusion; domain
AB Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide(1,2). The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established(3). Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS(4-7) as well as several copy-number alterations in the pathogenesis of cervical carcinomas(8,9). Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.
C1 [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Pugh, Trevor J.; Wright, Alexi A.; Duke, Fujiko; Kaplan, Bethany; Wang, Rui; Greulich, Heidi; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Ojesina, Akinyemi I.; Lichtenstein, Lee; Freeman, Samuel S.; Pedamallu, Chandra Sekhar; Pugh, Trevor J.; Cherniack, Andrew D.; Ambrogio, Lauren; Cibulskis, Kristian; Rosenberg, Mara W.; Kaplan, Bethany; Nickerson, Elizabeth; Lawrence, Michael S.; Stewart, Chip; Carter, Scott L.; McKenna, Aaron; Cortes, Maria L.; Greulich, Heidi; Gabriel, Stacey B.; Getz, Gad; Meyerson, Matthew] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Imaz-Rosshandler, Ivan; Romero-Cordoba, Sandra; Vazquez-Santillan, Karla; Salido Guadarrama, Alberto; Espinosa-Castilla, Magali; Belem Gabino, Nayeli; Hidalgo-Miranda, Alfredo; Escareno, Claudia Rangel; Melendez-Zajgla, Jorge] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
   [Bertelsen, Bjorn; Akslen, Lars A.; Vintermyr, Olav K.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
   [Trevino, Victor] Tecnol Monterrey, Monterrey 64849, Mexico.
   [Wright, Alexi A.; Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Wang, Rui] Fudan Univ, Shanghai Canc Ctr, Dept Thorac Surg, Shanghai 200032, Peoples R China.
   [Walline, Heather M.] Univ Michigan, Rackham Grad Sch, Program Biomed Sci, Canc Biol Program, Ann Arbor, MI 48109 USA.
   [Rodriguez-Sanchez, Iram P.; Sofia Gomez-Macias, Gabriela; Valdez-Chapa, Lezmes D.; Lourdes Garza-Rodriguez, Maria; Barrera-Saldana, Hugo A.] Univ Autonoma Nuevo Leon, Fac Med, Monterrey 64460, Nuevo Leon, Mexico.
   [Rodriguez-Sanchez, Iram P.; Sofia Gomez-Macias, Gabriela; Valdez-Chapa, Lezmes D.; Lourdes Garza-Rodriguez, Maria; Barrera-Saldana, Hugo A.] Univ Autonoma Nuevo Leon, Hosp Univ Dr Jose Eluterio Gonzalez, Monterrey 64460, Nuevo Leon, Mexico.
   [Woie, Kathrine; Bjorge, Line; Wik, Elisabeth; Halle, Mari K.; Hoivik, Erling A.; Krakstad, Camilla; Salvesen, Helga B.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
   [Bjorge, Line; Wik, Elisabeth; Halle, Mari K.; Hoivik, Erling A.; Krakstad, Camilla; Salvesen, Helga B.] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway.
   [Maytorena, German; Vazquez, Jorge; Rodea, Carlos; Cravioto, Adrian] Inst Mexicano Seguro Social, Mexico City 06720, DF, Mexico.
   [Crum, Christopher P.; Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Escareno, Claudia Rangel] Claremont Grad Univ, Claremont, CA 91711 USA.
   [Akslen, Lars A.; Vintermyr, Olav K.] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, N-5020 Bergen, Norway.
   [Carey, Thomas E.] Univ Michigan, Ctr Comprehens Canc, Head & Neck Oncol Program, Ann Arbor, MI 48109 USA.
   [Carey, Thomas E.] Univ Michigan, Ctr Comprehens Canc, Dept Otolaryngol, Ann Arbor, MI 48109 USA.
   [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Getz, Gad] Harvard Univ, Sch Med, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Instituto Nacional de Medicina Genomica; University of Bergen; Haukeland University Hospital; Tecnologico de Monterrey; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Fudan University; University of Michigan System; University of Michigan; Universidad Autonoma de Nuevo Leon; Universidad Autonoma de Nuevo Leon; University of Bergen; Haukeland University Hospital; University of Bergen; Instituto Mexicano del Seguro Social; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Claremont Colleges; Claremont Graduate University; University of Bergen; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Meyerson, M (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM helga.salvesen@uib.no; matthew_meyerson@dfci.harvard.edu
FU Carlos Slim Health Institute in Mexico; Rebecca Ridley Kry Fellowship of the Damon Runyon Cancer Research Foundation; MMRF Research Fellow Award; Helse Vest; Research Council of Norway; Norwegian Cancer Society; Harald Andersens legat; CONACyT [SALUD-2008-C01-87625, 161619]; UANL PAICyT [CS1038-1]; Instituto Mexicano del Seguro Social (IMSS); National Cancer Institute [T32CA009676] Funding Source: NIH RePORTER
NR 56
TC 707
Z9 770
U1 1
U2 201
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 20
PY 2014
VL 506
IS 7488
BP 371
EP +
DI 10.1038/nature12881
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800042
PM 24390348
DA 2026-03-09
ER

PT J
AU Di Mitri, D
   Toso, A
   Chen, JJ
   Sarti, M
   Pinton, S
   Jost, TR
   D'Antuono, R
   Montani, E
   Garcia-Escudero, R
   Guccini, I
   Da Silva-Alvarez, S
   Collado, M
   Eisenberger, M
   Zhang, Z
   Catapano, C
   Grassi, F
   Alimonti, A
AF Di Mitri, Diletta
   Toso, Alberto
   Chen, Jing Jing
   Sarti, Manuela
   Pinton, Sandra
   Jost, Tanja Rezzonico
   D'Antuono, Rocco
   Montani, Erica
   Garcia-Escudero, Ramon
   Guccini, Ilaria
   Da Silva-Alvarez, Sabela
   Collado, Manuel
   Eisenberger, Mario
   Zhang, Zhe
   Catapano, Carlo
   Grassi, Fabio
   Alimonti, Andrea
TI Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer
SO NATURE
LA English
DT Article
ID cellular senescence; pten; deficient; secretion; screen; genes; mice
AB Aberrant activation of oncogenes or loss of tumour suppressor genes opposes malignant transformation by triggering a stable arrest in cell growth, which is termed cellular senescence(1-3). This process is finely tuned by both cell-autonomous and non-cell-autonomous mechanisms that regulate the entry of tumour cells to senescence(4-6). Whether tumour-infiltrating immune cells can oppose senescence is unknown. Here we show that at the onset of senescence, PTEN null prostate tumours inmice(2,7) are massively infiltrated by a population of CD11b(+)Gr-1(+) myeloid cells that protect a fraction of proliferating tumour cells from senescence, thus sustaining tumour growth. Mechanistically, we found that Gr-1(+) cells antagonize senescence in a paracrine manner by interfering with the senescence-associated secretory phenotype of the tumour through the secretion of interleukin-1 receptor antagonist (IL-1RA). Strikingly, Pten-loss-induced cellular senescence was enhanced in vivo when Il1ra knockout myeloid cells were adoptively transferred to PTEN null mice. Therapeutically, docetaxel-induced senescence and efficacy were higher in PTEN null tumours when the percentage of tumour-infiltrating CD11b(+)Gr-1(+)myeloid cells was reduced using an antagonist of CXC chemokine receptor 2 (CXCR2)(8). Taken together, our findings identify a novel non-cell-autonomous network, established by innate immunity, that controls senescence evasion and chemoresistance. Targeting this network provides novel opportunities for cancer therapy.
C1 [Di Mitri, Diletta; Toso, Alberto; Chen, Jing Jing; Sarti, Manuela; Pinton, Sandra; Garcia-Escudero, Ramon; Guccini, Ilaria; Catapano, Carlo; Alimonti, Andrea] Oncol Inst Southern Switzerland, Inst Oncol Res IOR, CH-6500 Bellinzona, Switzerland.
   [Chen, Jing Jing; Alimonti, Andrea] Univ Lausanne UNIL, Fac Biol & Med, CH-1011 Lausanne, Switzerland.
   [Jost, Tanja Rezzonico; D'Antuono, Rocco; Montani, Erica; Grassi, Fabio] Inst Res Biomed IRB, CH-6500 Bellinzona, Switzerland.
   [Garcia-Escudero, Ramon] CIEMAT, Mol Oncol Unit, E-28040 Madrid, Spain.
   [Da Silva-Alvarez, Sabela; Collado, Manuel] Clin Univ Hosp CHUS, StemCHUS Hlth Res Inst Santiago de Compostela IDI, Lab Stem Cells Canc & Aging, E-15706 Santiago De Compostela, Spain.
   [Eisenberger, Mario] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Zhang, Zhe] Johns Hopkins Univ, Div Biostat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Grassi, Fabio] Univ Milan, Dept Med Biotechnol & Translat Med, I-20100 Milan, Italy.
C3 Institute of Oncology Research (IOR); Universita della Svizzera Italiana; University of Lausanne; Universita della Svizzera Italiana; Centro de Investigaciones Energeticas, Medioambientales Tecnologicas; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; University of Milan
RP Alimonti, A (corresponding author), Oncol Inst Southern Switzerland, Inst Oncol Res IOR, CH-6500 Bellinzona, Switzerland.
EM andrea.alimonti@ior.iosi.ch
FU Department of Defense Prostate Cancer Research Program [W81XWH-10-2-0056, W81XWH-10-2-0046]; Swiss national science foundation (SNF) grant Ambizione [PZ00P3_136612/1]; European Society for Medical Oncology (ESMO) translational research award; Swiss Bridge Award; PEOPLE-IRG [22484]; European Research Council [ERCsg 261342]; ABREOC; Train COFUND Marie Curie; Fondazione IBSA; Swiss National Science Foundation (SNF) [PZ00P3_136612] Funding Source: Swiss National Science Foundation (SNF)
NR 31
TC 318
Z9 348
U1 2
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 NOV 6
PY 2014
VL 515
IS 7525
BP 134
EP +
DI 10.1038/nature13638
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500044
PM 25156255
DA 2026-03-09
ER

PT J
AU Zhang, WK
   Alonso-Mori, R
   Bergmann, U
   Bressler, C
   Chollet, M
   Galler, A
   Gawelda, W
   Hadt, RG
   Hartsock, RW
   Kroll, T
   Kjær, KS
   Kubicek, K
   Lemke, HT
   Liang, HYW
   Meyer, DA
   Nielsen, MM
   Purser, C
   Robinson, JS
   Solomon, EI
   Sun, Z
   Sokaras, D
   van Driel, TB
   Vankó, G
   Weng, TC
   Zhu, DL
   Gaffney, KJ
AF Zhang, Wenkai
   Alonso-Mori, Roberto
   Bergmann, Uwe
   Bressler, Christian
   Chollet, Matthieu
   Galler, Andreas
   Gawelda, Wojciech
   Hadt, Ryan G.
   Hartsock, Robert W.
   Kroll, Thomas
   Kjaer, Kasper S.
   Kubicek, Katharina
   Lemke, Henrik T.
   Liang, Huiyang W.
   Meyer, Drew A.
   Nielsen, Martin M.
   Purser, Carola
   Robinson, Joseph S.
   Solomon, Edward I.
   Sun, Zheng
   Sokaras, Dimosthenis
   van Driel, Tim B.
   Vanko, Gyoergy
   Weng, Tsu-Chien
   Zhu, Diling
   Gaffney, Kelly J.
TI Tracking excited-state charge and spin dynamics in iron coordination complexes
SO NATURE
LA English
DT Article
ID x-ray-emission; transition-metal-complexes; absorption spectroscopy; crossover
AB Crucial to many light-driven processes in transition metal complexes is the absorption and dissipation of energy by 3d electrons(1-4). But a detailed understanding of such non-equilibrium excited-state dynamics and their interplay with structural changes is challenging: a multitude of excited states and possible transitions result in phenomena too complex to unravel when faced with the indirect sensitivity of optical spectroscopy to spin dynamics(5) and the flux limitations of ultrafast X-ray sources(6,7). Such a situation exists for archetypal poly-pyridyl iron complexes, such as [Fe(2,2'-bipyridine)(3)](2+), where the excited-state charge and spin dynamics involved in the transition from a low-to a high-spin state (spin crossover) have long been a source of interest and controversy(6-15). Here we demonstrate that femtosecond resolution X-ray fluorescence spectroscopy, with its sensitivity to spin state, can elucidate the spin crossover dynamics of [Fe(2,2'-bipyridine)(3)](2+) on photoinduced metal-to-ligand charge transfer excitation. We are able to track the charge and spin dynamics, and establish the critical role of intermediate spin states in the crossover mechanism. We anticipate that these capabilities will make our method a valuable tool for mapping in unprecedented detail the fundamental electronic excited-state dynamics that underpin many useful light-triggered molecular phenomena involving 3d transition metal complexes.
C1 [Zhang, Wenkai; Hartsock, Robert W.; Liang, Huiyang W.; Meyer, Drew A.; Purser, Carola; Sun, Zheng; Gaffney, Kelly J.] Stanford Univ, PULSE Inst, SLAC Natl Accelerator Lab, Stanford, CA 94305 USA.
   [Alonso-Mori, Roberto; Bergmann, Uwe; Chollet, Matthieu; Lemke, Henrik T.; Robinson, Joseph S.; Zhu, Diling] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Bressler, Christian; Galler, Andreas; Gawelda, Wojciech] European XFEL, D-22761 Hamburg, Germany.
   [Hadt, Ryan G.; Hartsock, Robert W.; Kroll, Thomas; Liang, Huiyang W.; Meyer, Drew A.; Solomon, Edward I.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Kjaer, Kasper S.] Univ Copenhagen, Niels Bohr Inst, Ctr Mol Movies, DK-2100 Copenhagen, Denmark.
   [Kjaer, Kasper S.; Nielsen, Martin M.; van Driel, Tim B.] Tech Univ Denmark, Dept Phys, Ctr Mol Movies, DK-2800 Lyngby, Denmark.
   [Kubicek, Katharina] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany.
   [Kubicek, Katharina] DESY, D-22607 Hamburg, Germany.
   [Solomon, Edward I.; Sokaras, Dimosthenis; Weng, Tsu-Chien] SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA.
   [Vanko, Gyoergy] Hungarian Acad Sci, Wigner Res Ctr Phys, H-1525 Budapest, Hungary.
C3 Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; European XFEL; Stanford University; University of Copenhagen; Niels Bohr Institute; Technical University of Denmark; Max Planck Society; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; HUN-REN; HUN-REN Wigner Research Centre for Physics; Hungarian Academy of Sciences
RP Gaffney, KJ (corresponding author), Stanford Univ, PULSE Inst, SLAC Natl Accelerator Lab, Stanford, CA 94305 USA.
EM kgaffney@slac.stanford.edu
FU AMOS programme within the Chemical Sciences, Geosciences and Biosciences Division of the Office of Basic Energy Sciences, Office of Science, US Department of Energy; NSF [CHE-0948211]; German Research Foundation (DFG) [KR3611/2-1]; Danish National Research Foundation; DANSCATT; Volkswagen Foundation [I/85832]; European Research Council [ERC-StG-259709]; Lendulet Programme of the Hungarian Academy of Sciences; DFG [SFB925]; European XFEL; Division Of Chemistry; Direct For Mathematical & Physical Scien [0948211] Funding Source: National Science Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK031450] Funding Source: NIH RePORTER
NR 40
TC 390
Z9 442
U1 10
U2 507
PU NATURE PUBLISHING 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 15
PY 2014
VL 509
IS 7500
BP 345
EP +
DI 10.1038/nature13252
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200035
PM 24805234
DA 2026-03-09
ER

PT J
AU Heron, JT
   Bosse, JL
   He, Q
   Gao, Y
   Trassin, M
   Ye, L
   Clarkson, JD
   Wang, C
   Liu, J
   Salahuddin, S
   Ralph, DC
   Schlom, DG
   Iñiguez, J
   Huey, BD
   Ramesh, R
AF Heron, J. T.
   Bosse, J. L.
   He, Q.
   Gao, Y.
   Trassin, M.
   Ye, L.
   Clarkson, J. D.
   Wang, C.
   Liu, Jian
   Salahuddin, S.
   Ralph, D. C.
   Schlom, D. G.
   Iniguez, J.
   Huey, B. D.
   Ramesh, R.
TI Deterministic switching of ferromagnetism at room temperature using an electric field
SO NATURE
LA English
DT Article
ID domains; oxide
AB The technological appeal of multiferroics is the ability to control magnetism with electric field(1-3). For devices to be useful, such control must be achieved at room temperature. The only single-phase multiferroic material exhibiting unambiguous magnetoelectric coupling at room temperature is BiFeO3 (refs 4 and 5). Its weak ferromagnetism arises from the canting of the antiferromagnetically aligned spins by the Dzyaloshinskii-Moriya (DM) interaction(6-9). Prior theory considered the symmetry of the thermodynamic ground state and concluded that direct 180-degree switching of the DM vector by the ferroelectric polarization was forbidden(10,11). Instead, we examined the kinetics of the switching process, something not considered previously in theoretical work(10-12). Here we show a deterministic reversal of the DM vector and canted moment using an electric field at room temperature. First-principles calculations reveal that the switching kinetics favours a two-step switching process. In each step the DM vector and polarization are coupled and 180-degree deterministic switching of magnetization hence becomes possible, in agreement with experimental observation. We exploit this switching to demonstrate energy-efficient control of a spin-valve device at room temperature. The energy per unit area required is approximately an order of magnitude less than that needed for spin-transfer torque switching(13,14). Given that the DM interaction is fundamental to singlephase multiferroics and magnetoelectrics(3,9), our results suggest ways to engineer magnetoelectric switching and tailor technologically pertinent functionality for nanometre-scale, low-energy-consumption, non-volatile magnetoelectronics.
C1 [Heron, J. T.; Schlom, D. G.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
   [Bosse, J. L.; Ye, L.; Huey, B. D.] Univ Connecticut, Dept Mat Sci & Engn, Storrs, CT 06269 USA.
   [He, Q.] Univ Durham, Dept Phys, Durham DH1 3LE, England.
   [Gao, Y.; Liu, Jian; Ramesh, R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Gao, Y.] Tsinghua Univ, Sch Mat Sci & Engn, Beijing 100084, Peoples R China.
   [Gao, Y.] Tsinghua Univ, State Key Lab New Ceram & Fine Proc, Beijing 100084, Peoples R China.
   [Trassin, M.] ETH, Dept Mat, CH-8093 Zurich, Switzerland.
   [Clarkson, J. D.; Ramesh, R.] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
   [Wang, C.; Ralph, D. C.] Cornell Univ, Dept Phys, Ithaca, NY 14853 USA.
   [Salahuddin, S.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.
   [Ralph, D. C.; Schlom, D. G.] Kavli Inst Cornell Nanoscale Sci, Ithaca, NY 14853 USA.
   [Iniguez, J.] Inst Ciencia Mat Barcelona ICMAB CSIC, Bellaterra 08193, Spain.
   [Huey, B. D.] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA.
   [Ramesh, R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 Cornell University; University of Connecticut; Durham University; University of California System; University of California Berkeley; Tsinghua University; Tsinghua University; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of California System; University of California Berkeley; Cornell University; University of California System; University of California Berkeley; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB); University of Connecticut; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Heron, JT (corresponding author), Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
EM jth247@cornell.edu
FU National Science Foundation (Nanosystems Engineering Research Center for Translational Applications of Nanoscale Multiferroic Systems) [EEC-1160504]; DOD-ARO MURI - Army Research Office [W911NF-08-2-0032]; FENA-FAME; NSF/MRSEC through the Cornell Center for Materials Research [DMR-1120296]; MINECO-Spain [MAT2010-18113, CSD2007-00041]; DOE ESPM [DE-SC0005037]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; U.S. Department of Energy (DOE) [DE-SC0005037] Funding Source: U.S. Department of Energy (DOE); Direct For Computer & Info Scie & Enginr [1017575] Funding Source: National Science Foundation; Division of Computing and Communication Foundations [1017575] Funding Source: National Science Foundation
NR 56
TC 647
Z9 737
U1 8
U2 979
PU NATURE PUBLISHING 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 18
PY 2014
VL 516
IS 7531
BP 370
EP +
DI 10.1038/nature14004
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800041
PM 25519134
DA 2026-03-09
ER

PT J
AU Mancias, JD
   Wang, XX
   Gygi, SP
   Harper, JW
   Kimmelman, AC
AF Mancias, Joseph D.
   Wang, Xiaoxu
   Gygi, Steven P.
   Harper, J. Wade
   Kimmelman, Alec C.
TI Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy
SO NATURE
LA English
DT Article
ID androgen receptor; rat-liver; iron; autophagy; coactivator; mechanisms
AB Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration(1,2). Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo, including organelles, proteins or intracellular pathogens, are targeted for selective autophagy is limited(3). Here we use quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins in human cells, including cargo receptors. Like known cargo receptors, nuclear receptor coactivator 4 (NCOA4) was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species(4) but is degraded via autophagy to release iron(5,6) through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin led to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy), which is critical for iron homeostasis, and provides a resource for further dissection of autophagosomal cargo-receptor connectivity.
C1 [Mancias, Joseph D.; Wang, Xiaoxu; Kimmelman, Alec C.] Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02215 USA.
   [Mancias, Joseph D.; Gygi, Steven P.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Mancias, Joseph D.] Harvard Radiat Oncol Program, Boston, MA 02115 USA.
   [Mancias, Joseph D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Kimmelman, AC (corresponding author), Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02215 USA.
EM wade_harper@hms.harvard.edu; alec_kimmelman@dfci.harvard.edu
FU National Institutes of Health [GM070565, GM095567]; National Cancer Institute [R01CA157490]; American Cancer Society [RSG-13-298-01-TBG]; Lustgarten Foundation; American Board of Radiology Holman Research Pathway Post-doctoral Fellowship; American Society of Radiation Oncology Junior Faculty Career Research Training Award [JF2013-2]; National Cancer Institute [P50CA127003] Funding Source: NIH RePORTER
NR 30
TC 1678
Z9 1859
U1 10
U2 316
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 1
PY 2014
VL 509
IS 7498
BP 105
EP +
DI 10.1038/nature13148
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100048
PM 24695223
DA 2026-03-09
ER

PT J
AU Kvon, EZ
   Kazmar, T
   Stampfel, G
   Yáñez-Cuna, JO
   Pagani, M
   Schernhuber, K
   Dickson, BJ
   Stark, A
AF Kvon, Evgeny Z.
   Kazmar, Tomas
   Stampfel, Gerald
   Yanez-Cuna, J. Omar
   Pagani, Michaela
   Schernhuber, Katharina
   Dickson, Barry J.
   Stark, Alexander
TI Genome-scale functional characterization of Drosophila developmental enhancers in vivo
SO NATURE
LA English
DT Article
ID gene-expression patterns; situ hybridization; tissue; elements; specificity; resource; database; protein; tools
AB Transcriptional enhancers are crucial regulators of gene expression and animal development(1) and the characterization of their genomic organization, spatiotemporal activities and sequence properties is a key goal in modern biology(2-8). Here we characterize the in vivo activity of 7,705 Drosophila melanogaster enhancer candidates covering 13.5% of the non-coding non-repetitive genome throughout embryogenesis. 3,557 (46%) candidates are active, suggesting a high density with 50,000 to 100,000 developmental enhancers genome-wide. The vast majority of enhancers display specific spatial patterns that are highly dynamic during development. Most appear to regulate their neighbouring genes, suggesting that the cis-regulatory genome is organized locally into domains, which are supported by chromosomal domains, insulator binding and genome evolution. However, 12 to 21 per cent of enhancers appear to skip non-expressed neighbours and regulate a more distal gene. Finally, we computationally identify cis-regulatory motifs that are predictive and required for enhancer activity, as we validate experimentally. This work provides global insights into the organization of an animal regulatory genome and the make-up of enhancer sequences and confirms and generalizes principles from previous studies(1,9). All enhancer patterns are annotated manually with a controlled vocabulary and all results are available through a web interface (http://enhancers.starklab.org), including the raw images of all microscopy slides for manual inspection at arbitrary zoom levels.
C1 [Kvon, Evgeny Z.; Kazmar, Tomas; Stampfel, Gerald; Yanez-Cuna, J. Omar; Pagani, Michaela; Schernhuber, Katharina; Dickson, Barry J.; Stark, Alexander] Vienna Bioctr VBC, Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Stark, A (corresponding author), Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM stark@starklab.org
FU European Research Council (ERC) from the European Community [242922]; Austrian Science Fund (FWF) [F4303-B09]; ERC; Boehringer Ingelheim GmbH
NR 51
TC 325
Z9 417
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 AUG 7
PY 2014
VL 512
IS 7512
BP 91
EP +
DI 10.1038/nature13395
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000038
PM 24896182
DA 2026-03-09
ER

PT J
AU Litos, M
   Adli, E
   An, W
   Clarke, CI
   Clayton, CE
   Corde, S
   Delahaye, JP
   England, RJ
   Fisher, AS
   Frederico, J
   Gessner, S
   Green, SZ
   Hogan, MJ
   Joshi, C
   Lu, W
   Marsh, KA
   Mori, WB
   Muggli, P
   Vafaei-Najafabadi, N
   Walz, D
   White, G
   Wu, Z
   Yakimenko, V
   Yocky, G
AF Litos, M.
   Adli, E.
   An, W.
   Clarke, C. I.
   Clayton, C. E.
   Corde, S.
   Delahaye, J. P.
   England, R. J.
   Fisher, A. S.
   Frederico, J.
   Gessner, S.
   Green, S. Z.
   Hogan, M. J.
   Joshi, C.
   Lu, W.
   Marsh, K. A.
   Mori, W. B.
   Muggli, P.
   Vafaei-Najafabadi, N.
   Walz, D.
   White, G.
   Wu, Z.
   Yakimenko, V.
   Yocky, G.
TI High-efficiency acceleration of an electron beam in a plasma wakefield accelerator
SO NATURE
LA English
DT Article
AB High-efficiency acceleration of charged particle beams at high gradients of energy gain per unit length is necessary to achieve an affordable and compact high-energy collider. The plasma wakefield accelerator is one concept(1-3) being developed for this purpose. In plasma wakefield acceleration, a charge-density wake with high accelerating fields is driven by the passage of an ultra-relativistic bunch of charged particles (the drive bunch) through a plasma(4-6). If a second bunch of relativistic electrons (the trailing bunch) with sufficient charge follows in the wake of the drive bunch at an appropriate distance, it can be efficiently accelerated to high energy. Previous experiments using just a single 42-gigaelectronvolt drive bunch have accelerated electrons with a continuous energy spectrum and a maximum energy of upto 85 gigaelectronvolts from the tail of the same bunch in less than a metre of plasma(7). However, the total charge of these accelerated electrons was insufficient to extract a substantial amount of energy from the wake. Here we report high-efficiency acceleration of a discrete trailing bunch of electrons that contains sufficient charge to extract a substantial amount of energy from the high-gradient, non-linear plasma wakefield accelerator. Specifically, we show the acceleration of about 74 picocoulombs of charge contained in the core of the trailing bunch in an accelerating gradient of about 4.4 gigavolts per metre. These core particles gain about 1.6 gigaelectronvolts of energy per particle, with a final energy spread as low as 0.7 per cent (2.0 per cent on average), and an energy-transfer efficiency from the wake to the bunch that can exceed 30 per cent (17.7 per cent on average). This acceleration of a distinct bunch of electrons containing a substantial charge and having a small energy spread with both a high accelerating gradient and a high energy-transfer efficiency represents a milestone in the development of plasma wakefield acceleration into a compact and affordable accelerator technology.
C1 [Litos, M.; Adli, E.; Clarke, C. I.; Corde, S.; Delahaye, J. P.; England, R. J.; Fisher, A. S.; Frederico, J.; Gessner, S.; Green, S. Z.; Hogan, M. J.; Walz, D.; White, G.; Wu, Z.; Yakimenko, V.; Yocky, G.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Adli, E.] Univ Oslo, Dept Phys, N-0316 Oslo, Norway.
   [An, W.; Mori, W. B.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Clayton, C. E.; Joshi, C.; Marsh, K. A.; Vafaei-Najafabadi, N.] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA.
   [Lu, W.] Tsinghua Univ, Dept Engn Phys, Beijing 100084, Peoples R China.
   [Muggli, P.] Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany.
C3 Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; University of Oslo; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Tsinghua University; Max Planck Society
RP Litos, M (corresponding author), SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
EM litos@slac.stanford.edu
FU United States Department of Energy; DOE [DE-AC02-76SF00515, DE-FG02-92-ER40727, DE-SC0010064, DE-SC0008491, DE-SC0008316]; Research Council of Norway; NSF [ACI-1339893, PHY-0960344]; NSFC [11175102]; Thousand Young Talents Program; Tsinghua University Initiative Scientific Research Program; Direct For Computer & Info Scie & Enginr [1339893] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Office of Advanced Cyberinfrastructure (OAC) [1440071] Funding Source: National Science Foundation; Office of Advanced Cyberinfrastructure (OAC) [1339893] Funding Source: National Science Foundation
NR 19
TC 443
Z9 508
U1 3
U2 156
PU NATURE PUBLISHING 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 6
PY 2014
VL 515
IS 7525
BP 92
EP +
DI 10.1038/nature13882
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500035
PM 25373678
DA 2026-03-09
ER

PT J
AU Nakamura, N
   Lill, JR
   Phung, Q
   Jiang, ZS
   Bakalarski, C
   de Mazière, A
   Klumperman, J
   Schlatter, M
   Delamarre, L
   Mellman, I
AF Nakamura, Norihiro
   Lill, Jennie R.
   Phung, Qui
   Jiang, Zhaoshi
   Bakalarski, Corey
   de Maziere, Ann
   Klumperman, Judith
   Schlatter, Megan
   Delamarre, Lelia
   Mellman, Ira
TI Endosomes are specialized platforms for bacterial sensing and NOD2 signalling
SO NATURE
LA English
DT Article
ID mhc class-ii; dendritic cells; host recognition; plasma-membrane; crohns-disease; kappa-b; protein; susceptibility; peptidoglycan; salmonella
AB The detection of microbial pathogens involves the recognition of conserved microbial components by host cell sensors such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs are membrane receptors that survey the extracellular environment for microbial infections, whereas NLRs are cytosolic complexes that detect microbial products that reach the cytosol. Upon detection, both sensor classes trigger innate inflammatory responses and allow the engagement of adaptive immunity(1,2). Endo-lysosomes are the entry sites for a variety of pathogens, and therefore the sites at which the immune system first senses their presence. Pathogens internalized by endocytosis are well known to activate TLRs 3 and 7-9 that are localized to endocytic compartments and detect ligands present in the endosomal lumen(3). Internalized pathogens also activate sensors in the cytosol such as NOD1 and NOD2 (ref. 2), indicating that endosomes also provide for the translocation of bacterial components across the endosomal membrane. Despite the fact that NOD2 is well understood to have a key role in regulating innate immune responses and that mutations at the NOD2 locus are a common risk factor in inflammatory bowel disease and possibly other chronic inflammatory states(4,5), little is known about how its ligands escape from endosomes. Here we show that two endo-lysosomal peptide transporters, SLC15A3 and SLC15A4, are preferentially expressed by dendritic cells, especially after TLR stimulation. The transporters mediate the egress of bacterially derived components, such as the NOD2 cognate ligand muramyl dipeptide (MDP)(6,7), and are selectively required for NOD2 responses to endosomally derived MDP. Enhanced expression of the transporters also generates endosomal membrane tubules characteristic of dendritic cells, which further enhanced the NOD2-dependent response to MDP. Finally, sensing required the recruitment of NOD2 and its effector kinase RIPK2 (refs 8, 9) to the endosomal membrane, possibly by forming a complex with SLC15A3 or SLC15A4. Thus, dendritic cell endosomes are specialized platforms for both the lumenal and cytosolic sensing of pathogens.
C1 [Nakamura, Norihiro; Lill, Jennie R.; Phung, Qui; Jiang, Zhaoshi; Bakalarski, Corey; Schlatter, Megan; Delamarre, Lelia; Mellman, Ira] Genentech Inc, San Francisco, CA 94080 USA.
   [de Maziere, Ann; Klumperman, Judith] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
C3 Roche Holding; Roche Holding USA; Genentech; Utrecht University; Utrecht University Medical Center
RP Mellman, I (corresponding author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM mellman.ira@gene.com
FU Genentech
NR 40
TC 243
Z9 287
U1 3
U2 68
PU NATURE PUBLISHING 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 8
PY 2014
VL 509
IS 7499
BP 240
EP +
DI 10.1038/nature13133
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300042
PM 24695226
DA 2026-03-09
ER

PT J
AU Godinho, SA
   Picone, R
   Burute, M
   Dagher, R
   Su, Y
   Leung, CT
   Polyak, K
   Brugge, JS
   Théry, M
   Pellman, D
AF Godinho, Susana A.
   Picone, Remigio
   Burute, Mithila
   Dagher, Regina
   Su, Ying
   Leung, Cheuk T.
   Polyak, Kornelia
   Brugge, Joan S.
   Thery, Manuel
   Pellman, David
TI Oncogene-like induction of cellular invasion from centrosome amplification
SO NATURE
LA English
DT Article
ID human breast-cancer; centriole duplication; chromosomal instability; spindle checkpoint; junction formation; cells; expression; roles; rac; tumorigenesis
AB Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear(1). Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost(2). Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours(3), raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumour progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behaviour is similar to that induced by overexpression of the breast cancer oncogene ERBB2 (ref.4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.
C1 [Godinho, Susana A.; Picone, Remigio; Dagher, Regina; Pellman, David] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Godinho, Susana A.; Picone, Remigio; Dagher, Regina; Pellman, David] Childrens Hosp, Boston, MA 02115 USA.
   [Godinho, Susana A.; Picone, Remigio; Dagher, Regina; Leung, Cheuk T.; Brugge, Joan S.; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Burute, Mithila; Thery, Manuel] UMR5168 CEA UJF INRA CNRS, Inst Rech Technol & Sci Vivant, Grenoble, France.
   [Burute, Mithila; Thery, Manuel] U1160 INSERM AP HP Univ Paris Diderot, Inst Univ Hematol, Hop St Louis, F-75010 Paris, France.
   [Burute, Mithila] CYTOO SA, F-38054 Grenoble, France.
   [Su, Ying; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); INRAE; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Saint-Louis - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Godinho, SA (corresponding author), Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
EM s.godinho@qmul.ac.uk; david_pellman@dfci.harvard.edu
FU FCT [HMSP-CT/SAU-ICT/0075/2009]; ERC [310472]; ISI program of BPIFrance; NIH [GM083299-1]; Fundação para a Ciência e a Tecnologia [HMSP-CT/SAU-ICT/0075/2009] Funding Source: FCT; European Research Council (ERC) [310472] Funding Source: European Research Council (ERC)
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   Bettencourt-Dias M, 2007, NAT REV MOL CELL BIO, V8, P451, DOI 10.1038/nrm2180
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NR 46
TC 332
Z9 387
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 JUN 5
PY 2014
VL 510
IS 7503
BP 167
EP +
DI 10.1038/nature13277
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900050
PM 24739973
DA 2026-03-09
ER

PT J
AU Lawrence, MS
   Stojanov, P
   Mermel, CH
   Robinson, JT
   Garraway, LA
   Golub, TR
   Meyerson, M
   Gabriel, SB
   Lander, ES
   Getz, G
AF Lawrence, Michael S.
   Stojanov, Petar
   Mermel, Craig H.
   Robinson, James T.
   Garraway, Levi A.
   Golub, Todd R.
   Meyerson, Matthew
   Gabriel, Stacey B.
   Lander, Eric S.
   Getz, Gad
TI Discovery and saturation analysis of cancer genes across 21 tumour types
SO NATURE
LA English
DT Article
ID mutations
AB Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 6005,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.
C1 [Lawrence, Michael S.; Stojanov, Petar; Mermel, Craig H.; Robinson, James T.; Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Stojanov, Petar; Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02215 USA.
   [Mermel, Craig H.; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Mermel, Craig H.; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Lander, Eric S.] MIT, Cambridge, MA 02139 USA.
C3 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; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Lander, ES (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM lander@broadinstitute.org; gadgetz@broadinstitute.org
FU Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA157304] Funding Source: Medline; NHGRI NIH HHS [U54 HG003067] Funding Source: Medline; NIGMS NIH HHS [T32 GM007753] Funding Source: Medline; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
CR Carter SL, 2012, NAT BIOTECHNOL, V30, P413, DOI 10.1038/nbt.2203
   Cibulskis K, 2013, NAT BIOTECHNOL, V31, P213, DOI 10.1038/nbt.2514
   Ferlay J, 2010, INT J CANCER, V127, P2893, DOI 10.1002/ijc.25516
   Garraway LA, 2013, CELL, V153, P17, DOI 10.1016/j.cell.2013.03.002
   Getz G, 2013, NATURE, V497, P67, DOI 10.1038/nature12113
   Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013
   Imielinski M, 2012, CELL, V150, P1107, DOI 10.1016/j.cell.2012.08.029
   Kandoth C, 2013, NATURE, V502, P333, DOI 10.1038/nature12634
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NR 13
TC 2493
Z9 2945
U1 4
U2 355
PU NATURE PUBLISHING 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 23
PY 2014
VL 505
IS 7484
BP 495
EP +
DI 10.1038/nature12912
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 293SW
UT WOS:000329995000029
PM 24390350
DA 2026-03-09
ER

PT J
AU Gao, ZH
   Lee, P
   Stafford, JM
   von Schimmelmann, M
   Schaefer, A
   Reinberg, D
AF Gao, Zhonghua
   Lee, Pedro
   Stafford, James M.
   von Schimmelmann, Melanie
   Schaefer, Anne
   Reinberg, Danny
TI An AUTS2-Polycomb complex activates gene expression in the CNS
SO NATURE
LA English
DT Article
ID histone methyltransferase activity; stem-cells; polycomb; protein; mechanisms; chromatin; enhancer; h2a; ubiquitylation; vocalizations
AB Naturally occurring variations of Polycomb repressive complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, autism susceptibility candidate 2 (AUTS2). Although AUTS2 is often disrupted in patients with neuronal disorders, the mechanism underlying the pathogenesis is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.
C1 [Gao, Zhonghua; Lee, Pedro; Stafford, James M.; Reinberg, Danny] NYU, Howard Hughes Med Inst, Langone Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [von Schimmelmann, Melanie; Schaefer, Anne] Mt Sinai Sch Med, Dept Neurosci, Friedman Brain Inst, New York, NY 10029 USA.
C3 NYU Langone Medical Center; New York University; Howard Hughes Medical Institute; Icahn School of Medicine at Mount Sinai
RP Reinberg, D (corresponding author), NYU, Howard Hughes Med Inst, Langone Sch Med, Dept Biochem & Mol Pharmacol, 550 1St Ave, New York, NY 10016 USA.
EM danny.reinberg@nyumc.org
FU National Institute of Health [GM-64844]; Simons Foundation Autism Research Initiative (SFARI); NIH [1DP2MH100012-01, 5T32CA160002, 1F32GM105275, F32AA022842]; Seaver Autism Foundation; Brain and Behavioral Research Fund [18194]; SFARI; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 45
TC 253
Z9 304
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 18
PY 2014
VL 516
IS 7531
BP 349
EP +
DI 10.1038/nature13921
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800037
PM 25519132
DA 2026-03-09
ER

PT J
AU Amos, CB
   Audet, P
   Hammond, WC
   Bürgmann, R
   Johanson, IA
   Blewitt, G
AF Amos, Colin B.
   Audet, Pascal
   Hammond, William C.
   Buergmann, Roland
   Johanson, Ingrid A.
   Blewitt, Geoffrey
TI Uplift and seismicity driven by groundwater depletion in central California
SO NATURE
LA English
DT Article
ID sierra-nevada; seasonal-variation; rock uplift; gps; subsidence; parkfield; strain; region; model; fault
AB Groundwater use in California's San Joaquin Valley exceeds replenishment of the aquifer, leading to substantial diminution of this resource(1-4) and rapid subsidence of the valley floor(5). The volume of groundwater lost over the past century and a half also represents a substantial reduction in mass and a large-scale unburdening of the lithosphere, with significant but unexplored potential impacts on crustal deformation and seismicity. Here we use vertical global positioning system measurements to show that a broad zone of rock uplift of up to 1-3 mm per year surrounds the southern San Joaquin Valley. The observed uplift matches well with predicted flexure from a simple elastic model of current rates of water-storage loss, most of which is caused by groundwater depletion(3). The height of the adjacent central Coast Ranges and the Sierra Nevada is strongly seasonal and peaks during the dry late summer and autumn, out of phase with uplift of the valley floor during wetter months. Our results suggest that long-term and late-summer flexural uplift of the Coast Ranges reduce the effective normal stress resolved on the San Andreas Fault. This process brings the fault closer to failure, thereby providing a viable mechanism for observed seasonality in microseismicity at Parkfield(6) and potentially affecting long-term seismicity rates for fault systems adjacent to the valley. We also infer that the observed contemporary uplift of the southern Sierra Nevada previously attributed to tectonic or mantle-derived forces(7-10) is partly a consequence of human-caused groundwater depletion.
C1 [Amos, Colin B.] Western Washington Univ, Dept Geol, Bellingham, WA 98225 USA.
   [Audet, Pascal] Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
   [Hammond, William C.; Blewitt, Geoffrey] Univ Nevada, Nevada Geodet Lab, Nevada Bur Mines & Geol, Reno, NV 89557 USA.
   [Hammond, William C.; Blewitt, Geoffrey] Univ Nevada, Nevada Seismol Lab, Reno, NV 89557 USA.
   [Buergmann, Roland; Johanson, Ingrid A.] Univ Calif Berkeley, Berkeley Seismol Lab, Berkeley, CA 94720 USA.
   [Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 Western Washington University; University of Ottawa; Nevada System of Higher Education (NSHE); University of Nevada Reno; Nevada System of Higher Education (NSHE); University of Nevada Reno; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Amos, CB (corresponding author), Western Washington Univ, Dept Geol, Bellingham, WA 98225 USA.
EM colin.amos@wwu.edu
FU NSF Earth Scope award [EAR-1252210]; Directorate For Geosciences [0951430] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1252210] Funding Source: National Science Foundation; Division Of Earth Sciences [0951430] Funding Source: National Science Foundation
NR 40
TC 210
Z9 254
U1 6
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 MAY 22
PY 2014
VL 509
IS 7501
BP 483
EP +
DI 10.1038/nature13275
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000037
PM 24828048
DA 2026-03-09
ER

PT J
AU Chera, S
   Baronnier, D
   Ghila, L
   Cigliola, V
   Jensen, JN
   Gu, GQ
   Furuyama, K
   Thorel, F
   Gribble, FM
   Reimann, F
   Herrera, PL
AF Chera, Simona
   Baronnier, Delphine
   Ghila, Luiza
   Cigliola, Valentina
   Jensen, Jan N.
   Gu, Guoqiang
   Furuyama, Kenichiro
   Thorel, Fabrizio
   Gribble, Fiona M.
   Reimann, Frank
   Herrera, Pedro L.
TI Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers
SO NATURE
LA English
DT Article
ID alpha; glucose; humans
AB Total or near-total loss of insulin-producing beta-cells occurs in type 1 diabetes(1,2). Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which beta-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity(3). The process involves the contribution of islet non-beta-cells; specifically, glucagon-producing alpha-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation(3). Here we show the influence of age on beta-cell reconstitution from heterologous islet cells after near-total beta-cell loss in mice. We found that senescence does not alter alpha-cell plasticity: alpha-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after beta-cell loss. In contrast, before puberty there is no detectable alpha-cell conversion, although beta-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing delta-cells. The juveniles display somatostatin-to-insulin delta-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-beta-cell origins is thus enabled throughout life via delta- or alpha-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.
C1 [Chera, Simona; Baronnier, Delphine; Ghila, Luiza; Cigliola, Valentina; Furuyama, Kenichiro; Thorel, Fabrizio; Herrera, Pedro L.] Univ Geneva, Fac Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland.
   [Jensen, Jan N.] Novo Nordisk AS, DK-2820 Gentofte, Denmark.
   [Gu, Guoqiang] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
   [Gribble, Fiona M.; Reimann, Frank] Cambridge Inst Med Res, Cambridge CB2 0XY, England.
C3 University of Geneva; Novo Nordisk; Vanderbilt University; University of Cambridge
RP Herrera, PL (corresponding author), Univ Geneva, Fac Med, Dept Genet Med & Dev, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
EM pedro.herrera@unige.ch
FU Wellcome Trust [WT088357/Z/09/Z, WT084210/Z/07/Z]; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (Beta Cell Biology Consortium); Juvenile Diabetes Research Foundation; Swiss National Science Foundation [NRP63]; Medical Research Council [MC_UU_12012/3] Funding Source: researchfish; MRC [MC_UU_12012/3] Funding Source: UKRI
NR 23
TC 327
Z9 408
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 23
PY 2014
VL 514
IS 7523
BP 503
EP +
DI 10.1038/nature13633
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900043
PM 25141178
DA 2026-03-09
ER

PT J
AU Guo, HS
   Zhu, P
   Yan, LY
   Li, R
   Hu, BQ
   Lian, Y
   Yan, J
   Ren, XL
   Lin, SL
   Li, JS
   Jin, XH
   Shi, XD
   Liu, P
   Wang, XY
   Wang, W
   Wei, Y
   Li, XL
   Guo, F
   Wu, XL
   Fan, XY
   Yong, J
   Wen, L
   Xie, SX
   Tang, FC
   Qiao, J
AF Guo, Hongshan
   Zhu, Ping
   Yan, Liying
   Li, Rong
   Hu, Boqiang
   Lian, Ying
   Yan, Jie
   Ren, Xiulian
   Lin, Shengli
   Li, Junsheng
   Jin, Xiaohu
   Shi, Xiaodan
   Liu, Ping
   Wang, Xiaoye
   Wang, Wei
   Wei, Yuan
   Li, Xianlong
   Guo, Fan
   Wu, Xinglong
   Fan, Xiaoying
   Yong, Jun
   Wen, Lu
   Xie, Sunney X.
   Tang, Fuchou
   Qiao, Jie
TI The DNA methylation landscape of human early embryos
SO NATURE
LA English
DT Article
ID stem-cells; preimplantation development; single-cell; chromatin state; human genome; patterns; maintenance; evolution; dynamics; oocytes
AB DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development(1-5). However, its dynamic patterns have not been analysed at the genome scale in human preimplantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronudei is already lower than that in female pronudei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements.
C1 [Guo, Hongshan; Zhu, Ping; Yan, Liying; Li, Rong; Hu, Boqiang; Lian, Ying; Yan, Jie; Ren, Xiulian; Lin, Shengli; Li, Junsheng; Jin, Xiaohu; Shi, Xiaodan; Liu, Ping; Li, Xianlong; Guo, Fan; Wu, Xinglong; Fan, Xiaoying; Yong, Jun; Wen, Lu; Xie, Sunney X.; Tang, Fuchou; Qiao, Jie] Peking Univ, Hosp 3, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.
   [Guo, Hongshan; Zhu, Ping; Yan, Liying; Li, Rong; Hu, Boqiang; Lian, Ying; Yan, Jie; Ren, Xiulian; Lin, Shengli; Li, Junsheng; Jin, Xiaohu; Shi, Xiaodan; Liu, Ping; Li, Xianlong; Guo, Fan; Wu, Xinglong; Fan, Xiaoying; Yong, Jun; Wen, Lu; Xie, Sunney X.; Tang, Fuchou; Qiao, Jie] Peking Univ, Hosp 3, Coll Life Sci, Ctr Reprod Med, Beijing 100871, Peoples R China.
   [Zhu, Ping] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.
   [Yan, Liying; Li, Rong; Lian, Ying; Yan, Jie; Ren, Xiulian; Lin, Shengli; Li, Junsheng; Jin, Xiaohu; Shi, Xiaodan; Liu, Ping; Qiao, Jie] Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China.
   [Wang, Xiaoye; Wang, Wei; Wei, Yuan] Peking Univ, Hosp 3, Dept Obstet & Gynecol, Beijing 100191, Peoples R China.
   [Yong, Jun; Xie, Sunney X.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Tang, Fuchou] Minist Educ, Key Lab Cell Proliferat & Differentia, Beijing 100871, Peoples R China.
C3 Peking University; Peking University; Peking University; Peking University; Harvard University
RP Tang, FC (corresponding author), Peking Univ, Hosp 3, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.
EM tangfuchou@pku.edu.cn; jie.qiao@263.net
FU National Basic Research Program of China [2012CB966704, 2011CB944504, 2011CB966303, 2011CB944503]; National Natural Science of China [31322037, 31230047, 31271543, 81170538]; Beijing Municipal Science and Technology Commission [Z131100005213006]; National Natural Science Foundation of China [81000275]; National Key Technologies Research and Development Program [2012BAI32B01]
NR 40
TC 740
Z9 859
U1 6
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 JUL 30
PY 2014
VL 511
IS 7511
BP 606
EP +
DI 10.1038/nature13544
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300038
PM 25079557
DA 2026-03-09
ER

PT J
AU Zanne, AE
   Tank, DC
   Cornwell, WK
   Eastman, JM
   Smith, SA
   FitzJohn, RG
   McGlinn, DJ
   O'Meara, BC
   Moles, AT
   Reich, PB
   Royer, DL
   Soltis, DE
   Stevens, PF
   Westoby, M
   Wright, IJ
   Aarssen, L
   Bertin, RI
   Calaminus, A
   Govaerts, R
   Hemmings, F
   Leishman, MR
   Oleksyn, J
   Soltis, PS
   Swenson, NG
   Warman, L
   Beaulieu, JM
AF Zanne, Amy E.
   Tank, David C.
   Cornwell, William K.
   Eastman, Jonathan M.
   Smith, Stephen A.
   FitzJohn, Richard G.
   McGlinn, Daniel J.
   O'Meara, Brian C.
   Moles, Angela T.
   Reich, Peter B.
   Royer, Dana L.
   Soltis, Douglas E.
   Stevens, Peter F.
   Westoby, Mark
   Wright, Ian J.
   Aarssen, Lonnie
   Bertin, Robert I.
   Calaminus, Andre
   Govaerts, Rafael
   Hemmings, Frank
   Leishman, Michelle R.
   Oleksyn, Jacek
   Soltis, Pamela S.
   Swenson, Nathan G.
   Warman, Laura
   Beaulieu, Jeremy M.
TI Three keys to the radiation of angiosperms into freezing environments
SO NATURE
LA English
DT Article
ID evolution; character; diversification; anatomy; height; origin; genes; habit
AB Early flowering plants are thought to have been woody species restricted to warm habitats(1-3). This lineage has since radiated into almost every climate, with manifold growth forms(4). As angiosperms spread and climate changed, they evolved mechanisms to cope with episodic freezing. To explore the evolution of traits underpinning the ability to persist in freezing conditions, we assembled a large species-level database of growth habit (woody or herbaceous; 49,064 species), as well as leaf phenology (evergreen or deciduous), diameter of hydraulic conduits (that is, xylem vessels and tracheids) and climate occupancies (exposure to freezing). To model the evolution of species' traits and climate occupancies, we combined these data with an unparalleled dated molecular phylogeny (32,223 species) for land plants. Here we show that woody clades successfully moved into freezing-prone environments by either possessing transport networks of small safe conduits(5) and/or shutting down hydraulic function by dropping leaves during freezing. Herbaceous species largely avoided freezing periods by senescing cheaply constructed aboveground tissue. Growth habit has long been considered labile(6), but we find that growth habit was less labile than climate occupancy. Additionally, freezing environments were largely filled by lineages that had already become herbs or, when remaining woody, already had small conduits (that is, the trait evolved before the climate occupancy). By contrast, most deciduous woody lineages had an evolutionary shift to seasonally shedding their leaves only after exposure to freezing (that is, the climate occupancy evolved before the trait). For angiosperms to inhabit novel cold environments they had to gain new structural and functional trait solutions; our results suggest that many of these solutions were probably acquired before their foray into the cold.
C1 [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.
   [Tank, David C.; Eastman, Jonathan M.] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA.
   [Tank, David C.; Eastman, Jonathan M.] Univ Idaho, Inst Bioinformat & Evolutionary Studies, Moscow, ID 83844 USA.
   [Cornwell, William K.] Dept Ecol Sci, NL-1081 HV Amsterdam, Netherlands.
   [Cornwell, William K.; Moles, Angela T.; Hemmings, Frank; Warman, Laura] Univ New S Wales, Evolut & Ecol Res Ctr, Sch Biol Earth & Environm Sci, Sydney, NSW 2052, Australia.
   [Smith, Stephen A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [FitzJohn, Richard G.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [FitzJohn, Richard G.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
   [FitzJohn, Richard G.; Westoby, Mark; Wright, Ian J.; Leishman, Michelle R.] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [McGlinn, Daniel J.] Utah State Univ, Dept Biol, Logan, UT 84322 USA.
   [McGlinn, Daniel J.] Utah State Univ, Ctr Ecol, Logan, UT 84322 USA.
   [O'Meara, Brian C.] Univ Tennessee, Dept Ecol & Evolutionary Biol, Knoxville, TN 37996 USA.
   [Reich, Peter B.; Oleksyn, Jacek] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Reich, Peter B.] Univ Western Sydney, Hawkesbury Inst Environm, Penrith, NSW 2751, Australia.
   [Royer, Dana L.] Wesleyan Univ, Dept Earth & Environm Sci, Middletown, CT 06459 USA.
   [Soltis, Douglas E.; Calaminus, Andre] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Soltis, Douglas E.; Soltis, Pamela S.] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [Soltis, Douglas E.; Soltis, Pamela S.] Univ Florida, Genet Inst, Gainesville, FL 32611 USA.
   [Stevens, Peter F.] Univ Missouri, Dept Biol, St Louis, MO 63121 USA.
   [Aarssen, Lonnie] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
   [Bertin, Robert I.] Coll Holy Cross, Dept Biol, Worcester, MA 01610 USA.
   [Govaerts, Rafael] Royal Bot Gardens, Richmond TW9 3AB, Surrey, England.
   [Oleksyn, Jacek] Polish Acad Sci, Inst Dendrol, PL-62035 Kornik, Poland.
   [Swenson, Nathan G.] Michigan State Univ, Dept Plant Biol & Ecol, E Lansing, MI 48824 USA.
   [Warman, Laura] US Forest Serv, Inst Pacific Isl Forestry, USDA, Hilo, HI 96720 USA.
   [Beaulieu, Jeremy M.] Univ Tennessee, Natl Inst Math & Biol Synth, Knoxville, TN 37996 USA.
C3 George Washington University; Missouri Botanical Gardens; University of Idaho; University of Idaho; Vrije Universiteit Amsterdam; University of New South Wales Sydney; University of Michigan System; University of Michigan; University of British Columbia; University of British Columbia; Macquarie University; Utah System of Higher Education; Utah State University; Utah System of Higher Education; Utah State University; University of Tennessee System; University of Tennessee Knoxville; University of Minnesota System; University of Minnesota Twin Cities; Western Sydney University; Wesleyan University; State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; University of Missouri System; University of Missouri Saint Louis; Queens University - Canada; College of the Holy Cross; Royal Botanic Gardens, Kew; Polish Academy of Sciences; Michigan State University; United States Department of Agriculture (USDA); United States Forest Service; University of Tennessee System; University of Tennessee Knoxville
RP Zanne, AE (corresponding author), George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
EM aezanne@gmail.com
FU National Evolutionary Synthesis Center (NESCent), National Science Foundation [EF- 0905606]; Macquarie University Genes to Geoscience Research Centre; Division Of Environmental Biology; Direct For Biological Sciences [1242531] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1300426] Funding Source: National Science Foundation
NR 29
TC 1350
Z9 1496
U1 13
U2 707
PU NATURE PUBLISHING 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 6
PY 2014
VL 506
IS 7486
BP 89
EP +
DI 10.1038/nature12872
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100037
PM 24362564
DA 2026-03-09
ER

PT J
AU Wasmuth, EV
   Januszyk, K
   Lima, CD
AF Wasmuth, Elizabeth V.
   Januszyk, Kurt
   Lima, Christopher D.
TI Structure of an Rrp6-RNA exosome complex bound to poly(A) RNA
SO NATURE
LA English
DT Article
ID crystal-structure; degradation; rrp6p; core; reconstitution; exonuclease; cofactor; binding
AB The eukaryotic RNA exosome processes and degrades RNA by directing substrates to the distributive or processive 3' to 5' exoribonuclease activities of Rrp6 or Rrp44, respectively. The non-catalytic nine-subunit exosome core (Exo9) features a prominent central channel. Although RNA can pass through the channel to engage Rrp44, it is not clear how RNA is directed to Rrp6 or whether Rrp6 uses the central channel. Here we report a 3.3 angstrom crystal structure of a ten-subunit RNA exosome complex from Saccharomyces cerevisiae composed of the Exo9 core and Rrp6 bound to single-stranded poly(A) RNA. The Rrp6 catalytic domain rests on top of the Exo9 S1/KH ring above the central channel, the RNA 3' end is anchored in the Rrp6 active site, and the remaining RNA traverses the S1/KH ring in an opposite orientation to that observed in a structure of a Rrp44-containing exosome complex. Solution studies with human and yeast RNA exosome complexes suggest that the RNA path to Rrp6 is conserved and dependent on the integrity of the S1/KH ring. Although path selection to Rrp6 or Rrp44 is stochastic in vitro, the fate of a particular RNA may be determined in vivo by the manner in which cofactors present RNA to the RNA exosome.
C1 [Wasmuth, Elizabeth V.; Januszyk, Kurt; Lima, Christopher D.] Sloan Kettering Inst, Struct Biol Program, New York, NY 10065 USA.
   [Wasmuth, Elizabeth V.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Louis Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA.
   [Lima, Christopher D.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; 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.
EM limac@mskcc.org
FU US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]; National Institute of General Medical Sciences of the National Institutes of Health [F31GM097910, R01GM079196]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 36
TC 122
Z9 150
U1 2
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 JUL 24
PY 2014
VL 511
IS 7510
BP 435
EP +
DI 10.1038/nature13406
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700039
PM 25043052
DA 2026-03-09
ER

PT J
AU Pasham, DR
   Strohmayer, TE
   Mushotzky, RF
AF Pasham, Dheeraj R.
   Strohmayer, Tod E.
   Mushotzky, Richard F.
TI A 400-solar-mass black hole in the galaxy M82
SO NATURE
LA English
DT Article
ID quasi-periodic oscillations; x-ray source; microquasar gro j1655-40; xte j1550-564; rxte observations; timing explorer; dominant state; mass; x-1; discovery
AB M82 X-1, the brightest X-ray source in the galaxy M82, has been thought to be an intermediate-mass black hole (100 to 10,000 solar masses) because of its extremely high luminosity and variability characteristics(1-6), although some models suggest that its mass may be only about 20 solar masses(3,7). The previous mass estimates were based on scaling relations that use low-frequency characteristic time-scales which have large intrinsic uncertainties(8,9). For stellar-mass black holes, we know that the high-frequency quasi-periodic oscillations (100-450 hertz) in the X-ray emission that occur in a 3: 2 frequency ratio are stable and scale in frequency inversely with black hole mass with a reasonably small dispersion(10-15). The discovery of such stable oscillations thus potentially offers an alternative and less ambiguous means of mass determination for intermediate-mass black holes, but has hitherto not been realized. Here we report stable, twin-peak (3: 2 frequency ratio) X-ray quasi-periodic oscillations from M82 X-1 at frequencies of 3.32+/-0.06 hertz and 5.07+/-0.06 hertz. Assuming that we can extrapolate the inverse-mass scaling that holds for stellar-mass black holes, we estimate the black hole mass of M82 X-1 to be 428+/-105 solar masses. In addition, we can estimate the mass using the relativistic precession model, from which we get a value of 415+/-63 solar masses.
C1 [Pasham, Dheeraj R.; Mushotzky, Richard F.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Pasham, Dheeraj R.; Strohmayer, Tod E.] NASA, Goddard Space Flight Ctr, Astrophys Sci Div, Greenbelt, MD 20771 USA.
   [Pasham, Dheeraj R.; Strohmayer, Tod E.] NASA, Goddard Space Flight Ctr, Joint Space Sci Inst, Greenbelt, MD 20771 USA.
C3 University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Pasham, DR (corresponding author), Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
EM dheeraj@astro.umd.edu
NR 48
TC 183
Z9 199
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 SEP 4
PY 2014
VL 513
IS 7516
BP 74
EP +
DI 10.1038/nature13710
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800032
PM 25132552
DA 2026-03-09
ER

PT J
AU Hallmann, CA
   Foppen, RPB
   van Turnhout, CAM
   de Kroon, H
   Jongejans, E
AF Hallmann, Caspar A.
   Foppen, Ruud P. B.
   van Turnhout, Chris A. M.
   de Kroon, Hans
   Jongejans, Eelke
TI Declines in insectivorous birds are associated with high neonicotinoid concentrations
SO NATURE
LA English
DT Article
ID farmland birds; insecticides; pesticides; scale; bees
AB Recent studies have shown that neonicotinoid insecticides have adverse effects on non-target invertebrate species(1-6). Invertebrates constitute a substantial part of the diet of many bird species during the breeding season and are indispensable for raising offspring(7). We investigated the hypothesis that the most widely used neonicotinoid insecticide, imidacloprid, has a negative impact on insectivorous bird populations. Here we show that, in the Netherlands, local population trends were significantly more negative in areas with higher surface-water concentrations of imidacloprid. At imidacloprid concentrations of more than 20 nanograms per litre, bird populations tended to decline by 3.5 per cent on average annually. Additional analyses revealed that this spatial pattern of decline appeared only after the introduction of imidacloprid to the Netherlands, in the mid-1990s. We further show that the recent negative relationship remains after correcting for spatial differences in land-use changes that are known to affect bird populations in farmland. Our results suggest that the impact of neonicotinoids on the natural environment is even more substantial than has recently been reported and is reminiscent of the effects of persistent insecticides in the past. Future legislation should take into account the potential cascading effects of neonicotinoidson ecosystems.
C1 [Hallmann, Caspar A.; de Kroon, Hans; Jongejans, Eelke] Radboud Univ Nijmegen, Inst Water & Wetland Res, Dept Expt Plant Ecol, NL-6500 GL Nijmegen, Netherlands.
   [Hallmann, Caspar A.; de Kroon, Hans; Jongejans, Eelke] Radboud Univ Nijmegen, Inst Water & Wetland Res, Dept Anim Ecol & Ecophysiol, NL-6500 GL Nijmegen, Netherlands.
   [Hallmann, Caspar A.; Foppen, Ruud P. B.; van Turnhout, Chris A. M.] Dutch Ctr Field Ornithol, Sovon, NL-6503 GA Nijmegen, Netherlands.
   [Foppen, Ruud P. B.] Birdlife Netherlands, NL-3700 AX Zeist, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen
RP Hallmann, CA (corresponding author), Radboud Univ Nijmegen, Inst Water & Wetland Res, Dept Expt Plant Ecol, POB 9100 Mail Box 31, NL-6500 GL Nijmegen, Netherlands.
EM c.hallmann@science.ru.nl
FU Dutch Ministry of EZ; NWO [840.11.001, 841.11.007]
NR 28
TC 764
Z9 907
U1 13
U2 962
PU NATURE PUBLISHING 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 17
PY 2014
VL 511
IS 7509
BP 341
EP +
DI 10.1038/nature13531
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200034
PM 25030173
DA 2026-03-09
ER

PT J
AU Myers, SS
   Zanobetti, A
   Kloog, I
   Huybers, P
   Leakey, ADB
   Bloom, AJ
   Carlisle, E
   Dietterich, LH
   Fitzgerald, G
   Hasegawa, T
   Holbrook, NM
   Nelson, RL
   Ottman, MJ
   Raboy, V
   Sakai, H
   Sartor, KA
   Schwartz, J
   Seneweera, S
   Tausz, M
   Usui, Y
AF Myers, Samuel S.
   Zanobetti, Antonella
   Kloog, Itai
   Huybers, Peter
   Leakey, Andrew D. B.
   Bloom, Arnold J.
   Carlisle, Eli
   Dietterich, Lee H.
   Fitzgerald, Glenn
   Hasegawa, Toshihiro
   Holbrook, N. Michele
   Nelson, Randall L.
   Ottman, Michael J.
   Raboy, Victor
   Sakai, Hidemitsu
   Sartor, Karla A.
   Schwartz, Joel
   Seneweera, Saman
   Tausz, Michael
   Usui, Yasuhiro
TI Increasing CO2 threatens human nutrition
SO NATURE
LA English
DT Article
ID carbon-dioxide concentration; elevated co2; enrichment face; spring wheat; grain-yield; nitrogen; quality; protein; cereals; growth
AB Dietary deficiencies of zinc and iron are a substantial global public health problem. An estimated two billion people suffer these deficiencies(1), causing a loss of 63 million life-years annually(2,3). Most of these people depend on C-3 grains and legumes as their primary dietary source of zinc and iron. Here we report that C-3 grains and legumes have lower concentrations of zinc and iron when grown under field conditions at the elevated atmospheric CO2 concentration predicted for the middle of this century. C-3 crops other than legumes also have lower concentrations of protein, whereas C-4 crops seem to be less affected. Differences between cultivars of a single crop suggest that breeding for decreased sensitivity to atmospheric CO2 concentration could partly address these new challenges to global health.
C1 [Myers, Samuel S.; Zanobetti, Antonella; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
   [Myers, Samuel S.] Harvard Univ, Ctr Environm, Cambridge, MA 02138 USA.
   [Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, IL-84105 Beer Sheva, Israel.
   [Huybers, Peter] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Leakey, Andrew D. B.] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA.
   [Leakey, Andrew D. B.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Bloom, Arnold J.; Carlisle, Eli] Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA.
   [Dietterich, Lee H.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Fitzgerald, Glenn] Dept Environm & Primary Ind, Horsham, Vic 3001, Australia.
   [Hasegawa, Toshihiro; Sakai, Hidemitsu; Usui, Yasuhiro] Natl Inst Agroenvironm Sci, Tsukuba, Ibaraki 3058604, Japan.
   [Holbrook, N. Michele] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Nelson, Randall L.] Univ Illinois, USDA ARS, Soybean Maize Germplasm Pathol & Genet Res Unit, Dept Crop Sci, Urbana, IL 61801 USA.
   [Ottman, Michael J.] Univ Arizona, Sch Plant Sci, Tucson, AZ 85721 USA.
   [Raboy, Victor] USDA ARS, Aberdeen, ID 83210 USA.
   [Sartor, Karla A.] Nature Conservancy, Santa Fe, NM 87544 USA.
   [Seneweera, Saman] Univ Melbourne, Dept Agr & Food Syst, Melbourne Sch Land & Environm, Creswick, Vic 3363, Australia.
   [Tausz, Michael] Univ Melbourne, Dept Forest & Ecosyst Sci, Melbourne Sch Land & Environm, Creswick, Vic 3363, Australia.
C3 Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Ben-Gurion University of the Negev; Harvard University; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of California System; University of California Davis; University of Pennsylvania; National Institute for Agro-Environmental Sciences (NIAES) Japan; Harvard University; United States Department of Agriculture (USDA); University of Illinois System; University of Illinois Urbana-Champaign; University of Arizona; United States Department of Agriculture (USDA); Nature Conservancy; University of Melbourne; University of Melbourne
RP Myers, SS (corresponding author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
EM smyers@hsph.harvard.edu
FU Bill & Melinda Gates Foundation; Winslow Foundation; Commonwealth Department of Agriculture (Australia); International Plant Nutrition Institute, (Australia); Grains Research and Development Corporation (Australia); Ministry of Agriculture, Forestry and Fisheries (Japan); National Science Foundation (NSF) [IOS-08-18435]; USDA NIFA [2008-35100-044459]; US Department of Agriculture Agricultural Research Service; Illinois Council for Food and Agricultural Research (CFAR); Department of Energy's Office of Science (BER) Midwestern Regional Center of the National Institute for Climatic Change Research at Michigan Technological University [DEFC02- 06ER64158]; National Research Initiative of Agriculture and Food Research Initiative Competitive Grants Program from the USDA National Institute of Food and Agriculture [2010-65114-20343]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; National Institute of Environmental Health Sciences [P30ES000002] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1358675] Funding Source: National Science Foundation
NR 41
TC 983
Z9 1148
U1 17
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 JUN 5
PY 2014
VL 510
IS 7503
BP 139
EP +
DI 10.1038/nature13179
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900044
PM 24805231
DA 2026-03-09
ER

PT J
AU Belew, AT
   Meskauskas, A
   Musalgaonkar, S
   Advani, VM
   Sulima, SO
   Kasprzak, WK
   Shapiro, BA
   Dinman, JD
AF Belew, Ashton Trey
   Meskauskas, Arturas
   Musalgaonkar, Sharmishtha
   Advani, Vivek M.
   Sulima, Sergey O.
   Kasprzak, Wojciech K.
   Shapiro, Bruce A.
   Dinman, Jonathan D.
TI Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway
SO NATURE
LA English
DT Article
ID translational fidelity; sequence alignment; gene; model; efficiency; database; binding; version; signal; cells
AB Programmed -1 ribosomal frameshift (-1 PRF) signals redirect translating ribosomes to slip back one base on messenger RNAs. Although well characterizedin viruses, how these elements may regulate cellular gene expression is not understood. Here we describe a -1 PRF signal in the human mRNA encoding CCR5, the HIV-1 co-receptor. CCR5 mRNA-mediated -1 PRF is directed by an mRNA pseudoknot, and is stimulated by at least two microRNAs. Mapping the mRNA-miRNA interaction suggests that formation of a triplex RNA structure stimulates -1 PRF. A -1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved. Functional -1 PRF signals that seem to be regulated by miRNAs are also demonstrated in mRNAs encoding six other cytokine receptors, suggesting a novel mode through which immune responses may be fine-tuned in mammalian cells.
C1 [Belew, Ashton Trey; Meskauskas, Arturas; Musalgaonkar, Sharmishtha; Advani, Vivek M.; Sulima, Sergey O.; Dinman, Jonathan D.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
   [Meskauskas, Arturas] Vilnius State Univ, Dept Biotechnol & Microbiol, LT-03101 Vilnius, Lithuania.
   [Kasprzak, Wojciech K.] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Shapiro, Bruce A.] NCI, Basic Res Lab, Frederick, MD 21702 USA.
C3 University System of Maryland; University of Maryland College Park; Vilnius University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Dinman, JD (corresponding author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
EM dinman@umd.edu
FU National Institutes of Health [5 R01GM058859, R21GM068123]; National Science Foundation [MCB-0084559]; University of Maryland College of CMNS Hockmeyer Fellowship; NIH/NIGMS [T32GM080201]; Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E]; Intramural Research Program of the National Institutes of Health, Center for Cancer Research;  [NIH/NIAIDT32AI051967]; National Cancer Institute [ZIABC008382] Funding Source: NIH RePORTER
NR 48
TC 125
Z9 161
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 AUG 21
PY 2014
VL 512
IS 7514
BP 265
EP +
DI 10.1038/nature13429
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200025
PM 25043019
DA 2026-03-09
ER

PT J
AU Zid, BM
   O'Shea, EK
AF Zid, Brian M.
   O'Shea, Erin K.
TI Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast
SO NATURE
LA English
DT Article
ID shock transcription factor; saccharomyces-cerevisiae; heat-shock; processing body; stress granules; p-body; in-vivo; gene; stability; expression
AB A universal feature of the response to stress and nutrient limitation is transcriptional upregulation of genes that encode proteins important for survival. Under many such conditions, the overall protein synthesis level is reduced, thereby dampening the stress response at the level of protein expression(1). For example, during glucose starvation in Saccharomyces cerevisiae (yeast), translation is rapidly repressed, yet the transcription of many stress-and glucose-repressed genes is increased(2,3). Here we show, using ribosomal profiling and microscopy, that this transcriptionally upregulated gene set consists of two classes: one class produces messenger RNAs that are translated during glucose starvation and are diffusely localized in the cytoplasm, including many heat-shock protein mRNAs; and the other class produces mRNAs that are not efficiently translated during glucose starvation and are concentrated in foci that co-localize with P bodies and stress granules, a class that isenriched for mRNAs involved in glucose metabolism. Surprisingly, the information specifying the differential localization and protein production of these two classes of mRNA is encoded in the promoter sequence: promoter responsiveness to heat-shock factor 1 (Hsf1) specifies diffuse cytoplasmic localization and higher protein production on glucose starvation. Thus, promoter sequences can influence not only the levels of mRNAs but also the subcellular localization of mRNAs and the efficiency with which they are translated, enabling cells to tailor protein production to the environmental conditions.
C1 [Zid, Brian M.; O'Shea, Erin K.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA.
   [Zid, Brian M.; O'Shea, Erin K.] Harvard Univ, Ctr Syst Biol, Fac Arts & Sci, Cambridge, MA 02138 USA.
   [O'Shea, Erin K.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [O'Shea, Erin K.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University; Howard Hughes Medical Institute; Harvard University
RP O'Shea, EK (corresponding author), Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA.
EM Erin_Oshea@harvard.edu
FU American Cancer Society; New England Division Funding A Cure initiative; Howard Hughes Medical Institute
NR 29
TC 157
Z9 210
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 OCT 2
PY 2014
VL 514
IS 7520
BP 117
EP +
DI 10.1038/nature13578
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800047
PM 25119046
DA 2026-03-09
ER

PT J
AU Schaefer, GH
   ten Brummelaar, T
   Gies, DR
   Farrington, CD
   Kloppenborg, B
   Chesneau, O
   Monnier, JD
   Ridgway, ST
   Scott, N
   Tallon-Bosc, I
   McAlister, HA
   Boyajian, T
   Maestro, V
   Mourard, D
   Meilland, A
   Nardetto, N
   Stee, P
   Sturmann, J
   Vargas, N
   Baron, F
   Ireland, M
   Baines, EK
   Che, X
   Jones, J
   Richardson, ND
   Roettenbacher, RM
   Sturmann, L
   Turner, NH
   Tuthill, P
   van Belle, G
   von Braun, K
   Zavala, RT
   Banerjee, DPK
   Ashok, NM
   Joshi, V
   Becker, J
   Muirhead, PS
AF Schaefer, G. H.
   ten Brummelaar, T.
   Gies, D. R.
   Farrington, C. D.
   Kloppenborg, B.
   Chesneau, O.
   Monnier, J. D.
   Ridgway, S. T.
   Scott, N.
   Tallon-Bosc, I.
   McAlister, H. A.
   Boyajian, T.
   Maestro, V.
   Mourard, D.
   Meilland, A.
   Nardetto, N.
   Stee, P.
   Sturmann, J.
   Vargas, N.
   Baron, F.
   Ireland, M.
   Baines, E. K.
   Che, X.
   Jones, J.
   Richardson, N. D.
   Roettenbacher, R. M.
   Sturmann, L.
   Turner, N. H.
   Tuthill, P.
   van Belle, G.
   von Braun, K.
   Zavala, R. T.
   Banerjee, D. P. K.
   Ashok, N. M.
   Joshi, V.
   Becker, J.
   Muirhead, P. S.
TI The expanding fireball of Nova Delphini 2013
SO NATURE
LA English
DT Article
ID classical novae; interferometric observations; spectroscopic evolution; recurrent novae; t pyxidis; outburst; shells; spectrograph; remnants; phase
AB A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway(1,2). Complex structures observed in the ejecta at late stages(3-5) could result from interactions with the companion during the common-envelope phase(6,7). Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf(8) or as a consequence of rotational distortion(9,10). Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes(11). Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 60.59 kiloparsecs from the Sun.
C1 [Schaefer, G. H.; ten Brummelaar, T.; Farrington, C. D.; Scott, N.; Sturmann, J.; Vargas, N.; Sturmann, L.; Turner, N. H.] Georgia State Univ, CHARA Array, Mt Wilson Observ, Mt Wilson, CA 91023 USA.
   [Gies, D. R.; Kloppenborg, B.; McAlister, H. A.; Baron, F.; Jones, J.] Georgia State Univ, Ctr High Angular Resolut Astron, Atlanta, GA 30302 USA.
   [Gies, D. R.; Kloppenborg, B.; McAlister, H. A.; Baron, F.; Jones, J.] Georgia State Univ, Dept Phys & Astron, Atlanta, GA 30302 USA.
   [Chesneau, O.; Mourard, D.; Meilland, A.; Nardetto, N.; Stee, P.] Univ Sophia Antipolis UNS, CNRS, Observ Cote Azur, Lab Lagrange,UMR 7293, F-06304 Nice 4, France.
   [Monnier, J. D.; Che, X.; Roettenbacher, R. M.; Becker, J.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Ridgway, S. T.] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [Tallon-Bosc, I.] Univ Lyon 1, Observ Lyon, F-69230 St Genis Laval, France.
   [Tallon-Bosc, I.] Ecole Normale Super Lyon, Ctr Rech Astrophys Lyon, CNRS, UMR 5574, F-69007 Lyon, France.
   [Boyajian, T.] Yale Univ, Dept Astron, New Haven, CT 06511 USA.
   [Maestro, V.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
   [Ireland, M.] Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT 2611, Australia.
   [Baines, E. K.] Naval Res Lab, Remote Sensing Div, Washington, DC 20375 USA.
   [Richardson, N. D.] Univ Montreal, Dept Phys, Montreal, PQ H3C 3J7, Canada.
   [Richardson, N. D.] Univ Montreal, CRAQ, Montreal, PQ H3C 3J7, Canada.
   [van Belle, G.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [von Braun, K.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Zavala, R. T.] US Naval Observ, Flagstaff Stn, Flagstaff, AZ 86001 USA.
   [Banerjee, D. P. K.; Ashok, N. M.; Joshi, V.] Phys Res Lab, Astron & Astrophys Div, Ahmadabad 380009, Gujarat, India.
   [Becker, J.] CALTECH, Cahill Ctr Astron & Astrophys, Pasadena, CA 91106 USA.
   [Muirhead, P. S.] Boston Univ, Dept Astron, Boston, MA 02215 USA.
C3 University System of Georgia; Georgia State University; University System of Georgia; Georgia State University; University System of Georgia; Georgia State University; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Michigan System; University of Michigan; National Optical Astronomy Observatory; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON); Yale University; University of Sydney; Australian National University; United States Department of Defense; United States Navy; United States Naval Research Laboratory; Universite de Montreal; Universite de Montreal; Max Planck Society; Department of Space (DoS), Government of India; Physical Research Laboratory - India; California Institute of Technology; Boston University
RP Schaefer, GH (corresponding author), Georgia State Univ, CHARA Array, Mt Wilson Observ, Mt Wilson, CA 91023 USA.
EM schaefer@chara-array.org
FU National Science Foundation [AST-1009080]; National Science Foundation through NSF grants [AST 0908253, AST 1211129]; Georgia State University through the College of Arts and Sciences; National Aeronautics and Space Administration; National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1411654, 1445935, 1009080] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1211929] Funding Source: National Science Foundation
NR 49
TC 63
Z9 66
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 NOV 13
PY 2014
VL 515
IS 7526
BP 234
EP U182
DI 10.1038/nature13834
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400042
PM 25363778
DA 2026-03-09
ER

PT J
AU Prüfer, K
   Racimo, F
   Patterson, N
   Jay, F
   Sankararaman, S
   Sawyer, S
   Heinze, A
   Renaud, G
   Sudmant, PH
   de Filippo, C
   Li, H
   Mallick, S
   Dannemann, M
   Fu, QM
   Kircher, M
   Kuhlwilm, M
   Lachmann, M
   Meyer, M
   Ongyerth, M
   Siebauer, M
   Theunert, C
   Tandon, A
   Moorjani, P
   Pickrell, J
   Mullikin, JC
   Vohr, SH
   Green, RE
   Hellmann, I
   Johnson, PLF
   Blanche, H
   Cann, H
   Kitzman, JO
   Shendure, J
   Eichler, EE
   Lein, ES
   Bakken, TE
   Golovanova, LV
   Doronichev, VB
   Shunkov, MV
   Derevianko, AP
   Viola, B
   Slatkin, M
   Reich, D
   Kelso, J
   Pääbo, S
AF Pruefer, Kay
   Racimo, Fernando
   Patterson, Nick
   Jay, Flora
   Sankararaman, Sriram
   Sawyer, Susanna
   Heinze, Anja
   Renaud, Gabriel
   Sudmant, Peter H.
   de Filippo, Cesare
   Li, Heng
   Mallick, Swapan
   Dannemann, Michael
   Fu, Qiaomei
   Kircher, Martin
   Kuhlwilm, Martin
   Lachmann, Michael
   Meyer, Matthias
   Ongyerth, Matthias
   Siebauer, Michael
   Theunert, Christoph
   Tandon, Arti
   Moorjani, Priya
   Pickrell, Joseph
   Mullikin, James C.
   Vohr, Samuel H.
   Green, Richard E.
   Hellmann, Ines
   Johnson, Philip L. F.
   Blanche, Helene
   Cann, Howard
   Kitzman, Jacob O.
   Shendure, Jay
   Eichler, Evan E.
   Lein, Ed S.
   Bakken, Trygve E.
   Golovanova, Liubov V.
   Doronichev, Vladimir B.
   Shunkov, Michael V.
   Derevianko, Anatoli P.
   Viola, Bence
   Slatkin, Montgomery
   Reich, David
   Kelso, Janet
   Paeaebo, Svante
TI The complete genome sequence of a Neanderthal from the Altai Mountains
SO NATURE
LA English
DT Article
ID mezmaiskaya cave; denisova cave; dna-sequences; great ape; ancient; hominin; admixture; ancestry; history
AB We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.
C1 [Pruefer, Kay; Sawyer, Susanna; Heinze, Anja; Renaud, Gabriel; de Filippo, Cesare; Dannemann, Michael; Fu, Qiaomei; Kircher, Martin; Kuhlwilm, Martin; Lachmann, Michael; Meyer, Matthias; Ongyerth, Matthias; Siebauer, Michael; Theunert, Christoph; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionare Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Racimo, Fernando; Jay, Flora; Slatkin, Montgomery] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Patterson, Nick; Sankararaman, Sriram; Li, Heng; Mallick, Swapan; Tandon, Arti; Reich, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Sankararaman, Sriram; Mallick, Swapan; Tandon, Arti; Moorjani, Priya; Pickrell, Joseph; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sudmant, Peter H.; Kircher, Martin; Kitzman, Jacob O.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Fu, Qiaomei] Chinese Acad Sci, Key Lab Vertebrate Evolut & Human Origins, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Mallick, Swapan] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Mallick, Swapan] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
   [Vohr, Samuel H.; Green, Richard E.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Hellmann, Ines] Max F Perutz Labs, Math & Biosci Grp, Campus Vienna Bioctr 5, A-1030 Vienna, Austria.
   [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
   [Blanche, Helene; Cann, Howard] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
   [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Lein, Ed S.; Bakken, Trygve E.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
   [Golovanova, Liubov V.; Doronichev, Vladimir B.] ANO Lab Prehist 14 Linia 3 11, St Petersburg 199034, Russia.
   [Shunkov, Michael V.; Derevianko, Anatoli P.] Russian Acad Sci, Inst Archaeol & Ethnog, Palaeolith Dept, Siberian Branch, Novosibirsk 630090, Russia.
   [Viola, Bence] Max Planck Inst Evolutionare Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
C3 Max Planck Society; University of California System; University of California Berkeley; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; University of Washington; University of Washington Seattle; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of California System; University of California Santa Cruz; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); Emory University; Foundation Jean Dausset-CEPH; Howard Hughes Medical Institute; Allen Institute for Brain Science; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Archaeology & Ethnography, Siberian Branch of Russian Academy of Sciences; Max Planck Society; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Slatkin, M (corresponding author), Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
EM slatkin@berkeley.edu; reich@genetics.med.harvard.edu
FU NSF [1032255]; NIH [GM100233, HG002385, R01-GM40282]; National Genome Research Institute (NHGRI) [HG006283]; Harvard University Science of the Human Past Program; HHMI International Student Fellowship; Paul G. Allen Family Foundation; Presidential Innovation Fund of the Max Planck Society; National Human Genome Research Institute [R01HG002385, ZIAHG200330, ZIBHG000196] Funding Source: NIH RePORTER; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1032255] Funding Source: National Science Foundation
NR 46
TC 1472
Z9 1715
U1 10
U2 936
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 2
PY 2014
VL 505
IS 7481
BP 43
EP +
DI 10.1038/nature12886
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300020
PM 24352235
DA 2026-03-09
ER

PT J
AU Hashimoto, H
   Pais, JE
   Zhang, X
   Saleh, L
   Fu, ZQ
   Dai, N
   Corrêa, IR
   Zheng, Y
   Cheng, XD
AF Hashimoto, Hideharu
   Pais, June E.
   Zhang, Xing
   Saleh, Lana
   Fu, Zheng-Qing
   Dai, Nan
   Correa, Ivan R., Jr.
   Zheng, Yu
   Cheng, Xiaodong
TI Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA
SO NATURE
LA English
DT Article
ID 5-hydroxymethylcytosine content; crystal-structures; base; 5-carboxylcytosine; 5-formylcytosine; glycosylase; proteins; demethylation; intermediate; conversion
AB Cytosine residues in mammalian DNA occur in five forms: cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The ten-eleven translocation (Tet) dioxygenases convert 5mC to 5hmC, 5fC and 5caC in three consecutive, Fe(II)- and alpha-ketoglutarate-dependent oxidation reactions(1-4). The Tet family of dioxygenases is widely distributed across the tree of life(5), including in the heterolobosean amoeboflagellate Naegleria gruberi. The genome of Naegleria(6) encodes homologues of mammalian DNA methyltransferase and Tet proteins(7). Here we study biochemically and structurally one of the Naegleria Tet-like proteins (NgTet1), which shares significant sequence conservation (approximately 14% identity or 39% similarity) with mammalian Tet1. Like mammalian Tet proteins, NgTet1 acts on 5mC and generates 5hmC, 5fC and 5caC. The crystal structure of NgTet1 in complex with DNA containing a 5mCpG site revealed that NgTet1 uses a base-flipping mechanism to access 5mC. The DNA is contacted from the minor groove and bent towards the major groove. The flipped 5mC is positioned in the active-site pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5mC. The sequence conservation between NgTet1 and mammalian Tet1, including residues involved in structural integrity and functional significance, suggests structural conservation across phyla.
C1 [Hashimoto, Hideharu; Zhang, Xing; Cheng, Xiaodong] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
   [Pais, June E.; Saleh, Lana; Dai, Nan; Correa, Ivan R., Jr.; Zheng, Yu] New England Biolabs Inc, Ipswich, MA 01938 USA.
   [Fu, Zheng-Qing] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
   [Fu, Zheng-Qing] Argonne Natl Lab, Adv Photon Source, Sect 22, Argonne, IL 60439 USA.
C3 Emory University; New England Biolabs; University System of Georgia; University of Georgia; United States Department of Energy (DOE); Argonne National Laboratory
RP Cheng, XD (corresponding author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM zhengy@neb.com; xcheng@emory.edu
FU National Institutes of Health [GM049245, GM095209, GM105132]
NR 42
TC 116
Z9 137
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 FEB 20
PY 2014
VL 506
IS 7488
BP 391
EP +
DI 10.1038/nature12905
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800046
PM 24390346
DA 2026-03-09
ER

PT J
AU Meng, FK
   McGrath, KP
   Hoveyda, AH
AF Meng, Fanke
   McGrath, Kevin P.
   Hoveyda, Amir H.
TI Multifunctional organoboron compounds for scalable natural product synthesis
SO NATURE
LA English
DT Article
ID carbon stereogenic centers; cu-catalyzed hydroboration; enantioselective synthesis; conjugate additions; nhc ligands; efficient; aryl; metathesis; nafuredin; reagents
AB Efficient catalytic reactions that can generate C-C bonds enantioselectively, and ones that can produce trisubstituted alkenes diastereoselectively, are central to research in organic chemistry. Transformations that accomplish these two tasks simultaneously are in high demand, particularly if the catalysts, substrates and reagents are inexpensive and if the reaction conditions are mild. Here we report a facile multicomponent catalytic process that begins with a chemoselective, site-selective and diastereoselective copper-boron addition to a monosubstituted allene; the resulting boron-substituted organocopper intermediates then participate in a similarly selective allylic substitution. The products, which contain a stereogenic carbon centre, a monosubstituted alkene and an easily functionalizable Z-trisubstituted alkenylboron group, are obtained in up to 89 per cent yield, with more than 98 per cent branch-selectivity and stereoselectivity and an enantiomeric ratio greater than 99: 1. The copper-based catalyst is derived from a robust heterocyclic salt that can be prepared in multigram quantities from inexpensive starting materials and without costly purification procedures. The utility of the approach is demonstrated through enantioselective synthesis of gram quantities of two natural products, namely rottnestol and herboxidiene (also known as GEX1A).
C1 [Meng, Fanke; McGrath, Kevin P.; 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 National Institutes of Health, Institute of General Medical Sciences [GM-47480]; National Science Foundation [CHE-1111074, CHE-1362763]; LaMattina graduate fellowship in organic synthesis
NR 48
TC 204
Z9 229
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 SEP 18
PY 2014
VL 513
IS 7518
BP 367
EP 374
DI 10.1038/nature13735
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900050
PM 25230659
DA 2026-03-09
ER

PT J
AU Shin, J
   Wallingford, MC
   Gallant, J
   Marcho, C
   Jiao, BW
   Byron, M
   Bossenz, M
   Lawrence, JB
   Jones, SN
   Mager, J
   Bach, I
AF Shin, JongDae
   Wallingford, Mary C.
   Gallant, Judith
   Marcho, Chelsea
   Jiao, Baowei
   Byron, Meg
   Bossenz, Michael
   Lawrence, Jeanne B.
   Jones, Stephen N.
   Mager, Jesse
   Bach, Ingolf
TI RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast
SO NATURE
LA English
DT Article
ID functional-activity; rnf12; rna; pluripotency; rlim/rnf12; nanog; gene; jpx
AB In female mice, two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X chromosome. Later, around implantation, epiblast cells of the inner cell mass that give rise to the embryo reactivate the paternal X chromosome and undergo a random form of XCI (rXCI)(1,2). Xist, a long non-coding RNA crucial for both forms of XCI, is activated by the ubiquitin ligase RLIM (also known as Rnf12)(3-5). Although RLIM is required for triggering iXCI in mice, its importance for rXCI has been controversial. Here we show that RLIM levels are downregulated in embryonic cells undergoing rXCI. Using mouse genetics we demonstrate that female cells lacking RLIM from pre-implantation stages onwards show hallmarks of XCI, including Xist clouds and H3K27me3 foci, and have full embryogenic potential. These results provide evidence that RLIM is dispensable for rXCI, indicating that in mice an RLIM-independent mechanism activates Xist in the embryo proper.
C1 [Shin, JongDae; Jiao, Baowei; Bach, Ingolf] UMMS, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Wallingford, Mary C.; Marcho, Chelsea; Mager, Jesse] Univ Massachusetts, Amherst, MA 01003 USA.
   [Gallant, Judith; Byron, Meg; Lawrence, Jeanne B.; Jones, Stephen N.] UMMS, Dept Cell & Dev Biol, Worcester, MA 01605 USA.
   [Bossenz, Michael] Ortenau Klinikum Lahr Ettenheim, Inst Pathol, D-77933 Lahr, Germany.
   [Bach, Ingolf] UMMS, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Amherst
RP Bach, I (corresponding author), UMMS, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM Ingolf.bach@umassmed.edu
FU National Institutes of Health grants [CA131158, CA077735, GM053234]
NR 29
TC 52
Z9 61
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 3
PY 2014
VL 511
IS 7507
BP 86
EP U443
DI 10.1038/nature13286
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400041
PM 24870238
DA 2026-03-09
ER

PT J
AU Geng, J
   Kim, K
   Zhang, JF
   Escalada, A
   Tunuguntla, R
   Comolli, LR
   Allen, FI
   Shnyrova, AV
   Cho, KR
   Munoz, D
   Wang, YM
   Grigoropoulos, CP
   Ajo-Franklin, CM
   Frolov, VA
   Noy, A
AF Geng, Jia
   Kim, Kyunghoon
   Zhang, Jianfei
   Escalada, Artur
   Tunuguntla, Ramya
   Comolli, Luis R.
   Allen, Frances I.
   Shnyrova, Anna V.
   Cho, Kang Rae
   Munoz, Dayannara
   Wang, Y. Morris
   Grigoropoulos, Costas P.
   Ajo-Franklin, Caroline M.
   Frolov, Vadim A.
   Noy, Aleksandr
TI Stochastic transport through carbon nanotubes in lipid bilayers and live cell membranes
SO NATURE
LA English
DT Article
ID alpha-hemolysin; water; channel; dna; insertion
AB There is much interest in developing synthetic analogues of biological membrane channels(1) with high efficiency and exquisite selectivity for transporting ions and molecules. Bottom-up(2) and top-down(3) methods can produce nanopores of a size comparable to that of endogenous protein channels, but replicating their affinity and transport properties remains challenging. In principle, carbon nanotubes (CNTs) should be an ideal membrane channel platform: they exhibit excellent transport properties(4-8) and their narrow hydrophobic inner pores mimic structural motifs typical of biological channels(1). Moreover, simulations predict that CNTs with a length comparable to the thickness of a lipid bilayer membrane can self-insert into the membrane(9,10). Functionalized CNTs have indeed been found to penetrate lipid membranes and cell walls(11,12), and short tubes have been forced into membranes to create sensors(13), yet membrane transport applications of short CNTs remain underexplored. Here we show that short CNTs spontaneously insert into lipid bilayers and live cell membranes to form channels that exhibit a unitary conductance of 70-100 picosiemens under physiological conditions. Despite their structural simplicity, these 'CNT porins' transport water, protons, small ions and DNA, stochastically switch between metastable conductance substates, and display characteristic macromolecule-induced ionic current blockades. We also show that local channel and membrane charges can control the conductance and ion selectivity of the CNT porins, thereby establishing these nanopores as a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating stochastic sensors.
C1 [Geng, Jia; Kim, Kyunghoon; Tunuguntla, Ramya; Cho, Kang Rae; Munoz, Dayannara; Noy, Aleksandr] Lawrence Livermore Natl Lab, Phys & Life Sci Directorate, Biol & Biotechnol Div, Livermore, CA 94550 USA.
   [Geng, Jia; Zhang, Jianfei; Noy, Aleksandr] Univ Calif, Sch Nat Sci, Merced, CA 95340 USA.
   [Geng, Jia; Kim, Kyunghoon; Tunuguntla, Ramya; Noy, Aleksandr] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, Berkeley, CA 94720 USA.
   [Kim, Kyunghoon; Grigoropoulos, Costas P.] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
   [Escalada, Artur; Shnyrova, Anna V.; Frolov, Vadim A.] Univ Basque Country, CSIC, Biophys Unit, Leioa 48940, Spain.
   [Escalada, Artur; Shnyrova, Anna V.; Frolov, Vadim A.] Univ Basque Country, Dept Biochem & Mol Biol, Leioa 48940, Spain.
   [Comolli, Luis R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Allen, Frances I.] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA.
   [Allen, Frances I.; Ajo-Franklin, Caroline M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Allen, Frances I.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Ctr Electron Microscopy, Berkeley, CA 94720 USA.
   [Wang, Y. Morris] Lawrence Livermore Natl Lab, Div Mat Sci, Livermore, CA 94550 USA.
   [Ajo-Franklin, Caroline M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
   [Frolov, Vadim A.] Basque Fdn Sci, Ikerbasque, Bilbao 48011, Spain.
C3 United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California Merced; 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; Consejo Superior de Investigaciones Cientificas (CSIC); University of Basque Country; CSIC - UPV EHU - Instituto Biofisika; University of Basque Country; 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; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Basque Foundation for Science
RP Noy, A (corresponding author), Lawrence Livermore Natl Lab, Phys & Life Sci Directorate, Biol & Biotechnol Div, Livermore, CA 94550 USA.
EM noy1@llnl.gov
FU US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering; LDRD programme at LLNL [12-ERD-073]; LSP programme at LLNL; ROTC summer fellowship; Spanish Ministry of Economy and Competitiveness [BFU2012-34885]; European FEDER funds; Basque Government [IE12-332]; US Department of Energy [DE-AC52-07NA27344]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]
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NR 33
TC 373
Z9 431
U1 4
U2 666
PU NATURE PUBLISHING 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 30
PY 2014
VL 514
IS 7524
BP 612
EP +
DI 10.1038/nature13817
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500045
PM 25355362
DA 2026-03-09
ER

PT J
AU Hwang, WL
   Deindl, S
   Harada, BT
   Zhuang, XW
AF Hwang, William L.
   Deindl, Sebastian
   Harada, Bryan T.
   Zhuang, Xiaowei
TI Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA
SO NATURE
LA English
DT Article
ID single-molecule; core particle; chromatin; iswi; acf; complexes; resolution; contains; dynamics; subunits
AB Imitation switch (ISWI)-family remodelling enzymes regulate access to genomic DNA by mobilizing nucleosomes(1). These ATP-dependent chromatin remodellers promote heterochromatin formation and transcriptional silencing(1) by generating regularly spaced nucleosome arrays(2-5). The nucleosome-spacing activity arises from the dependence of nucleosome translocation on the length of extranucleosomal linker DNA(6-10), but the underlying mechanism remains unclear. Here we study nucleosome remodelling by human ATP-dependent chromatin assembly and remodelling factor (ACF), an ISWI enzyme comprising a catalytic subunit, Snf2h, and an accessory subunit, Acf1 (refs 2, 11-13). We find that ACF senses linker DNA length through an interplay between its accessory and catalytic subunits mediated by the histone H4 tail of the nucleosome. Mutation of AutoN, an auto-inhibitory domain within Snf2h that bears sequence homology to the H4 tail(14), abolishes the linker-length sensitivity in remodelling. Addition of exogenous H4-tail peptide or deletion of the nucleosomal H4 tail also diminishes the linker-length sensitivity. Moreover, Acf1 binds both the H4-tail peptide and DNA in an amino (N)-terminal domain dependent manner, and in the ACF-bound nucleosome, lengthening the linker DNA reduces the Acf1-H4 tail proximity. Deletion of the N-terminal portion of Acf1 (or itshomologue in yeast) abolishes linker-length sensitivity in remodelling and leads to severe growth defects in vivo. Taken together, our results suggest a mechanism for nucleosome spacing where linker DNA sensing by Acf1 is allosterically transmitted to Snf2h through the H4 tail of the nucleosome. For nucleosomes with short linker DNA, Acf1 preferentially binds to the H4 tail, allowing AutoN to inhibit the ATPase activity of Snf2h. As the linker DNA lengthens, Acf1 shifts its binding preference to the linker DNA, freeing the H4 tail to compete Auto N off the ATPase and thereby activating ACF.
C1 [Hwang, William L.; Deindl, Sebastian; Harada, Bryan T.; Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
   [Hwang, William L.; Harada, Bryan T.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA.
   [Hwang, William L.] Harvard Univ, Sch Med, Harvard MIT MD PhD Program, Boston, MA 02115 USA.
   [Deindl, Sebastian; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University; Howard Hughes Medical Institute; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University
RP Zhuang, XW (corresponding author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM zhuang@chemistry.harvard.edu
FU National Institutes of Health [GM105637, T32G007753]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 36
TC 70
Z9 86
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 AUG 14
PY 2014
VL 512
IS 7513
BP 213
EP +
DI 10.1038/nature13380
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700036
PM 25043036
DA 2026-03-09
ER

PT J
AU Zhang, B
   Wang, J
   Wang, X
   Zhu, J
   Liu, Q
   Shi, Z
   Chambers, MC
   Zimmerman, LJ
   Shaddox, KF
   Kim, S
   Davies, SR
   Wang, S
   Wang, P
   Kinsinger, CR
   Rivers, RC
   Rodriguez, H
   Townsend, RR
   Ellis, MJC
   Carr, SA
   Tabb, DL
   Coffey, RJ
   Slebos, RJC
   Liebler, DC
AF Zhang, Bing
   Wang, Jing
   Wang, Xiaojing
   Zhu, Jing
   Liu, Qi
   Shi, Zhiao
   Chambers, Matthew C.
   Zimmerman, Lisa J.
   Shaddox, Kent F.
   Kim, Sangtae
   Davies, Sherri R.
   Wang, Sean
   Wang, Pei
   Kinsinger, Christopher R.
   Rivers, Robert C.
   Rodriguez, Henry
   Townsend, R. Reid
   Ellis, Matthew J. C.
   Carr, Steven A.
   Tabb, David L.
   Coffey, Robert J.
   Slebos, Robbert J. C.
   Liebler, Daniel C.
TI Proteogenomic characterization of human colon and rectal cancer
SO NATURE
LA English
DT Article
ID rna-seq data; protein expression; colorectal-cancer; peptide identification; proteomic analysis; mass-spectrometry; analysis reveals; gene; abundance; hnf4-alpha
AB Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A(hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.
C1 [Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Chambers, Matthew C.; Tabb, David L.] Vanderbilt Univ Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA.
   [Zhang, Bing; Slebos, Robbert J. C.] Vanderbilt Univ Sch Med, Dept Canc Biol, Nashville, TN 37232 USA.
   [Shi, Zhiao] Vanderbilt Univ, Adv Comp Ctr Res & Educ, Nashville, TN 37232 USA.
   [Shi, Zhiao] Vanderbilt Univ, Dept Elect Engn & Comp Sci, Nashville, TN 37232 USA.
   [Zimmerman, Lisa J.; Liebler, Daniel C.] Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN 37232 USA.
   [Zimmerman, Lisa J.; Shaddox, Kent F.; Slebos, Robbert J. C.; Liebler, Daniel C.] Vanderbilt Ingram Canc Ctr, Jim Ayers Inst Precanc Detect & Diag, Nashville, TN 37232 USA.
   [Kim, Sangtae] Pacific NW Natl Lab, Directorate Fundamental & Computat Sci, Richland, WA 99352 USA.
   [Davies, Sherri R.; Townsend, R. Reid; Ellis, Matthew J. C.] Washington Univ Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
   [Wang, Sean] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Wang, Pei] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Kinsinger, Christopher R.; Rivers, Robert C.; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.
   [Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Coffey, Robert J.] Vanderbilt Univ Sch Med, Dept Med, Nashville, TN 37232 USA.
C3 Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Washington University (WUSTL); Fred Hutchinson Cancer Center; Icahn School of Medicine at Mount Sinai; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Vanderbilt University
RP Liebler, DC (corresponding author), Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN 37232 USA.
EM daniel.liebler@vanderbilt.edu
FU National Cancer Institute (NCI) CPTAC awards [U24CA159988, U24CA160035, U24CA160034]; NCI SPORE award [P50CA095103]; NCI Cancer Center Support Grant [P30CA068485]; National Institutes of Health [GM088822]; Leidos Biomedical Research, Inc. [13XS029]; National Cancer Institute [P30CA068485] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK058404] Funding Source: NIH RePORTER
NR 81
TC 1153
Z9 1318
U1 8
U2 374
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2014
VL 513
IS 7518
BP 382
EP +
DI 10.1038/nature13438
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900052
PM 25043054
DA 2026-03-09
ER

PT J
AU Shen, Y
   Ho, LC
AF Shen, Yue
   Ho, Luis C.
TI The diversity of quasars unified by accretion and orientation
SO NATURE
LA English
DT Article
ID active galactic nuclei; black-hole masses; x-ray-property; data release; scaling relationships; stellar objects; emission-lines; host galaxy; radio-loud; dependence
AB Quasars are rapidly accreting supermassive black holes at the centres of massive galaxies. They display a broad range of properties across all wavelengths, reflecting the diversity in the physical conditions of the regions close to the central engine. These properties, however, are not random, but form well-defined trends. The dominant trend is known as 'Eigenvector l', in which many properties correlate with the strength of optical iron and [O III] emission(1-3). The main physical driver of Eigenvector 1 has long been suspected(4) to be the quasar luminosity normalized by the mass of the hole (the 'Eddington ratio'), which is an important parameter of the black hole accretion process. But a definitive proof has been missing. Here we report an analysis of archival data that reveals that the Eddington ratio indeed drives Eigenvector 1. We also find that orientation plays a significant role in determining the observed kinematics of the gas in the broad-line region, implying a flattened, disk-like geometry for the fast-moving clouds close to the black hole. Our results show that most of the diversity of quasar phenomenology can be unified using two simple quantities: Eddington ratio and orientation.
C1 [Shen, Yue] Carnegie Observ, Pasadena, CA 91101 USA.
   [Shen, Yue; Ho, Luis C.] Peking Univ, Kavli Inst Astron & Astrophys, Beijing 100871, Peoples R China.
   [Ho, Luis C.] Peking Univ, Sch Phys, Dept Astron, Beijing 100871, Peoples R China.
C3 Carnegie Institution for Science; Peking University; Peking University
RP Shen, Y (corresponding author), Carnegie Observ, 813 Santa Barbara St, Pasadena, CA 91101 USA.
EM yshen@obs.carnegiescience.edu
FU NASA through Hubble Fellowship - Space Telescope Science Institute [HST-HF-51314.01]; NASA [NAS 5-26555]; Kavli Foundation, Peking University; Chinese Academy of Science [XDB09030102]
NR 27
TC 334
Z9 359
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 SEP 11
PY 2014
VL 513
IS 7517
BP 210
EP +
DI 10.1038/nature13712
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800045
PM 25209799
DA 2026-03-09
ER

PT J
AU Meyerson, JR
   Kumar, J
   Chittori, S
   Rao, P
   Pierson, J
   Bartesaghi, A
   Mayer, ML
   Subramaniam, S
AF Meyerson, Joel R.
   Kumar, Janesh
   Chittori, Sagar
   Rao, Prashant
   Pierson, Jason
   Bartesaghi, Alberto
   Mayer, Mark L.
   Subramaniam, Sriram
TI Structural mechanism of glutamate receptor activation and desensitization
SO NATURE
LA English
DT Article
ID ligand-binding domain; ion-channel; crystal-structures; ampa; glur2; visualization; resolution; behavior; lipids; tilt
AB Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 angstrom structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating.
C1 [Meyerson, Joel R.; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Kumar, Janesh; Chittori, Sagar; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Pierson, Jason] FEI Co, Hillsboro, OR 97124 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); Thermo Fisher Scientific; FEI Company
RP Subramaniam, S (corresponding author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov; ss1@nih.gov
FU NCI; NICHD, NIH; IATAP program at NIH; NIH-FEI Living Lab for Structural Biology
NR 53
TC 189
Z9 217
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 OCT 16
PY 2014
VL 514
IS 7522
BP 328
EP +
DI 10.1038/nature13603
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600043
PM 25119039
DA 2026-03-09
ER

PT J
AU Li, J
   Hou, B
   Tumova, S
   Muraki, K
   Bruns, A
   Ludlow, MJ
   Sedo, A
   Hyman, AJ
   McKeown, L
   Young, RS
   Yuldasheva, NY
   Majeed, Y
   Wilson, LA
   Rode, B
   Bailey, MA
   Kim, HR
   Fu, ZJ
   Carter, DAL
   Bilton, J
   Imrie, H
   Ajuh, P
   Dear, TN
   Cubbon, RM
   Kearney, MT
   Prasad, KR
   Evans, PC
   Ainscough, JFX
   Beech, DJ
AF Li, Jing
   Hou, Bing
   Tumova, Sarka
   Muraki, Katsuhiko
   Bruns, Alexander
   Ludlow, Melanie J.
   Sedo, Alicia
   Hyman, Adam J.
   McKeown, Lynn
   Young, Richard S.
   Yuldasheva, Nadira Y.
   Majeed, Yasser
   Wilson, Lesley A.
   Rode, Baptiste
   Bailey, Marc A.
   Kim, Hyejeong R.
   Fu, Zhaojun
   Carter, Deborah A. L.
   Bilton, Jan
   Imrie, Helen
   Ajuh, Paul
   Dear, T. Neil
   Cubbon, Richard M.
   Kearney, Mark T.
   Prasad, K. Raj
   Evans, Paul C.
   Ainscough, Justin F. X.
   Beech, David J.
TI Piezol integration of vascular architecture with physiological force
SO NATURE
LA English
DT Article
ID activated cation channels; fluid shear-stress; endothelial-cells; proteome analysis; disturbed flow; calpain; mechanotransduction; tissue; gene; mice
AB The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic(1-5). Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact(6-8). Here we show Piezol (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezol profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezol channels as sensors of blood flow was shown by Piezol dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezol to confer sensitivity to shear stress on otherwise resistant cells. Down-stream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezol channels function as pivotal integrators in vascular biology.
C1 [Li, Jing; Hou, Bing; Tumova, Sarka; Bruns, Alexander; Ludlow, Melanie J.; Sedo, Alicia; Hyman, Adam J.; McKeown, Lynn; Young, Richard S.; Yuldasheva, Nadira Y.; Majeed, Yasser; Wilson, Lesley A.; Rode, Baptiste; Bailey, Marc A.; Fu, Zhaojun; Carter, Deborah A. L.; Bilton, Jan; Imrie, Helen; Dear, T. Neil; Cubbon, Richard M.; Kearney, Mark T.; Ainscough, Justin F. X.; Beech, David J.] Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England.
   [Li, Jing; Hou, Bing; Tumova, Sarka; Bruns, Alexander; Ludlow, Melanie J.; Sedo, Alicia; Hyman, Adam J.; McKeown, Lynn; Young, Richard S.; Yuldasheva, Nadira Y.; Majeed, Yasser; Wilson, Lesley A.; Rode, Baptiste; Bailey, Marc A.; Fu, Zhaojun; Carter, Deborah A. L.; Bilton, Jan; Imrie, Helen; Dear, T. Neil; Cubbon, Richard M.; Kearney, Mark T.; Ainscough, Justin F. X.; Beech, David J.] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds LS2 9JT, W Yorkshire, England.
   [Muraki, Katsuhiko] Aichi Gakuin Univ, Sch Pharm, Chikusa Ku, Nagoya, Aichi 4648650, Japan.
   [Prasad, K. Raj] St James Univ Hosp, Dept Hepatobiliary & Transplant Surg, Leeds LS9 7TF, W Yorkshire, England.
   [Kim, Hyejeong R.; Evans, Paul C.] Univ Sheffield, Sheffield S10 2RX, S Yorkshire, England.
   [Ajuh, Paul] Dundee Cell Prod Ltd, Dundee DD1 5JJ, Scotland.
C3 University of Leeds; University of Leeds; Aichi Gakuin University; Saint James's University Hospital; University of Sheffield
RP Beech, DJ (corresponding author), Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England.
EM d.j.beech@leeds.ac.uk
FU Wellcome Trust; Medical Research Council; Leeds Teaching Hospitals Trust Charitable Foundation; British Heart Foundation; University of Leeds; China Scholarship Council; BBSRC PhD Studentship; Cancer Research UK Clinical Fellowship; BBSRC-AstraZeneca PhD Studentship; British Heart Foundation Fellowship; MRC [G1002076, MR/L019051/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [1360947] Funding Source: researchfish; British Heart Foundation [FS/12/54/29671, FS/14/22/30734, FS/12/80/29821, RG/13/1/30042, RG/09/010/28087] Funding Source: researchfish; Medical Research Council [G1002076, MR/L019051/1] Funding Source: researchfish
NR 37
TC 924
Z9 1093
U1 5
U2 306
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 279
EP U308
DI 10.1038/nature13701
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400053
PM 25119035
DA 2026-03-09
ER

PT J
AU Fridman, O
   Goldberg, A
   Ronin, I
   Shoresh, N
   Balaban, NQ
AF Fridman, Ofer
   Goldberg, Amir
   Ronin, Irine
   Shoresh, Noam
   Balaban, Nathalie Q.
TI Optimization of lag time underlies antibiotic tolerance in evolved bacterial populations
SO NATURE
LA English
DT Article
ID escherichia-coli; persistence; ampicillin; resistance; evolution
AB The great therapeutic achievements of antibiotics have been dramatically undercut by the evolution of bacterial strategies that overcome antibiotic stress(1),(2). These strategies fall into two classes. 'Resistance' makes it possible for a microorganism to grow in the constant presence of the antibiotic, provided that the concentration of the antibiotic is not too high. 'Tolerance' allows a microorganism to survive antibiotic treatment, even at high antibiotic concentrations, as long as the duration of the treatment is limited. Although both resistance and tolerance are important reasons for the failure of antibiotic treatments(3-6), the evolution of resistance(7-9) is much better understood than that of tolerance. Here we followed the evolution of bacterial populations under intermittent exposure to the high concentrations of antibiotics used in the clinic and characterized the evolved strains in terms of both resistance and tolerance. We found that all strains adapted by specific genetic mutations, which became fixed in the evolved populations. By monitoring the phenotypic changes at the population and single-cell levels, we found that the first adaptive change to antibiotic stress was the development of tolerance through a major adjustment in the single-cell lag-time distribution, without a change in resistance. Strikingly, we found that the lag time of bacteria before regrowth was optimized to match the duration of the antibiotic-exposure interval. Whole genome sequencing of the evolved strains and restoration of the wild-type alleles allowed us to identify target genes involved in this antibiotic-driven phenotype: 'tolerance by lag' (tbl). Better understanding of lag-time evolution as a key determinant of the survival of bacterial populations under high antibiotic concentrations could lead to new approaches to impeding the evolution of antibiotic resistance.
C1 [Fridman, Ofer; Goldberg, Amir; Ronin, Irine; Balaban, Nathalie Q.] Hebrew Univ Jerusalem, Sudarsky Ctr Computat Biol, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Fridman, Ofer; Goldberg, Amir; Ronin, Irine; Balaban, Nathalie Q.] Hebrew Univ Jerusalem, Ctr NanoSci, IL-91904 Jerusalem, Israel.
   [Shoresh, Noam] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Balaban, NQ (corresponding author), Hebrew Univ Jerusalem, Sudarsky Ctr Computat Biol, Racah Inst Phys, Edmond J Safra Campus, IL-91904 Jerusalem, Israel.
EM nathalieqb@phys.huji.ac.il
FU European Research Council [260871]; Israel Science Foundation [592/10]; Levtzion Fellowship; Academy of Finland (AKA) [260871] Funding Source: Academy of Finland (AKA); European Research Council (ERC) [260871] Funding Source: European Research Council (ERC)
NR 30
TC 461
Z9 561
U1 5
U2 309
PU NATURE PUBLISHING 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 18
PY 2014
VL 513
IS 7518
BP 418
EP +
DI 10.1038/nature13469
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900060
PM 25043002
DA 2026-03-09
ER

PT J
AU Boussemart, L
   Malka-Mahieu, H
   Girault, I
   Allard, D
   Hemmingsson, O
   Tomasic, G
   Thomas, M
   Basmadjian, C
   Ribeiro, N
   Thuaud, F
   Mateus, C
   Routier, E
   Kamsu-Kom, N
   Agoussi, S
   Eggermont, AM
   Desaubry, L
   Robert, C
   Vagner, S
AF Boussemart, Lise
   Malka-Mahieu, Helene
   Girault, Isabelle
   Allard, Delphine
   Hemmingsson, Oskar
   Tomasic, Gorana
   Thomas, Marina
   Basmadjian, Christine
   Ribeiro, Nigel
   Thuaud, Frederic
   Mateus, Christina
   Routier, Emilie
   Kamsu-Kom, Nyam
   Agoussi, Sandrine
   Eggermont, Alexander M.
   Desaubry, Laurent
   Robert, Caroline
   Vagner, Stephan
TI eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies
SO NATURE
LA English
DT Article
ID translation initiation; acquired-resistance; feedback inhibition; raf; silvestrol
AB In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3) K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade(1-3). All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m(7)G) at the 59 end of messenger RNA, thereby modulating the translation of specific mRNAs(4,5). Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF(and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers.
C1 [Boussemart, Lise; Malka-Mahieu, Helene; Girault, Isabelle; Allard, Delphine; Hemmingsson, Oskar; Kamsu-Kom, Nyam; Agoussi, Sandrine; Robert, Caroline; Vagner, Stephan] Inserm UMR981, F-94805 Villejuif, France.
   [Boussemart, Lise; Malka-Mahieu, Helene; Eggermont, Alexander M.; Robert, Caroline; Vagner, Stephan] Univ Paris Sud, Univ Paris 11, F-94276 Le Kremlin Bicetre, France.
   [Boussemart, Lise; Thomas, Marina; Mateus, Christina; Routier, Emilie; Eggermont, Alexander M.; Robert, Caroline; Vagner, Stephan] Gustave Roussy, Dermatooncol, F-94805 Villejuif, France.
   [Tomasic, Gorana] Gustave Roussy, Dept Pathol, F-94805 Villejuif, France.
   [Basmadjian, Christine; Ribeiro, Nigel; Thuaud, Frederic; Desaubry, Laurent] Strasbourg Univ, CNRS, UMR7200, F-67400 Illkirch Graffenstaden, France.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; UNICANCER; Gustave Roussy; UNICANCER; Gustave Roussy; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC)
RP Robert, C (corresponding author), Inserm UMR981, F-94805 Villejuif, France.
EM caroline.robert@gustaveroussy.fr; stephan.vagner@inserm.fr
FU Institut National du CAncer (INCA); Association pour la Recherche sur le Cancer (ARC); Ligue contre le Cancer via an Integrated Research Action Program Melanoma (PAIR Melanome); Canceropole Ile de France and Ensemble Contre le Melanome; ARC; AAREC Filia Research for fellowships; Wenner-Gren Foundation; Swedish Society of Medicine
NR 21
TC 290
Z9 351
U1 1
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 SEP 4
PY 2014
VL 513
IS 7516
BP 105
EP +
DI 10.1038/nature13572
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800039
PM 25079330
DA 2026-03-09
ER

PT J
AU Chen, XP
   Cui, ZL
   Fan, MS
   Vitousek, P
   Zhao, M
   Ma, WQ
   Wang, ZL
   Zhang, WJ
   Yan, XY
   Yang, JC
   Deng, XP
   Gao, Q
   Zhang, Q
   Guo, SW
   Ren, J
   Li, SQ
   Ye, YL
   Wang, ZH
   Huang, JL
   Tang, QY
   Sun, YX
   Peng, XL
   Zhang, JW
   He, MR
   Zhu, YJ
   Xue, JQ
   Wang, GL
   Wu, L
   An, N
   Wu, LQ
   Ma, L
   Zhang, WF
   Zhang, FS
AF Chen, Xinping
   Cui, Zhenling
   Fan, Mingsheng
   Vitousek, Peter
   Zhao, Ming
   Ma, Wenqi
   Wang, Zhenlin
   Zhang, Weijian
   Yan, Xiaoyuan
   Yang, Jianchang
   Deng, Xiping
   Gao, Qiang
   Zhang, Qiang
   Guo, Shiwei
   Ren, Jun
   Li, Shiqing
   Ye, Youliang
   Wang, Zhaohui
   Huang, Jianliang
   Tang, Qiyuan
   Sun, Yixiang
   Peng, Xianlong
   Zhang, Jiwang
   He, Mingrong
   Zhu, Yunji
   Xue, Jiquan
   Wang, Guiliang
   Wu, Liang
   An, Ning
   Wu, Liangquan
   Ma, Lin
   Zhang, Weifeng
   Zhang, Fusuo
TI Producing more grain with lower environmental costs
SO NATURE
LA English
DT Article
ID greenhouse-gas emissions; yield; fertilizer; productivity; management; efficiency; nitrogen; demand; maize; wheat
AB Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs(1,2). Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment(3) show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.
C1 [Chen, Xinping; Cui, Zhenling; Fan, Mingsheng; Wang, Guiliang; Wu, Liang; An, Ning; Wu, Liangquan; Ma, Lin; Zhang, Weifeng; Zhang, Fusuo] China Agr Univ, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
   [Vitousek, Peter] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Zhao, Ming; Zhang, Weijian] Chinese Acad Agr Sci, Inst Crop Sci, Beijing 100081, Peoples R China.
   [Ma, Wenqi] Agr Univ Hebei, Coll Resources & Environm Sci, Baoding 071001, Peoples R China.
   [Wang, Zhenlin; Zhang, Jiwang; He, Mingrong] Shandong Agr Univ, Coll Agron, Tai An 271000, Shandong, Peoples R China.
   [Yan, Xiaoyuan] Chinese Acad Sci, Inst Soil Sci, Nanjing 210008, Peoples R China.
   [Yang, Jianchang] Yangzhou Univ, Key Lab Crop Genet & Physiol Jiangsu Prov, Yangzhou 225009, Peoples R China.
   [Deng, Xiping; Li, Shiqing] Northwest Agr & Forestry Univ, State Key Lab Soil Eros & Dryland Farming Loess P, Yangling 712100, Peoples R China.
   [Gao, Qiang] Jilin Agr Univ, Coll Resources & Environm Sci, Changchun 130118, Peoples R China.
   [Zhang, Qiang] Shanxi Acad Agr Sci, Inst Agr Environm & Resource, Taiyuan 030031, Peoples R China.
   [Guo, Shiwei] Nanjing Agr Univ, Coll Resources & Environm Sci, Nanjing 210095, Jiangsu, Peoples R China.
   [Ren, Jun] Jilin Acad Agr Sci, Res Ctr Agr Environm & Resources, Changchun 130033, Peoples R China.
   [Ye, Youliang; Zhu, Yunji] Henan Agr Univ, Coll Resources & Environm Sci, Zhengzhou 450000, Peoples R China.
   [Wang, Zhaohui; Xue, Jiquan] Northwest Agr & Forestry Univ, Yangling 712100, Peoples R China.
   [Huang, Jianliang] Huazhong Agr Univ, Coll Plant Sci & Technol, Wuhan 430070, Peoples R China.
   [Tang, Qiyuan] Hunan Agr Univ, Crop Physiol Ecol & Prod Ctr, Changsha 410128, Hunan, Peoples R China.
   [Sun, Yixiang] Anhui Acad Agr Sci, Soil & Fertilizer Res Inst, Hefei 230031, Peoples R China.
   [Peng, Xianlong] Northeast Agr Univ, Coll Resources & Environm Sci, Harbin 150030, Peoples R China.
C3 China Agricultural University; Stanford University; Chinese Academy of Agricultural Sciences; Institute of Crop Sciences, CAAS; Hebei Agricultural University; Shandong Agricultural University; Chinese Academy of Sciences; Nanjing Institute of Soil Science, CAS; Yangzhou University; Northwest A&F University - China; Jilin Agricultural University; Shanxi Agricultural University; Nanjing Agricultural University; Jilin Academy of Agricultural Sciences; Henan Agricultural University; Northwest A&F University - China; Huazhong Agricultural University; Hunan Agricultural University; Anhui Academy of Agricultural Sciences; Northeast Agricultural University - China
RP Zhang, FS (corresponding author), China Agr Univ, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
EM zhangfs@cau.edu.cn
FU Chinese National Basic Research Program [2009CB118600]; NSFC [31121062]; Special Fund for Agro-scientific Research in the Public Interest [201103003]
NR 38
TC 1592
Z9 1996
U1 90
U2 2961
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2014
VL 514
IS 7523
BP 486
EP +
DI 10.1038/nature13609
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900039
PM 25186728
DA 2026-03-09
ER

PT J
AU Krashes, MJ
   Shah, BP
   Madara, JC
   Olson, DP
   Strochlic, DE
   Garfield, AS
   Vong, L
   Pei, HJ
   Watabe-Uchida, M
   Uchida, N
   Liberles, SD
   Lowell, BB
AF Krashes, Michael J.
   Shah, Bhavik P.
   Madara, Joseph C.
   Olson, David P.
   Strochlic, David E.
   Garfield, Alastair S.
   Linh Vong
   Pei, Hongjuan
   Watabe-Uchida, Mitsuko
   Uchida, Naoshige
   Liberles, Stephen D.
   Lowell, Bradford B.
TI An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger
SO NATURE
LA English
DT Article
ID energy-expenditure; feeding-behavior; pomc neurons; food-intake; cell-types; npy; protein; leptin; hypothalamus; receptors
AB Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake(1-5). Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding(3,6,7). Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity(8-10). Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.
C1 [Krashes, Michael J.; Shah, Bhavik P.; Madara, Joseph C.; Olson, David P.; Garfield, Alastair S.; Linh Vong; Lowell, Bradford B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA.
   [Strochlic, David E.; Liberles, Stephen D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Strochlic, David E.; Uchida, Naoshige; Liberles, Stephen D.; Lowell, Bradford B.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
   [Garfield, Alastair S.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
   [Pei, Hongjuan] Univ Michigan, Div Pediat Endocrinol, Dept Pediat, Ann Arbor, MI 48105 USA.
   [Watabe-Uchida, Mitsuko; Uchida, Naoshige] Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; University of Edinburgh; University of Michigan System; University of Michigan; Harvard University
RP Lowell, BB (corresponding author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA.
EM blowell@bidmc.harvard.edu
FU NIH [R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, P30 DK046200, P30 DK57521, F32 DK089710, K08 DK071561, F32 DK078478, R01 MH095953]; ADA; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK046200, R01DK096010, P30DK020572, R01DK075632, R01DK089044] Funding Source: NIH RePORTER
NR 33
TC 472
Z9 579
U1 0
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 MAR 13
PY 2014
VL 507
IS 7491
BP 238
EP +
DI 10.1038/nature12956
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800040
PM 24487620
DA 2026-03-09
ER

PT J
AU Ott, C
   Kaldun, A
   Argenti, L
   Raith, P
   Meyer, K
   Laux, M
   Zhang, YZ
   Blättermann, A
   Hagstotz, S
   Ding, T
   Heck, R
   Madroñero, J
   Martín, F
   Pfeifer, T
AF Ott, Christian
   Kaldun, Andreas
   Argenti, Luca
   Raith, Philipp
   Meyer, Kristina
   Laux, Martin
   Zhang, Yizhu
   Blaettermann, Alexander
   Hagstotz, Steffen
   Ding, Thomas
   Heck, Robert
   Madronero, Javier
   Martin, Fernando
   Pfeifer, Thomas
TI Reconstruction and control of a time-dependent two-electron wave packet
SO NATURE
LA English
DT Article
ID double-excitation states; autoionizing states; ionization; absorption; helium; phase; photoionization; spectroscopy; resonances; dynamics
AB The concerted motion of two or more bound electrons governs atomic(1) and molecular(2,3) non-equilibrium processes including chemical reactions, and hence there is much interest in developing a detailed understanding of such electron dynamics in the quantum regime. However, there is no exact solution for the quantum three-body problem, and as a result even the minimal system of two active electrons and a nucleus is analytically intractable(4). This makes experimental measurements of the dynamics of two bound and correlated electrons, as found in the helium atom, an attractive prospect. However, although the motion of single active electrons and holes has been observed with attosecond time resolution(5-7), comparable experiments on two-electron motion have so far remained out of reach. Here we show that a correlated two-electron wave packet can be reconstructed from a 1.2-femtosecond quantum beat among low-lying doubly excited states in helium. The beat appears in attosecond transient-absorption spectra(5,7-9) measured with unprecedentedly high spectral resolution and in the presence of an intensity-tunable visible laser field. We tune the coupling(10-12) between the two low-lying quantum states by adjusting the visible laser intensity, and use the Fano resonance as a phase-sensitive quantum interferometer(13) to achieve coherent control of the two correlated electrons. Given the excellent agreement with large-scalequantum-mechanical calculations for the helium atom, we anticipate that multidimensional spectroscopy experiments of the type we report here will provide benchmark data for testing fundamental few-body quantum dynamics theory in more complex systems. They might also provide a route to the site-specific measurement and control of metastable electronic transition states that are at the heart of fundamental chemical reactions.
C1 [Ott, Christian; Kaldun, Andreas; Raith, Philipp; Meyer, Kristina; Laux, Martin; Zhang, Yizhu; Blaettermann, Alexander; Hagstotz, Steffen; Ding, Thomas; Heck, Robert; Pfeifer, Thomas] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Argenti, Luca; Martin, Fernando] Univ Autonoma Madrid, Dept Quim, E-28049 Madrid, Spain.
   [Madronero, Javier] Tech Univ Munich, Phys Dept, D-85747 Garching, Germany.
   [Martin, Fernando] Inst Madrileno Estudios Avanzados Nanociencia, Madrid 28049, Spain.
   [Pfeifer, Thomas] Heidelberg Univ, Ctr Quantum Dynam, D-69120 Heidelberg, Germany.
C3 Max Planck Society; Autonomous University of Madrid; Technical University of Munich; Ruprecht Karls University Heidelberg
RP Pfeifer, T (corresponding author), Max Planck Inst Kernphys, Saupfercheckweg 1, D-69117 Heidelberg, Germany.
EM fernando.martin@uam.es; thomas.pfeifer@mpi-hd.mpg.de
FU Max Planck Research Group Program of the Max Planck Gesellschaft (MPG); Deutsche Forschungsgemeinschaft [PF 790/1-1]; European COST Action [CM1204 XLIC]; European Research Council [290853 XCHEM]; Ministerio de Economia y Competitividad [FIS2010-15127, FIS2013-42002-R, ERA-Chemistry PIM2010EEC-00751]; European grant MC-ITN CORINF
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NR 38
TC 264
Z9 301
U1 1
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 DEC 18
PY 2014
VL 516
IS 7531
BP 374
EP +
DI 10.1038/nature14026
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800042
PM 25519135
DA 2026-03-09
ER

PT J
AU Miller, JA
   Ding, SL
   Sunkin, SM
   Smith, KA
   Ng, L
   Szafer, A
   Ebbert, A
   Riley, ZL
   Royall, JJ
   Aiona, K
   Arnold, JM
   Bennet, C
   Bertagnolli, D
   Brouner, K
   Butler, S
   Caldejon, S
   Carey, A
   Cuhaciyan, C
   Dalley, RA
   Dee, N
   Dolbeare, TA
   Facer, BAC
   Feng, D
   Fliss, TP
   Gee, G
   Goldy, J
   Gourley, L
   Gregor, BW
   Gu, GY
   Howard, RE
   Jochim, JM
   Kuan, CL
   Lau, C
   Lee, CK
   Lee, F
   Lemon, TA
   Lesnar, P
   McMurray, B
   Mastan, N
   Mosqueda, N
   Naluai-Cecchini, T
   Ngo, NK
   Nyhus, J
   Oldre, A
   Olson, E
   Parente, J
   Parker, PD
   Parry, SE
   Stevens, A
   Pletikos, M
   Reding, M
   Roll, K
   Sandman, D
   Sarreal, M
   Shapouri, S
   Shapovalova, NV
   Shen, EH
   Sjoquist, N
   Slaughterbeck, CR
   Smith, M
   Sodt, AJ
   Williams, D
   Zöllei, L
   Fischl, B
   Gerstein, MB
   Geschwind, DH
   Glass, IA
   Hawrylycz, MJ
   Hevner, RF
   Huang, H
   Jones, AR
   Knowles, JA
   Levitt, P
   Phillips, JW
   Sestan, N
   Wohnoutka, P
   Dang, C
   Bernard, A
   Hohmann, JG
   Lein, ES
AF Miller, Jeremy A.
   Ding, Song-Lin
   Sunkin, Susan M.
   Smith, Kimberly A.
   Ng, Lydia
   Szafer, Aaron
   Ebbert, Amanda
   Riley, Zackery L.
   Royall, Joshua J.
   Aiona, Kaylynn
   Arnold, James M.
   Bennet, Crissa
   Bertagnolli, Darren
   Brouner, Krissy
   Butler, Stephanie
   Caldejon, Shiella
   Carey, Anita
   Cuhaciyan, Christine
   Dalley, Rachel A.
   Dee, Nick
   Dolbeare, Tim A.
   Facer, Benjamin A. C.
   Feng, David
   Fliss, Tim P.
   Gee, Garrett
   Goldy, Jeff
   Gourley, Lindsey
   Gregor, Benjamin W.
   Gu, Guangyu
   Howard, Robert E.
   Jochim, Jayson M.
   Kuan, Chihchau L.
   Lau, Christopher
   Lee, Chang-Kyu
   Lee, Felix
   Lemon, Tracy A.
   Lesnar, Phil
   McMurray, Bergen
   Mastan, Naveed
   Mosqueda, Nerick
   Naluai-Cecchini, Theresa
   Ngo, Nhan-Kiet
   Nyhus, Julie
   Oldre, Aaron
   Olson, Eric
   Parente, Jody
   Parker, Patrick D.
   Parry, Sheana E.
   Stevens, Allison
   Pletikos, Mihovil
   Reding, Melissa
   Roll, Kate
   Sandman, David
   Sarreal, Melaine
   Shapouri, Sheila
   Shapovalova, Nadiya V.
   Shen, Elaine H.
   Sjoquist, Nathan
   Slaughterbeck, Clifford R.
   Smith, Michael
   Sodt, Andy J.
   Williams, Derric
   Zoellei, Lilla
   Fischl, Bruce
   Gerstein, Mark B.
   Geschwind, Daniel H.
   Glass, Ian A.
   Hawrylycz, Michael J.
   Hevner, Robert F.
   Huang, Hao
   Jones, Allan R.
   Knowles, James A.
   Levitt, Pat
   Phillips, John W.
   Sestan, Nenad
   Wohnoutka, Paul
   Dang, Chinh
   Bernard, Amy
   Hohmann, John G.
   Lein, Ed S.
TI Transcriptional landscape of the prenatal human brain
SO NATURE
LA English
DT Article
ID outer subventricular zone; radial glial-cells; cerebral-cortex; gene-expression; messenger-rna; neurons; networks; subplate; connections; astrocytes
AB The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging(MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.
C1 [Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Royall, Joshua J.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Hawrylycz, Michael J.; Jones, Allan R.; Phillips, John W.; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
   [Naluai-Cecchini, Theresa; Glass, Ian A.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA.
   [Stevens, Allison; Zoellei, Lilla; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA.
   [Stevens, Allison; Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA.
   [Pletikos, Mihovil; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
   [Pletikos, Mihovil; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
   [Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Hevner, Robert F.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 USA.
   [Hevner, Robert F.] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98105 USA.
   [Huang, Hao] UT Southwestern Med Ctr, Adv Imaging Res Ctr, Dallas, TX 75390 USA.
   [Knowles, James A.] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
   [Knowles, James A.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90033 USA.
   [Levitt, Pat] Childrens Hosp, Dept Pediat, Los Angeles, CA 90027 USA.
   [Levitt, Pat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
C3 Allen Institute for Brain Science; University of Washington; University of Washington Seattle; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Yale University; Yale University; Yale University; Yale University; 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; Seattle Children's Hospital; University of Washington; University of Washington Seattle; University of Texas System; University of Texas Southwestern Medical Center; University of Southern California; University of Southern California; Children's Hospital Los Angeles; University of Southern California
RP Lein, ES (corresponding author), Allen Inst Brain Sci, Seattle, WA 98103 USA.
EM edl@alleninstitute.org
FU National Institutes of Health (NIH) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [5R24HD0008836]; National Institute of Mental Health [RC2MH089921]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Institute of Allergy and Infectious Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Mental Health [R24HD000836] Funding Source: NIH RePORTER
NR 64
TC 955
Z9 1066
U1 0
U2 179
PU NATURE PUBLISHING 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 10
PY 2014
VL 508
IS 7495
BP 199
EP +
DI 10.1038/nature13185
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900036
PM 24695229
DA 2026-03-09
ER

PT J
AU Buchhave, LA
   Bizzarro, M
   Latham, DW
   Sasselov, D
   Cochran, WD
   Endl, M
   Isaacson, H
   Juncher, D
   Marcy, GW
AF Buchhave, Lars A.
   Bizzarro, Martin
   Latham, David W.
   Sasselov, Dimitar
   Cochran, William D.
   Endl, Michael
   Isaacson, Howard
   Juncher, Diana
   Marcy, Geoffrey W.
TI Three regimes of extrasolar planet radius inferred from host star metallicities
SO NATURE
LA English
DT Article
ID kepler planets; mass planets; migration; parameters; exoplanets; range
AB Approximately half of the extrasolar planets (exoplanets) with radii less than four Earth radii are in orbits with short periods(1). Despite their sheer abundance, the compositions of such planets are largely unknown. The available evidence suggests that they range in composition from small, high-density rocky planets to low-density planets consisting of rocky cores surrounded by thick hydrogen and helium gas envelopes. Here we report the metallicities (that is, the abundances of elements heavier than hydrogen and helium) of more than 400 stars hosting 600 exoplanet candidates, and find that the exoplanets can be categorized into three populations defined by statistically distinct (similar to 4.5 sigma) metallicity regions. We interpret these regions as reflecting the formation regimes of terrestrial-like planets (radii less than 1.7 Earth radii), gas dwarf planets with rocky cores and hydrogen-helium envelopes (radii between 1.7 and 3.9 Earth radii) and ice or gas giant planets (radii greater than 3.9 Earth radii). These transitions correspond well with those inferred from dynamical mass estimates(2,3), implying that host star metallicity, which is a proxy for the initial solids inventory of the protoplanetary disk, is a key ingredient regulating the structure of planetary systems.
C1 [Buchhave, Lars A.; Latham, David W.; Sasselov, Dimitar] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Buchhave, Lars A.; Bizzarro, Martin; Juncher, Diana] Univ Copenhagen, Nat Hist Museum Denmark, Ctr Star & Planet Format, DK-1350 Copenhagen, Denmark.
   [Cochran, William D.; Endl, Michael] Univ Texas Austin, McDonald Observ, Austin, TX 78712 USA.
   [Isaacson, Howard; Marcy, Geoffrey W.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Juncher, Diana] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
C3 Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; University of Copenhagen; University of Texas System; University of Texas Austin; University of California System; University of California Berkeley; University of Copenhagen; Niels Bohr Institute
RP Buchhave, LA (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM lbuchhave@cfa.harvard.edu
FU Harvard Origins of Life Initiative; Danish National Research Foundation [DNRF97]; European Research Council [616027- STARDUST2ASTEROIDS]; Kepler Mission under NASA [NCC2-1390, NNX11AB99A, NNX13AB58A]; Smithsonian Astrophysical Observatory
CR Batalha NM, 2013, ASTROPHYS J SUPPL S, V204, P0, DOI 10.1088/0067-0049/204/2/24
   Batalha NM, 2011, ASTROPHYS J, V729, P0, DOI 10.1088/0004-637X/729/1/27
   Buchhave LA, 2012, NATURE, V486, P375, DOI 10.1038/nature11121
   Chiang E, 2013, MON NOT R ASTRON SOC, V431, P3444, DOI 10.1093/mnras/stt424
   Everett ME, 2013, ASTROPHYS J, V771, P0, DOI 10.1088/0004-637X/771/2/107
   Fischer DA, 2005, ASTROPHYS J, V622, P1102, DOI 10.1086/428383
   Fressin F, 2013, ASTROPHYS J, V766, P0, DOI 10.1088/0004-637X/766/2/81
   Ghezzi L, 2010, ASTROPHYS J, V720, P1290, DOI 10.1088/0004-637X/720/2/1290
   GOLDREICH P, 1979, ASTROPHYS J, V233, P857, DOI 10.1086/157448
   Gonzalez G, 1997, MON NOT R ASTRON SOC, V285, P403, DOI 10.1093/mnras/285.2.403
   Hansen BMS, 2013, ASTROPHYS J, V775, P0, DOI 10.1088/0004-637X/775/1/53
   Hansen BMS, 2012, ASTROPHYS J, V751, P0, DOI 10.1088/0004-637X/751/2/158
   Ida S, 2004, ASTROPHYS J, V616, P567, DOI 10.1086/424830
   Lin DNC, 1996, NATURE, V380, P606, DOI 10.1038/380606a0
   Lissauer JJ, 2013, ASTROPHYS J, V770, P0, DOI 10.1088/0004-637X/770/2/131
   Lissauer JJ, 2011, ASTROPHYS J SUPPL S, V197, P0, DOI 10.1088/0067-0049/197/1/8
   Lopez ED, 2013, UNDERSTANDING MASS R, V0, P0
   Marcy GW, 2014, ASTROPHYS J SUPPL S, V210, P0, DOI 10.1088/0067-0049/210/2/20
   McNeil DS, 2010, MON NOT R ASTRON SOC, V401, P1691, DOI 10.1111/j.1365-2966.2009.15805.x
   Owen JE, 2013, ASTROPHYS J, V775, P0, DOI 10.1088/0004-637X/775/2/105
   Papaloizou JCB, 1999, ASTROPHYS J, V521, P823, DOI 10.1086/307581
   Rafikov RR, 2006, ASTROPHYS J, V648, P666, DOI 10.1086/505695
   Raymond SN, 2014, NO UNIVERSAL MINIMUM, V0, P0
   Santos NC, 2000, ASTRON ASTROPHYS, V363, P228
   Sousa SG, 2008, ASTRON ASTROPHYS, V487, P373, DOI 10.1051/0004-6361:200809698
   Sousa SG, 2011, ASTRON ASTROPHYS, V533, P0, DOI 10.1051/0004-6361/201117699
   Terquem C, 2007, ASTROPHYS J, V654, P1110, DOI 10.1086/509497
   Weiss LM, 2014, ASTROPHYS J LETT, V783, P0, DOI 10.1088/2041-8205/783/1/L6
   Yi S, 2001, ASTROPHYS J SUPPL S, V136, P417, DOI 10.1086/321795
NR 29
TC 257
Z9 287
U1 0
U2 20
PU NATURE PUBLISHING 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 29
PY 2014
VL 509
IS 7502
BP 593
EP +
DI 10.1038/nature13254
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100043
PM 24870544
DA 2026-03-09
ER

PT J
AU Sebastian, SE
   Harrison, N
   Balakirev, FF
   Altarawneh, MM
   Goddard, PA
   Liang, RX
   Bonn, DA
   Hardy, WN
   Lonzarich, GG
AF Sebastian, Suchitra E.
   Harrison, N.
   Balakirev, F. F.
   Altarawneh, M. M.
   Goddard, P. A.
   Liang, Ruixing
   Bonn, D. A.
   Hardy, W. N.
   Lonzarich, G. G.
TI Normal-state nodal electronic structure in underdoped high-Tc copper oxides
SO NATURE
LA English
DT Article
ID quantum oscillations; fermi-surface; magnetic breakdown; density-wave; pseudogap; order; superconductivity; magnetoresistance; interference; fluctuations
AB An outstanding problem in the field of high-transition-temperature (high-T-c) superconductivity is the identification of the normal state out of which superconductivity emerges in the mysterious underdoped regime(1). The normal state uncomplicated by thermal fluctuations can be studied using applied magnetic fields that are sufficiently strong to suppress long-range superconductivity at low temperatures(2,3). Proposals in which the normal ground state is characterized by small Fermi surface pockets that exist in the absence of symmetry breaking(1,4-8) have been superseded by models based on the existence of a superlattice that breaks the translational symmetry of the underlying lattice(7-15). Recently, a charge superlattice model that positions a small electron-like Fermi pocket in the vicinity of the nodes (where the superconducting gap is minimum)(8,9,16,17) has been proposed as a replacement for the prevalent superlatticemodels(10-14) that position the Fermi pocket in the vicinity of the pseudogap at the antinodes (where the superconducting gap is maximum)(18). Although some ingredients of symmetry breaking have been recently revealed by crystallographic studies, their relevance to the electronic structure remains unresolved(19-21). Here we report angle-resolved quantum oscillation measurements in the underdoped copper oxide YBa2Cu3O6+x. These measurements reveal a normal ground state comprising electron-like Fermi surface pockets located in the vicinity of the nodes, and also point to an underlying superlattice structure of low frequency and long wavelength with features in common with the charge order identified recently by complementary spectroscopic techniques(14,19-22).
C1 [Sebastian, Suchitra E.; Lonzarich, G. G.] Univ Cambridge, Cavendish Lab, Cambridge CB3 OHE, England.
   [Harrison, N.; Balakirev, F. F.; Altarawneh, M. M.] Los Alamos Natl Lab, Natl High Magnet Field Lab, Los Alamos, NM 87504 USA.
   [Altarawneh, M. M.] Mutah Univ, Dept Phys, Mutah 61710, Karak, Jordan.
   [Goddard, P. A.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Liang, Ruixing; Bonn, D. A.; Hardy, W. N.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z4, Canada.
   [Liang, Ruixing; Bonn, D. A.; Hardy, W. N.] Canadian Inst Adv Res, Quantum Mat Program, Toronto, ON M5G 1Z8, Canada.
C3 University of Cambridge; United States Department of Energy (DOE); Los Alamos National Laboratory; Mutah University; University of Warwick; University of British Columbia; Canadian Institute for Advanced Research (CIFAR)
RP Sebastian, SE (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 OHE, England.
EM suchitra@phy.cam.ac.uk; nharrison@lanl.gov
FU Royal Society, King's College Cambridge; Winton Programme for the Physics of Sustainability; European Research Council under the European Union [337425-SUPERCONDUCTINGMOTT]; Engineering and Physical Sciences Research Council (EPSRC) grant [EP/K012894/1]; EPSRC; Canadian Institute for Advanced Research; Natural Science and Engineering Research Council; NSF [DMR-0654118]; state of Florida; DOE; EPSRC [EP/H00324X/2, EP/H00324X/1, EP/K012894/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/K012894/1, EP/H00324X/2, EP/H00324X/1] Funding Source: researchfish
NR 107
TC 81
Z9 92
U1 6
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 JUL 3
PY 2014
VL 511
IS 7507
BP 61
EP U378
DI 10.1038/nature13326
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400035
PM 24930767
DA 2026-03-09
ER

PT J
AU Obri, A
   Ouararhni, K
   Papin, C
   Diebold, ML
   Padmanabhan, K
   Marek, M
   Stoll, I
   Roy, L
   Reilly, PT
   Mak, TW
   Dimitrov, S
   Romier, C
   Hamiche, A
AF Obri, Arnaud
   Ouararhni, Khalid
   Papin, Christophe
   Diebold, Marie-Laure
   Padmanabhan, Kiran
   Marek, Martin
   Stoll, Isabelle
   Roy, Ludovic
   Reilly, Patrick T.
   Mak, Tak W.
   Dimitrov, Stefan
   Romier, Christophe
   Hamiche, Ali
TI ANP32E is a histone chaperone that removes H2A.Z from chromatin
SO NATURE
LA English
DT Article
ID nucleosome core particle; variant h2a.z; crystal-structure; dna methylation; complex; protein; model; acetyltransferase; purification; deposition
AB H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 angstrom resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.
C1 [Obri, Arnaud; Ouararhni, Khalid; Papin, Christophe; Stoll, Isabelle; Roy, Ludovic; Hamiche, Ali] Univ Strasbourg, CNRS, INSERM, Dept Genom Fonct & Canc,IGBMC, F-67404 Illkirch Graffenstaden, France.
   [Diebold, Marie-Laure; Marek, Martin; Romier, Christophe] Univ Strasbourg, CNRS, INSERM, Dept Biol Struct Integrat,IGBMC, F-67404 Illkirch Graffenstaden, France.
   [Padmanabhan, Kiran; Dimitrov, Stefan] Univ Grenoble 1, INSERM, U823, Equipe Labelisee Ligue Canc,Inst Albert Bonniot, F-38042 Grenoble 9, France.
   [Reilly, Patrick T.; Mak, Tak W.] Natl Canc Ctr, Div Cellular & Mol Res, Lab Inflammat Biol, Singapore, Singapore.
   [Mak, Tak W.] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada.
C3 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); 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; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut National de la Sante et de la Recherche Medicale (Inserm); National Cancer Centre Singapore (NCCS); University of Toronto; University Health Network Toronto
RP Hamiche, A (corresponding author), Univ Strasbourg, CNRS, INSERM, Dept Genom Fonct & Canc,IGBMC, 1 Rue Laurent Fries,bp 10142, F-67404 Illkirch Graffenstaden, France.
EM dimitrov@ujf-grenoble.fr; romier@igbmc.fr; hamiche@igbmc.fr
FU CNRS; INSERM; Universite de Strasbourg; INCa [INCa_4496, INCa_4454]; ANR (VariZome) [ANR-12-BSV8-0018-01]; ANR (Nucleoplat) [NT09_476241]; Association pour la Recherche sur le Cancer; La Fondation pour la Recherche Medicale; La Ligue Nationale contre le Cancer (Equipe labellisee); French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01]; Instruct (ESFRI); Ligue Nationale contre le Cancer; Agence Nationale de la Recherche (ANR) [ANR-12-BSV8-0018] Funding Source: Agence Nationale de la Recherche (ANR)
NR 64
TC 210
Z9 266
U1 0
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 JAN 30
PY 2014
VL 505
IS 7485
BP 648
EP +
DI 10.1038/nature12922
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000033
PM 24463511
DA 2026-03-09
ER

PT J
AU Mony, BM
   MacGregor, P
   Ivens, A
   Rojas, F
   Cowton, A
   Young, J
   Horn, D
   Matthews, K
AF Mony, Binny M.
   MacGregor, Paula
   Ivens, Alasdair
   Rojas, Federico
   Cowton, Andrew
   Young, Julie
   Horn, David
   Matthews, Keith
TI Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei
SO NATURE
LA English
DT Article
ID protein-kinase; cell-cycle; stage differentiation; african trypanosm; life-cycle; expression; virulence; malaria; forms; transmission
AB The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy' forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission(1). This response is triggered by an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP(pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target sequencing identified cohorts of genes implicated in each step of the signalling pathway, from purine metabolism, through signal transducers (kinases, phosphatases) to gene expression regulators. Genes at each step were independently validated in cells naturally capable of stumpy formation, confirming their role in density sensing in vivo. The putative RNA-binding protein, RBP7, was required for normal quorum sensing and promoted cell-cycle arrest and transmission competence when overexpressed. This study reveals that quorum sensing signalling in trypanosomes shares similarities to fundamental quiescence pathways in eukaryotic cells, its components providing targets for quorum-sensing interference-based therapeutics.
C1 [Mony, Binny M.; MacGregor, Paula; Ivens, Alasdair; Rojas, Federico; Cowton, Andrew; Young, Julie; Matthews, Keith] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Horn, David] Univ Dundee, Coll Life Sci, Dundee DD1 5EH, Scotland.
C3 University of Edinburgh; University of Dundee
RP Matthews, K (corresponding author), Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
EM keith.matthews@ed.ac.uk
FU Wellcome Trust [088293MA, 095831MA, 100320/Z/12/Z]; BBSRC [BB/I004602/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/I004602/1] Funding Source: researchfish; Wellcome Trust [100320/Z/12/Z] Funding Source: researchfish
NR 41
TC 167
Z9 192
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 JAN 30
PY 2014
VL 505
IS 7485
BP 681
EP +
DI 10.1038/nature12864
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000041
PM 24336212
DA 2026-03-09
ER

PT J
AU Kim, JS
   Greene, MJ
   Zlateski, A
   Lee, K
   Richardson, M
   Turaga, SC
   Purcaro, M
   Balkam, M
   Robinson, A
   Behabadi, BF
   Campos, M
   Denk, W
   Seung, HS
AF Kim, Jinseop S.
   Greene, Matthew J.
   Zlateski, Aleksandar
   Lee, Kisuk
   Richardson, Mark
   Turaga, Srinivas C.
   Purcaro, Michael
   Balkam, Matthew
   Robinson, Amy
   Behabadi, Bardia F.
   Campos, Michael
   Denk, Winfried
   Seung, H. Sebastian
TI Space-time wiring specificity supports direction selectivity in the retina
SO NATURE
LA English
DT Article
ID bipolar cells; dendrites; mechanism; circuit; models; map
AB How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.
C1 [Kim, Jinseop S.; Greene, Matthew J.; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Seung, H. Sebastian] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Zlateski, Aleksandar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Behabadi, Bardia F.; Campos, Michael] Qualcomm Res, San Diego, CA 92121 USA.
   [Denk, Winfried] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Qualcomm; Max Planck Society
RP Seung, HS (corresponding author), Princeton Neurosci Inst, Princeton, NJ 08544 USA.
EM sseung@princeton.edu
FU Gatsby Charitable Foundation; Howard Hughes Medical Institute; Human Frontier Science Program; National Institutes of Health; Samsung Scholarship; AWS Research Grants Program gave EyeWire global reach through Amazon Cloudfront
NR 46
TC 327
Z9 397
U1 0
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 MAY 15
PY 2014
VL 509
IS 7500
BP 331
EP +
DI 10.1038/nature13240
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200032
PM 24805243
DA 2026-03-09
ER

PT J
AU Althoff, T
   Hibbs, RE
   Banerjee, S
   Gouaux, E
AF Althoff, Thorsten
   Hibbs, Ryan E.
   Banerjee, Surajit
   Gouaux, Eric
TI X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors
SO NATURE
LA English
DT Article
ID gated ion-channel; nicotinic acetylcholine-receptor; coupling agonist binding; m2 domain; pharmacology; antagonists; permeation; complexes
AB Cys-loop receptors are neurotransmitter-gated ion channels that are essential mediators of fast chemical neurotransmission and are associated with a large number of neurological diseases and disorders, as well as parasitic infections(1-4). Members of this ion channel superfamily mediate excitatory or inhibitory neurotransmission depending on their ligand and ion selectivity. Structural information for Cys-loop receptors comes from several sources including electron microscopic studies of the nicotinic acetylcholine receptor(5), high-resolution X-ray structures of extracellular domains(6) and X-ray structures of bacterial orthologues(7-10). In 2011 our group published structures of the Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in complex with the allosteric partial agonist ivermectin, which provided insights into the structure of a possibly open state of a eukaryotic Cys-loop receptor, the basis for anion selectivity and channel block, and the mechanism by which ivermectin and related molecules stabilize the open state and potentiate neurotransmitter binding(11). However, there remain unanswered questions about the mechanism of channel opening and closing, the location and nature of the shut ion channel gate, the transitions between the closed/resting, open/activated and closed/desensitized states, and the mechanism by which conformational changes are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane, ion channel domain. Here we present two conformationally distinct structures of C. elegans GluCl in the absence of ivermectin. Structural comparisons reveal a quaternary activation mechanism arising from rigid-body movements between the extracellular and transmembrane domains and a mechanism for modulation of the receptor by phospholipids.
C1 [Althoff, Thorsten; Hibbs, Ryan E.; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Banerjee, Surajit] Cornell Univ, NE CAT, Argonne, IL 60439 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Cornell University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU Deutsche Forschungsgemeinschaft [AL 1725-1/1]; NIH National Research Service Award [F32NS061404]; NIH; Howard Hughes Medical Institute
NR 46
TC 209
Z9 240
U1 0
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 AUG 21
PY 2014
VL 512
IS 7514
BP 333
EP +
DI 10.1038/nature13669
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200040
PM 25143115
DA 2026-03-09
ER

PT J
AU Ariey, F
   Witkowski, B
   Amaratunga, C
   Beghain, J
   Langlois, AC
   Khim, N
   Kim, S
   Duru, V
   Bouchier, C
   Ma, L
   Lim, P
   Leang, R
   Duong, S
   Sreng, S
   Suon, S
   Chuor, CM
   Bout, DM
   Ménard, S
   Rogers, WO
   Genton, B
   Fandeur, T
   Miotto, O
   Ringwald, P
   Le Bras, J
   Berry, A
   Barale, JC
   Fairhurst, RM
   Benoit-Vical, F
   Mercereau-Puijalon, O
   Ménard, D
AF Ariey, Frederic
   Witkowski, Benoit
   Amaratunga, Chanaki
   Beghain, Johann
   Langlois, Anne-Claire
   Khim, Nimol
   Kim, Saorin
   Duru, Valentine
   Bouchier, Christiane
   Ma, Laurence
   Lim, Pharath
   Leang, Rithea
   Duong, Socheat
   Sreng, Sokunthea
   Suon, Seila
   Chuor, Char Meng
   Bout, Denis Mey
   Menard, Sandie
   Rogers, William O.
   Genton, Blaise
   Fandeur, Thierry
   Miotto, Olivo
   Ringwald, Pascal
   Le Bras, Jacques
   Berry, Antoine
   Barale, Jean-Christophe
   Fairhurst, Rick M.
   Benoit-Vical, Franoise
   Mercereau-Puijalon, Odile
   Menard, Didier
TI A molecular marker of artemisinin-resistant Plasmodium falciparum malaria
SO NATURE
LA English
DT Article
ID kelch-repeat superfamily; in-vitro; parasite clearance; chloroquine resistance; antimalarial-drugs; point mutations; susceptibility; disruption; mefloquine; artesunate
AB Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.
C1 [Ariey, Frederic; Beghain, Johann; Langlois, Anne-Claire; Fandeur, Thierry; Barale, Jean-Christophe; Mercereau-Puijalon, Odile] Inst Pasteur, Parasite Mol Immunol Unit, F-75724 Paris 15, France.
   [Ariey, Frederic; Beghain, Johann; Langlois, Anne-Claire; Barale, Jean-Christophe; Mercereau-Puijalon, Odile] CNRS, URA 2581, F-75724 Paris 15, France.
   [Witkowski, Benoit; Khim, Nimol; Kim, Saorin; Duru, Valentine; Lim, Pharath; Fandeur, Thierry; Menard, Didier] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia.
   [Amaratunga, Chanaki; Lim, Pharath; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Bouchier, Christiane; Ma, Laurence] Inst Pasteur, Dept Genomes & Genet, F-75724 Paris 15, France.
   [Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
   [Bout, Denis Mey] Natl Ctr Parasitol Entomol & Malaria Control, SSA WHO, Phnom Penh, Cambodia.
   [Menard, Sandie; Berry, Antoine] Ctr Hosp Univ Toulouse, Serv Parasitol & Mycol, F-31059 Toulouse 9, France.
   [Rogers, William O.] Naval Med Res Unit 2 Detachment, Phnom Penh, Cambodia.
   [Genton, Blaise] Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland.
   [Miotto, Olivo] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford OX3 7BN, England.
   [Miotto, Olivo] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand.
   [Miotto, Olivo] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Ringwald, Pascal] WHO, Global Malaria Program, CH-1211 Geneva, Switzerland.
   [Le Bras, Jacques] CHU Bichat Claude Bernard, APHP, PRES Sorbonne Paris Cite, Ctr Natl Reference Paludisme, F-75018 Paris, France.
   [Benoit-Vical, Franoise] CNRS, Lab Chim Coordinat, UPR8241, F-31077 Toulouse 4, France.
   [Benoit-Vical, Franoise] Univ Toulouse, UPS, Inst Natl Polytech Toulouse, F-31077 Toulouse 4, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Institut Pasteur Cambodia; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; National Center Parasitology, Entomology & Malaria Control; National Center Parasitology, Entomology & Malaria Control; CHU de Toulouse; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Swiss School of Public Health (SSPH+); University of Basel; Swiss Tropical & Public Health Institute; University of Oxford; Mahidol University; Mahidol Oxford Tropical Medicine Research Unit (MORU); Wellcome Trust Sanger Institute; World Health Organization; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Ambroise-Pare - APHP; Universite Paris Cite; Hopital Universitaire Hotel-Dieu - APHP; Hopital Universitaire Bichat-Claude Bernard - APHP; Centre National de la Recherche Scientifique (CNRS); Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite de Toulouse; Institut National Polytechnique de Toulouse; Universite Toulouse III - Paul Sabatier
RP Ariey, F (corresponding author), Inst Pasteur, Genet & Genom Insect Vectors Unit, F-75724 Paris 15, France.
EM frederic.ariey@pasteur.fr; rfairhurst@niaid.nih.gov; Francoise.Vical@inserm.fr; odile.puijalon@pasteur.fr; dmenard@pasteur-kh.org
FU Global Fund Grant Malaria Program [CAM-607-G10M-CNM3, CAM-S10-G14-M]; Bill and Melinda Gates Foundation; USAID (through the World Health Organization); US DOD Global Epidemic Information System; Intramural Research Program, NIAID, NIH; Banque Natixis; Laboratoire d'Excellence IBEID (Agence Nationale de la Recherche, France); Institut Pasteur, Division International [ACIP A-10-2010]; Institut Pasteur, Division International; French Ministry of Foreign Affairs; Wellcome Trust [098051, 090770/Z/09/Z]; MRC [G0600718]; Rotary Club-Versailles; MRC [G0600718] Funding Source: UKRI; Medical Research Council [G0600718] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [ZIAAI001066] Funding Source: NIH RePORTER
NR 62
TC 1550
Z9 1823
U1 3
U2 607
PU NATURE PUBLISHING 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 2
PY 2014
VL 505
IS 7481
BP 50
EP +
DI 10.1038/nature12876
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300021
PM 24352242
DA 2026-03-09
ER

PT J
AU Galeazzi, M
   Chiao, M
   Collier, MR
   Cravens, T
   Koutroumpa, D
   Kuntz, KD
   Lallement, R
   Lepri, ST
   McCammon, D
   Morgan, K
   Porter, FS
   Robertson, IP
   Snowden, SL
   Thomas, NE
   Uprety, Y
   Ursino, E
   Walsh, BM
AF Galeazzi, M.
   Chiao, M.
   Collier, M. R.
   Cravens, T.
   Koutroumpa, D.
   Kuntz, K. D.
   Lallement, R.
   Lepri, S. T.
   McCammon, D.
   Morgan, K.
   Porter, F. S.
   Robertson, I. P.
   Snowden, S. L.
   Thomas, N. E.
   Uprety, Y.
   Ursino, E.
   Walsh, B. M.
TI The origin of the local 1/4-keV X-ray flux in both charge exchange and a hot bubble
SO NATURE
LA English
DT Article
ID solar-wind; background flux; emission; gas; inferences; model
AB The solar neighbourhood is the closest and most easily studied sample of the Galactic interstellar medium, an understanding of which is essential for models of star formation and galaxy evolution. Observations of an unexpectedly intense diffuse flux of easily absorbed 1/4-kiloelectronvolt X-rays(1,2), coupled with the discovery that interstellar space within about a hundred parsecs of the Sun is almost completely devoid of cool absorbing gas(3), led to a picture of a 'local cavity' filled with X-ray-emitting hot gas, dubbed the local hot bubble(4-6). This model was recently challenged by suggestions that the emission could instead be readily produced within the Solar System by heavy solar-wind ions exchanging electrons with neutral H and He in interplanetary space(7-11), potentially removing the major piece of evidence for the local existence of million-degree gas within the Galactic disk(12-15). Here we report observations showing that the total solar-wind charge-exchange contribution is approximately 40 per cent of the 1/4-keV flux in the Galactic plane. The fact that the measured flux is not dominated by charge exchange supports the notion of a million-degree hot bubble extending about a hundred parsecs from the Sun.
C1 [Galeazzi, M.; Uprety, Y.; Ursino, E.] Univ Miami, Dept Phys, Coral Gables, FL 33124 USA.
   [Chiao, M.; Collier, M. R.; Porter, F. S.; Snowden, S. L.; Thomas, N. E.; Walsh, B. M.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Cravens, T.; Robertson, I. P.] Univ Kansas, Dept Phys & Astron, Lawrence, KS 66045 USA.
   [Koutroumpa, D.] Univ Paris 06, Sorbonne Univ, Univ Versailles St Quentin, CNRS,INSU,LATMOS IPSL, F-78280 Guyancourt, France.
   [Kuntz, K. D.] Johns Hopkins Univ, Henry A Rowland Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Lallement, R.] Univ Paris Diderot, GEPI Observ Paris, CNRS, UMR 8111, F-92190 Meudon, France.
   [Lepri, S. T.] Univ Michigan, Dept Atmospher Ocean & Space Sci, Ann Arbor, MI 48109 USA.
   [McCammon, D.; Morgan, K.] Univ Wisconsin, Dept Phys, Madison, WI 53706 USA.
C3 University of Miami; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Kansas; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Universite Paris Saclay; Johns Hopkins University; Universite PSL; Observatoire de Paris; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Michigan System; University of Michigan; University of Wisconsin System; University of Wisconsin Madison
RP Galeazzi, M (corresponding author), Univ Miami, Dept Phys, Coral Gables, FL 33124 USA.
EM galeazzi@physics.miami.edu
FU NASA [NNX11AF04G, NNX09AF09G]; French space agency CNES; National Program 'Physique Chimie du Milieu Interstellaire' of the Institut National des Sciences de l'Univers (INSU); NASA [118553, NNX09AF09G, NNX11AF04G, 147463] Funding Source: Federal RePORTER
NR 24
TC 71
Z9 78
U1 0
U2 12
PU NATURE PUBLISHING 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 14
PY 2014
VL 512
IS 7513
BP 171
EP +
DI 10.1038/nature13525
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700026
PM 25079321
DA 2026-03-09
ER

PT J
AU Naganuma, M
   Sekine, S
   Chong, YE
   Guo, M
   Yang, XL
   Gamper, H
   Hou, YM
   Schimmel, P
   Yokoyama, S
AF Naganuma, Masahiro
   Sekine, Shun-ichi
   Chong, Yeeting Esther
   Guo, Min
   Yang, Xiang-Lei
   Gamper, Howard
   Hou, Ya-Ming
   Schimmel, Paul
   Yokoyama, Shigeyuki
TI The selective tRNA aminoacylation mechanism based on a single G•U pair
SO NATURE
LA English
DT Article
ID crystal-structure; acceptor-stem; major determinant; synthetase; recognition; identity; trna(ala); sequence; crystallography; specificity
AB Ligation of tRNAs with their cognate amino acids, by aminoacyl-tRNA synthetases, establishes the genetic code. Throughout evolution, tRNA(Ala) selection by alanyl-tRNAsynthetase (AlaRS) has depended predominantly on a single wobble base pair in the acceptor stem, G3 center dot U70, mainly on the k(cat) level. Here we report the crystal structures of an archaeal AlaRS in complex with tRNAAla with G3 center dot U70 and its A3 center dot U70 variant. AlaRS interacts with both the minor-and the major-groove sides of G3 center dot U70, widening the major groove. The geometry difference between G3 center dot U70 and A3 center dot U70 is transmitted along the acceptor stemto the 3'-CCA region. Thus, the 3'-CCA region of tRNA(Ala) with G3 center dot U70 is oriented to the reactive route that reaches the active site, whereas that of the A3 center dot U70 variant is folded back into the non-reactive route. This novel mechanism enables the single wobble pair to dominantly determine the specificity of tRNA selection, by an approximate 100-fold difference in k(cat) .
C1 [Naganuma, Masahiro; Sekine, Shun-ichi; Yokoyama, Shigeyuki] RIKEN Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Naganuma, Masahiro; Sekine, Shun-ichi; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem & Lab Struct Biol, Bunkyo Ku, Tokyo 1130033, Japan.
   [Naganuma, Masahiro; Yokoyama, Shigeyuki] RIKEN Struct Biol Lab, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Sekine, Shun-ichi] RIKEN Ctr Life Sci Technol, Div Struct & Synthet Biol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Chong, Yeeting Esther; Guo, Min; Yang, Xiang-Lei; Schimmel, Paul] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Chong, Yeeting Esther; Guo, Min; Yang, Xiang-Lei; Schimmel, Paul] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
   [Gamper, Howard; Hou, Ya-Ming] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
   [Schimmel, Paul] Scripps Florida Res Inst, Jupiter, FL 33458 USA.
C3 RIKEN; University of Tokyo; RIKEN; RIKEN; Scripps Research Institute; Scripps Research Institute; Thomas Jefferson University; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
RP Yokoyama, S (corresponding author), RIKEN Syst & Struct Biol Ctr, Tsurumi Ku, 1-7-22 Suehiro cho, Yokohama, Kanagawa 2300045, Japan.
EM yokoyama@riken.jp
FU Targeted Proteins Research Program; Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; Japan Society for the Promotion of Science [20247008]; MEXT; Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from MEXT; National Institutes of Health [GM015539, GM023562, NS085092]; Grants-in-Aid for Scientific Research [20247008] Funding Source: KAKEN
NR 61
TC 83
Z9 97
U1 0
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 JUN 26
PY 2014
VL 510
IS 7506
BP 507
EP 511
DI 10.1038/nature13440
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300040
PM 24919148
DA 2026-03-09
ER

PT J
AU Vogelsberger, M
   Genel, S
   Springel, V
   Torrey, P
   Sijacki, D
   Xu, D
   Snyder, G
   Bird, S
   Nelson, D
   Hernquist, L
AF Vogelsberger, M.
   Genel, S.
   Springel, V.
   Torrey, P.
   Sijacki, D.
   Xu, D.
   Snyder, G.
   Bird, S.
   Nelson, D.
   Hernquist, L.
TI Properties of galaxies reproduced by a hydrodynamic simulation
SO NATURE
LA English
DT Article
ID moving-mesh cosmology; cold dark-matter; ly-alpha systems; star-formation; power spectrum; radial-distribution; scaling relations; massive galaxy; dwarf galaxy; local universe
AB Previous simulations of the growth of cosmic structures have broadly reproduced the 'cosmic web' of galaxies that we see in the Universe, but failed to create a mixed population of elliptical and spiral galaxies, because of numerical inaccuracies and incomplete physical models. Moreover, they were unable to track the small-scale evolution of gas and stars to the present epoch within a representative portion of the Universe. Here we report a simulation that starts 12 million years after the Big Bang, and traces 13 billion years of cosmic evolution with 12 billion resolution elements in a cube of 106.5 megaparsecs a side. It yields a reasonable population of ellipticals and spirals, reproduces the observed distribution of galaxies in clusters and characteristics of hydrogen on large scales, and at the same time matches the 'metal' and hydrogen content of galaxies on small scales.
C1 [Vogelsberger, M.] MIT, Dept Phys, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Genel, S.; Torrey, P.; Nelson, D.; Hernquist, L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Springel, V.; Xu, D.] Heidelberg Inst Theoret Studies, D-69118 Heidelberg, Germany.
   [Springel, V.] Heidelberg Univ, Zentrum Astron, ARI, D-69120 Heidelberg, Germany.
   [Sijacki, D.] Kavli Inst Cosmol, Cambridge CB3 0HA, England.
   [Sijacki, D.] Inst Astron, Cambridge CB3 0HA, England.
   [Snyder, G.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Bird, S.] Inst Adv Study, Princeton, NJ 08540 USA.
C3 Massachusetts Institute of Technology (MIT); Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; Heidelberg Institute for Theoretical Studies; Ruprecht Karls University Heidelberg; University of Cambridge; University of Cambridge; Space Telescope Science Institute; Institute for Advanced Study - USA
RP Vogelsberger, M (corresponding author), MIT, Dept Phys, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
EM mvogelsb@mit.edu
FU DFG Research Centre SFB-881; European Research Council [ERC-StG EXAGAL-308037]; HST [HST-AR-12856.01-A]; NASA from the Space Telescope Science Institute [12856, NAS 5-26555]; NASA [NNX12AC67G]; NSF [AST-1312095, AST-0907969]; Alexander von Humboldt Foundation; GCS [pr85je]; NASA Office of Space Science [NNX13AC07G];  [9,352];  [9,425]; [9,488];  [9,575];  [9,793];  [9,978];  [10,086];  [10,189];  [10,258];  [10,340];  [10,530];  [11,359];  [11,563];  [12,060];  [12,061];  [12,062];  [12,099];  [12,177]; Science and Technology Facilities Council [ST/L000725/1] Funding Source: researchfish; STFC [ST/L000725/1] Funding Source: UKRI; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0907969, 1312095] Funding Source: National Science Foundation
NR 75
TC 1117
Z9 1247
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 MAY 8
PY 2014
VL 509
IS 7499
BP 177
EP +
DI 10.1038/nature13316
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300029
PM 24805343
DA 2026-03-09
ER

PT J
AU Goodarzi, H
   Zhang, S
   Buss, CG
   Fish, L
   Tavazoie, S
   Tavazoie, SF
AF Goodarzi, Hani
   Zhang, Steven
   Buss, Colin G.
   Fish, Lisa
   Tavazoie, Saeed
   Tavazoie, Sohail F.
TI Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins
SO NATURE
LA English
DT Article
ID breast-cancer metastasis; gene-expression; regulatory elements; protein; seq; stability; discovery; invasion; disease; complex
AB Aberrant regulation of RNA stability has an important role in many disease states(1,2). Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types(3-7). A defining feature of RNA is its ability to fold into structures. However, the roles of structural mRNA elements in cancer progression remain unexplored. Here we performed an unbiased search for post-transcriptional modulators of mRNA stability in breast cancer by conducting whole-genome transcript stability measurements in poorly and highly metastatic isogenic human breast cancer lines. Using a computational framework that searches RNA sequence and structure space(8), we discovered a family of GC-rich structural cis-regulatory RNA elements, termed sRSEs for structural RNA stability elements, which are significantly overrepresented in transcripts displaying reduced stability in highly metastatic cells. By integrating computational and biochemical approaches, we identified TARBP2, a double-stranded RNA-binding protein implicated in microRNA processing, as the trans factor that binds the sRSE family and similar structural elements collectively termed TARBP2-binding structural elements (TBSEs) in transcripts. TARBP2 is overexpressed in metastatic cells and metastatic human breast tumours and destabilizes transcripts containing TBSEs. Endogenous TARBP2 promotes metastatic cell invasion and colonization by destabilizing amyloid precursor protein (APP) and ZNF395 transcripts, two genes previously associated with Alzheimer's and Huntington's disease, respectively. We reveal these genes to be novel metastasis suppressor genes in breast cancer. The cleavage product of APP, extracellular alpha-myloida peptide, directly suppresses invasion while ZNF395 transcriptionally represses a pro-metastatic gene expression program. The expression levels of TARBP2, APP and ZNF395 in human breast carcinomas support their experimentally uncovered roles in metastasis. Our findings establish a non-canonical and direct role for TARBP2 in mammalian gene expression regulation and reveal that regulated RNA destabilization through protein-mediated binding of mRNA structural elements can govern cancer progression.
C1 [Goodarzi, Hani; Zhang, Steven; Buss, Colin G.; Fish, Lisa; Tavazoie, Sohail F.] Rockefeller Univ, Lab Syst Canc Biol, New York, NY 10065 USA.
   [Tavazoie, Saeed] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Tavazoie, Saeed] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA.
C3 Rockefeller University; Columbia University; Columbia University
RP Tavazoie, S (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
EM st2744@columbia.edu; stavazoie@rockefeller.edu
FU Department of Defense Era of Hope Scholar; Department of Defense Breast Cancer Collaborative Scholars and Innovators Award; National Human Genome Research Institute [R01 HG003219]
NR 47
TC 75
Z9 88
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 SEP 11
PY 2014
VL 513
IS 7517
BP 256
EP +
DI 10.1038/nature13466
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800055
PM 25043050
DA 2026-03-09
ER

PT J
AU Fonseca-Pereira, D
   Arroz-Madeira, S
   Rodrigues-Campos, M
   Barbosa, IAM
   Domingues, RG
   Bento, T
   Almeida, ARM
   Ribeiro, H
   Potocnik, AJ
   Enomoto, H
   Veiga-Fernandes, H
AF Fonseca-Pereira, Diogo
   Arroz-Madeira, Silvia
   Rodrigues-Campos, mariana
   Barbosa, Ines A. M.
   Domingues, Rita G.
   Bento, Teresa
   Almeida, Afonso R. M.
   Ribeiro, Helder
   Potocnik, Alexandre J.
   Enomoto, Hideki
   Veiga-Fernandes, Henrique
TI The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function
SO NATURE
LA English
DT Article
ID nervous-system; mice lacking; fetal; expression; migration; component; kidney; death
AB Haematopoiesis is a developmental cascade that generates all blood cell lineages in health and disease. This process relies on quiescent haematopoietic stem cells capable of differentiating, self renewing and expanding upon physiological demand(1,2). However, the mechanisms that regulate haematopoietic stem cell homeostasis and function remain largely unknown. Here we show that the neurotrophic factor receptor RET (rearranged during transfection) drives haematopoietic stem cell survival, expansion and function. We find that haematopoietic stem cells express RET and that its neurotrophic factor partners are produced in the haematopoietic stem cell environment. Ablation of Ret leads to impaired survival and reduced numbers of haematopoietic stem cells with normal differentiation potential, but loss of cell-autonomous stress response and reconstitution potential. Strikingly, RET signals provide haematopoietic stem cells with critical Bcl2 and Bcl2l1 surviving cues, downstream of p38 mitogen-activated protein (MAP) kinase and cyclic-AMP-response element binding protein (CREB) activation. Accordingly, enforced expression of RET downstream targets, Bcl2 or Bcl2l1, is sufficient to restore the activity of Ret null progenitors in vivo. Activation of RET results in improved haematopoietic stem cell survival, expansion and in vivo transplantation efficiency. Remarkably, human cord-blood progenitor expansion and transplantation is also improved by neurotrophic factors, opening the way for exploration of RET agonists in human haematopoietic stem cell transplantation. Ourwork shows that neurotrophic factors are novel components of the haematopoietic stem cell microenvironment, revealing that
C1 [Fonseca-Pereira, Diogo; Arroz-Madeira, Silvia; Rodrigues-Campos, mariana; Barbosa, Ines A. M.; Domingues, Rita G.; Bento, Teresa; Almeida, Afonso R. M.; Ribeiro, Helder; Veiga-Fernandes, Henrique] Fac Med Lisbon, Inst Mol Med, P-1649028 Lisbon, Portugal.
   [Potocnik, Alexandre J.] MRC Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England.
   [Potocnik, Alexandre J.] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Enomoto, Hideki] RIKEN Ctr Dev Biol, Lab Neuronal Differentiat & Regenerat, Kobe, Hyogo 6500047, Japan.
   [Enomoto, Hideki] Kobe Univ, Grad Sch Med, Chuo Ku, Kobe, Hyogo 6500017, Japan.
C3 Universidade de Lisboa; MRC National Institute for Medical Research; University of Edinburgh; RIKEN; Kobe University
RP Veiga-Fernandes, H (corresponding author), Fac Med Lisbon, Inst Mol Med, Ave Prof Egas Moniz,Edif Egas Moniz, P-1649028 Lisbon, Portugal.
EM jhfernandes@medicina.ulisboa.pt
FU Fundacao para a Ciencia e Tecnologia, Portugal; Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/SAU-MII/104931/2008]; European Molecular Biology Organisation [1648]; European Research Council [207057]; National Blood Foundation, USA; MRC [MC_U117565359] Funding Source: UKRI; European Research Council (ERC) [207057] Funding Source: European Research Council (ERC); Fundação para a Ciência e a Tecnologia [PTDC/SAU-MII/104931/2008] Funding Source: FCT; Grants-in-Aid for Scientific Research [22122005] Funding Source: KAKEN; Medical Research Council [MC_U117565359] Funding Source: researchfish
NR 34
TC 89
Z9 108
U1 0
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 OCT 2
PY 2014
VL 514
IS 7520
BP 98
EP +
DI 10.1038/nature13498
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800043
PM 25079320
DA 2026-03-09
ER

PT J
AU Poon, IKH
   Chiu, YH
   Armstrong, AJ
   Kinchen, JM
   Juncadella, IJ
   Bayliss, DA
   Ravichandran, KS
AF Poon, Ivan K. H.
   Chiu, Yu-Hsin
   Armstrong, Allison J.
   Kinchen, Jason M.
   Juncadella, Ignacio J.
   Bayliss, Douglas A.
   Ravichandran, Kodi S.
TI Unexpected link between an antibiotic, pannexin channels and apoptosis
SO NATURE
LA English
DT Article
ID find-me signal; atp release; cell-death; in-vivo; rock-i; safety; activation; pharmacokinetics; fluoroquinolones; trovafloxacin
AB Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor, by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections, some quinolones have unexplained side effects, including deaths among children. PANX1 is a direct target of trovafloxacin at drug concentrations seen in human plasma, and its inhibition led to dysregulated fragmentation of apoptotic cells. Genetic loss of PANX1 phenocopied trovafloxacin effects, revealing a non-redundant role for pannexin channels in regulating cellulardisassemblyduring apoptosis. Increase in drug-resistant bacteria worldwide and the dearth of new antibiotics is a major human health challenge. Comparing different quinolone antibiotics suggests that certain structural features may contribute to PANX1 blockade. These data identify a novel linkage between an antibiotic, pannexin channels and cellular integrity, and suggest that re-engineering certain quinolones might help develop newer antibacterials.
C1 [Poon, Ivan K. H.; Armstrong, Allison J.; Kinchen, Jason M.; Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Poon, Ivan K. H.; Armstrong, Allison J.; Kinchen, Jason M.; Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
   [Poon, Ivan K. H.; Armstrong, Allison J.; Kinchen, Jason M.; Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Poon, Ivan K. H.] La Trobe Univ, La Trobe Inst Mol Sci, Melbourne, Vic, Australia.
   [Chiu, Yu-Hsin; Bayliss, Douglas A.] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; La Trobe University; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
EM Ravi@virginia.edu
FU US National Institutes of Health [NIGMS 107848]; National Health & Medical Research Council of Australia; American Heart Association; National Institute of Allergy and Infectious Diseases [T32AI007496] Funding Source: NIH RePORTER
NR 40
TC 236
Z9 270
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 20
PY 2014
VL 507
IS 7492
BP 329
EP +
DI 10.1038/nature13147
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000027
PM 24646995
DA 2026-03-09
ER

PT J
AU Ralston, KS
   Solga, MD
   Mackey-Lawrence, NM
   Somlata
   Bhattacharya, A
   Petri, WA
AF Ralston, Katherine S.
   Solga, Michael D.
   Mackey-Lawrence, Nicole M.
   Somlata
   Bhattacharya, Alok
   Petri, William A., Jr.
TI Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion
SO NATURE
LA English
DT Article
ID cytopathogenic mechanisms; target-cells; phagocytosis; adherence; internalization; microscopy; antibody; synapse
AB Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named "histolytica'' for its ability to destroy host tissues, which is probably driven by direct killing of human cells. The mechanism of human cell killing has been unclear, although the accepted model was that the parasites use secreted toxic effectors to kill cells before ingestion(1). Here we report the discovery that amoebae kill by ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. After cell killing, amoebae detach and cease ingestion. Ingestion of human cell fragments is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of fragments of living human cells is reminiscent of trogocytosis (from Greek trogo, nibble) observed between immune cells(2-6), but amoebic trogocytosis differs because it results in death. The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms(7). These findings change the model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.
C1 [Ralston, Katherine S.; Mackey-Lawrence, Nicole M.; Petri, William A., Jr.] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
   [Solga, Michael D.; Petri, William A., Jr.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
   [Somlata; Bhattacharya, Alok] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
   [Petri, William A., Jr.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; Jawaharlal Nehru University, New Delhi; University of Virginia
RP Petri, WA (corresponding author), Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
EM wap3g@virginia.edu
FU Howard Hughes Medical Institute from the Life Sciences Research Foundation; Hartwell Foundation; NIH [AI07046-32, 5R01 AI-26649]; National Institute of Allergy and Infectious Diseases [T32AI007046, T32AI055432] Funding Source: NIH RePORTER
NR 28
TC 169
Z9 203
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 APR 24
PY 2014
VL 508
IS 7497
BP 526
EP +
DI 10.1038/nature13242
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600037
PM 24717428
DA 2026-03-09
ER

PT J
AU Goldberg, GW
   Jiang, WY
   Bikard, D
   Marraffini, LA
AF Goldberg, Gregory W.
   Jiang, Wenyan
   Bikard, David
   Marraffini, Luciano A.
TI Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting
SO NATURE
LA English
DT Article
ID staphylococcus-aureus; antiviral defense; immunity; rna; interference; complex; systems; dna; sequence; protein
AB A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter(1). Prokaryotic CRISPR-Cas immune systems defend against phage infection byusing Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome(2,3). Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host(4,5). However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages(6)-compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of 'tolerance to non-self' to the prokaryotic branch of adaptive immunity.
C1 [Goldberg, Gregory W.; Jiang, Wenyan; Bikard, David; Marraffini, Luciano A.] Rockefeller Univ, Bacteriol Lab, New York, NY 10065 USA.
C3 Rockefeller University
RP Marraffini, LA (corresponding author), Rockefeller Univ, Bacteriol Lab, New York, NY 10065 USA.
EM marraffini@rockefeller.edu
FU Searle Scholars Program; Rita Allen Scholars Program; Irma T. Hirschl Award; Sinsheimer Foundation Award; National Institutes of Health Director's New Innovator Award [1DP2AI104556-01]; National Institute of Allergy and Infectious Diseases [T32AI070084] Funding Source: NIH RePORTER
NR 37
TC 218
Z9 273
U1 3
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 OCT 30
PY 2014
VL 514
IS 7524
BP 633
EP +
DI 10.1038/nature13637
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500050
PM 25174707
DA 2026-03-09
ER

PT J
AU Chen, J
   Petrov, A
   Johansson, M
   Tsai, A
   O'Leary, SE
   Puglisi, JD
AF Chen, Jin
   Petrov, Alexey
   Johansson, Magnus
   Tsai, Albert
   O'Leary, Sean E.
   Puglisi, Joseph D.
TI Dynamic pathways of-1 translational frameshifting
SO NATURE
LA English
DT Article
ID single-molecule fluorescence; transfer-rna selection; messenger-rna; hybrid state; real-time; compositional dynamics; p-site; ribosome; translocation; codon
AB Spontaneous changes in the reading frame of translation are rare (frequency of 10(-3) to 10(-4) per codon)(1), but can be induced by specific features in the messenger RNA (mRNA). In the presence of mRNA secondary structures, a heptanucleotide 'slippery sequence' usually defined by the motif X XXY YYZ, and (in some prokaryotic cases) mRNA sequences that base pair with the 39 end of the 16S ribosomal rRNA (internal Shine-Dalgarno sequences), there is an increased probability that a specific programmed change of frame occurs, wherein the ribosome shifts one nucleotide backwards into an overlapping reading frame(-1 frame) and continues by translating a new sequence of amino acids(2,3). Despite extensive biochemical and genetic studies, there is no clear mechanistic description for frameshifting. Here we apply single-molecule fluorescence to track the compositional and conformational dynamics of individual ribosomes at each codon during translation of a frameshift-inducing mRNA from the dnaX gene in Escherichia coli. Ribosomes that frameshift into the -1 frame are characterized by a tenfold longer pause in elongation compared to non-frameshifted ribosomes, which translate through unperturbed. During the pause, interactions of the ribosome with the mRNA stimulatory elements uncouple EF-Gcatalysed translocation from normal ribosomal subunit reverse-rotation, leaving the ribosome in a non-canonical intersubunit rotated state with an exposed codon in the aminoacyl-tRNA site (A site). tRNA(Lys) sampling and accommodation to the empty A site and EF-G action either leads to the slippage of the tRNAs into the-1 frame or maintains the ribosome into the 0 frame. Our results provide a general mechanistic and conformational framework for -1 frameshifting, highlighting multiple kinetic branchpoints during elongation.
C1 [Chen, Jin; Tsai, Albert] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Chen, Jin; Petrov, Alexey; Johansson, Magnus; Tsai, Albert; O'Leary, Sean E.; Puglisi, Joseph D.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Puglisi, JD (corresponding author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
EM puglisi@stanford.edu
FU US National Institutes of Health (NIH) [GM51266]; NIH [GM099687]; Wenner-Gren Foundations (Stockholm); Stanford Interdisciplinary Graduate Fellowship; National Institute of General Medical Sciences [R01GM051266] Funding Source: NIH RePORTER
NR 43
TC 127
Z9 168
U1 0
U2 68
PU NATURE PUBLISHING 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 21
PY 2014
VL 512
IS 7514
BP 328
EP +
DI 10.1038/nature13428
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200039
PM 24919156
DA 2026-03-09
ER

PT J
AU Greber, BJ
   Boehringer, D
   Leibundgut, M
   Bieri, P
   Leitner, A
   Schmitz, N
   Aebersold, R
   Ban, N
AF Greber, Basil J.
   Boehringer, Daniel
   Leibundgut, Marc
   Bieri, Philipp
   Leitner, Alexander
   Schmitz, Nikolaus
   Aebersold, Ruedi
   Ban, Nenad
TI The complete structure of the large subunit of the mammalian mitochondrial ribosome
SO NATURE
LA English
DT Article
ID peptidyl transferase center; transfer-rna; system; identification; visualization; antibiotics; initiation; evolution; software; proteins
AB Mitochondrial ribosomes (mitoribosomes) are extensively modified ribosomes of bacterial descent specialized for the synthesis and insertion of membrane proteins that are critical for energy conversion and ATP production inside mitochondria(1). Mammalian mitoribosomes, which comprise 39S and 28S subunits(2), have diverged markedly from the bacterial ribosomes from which they are derived, rendering them unique compared to bacterial, eukaryotic cytosolic and fungal mitochondrial ribosomes(3-5). We have previously determined at 4.9 angstrom resolution the architecture of the porcine (Sus scrofa) 39S subunit(6), which is highly homologous to the human mitoribosomal large subunit. Here we present the complete atomic structure of the porcine 39S large mitoribosomal subunit determined in the context of a stalled translating mitoribosome at 3.4 angstrom resolution by cryo-electron microscopy and chemical crosslinking/mass spectrometry. The structure reveals the locations and the detailed folds of 50 mitoribosomal proteins, shows the highly conserved mitoribosomal peptidyl transferase active site in complex with its substrate transfer RNAs, and defines the path of the nascent chain in mammalian mitoribosomes along their idiosyncratic exit tunnel. Furthermore, we present evidence that a mitochondrial tRNA has become an integral component of the central protuberance of the 39S subunit where it architecturally substitutes for the absence of the 5S ribosomal RNA, a ubiquitous component of all cytoplasmic ribosomes.
C1 [Greber, Basil J.; Boehringer, Daniel; Leibundgut, Marc; Bieri, Philipp; Schmitz, Nikolaus; Ban, Nenad] Swiss Fed Inst Technol, Inst Mol Biol & Biophys, Dept Biol, CH-8093 Zurich, Switzerland.
   [Leitner, Alexander; Aebersold, Ruedi] Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich
RP Ban, N (corresponding author), Swiss Fed Inst Technol, Inst Mol Biol & Biophys, Dept Biol, Otto Stern Weg 5, CH-8093 Zurich, Switzerland.
EM ban@mol.biol.ethz.ch
FU Swiss National Science Foundation (SNSF); National Center of Excellence in Research (NCCR) Structural Biology program of the Swiss National Science Foundation (SNSF); European Research Council (ERC) under the European Community [250071]; Commission of the European Communities through the PROSPECTS consortium (EU FP7 projects) [201648, 233226]; European Research Council [ERC-2008-AdG 233226]; European Research Council (ERC) [250071] Funding Source: European Research Council (ERC)
NR 58
TC 210
Z9 232
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 NOV 13
PY 2014
VL 515
IS 7526
BP 283
EP U326
DI 10.1038/nature13895
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400054
PM 25271403
DA 2026-03-09
ER

PT J
AU Hovestadt, V
   Jones, DTW
   Picelli, S
   Wang, W
   Kool, M
   Northcott, PA
   Sultan, M
   Stachurski, K
   Ryzhova, M
   Warnatz, HJ
   Ralser, M
   Brun, S
   Bunt, J
   Jäger, N
   Kleinheinz, K
   Erkek, S
   Weber, UD
   Bartholomae, CC
   von Kalle, C
   Lawerenz, C
   Eils, J
   Koster, J
   Versteeg, R
   Milde, T
   Witt, O
   Schmidt, S
   Wolf, S
   Pietsch, T
   Rutkowski, S
   Scheurlen, W
   Taylor, MD
   Brors, B
   Felsberg, J
   Reifenberger, G
   Borkhardt, A
   Lehrach, H
   Wechsler-Reya, RJ
   Eils, R
   Yaspo, ML
   Landgraf, P
   Korshunov, A
   Zapatka, M
   Radlwimmer, B
   Pfister, SM
   Lichter, P
AF Hovestadt, Volker
   Jones, David T. W.
   Picelli, Simone
   Wang, Wei
   Kool, Marcel
   Northcott, Paul A.
   Sultan, Marc
   Stachurski, Katharina
   Ryzhova, Marina
   Warnatz, Hans-Joerg
   Ralser, Meryem
   Brun, Sonja
   Bunt, Jens
   Jaeger, Natalie
   Kleinheinz, Kortine
   Erkek, Scrap
   Weber, Ursula D.
   Bartholomae, Cynthia C.
   von Kalle, Christof
   Lawerenz, Chris
   Eils, Jurgen
   Koster, Jan
   Versteeg, Rogier
   Milde, Till
   Witt, Olaf
   Schmidt, Sabine
   Wolf, Stephan
   Pietsch, Torsten
   Rutkowski, Stefan
   Scheurlen, Wolfram
   Taylor, Michael D.
   Brors, Benedikt
   Felsberg, Joerg
   Reifenberger, Guido
   Borkhardt, Arndt
   Lehrach, Hans
   Wechsler-Reya, Robert J.
   Eils, Roland
   Yaspo, Marie-Laure
   Landgraf, Pablo
   Korshunov, Andrey
   Zapatka, Marc
   Radlwimmer, Bernhard
   Pfister, Stefan M.
   Lichter, Peter
TI Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing
SO NATURE
LA English
DT Article
ID cancer genome; gene; differentiation; hypermethylation; identification; suppressor; methylome; ultrafast; alignment; mutation
AB Epigenetic alterations, that is, disruption of DNA methylation and chromatin architecture, are now acknowledged as a universal feature of tumorigenesis(1). Medulloblastoma, a clinically challenging, malignant childhood brain tumour, is no exception. Despite much progress from recent genomics studies, with recurrent changes identified in each of the four distinct tumour subgroups(WNT-pathway-activated, SHH-pathway-activated, and the less-well-characterized Group 3 and Group 4)(2-4), many cases still lack an obvious genetic driver. Here we present whole-genome bisulphite-sequencing data from thirty-four human and five murine tumours plus eight human and three murine normal controls, augmented with matched whole-genome, RNA and chromatin immunoprecipitation sequencing data. This comprehensive data set allowed us to decipher several features underlying the interplay between the genome, epigenome and transcriptome, and its effects on medulloblastoma pathophysiology. Most notable were highly prevalent regions of hypomethylation correlating with increased gene expression, extending tens of kilobases downstream of transcription start sites. Focal regions of low methylation linked to transcription-factor-binding sites shed light on differential transcriptional networks between subgroups, whereas increased methylation due to re-normalization of repressed chromatin in DNA methylation valleys was positively correlated with gene expression. Large, partially methylated domains affecting up to one-third of the genome showed increased mutation rates and gene silencing in a subgroup-specific fashion. Epigenetic alterations also affected novel medulloblastoma candidate genes (for example, LIN28B), resulting in alternative promoter usage and/or differential messenger RNA/microRNA expression. Analysis of mouse medulloblastoma and precursor-cell methylation demonstrated a somatic origin for many alterations. Our data provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis, which are probably also of importance in a wider developmental and disease context.
C1 [Hovestadt, Volker; Picelli, Simone; Wang, Wei; Kleinheinz, Kortine; Weber, Ursula D.; Zapatka, Marc; Radlwimmer, Bernhard; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Erkek, Scrap; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Sultan, Marc; Warnatz, Hans-Joerg; Ralser, Meryem; Lehrach, Hans; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Stachurski, Katharina; Borkhardt, Arndt; Landgraf, Pablo] Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany.
   [Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow 125047, Russia.
   [Brun, Sonja; Wechsler-Reya, Robert J.] Sanford Burnham Med Res Inst, Designated Canc Ctr, NCI, Tumor Initiat & Maintenance Program, La Jolla, CA 92037 USA.
   [Bunt, Jens] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
   [Bunt, Jens; Koster, Jan; Versteeg, Rogier] Univ Amsterdam, AMC, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands.
   [Jaeger, Natalie; Kleinheinz, Kortine; Brors, Benedikt; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Erkek, Scrap] EMBL, D-69117 Heidelberg, Germany.
   [Bartholomae, Cynthia C.; von Kalle, Christof] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany.
   [Bartholomae, Cynthia C.; von Kalle, Christof] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany.
   [Lawerenz, Chris; Eils, Jurgen] German Canc Res Ctr, Data Management Facil, D-69120 Heidelberg, Germany.
   [Milde, Till; Witt, Olaf; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
   [Milde, Till; Witt, Olaf] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, D-69120 Heidelberg, Germany.
   [Schmidt, Sabine; Wolf, Stephan] German Canc Res Ctr, Genom & Prote Core Facil, D-69120 Heidelberg, Germany.
   [Pietsch, Torsten] Univ Bonn, Med Ctr, Dept Neuropathol, D-53105 Bonn, Germany.
   [Rutkowski, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Paediat Haematol & Oncol, D-20246 Hamburg, Germany.
   [Scheurlen, Wolfram] Nurnberg Childrens Hosp, Cnopfsche Kinderklin, D-90419 Nurnberg, Germany.
   [Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada.
   [Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
   [Taylor, Michael D.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada.
   [Felsberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany.
   [Felsberg, Joerg; Reifenberger, Guido] German Canc Res Ctr, German Consortium Translat Canc Res DKTK, D-69120 Heidelberg, Germany.
   [Eils, Roland] Heidelberg Univ, IPMB, D-69120 Heidelberg, Germany.
   [Eils, Roland] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany.
   [Eils, Roland; Lichter, Peter] Heidelberg Ctr Personalised Oncol DKFZ HIPO, D-69120 Heidelberg, Germany.
   [Korshunov, Andrey] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Korshunov, Andrey] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Max Planck Society; Heinrich Heine University Dusseldorf; Russian Academy of Medical Sciences; N.N.Burdenko National Medical Research Center of Neurosurgery; Sanford Burnham Prebys Medical Discovery Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Queensland; University of Amsterdam; Academic Medical Center Amsterdam; Helmholtz Association; German Cancer Research Center (DKFZ); European Molecular Biology Laboratory (EMBL); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); University of Bonn; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Heinrich Heine University Dusseldorf; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Hovestadt, V (corresponding author), German Canc Res Ctr, Div Mol Genet, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
FU German Cancer Aid [109252]; German Federal Ministry of Education and Research (BMBF) [01KU1201A]; German Federal Ministry of Education and Research (MedSys) [0315416C]; German Federal Ministry of Education and Research (NGFNplus) [01GS0883]; DKFZ-Heidelberg Center for Personalized Oncology (DKFZ-HIPO); Dutch Cancer Foundations KWF [2010-4713]; KIKA; German Research Foundation (DFG) [LA2983/2-1]
NR 48
TC 357
Z9 413
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 JUN 26
PY 2014
VL 510
IS 7506
BP 537
EP +
DI 10.1038/nature13268
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300047
PM 24847876
DA 2026-03-09
ER

PT J
AU Xu, Y
   Tao, YY
   Cheung, LS
   Fan, C
   Chen, LQ
   Xu, S
   Perry, K
   Frommer, WB
   Feng, L
AF Xu, Yan
   Tao, Yuyong
   Cheung, Lily S.
   Fan, Chao
   Chen, Li-Qing
   Xu, Sophia
   Perry, Kay
   Frommer, Wolf B.
   Feng, Liang
TI Structures of bacterial homologues of SWEET transporters in two distinct conformations
SO NATURE
LA English
DT Article
ID crystal-structure; protein; oligomerization; drosophila; yeast
AB SWEETs and their prokaryotic homologues are monosaccharide and disaccharide transporters that are present from Archaea to plants and humans(1-3). SWEETs play crucial roles in cellular sugar efflux processes: that is, in phloem loading(4), pollen nutrition(5) and nectar secretion(6). Their bacterial homologues, which are called SemiSWEETs, are among the smallest known transporters(1,3). Here we show that SemiSWEET molecules, which consist of a triple-helix bundle, form symmetrical, parallel dimers, thereby generating the translocation pathway. Two SemiSWEET isoforms were crystallized, one in an apparently open state and one in an occluded state, indicating that SemiSWEETs and SWEETs are transporters that undergo rocking-type movements during the transport cycle. The topology of the triple-helix bundle is similar yet distinct to that of the basic building block of animal and plant major facilitator superfamily (MFS) transporters (for example, GLUTs and SUTs). This finding indicates two possibilities: that SWEETs and MFS transporters evolved from an ancestral triple-helix bundle or that the triple-helix bundle represents convergent evolution. In SemiSWEETs and SWEETs, two triple-helix bundles are arranged in a parallel configuration to produce the 6-and 6+1-transmembranehelix pores, respectively. In the 12-transmembrane-helix MFS transporters, four triple-helix bundles are arranged into an alternating antiparallel configuration, resulting in a much larger 2 X 2 triplehelix bundle forming the pore. Given the similarity of SemiSWEETs and SWEETs to PQ-loop amino acid transporters and to mitochondrial pyruvate carriers (MPCs), the structures characterized here may also be relevant to other transporters in the MtN3 clan(7-9). The insight gained from the structures of these transporters and from the analysis of mutations of conserved residues will improve the understanding of the transport mechanism, as well as allow comparative studies of the different superfamilies involved in sugar transport and the evolution of transporters in general.
C1 [Xu, Yan; Tao, Yuyong; Fan, Chao; Feng, Liang] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Cheung, Lily S.; Chen, Li-Qing; Frommer, Wolf B.] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA.
   [Xu, Sophia; Frommer, Wolf B.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Perry, Kay] Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL 60439 USA.
   [Perry, Kay] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Argonne, IL 60439 USA.
C3 Stanford University; Carnegie Institution for Science; Stanford University; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory
RP Feng, L (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM liangf@stanford.edu
FU Stanford University; Harold and Leila Y. Mathers Charitable Foundation; Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences at the US Department of Energy (DOE) [DE-FG02-04ER15542]; National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]; DOE [DE-AC02-06CH11357]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1258018, 1401855] Funding Source: National Science Foundation
NR 43
TC 136
Z9 161
U1 1
U2 143
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 20
PY 2014
VL 515
IS 7527
BP 448
EP +
DI 10.1038/nature13670
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600054
PM 25186729
DA 2026-03-09
ER

PT J
AU Liechti, GW
   Kuru, E
   Hall, E
   Kalinda, A
   Brun, YV
   VanNieuwenhze, M
   Maurelli, AT
AF Liechti, G. W.
   Kuru, E.
   Hall, E.
   Kalinda, A.
   Brun, Y. V.
   VanNieuwenhze, M.
   Maurelli, A. T.
TI A new metabolic cell-wall labelling method reveals peptidoglycan in Chlamydia trachomatis
SO NATURE
LA English
DT Article
ID d-cycloserine; penicillin; acid; inhibition; proteins; bacteria; humans; murc
AB Peptidoglycan (PG), an essential structure in the cell walls of the vast majority of bacteria, is critical for division and maintaining cell shape and hydrostatic pressure(1). Bacteria comprising the Chlamydiales were thought to be one of the few exceptions. Chlamydia harbour genes for PG biosynthesis(2-7) and exhibit susceptibility to 'anti-PG' antibiotics(8,9), yet attempts to detect PG in any chlamydial species have proven unsuccessful (the 'chlamydial anomaly'(10)). We used a novel approach to metabolically label chlamydial PG using D-amino acid dipeptide probes and click chemistry. Replicating Chlamydia trachomatis were labelled with these probes throughout their biphasic developmental life cycle, and the results of differential probe incorporation experiments conducted in the presence of ampicillin are consistent with the presence of chlamydial PG-modifying enzymes. These findings culminate 50 years of speculation and debate concerning the chlamydial anomaly and are the strongest evidence so far that chlamydial species possess functional PG.
C1 [Liechti, G. W.; Maurelli, A. T.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
   [Kuru, E.] Indiana Univ, Interdisciplinary Biochem Program, Bloomington, IN 47405 USA.
   [Hall, E.; Kalinda, A.; VanNieuwenhze, M.] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.
   [Brun, Y. V.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
C3 Uniformed Services University of the Health Sciences - USA; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington
RP Maurelli, AT (corresponding author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mvannieu@indiana.edu; anthony.maurelli@usuhs.edu
FU NIH [AI044033, GM51986]
NR 38
TC 277
Z9 367
U1 3
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 FEB 27
PY 2014
VL 506
IS 7489
BP 507
EP +
DI 10.1038/nature12892
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100042
PM 24336210
DA 2026-03-09
ER

PT J
AU Epshtein, V
   Kamarthapu, V
   McGary, K
   Svetlov, V
   Ueberheide, B
   Proshkin, S
   Mironov, A
   Nudler, E
AF Epshtein, Vitaly
   Kamarthapu, Venu
   McGary, Katelyn
   Svetlov, Vladimir
   Ueberheide, Beatrix
   Proshkin, Sergey
   Mironov, Alexander
   Nudler, Evgeny
TI UvrD facilitates DNA repair by pulling RNA polymerase backwards
SO NATURE
LA English
DT Article
ID nucleotide excision-repair; escherichia-coli-uvrd; transcription elongation; helicase-ii; genome instability; gene-product; in-vitro; e. coli; damage; protein
AB UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. Furthermore, we show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.
C1 [Epshtein, Vitaly; Kamarthapu, Venu; McGary, Katelyn; Svetlov, Vladimir; Ueberheide, Beatrix; Nudler, Evgeny] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [Kamarthapu, Venu; Nudler, Evgeny] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Proshkin, Sergey; Mironov, Alexander] State Res Inst Genet & Select Ind Microorganisms, Moscow 117545, Russia.
   [Mironov, Alexander] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia.
C3 New York University; Howard Hughes Medical Institute; New York University; National Research Centre - Kurchatov Institute; Institute of Genetics & Selection of Industrial Microorganisms; Russian Academy of Sciences; Engelhardt Institute of Molecular Biology, RAS
RP Nudler, E (corresponding author), NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
EM evgeny.nudler@nyumc.org
FU Russian Foundation for Basic Research; NIH; BGRF; Dynasty foundation; Howard Hughes Medical Institute
NR 54
TC 188
Z9 224
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 JAN 16
PY 2014
VL 505
IS 7483
BP 372
EP +
DI 10.1038/nature12928
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800036
PM 24402227
DA 2026-03-09
ER

PT J
AU Anders, C
   Niewoehner, O
   Duerst, A
   Jinek, M
AF Anders, Carolin
   Niewoehner, Ole
   Duerst, Alessia
   Jinek, Martin
TI Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease
SO NATURE
LA English
DT Article
ID rna; crispr; specificity; system; refinement; drosophila
AB The CRISPR-associated protein Cas9 is anRNA-guided endonuclease that cleaves double-stranded DNA bearing sequences complementary to a 20-nucleotide segment in the guideRNA(1,2). Cas9 hase merged as a versatile molecular tool for genome editing and gene expression control(3). RNA-guided DNA recognition and cleavage strictly require the presence of a protospacer adjacent motif (PAM) in the target DNA(1,4-6). Here we report a crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5'-NGG-3' PAM. The structure reveals that the PAM motif resides in a base-paired DNA duplex. The non-complementary strand GG dinucleotide is read out via major-groove interactions with conserved arginine residues from the carboxyterminal domain of Cas9. Interactions with the minor groove of the PAM duplex and the phosphodiester group at the +1 position in the target DNA strand contribute to local strand separation immediately upstream of the PAM. These observations suggest a mechanism for PAM-dependent target DNA melting and RNA-DNA hybrid formation. Furthermore, this study establishes a framework for the rational engineering of Cas9 enzymes with novel PAM specificities.
C1 [Anders, Carolin; Niewoehner, Ole; Duerst, Alessia; Jinek, Martin] Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland.
C3 University of Zurich
RP Jinek, M (corresponding author), Univ Zurich, Inst Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM jinek@bioc.uzh.ch
FU European Research Council [337284 ANTIVIRNA]; University of Zurich
NR 36
TC 1021
Z9 1431
U1 7
U2 470
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 569
EP +
DI 10.1038/nature13579
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800045
PM 25079318
DA 2026-03-09
ER

PT J
AU Lazaridis, I
   Patterson, N
   Mittnik, A
   Renaud, G
   Mallick, S
   Kirsanow, K
   Sudmant, PH
   Schraiber, JG
   Castellano, S
   Lipson, M
   Berger, B
   Economou, C
   Bollongino, R
   Fu, QM
   Bos, KI
   Nordenfelt, S
   Li, H
   de Filippo, C
   Prüfer, K
   Sawyer, S
   Posth, C
   Haak, W
   Hallgren, F
   Fornander, E
   Rohland, N
   Delsate, D
   Francken, M
   Guinet, JM
   Wahl, J
   Ayodo, G
   Babiker, HA
   Bailliet, G
   Balanovska, E
   Balanovsky, O
   Barrantes, R
   Bedoya, G
   Ben-Ami, H
   Bene, J
   Berrada, F
   Bravi, CM
   Brisighelli, F
   Busby, GBJ
   Cali, F
   Churnosov, M
   Cole, DEC
   Corach, D
   Damba, L
   van Driem, G
   Dryomov, S
   Dugoujon, JM
   Fedorova, SA
   Romero, IG
   Gubina, M
   Hammer, M
   Henn, BM
   Hervig, T
   Hodoglugil, U
   Jha, AR
   Karachanak-Yankova, S
   Khusainova, R
   Khusnutdinova, E
   Kittles, R
   Kivisild, T
   Klitz, W
   Kucinskas, V
   Kushniarevich, A
   Laredj, L
   Litvinov, S
   Loukidis, T
   Mahley, RW
   Melegh, B
   Metspalu, E
   Molina, J
   Mountain, J
   Näkkäläjärvi, K
   Nesheva, D
   Nyambo, T
   Osipova, L
   Parik, J
   Platonov, F
   Posukh, O
   Romano, V
   Rothhammer, F
   Rudan, I
   Ruizbakiev, R
   Sahakyan, H
   Sajantila, A
   Salas, A
   Starikovskaya, EB
   Tarekegn, A
   Toncheva, D
   Turdikulova, S
   Uktveryte, I
   Utevska, O
   Vasquez, R
   Villena, M
   Voevoda, M
   Winkler, CA
   Yepiskoposyan, L
   Zalloua, P
   Zemunik, T
   Cooper, A
   Capelli, C
   Thomas, MG
   Ruiz-Linares, A
   Tishkoff, SA
   Singh, L
   Thangaraj, K
   Villems, R
   Comas, D
   Sukernik, R
   Metspalu, M
   Meyer, M
   Eichler, EE
   Burger, J
   Slatkin, M
   Pääbo, S
   Kelso, J
   Reich, D
   Krause, J
AF Lazaridis, Iosif
   Patterson, Nick
   Mittnik, Alissa
   Renaud, Gabriel
   Mallick, Swapan
   Kirsanow, Karola
   Sudmant, Peter H.
   Schraiber, Joshua G.
   Castellano, Sergi
   Lipson, Mark
   Berger, Bonnie
   Economou, Christos
   Bollongino, Ruth
   Fu, Qiaomei
   Bos, Kirsten I.
   Nordenfelt, Susanne
   Li, Heng
   de Filippo, Cesare
   Pruefer, Kay
   Sawyer, Susanna
   Posth, Cosimo
   Haak, Wolfgang
   Hallgren, Fredrik
   Fornander, Elin
   Rohland, Nadin
   Delsate, Dominique
   Francken, Michael
   Guinet, Jean-Michel
   Wahl, Joachim
   Ayodo, George
   Babiker, Hamza A.
   Bailliet, Graciela
   Balanovska, Elena
   Balanovsky, Oleg
   Barrantes, Ramiro
   Bedoya, Gabriel
   Ben-Ami, Haim
   Bene, Judit
   Berrada, Fouad
   Bravi, Claudio M.
   Brisighelli, Francesca
   Busby, George B. J.
   Cali, Francesco
   Churnosov, Mikhail
   Cole, David E. C.
   Corach, Daniel
   Damba, Larissa
   van Driem, George
   Dryomov, Stanislav
   Dugoujon, Jean-Michel
   Fedorova, Sardana A.
   Romero, Irene Gallego
   Gubina, Marina
   Hammer, Michael
   Henn, Brenna M.
   Hervig, Tor
   Hodoglugil, Ugur
   Jha, Aashish R.
   Karachanak-Yankova, Sena
   Khusainova, Rita
   Khusnutdinova, Elza
   Kittles, Rick
   Kivisild, Toomas
   Klitz, William
   Kucinskas, Vaidutis
   Kushniarevich, Alena
   Laredj, Leila
   Litvinov, Sergey
   Loukidis, Theologos
   Mahley, Robert W.
   Melegh, Bela
   Metspalu, Ene
   Molina, Julio
   Mountain, Joanna
   Nakkalajarvi, Klemetti
   Nesheva, Desislava
   Nyambo, Thomas
   Osipova, Ludmila
   Parik, Jueri
   Platonov, Fedor
   Posukh, Olga
   Romano, Valentino
   Rothhammer, Francisco
   Rudan, Igor
   Ruizbakiev, Ruslan
   Sahakyan, Hovhannes
   Sajantila, Antti
   Salas, Antonio
   Starikovskaya, Elena B.
   Tarekegn, Ayele
   Toncheva, Draga
   Turdikulova, Shahlo
   Uktveryte, Ingrida
   Utevska, Olga
   Vasquez, Rene
   Villena, Mercedes
   Voevoda, Mikhail
   Winkler, Cheryl A.
   Yepiskoposyan, Levon
   Zalloua, Pierre
   Zemunik, Tatijana
   Cooper, Alan
   Capelli, Cristian
   Thomas, Mark G.
   Ruiz-Linares, Andres
   Tishkoff, Sarah A.
   Singh, Lalji
   Thangaraj, Kumarasamy
   Villems, Richard
   Comas, David
   Sukernik, Rem
   Metspalu, Mait
   Meyer, Matthias
   Eichler, Evan E.
   Burger, Joachim
   Slatkin, Montgomery
   Paeaebo, Svante
   Kelso, Janet
   Reich, David
   Krause, Johannes
TI Ancient human genomes suggest three ancestral populations for present-day Europeans
SO NATURE
LA English
DT Article
ID hunter-gatherers; dna extraction; sequence; admixture; neanderthal; africa; stratification; algorithm; evolution; inference
AB We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
C1 [Lazaridis, Iosif; Mallick, Swapan; Fu, Qiaomei; Nordenfelt, Susanne; Li, Heng; Rohland, Nadin; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Lazaridis, Iosif; Patterson, Nick; Mallick, Swapan; Berger, Bonnie; Nordenfelt, Susanne; Li, Heng; Rohland, Nadin; Reich, David] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Mittnik, Alissa; Bos, Kirsten I.; Posth, Cosimo; Krause, Johannes] Univ Tubingen, Inst Archaeol Sci, D-72074 Tubingen, Germany.
   [Renaud, Gabriel; Castellano, Sergi; Fu, Qiaomei; de Filippo, Cesare; Pruefer, Kay; Sawyer, Susanna; Meyer, Matthias; Paeaebo, Svante; Kelso, Janet] Max Planck Inst Evolutionare Anthropol, D-04103 Leipzig, Germany.
   [Kirsanow, Karola; Bollongino, Ruth; Burger, Joachim] Johannes Gutenberg Univ Mainz, Inst Anthropol, D-55128 Mainz, Germany.
   [Sudmant, Peter H.; Schraiber, Joshua G.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Schraiber, Joshua G.; Klitz, William; Slatkin, Montgomery] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Lipson, Mark; Berger, Bonnie] MIT, Dept Math & Comp Sci, Cambridge, MA 02139 USA.
   [Lipson, Mark; Berger, Bonnie] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Economou, Christos] Stockholm Univ, Archaeol Res Lab, S-11418 Stockholm, Sweden.
   [Fu, Qiaomei] Chinese Acad Sci, IVPP, Key Lab Vertebrate Evolut & Human Origins, Beijing 100049, Peoples R China.
   [Haak, Wolfgang; Cooper, Alan] Univ Adelaide, Sch Earth & Environm Sci, Australian Ctr Ancient DNA & Environm Inst, Adelaide, SA 5005, Australia.
   [Hallgren, Fredrik; Fornander, Elin] Cultural Heritage Fdn, S-72212 Vasteras, Sweden.
   [Delsate, Dominique; Guinet, Jean-Michel] Natl Museum Nat Hist, L-2160 Luxembourg, Luxembourg.
   [Delsate, Dominique] Natl Museum Nat Hist, Natl Ctr Archaeol Res, L-2160 Luxembourg, Luxembourg.
   [Francken, Michael] Univ Tubingen, Senckenberg Ctr Human Evolut & Paleoenvironm, Dept Paleoanthropol, D-72070 Tubingen, Germany.
   [Wahl, Joachim] State Off Cultural Heritage Management Baden Wurt, D-78467 Constance, Germany.
   [Ayodo, George] Ctr Global Hlth & Child Dev, Kisumu 40100, Kenya.
   [Babiker, Hamza A.] Univ Edinburgh, Sch Biol Sci, Inst Evolut Res, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Babiker, Hamza A.] Univ Edinburgh, Sch Biol Sci, Inst Immunol Res, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Babiker, Hamza A.] Univ Edinburgh, Sch Biol Sci, Inst Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Babiker, Hamza A.] Sultan Qaboos Univ, Fac Med, Dept Biochem, Muscat 123, Oman.
   [Bailliet, Graciela; Bravi, Claudio M.] Consejo Nacl Invest Cient & Tecn, CCT, Inst Multidisciplinario Biol Celular IMBICE, Lab Genet Mol Poblac, La Plata, Buenos Aires, Argentina.
   [Bailliet, Graciela; Bravi, Claudio M.] CICPBA, La Plata, Buenos Aires, Argentina.
   [Balanovska, Elena; Balanovsky, Oleg] Russian Acad Med Sci, Med Genet Res Ctr, Moscow 115478, Russia.
   [Balanovsky, Oleg] NI Vavilov Gen Genet Res Inst, Moscow 119991, Russia.
   [Barrantes, Ramiro] Univ Costa Rica, Escuela Biol, San Jose 2060, Costa Rica.
   [Bedoya, Gabriel] Univ Antioquia, Res Grp GENMOL, Inst Biol, Medellin, Colombia.
   [Ben-Ami, Haim] Rambam Hlth Care Campus, IL-31096 Haifa, Israel.
   [Bene, Judit; Melegh, Bela] Univ Pecs, Dept Med Genet, H-7624 Pecs, Hungary.
   [Bene, Judit; Melegh, Bela] Univ Pecs, Szentagothai Res Ctr, H-7624 Pecs, Hungary.
   [Berrada, Fouad] Al Akhawayn Univ Ifrane AUI, Sch Sci & Engn, Ifrane 53000, Morocco.
   [Brisighelli, Francesca] Univ Cattolica Sacro Cuore, Inst Legal Med, Forens Genet Lab, I-00168 Rome, Italy.
   [Busby, George B. J.; Capelli, Cristian] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Busby, George B. J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Cali, Francesco] IRCCS Assoc Oasi Maria SS, Genet Mol Lab, I-94018 Troina, Italy.
   [Churnosov, Mikhail] Belgorod State Univ, Belgorod 308015, Russia.
   [Cole, David E. C.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L5, Canada.
   [Corach, Daniel] Univ Buenos Aires, Sch Pharm & Biochem, Serv Huellas Digitales Genet, RA-1113 Caba, Argentina.
   [Damba, Larissa; Gubina, Marina; Osipova, Ludmila; Posukh, Olga; Voevoda, Mikhail] Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia.
   [van Driem, George] Univ Bern, Inst Linguist, CH-3012 Bern, Switzerland.
   [Dryomov, Stanislav; Starikovskaya, Elena B.; Sukernik, Rem] Russian Acad Sci, Inst Mol & Cellular Biol, Siberian Branch, Lab Human Mol Genet, Novosibirsk 630090, Russia.
   [Dugoujon, Jean-Michel] Univ Toulouse 3, CNRS UMR 5288, F-31000 Toulouse, France.
   [Fedorova, Sardana A.] North Eastern Fed Univ, Yakutsk 677013, Russia.
   [Fedorova, Sardana A.] Yakut Res Ctr Complex Med Problems, Yakutsk 677013, Russia.
   [Romero, Irene Gallego; Jha, Aashish R.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Hammer, Michael] Univ Arizona, ARL Div Biotechnol, Tucson, AZ 85721 USA.
   [Henn, Brenna M.] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA.
   [Hervig, Tor] Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.
   [Hodoglugil, Ugur] Illumina, NextBio, Santa Clara, CA 95050 USA.
   [Karachanak-Yankova, Sena; Nesheva, Desislava; Toncheva, Draga] Med Univ Sofia, Natl Human Genome Ctr, Dept Med Genet, Sofia 1431, Bulgaria.
   [Khusainova, Rita; Khusnutdinova, Elza; Litvinov, Sergey] Russian Acad Sci, Ufa Res Ctr, Inst Biochem & Genet, Ufa 450054, Russia.
   [Khusainova, Rita; Khusnutdinova, Elza; Litvinov, Sergey] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450074, Russia.
   [Kittles, Rick] Univ Arizona, Coll Med, Tucson, AZ 85724 USA.
   [Kivisild, Toomas] Univ Cambridge, Div Biol Anthropol, Cambridge CB2 1QH, England.
   [Kucinskas, Vaidutis; Uktveryte, Ingrida] Vilnius State Univ, Dept Human & Med Genet, LT-08661 Vilnius, Lithuania.
   [Kushniarevich, Alena; Litvinov, Sergey; Sahakyan, Hovhannes; Villems, Richard; Metspalu, Mait] Estonian Bioctr, Evolutionary Biol Grp, EE-51010 Tartu, Estonia.
   [Laredj, Leila] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
   [Loukidis, Theologos; Thomas, Mark G.; Ruiz-Linares, Andres] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Mahley, Robert W.] Gladstone Inst, San Francisco, CA 94158 USA.
   [Metspalu, Ene; Parik, Jueri; Villems, Richard] Univ Tartu, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Molina, Julio] Ctr Invest Biomed Guatemala, Guatemala City, Guatemala.
   [Mountain, Joanna] 23andMe, Res Dept, Mountain View, CA 94043 USA.
   [Nakkalajarvi, Klemetti] Univ Oulu, Cultural Anthropol Program, Oulu 90014, Finland.
   [Nyambo, Thomas] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam 65001, Tanzania.
   [Platonov, Fedor] North Eastern Fed Univ, Res Inst Hlth, Yakutsk 677000, Russia.
   [Romano, Valentino] Univ Palermo, Dipartimento Fis & Chim, I-90128 Palermo, Italy.
   [Rothhammer, Francisco] Univ Tarapaca, Inst Alta Invest, Arica 1000000, Chile.
   [Rothhammer, Francisco] Univ Chile, Fac Med, Programa Genet Humana, ICBM, Santiago 8320000, Chile.
   [Rothhammer, Francisco] Ctr Invest Hombre Desierto, Arica 1000000, Chile.
   [Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Ruizbakiev, Ruslan] Uzbek Acad Sci, Inst Immunol, Tashkent 70000, Uzbekistan.
   [Sahakyan, Hovhannes; Yepiskoposyan, Levon] Natl Acad Sci Armenia, Inst Mol Biol, Lab Ethnogenom, Yerevan 0014, Armenia.
   [Sajantila, Antti] Univ Helsinki, Dept Forens Med, Hjelt Inst, Helsinki 00014, Finland.
   [Sajantila, Antti] Univ North Texas Hlth Sci Ctr, Dept Mol & Med Genet, Inst Appl Genet, Ft Worth, TX 76107 USA.
   [Salas, Antonio] Univ Santiago de Compostela, Fac Med, GMX, Dept Anat Patol & Ciencias Forenses,Unidade Xenet, Galcia 15872, Spain.
   [Salas, Antonio] Univ Santiago de Compostela, Fac Med, GMX, Inst Ciencias Forenses, Galcia 15872, Spain.
   [Tarekegn, Ayele] Henry Stewart Grp, London WC1A 2HN, England.
   [Turdikulova, Shahlo] Acad Sci Uzbek, Inst Bioorgan Chem, Tashkent 100125, Uzbekistan.
   [Utevska, Olga] Kharkov Natl Univ, Dept Genet & Cytol, UA-61077 Kharkov, Ukraine.
   [Vasquez, Rene; Villena, Mercedes] Univ Mayor San Andres, Inst Boliviano Biol Altura, La Paz 5912, Bolivia.
   [Vasquez, Rene; Villena, Mercedes] Univ Autonoma Tomas Frias, Potosi, Bolivia.
   [Voevoda, Mikhail] Russian Acad Med Sci, Siberian Branch, Inst Internal Med, Novosibirsk 630089, Russia.
   [Voevoda, Mikhail] Novosibirsk State Univ, Novosibirsk 630090, Russia.
   [Winkler, Cheryl A.] NCI, Basic Res Lab, NIH, Frederick Natl Lab,Leidos Biomed, Frederick, MD 21702 USA.
   [Zalloua, Pierre] Lebanese Amer Univ, Sch Med, Beirut 135053, Lebanon.
   [Zalloua, Pierre] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Zemunik, Tatijana] Univ Split, Sch Med, Dept Med Biol, Split 21000, Croatia.
   [Tishkoff, Sarah A.] Univ Penn, Dept Biol & Genet, Philadelphia, PA 19104 USA.
   [Singh, Lalji; Thangaraj, Kumarasamy] CSIR Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India.
   [Villems, Richard] Estonian Acad Sci, EE-10130 Tallinn, Estonia.
   [Comas, David] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Inst Biol Evolut CSIC UPF, Barcelona 08003, Spain.
   [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Krause, Johannes] Univ Tubingen, Senckenberg Ctr Human Evolut & Palaeoenvironm, D-72070 Tubingen, Germany.
   [Krause, Johannes] Max Planck Inst Geschichte & Nat Wissensch, D-07745 Jena, Germany.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Eberhard Karls University of Tubingen; Max Planck Society; Johannes Gutenberg University of Mainz; University of Washington; University of Washington Seattle; University of California System; University of California Berkeley; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Stockholm University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Adelaide University; University of Adelaide; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Eberhard Karls University of Tubingen; University of Edinburgh; University of Edinburgh; University of Edinburgh; Sultan Qaboos University; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Research Centre for Medical Genetics; Russian Academy of Medical Sciences; Russian Academy of Sciences; Vavilov Institute of General Genetics; Universidad Costa Rica; Universidad de Antioquia; Technion Israel Institute of Technology; Rambam Health Care Campus; University of Pecs; University of Pecs; Al Akhawayn University; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; IRCCS - Oasi Research Institute; Belgorod State University; University of Toronto; University of Buenos Aires; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; University of Bern; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); North-Eastern Federal University in Yakutsk; Yakut Science Centre of Complex Medical Problems; University of Chicago; University of Arizona; State University of New York (SUNY) System; Stony Brook University; University of Bergen; Illumina; Medical University Sofia; Russian Academy of Sciences; Institute of Biochemistry & Genetics of Ufa Science Centre of the RAS; Ufa University of Science & Technology; University of Arizona; University of Cambridge; Vilnius University; Estonian Biocentre; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); University of London; University College London; University of California System; University of California San Francisco; The J David Gladstone Institutes; University of Tartu; 23andMe, Inc.; University of Oulu; Muhimbili University of Health & Allied Sciences; North-Eastern Federal University in Yakutsk; University of Palermo; Universidad de Tarapaca; Universidad de Chile; University of Edinburgh; Academy of Sciences of Uzbekistan; Institute of Immunology & Human Genomics, Academy of Sciences of the Republic of Uzbekistan; National Academy of Sciences of Armenia; Institute of Molecular Biology - NAS RA; University of Helsinki; Universidade de Santiago de Compostela; Universidade de Santiago de Compostela; Academy of Sciences of Uzbekistan; Sadykov Institute of Bioorganic Chemistry; Ministry of Education & Science of Ukraine; VN Karazin Kharkiv National University; Universidad Mayor de San Andres; Instituto Boliviano de Biologica de Altura; Russian Academy of Medical Sciences; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Lebanese American University; Harvard University; Harvard T.H. Chan School of Public Health; University of Split; University of Pennsylvania; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); Estonian Academy of Sciences; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Eberhard Karls University of Tubingen; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN)
RP Reich, D (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM reich@genetics.med.harvard.edu; johannes.krause@uni-tuebingen.de
FU DFG [KR 4015/1-1]; Carl-Zeiss Foundation; Baden Wurttemberg Foundation; Max Planck Society; NSERC; NSF [OCI-1053575]; RFBR [13-06-00670, 13-04-01711, 13-04-90420]; Molecular and Cell Biology Program of the Presidium, Russian Academy of Sciences; OTKA [73430, 103983]; Finnish Professorpool (Paulo Foundation) Grant; LITGEN project - European Social Fund under Global Grant Measure [VP1-3.1-SMM-07-K-01-013]; Ukrainian SFFS grant [F53.4/071]; NIH [8DP1ES022577-04, GM40282, HG004120, HG002385, GM100233]; NSF HOMINID [BCS-0827436, BCS-1032255]; Indian CSIR Network Project [BSC0121]; Indian CSIR Bhatnagar Fellowship; European Union Regional Development Fund through Centre of Excellence in Genomics; University of Tartu; Estonian Basic Research grant [SF0270177As08]; Estonian Science Foundation [8973]; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer Research;  [SAF2011-26983]; [EM2012/045]; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1032255] Funding Source: National Science Foundation; Wellcome Trust [100719/Z/12/Z] Funding Source: researchfish; National Cancer Institute [ZIABC010022] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG002385, R01HG006399] Funding Source: NIH RePORTER
NR 69
TC 966
Z9 1090
U1 8
U2 573
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 18
PY 2014
VL 513
IS 7518
BP 409
EP +
DI 10.1038/nature13673
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900058
PM 25230663
DA 2026-03-09
ER

PT J
AU Zhou, PH
   Shaffer, DR
   Arias, DAA
   Nakazaki, Y
   Pos, W
   Torres, AJ
   Cremasco, V
   Dougan, SK
   Cowley, GS
   Elpek, K
   Brogdon, J
   Lamb, J
   Turley, SJ
   Ploegh, HL
   Root, DE
   Love, JC
   Dranoff, G
   Hacohen, N
   Cantor, H
   Wucherpfennig, KW
AF Zhou, Penghui
   Shaffer, Donald R.
   Arias, Diana A. Alvarez
   Nakazaki, Yukoh
   Pos, Wouter
   Torres, Alexis J.
   Cremasco, Viviana
   Dougan, Stephanie K.
   Cowley, Glenn S.
   Elpek, Kutlu
   Brogdon, Jennifer
   Lamb, John
   Turley, Shannon J.
   Ploegh, Hidde L.
   Root, David E.
   Love, J. Christopher
   Dranoff, Glenn
   Hacohen, Nir
   Cantor, Harvey
   Wucherpfennig, Kai W.
TI In vivo discovery of immunotherapy targets in the tumour microenvironment
SO NATURE
LA English
DT Article
ID cd8+ t-cells; prognostic-factors; immune cells; cancer; melanoma; phosphatase; suppressors; lymphocytes; proteins; survival
AB Recent clinical trials showed that targeting of inhibitory receptors on T cells induces durable responses in a subset of cancer patients, despite advanced disease. However, the regulatory switches controlling T-cell function in immunosuppressive tumours are not well understood. Here we show that such inhibitory mechanisms can be systematically discovered in the tumour microenvironment. We devised an in vivo pooled short hairpin RNA (shRNA) screen in which shRNAs targeting negative regulators became highly enriched in murine tumours by releasing a block on T-cell proliferation upon tumour antigen recognition. Such shRNAs were identified by deep sequencing of the shRNA cassette from T cells infiltrating tumour or control tissues. One of the target genes was Ppp2r2d, a regulatory subunit of the PP2A phosphatase family. In tumours, Ppp2r2d knockdown inhibited T-cell apoptosis and enhanced T-cell proliferation as well as cytokine production. Key regulators of immune function can therefore be discovered in relevant tissue microenvironments.
C1 [Zhou, Penghui; Shaffer, Donald R.; Arias, Diana A. Alvarez; Nakazaki, Yukoh; Pos, Wouter; Cremasco, Viviana; Elpek, Kutlu; Turley, Shannon J.; Dranoff, Glenn; Cantor, Harvey; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Torres, Alexis J.; Love, J. Christopher] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
   [Dougan, Stephanie K.; Ploegh, Hidde L.] MIT, Whitehead Inst, Cambridge, MA 02142 USA.
   [Cowley, Glenn S.; Root, David E.; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Brogdon, Jennifer] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Lamb, John] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Novartis; Novartis USA; Novartis; Novartis USA
RP Wucherpfennig, KW (corresponding author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM kai_wucherpfennig@dfci.harvard.edu
FU National Institutes of Health [1R01CA173750]; Melanoma Research Alliance; DF/HCC-MIT Bridge Project; Lustgarten Foundation; Novartis Institutes of Biomedical Research; Koch Institute from the National Cancer Institute [P30-CA14051]; American Cancer Society; Terri Brodeur Breast Cancer Foundation; NIH [AI07386]; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007386] Funding Source: NIH RePORTER
NR 48
TC 197
Z9 253
U1 1
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 FEB 6
PY 2014
VL 506
IS 7486
BP 52
EP +
DI 10.1038/nature12988
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100029
PM 24476824
DA 2026-03-09
ER

PT J
AU Kupitz, C
   Basu, S
   Grotjohann, I
   Fromme, R
   Zatsepin, NA
   Rendek, KN
   Hunter, MS
   Shoeman, RL
   White, TA
   Wang, DJ
   James, D
   Yang, JH
   Cobb, DE
   Reeder, B
   Sierra, RG
   Liu, HG
   Barty, A
   Aquila, AL
   Deponte, D
   Kirian, RA
   Bari, S
   Bergkamp, JJ
   Beyerlein, KR
   Bogan, MJ
   Caleman, C
   Chao, TC
   Conrad, CE
   Davis, KM
   Fleckenstein, H
   Galli, L
   Hau-Riege, SP
   Kassemeyer, S
   Laksmono, H
   Liang, MN
   Lomb, L
   Marchesini, S
   Martin, AV
   Messerschmidt, M
   Milathianaki, D
   Nass, K
   Ros, A
   Roy-Chowdhury, S
   Schmidt, K
   Seibert, M
   Steinbrener, J
   Stellato, F
   Yan, LF
   Yoon, C
   Moore, TA
   Moore, AL
   Pushkar, Y
   Williams, GJ
   Boutet, S
   Doak, RB
   Weierstall, U
   Frank, M
   Chapman, HN
   Spence, JCH
   Fromme, P
AF Kupitz, Christopher
   Basu, Shibom
   Grotjohann, Ingo
   Fromme, Raimund
   Zatsepin, Nadia A.
   Rendek, Kimberly N.
   Hunter, Mark S.
   Shoeman, Robert L.
   White, Thomas A.
   Wang, Dingjie
   James, Daniel
   Yang, Jay-How
   Cobb, Danielle E.
   Reeder, Brenda
   Sierra, Raymond G.
   Liu, Haiguang
   Barty, Anton
   Aquila, Andrew L.
   Deponte, Daniel
   Kirian, Richard A.
   Bari, Sadia
   Bergkamp, Jesse J.
   Beyerlein, Kenneth R.
   Bogan, Michael J.
   Caleman, Carl
   Chao, Tzu-Chiao
   Conrad, Chelsie E.
   Davis, Katherine M.
   Fleckenstein, Holger
   Galli, Lorenzo
   Hau-Riege, Stefan P.
   Kassemeyer, Stephan
   Laksmono, Hartawan
   Liang, Mengning
   Lomb, Lukas
   Marchesini, Stefano
   Martin, Andrew V.
   Messerschmidt, Marc
   Milathianaki, Despina
   Nass, Karol
   Ros, Alexandra
   Roy-Chowdhury, Shatabdi
   Schmidt, Kevin
   Seibert, Marvin
   Steinbrener, Jan
   Stellato, Francesco
   Yan, Lifen
   Yoon, Chunhong
   Moore, Thomas A.
   Moore, Ana L.
   Pushkar, Yulia
   Williams, Garth J.
   Boutet, Sebastien
   Doak, R. Bruce
   Weierstall, Uwe
   Frank, Matthias
   Chapman, Henry N.
   Spence, John C. H.
   Fromme, Petra
TI Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser
SO NATURE
LA English
DT Article
ID oxygen-evolving complex; free-electron laser; water oxidation; protein nanocrystallography; mn4ca cluster; structural models; crystal-structure; d1 polypeptide; s-3 states; omit maps
AB Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere(1). In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S-0 to S-4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed(2) technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S-1 state and after double laser excitation (putative S-3 state) at 5 and 5.5 angstrom resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S-2 to S-3 transition, as predicted by spectroscopic and computational studies(3,4). This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.
C1 [Kupitz, Christopher; Basu, Shibom; Grotjohann, Ingo; Fromme, Raimund; Rendek, Kimberly N.; Hunter, Mark S.; Yang, Jay-How; Cobb, Danielle E.; Reeder, Brenda; Bergkamp, Jesse J.; Chao, Tzu-Chiao; Conrad, Chelsie E.; Ros, Alexandra; Roy-Chowdhury, Shatabdi; Moore, Thomas A.; Moore, Ana L.; Fromme, Petra] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Zatsepin, Nadia A.; Wang, Dingjie; James, Daniel; Liu, Haiguang; Kirian, Richard A.; Schmidt, Kevin; Doak, R. Bruce; Weierstall, Uwe; Spence, John C. H.] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Hunter, Mark S.; Hau-Riege, Stefan P.; Frank, Matthias] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Shoeman, Robert L.; Kassemeyer, Stephan; Lomb, Lukas; Nass, Karol; Steinbrener, Jan] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [White, Thomas A.; Barty, Anton; Aquila, Andrew L.; Deponte, Daniel; Kirian, Richard A.; Beyerlein, Kenneth R.; Caleman, Carl; Fleckenstein, Holger; Galli, Lorenzo; Liang, Mengning; Martin, Andrew V.; Nass, Karol; Stellato, Francesco; Yoon, Chunhong; Chapman, Henry N.] Ctr Free Elect Laser Sci, DESY, D-22607 Hamburg, Germany.
   [Sierra, Raymond G.; Bogan, Michael J.; Laksmono, Hartawan] SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA.
   [Aquila, Andrew L.; Yoon, Chunhong] European XFEL GmbH, D-22607 Hamburg, Germany.
   [Deponte, Daniel; Messerschmidt, Marc; Milathianaki, Despina; Seibert, Marvin; Williams, Garth J.; Boutet, Sebastien] Natl Accelerator Lab, Stanford Linear Accelerator Ctr SLAC, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
   [Bari, Sadia; Kassemeyer, Stephan] Ctr Free Elect Laser Sci CFEL, Max Planck Adv Study Grp, D-22607 Hamburg, Germany.
   [Bari, Sadia] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Caleman, Carl] Uppsala Univ, Dept Phys & Astron, SE-75237 Uppsala, Sweden.
   [Chao, Tzu-Chiao] Univ Regina, Regina, SK S4S 0A2, Canada.
   [Davis, Katherine M.; Yan, Lifen; Pushkar, Yulia] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA.
   [Galli, Lorenzo; Nass, Karol; Chapman, Henry N.] Univ Hamburg, D-22761 Hamburg, Germany.
   [Marchesini, Stefano] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Martin, Andrew V.] Univ Melbourne, Dept Phys, Ctr Excellence Coherent Xray Sci, Dept ARC, Melbourne, Vic 3010, Australia.
   [Seibert, Marvin] Uppsala Univ, S-75312 Uppsala, Sweden.
   [Chapman, Henry N.] Ctr Ultrafast Imaging, D-22761 Hamburg, Germany.
C3 Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Max Planck Society; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; European XFEL; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Max Planck Society; Max Planck Society; Uppsala University; University of Regina; Purdue University System; Purdue University; University of Hamburg; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Melbourne; Uppsala University
RP Fromme, P (corresponding author), Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
EM pfromme@asu.edu
FU Center for Bio-Inspired Solar Fuel Production, an Energy Frontier Research Center - DOE, Office of Basic Energy Sciences [DE-SC0001016]; National Institutes of Health [1R01GM095583]; US National Science Foundation [MCB-1021557, MCB-1120997]; DFG Clusters of Excellence 'Inflammation at Interfaces' [EXC 306]; DFG Clusters of Excellence 'Center for Ultrafast Imaging'; Max Planck Society, the Atomic, Molecular and Optical Sciences Program; Deutsche Forschungsgemeinschaft (DFG); Chemical Sciences Geosciences and Biosciences Division, DOE OBES; SLAC LDRD program; US DOE through Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; UCOP Lab Fee Program [118036]; LLNL LDRD program [12-ERD-031]; Hamburg Ministry of Science and Research; Joachim Herz Stiftung as part of the Hamburg Initiative for Excellence in Research; U.S. Department of Energy (DOE), Office of Basic Energy Sciences [DE-FG02-12ER16340]; National Science Foundation Graduate Research Fellowship [0833366]; National Science Foundation through the BioFEL Science Technology Center [1231306]; Direct For Education and Human Resources; Division Of Graduate Education [0833366] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM095583] Funding Source: NIH RePORTER
NR 59
TC 390
Z9 466
U1 2
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 SEP 11
PY 2014
VL 513
IS 7517
BP 261
EP +
DI 10.1038/nature13453
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800056
PM 25043005
DA 2026-03-09
ER

PT J
AU Jiang, C
   Brown, PJB
   Ducret, A
   Brun, YV
AF Jiang, Chao
   Brown, Pamela J. B.
   Ducret, Adrien
   Brun, Yves V.
TI Sequential evolution of bacterial morphology by co-option of a developmental regulator
SO NATURE
LA English
DT Article
ID caulobacter; elongation; adhesive; division; growth; stalk; shape
AB What mechanisms under lie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies(1), the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk(2,3). The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis(4). Here we show that a developmental regulator of Caulobacter crescentus, SpmX(5), is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.
C1 [Jiang, Chao; Brown, Pamela J. B.; Ducret, Adrien; Brun, Yves V.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
C3 Indiana University System; Indiana University Bloomington
RP Brun, YV (corresponding author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
EM ybrun@indiana.edu
FU National Institutes of Health [S10RR028697-01, GM051986]; National Science Foundation [MCB0731950]; Indiana University Metabolomics and Cytomics Initiative (METACyt) program; Lilly Foundation; National Institutes of Health National Research Service Award [AI072992]
NR 40
TC 59
Z9 75
U1 1
U2 55
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 27
PY 2014
VL 506
IS 7489
BP 489
EP +
DI 10.1038/nature12900
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100038
PM 24463524
DA 2026-03-09
ER

PT J
AU Wumesh, KC
   Satpathy, AT
   Rapaport, AS
   Briseño, CG
   Wu, XD
   Albring, JC
   Russler-Germain, EV
   Kretzer, NM
   Durai, V
   Persaud, SP
   Edelson, BT
   Loschko, J
   Cella, M
   Allen, PM
   Nussenzweig, MC
   Colonna, M
   Sleckman, BP
   Murphy, TL
   Murphy, KM
AF Wumesh, K. C.
   Satpathy, Ansuman T.
   Rapaport, Aaron S.
   Briseno, Carlos G.
   Wu, Xiaodi
   Albring, Joern C.
   Russler-Germain, Emilie V.
   Kretzer, Nicole M.
   Durai, Vivek
   Persaud, Stephen P.
   Edelson, Brian T.
   Loschko, Jakob
   Cella, Marina
   Allen, Paul M.
   Nussenzweig, Michel C.
   Colonna, Marco
   Sleckman, Barry P.
   Murphy, Theresa L.
   Murphy, Kenneth M.
TI L-Myc expression by dendritic cells is required for optimal T-cell priming
SO NATURE
LA English
DT Article
ID colony-stimulating factor; c-myc; listeria-monocytogenes; in-vivo; mouse; receptor; mice; lymphocyte; activation; macrophage
AB The transcription factors c-Myc and N-Myc-encoded by Myc and Mycn, respectively-regulate cellular growth(1) and are required for embryonic development(2,3). A third paralogue, Mycl1, is dispensable for normal embryonic development but its biological function has remained unclear(4). To examine the in vivo function of Mycl1 in mice, we generated an inactivating Mycl1(gfp) allele that also reports Mycl1 expression. We find that Mycl1 is selectively expressed in dendritic cells (DCs) of the immune system and controlled by IRF8, and that during DC development, Mycl1 expression is initiated in the common DC progenitor(5) concurrent with reduction in c-Myc expression. Mature DCs lack expression of c-Myc and N-Myc but maintain L-Myc expression even in the presence of inflammatory signals such as granulocyte-macrophage colony-stimulating factor. All DC subsets develop in Mycl1-deficient mice, but some subsets such as migratory CD103(+) conventional DCs in the lung and liver are greatly reduced at steady state. Importantly, loss of L-Myc by DCs causes a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. The replacement of c-Myc by L-Myc in immature DCs may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming(6).
C1 [Wumesh, K. C.; Satpathy, Ansuman T.; Rapaport, Aaron S.; Briseno, Carlos G.; Wu, Xiaodi; Russler-Germain, Emilie V.; Kretzer, Nicole M.; Durai, Vivek; Persaud, Stephen P.; Edelson, Brian T.; Cella, Marina; Allen, Paul M.; Colonna, Marco; Sleckman, Barry P.; Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
   [Albring, Joern C.] Univ Munster, Dept Med Hematol & Oncol A, D-48149 Munster, Germany.
   [Loschko, Jakob; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10065 USA.
   [Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); University of Munster; Howard Hughes Medical Institute; Rockefeller University; Washington University (WUSTL); Howard Hughes Medical Institute
RP Murphy, KM (corresponding author), Washington Univ, Dept Pathol & Immunol, Sch Med, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM kmurphy@wustl.edu
FU Howard Hughes Medical Institute; Siteman Cancer Center; American Heart Association [12PRE8610005, 12PRE12050419]; German Research Foundation [AL 1038/1-1]; American Society of Hematology Scholar Award; Burroughs Wellcome Fund Career Award; NCI Cancer Center Support Grant [P30 CA91842]; National Cancer Institute [P30CA091842] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007163, R01AI047829] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007200] Funding Source: NIH RePORTER; American Heart Association (AHA) [12PRE12050419, 12PRE8610005] Funding Source: American Heart Association (AHA)
NR 49
TC 64
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 13
PY 2014
VL 507
IS 7491
BP 243
EP +
DI 10.1038/nature12967
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800041
PM 24509714
DA 2026-03-09
ER

PT J
AU Alexandre, C
   Baena-Lopez, A
   Vincent, JP
AF Alexandre, Cyrille
   Baena-Lopez, Alberto
   Vincent, Jean-Paul
TI Patterning and growth control by membrane-tethered Wingless
SO NATURE
LA English
DT Article
ID long-range action; gene-expression; imaginal discs; morphogen gradient; signaling pathway; drosophila leg; senseless; margin; cells; notch
AB Wnts are evolutionarily conserved secreted signalling proteins that, in various developmental contexts, spread from their site of synthesis to form a gradient and activate target-gene expression at a distance. However, the requirement for Wnts to spread has never been directly tested. Here we used genome engineering to replace the endogenous wingless gene, which encodes the main Drosophila Wnt, with one that expresses a membrane-tethered form of the protein. Surprisingly, the resulting flies were viable and produced normally patterned appendages of nearly the right size, albeit with a delay. We show that, in the prospective wing, prolonged wingless transcription followed by memory of earlier signalling allows persistent expression of relevant target genes. We suggest therefore that the spread of Wingless is dispensable for patterning and growth even though it probably contributes to increasing cell proliferation.
C1 [Alexandre, Cyrille; Baena-Lopez, Alberto; Vincent, Jean-Paul] Natl Inst Med Res, MRC, London NW7 1AA, England.
C3 MRC National Institute for Medical Research
RP Vincent, JP (corresponding author), Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England.
EM jvincen@nimr.mrc.ac.uk
FU UK Medical Research Council [U117584268]; ERC grant (WNTEXPORT) from the European Union; Sir Henry Wellcome post-doctoral fellowship [082694/Z/07/Z]; Wellcome Trust [082694/Z/07/Z] Funding Source: Wellcome Trust; Medical Research Council [MC_U117584268] Funding Source: researchfish
NR 39
TC 234
Z9 275
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 JAN 9
PY 2014
VL 505
IS 7482
BP 180
EP +
DI 10.1038/nature12879
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500031
PM 24390349
DA 2026-03-09
ER

PT J
AU Brady, DC
   Crowe, MS
   Turski, ML
   Hobbs, GA
   Yao, XJ
   Chaikuad, A
   Knapp, S
   Xiao, KH
   Campbell, SL
   Thiele, DJ
   Counter, CM
AF Brady, Donita C.
   Crowe, Matthew S.
   Turski, Michelle L.
   Hobbs, G. Aaron
   Yao, Xiaojie
   Chaikuad, Apirat
   Knapp, Stefan
   Xiao, Kunhong
   Campbell, Sharon L.
   Thiele, Dennis J.
   Counter, Christopher M.
TI Copper is required for oncogenic BRAF signalling and tumorigenesis
SO NATURE
LA English
DT Article
ID catalyzed oxidation reactions; mek inhibition; in-vivo; beta(2)-adrenergic receptor; mass-spectrometry; ras oncogenesis; cancer; mutations; activation; melanoma
AB The BRAF kinase is mutated, typically Val 600 -> Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers(1,2). BRAF(V600E) phosphorylates and activates the MEK1 andMEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, stimulating the mitogen-activated protein kinase (MAPK) pathway to promote cancer(3). Targeting MEK1/2 is proving to be an important therapeutic strategy, given that a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma(4), an effect that is increased when administered together with a BRAF(V600E) inhibitor(5). We previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction(6). Here we show decreasing the levels of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driven signalling and tumorigenesis in mice and human cell settings. Conversely, a MEK1-MEK5 chimaera that phosphorylated ERK1/2 independently of Cu or an active ERK2 restored the tumour growth of murine cells lacking Ctrl1. Cu chelators used in the treatment of Wilson disease(7) decreased tumour growth of human or murine cells transformed by BRAF(V600E) or engineered to be resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat cancers containing the BRAF(V600E) mutation.
C1 [Brady, Donita C.; Crowe, Matthew S.; Turski, Michelle L.; Thiele, Dennis J.; Counter, Christopher M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Hobbs, G. Aaron; Campbell, Sharon L.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   [Yao, Xiaojie; Xiao, Kunhong] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Chaikuad, Apirat; Knapp, Stefan] Univ Oxford, Target Discovery Inst, Nuffield Dept Clin Med, Oxford OX3 7DQ, England.
   [Chaikuad, Apirat; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England.
   [Counter, Christopher M.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA.
C3 Duke University; University of North Carolina; University of North Carolina Chapel Hill; Duke University; University of Oxford; University of Oxford; Duke University
RP Counter, CM (corresponding author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
EM chris.counter@duke.edu
FU National Institutes of Health [CA178145, HL075443, DK074192, CA094184, CA172104]; Structural Genomics Consortium (Welcome Trust) [092809/Z/10/Z]; FP7 grant [278568]; Stewart Trust; Edward Spiegel Fund of the Lymphoma Foundation; National Cancer Institute [P30CA014236, P30CA016086] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008570] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK074192] Funding Source: NIH RePORTER
NR 42
TC 508
Z9 591
U1 1
U2 206
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 492
EP +
DI 10.1038/nature13180
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000039
PM 24717435
DA 2026-03-09
ER

PT J
AU Hall, CN
   Reynell, C
   Gesslein, B
   Hamilton, NB
   Mishra, A
   Sutherland, BA
   O'Farrell, FM
   Buchan, AM
   Lauritzen, M
   Attwell, D
AF Hall, Catherine N.
   Reynell, Clare
   Gesslein, Bodil
   Hamilton, Nicola B.
   Mishra, Anusha
   Sutherland, Brad A.
   O'Farrell, Fergus M.
   Buchan, Alastair M.
   Lauritzen, Martin
   Attwell, David
TI Capillary pericytes regulate cerebral blood flow in health and disease
SO NATURE
LA English
DT Article
ID in-vivo; neuronal-activity; ischemic-stroke; brain; cells; stimulation; reperfusion; glycolysis; perfusion; diameter
AB Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD(blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E-2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.
C1 [Hall, Catherine N.; Reynell, Clare; Hamilton, Nicola B.; Mishra, Anusha; O'Farrell, Fergus M.; Attwell, David] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
   [Gesslein, Bodil; Lauritzen, Martin] Univ Copenhagen, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
   [Gesslein, Bodil; Lauritzen, Martin] Univ Copenhagen, Ctr Hlth Aging, DK-2200 Copenhagen N, Denmark.
   [Sutherland, Brad A.; Buchan, Alastair M.] Univ Oxford, Radcliffe Dept Med, Acute Stroke Programme, Oxford OX3 9DU, England.
   [Lauritzen, Martin] Glostrup Univ Hosp, Dept Clin Neurophysiol, DK-2600 Glostrup, Denmark.
C3 University of London; University College London; University of Copenhagen; University of Copenhagen; University of Oxford; University of Copenhagen; Copenhagen University Hospital
RP Attwell, D (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England.
EM mlauritz@sund.ku.dk; d.attwell@ucl.ac.uk
FU Fondation Leducq; European Research Council; Wellcome Trust; UK Medical Research Council; Rosetrees Trust; Nordea Foundation via the Center for Healthy Aging; Lundbeck Foundation; NOVO-Nordisk Foundation; Danish Medical Research Council; Medical Research Council [G0500495, 1075001] Funding Source: researchfish; Wellcome Trust [099222/Z/12/Z] Funding Source: researchfish
NR 50
TC 1476
Z9 1717
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 APR 3
PY 2014
VL 508
IS 7494
BP 55
EP +
DI 10.1038/nature13165
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900041
PM 24670647
DA 2026-03-09
ER

PT J
AU Wilson, AC
   Colombe, Y
   Brown, KR
   Knill, E
   Leibfried, D
   Wineland, DJ
AF Wilson, A. C.
   Colombe, Y.
   Brown, K. R.
   Knill, E.
   Leibfried, D.
   Wineland, D. J.
TI Tunable spin-spin interactions and entanglement of ions in separate potential wells
SO NATURE
LA English
DT Article
ID quantum simulation; trapped ions; computers; physics
AB Quantum simulation(1,2)-the use of one quantum system to simulate a less controllable one-may provide an understanding of the many quantum systems which cannot be modelled using classical computers. Considerable progress in control and manipulation has been achieved for various quantum systems(3-5), but one of the remaining challenges is the implementation of scalable devices. In this regard, individual ions trapped in separate tunable potential wells are promising(6-8). Here we implement the basic features of this approach and demonstrate deterministic tuning of the Coulomb interaction between two ions, independently controlling their local wells. The scheme is suitable for emulating a range of spin-spin interactions, but to characterize the performance of our set-up we select one that entangles the internal states of the two ions with a fidelity of 0.82(1) (the digit inparentheses shows the standard error of the mean). Extension of this building block to a two-dimensional network, which is possible using ion-trap microfabrication processes(9), may provide a new quantum simulator architecture with broad flexibility in designing and scaling the arrangement of ions and their mutual interactions. To perform useful quantum simulations, including those of condensed-matter phenomena such as the fractional quantum Hall effect, an array of tens of ions might be sufficient(4,10,11).
C1 [Wilson, A. C.; Colombe, Y.; Knill, E.; Leibfried, D.; Wineland, D. J.] NIST, Boulder, CO 80305 USA.
   [Brown, K. R.] Georgia Tech Res Inst, Atlanta, GA 30332 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Georgia; Georgia Institute of Technology
RP Wilson, AC (corresponding author), NIST, 325 Broadway, Boulder, CO 80305 USA.
EM andrew.wilson@nist.gov
FU Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA); ONR; NIST Quantum Information Program
NR 39
TC 78
Z9 91
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 AUG 7
PY 2014
VL 512
IS 7512
BP 57
EP +
DI 10.1038/nature13565
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000030
PM 25100480
DA 2026-03-09
ER

PT J
AU Snellen, IAG
   Brandl, BR
   de Kok, RJ
   Brogi, M
   Birkby, J
   Schwarz, H
AF Snellen, Ignas A. G.
   Brandl, Bernhard R.
   de Kok, Remco J.
   Brogi, Matteo
   Birkby, Jayne
   Schwarz, Henriette
TI Fast spin of the young extrasolar planet β Pictoris b
SO NATURE
LA English
DT Article
ID collision-induced absorption; water-absorption; carbon-monoxide; doppler images; rotating stars; c/o ratio; h-2 pairs; spectroscopy; velocity; atmosphere
AB The spin of a planet arises from the accretion of angular momentum during its formation(1-3), but the details of this process are still unclear. In the Solar System, the equatorial rotation velocities and, consequently, spin angular momenta of most of the planets increase with planetary mass(4); the exceptions to this trend are Mercury and Venus, which, since formation, have significantly spun down because of tidal interactions(5,6). Here we report near-infrared spectroscopic observations, at a resolving power of 100,000, of the young extrasolar gas giant planet beta Pictoris b (refs 7, 8). The absorption signal from carbon monoxide in the planet's thermal spectrum is found to be blueshifted with respect to that from the parent star by approximately 15 kilometres per second, consistent with a circular orbit(9). The combined line profile exhibits a rotational broadening of about 25 kilometres per second, meaning that beta Pictoris b spins significantly faster than any planet in the Solar System, in line with the extrapolation of the known trend in spin velocity with planet mass.
C1 [Snellen, Ignas A. G.; Brandl, Bernhard R.; de Kok, Remco J.; Brogi, Matteo; Birkby, Jayne; Schwarz, Henriette] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [de Kok, Remco J.] Netherlands Inst Space Res SRON, NL-3584 CA Utrecht, Netherlands.
C3 Leiden University; Leiden University - Excl LUMC
RP Snellen, IAG (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM snellen@strw.leidenuniv.nl
FU NWO VICI
NR 42
TC 308
Z9 361
U1 0
U2 20
PU NATURE PUBLISHING 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 1
PY 2014
VL 509
IS 7498
BP 63
EP +
DI 10.1038/nature13253
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100039
PM 24784216
DA 2026-03-09
ER

PT J
AU Trobaugh, DW
   Gardner, CL
   Sun, CQ
   Haddow, AD
   Wang, EY
   Chapnik, E
   Mildner, A
   Weaver, SC
   Ryman, KD
   Klimstra, WB
AF Trobaugh, Derek W.
   Gardner, Christina L.
   Sun, Chengqun
   Haddow, Andrew D.
   Wang, Eryu
   Chapnik, Elik
   Mildner, Alexander
   Weaver, Scott C.
   Ryman, Kate D.
   Klimstra, William B.
TI RNA viruses can hijack vertebrate microRNAs to suppress innate immunity
SO NATURE
LA English
DT Article
ID eastern equine encephalitis; interferon sensitivity; messenger-rna; protein; replication; emergence; infection
AB Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses(1). This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs(2,3). Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.
C1 [Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Ryman, Kate D.; Klimstra, William B.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
   [Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Ryman, Kate D.; Klimstra, William B.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
   [Haddow, Andrew D.; Wang, Eryu; Weaver, Scott C.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Inst Human Infect & Immun, Galveston, TX 77555 USA.
   [Haddow, Andrew D.; Wang, Eryu; Weaver, Scott C.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
   [Chapnik, Elik] Weizmann Inst Sci, Dept Mol Genet, IL-7610001 Rehovot, Israel.
   [Mildner, Alexander] Weizmann Inst Sci, Dept Immunol, IL-7610001 Rehovot, Israel.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; Weizmann Institute of Science; Weizmann Institute of Science
RP Klimstra, WB (corresponding author), Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
EM klimstra@pitt.edu
FU National Institutes of Health (NIH) [AI049820-10, AI060525-08, AI083383, AI095436]; National Institute of Allergy and Infectious Diseases through the Pacific Northwest Regional Centers for Excellence in Biodefense and Emerging Infectious Diseases Research [U54 AI081680]; National Institute of Allergy and Infectious Diseases [T32AI049820, R01AI095436] Funding Source: NIH RePORTER
NR 31
TC 194
Z9 225
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 FEB 13
PY 2014
VL 506
IS 7487
BP 245
EP +
DI 10.1038/nature12869
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700043
PM 24352241
DA 2026-03-09
ER

PT J
AU Yvon-Durocher, G
   Allen, AP
   Bastviken, D
   Conrad, R
   Gudasz, C
   St-Pierre, A
   Thanh-Duc, N
   del Giorgio, PA
AF Yvon-Durocher, Gabriel
   Allen, Andrew P.
   Bastviken, David
   Conrad, Ralf
   Gudasz, Cristian
   St-Pierre, Annick
   Nguyen Thanh-Duc
   del Giorgio, Paul A.
TI Methane fluxes show consistent temperature dependence across microbial to ecosystem scales
SO NATURE
LA English
DT Article
ID emissions; carbon; wetlands; model; methanogenesis; respiration
AB Methane (CH4) is an important greenhouse gas because it has 25 times the global warming potential of carbon dioxide (CO2) by mass over a century(1). Recent calculations suggest that atmospheric CH4 emissions have been responsible for approximately 20% of Earth's warming since pre-industrial times(2). Understanding how CH4 emissions from ecosystems will respond to expected increases in global temperature is therefore fundamental to predicting whether the carbon cycle will mitigate or accelerate climate change. Methanogenesis is the terminal step in the remineralization of organic matter and is carried out by strictly anaerobic Archaea(3). Like most other forms of metabolism, methanogenesis is temperature-dependent(4,5). However, it is not yet known how this physiological response combines with other biotic processes (for example, methanotrophy(6), substrate supply(3,7), microbial community composition(8)) and abiotic processes (for example, water-table depth(9,10)) to determine the temperature dependence of ecosystem-level CH4 emissions. It is also not known whether CH4 emissions at the ecosystem level have a fundamentally different temperature dependence than other key fluxes in the carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses to show that seasonal variations in CH4 emissions from a wide range of ecosystems exhibit an average temperature dependence similar to that of CH4 production derived from pure cultures of methanogens and anaerobic microbial communities. This average temperature dependence (0.96 electron volts (eV)), which corresponds to a 57-fold increase between 0 and 30 degrees C, is considerably higher than previously observed for respiration (approximately 0.65 eV)(11) and photosynthesis (approximately 0.3 eV)(12). As a result, we show that both the emission of CH4 and the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in temperature. Our findings suggest that global warming may have a large impact on the relative contributions of CO2 and CH4 to total greenhouse gas emissions from aquatic ecosystems, terrestrial wetlands and rice paddies.
C1 [Yvon-Durocher, Gabriel] Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
   [Allen, Andrew P.] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [Bastviken, David] Linkoping Univ, Dept Themat Studies Water & Environm Studies, SE-58183 Linkoping, Sweden.
   [Conrad, Ralf] Max Planck Inst Terr Microbiol, D-35043 Marburg, Germany.
   [Gudasz, Cristian] Umea Univ, Dept Ecol & Environm Sci, SE-90187 Umea, Sweden.
   [Gudasz, Cristian] Uppsala Univ, Dept Ecol & Genet, SE-75236 Uppsala, Sweden.
   [St-Pierre, Annick; del Giorgio, Paul A.] Univ Quebec, Dept Sci Biol, Montreal, PQ H2X 3X8, Canada.
   [Nguyen Thanh-Duc] Univ New Hampshire, Inst Study Earth Oceans & Space, Earth Syst Res Ctr, Durham, NH 03824 USA.
C3 University of Exeter; Macquarie University; Linkoping University; Max Planck Society; Umea University; Uppsala University; University of Quebec; University of Quebec Montreal; University System Of New Hampshire; University of New Hampshire
RP Yvon-Durocher, G (corresponding author), Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
EM g.yvon-durocher@exeter.ac.uk
NR 38
TC 820
Z9 980
U1 27
U2 1222
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2014
VL 507
IS 7493
BP 488
EP 491
DI 10.1038/nature13164
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000038
PM 24670769
DA 2026-03-09
ER

PT J
AU Lemos, GB
   Borish, V
   Cole, GD
   Ramelow, S
   Lapkiewicz, R
   Zeilinger, A
AF Lemos, Gabriela Barreto
   Borish, Victoria
   Cole, Garrett D.
   Ramelow, Sven
   Lapkiewicz, Radek
   Zeilinger, Anton
TI Quantum imaging with undetected photons
SO NATURE
LA English
DT Article
ID parametric down-conversion; induced coherence; induced emission; 2-particle interferometry; indistinguishability; interference; optics
AB Information is central to quantum mechanics. In particular, quantum interference occurs only if there exists no information to distinguish between the superposed states. The mere possibility of obtaining information that could distinguish between overlapping states inhibits quantum interference(1,2). Here we introduce and experimentally demonstrate a quantum imaging concept based on induced coherence without induced emission(3,4). Our experiment uses two separate down-conversion nonlinear crystals (numbered NL1 and NL2), each illuminated by the same pump laser, creating one pair of photons (denoted idler and signal). If the photon pair is created in NL1, one photon (the idler) passes through the object to be imaged and is overlapped with the idler amplitude created in NL2, its source thus being undefined. Interference of the signal amplitudes coming from the two crystals then reveals the image of the object. The photons that pass through the imaged object (idler photons from NL1) are never detected, while we obtain images exclusively with the signal photons (from NL1 and NL2), which do not interact with the object. Our experiment is fundamentally different from previous quantum imaging techniques, such as interaction-free imaging(5) or ghostimaging(6-9), because now the photons used to illuminate the object do not have to be detected at all and no coincidence detection is necessary. This enables the probe wavelength to be chosen in a range for which suitable detectors are not available. To illustrate this, we show images of objects that are either opaque or invisible to the detected photons. Our experiment is a prototype in quantum information-knowledge can be extracted by, and about, a photon that is never detected.
C1 [Lemos, Gabriela Barreto; Borish, Victoria; Ramelow, Sven; Lapkiewicz, Radek; Zeilinger, Anton] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-1090 Vienna, Austria.
   [Lemos, Gabriela Barreto; Cole, Garrett D.; Zeilinger, Anton] Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol VCQ, A-1090 Vienna, Austria.
   [Borish, Victoria; Cole, Garrett D.; Ramelow, Sven; Lapkiewicz, Radek; Zeilinger, Anton] Univ Vienna, A-1090 Vienna, Austria.
C3 Austrian Academy of Sciences; University of Vienna; University of Vienna
RP Lemos, GB (corresponding author), Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, Boltzmanngasse 3, A-1090 Vienna, Austria.
EM gabriela.barreto.lemos@univie.ac.at; anton.zeilinger@univie.ac.at
FU Austrian Academy of Sciences (OAW) through Vienna Center for Science and Technology (VCQ); EU Marie Curie Fellowship [PIOF-GA-2012-329851]; OAW; European Research Council (ERC) [227844, 600645]; European Research Council (ERC) [227844] Funding Source: European Research Council (ERC)
NR 25
TC 531
Z9 584
U1 4
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 AUG 28
PY 2014
VL 512
IS 7515
BP 409
EP U382
DI 10.1038/nature13586
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600028
PM 25164751
DA 2026-03-09
ER

PT J
AU Gubin, MM
   Zhang, XL
   Schuster, H
   Caron, E
   Ward, JP
   Noguchi, T
   Ivanova, Y
   Hundal, J
   Arthur, CD
   Krebber, WJ
   Mulder, GE
   Toebes, M
   Vesely, MD
   Lam, SSK
   Korman, AJ
   Allison, JP
   Freeman, GJ
   Sharpe, AH
   Pearce, EL
   Schumacher, TN
   Aebersold, R
   Rammensee, HG
   Melief, CJM
   Mardis, ER
   Gillanders, WE
   Artyomov, MN
   Schreiber, RD
AF Gubin, Matthew M.
   Zhang, Xiuli
   Schuster, Heiko
   Caron, Etienne
   Ward, Jeffrey P.
   Noguchi, Takuro
   Ivanova, Yulia
   Hundal, Jasreet
   Arthur, Cora D.
   Krebber, Willem-Jan
   Mulder, Gwenn E.
   Toebes, Mireille
   Vesely, Matthew D.
   Lam, Samuel S. K.
   Korman, Alan J.
   Allison, James P.
   Freeman, Gordon J.
   Sharpe, Arlene H.
   Pearce, Erika L.
   Schumacher, Ton N.
   Aebersold, Ruedi
   Rammensee, Hans-Georg
   Melief, Cornelis J. M.
   Mardis, Elaine R.
   Gillanders, William E.
   Artyomov, Maxim N.
   Schreiber, Robert D.
TI Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
SO NATURE
LA English
DT Article
ID exome analysis reveals; quantitative proteomics; t-cells; pd-1; inflammation; responses; equilibrium; predictions; ipilimumab; tolerance
AB The immune system influences the fate of developing cancers by not only functioning as a tumour promoter that facilitates cellular transformation, promotes tumour growth and sculpts tumour cell immunogenicity(1-6), but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion(1,2,7). Yet, clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer-induced immunosuppression. In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD -1), two immunomodulatory receptors expressed on T cells(8,9). Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits including durable responses to patients with different malignancies(10-13). However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Here we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and we show that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Although mutant tumour-antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with anti-PD-1 and/or anti-CTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles, rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy, but they can also be used to develop personalized cancer-specific vaccines and to probe the mechanistic
C1 [Gubin, Matthew M.; Ward, Jeffrey P.; Noguchi, Takuro; Ivanova, Yulia; Arthur, Cora D.; Vesely, Matthew D.; Lam, Samuel S. K.; Pearce, Erika L.; Artyomov, Maxim N.; Schreiber, Robert D.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Zhang, Xiuli; Gillanders, William E.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
   [Schuster, Heiko; Rammensee, Hans-Georg] German Canc Res Ctr, Dept Immunol, Inst Cell Biol, D-72076 Tubingen, Germany.
   [Schuster, Heiko; Rammensee, Hans-Georg] German Canc Res Ctr, German Canc Consortium DKTK, D-72076 Tubingen, Germany.
   [Caron, Etienne; Aebersold, Ruedi] ETH, Dept Biol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Ward, Jeffrey P.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA.
   [Hundal, Jasreet; Mardis, Elaine R.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Krebber, Willem-Jan; Mulder, Gwenn E.; Melief, Cornelis J. M.] ISA Therapeut BV, NL-2333 CH Leiden, Netherlands.
   [Toebes, Mireille; Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands.
   [Korman, Alan J.] Bristol Myers Squibb Co, Redwood City, CA 94063 USA.
   [Allison, James P.] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
   [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8093 Zurich, Switzerland.
   [Melief, Cornelis J. M.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands.
   [Mardis, Elaine R.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Helmholtz Association; German Cancer Research Center (DKFZ); Eberhard Karls University of Tubingen; Helmholtz Association; German Cancer Research Center (DKFZ); Swiss Federal Institutes of Technology Domain; ETH Zurich; Washington University (WUSTL); Washington University (WUSTL); Netherlands Cancer Institute; Bristol-Myers Squibb; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; University of Zurich; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Washington University (WUSTL)
RP Schreiber, RD (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA.
EM schreiber@immunology.wustl.edu
FU National Cancer Institute [R01 CA043059, U01 CA141541, T32 CA00954729]; Cancer Research Institute; WWWW Foundation; Siteman Cancer Center/Barnes-Jewish Hospital (Cancer Frontier Fund); Susan G. Komen for the Cure (Promise grant); National Human Genome Research Institute; National Institute of Health [P50 CA101942, P01 A1054456]; Dutch Cancer Society (Queen Wilhelmina Research Award); Marie Curie Intra-European Fellowship within the Seventh Framework Programme of the European Community for Research; postdoctoral training grant(Irvington Postdoctoral Fellowship)from the Cancer Research Institute; National Cancer Institute [P30CA091842, P30CA016672, P50CA101942, T32CA009547] Funding Source: NIH RePORTER
NR 46
TC 1669
Z9 1951
U1 4
U2 643
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 577
EP +
DI 10.1038/nature13988
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600056
PM 25428507
DA 2026-03-09
ER

PT J
AU Larsbrink, J
   Rogers, TE
   Hemsworth, GR
   McKee, LS
   Tauzin, AS
   Spadiut, O
   Klinter, S
   Pudlo, NA
   Urs, K
   Koropatkin, NM
   Creagh, AL
   Haynes, CA
   Kelly, AG
   Cederholm, SN
   Davies, GJ
   Martens, EC
   Brumer, H
AF Larsbrink, Johan
   Rogers, Theresa E.
   Hemsworth, Glyn R.
   McKee, Lauren S.
   Tauzin, Alexandra S.
   Spadiut, Oliver
   Klinter, Stefan
   Pudlo, Nicholas A.
   Urs, Karthik
   Koropatkin, Nicole M.
   Creagh, A. Louise
   Haynes, Charles A.
   Kelly, Amelia G.
   Cederholm, Stefan Nilsson
   Davies, Gideon J.
   Martens, Eric C.
   Brumer, Harry
TI A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes
SO NATURE
LA English
DT Article
ID carbohydrate-active enzymes; maximum-likelihood; cell walls; microbiome; proteins; bacteria; metagenomics; degradation; specificity; recognition
AB A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed 'dietary fibre', from the cell walls of diverse fruits and vegetables(1). Owing to the paucity of alimentary enzymes encoded by the human genome(2), our ability to derive energy from dietary fibre depends on the saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut(3,4). The xyloglucans (XyGs) are a ubiquitous family of highly branched plant cell wall polysaccharides(5,6) whose mechanism(s) of degradation in the human gut and consequent importance in nutrition have been unclear(1,7,8). Here we demonstrate that a single, complex gene locus in Bacteroides ovatus confers XyG catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard endo-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous XyG utilization loci (XyGULs) serve as genetic markers of XyG catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health(9-12).
C1 [Larsbrink, Johan; McKee, Lauren S.; Spadiut, Oliver; Klinter, Stefan; Cederholm, Stefan Nilsson; Brumer, Harry] AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Glycosci, S-10691 Stockholm, Sweden.
   [Rogers, Theresa E.; Pudlo, Nicholas A.; Urs, Karthik; Koropatkin, Nicole M.; Kelly, Amelia G.; Martens, Eric C.] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48109 USA.
   [Hemsworth, Glyn R.; Davies, Gideon J.] Univ York, Dept Chem, Struct Biol Lab, York YO10 5DD, N Yorkshire, England.
   [McKee, Lauren S.; Spadiut, Oliver] Royal Inst Technol KTH, Wallenberg Wood Sci Ctr, S-10044 Stockholm, Sweden.
   [Tauzin, Alexandra S.; Brumer, Harry] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada.
   [Tauzin, Alexandra S.; Brumer, Harry] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z4, Canada.
   [Creagh, A. Louise; Haynes, Charles A.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada.
   [Creagh, A. Louise; Haynes, Charles A.] Univ British Columbia, Dept Chem & Biol Engn, Vancouver, BC V6T 1Z4, Canada.
C3 Royal Institute of Technology; University of Michigan System; University of Michigan; University of York - UK; Royal Institute of Technology; University of British Columbia; University of British Columbia; University of British Columbia; University of British Columbia
RP Brumer, H (corresponding author), AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Glycosci, S-10691 Stockholm, Sweden.
EM gideon.davies@york.ac.uk; emartens@umich.edu; brumer@msl.ubc.ca
FU Mizutani Foundation for Glycoscience; Swedish Research Council Formas (via CarboMat-the KTH Advanced Carbohydrate Materials Centre); Swedish Research Council (Vetenskapsradet); Wallenberg Wood Science Centre; Michael Smith Laboratories, University of British Columbia; Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation; British Columbia Knowledge Development Fund; Biotechnology and Biological Sciences Research Council [BB/I014802/1]; National Institutes of Health [DK084214, GM099513]; Global Probiotics Council Young Investigator Grant for Probiotics Research; Biotechnology and Biological Sciences Research Council [BB/I014802/1] Funding Source: researchfish; BBSRC [BB/I014802/1] Funding Source: UKRI
NR 59
TC 388
Z9 469
U1 7
U2 335
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 27
PY 2014
VL 506
IS 7489
BP 498
EP +
DI 10.1038/nature12907
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100040
PM 24463512
DA 2026-03-09
ER

PT J
AU Gilissen, C
   Hehir-Kwa, JY
   Thung, DT
   van de Vorst, M
   van Bon, BWM
   Willemsen, MH
   Kwint, M
   Janssen, IM
   Hoischen, A
   Schenck, A
   Leach, R
   Klein, R
   Tearle, R
   Bo, T
   Pfundt, R
   Yntema, HG
   de Vries, BBA
   Kleefstra, T
   Brunner, HG
   Vissers, LELM
   Veltman, JA
AF Gilissen, Christian
   Hehir-Kwa, Jayne Y.
   Thung, Djie Tjwan
   van de Vorst, Maartje
   van Bon, Bregje W. M.
   Willemsen, Marjolein H.
   Kwint, Michael
   Janssen, Irene M.
   Hoischen, Alexander
   Schenck, Annette
   Leach, Richard
   Klein, Robert
   Tearle, Rick
   Bo, Tan
   Pfundt, Rolph
   Yntema, Helger G.
   de Vries, Bert B. A.
   Kleefstra, Tjitske
   Brunner, Han G.
   Vissers, Lisenka E. L. M.
   Veltman, Joris A.
TI Genome sequencing identifies major causes of severe intellectual disability
SO NATURE
LA English
DT Article
ID de-novo mutations; copy-number variation; mental-retardation; autism; schizophrenia; variants; spectrum; protein; paradigm; network
AB Severe intellectual disability (ID) occurs in 0.5% of newborns and is thought to be largely genetic in origin(1,2). The extensive genetic heterogeneity of this disorder requires a genome-wide detection of all types of genetic variation. Microarray studies and, more recently, exome sequencing have demonstrated the importance of de novo copy number variations (CNVs) and single-nucleotide variations (SNVs) in ID, but the majority of cases remain undiagnosed(3-6). Here we applied whole-genome sequencing to 50 patients with severe ID and their unaffected parents. All patients included had not received a molecular diagnosis after extensive genetic prescreening, including microarray-based CNV studies and exome sequencing. Notwithstanding this prescreening, 84 de novo SNVs affecting the coding region were identified, which showed a statistically significant enrichment of loss-of-function mutations as well as an enrichment for genes previously implicated in ID-related disorders. In addition, we identified eight de novo CNVs, including single-exon and intra-exonic deletions, as well as interchromosomal duplications. These CNVs affected known ID genes more frequently than expected. On the basis of diagnostic interpretation of all de novo variants, a conclusive genetic diagnosis was reached in 20 patients. Together with one compound heterozygous CNV causing disease in a recessive mode, this results in a diagnostic yield of 42% in this extensively studied cohort, and 62% as a cumulative estimate in an unselected cohort. These results suggest that de novo SNVs and CNVs affecting the coding region are a major cause of severe ID. Genome sequencing can be applied as a single genetic test to reliably identify and characterize the comprehensive spectrum of genetic variation, providing a genetic diagnosis in the majority of patients with severe ID.
C1 [Gilissen, Christian; Hehir-Kwa, Jayne Y.; Thung, Djie Tjwan; van de Vorst, Maartje; van Bon, Bregje W. M.; Willemsen, Marjolein H.; Kwint, Michael; Janssen, Irene M.; Hoischen, Alexander; Schenck, Annette; Bo, Tan; Pfundt, Rolph; Yntema, Helger G.; de Vries, Bert B. A.; Kleefstra, Tjitske; Brunner, Han G.; Vissers, Lisenka E. L. M.; Veltman, Joris A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Human Genet, NL-6525 GA Nijmegen, Netherlands.
   [Gilissen, Christian; Hehir-Kwa, Jayne Y.; Thung, Djie Tjwan; van de Vorst, Maartje; van Bon, Bregje W. M.; Willemsen, Marjolein H.; Kwint, Michael; Janssen, Irene M.; Hoischen, Alexander; Schenck, Annette; Bo, Tan; Pfundt, Rolph; Yntema, Helger G.; de Vries, Bert B. A.; Kleefstra, Tjitske; Brunner, Han G.; Vissers, Lisenka E. L. M.; Veltman, Joris A.] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Neurosci, NL-6525 GA Nijmegen, Netherlands.
   [Leach, Richard; Klein, Robert; Tearle, Rick] Complete Genom Inc, Mountain View, CA 94043 USA.
   [Bo, Tan] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
   [Gilissen, Christian; Brunner, Han G.; Veltman, Joris A.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6229 ER Maastricht, Netherlands.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Central South University; Maastricht University
RP Veltman, JA (corresponding author), Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Human Genet, Geert Grootepl 10, NL-6525 GA Nijmegen, Netherlands.
EM joris.veltman@radboudumc.nl
FU Netherlands Organization for Scientific Research [912-12-109, 916-14-043, 916-12-095, 907-00-365, SH-271-13]; European Research Council (ERC) [DENOVO 281964]
NR 30
TC 879
Z9 1069
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 JUL 17
PY 2014
VL 511
IS 7509
BP 344
EP +
DI 10.1038/nature13394
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200035
PM 24896178
DA 2026-03-09
ER

PT J
AU Nguyen, LN
   Ma, DL
   Shui, GH
   Wong, PY
   Cazenave-Gassiot, A
   Zhang, XD
   Wenk, MR
   Goh, ELK
   Silver, DL
AF Nguyen, Long N.
   Ma, Dongliang
   Shui, Guanghou
   Wong, Peiyan
   Cazenave-Gassiot, Amaury
   Zhang, Xiaodong
   Wenk, Markus R.
   Goh, Eyleen L. K.
   Silver, David L.
TI Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid
SO NATURE
LA English
DT Article
ID cardiovascular-disease; brain; deficiency; mechanism
AB Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function(1-4). Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids(5-7). Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily-Mfsd2a (previously an orphan transporter)-as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.
C1 [Nguyen, Long N.; Silver, David L.] Duke NUS Grad Med Sch Singapore, Signature Res Program Cardiovasc & Metab Disorder, Singapore 169857, Singapore.
   [Ma, Dongliang; Wong, Peiyan; Zhang, Xiaodong; Goh, Eyleen L. K.] Duke NUS Grad Med Sch Singapore, Signature Res Program Neurosci & Behav Disorders, Singapore 169857, Singapore.
   [Shui, Guanghou; Cazenave-Gassiot, Amaury; Wenk, Markus R.] Natl Univ Singapore, Dept Biochem, Singapore 117597, Singapore.
C3 National University of Singapore; National University of Singapore; National University of Singapore
RP Silver, DL (corresponding author), Duke NUS Grad Med Sch Singapore, Signature Res Program Cardiovasc & Metab Disorder, 8 Coll Rd, Singapore 169857, Singapore.
EM david.silver@duke-nus.edu.sg
FU Singapore Ministry of Health's National Medical Research Council [CBRG/0012/2012]; Singapore National Research Foundation Competitive Research Program [2008-01, 2007-04]; National University of Singapore's Life Sciences Institute; Singapore National Medical Research Council Translational and Clinical Research Program [NMRC/TCR/003-GMS/2008]
NR 19
TC 811
Z9 918
U1 5
U2 229
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 503
EP +
DI 10.1038/nature13241
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000041
PM 24828044
DA 2026-03-09
ER

PT J
AU Kumar, RM
   Cahan, P
   Shalek, AK
   Satija, R
   DaleyKeyser, A
   Li, H
   Zhang, J
   Pardee, K
   Gennert, D
   Trombetta, JJ
   Ferrante, TC
   Regev, A
   Daley, GQ
   Collins, JJ
AF Kumar, Roshan M.
   Cahan, Patrick
   Shalek, Alex K.
   Satija, Rahul
   DaleyKeyser, Ajay
   Li, Hu
   Zhang, Jin
   Pardee, Keith
   Gennert, David
   Trombetta, John J.
   Ferrante, Thomas C.
   Regev, Aviv
   Daley, George Q.
   Collins, James J.
TI Deconstructing transcriptional heterogeneity in pluripotent stem cells
SO NATURE
LA English
DT Article
ID rna-seq; ground-state; self-renewal; microrna; generation; expression; noise; differentiation; quantification; maintenance
AB Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.
C1 [Kumar, Roshan M.; DaleyKeyser, Ajay; Pardee, Keith; Ferrante, Thomas C.; Collins, James J.] Harvard Univ, Wyss lnst Biologically Inspired Engn, Boston, MA 02115 USA.
   [Kumar, Roshan M.; Pardee, Keith; Collins, James J.] Boston Univ, Ctr Synthet Biol, Dept Biomed Engn, Howard Hughes Inst, Boston, MA 02215 USA.
   [Cahan, Patrick; Zhang, Jin; Daley, George Q.] Boston Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA.
   [Cahan, Patrick; Daley, George Q.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Biol Chem & Mol Pharma, Boston, MA 02115 USA.
   [Shalek, Alex K.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Shalek, Alex K.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Satija, Rahul; Gennert, David; Trombetta, John J.; Regev, Aviv] Harvard Univ, MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Li, Hu] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Ctr Individualized Med, Rochester, MN 55905 USA.
   [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA.
C3 Harvard University; Howard Hughes Medical Institute; Boston University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Mayo Clinic; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Daley, GQ (corresponding author), Harvard Univ, Sch Med,Manton Ctr Orphan Dis Res, Harvard Stem Cell Inst,Howard Hughes Med Inst, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu; jcollins@bu.edu
FU NIH [R24DK092760, R01GM107536, P50HG005550]; HHMI; Broad Institute; Klarman Cell Observatory at the Broad Institute; NIH CEGS [1P50HG006193-01]; NIH Pioneer Award [DP1OD003958-01]; Wyss Institute; NIDDK [K01DK096013]; NHLBI [T32HL066987, T32HL007623]; Manton Center for Orphan Disease Research; NIH Postdoctoral Fellowship [1F32HD075541-01]; Mayo Clinic Center for Individualized Medicine;  [NIH-P30-HD18655]; National Heart Lung and Blood Institute [T32HL066987] Funding Source: NIH RePORTER
NR 69
TC 282
Z9 327
U1 0
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 DEC 4
PY 2014
VL 516
IS 7529
BP 56
EP U112
DI 10.1038/nature13920
PG 26
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800037
PM 25471879
DA 2026-03-09
ER

PT J
AU Barends, TRM
   Foucar, L
   Botha, S
   Doak, RB
   Shoeman, RL
   Nass, K
   Koglin, JE
   Williams, GJ
   Boutet, S
   Messerschmidt, M
   Schlichting, I
AF Barends, Thomas R. M.
   Foucar, Lutz
   Botha, Sabine
   Doak, R. Bruce
   Shoeman, Robert L.
   Nass, Karol
   Koglin, Jason E.
   Williams, Garth J.
   Boutet, Sebastien
   Messerschmidt, Marc
   Schlichting, Ilme
TI De novo protein crystal structure determination from X-ray free-electron laser data
SO NATURE
LA English
DT Article
ID serial femtosecond crystallography; room-temperature; radiation-damage; photosystem-ii; diffraction; nanocrystallography; software
AB The determination of protein crystal structures is hampered by the need for macroscopic crystals. X-ray free-electron lasers (FELs) provide extremely intense pulses of femtosecond duration, which allow data collection from nanometre- to micrometre-sized crystals(1-4) in a 'diffraction-before-destruction' approach. So far, all protein structure determinations carried out using FELs have been based on previous knowledge of related, known structures(1-5). Here we show that X-ray FEL data can be used for de novo protein structure determination, that is, without previous knowledge about the structure. Using the emerging technique of serial femtosecond crystallography(1-4,6), we performed single-wavelength anomalous scattering measurements on microcrystals of the well-established model system lysozyme, in complex with a lanthanide compound. Using Monte-Carlo integration(6,7), we obtained high-quality diffraction intensities from which experimental phases could be determined, resulting in an experimental electron density map good enough for automated building of the protein structure. This demonstrates the feasibility of determining novel protein structures using FELs. We anticipate that serial femtosecond crystallography will become an important tool for the structure determination of proteins that are difficult to crystallize, such as membrane proteins(1,2,8).
C1 [Barends, Thomas R. M.; Foucar, Lutz; Botha, Sabine; Doak, R. Bruce; Shoeman, Robert L.; Nass, Karol; Schlichting, Ilme] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [Doak, R. Bruce] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Koglin, Jason E.; Williams, Garth J.; Boutet, Sebastien; Messerschmidt, Marc] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
C3 Max Planck Society; Arizona State University; Arizona State University-Tempe; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Barends, TRM (corresponding author), Max Planck Inst Med Res, Jahnstr 29, D-69120 Heidelberg, Germany.
EM thomas.barends@mpimf-heidelberg.mpg.de; ilme.schlichting@mpimf-heidelberg.mpg.de
FU LCLS Ultrafast Science Instruments (LUSI) project; US Department of Energy, Office of Basic Energy Sciences; Max Planck Society; EU
NR 30
TC 229
Z9 256
U1 0
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 JAN 9
PY 2014
VL 505
IS 7482
BP 244
EP +
DI 10.1038/nature12773
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500044
PM 24270807
DA 2026-03-09
ER

PT J
AU Choudhuri, K
   Llodrá, J
   Roth, EW
   Tsai, J
   Gordo, S
   Wucherpfennig, KW
   Kam, LC
   Stokes, DL
   Dustin, ML
AF Choudhuri, Kaushik
   Llodra, Jaime
   Roth, Eric W.
   Tsai, Jones
   Gordo, Susana
   Wucherpfennig, Kai W.
   Kam, Lance C.
   Stokes, David L.
   Dustin, Michael L.
TI Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse
SO NATURE
LA English
DT Article
ID class-ii; activation; protein; proliferation; microscopy; molecules; dynamics; adhesion; tsg101
AB The recognition events that mediate adaptive cellular immunity and regulate antibody responses depend on intercellular contacts between T cells and antigen-presenting cells (APCs)(1). T-cell signalling is initiated at these contacts when surface-expressed T-cell receptors (TCRs) recognize peptide fragments (antigens) of pathogens bound to major histocompatibility complex molecules (pMHC) on APCs. This, along with engagement of adhesion receptors, leads to the formation of a specialized junction between T cells and APCs, known as the immunological synapse(2), which mediates efficient delivery of effector molecules and intercellular signals across the synaptic cleft(3). T-cell recognition of pMHC and the adhesion ligand intercellular adhesion molecule-1 (ICAM-1) on supported planar bilayers recapitulates the domain organization of the immunological synapse(4,5), which is characterized by central accumulation of TCRs(5), adjacent to a secretory domain(2), both surrounded by an adhesive ring(4,5). Although accumulation of TCRs at the immunological synapse centre correlates with T-cell function(4), this domain is itself largely devoid of TCR signalling activity(5,6), and is characterized by an unexplained immobilization of TCR-pMHC complexes relative to the highly dynamic immunological synapse periphery(4,5). Here we show that centrally accumulated TCRs are located on the surface of extracellular microvesicles that bud at the immunological synapse centre. Tumour susceptibility gene 101 (TSG101)(6) sorts TCRs for inclusion in microvesicles, whereas vacuolar protein sorting 4 (VPS4)(7,8) mediates scission of microvesicles from the T-cell plasma membrane. The human immunodeficiency virus polyprotein Gag co-opts this process for budding of virus-like particles. B cells bearing cognate pMHC receive TCRs from T cells and initiate intracellular signals in response to isolated synaptic microvesicles. We conclude that the immunological synapse orchestrates TCR sorting and release in extracellular microvesicles. These microvesicles deliver transcellular signals across antigen-dependent synapses by engaging cognate pMHC on APCs.
C1 [Choudhuri, Kaushik] Skirball Inst Biomol Med, Program Mol Pathogenesis, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Llodra, Jaime; Stokes, David L.] Skirball Inst Biomol Med, Program Struct Biol, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Roth, Eric W.] Northwestern Univ, Atom & Nanoscale Characterizat Expt Ctr, Evanston, IL 60208 USA.
   [Tsai, Jones; Kam, Lance C.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
   [Gordo, Susana; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
   [Gordo, Susana; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02215 USA.
   [Stokes, David L.] New York Struct Biol Ctr, New York, NY 10027 USA.
   [Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Dustin, Michael L.] Univ Oxford, Kennedy Inst Rheumatol, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7FY, England.
C3 Northwestern University; Columbia University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; New York University; University of Oxford; Kennedy Institute for Rheumatology
RP Dustin, ML (corresponding author), NYU, Sch Med, Dept Pathol, 540 First Ave, New York, NY 10016 USA.
EM stokes@nyu.edu; michael.dustin@kennedy.ox.ac.uk
FU New York Structural Biology Center; Cancer Research Institute; NIH [K99AI093884, AI043542, AI045757, AI055037, AI088377, AI093884, EY016586]; Wellcome Trust; Kennedy Trust; Wellcome Trust [100262/Z/12/Z] Funding Source: researchfish; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 39
TC 315
Z9 360
U1 1
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 MAR 6
PY 2014
VL 507
IS 7490
BP 118
EP +
DI 10.1038/nature12951
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400054
PM 24487619
DA 2026-03-09
ER

PT J
AU Oh, J
   Byrd, AL
   Deming, C
   Conlan, S
   Kong, HH
   Segre, JA
AF Oh, Julia
   Byrd, Allyson L.
   Deming, Clay
   Conlan, Sean
   Kong, Heidi H.
   Segre, Julia A.
TI Biogeography and individuality shape function in the human skin metagenome
SO NATURE
LA English
DT Article
ID maximum-likelihood; diversity; algorithms; alignment; genes
AB The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.
C1 [Oh, Julia; Byrd, Allyson L.; Deming, Clay; Conlan, Sean; Segre, Julia A.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
   [Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Kong, HH (corresponding author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@mail.nih.gov
FU National Institutes of Health (NIH) NHGRI; National Institutes of Health (NIH) NCI; National Institutes of Health [1UH2AR057504-01, 4UH3AR057504-02];  [1K99AR059222]; National Cancer Institute [ZIABC010938] Funding Source: NIH RePORTER; National Human Genome Research Institute [ZIBHG000196, ZIAHG000180] Funding Source: NIH RePORTER
NR 40
TC 848
Z9 1027
U1 5
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 OCT 2
PY 2014
VL 514
IS 7520
BP 59
EP +
DI 10.1038/nature13786
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800034
PM 25279917
DA 2026-03-09
ER

PT J
AU Fortunato, SAV
   Adamski, M
   Ramos, OM
   Leininger, S
   Liu, J
   Ferrier, DEK
   Adamska, M
AF Fortunato, Sofia A. V.
   Adamski, Marcin
   Ramos, Olivia Mendivil
   Leininger, Sven
   Liu, Jing
   Ferrier, David E. K.
   Adamska, Maja
TI Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes
SO NATURE
LA English
DT Article
ID rna-seq data; evolution; hox; genome; sponge; amphioxus; expansion; selection
AB Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors(1-4), including homeobox genes belonging to the Antennapedia (ANTP) class(5,6), which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queens-landica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians(5). It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians(5,7). On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis)(8). Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis(8), and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.
C1 [Fortunato, Sofia A. V.; Adamski, Marcin; Leininger, Sven; Liu, Jing; Adamska, Maja] Univ Bergen, Sars Int Ctr Marine Mol Biol, N-5008 Bergen, Norway.
   [Fortunato, Sofia A. V.] Univ Bergen, Dept Biol, N-5008 Bergen, Norway.
   [Ramos, Olivia Mendivil; Ferrier, David E. K.] Univ St Andrews, Scottish Oceans Inst, Sch Biol, Gatty Marine Lab, St Andrews KY16 8LB, Fife, Scotland.
C3 University of Bergen; University of Bergen; University of St Andrews
RP Adamska, M (corresponding author), Univ Bergen, Sars Int Ctr Marine Mol Biol, Thormohlensgate 55, N-5008 Bergen, Norway.
EM maja.adamska@sars.uib.no
FU Sars Centre core budget; Norwegian Research Council; BBSRC; School of Biology, University of St Andrews
NR 30
TC 77
Z9 84
U1 0
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 OCT 30
PY 2014
VL 514
IS 7524
BP 620
EP +
DI 10.1038/nature13881
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500047
PM 25355364
DA 2026-03-09
ER

PT J
AU Huang, Q
   Yu, DL
   Xu, B
   Hu, WT
   Ma, YM
   Wang, YB
   Zhao, ZS
   Wen, B
   He, JL
   Liu, ZY
   Tian, YJ
AF Huang, Quan
   Yu, Dongli
   Xu, Bo
   Hu, Wentao
   Ma, Yanming
   Wang, Yanbin
   Zhao, Zhisheng
   Wen, Bin
   He, Julong
   Liu, Zhongyuan
   Tian, Yongjun
TI Nanotwinned diamond with unprecedented hardness and stability
SO NATURE
LA English
DT Article
ID cubic boron-nitride; polycrystalline diamonds; maximum strength; carbon onions; high-pressure; oxidation; microstructures; temperature; graphite; crystals
AB Although diamond is the hardest material for cutting tools, poor thermal stability has limited its applications, especially at high temperatures. Simultaneous improvement of the hardness and thermal stability of diamond has long been desirable. According to the Hall-Petch effect(1,2), the hardness of diamond can be enhanced by nanostructuring (by means of nanograined and nanotwinned microstructures), as shown in previous studies(3-7). However, for well-sintered nanograined diamonds, the grain sizes are technically limited to 10-30 nm (ref. 3), with degraded thermal stability(4) compared with that of natural diamond. Recent success in synthesizing nanotwinned cubic boron nitride (nt-cBN) with a twin thickness down to similar to 3.8 nm makes it feasible to simultaneously achieve smaller nanosize, ultrahardness and superior thermal stability(5). At present, nanotwinned diamond (nt-diamond) has not been fabricated successfully through direct conversions of various carbon precursors(3,6,7) (such as graphite, amorphous carbon, glassy carbon and C-60). Here we report the direct synthesis of nt-diamond with an average twin thickness of similar to 5 nm, using a precursor of onion carbon nanoparticles at high pressure and high temperature, and the observation of a new monoclinic crystalline form of diamond coexisting with nt-diamond. The pure synthetic bulk nt-diamond material shows unprecedented hardness and thermal stability, with Vickers hardness up to similar to 200 GPa and an in-air oxidization temperature more than 200 degrees C higher than that of natural diamond. The creation of nanotwinned microstructures offers a general pathway for manufacturing new advanced carbon-based materials with exceptional thermal stability and mechanical properties.
C1 [Huang, Quan; Yu, Dongli; Xu, Bo; Hu, Wentao; Zhao, Zhisheng; Wen, Bin; He, Julong; Liu, Zhongyuan; Tian, Yongjun] Yanshan Univ, State Key Lab Metastable Mat Sci & Technol, Qinhuangdao 066004, Peoples R China.
   [Ma, Yanming] Jilin Univ, State Key Lab Superhard Mat, Changchun 130012, Peoples R China.
   [Wang, Yanbin] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60439 USA.
C3 Yanshan University; Jilin University; University of Chicago
RP Tian, YJ (corresponding author), Yanshan Univ, State Key Lab Metastable Mat Sci & Technol, Qinhuangdao 066004, Peoples R China.
EM fhcl@ysu.edu.cn
FU National Natural Science Foundation of China [51121061, 51332005, 51172197, 11025418, 91022029]; Ministry of Science and Technology of China [2011CB808205, 2010CB731605]; US National Science Foundation [EAR-0968456]; Directorate For Geosciences; Division Of Earth Sciences [0968863, 0968823, 1361276] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0968456, 0968858] Funding Source: National Science Foundation
NR 30
TC 756
Z9 852
U1 30
U2 1463
PU NATURE PUBLISHING 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 12
PY 2014
VL 510
IS 7504
BP 250
EP +
DI 10.1038/nature13381
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400046
PM 24919919
DA 2026-03-09
ER

PT J
AU Arranz, L
   Sánchez-Aguilera, A
   Martín-Pérez, D
   Isern, J
   Langa, X
   Tzankov, A
   Lundberg, P
   Muntión, S
   Tzeng, YS
   Lai, DM
   Schwaller, J
   Skoda, RC
   Méndez-Ferrer, S
AF Arranz, Lorena
   Sanchez-Aguilera, Abel
   Martin-Perez, Daniel
   Isern, Joan
   Langa, Xavier
   Tzankov, Alexandar
   Lundberg, Pontus
   Muntion, Sandra
   Tzeng, Yi-Shiuan
   Lai, Dar-Ming
   Schwaller, Juerg
   Skoda, Radek C.
   Mendez-Ferrer, Simon
TI Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms
SO NATURE
LA English
DT Article
ID tyrosine kinase jak2; activating mutation; polycythemia-vera; bone; jak2-v617f
AB Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs1-4 that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow microenvironment might contribute to the clinical outcomes of this common event. We previously showed that bone marrow nestin(+) mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs5,6. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin(+) MSCs are consistently reduced in the bone marrow of MPN patients and mice expressing the human JAK2(V617F) mutation in HSCs. Unexpectedly, MSC reduction is not due to differentiation but is caused by bone marrow neural damage and Schwann cell death triggered by interleukin-1 beta produced by mutant HSCs. In turn, in vivo depletion of nestin(+) cells or their production of CXCL12 expanded mutant HSC number and accelerated MPN progression. In contrast, administration of neuroprotective or sympathomimetic drugs prevented mutant HSC expansion. Treatment with beta(3)-adrenergic agonists that restored the sympathetic regulation of nestin(+) MSCs5,6 prevented the loss of these cells and blocked MPN progression by indirectly reducing the number of leukaemic stem cells. Our results demonstrate that mutant-HSC-driven niche damage critically contributes to disease manifestation in MPN and identify niche-forming MSCs and their neural regulation as promising therapeutic targets.
C1 [Arranz, Lorena; Sanchez-Aguilera, Abel; Martin-Perez, Daniel; Isern, Joan; Langa, Xavier; Mendez-Ferrer, Simon] CNIC, Stem Cell Niche Pathophysiol Grp, Madrid 28029, Spain.
   [Tzankov, Alexandar; Lundberg, Pontus; Schwaller, Juerg; Skoda, Radek C.] Univ Basel Hosp, CH-4031 Basel, Switzerland.
   [Muntion, Sandra] IBSAL Hosp Univ Salamanca, Dept Haematol, Salamanca 37007, Spain.
   [Tzeng, Yi-Shiuan; Lai, Dar-Ming] Natl Taiwan Univ, Taipei 10002, Taiwan.
C3 Centro Nacional de Investigaciones Cardiovasculares (CNIC); University of Basel; National Taiwan University
RP Méndez-Ferrer, S (corresponding author), CNIC, Stem Cell Niche Pathophysiol Grp, Madrid 28029, Spain.
EM smendez@cnic.es
FU Fundacion CNIC; Spanish Ministry of Economy and Competitiveness (TerCel, Spanish Cell Therapy Network) [SAF-2011-30308]; ConSEPOC-Comunidad de Madrid [S2010/BMD-2542]; Ramon y Cajal Program [RYC-2009-04703/2011-09726]; Marie Curie grants [FP7-PEOPLE-2011-RG-294262/294096]; Swiss National Science Foundation [310000-120724/1, 32003BB_135712/1]; Swiss Cancer League [KLS-02398-02-2009]; European Hematology Association; Howard Hughes Medical Institute; Swiss National Science Foundation (SNF) [32003BB_135712] Funding Source: Swiss National Science Foundation (SNF)
NR 35
TC 372
Z9 414
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 AUG 7
PY 2014
VL 512
IS 7512
BP 78
EP +
DI 10.1038/nature13383
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000035
PM 25043017
DA 2026-03-09
ER

PT J
AU Zhao, L
   Lee, X
   Smith, RB
   Oleson, K
AF Zhao, Lei
   Lee, Xuhui
   Smith, Ronald B.
   Oleson, Keith
TI Strong contributions of local background climate to urban heat islands
SO NATURE
LA English
DT Article
ID city; urbanization; impact; exchanges; heatwaves; forests; system; model
AB The urban heat island(UHI), a common phenomenon in which surface temperatures are higher in urban areas than in surrounding rural areas, represents one of the most significant human-induced changes to Earth's surface climate(1,2). Even though they are localized hotspots in the landscape, UHIs have a profound impact on the lives of urban residents, who comprise more than half of the world's population(3). A barrier to UHI mitigation is the lack of quantitative attribution of the various contributions to UHI intensity(4) (expressed as the temperature difference between urban and rural areas, Delta T). A common perception is that reduction in evaporative cooling in urban land is the dominant driver of DT (ref. 5). Here we use a climate model to show that, for cities across North America, geographic variations in daytime Delta T are largely explained by variations in the efficiency with which urban and rural areas convect heat to the lower atmosphere. If urban areas are aerodynamically smoother than surrounding rural areas, urban heat dissipation is relatively less efficient and urban warming occurs (and vice versa). This convection effect depends on the local background climate, increasing daytime Delta T by 3.06 +/- 0.3 kelvin (mean and standard error) in humid climates but decreasing Delta T by 1.5 +/- 0.2 kelvin in dry climates. In the humid eastern United States, there is evidence of higher Delta T in drier years. These relationship simply that UHIs will exacerbate heat wave stress on human health in wet climates where high temperature effects are already compounded by high air humidity(6,7) and in drier years when positive temperature anomalies may be reinforced by a precipitation temperature feedback(8). Our results support albedo management as a viable means of reducing Delta T on large scales(9,10).
C1 [Zhao, Lei; Lee, Xuhui] Nanjing Univ Informat Sci & Technol, Yale NUIST Ctr Atmospher Environm, Nanjing 210044, Jiangsu, Peoples R China.
   [Zhao, Lei; Lee, Xuhui] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
   [Smith, Ronald B.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
   [Oleson, Keith] Natl Ctr Atmospher Res, Boulder, CO 80305 USA.
C3 Nanjing University of Information Science & Technology; Yale University; Yale University; National Center Atmospheric Research (NCAR) - USA
RP Lee, X (corresponding author), Nanjing Univ Informat Sci & Technol, Yale NUIST Ctr Atmospher Environm, Nanjing 210044, Jiangsu, Peoples R China.
EM xuhui.lee@yale.edu
FU Ministry of Education of China (grant PCSIRT); Yale Climate and Energy Institute; Yale Institute of Biospheric Studies; Yale University Graduate Fellowship; NASA [NNX10AK79G]; NCARWCIASP; US National Science Foundation
NR 36
TC 1173
Z9 1352
U1 43
U2 1223
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 216
EP 219
DI 10.1038/nature13462
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800042
PM 25008529
DA 2026-03-09
ER

PT J
AU Farokhipoor, S
   Magén, C
   Venkatesan, S
   Iñiguez, J
   Daumont, CJM
   Rubi, D
   Snoeck, E
   Mostovoy, M
   de Graaf, C
   Müller, A
   Döblinger, M
   Scheu, C
   Noheda, B
AF Farokhipoor, S.
   Magen, C.
   Venkatesan, S.
   Iniguez, J.
   Daumont, C. J. M.
   Rubi, D.
   Snoeck, E.
   Mostovoy, M.
   de Graaf, C.
   Mueller, A.
   Doeblinger, M.
   Scheu, C.
   Noheda, B.
TI Artificial chemical and magnetic structure at the domain walls of an epitaxial oxide
SO NATURE
LA English
DT Article
ID square-planar; perturbation-theory; ferroelectricity; complexes; manganese(ii); distortion; octahedra; oxidation
AB Progress in nanotechnology requires new approaches to materials synthesis that make it possible to control material functionality down to the smallest scales. An objective of materials research is to achieve enhanced control over the physical properties of materials such as ferromagnets(1), ferroelectrics(2) and superconductors(3). In this context, complex oxides and inorganic perovskites are attractive because slight adjustments of their atomic structures can produce large physical responses and result in multiple functionalities(4,5). In addition, these materials often contain ferroelastic domains(6). The intrinsic symmetry breaking that takes place at the domain walls can induce properties absent from the domains themselves(7), such as magnetic or ferroelectric order and other functionalities, as well as coupling between them. Moreover, large domain wall densities create intense strain gradients, which can also affect the material's properties(8,9). Here we show that, owing to large local stresses, domain walls can promote the formation of unusual phases. In this sense, the domain walls can function as nanoscale chemical reactors. We synthesize a two-dimensional ferromagnetic phase at the domain walls of the orthorhombic perovskite terbium manganite (TbMnO3), which was grown in thin layer sunder epitaxial strain on strontium titanate (SrTiO3) substrates. This phase is yet to be created by standard chemical routes. The density of the two-dimensional sheets can be tuned by changing the film thickness or the substrate lattice parameter (that is, the epitaxial strain), and the distance between sheets can be made as small as 5 nanometres in ultrathin films(10,) such that the new phase at domain walls represents up to 25 per cent of the film volume. The general concept of using domain walls of epitaxial oxides to promote the formation of unusual phases may be applicable to other materials systems, thus giving access to new classes of nanoscale materials for applications in nanoelectronics and spintronics.
C1 [Farokhipoor, S.; Daumont, C. J. M.; Rubi, D.; Mostovoy, M.; de Graaf, C.; Noheda, B.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Magen, C.] Univ Zaragoza, INA, ARAID, LMA, Zaragoza 50018, Spain.
   [Magen, C.] Univ Zaragoza, Dept Fis Mat Condensada, Zaragoza 50018, Spain.
   [Magen, C.; Snoeck, E.] Univ Zaragoza, CNRS, INA, TALEM,CEMES, F-30155 Toulouse, France.
   [Venkatesan, S.; Mueller, A.; Doeblinger, M.; Scheu, C.] Univ Munich, Dept Chem, D-81377 Munich, Germany.
   [Venkatesan, S.; Mueller, A.; Doeblinger, M.; Scheu, C.] Univ Munich, CENS, D-81377 Munich, Germany.
   [Iniguez, J.] CSIC, ICMAB, Bellaterra 08193, Spain.
   [Snoeck, E.] CNRS, CEMES, F-30155 Toulouse, France.
   [de Graaf, C.] Univ Rovira & Virgili, E-43007 Tarragona, Spain.
   [de Graaf, C.] ICREA, Barcelona 08010, Spain.
C3 University of Groningen; University of Zaragoza; University of Zaragoza; Centre National de la Recherche Scientifique (CNRS); University of Munich; University of Munich; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB); Centre National de la Recherche Scientifique (CNRS); Universitat Rovira i Virgili; ICREA
RP Noheda, B (corresponding author), Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
EM cmagend@unizar.es; b.noheda@rug.nl
FU NanoNextNL; micro- and nanotechnology consortium of the Government of the Netherlands; Foundation for Fundamental Research on Matter (FOM); Netherlands Organization for Scientific Research (NWO); European Union [312483-ESTEEM2]; Spanish Administration [CTQ2011-23140]; Generalitat de Catalunya [20095GR462]; MINECO-Spain [MAT2010-18113, C5D2007-00041]; German Science Foundation (DFG) via the Cluster of Excellence NIM; ICREA Funding Source: Custom
NR 56
TC 154
Z9 168
U1 4
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 20
PY 2014
VL 515
IS 7527
BP 379
EP +
DI 10.1038/nature13918
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600038
PM 25409828
DA 2026-03-09
ER

PT J
AU Burns, M
   Essafi, S
   Bame, JR
   Bull, SP
   Webster, MP
   Balieu, S
   Dale, JW
   Butts, CP
   Harvey, JN
   Aggarwal, VK
AF Burns, Matthew
   Essafi, Stephanie
   Bame, Jessica R.
   Bull, Stephanie P.
   Webster, Matthew P.
   Balieu, Sebastien
   Dale, James W.
   Butts, Craig P.
   Harvey, Jeremy N.
   Aggarwal, Varinder K.
TI Assembly-line synthesis of organic molecules with tailored shapes
SO NATURE
LA English
DT Article
ID reagent-controlled homologation; boronic esters; stereocontrolled synthesis; conformation design; natural-products; asymmetric-synthesis; grignard-reagents; chiral carbenoids; efficient; sequence
AB Molecular 'assembly lines', in which organic molecules undergo iterative processes such as chain elongation and functional group manipulation, are found in many natural systems, including polyketide biosynthesis. Here we report the creation of such an assembly line using the iterative, reagent-controlled homologation of a boronic ester. This process relies on the reactivity of alpha-lithioethyl tri-isopropylbenzoate, which inserts into carbon-boron bonds with exceptionally high fidelity and stereocontrol; each chain-extension step generates a new boronic ester, which is immediately ready for further homologation. We used this method to generate organic molecules that contain ten contiguous, stereochemically defined methyl groups. Several stereoisomers were synthesized and shown to adopt different shapes-helical or linear-depending on the stereochemistry of the methyl groups. This work should facilitate the rational design of molecules with predictable shapes, which could have an impact in areas of molecular sciences in which bespoke molecules are required.
C1 [Burns, Matthew; Essafi, Stephanie; Bame, Jessica R.; Bull, Stephanie P.; Webster, Matthew P.; Balieu, Sebastien; Butts, Craig P.; Harvey, Jeremy N.; Aggarwal, Varinder K.] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England.
   [Dale, James W.] Novartis Horsham Res Ctr, Horsham RH13 5AB, W Sussex, England.
C3 University of Bristol; Novartis; Novartis United Kingdom
RP Aggarwal, VK (corresponding author), Univ Bristol, Sch Chem, Cantocks Close, Bristol BS8 1TS, Avon, England.
EM craig.butts@bristol.ac.uk; jeremy.harvey@bristol.ac.uk; v.aggarwal@bristol.ac.uk
FU EPSRC [EP/I038071/1, EP/G036764/1]; European Research Council (FP7, ERC grant) [246785]; Novartis; BBSRC [BB/F011539/1] Funding Source: UKRI; EPSRC [EP/I038071/1, EP/K03927X/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F011539/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/I038071/1, EP/K03927X/1] Funding Source: researchfish; European Research Council (ERC) [246785] Funding Source: European Research Council (ERC)
NR 50
TC 235
Z9 263
U1 4
U2 132
PU NATURE PUBLISHING 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 11
PY 2014
VL 513
IS 7517
BP 183
EP 188
DI 10.1038/nature13711
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800041
PM 25209797
DA 2026-03-09
ER

PT J
AU Jotzu, G
   Messer, M
   Desbuquois, R
   Lebrat, M
   Uehlinger, T
   Greif, D
   Esslinger, T
AF Jotzu, Gregor
   Messer, Michael
   Desbuquois, Remi
   Lebrat, Martin
   Uehlinger, Thomas
   Greif, Daniel
   Esslinger, Tilman
TI Experimental realization of the topological Haldane model with ultracold fermions
SO NATURE
LA English
DT Article
ID insulator; lattice; phase
AB The Haldane model on a honeycomb lattice is a paradigmatic example of a Hamiltonian featuring topologically distinct phases of matter(1). It describes a mechanism through which a quantum Hall effect can appear as an intrinsic property of a band structure, rather than being caused by an external magnetic field(2). Although physical implementation has been considered unlikely, the Haldane model has provided the conceptual basis for theoretical and experimental research exploring topological insulators and superconductors(2-6). Here we report the experimental realization of the Haldane model and the characterization of its topological band structure, using ultracold fermionic atoms in a periodically modulated optical honeycomb lattice. The Haldane model is based on breaking both time-reversal symmetry and inversion symmetry. To break time-reversal symmetry, we introduce complex next-nearest-neighbour tunnelling terms, which we induce through circular modulation of the lattice position(7). To break inversion symmetry, we create an energy offset between neighbouring sites(8). Breaking either of these symmetries opens a gap in the band structure, which we probe using momentum-resolved interband transitions. We explore the resulting Berry curvatures, which characterize the topology of the lowest band, by applying a constant force to the atoms and find orthogonal drifts analogous to a Hall current. The competition between the two broken symmetries gives rise to a transition between topologically distinct regimes. By identifying the vanishing gap at a single Dirac point, we map out this transition line experimentally and quantitatively compare it to calculations using Floquet theory without free parameters. We verify that our approach, which allows us to tune the topological properties dynamically, is suitable even for interacting fermionic systems. Furthermore, we propose a direct extension to realize spin-dependent topological Hamiltonians.
C1 [Jotzu, Gregor; Messer, Michael; Desbuquois, Remi; Lebrat, Martin; Uehlinger, Thomas; Greif, Daniel; Esslinger, Tilman] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Esslinger, T (corresponding author), ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM esslinger@phys.ethz.ch
FU SNF; NCCR-QSIT; SQMS (ERC advanced grant)
NR 30
TC 1853
Z9 2042
U1 7
U2 286
PU NATURE PUBLISHING 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 13
PY 2014
VL 515
IS 7526
BP 237
EP U191
DI 10.1038/nature13915
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400043
PM 25391960
DA 2026-03-09
ER

PT J
AU Conway, TM
   John, SG
AF Conway, Tim M.
   John, Seth G.
TI Quantification of dissolved iron sources to the North Atlantic Ocean
SO NATURE
LA English
DT Article
ID continental-shelf; aerosol iron; isotopes; seawater; dust; fe; constraints; cycle; flux
AB Dissolved iron is an essential micronutrient for marine phytoplankton, and its availability controls patterns of primary productivity and carbon cycling throughout the oceans(1,2). The relative importance of different sources of iron to the oceans is not well known, however, and flux estimates from atmospheric dust, hydrothermal vents and oceanic sediments vary by orders of magnitude. Here we present a high-resolution transect of dissolved stable iron isotope ratios (delta Fe-56) and iron concentrations ([Fe]) along a section of the North Atlantic Ocean. The different iron sources can be identified by their unique delta Fe-56 signatures, which persist throughout the water column. This allows us to calculate the relative contribution from dust, hydrothermal venting and reductive and non-reductive sedimentary release to the dissolved phase. We find that Saharan dust aerosol is the dominant source of dissolved iron along the section, contributing 71-87 per cent of dissolved iron. Additional sources of iron are non-reductive release from oxygenated sediments on the North American margin (10-19 per cent), reductive sedimentary dissolution on the African margin (1-4 per cent) and hydrothermal venting at the Mid-Atlantic Ridge (2-6 per cent). Our data also indicate that hydrothermal vents in the North Atlantic are a source of isotopically light iron, which travels thousands of kilometres from vent sites, potentially influencing surface productivity. Changes in the relative importance of the different iron sources through time may affect interactions between the carbon cycle and climate.
C1 [Conway, Tim M.; John, Seth G.] Univ S Carolina, Dept Earth & Ocean Sci, Columbia, SC 29208 USA.
C3 University of South Carolina System; University of South Carolina Columbia
RP Conway, TM (corresponding author), ETH, Inst Geochem & Petrol, NWD81-4,Clausiusstr 25, CH-8092 Zurich, Switzerland.
EM conway.tm@gmail.com
FU National Science Foundation [OCE-1131387]; Directorate For Geosciences; Division Of Ocean Sciences [1131387] Funding Source: National Science Foundation
NR 28
TC 303
Z9 356
U1 6
U2 398
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 212
EP +
DI 10.1038/nature13482
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800041
PM 25008528
DA 2026-03-09
ER

PT J
AU Keskin, H
   Shen, Y
   Huang, F
   Patel, M
   Yang, T
   Ashley, K
   Mazin, AV
   Storici, F
AF Keskin, Havva
   Shen, Ying
   Huang, Fei
   Patel, Mikir
   Yang, Taehwan
   Ashley, Katie
   Mazin, Alexander V.
   Storici, Francesca
TI Transcript-RNA-templated DNA recombination and repair
SO NATURE
LA English
DT Article
ID double-strand break; homologous recombination; ty1 retrotransposition; reverse-transcriptase; reca protein; yeast; gene; replication; mutagenesis; complex
AB Homologous recombination is a molecular process that has multiple important roles in DNA metabolism, both for DNA repair and genetic variation in all forms of life(1). Generally, homologous recombination involves the exchange of genetic information between two identical or nearly identical DNA molecules(1); however, homologous recombination can also occur between RNA molecules, as shown for RNA viruses(2). Previous research showed that synthetic RNA oligonudeotides can act as templates for DNA double-strand break (DSB) repair in yeast and human cells(3,4), and artificial long RNA templates injected in ciliate cells can guide genomic rearrangements(5). Here we report that endogenous transcript RNA mediates homologous recombination with chromosomal DNA in yeast Saccharomyces cerevisiae. We developed a system to detect the events of homologous recombination initiated by transcript RNA following the repair of a chromosomal DSB occurring either in a homologous but remote locus, or in the same transcript-generating locus in reverse-transcription-defective yeast strains. We found that RNA-DNA recombination is blocked by ribonudeases H1 and H2. In the presence of H-type ribonudeases, DSB repair proceeds through a complementary DNA intermediate, whereas in their absence, it proceeds directly through RNA. The proximity of the transcript to its chromosomal DNA partner in the same locus facilitates Rad52-driven homologous recombination during DSB repair. We demonstrate that yeast and human Rad52 proteins efficiently catalyse annealing of RNA to a DSB-like DNA end in vitro. Our results reveal a novel mechanism of homologous recombination and DNA repair in which transcript RNA is used as a template for DSB repair. Thus, considering the abundance of RNA transcripts in cells, RNA may have a marked impact on genomic stability and plasticity.
C1 [Keskin, Havva; Shen, Ying; Yang, Taehwan; Ashley, Katie; Storici, Francesca] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Huang, Fei; Patel, Mikir; Mazin, Alexander V.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA.
C3 University System of Georgia; Georgia Institute of Technology; Drexel University
RP Storici, F (corresponding author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
EM storici@gatech.edu
FU National Science Foundation [MCB-1021763]; Georgia Research Alliance [R9028]; National Cancer Institute of the National Institutes of Health [CA100839, P30CA056036]; Ministry of Science of Turkey; National Cancer Institute [P30CA056036] Funding Source: NIH RePORTER; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1021763] Funding Source: National Science Foundation
NR 44
TC 265
Z9 337
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 NOV 20
PY 2014
VL 515
IS 7527
BP 436
EP +
DI 10.1038/nature13682
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600051
PM 25186730
DA 2026-03-09
ER

PT J
AU Khmelinskii, A
   Blaszczak, E
   Pantazopoulou, M
   Fischer, B
   Omnus, DJ
   Le Dez, G
   Brossard, A
   Gunnarsson, A
   Barry, JD
   Meurer, M
   Kirrmaier, D
   Boone, C
   Huber, W
   Rabut, G
   Ljungdahl, PO
   Knop, M
AF Khmelinskii, Anton
   Blaszczak, Ewa
   Pantazopoulou, Marina
   Fischer, Bernd
   Omnus, Deike J.
   Le Dez, Gaelle
   Brossard, Audrey
   Gunnarsson, Alexander
   Barry, Joseph D.
   Meurer, Matthias
   Kirrmaier, Daniel
   Boone, Charles
   Huber, Wolfgang
   Rabut, Gwenael
   Ljungdahl, Per O.
   Knop, Michael
TI Protein quality control at the inner nuclear membrane
SO NATURE
LA English
DT Article
ID transcription factor; yeast genes; domain; degradation; ubiquitination; proteasome; dynamics; envelope; genome; cue1p
AB The nuclear envelope is a double membrane that separates the nucleus from the cytoplasm. The inner nuclear membrane (INM) functions in essential nuclear processes including chromatin organization and regulation of gene expression(1). The outer nuclear membrane is continuous with the endoplasmic reticulum and is the site of membrane protein synthesis. Protein homeostasis in this compartment is ensured by endoplasmic-reticulum-associated protein degradation (ERAD) pathways that in yeast involve the integral membrane E3 ubiquitin ligases Hrd1 and Doa10 operating with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7 (refs 2, 3). However, little is known about protein quality control at the INM. Here we describe a protein degradation pathway at the INM in yeast (Saccharomyces cerevisiae) mediated by the Asicomplex consisting of the RING domain proteins Asi1 and Asi3 (ref. 4). We report that the Asi complex functions together with the ubiquitin-conjugating enzymes Ubc6 and Ubc7 to degrade soluble and integral membrane proteins. Genetic evidence suggests that the Asi ubiquitin ligase defines a pathway distinct from, but complementary to, ERAD. Using unbiased screening with a novel genome-wide yeast library based on a tandem fluorescent protein timer(5), we identify more than 50 substrates of the Asi, Hrd1 and Doa10 E3 ubiquitin ligases. We show that the Asi ubiquitin ligase is involved in degradation of mislocalized integral membrane proteins, thus acting to maintain and safeguard the identity of the INM.
C1 [Khmelinskii, Anton; Meurer, Matthias; Kirrmaier, Daniel; Knop, Michael] Univ Heidelberg ZMBH, Zentrum Mol Biol, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany.
   [Blaszczak, Ewa; Le Dez, Gaelle; Brossard, Audrey; Rabut, Gwenael] Ctr Natl Rech Sci, UMR 6290, F-35000 Rennes, France.
   [Blaszczak, Ewa; Le Dez, Gaelle; Brossard, Audrey; Rabut, Gwenael] Univ Rennes 1, Inst Genet & Dev Rennes, F-35000 Rennes, France.
   [Pantazopoulou, Marina; Omnus, Deike J.; Gunnarsson, Alexander; Ljungdahl, Per O.] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden.
   [Fischer, Bernd; Barry, Joseph D.; Huber, Wolfgang] European Mol Biol Lab EMBL, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Fischer, Bernd; Knop, Michael] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Boone, Charles] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; 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 de Rennes; Stockholm University; European Molecular Biology Laboratory (EMBL); Helmholtz Association; German Cancer Research Center (DKFZ); University of Toronto
RP Knop, M (corresponding author), Univ Heidelberg ZMBH, Zentrum Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
EM gwenael.rabut@inserm.fr; per.ljungdahl@su.se; m.knop@zmbh.uni-heidelberg.de
FU Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich 1036 (SFB1036), TP10]; Swedish Research Council [VR2011-5925]; INSERM; ANR [ANR-12-JSV8-0003-001]; Biosit; European Molecular Biology Organization [EMBO ALTF 1124-2010, EMBO ASTF 546-2012]; Ministere de la Recherche et de l'Enseignement Superieur; La Ligue Contre le Cancer; CellNetworks Cluster of Excellence (DFG); EC Network of Excellence Systems Microscopy; Canadian Institute for Advanced Research [GNE-BOON-141871]; National Institutes of Health [R01HG005853-01]; Canadian Institute for Health Research [MOP-102629]; National Science and Engineering Research Council [RGPIN 204899-6]; National Human Genome Research Institute [R01HG005853] Funding Source: NIH RePORTER; Agence Nationale de la Recherche (ANR) [ANR-12-JSV8-0003] Funding Source: Agence Nationale de la Recherche (ANR)
NR 43
TC 159
Z9 191
U1 0
U2 70
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 410
EP +
DI 10.1038/nature14096
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800050
PM 25519137
DA 2026-03-09
ER

PT J
AU van de Pavert, SA
   Ferreira, M
   Domingues, RG
   Ribeiro, H
   Molenaar, R
   Moreira-Santos, L
   Almeida, FF
   Ibiza, S
   Barbosa, I
   Goverse, G
   Labao-Almeida, C
   Godinho-Silva, C
   Konijn, T
   Schooneman, D
   O'Toole, T
   Mizee, MR
   Habani, Y
   Haak, E
   Santori, FR
   Littman, DR
   Schulte-Merker, S
   Dzierzak, E
   Simas, JP
   Mebius, RE
   Veiga-Fernandes, H
AF van de Pavert, Serge A.
   Ferreira, Manuela
   Domingues, Rita G.
   Ribeiro, Helder
   Molenaar, Rosalie
   Moreira-Santos, Lara
   Almeida, Francisca F.
   Ibiza, Sales
   Barbosa, Ines
   Goverse, Gera
   Labao-Almeida, Carlos
   Godinho-Silva, Cristina
   Konijn, Tanja
   Schooneman, Dennis
   O'Toole, Tom
   Mizee, Mark R.
   Habani, Yasmin
   Haak, Esther
   Santori, Fabio R.
   Littman, Dan R.
   Schulte-Merker, Stefan
   Dzierzak, Elaine
   Simas, J. Pedro
   Mebius, Reina E.
   Veiga-Fernandes, Henrique
TI Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
SO NATURE
LA English
DT Article
ID ror-gamma-t; acid; fetal; mice; responses; survival; organs; notch; ret
AB The impact of nutritional status during fetal life on the overall health of adults has been recognized(1); however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed(2,3). Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer(LTi) cells(2-5). Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor ROR gamma t. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
C1 [van de Pavert, Serge A.; Molenaar, Rosalie; Goverse, Gera; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Mebius, Reina E.] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 BT Amsterdam, Netherlands.
   [Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Helder; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Ines; Labao-Almeida, Carlos; Godinho-Silva, Cristina; Simas, J. Pedro; Veiga-Fernandes, Henrique] Fac Med Lisbon, Inst Med Mol, P-1649028 Lisbon, Portugal.
   [Haak, Esther; Dzierzak, Elaine] Erasmus MC, Erasmus Stem Cell Inst, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands.
   [Santori, Fabio R.; Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, Mol Pathogenesis Program,Skirball Inst Biomol Med, New York, NY 10016 USA.
   [Schulte-Merker, Stefan] Royal Netherlands Acad Arts & Sci, Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
   [Schulte-Merker, Stefan] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
C3 Vrije Universiteit Amsterdam; Universidade de Lisboa; Erasmus University Rotterdam; Erasmus MC; New York University; Howard Hughes Medical Institute; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center
RP Veiga-Fernandes, H (corresponding author), Fac Med Lisbon, Inst Med Mol, Av Prof Egas Moniz,Edificio Egas Moniz, P-1649028 Lisbon, Portugal.
EM jhfernandes@medicina.ulisboa.pt
FU FCT, Portugal; EMBO [1648]; ERC [207057]; NIH [RO1AI080885]; HHMI; Dutch MS research foundation [MS 12-797]; NGI Breakthrough Horizon [40-41009-98-9077]; VICI [918.56.612]; ALW-TOP [09.048]; European Research Council (ERC) [207057] Funding Source: European Research Council (ERC)
NR 42
TC 315
Z9 357
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 APR 3
PY 2014
VL 508
IS 7494
BP 123
EP +
DI 10.1038/nature13158
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900055
PM 24670648
DA 2026-03-09
ER

PT J
AU Schauder, CM
   Wu, XD
   Saheki, Y
   Narayanaswamy, P
   Torta, F
   Wenk, MR
   De Camilli, P
   Reinisch, KM
AF Schauder, Curtis M.
   Wu, Xudong
   Saheki, Yasunori
   Narayanaswamy, Pradeep
   Torta, Federico
   Wenk, Markus R.
   De Camilli, Pietro
   Reinisch, Karin M.
TI Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer
SO NATURE
LA English
DT Article
ID contact sites; crystal-structure; proteins; er; reveals; domains
AB Growing evidence suggests that close appositions between the endoplasmic reticulum(ER) and other membranes, including appositions with the plasma membrane (PM), mediate exchange of lipids between these bilayers. The mechanisms of such exchange, which allows lipid transfer independently of vesicular transport, remain poorly understood. The presence of a synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain, a proposed lipid-binding module, in several proteins localized at membrane contact sites has raised the possibility that such domains may be implicated in lipid transport(1,2). SMP-containing proteins include components of the ERMES complex, an ER-mitochondrial tether(3), and the extended synaptotagmins (known as tricalbins in yeast), which are ER-PM tethers(4-6). Here we present at 2.44 angstrom resolution the crystal structure of a fragment of human extended synaptotagmin 2 (E-SYT2), including an SMP domain and two adjacent C2 domains. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues, with the two C2A-C2B fragments forming arched structures flexibly linked to the SMP domain. Importantly, structural analysis complemented by mass spectrometry revealed the presence of glycerophospholipids in the E-SYT2 SMP channel, indicating a direct role for E-SYTs in lipid transport. These findings provide strong evidence for a role of SMP-domain-containing proteins in the control of lipid transfer at membrane contact sites and have broad implications beyond the field of ER-to-PM appositions.
C1 [Schauder, Curtis M.; Wu, Xudong; Saheki, Yasunori; De Camilli, Pietro; Reinisch, Karin M.] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA.
   [Saheki, Yasunori; De Camilli, Pietro] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA.
   [Saheki, Yasunori; De Camilli, Pietro] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
   [Narayanaswamy, Pradeep] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
   [Torta, Federico; Wenk, Markus R.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117599, Singapore.
C3 Yale University; Yale University; Howard Hughes Medical Institute; Yale University; National University of Singapore; National University of Singapore
RP Reinisch, KM (corresponding author), Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA.
EM pietro.decamilli@yale.edu; karin.reinisch@yale.edu
FU National Institutes of Health [GM080616, R37NS36251, DK082700]; National University of Singapore via the Life Sciences Institute (LSI); Biochemical Research Council [BMRC-SERC Diag-034]; National Science Foundation Graduate Research Fellowship [DGE-1122492]; Uehara Memorial Foundation; Japanese Society for Promotion of Science; National Institute on Drug Abuse [P30DA018343] Funding Source: NIH RePORTER
NR 30
TC 245
Z9 296
U1 2
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 JUN 26
PY 2014
VL 510
IS 7506
BP 552
EP +
DI 10.1038/nature13269
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300050
PM 24847877
DA 2026-03-09
ER

PT J
AU Nguyen, PD
   Hollway, GE
   Sonntag, C
   Miles, LB
   Hall, TE
   Berger, S
   Fernandez, KJ
   Gurevich, DB
   Cole, NJ
   Alaei, S
   Ramialison, M
   Sutherland, RL
   Polo, JM
   Lieschke, GJ
   Currie, PD
AF Phong Dang Nguyen
   Hollway, Georgina Elizabeth
   Sonntag, Carmen
   Miles, Lee Barry
   Hall, Thomas Edward
   Berger, Silke
   Fernandez, Kristine Joy
   Gurevich, David Baruch
   Cole, Nicholas James
   Alaei, Sara
   Ramialison, Mirana
   Sutherland, Robert Lyndsay
   Polo, Jose Maria
   Lieschke, Graham John
   Currie, Peter David
TI Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1
SO NATURE
LA English
DT Article
ID transgenic zebrafish; aortic endothelium; smooth-muscle; progenitors; blood; expression; hedgehog; identification; mesoderm; database
AB Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events(1-3). Previous studies have identified that signalling relayed from adjacent somites coordinates HSC induction, but the nature of this signal has remained elusive(4). Here we reveal that somite specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the zebrafish somite that we have defined as the endotome. Endothelial cells of the endotomeare specified within the nascent somite by the activity of the homeobox genemeox(1). Specified endotomal cells consequently migrate and colonize the DA, where they induce HSC formation through the deployment of chemokine signalling activated in these cells during endotome formation. Loss of meox(1) activity expands the endotome at the expense of a second somitic cell type, the muscle precursors of the dermomyotomal equivalent in zebrafish, the external cell layer. The resulting increase in endotome-derived cells that migrate to colonize the DA generates a dramatic increase in chemokine-dependent HSC induction. This study reveals the molecular basis for a novel somite lineage restriction mechanism and defines a new paradigm in induction of definitive HSCs.
C1 [Phong Dang Nguyen; Sonntag, Carmen; Miles, Lee Barry; Hall, Thomas Edward; Berger, Silke; Gurevich, David Baruch; Alaei, Sara; Ramialison, Mirana; Polo, Jose Maria; Lieschke, Graham John; Currie, Peter David] Monash Univ, Australian Regenerat Med Inst, Clayton, Vic 3800, Australia.
   [Hollway, Georgina Elizabeth; Fernandez, Kristine Joy; Sutherland, Robert Lyndsay] Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia.
   [Hollway, Georgina Elizabeth; Fernandez, Kristine Joy; Sutherland, Robert Lyndsay] Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia.
   [Hollway, Georgina Elizabeth; Sutherland, Robert Lyndsay] Univ New S Wales, Fac Med, St Vincents Clin Sch, Kensington, NSW 2052, Australia.
   [Cole, Nicholas James] Univ Sydney, Sch Med, Dept Anat, Camperdown, NSW 2006, Australia.
   [Cole, Nicholas James] Macquarie Univ, Australian Sch Adv Med, MND Res Program, N Ryde, NSW 2109, Australia.
   [Alaei, Sara] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia.
   [Currie, Peter David] Monash Univ, EMBL Australia, Clayton, Vic 3800, Australia.
C3 Monash University; Australian Regenerative Medicine Institute; Garvan Institute of Medical Research; The Kinghorn Cancer Centre; Garvan Institute of Medical Research; University of New South Wales Sydney; University of Sydney; Macquarie University; Monash University; Monash University; European Molecular Biology Laboratory (EMBL); EMBL Australia
RP Currie, PD (corresponding author), Monash Univ, Australian Regenerat Med Inst, Level 1,Bldg 75,Wellington Rd, Clayton, Vic 3800, Australia.
EM peter.currie@monash.edu
FU National Health and Medical Research Council of Australia (NHMRC); Australian Research Council; Cancer Institute NSW (CINSW); Australian Postgraduate Award; NHMRC; CINSW; RT Hall Foundation; State Government of Victoria; Australian Federal Government
NR 54
TC 118
Z9 142
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 AUG 21
PY 2014
VL 512
IS 7514
BP 314
EP +
DI 10.1038/nature13678
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200036
PM 25119043
DA 2026-03-09
ER

PT J
AU Mukherjee, S
   Zheng, H
   Derebe, MG
   Callenberg, KM
   Partch, CL
   Rollins, D
   Propheter, DC
   Rizo, J
   Grabe, M
   Jiang, QX
   Hooper, LV
AF Mukherjee, Sohini
   Zheng, Hui
   Derebe, Mehabaw G.
   Callenberg, Keith M.
   Partch, Carrie L.
   Rollins, Darcy
   Propheter, Daniel C.
   Rizo, Josep
   Grabe, Michael
   Jiang, Qiu-Xing
   Hooper, Lora V.
TI Antibacterial membrane attack by a pore-forming intestinal C-type lectin
SO NATURE
LA English
DT Article
ID antimicrobial peptides; promotes; channels; solvent
AB Human body-surface epithelia coexist in close association with complex bacterial communities and are protected by a variety of antibacterial proteins. C-type lectins of the RegIII family are bactericidal proteins that limit direct contact between bacteria and the intestinal epithelium and thus promote tolerance to the intestinal microbiota(1,2). RegIII lectins recognize their bacterial targets by binding peptidoglycan carbohydrate(1,3), but the mechanism by which they kill bacteria is unknown. Here we elucidate the mechanistic basis for RegIII bactericidal activity. We show that human RegIII alpha (also known as HIP/PAP) binds membrane phospholipids and kills bacteria by forming a hexameric membrane-permeabilizing oligomeric pore. We derive a three-dimensional model of the RegIII alpha pore by docking the RegIII alpha crystal structure into a cryo-electron microscopic map of the pore complex, and show that the model accords with experimentally determined properties of the pore. Lipopolysaccharide inhibits RegIII alpha pore-forming activity, explaining why RegIII alpha is bactericidal for Gram-positive but not Gram-negative bacteria. Our findings identify C-type lectins as mediators of membrane attack in the mucosal immune system, and provide detailed insight into an antibacterial mechanism that promotes mutualism with the resident microbiota.
C1 [Mukherjee, Sohini; Derebe, Mehabaw G.; Rollins, Darcy; Propheter, Daniel C.; Hooper, Lora V.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
   [Zheng, Hui; Jiang, Qiu-Xing] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Callenberg, Keith M.; Grabe, Michael] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15261 USA.
   [Callenberg, Keith M.; Grabe, Michael] Univ Pittsburgh, PhD Program Computat Biol, Joint Carnegie Mellon Univ, Pittsburgh, PA 15261 USA.
   [Partch, Carrie L.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
   [Rizo, Josep] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Rizo, Josep] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Hooper, Lora V.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, 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; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Carnegie Mellon University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Santa Cruz; 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
RP Hooper, LV (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
EM qiu-xing.jiang@utsouthwestern.edu; lora.hooper@utsouthwestern.edu
FU NIH [R01 DK070855, R01GM088745, GM093271, R01 NS40944, C06 RR30414]; Welch Foundation [I-1684]; NSF CAREER [MCB0845286]; Helen Hay Whitney Fellowship; Burroughs Wellcome Foundation New Investigators in the Pathogenesis of Infectious Diseases Award; Howard Hughes Medical Institute; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK070855] Funding Source: NIH RePORTER
NR 27
TC 266
Z9 312
U1 0
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 2
PY 2014
VL 505
IS 7481
BP 103
EP +
DI 10.1038/nature12729
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300032
PM 24256734
DA 2026-03-09
ER

PT J
AU Gu, LC
   Li, C
   Aach, J
   Hill, DE
   Vidal, M
   Church, GM
AF Gu, Liangcai
   Li, Chao
   Aach, John
   Hill, David E.
   Vidal, Marc
   Church, George M.
TI Multiplex single-molecule interaction profiling of DNA-barcoded proteins
SO NATURE
LA English
DT Article
ID coupled receptor; polymerase colony; in-vitro; discovery; binding; amplification; genome; assays; identification; transduction
AB In contrast with advances in massively parallel DNA sequencing(1), high-throughput protein analyses(2-4) are often limited by ensemble measurements, individual analyte purification and hence compromised quality and cost-effectiveness. Single-molecule protein detection using optical methods(5) is limited by the number of spectrally non-overlapping chromophores. Here we introduce a single-molecular-interaction sequencing (SMI-seq) technology for parallel protein interaction profiling leveraging single-molecule advantages. DNA barcodes are attached to proteins collectively via ribosome display(6) or individually via enzymatic conjugation. Barcoded proteins are assayed en masse in aqueous solution and subsequently immobilized in a polyacrylamide thin film to construct a random single-molecule array, where barcoding DNAs are amplified into in situ polymerase colonies (polonies)(7) and analysed by DNA sequencing. This method allows precise quantification of various proteins with a theoretical maximum array density of over one million polonies per square millimetre. Furthermore, protein interactions can be measured on the basis of the statistics of colocalized polonies arising from barcoding DNAs of interacting proteins. Two demanding applications, G-protein coupled receptor and antibody-binding profiling, are demonstrated. SMI-seq enables 'library versus library' screening in a one-pot assay, simultaneously interrogating molecular binding affinity and specificity.
C1 [Gu, Liangcai; Aach, John; Hill, David E.; Vidal, Marc; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Li, Chao; Church, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
   [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA.
   [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Gu, LC (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM liangcaigu@gmail.com; gchurch@genetics.med.harvard.edu
FU US Department of Energy [DE-FG02-02ER63445]; NIH NHGRI [HG001715]; Jane Coffin Childs Fund for Medical Research; Harvard Origins of Life Initiative
NR 50
TC 68
Z9 146
U1 3
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 NOV 27
PY 2014
VL 515
IS 7528
BP 554
EP +
DI 10.1038/nature13761
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600001
PM 25252978
DA 2026-03-09
ER

PT J
AU Qin, N
   Yang, FL
   Li, A
   Prifti, E
   Chen, YF
   Shao, L
   Guo, J
   Le Chatelier, E
   Yao, J
   Wu, LJ
   Zhou, JW
   Ni, SJ
   Liu, L
   Pons, N
   Batto, JM
   Kennedy, SP
   Leonard, P
   Yuan, CH
   Ding, WC
   Chen, YT
   Hu, XJ
   Zheng, BW
   Qian, GR
   Xu, W
   Ehrlich, SD
   Zheng, SS
   Li, LJ
AF Qin, Nan
   Yang, Fengling
   Li, Ang
   Prifti, Edi
   Chen, Yanfei
   Shao, Li
   Guo, Jing
   Le Chatelier, Emmanuelle
   Yao, Jian
   Wu, Lingjiao
   Zhou, Jiawei
   Ni, Shujun
   Liu, Lin
   Pons, Nicolas
   Batto, Jean Michel
   Kennedy, Sean P.
   Leonard, Pierre
   Yuan, Chunhui
   Ding, Wenchao
   Chen, Yuanting
   Hu, Xinjun
   Zheng, Beiwen
   Qian, Guirong
   Xu, Wei
   Ehrlich, S. Dusko
   Zheng, Shusen
   Li, Lanjuan
TI Alterations of the human gut microbiome in liver cirrhosis
SO NATURE
LA English
DT Article
ID bacterial translocation; intestinal microbiota; obesity; catalog; genm; impact; long
AB Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
C1 [Qin, Nan; Yang, Fengling; Li, Ang; Chen, Yanfei; Shao, Li; Guo, Jing; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Li, Lanjuan] Zhejiang Univ, Affiliated Hosp 1, Coll Med, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
   [Qin, Nan; Shao, Li; Yao, Jian; Zheng, Beiwen; Zheng, Shusen; Li, Lanjuan] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China.
   [Prifti, Edi; Le Chatelier, Emmanuelle; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P.; Leonard, Pierre; Ehrlich, S. Dusko] INRA, Metagenopolis, F-78350 Jouy En Josas, France.
   [Ehrlich, S. Dusko] Kings Coll London, Dent Inst Cent Off, Guys Hosp, Ctr Host Microbiome Interact, London SE1 9RT, England.
   [Zheng, Shusen] Zhejiang Univ, Affiliated Hosp 1, Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou 310003, Zhejiang, Peoples R China.
C3 Zhejiang University; Zhejiang University; Collaborative Innovation Center for Diagnosis & Treatment of Infectious Diseases; Universite Paris Saclay; INRAE; Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London; Zhejiang University
RP Li, LJ (corresponding author), Zhejiang Univ, Affiliated Hosp 1, Coll Med, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
EM dusko.ehrlich@jouy.inra.fr; zyzsss@zju.edu.cn; ljli@zju.edu.cn
FU National Program on Key Basic Research Project [2013CB531401]; National Natural Science Foundation of China [81301475, 81330011]; Science Fund for Creative Research Groups of the National Natural Science Foundation of China [81121002]; Technology Group Project for Infectious Disease Control of Zhejiang Province [2009R50041]; Metagenopolis [ANR-11-DPBS-0001]
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NR 55
TC 1694
Z9 1940
U1 7
U2 553
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 4
PY 2014
VL 513
IS 7516
BP 59
EP +
DI 10.1038/nature13568
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO2SD
UT WOS:000341174800029
PM 25079328
DA 2026-03-09
ER

PT J
AU Tumeh, PC
   Harview, CL
   Yearley, JH
   Shintaku, IP
   Taylor, EJM
   Robert, L
   Chmielowski, B
   Spasic, M
   Henry, G
   Ciobanu, V
   West, AN
   Carmona, M
   Kivork, C
   Seja, E
   Cherry, G
   Gutierrez, AJ
   Grogan, TR
   Mateus, C
   Tomasic, G
   Glaspy, JA
   Emerson, RO
   Robins, H
   Pierce, RH
   Elashoff, DA
   Robert, C
   Ribas, A
AF Tumeh, Paul C.
   Harview, Christina L.
   Yearley, Jennifer H.
   Shintaku, I. Peter
   Taylor, Emma J. M.
   Robert, Lidia
   Chmielowski, Bartosz
   Spasic, Marko
   Henry, Gina
   Ciobanu, Voicu
   West, Alisha N.
   Carmona, Manuel
   Kivork, Christine
   Seja, Elizabeth
   Cherry, Grace
   Gutierrez, Antonio J.
   Grogan, Tristan R.
   Mateus, Christine
   Tomasic, Gorana
   Glaspy, John A.
   Emerson, Ryan O.
   Robins, Harlan
   Pierce, Robert H.
   Elashoff, David A.
   Robert, Caroline
   Ribas, Antoni
TI PD-1 blockade induces responses by inhibiting adaptive immune resistance
SO NATURE
LA English
DT Article
ID advanced melanoma; t-cells; safety; survival; ipilimumab; expression; anti-pd-1; antibody
AB Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types(1-5). One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance)7. Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-Li immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and nextgeneration sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8(+) expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 T cells that are negatively regulated by PD-1 /PD-Li-mediated adaptive immune resistance.
C1 [Tumeh, Paul C.; Harview, Christina L.; Shintaku, I. Peter; Taylor, Emma J. M.; Robert, Lidia; Chmielowski, Bartosz; Spasic, Marko; Henry, Gina; Ciobanu, Voicu; West, Alisha N.; Carmona, Manuel; Kivork, Christine; Seja, Elizabeth; Cherry, Grace; Gutierrez, Antonio J.; Grogan, Tristan R.; Glaspy, John A.; Elashoff, David A.; Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Tumeh, Paul C.; Chmielowski, Bartosz; Glaspy, John A.; Elashoff, David A.; Ribas, Antoni] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Yearley, Jennifer H.; Pierce, Robert H.] Merck & Co Inc, Palo Alto, CA 94304 USA.
   [Mateus, Christine; Tomasic, Gorana; Robert, Caroline] Univ Paris Sud, Gustave Roussy, Villejuif, France.
   [Mateus, Christine; Tomasic, Gorana; Robert, Caroline] INSERM, U981, Villejuif, Paris Sud, France.
   [Emerson, Ryan O.; Robins, Harlan] Adapt Biotechnol, Seattle, WA 98102 USA.
   [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
C3 University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; Merck & Company; Merck & Company USA; Universite Paris Saclay; UNICANCER; Gustave Roussy; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Fred Hutchinson Cancer Center
RP Tumeh, PC (corresponding author), Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
EM ptumeh@mednet.ucla.edu; aribas@mednet.ucla.edu
FU National Institutes of Health [K08 AI091663]; Kure It Research Grant [UL1TR000124, P01 CA168585, U54 CA119347, R01 CA170689]; Ressler Family Fund; Dr Robert Vigen Memorial Fund; Wesley Coyle Memorial Fund; Garcia-Corsini Family Fund; Stand Up To Cancer-Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant [SU2C-AACR-DT1012]; Merck Sharp and Dome; Adaptive Biotechnologies; V Foundation-Gil Nickel Family Endowed Fellowship in Melanoma Research; Spanish Society of Medical Oncology for Translational Research in Reference Centers;  [P30 CA16042]; National Cancer Institute [P30CA016042] Funding Source: NIH RePORTER
NR 20
TC 5491
Z9 6328
U1 33
U2 1080
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 568
EP +
DI 10.1038/nature13954
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600054
PM 25428505
DA 2026-03-09
ER

PT J
AU Ding, QH
   Wallace, JM
   Battisti, DS
   Steig, EJ
   Gallant, AJE
   Kim, HJ
   Geng, L
AF Ding, Qinghua
   Wallace, John M.
   Battisti, David S.
   Steig, Eric J.
   Gallant, Ailie J. E.
   Kim, Hyung-Jin
   Geng, Lei
TI Tropical forcing of the recent rapid Arctic warming in northeastern Canada and Greenland
SO NATURE
LA English
DT Article
ID surface-temperature; sea-ice; climate
AB Rapid Arctic warming and sea-ice reduction in the Arctic Ocean are widely attributed to anthropogenic climate change(1-3). The Arctic warming exceeds the global average warming because of feedbacks that include sea-ice reduction(4,5) and other dynamical and radiative feedbacks(6-13). We find that the most prominent annual mean surface and tropospheric warming in the Arctic since 1979 has occurred in northeastern Canada and Greenland. In this region, much of the year-to-year temperature variability is associated with the leading mode of large-scale circulation variability in the North Atlantic, namely, the North Atlantic Oscillation(14,15). Here we show that the recent warming in this region is strongly associated with a negative trend in the North Atlantic Oscillation, which is a response to anomalous Rossby wave-train activity originating in the tropical Pacific. Atmospheric model experiments forced by prescribed tropical sea surface temperatures simulate the observed circulation changes and associated tropospheric and surface warming over northeastern Canada and Greenland. Experiments from the Coupled Model Intercomparison Project Phase 5 (ref. 16) models with prescribed anthropogenic forcing show no similar circulation changes related to the North Atlantic Oscillation or associated tropospheric warming. This suggests that a substantial portion of recent warming in the northeastern Canada and Greenland sector of the Arctic arises from unforced natural variability.
C1 [Ding, Qinghua; Steig, Eric J.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Ding, Qinghua; Steig, Eric J.] Univ Washington, Quaternary Res Ctr, Seattle, WA 98195 USA.
   [Wallace, John M.; Battisti, David S.; Geng, Lei] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Gallant, Ailie J. E.] Monash Univ, Sch Geog & Environm Sci, Clayton, Vic 3800, Australia.
   [Kim, Hyung-Jin] APEC Climate Ctr, Climate Res Dept, Pusan 612020, South Korea.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Monash University
RP Ding, QH (corresponding author), Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
EM qinghua@uw.edu
FU US National Science Foundation [OPP 1043092, ATM 1122989]; University of Washington's Quaternary Research Center; National Basic Research Program of China (973 Program) [2013CB430203]; APEC Climate Center; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1122989] Funding Source: National Science Foundation
NR 32
TC 341
Z9 390
U1 7
U2 195
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 8
PY 2014
VL 509
IS 7499
BP 209
EP +
DI 10.1038/nature13260
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300035
PM 24805345
DA 2026-03-09
ER

PT J
AU Jurcevic, P
   Lanyon, BP
   Hauke, P
   Hempel, C
   Zoller, P
   Blatt, R
   Roos, CF
AF Jurcevic, P.
   Lanyon, B. P.
   Hauke, P.
   Hempel, C.
   Zoller, P.
   Blatt, R.
   Roos, C. F.
TI Quasiparticle engineering and entanglement propagation in a quantum many-body system
SO NATURE
LA English
DT Article
ID lieb-robinson bounds; states; computation; emergence
AB The key to explaining and controlling a range of quantum phenomena is to study how information propagates around many-body systems. Quantum dynamics can be described by particle-like carriers of information that emerge in the collective behaviour of the underlying system, the so-called quasiparticles(1). These elementary excitations are predicted to distribute quantum information in a fashion determined by the system's interactions(2). Here we report quasiparticle dynamics observed in a quantum many-body system of trapped atomic ions(3,4). First, we observe the entanglement distributed by quasiparticles as they trace out light-cone-like wavefronts(5-11). Second, using the ability to tune the interaction range in our system, we observe information propagation in an experimental regime where the effective-light-cone picture does not apply(7,12). Our results will enable experimental studies of a range of quantum phenomena, including transport(13,14), thermalization(15), localization(16) and entanglement growth(17), and represent a first step towards a newquantum-optic regime of engineered quasiparticles with tunable nonlinear interactions.
C1 [Jurcevic, P.; Lanyon, B. P.; Hauke, P.; Hempel, C.; Zoller, P.; Blatt, R.; Roos, C. F.] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Jurcevic, P.; Lanyon, B. P.; Hempel, C.; Blatt, R.; Roos, C. F.] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Hauke, P.; Zoller, P.] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
C3 Austrian Academy of Sciences; University of Innsbruck; University of Innsbruck
RP Roos, CF (corresponding author), Austrian Acad Sci, Inst Quantenopt & Quanteninformat, Technikerstr 21a, A-6020 Innsbruck, Austria.
EM christian.roos@uibk.ac.at
FU Austrian Science Fund (FWF) [P25354-N20]; European Commission via the integrated project SIQS; Institut fur Quanteninformation; European Research Council through the CRYTERION Project [227959]; Austrian Science Fund (FWF) [P 25354] Funding Source: researchfish; Austrian Science Fund (FWF) [P25354] Funding Source: Austrian Science Fund (FWF); European Research Council (ERC) [227959] Funding Source: European Research Council (ERC)
NR 36
TC 713
Z9 774
U1 1
U2 103
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 202
EP +
DI 10.1038/nature13461
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800039
PM 25008526
DA 2026-03-09
ER

PT J
AU Cannavo, E
   Cejka, P
AF Cannavo, Elda
   Cejka, Petr
TI Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50-Xrs2 to resect DNA breaks
SO NATURE
LA English
DT Article
ID double-strand-break; saccharomyces-cerevisiae; end resection; nuclease activity; topoisomerase-i; mre11 nuclease; repair; exo1; complex; rad50
AB To repair double-strand DNA breaks by homologous recombination, the 5'-terminated DNA strand must first be resected, which generates 3' single-stranded DNA overhangs. Genetic evidence suggests that this process is initiated by the Mre11-Rad50-Xrs2 (MRX) complex(1-3). However, its involvement was puzzling, as the complex possesses exonuclease activity with the opposite (3' to 5') polarity from that required for homologous recombination(4,5). Consequently, a bidirectional model has been proposed(6-8) whereby dsDNA is first incised endonucleolytically and MRX then proceeds back to the dsDNA end using its 3' to 5' exonuclease. The endonuclease creates entry sites for Sgs1-Dna2 and/or Exo1, which then carry out long-range resection in the 5' to 3' direction. However, the identity of the endonuclease remained unclear. Using purified Saccharomyces cerevisiae proteins, we show that Sae2 promotes dsDNA-specific endonuclease activity by the Mre11 subunit within the MRX complex. The endonuclease preferentially cleaves the 5'-terminated dsDNA strand, which explains the polarity paradox. The dsDNA end clipping is strongly stimulated by protein blocks at the DNA end, and requires the ATPase activity ofRad50 and physical interactions between MRX and Sae2. Our results suggest that MRX initiates dsDNA break processing by dsDNA endonuclease rather than exonuclease activity, and that Sae2 is the key regulator of this process. These findings demonstrate a probable mechanism for the initiation of dsDNA break processing in both vegetative and meiotic cells.
C1 [Cannavo, Elda; Cejka, Petr] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland.
C3 University of Zurich
RP Cejka, P (corresponding author), Univ Zurich, Inst Mol Canc Res, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM cejka@imcr.uzh.ch
FU Swiss National Science Foundation [PP00P3 133636]; Swiss National Science Foundation (SNF) [PP00P3_133636] Funding Source: Swiss National Science Foundation (SNF)
NR 34
TC 352
Z9 432
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 OCT 2
PY 2014
VL 514
IS 7520
BP 122
EP +
DI 10.1038/nature13771
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800048
PM 25231868
DA 2026-03-09
ER

PT J
AU Sun, J
   Bankston, JR
   Payandeh, J
   Hinds, TR
   Zagotta, WN
   Zheng, N
AF Sun, Ji
   Bankston, John R.
   Payandeh, Jian
   Hinds, Thomas R.
   Zagotta, William N.
   Zheng, Ning
TI Crystal structure of the plant dual-affinity nitrate transporter NRT1.1
SO NATURE
LA English
DT Article
ID glucose transporters; chl1 functions; arabidopsis; mechanism; protein; membrane; reveals; encodes; system; dimer
AB Nitrate is a primary nutrient for plant growth, but its levels in soil can fluctuate by several orders of magnitude. Previous studies have identified Arabidopsis NRT1.1 as a dual-affinity nitrate transporter that can take up nitrate over a wide range of concentrations. The mode of action of NRT1.1 is controlled by phosphorylation of a key residue, Thr 101; however, how this post-translational modification switches the transporter between two affinity states remains unclear. Here we report the crystal structure of unphosphorylated NRT1.1, which reveals an unexpected homodimer in the inward-facing conformation. In this low-affinity state, the Thr 101 phosphorylation site is embedded in a pocket immediately adjacent to the dimer interface, linking the phosphorylation status of the transporter to its oligomeric state. Using a cell-based fluorescence resonance energy transfer assay, we show that functional NRT1.1 dimerizes in the cell membrane and that the phosphomimetic mutation of Thr 101 converts the protein into a monophasic high-affinity transporter by structurally decoupling the dimer. Together with analyses of the substrate transport tunnel, our results establish a phosphorylation-controlled dimerization switch that allows NRT1.1 to uptake nitrate with two distinct affinity modes.
C1 [Sun, Ji; Payandeh, Jian; Hinds, Thomas R.; Zheng, Ning] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Bankston, John R.; Zagotta, William N.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
   [Zheng, Ning] 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; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Zheng, N (corresponding author), Univ Washington, Dept Pharmacol, Box 357280, Seattle, WA 98195 USA.
EM nzheng@u.washington.edu
FU Howard Hughes Medical Institute; National Institutes of Health [R01EY10329, NS074545]; National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1157561] Funding Source: National Science Foundation; National Eye Institute [R01EY010329] Funding Source: NIH RePORTER
NR 40
TC 261
Z9 298
U1 5
U2 217
PU NATURE PUBLISHING 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 6
PY 2014
VL 507
IS 7490
BP 73
EP +
DI 10.1038/nature13074
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400044
PM 24572362
DA 2026-03-09
ER

PT J
AU Song, R
   Walentek, P
   Sponer, N
   Klimke, A
   Lee, JS
   Dixon, G
   Harland, R
   Wan, Y
   Lishko, P
   Lize, M
   Kessel, M
   He, L
AF Song, Rui
   Walentek, Peter
   Sponer, Nicole
   Klimke, Alexander
   Lee, Joon Sub
   Dixon, Gary
   Harland, Richard
   Wan, Ying
   Lishko, Polina
   Lize, Muriel
   Kessel, Michael
   He, Lin
TI miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110
SO NATURE
LA English
DT Article
ID primary ciliary dyskinesia; epithelial-cells; basal body; small rnas; c-elegans; microrna; xenopus; biogenesis; expression; mutations
AB The mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertility and strong respiratory dysfunction caused by defective mucociliary clearance. In both mouse and Xenopus, miR-34/449-deficient multiciliated cells (MCCs) exhibited a significant decrease in cilia length and number, due to defective basal body maturation and apical docking. The effect of miR-34/449 on ciliogenesis was mediated, at least in part, by post-transcriptional repression of Cp110, a centriolar protein suppressing cilia assembly. Consistent with this, cp110 knockdown in miR-34/449-deficient MCCs restored ciliogenesis by rescuing basal body maturation and docking. Altogether, our findings elucidate conserved cellular and molecular mechanisms through which miR-34/449 regulate motile ciliogenesis.
C1 [Song, Rui; Sponer, Nicole; Lee, Joon Sub; Dixon, Gary; Lishko, Polina; He, Lin] Univ Calif Berkeley, Div Cellular & Dev Biol, MCB Dept, Berkeley, CA 94705 USA.
   [Walentek, Peter; Harland, Richard] Univ Calif Berkeley, Div Genet Genom & Dev, MCB Dept, Ctr Integrat Genom, Berkeley, CA 94705 USA.
   [Klimke, Alexander; Kessel, Michael] Max Planck Inst Biophys Chem, Dept Mol Cell Biol, D-37077 Gottingen, Germany.
   [Wan, Ying] Third Mil Med Univ, Chongqing 400038, Peoples R China.
   [Lize, Muriel] Univ Gottingen, Dept Mol Oncol, D-37073 Gottingen, Germany.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; Max Planck Society; Army Medical University; University of Gottingen
RP He, L (corresponding author), Univ Calif Berkeley, Div Cellular & Dev Biol, MCB Dept, Berkeley, CA 94705 USA.
EM rui.song@berkeley.edu; lhe@berkeley.edu
FU NCI [R01 CA139067, 1R21CA175560-01]; CIRM new faculty award [RN2-00923-1]; TRDRP research grant [21RT-0133]; American Cancer Society (ACS) [123339-RSG-12-265-01-RMC]; Siebel postdoctoral fellowship; CIRM postdoctoral fellowship; Deutsche Forschungsgemeinschaft (DFG) [Wa 3365/1-1]; NIH [GM42341]; Dorothea Schloezer Fellowship; National Cancer Institute [R01CA139067] Funding Source: NIH RePORTER
NR 50
TC 181
Z9 203
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 JUN 5
PY 2014
VL 510
IS 7503
BP 115
EP +
DI 10.1038/nature13413
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900039
PM 24899310
DA 2026-03-09
ER

PT J
AU Weinstein, JN
   Akbani, R
   Broom, BM
   Wang, WY
   Verhaak, RGW
   McConkey, D
   Lerner, S
   Morgan, M
   Creighton, CJ
   Smith, C
   Kwiatkowski, DJ
   Cherniack, AD
   Kim, J
   Pedamallu, CS
   Noble, MS
   Al-Ahmadie, HA
   Reuter, VE
   Rosenberg, JE
   Bajorin, DF
   Bochner, BH
   Solit, DB
   Koppie, T
   Robinson, B
   Gordenin, DA
   Fargo, D
   Klimczak, LJ
   Roberts, SA
   Au, J
   Laird, PW
   Hinoue, T
   Schultz, N
   Ramirez, R
   Hansel, D
   Hoadley, KA
   Kim, WY
   Damrauer, JS
   Baylin, SB
   Mungall, AJ
   Robertson, AG
   Chu, A
   Kwiatkowski, DJ
   Sougnez, C
   Cibulskis, K
   Lichtenstein, L
   Sivachenko, A
   Stewart, C
   Lawrence, MS
   Getz, G
   Lander, E
   Gabriel, SB
   Creighton, CJ
   Donehower, L
   Cherniack, AD
   Kim, J
   Carter, SL
   Saksena, G
   Schumacher, SE
   Sougnez, C
   Freeman, SS
   Jung, J
   Pedamallu, CS
   Bhatt, AS
   Pugh, T
   Getz, G
   Beroukhim, R
   Gabriel, SB
   Meyerson, M
   Mungall, AJ
   Robertson, AG
   Chu, A
   Ally, A
   Balasundaram, M
   Butterfield, YSN
   Dhalla, N
   Hirst, C
   Holt, RA
   Jones, SJM
   Lee, D
   Li, HYI
   Marra, MA
   Mayo, M
   Moore, RA
   Schein, JE
   Sipahimalani, P
   Tam, A
   Thiessen, N
   Wong, T
   Wye, N
   Bowlby, R
   Chuah, E
   Guin, R
   Jones, SJM
   Marra, MA
   Hinoue, T
   Shen, H
   Bootwalla, MS
   Triche, T
   Lai, PH
   Van den Berg, DJ
   Weisenberger, DJ
   Laird, PW
   Hansel, D
   Hoadley, KA
   Balu, S
   Bodenheimer, T
   Damrauer, JS
   Hoyle, AP
   Jefferys, SR
   Meng, SW
   Mose, LE
   Simons, JV
   Soloway, MG
   Wu, JY
   Kim, WY
   Parker, JS
   Hayes, DN
   Roach, J
   Buda, E
   Jones, CD
   Mieczkowski, PA
   Tan, DH
   Veluvolu, U
   Waring, S
   Auman, JT
   Perou, CM
   Wilkerson, MD
   Santoso, N
   Parfenov, M
   Ren, XJ
   Pantazi, A
   Hadjipanayis, A
   Seidman, J
   Kucherlapati, R
   Lee, S
   Yang, LX
   Park, PJ
   Baylin, SB
   Xu, AW
   Protopopov, A
   Zhang, JH
   Bristow, C
   Mahadeshwar, HS
   Seth, S
   Song, XZ
   Tang, JB
   Zeng, D
   Chin, LD
   Guo, C
   Weinstein, JN
   Akbani, R
   Broom, BM
   McConkey, D
   Casasent, TD
   Liu, WB
   Ju, ZL
   Motter, T
   Peng, B
   Ryan, M
   Wang, WY
   Verhaak, RGW
   Su, XP
   Yang, JY
   Lorenzi, PL
   Yao, H
   Zhang, NX
   Zhang, JX
   Mills, GB
   Kim, J
   Noble, MS
   Cho, J
   DiCara, D
   Frazer, S
   Gehlenborg, N
   Heiman, DI
   Lin, P
   Liu, YC
   Stojanov, P
   Voet, D
   Zhang, HL
   Zou, LH
   Chin, LD
   Getz, G
   Bernard, B
   Kreisberg, D
   Reynolds, S
   Rovira, H
   Shmulevich, I
   Ramirez, R
   Schultz, N
   Gao, JJ
   Jacobsen, A
   Aksoy, BA
   Antipin, Y
   Ciriello, G
   Dresdner, G
   Gross, B
   Lee, W
   Reva, B
   Shen, RL
   Sinha, R
   Sumer, SO
   Weinhold, N
   Ladanyi, M
   Sander, C
   Benz, C
   Carlin, D
   Haussler, D
   Ng, S
   Paull, EO
   Stuart, J
   Zhu, J
   Liu, YX
   Zhang, W
   Taylor, BS
   Lichtenberg, TM
   Zmuda, E
   Barr, T
   Black, AD
   George, M
   Hanf, B
   Helsel, C
   McAllister, C
   Ramirez, NC
   Tabler, TR
   Weaver, S
   Wise, L
   Bowen, J
   Gastier-Foster, JM
   Weinstein, JN
   Lerner, S
   Jian, WG
   Tello, S
   Ittman, M
   Castro, P
   McClenden, WD
   Morgan, M
   Gibbs, R
   Liu, YC
   Saller, C
   Tarvin, K
   DiPiero, JM
   Owens, J
   Bollag, R
   Li, Q
   Weinberger, P
   Czerwinski, C
   Huelsenbeck-Dill, L
   Iacocca, M
   Petrelli, N
   Rabeno, B
   Swanson, P
   Shelton, T
   Curley, E
   Gardner, J
   Mallery, D
   Penny, R
   Bang, NV
   Hanh, PT
   Kohl, B
   Le, XV
   Phu, BD
   Thorp, R
   Tien, NV
   Vinh, LQ
   Sandusky, G
   Burks, E
   Christ, K
   Gee, J
   Holway, A
   Moinzadeh, A
   Sorcini, A
   Sullivan, T
   Al-Ahmadie, HA
   Bajorin, DF
   Bochner, BH
   Garcia-Grossman, IR
   Regazzi, AM
   Solit, DB
   Rosenberg, JE
   Reuter, VE
   Koppie, T
   Boice, L
   Rathmell, WK
   Thorne, L
   Bastacky, S
   Davies, B
   Dhir, R
   Gingrich, J
   Hrebinko, R
   Maranchie, J
   Nelson, J
   Parwani, A
   Bshara, W
   Gaudioso, C
   Morrison, C
   Alexopoulou, V
   Bartlett, J
   Engel, J
   Kodeeswaran, S
   Antic, T
   O'Donnell, PH
   Smith, ND
   Steinberg, GD
   Egea, S
   Gomez-Fernandez, C
   Herbert, L
   Jorda, M
   Soloway, M
   Beaver, A
   Carter, S
   Kapur, P
   Lewis, C
   Lotan, Y
   Robinson, B
   Hansel, D
   Guo, C
   Bondaruk, J
   Czerniak, B
   Akbani, R
   Broom, BM
   Liu, YX
   Zhang, W
   Weinstein, JN
   Lerner, S
   Morgan, M
   Kim, J
   Cherniack, AD
   Freeman, SS
   Pedamallu, CS
   Noble, MS
   Kwiatkowski, DJ
   Al-Ahmadie, HA
   Bajorin, DF
   Bochner, BH
   Solit, DB
   Rosenberg, JE
   Reuter, VE
   Koppie, T
   Robinson, B
   Skinner, E
   Ramirez, R
   Schultz, N
   Hansel, D
   Kim, WY
   Guo, C
   Bondaruk, J
   Aldape, K
   Czerniak, B
   Jensen, MA
   Kahn, AB
   Pihl, TD
   Pot, DA
   Srinivasan, D
   Wan, YH
   Ferguson, ML
   Zenklusen, JC
   Davidsen, T
   Demchok, JA
   Shaw, KRM
   Sheth, M
   Tarnuzzer, R
   Wang, ZN
   Yang, LM
   Hutter, C
   Ozenberger, BA
   Sofia, HJ
   Eley, G
AF Weinstein, John N.
   Akbani, Rehan
   Broom, Bradley M.
   Wang, Wenyi
   Verhaak, Roeland G. W.
   McConkey, David
   Lerner, Seth
   Morgan, Margaret
   Creighton, Chad J.
   Smith, Carolyn
   Kwiatkowski, David J.
   Cherniack, Andrew D.
   Kim, Jaegil
   Pedamallu, Chandra Sekhar
   Noble, Michael S.
   Al-Ahmadie, Hikmat A.
   Reuter, Victor E.
   Rosenberg, Jonathan E.
   Bajorin, Dean F.
   Bochner, Bernard H.
   Solit, David B.
   Koppie, Theresa
   Robinson, Brian
   Gordenin, Dmitry A.
   Fargo, David
   Klimczak, Leszek J.
   Roberts, Steven A.
   Au, Jessie
   Laird, Peter W.
   Hinoue, Toshinori
   Schultz, Nikolaus
   Ramirez, Ricardo
   Hansel, Donna
   Hoadley, Katherine A.
   Kim, William Y.
   Damrauer, Jeffrey S.
   Baylin, Stephen B.
   Mungall, Andrew J.
   Robertson, A. Gordon
   Chu, Andy
   Kwiatkowski, David J.
   Sougnez, Carrie
   Cibulskis, Kristian
   Lichtenstein, Lee
   Sivachenko, Andrey
   Stewart, Chip
   Lawrence, Michael S.
   Getz, Gad
   Lander, Eric
   Gabriel, Stacey B.
   Creighton, Chad J.
   Donehower, Lawrence
   Cherniack, Andrew D.
   Kim, Jaegil
   Carter, Scott L.
   Saksena, Gordon
   Schumacher, Steven E.
   Sougnez, Carrie
   Freeman, Samuel S.
   Jung, Joonil
   Pedamallu, Chandra Sekhar
   Bhatt, Ami S.
   Pugh, Trevor
   Getz, Gad
   Beroukhim, Rameen
   Gabriel, Stacey B.
   Meyerson, Matthew
   Mungall, Andrew J.
   Robertson, A. Gordon
   Chu, Andy
   Ally, Adrian
   Balasundaram, Miruna
   Butterfield, Yaron S. N.
   Dhalla, Noreen
   Hirst, Carrie
   Holt, Robert A.
   Jones, Steven J. M.
   Lee, Darlene
   Li, Haiyan I.
   Marra, Marco A.
   Mayo, Michael
   Moore, Richard A.
   Schein, Jacqueline E.
   Sipahimalani, Payal
   Tam, Angela
   Thiessen, Nina
   Wong, Tina
   Wye, Natasja
   Bowlby, Reanne
   Chuah, Eric
   Guin, Ranabir
   Jones, Steven J. M.
   Marra, Marco A.
   Hinoue, Toshinori
   Shen, Hui
   Bootwalla, Moiz S.
   Triche, Timothy, Jr.
   Lai, Phillip H.
   Van den Berg, David J.
   Weisenberger, Daniel J.
   Laird, Peter W.
   Hansel, Donna
   Hoadley, Katherine A.
   Balu, Saianand
   Bodenheimer, Tom
   Damrauer, Jeffrey S.
   Hoyle, Alan P.
   Jefferys, Stuart R.
   Meng, Shaowu
   Mose, Lisle E.
   Simons, Janae V.
   Soloway, Mathew G.
   Wu, Junyuan
   Kim, William Y.
   Parker, Joel S.
   Hayes, D. Neil
   Roach, Jeffrey
   Buda, Elizabeth
   Jones, Corbin D.
   Mieczkowski, Piotr A.
   Tan, Donghui
   Veluvolu, Umadevi
   Waring, Scot
   Auman, J. Todd
   Perou, Charles M.
   Wilkerson, Matthew D.
   Santoso, Netty
   Parfenov, Michael
   Ren, Xiaojia
   Pantazi, Angeliki
   Hadjipanayis, Angela
   Seidman, Jonathan
   Kucherlapati, Raju
   Lee, Semin
   Yang, Lixing
   Park, Peter J.
   Baylin, Stephen B.
   Xu, Andrew Wei
   Protopopov, Alexei
   Zhang, Jianhua
   Bristow, Christopher
   Mahadeshwar, Harshad S.
   Seth, Sahil
   Song, Xingzhi
   Tang, Jiabin
   Zeng, Dong
   Chin, Lynda
   Guo, Charles
   Weinstein, John N.
   Akbani, Rehan
   Broom, Bradley M.
   McConkey, David
   Casasent, Tod D.
   Liu, Wenbin
   Ju, Zhenlin
   Motter, Thomas
   Peng, Bo
   Ryan, Michael
   Wang, Wenyi
   Verhaak, Roeland G. W.
   Su, Xiaoping
   Yang, Ji-Yeon
   Lorenzi, Philip L.
   Yao, Hui
   Zhang, Nianxiang
   Zhang, Jiexin
   Mills, Gordon B.
   Kim, Jaegil
   Noble, Michael S.
   Cho, Juok
   DiCara, Daniel
   Frazer, Scott
   Gehlenborg, Nils
   Heiman, David I.
   Lin, Pei
   Liu, Yingchun
   Stojanov, Petar
   Voet, Doug
   Zhang, Hailei
   Zou, Lihua
   Chin, Lynda
   Getz, Gad
   Bernard, Brady
   Kreisberg, Dick
   Reynolds, Sheila
   Rovira, Hector
   Shmulevich, Ilya
   Ramirez, Ricardo
   Schultz, Nikolaus
   Gao, Jianjiong
   Jacobsen, Anders
   Aksoy, B. Arman
   Antipin, Yevgeniy
   Ciriello, Giovanni
   Dresdner, Gideon
   Gross, Benjamin
   Lee, William
   Reva, Boris
   Shen, Ronglai
   Sinha, Rileen
   Sumer, S. Onur
   Weinhold, Nils
   Ladanyi, Marc
   Sander, Chris
   Benz, Christopher
   Carlin, Daniel
   Haussler, David
   Ng, Sam
   Paull, Evan O.
   Stuart, Joshua
   Zhu, Jing
   Liu, Yuexin
   Zhang, Wei
   Taylor, Barry S.
   Lichtenberg, Tara M.
   Zmuda, Erik
   Barr, Thomas
   Black, Aaron D.
   George, Myra
   Hanf, Benjamin
   Helsel, Carmen
   McAllister, Cynthia
   Ramirez, Nilsa C.
   Tabler, Teresa R.
   Weaver, Stephanie
   Wise, Lisa
   Bowen, Jay
   Gastier-Foster, Julie M.
   Weinstein, John N.
   Lerner, Seth
   Jian, Weiguo
   Tello, Sebrina
   Ittman, Michael
   Castro, Patricia
   McClenden, Whitney D.
   Morgan, Margaret
   Gibbs, Richard
   Liu, Yingchun
   Saller, Charles
   Tarvin, Katherine
   DiPiero, Jennifer M.
   Owens, Jennifer
   Bollag, Roni
   Li, Qiang
   Weinberger, Paul
   Czerwinski, Christine
   Huelsenbeck-Dill, Lori
   Iacocca, Mary
   Petrelli, Nicholas
   Rabeno, Brenda
   Swanson, Pat
   Shelton, Troy
   Curley, Erin
   Gardner, Johanna
   Mallery, David
   Penny, Robert
   Nguyen Van Bang
   Phan Thi Hanh
   Kohl, Bernard
   Xuan Van Le
   Bui Duc Phu
   Thorp, Richard
   Nguyen Viet Tien
   Le Quang Vinh
   Sandusky, George
   Burks, Eric
   Christ, Kimberly
   Gee, Jason
   Holway, Antonia
   Moinzadeh, Alireza
   Sorcini, Andrea
   Sullivan, Travis
   Al-Ahmadie, Hikmat A.
   Bajorin, Dean F.
   Bochner, Bernard H.
   Garcia-Grossman, Ilana R.
   Regazzi, Ashley M.
   Solit, David B.
   Rosenberg, Jonathan E.
   Reuter, Victor E.
   Koppie, Theresa
   Boice, Lori
   Rathmell, Wendy Kimryn
   Thorne, Leigh
   Bastacky, Sheldon
   Davies, Benjamin
   Dhir, Rajiv
   Gingrich, Jeffrey
   Hrebinko, Ronald
   Maranchie, Jodi
   Nelson, Joel
   Parwani, Anil
   Bshara, Wiam
   Gaudioso, Carmelo
   Morrison, Carl
   Alexopoulou, Vina
   Bartlett, John
   Engel, Jay
   Kodeeswaran, Sugy
   Antic, Tatjana
   O'Donnell, Peter H.
   Smith, Norm D.
   Steinberg, Gary D.
   Egea, Sophie
   Gomez-Fernandez, Carmen
   Herbert, Lynn
   Jorda, Merce
   Soloway, Mark
   Beaver, Allison
   Carter, Suzie
   Kapur, Payal
   Lewis, Cheryl
   Lotan, Yair
   Robinson, Brian
   Hansel, Donna
   Guo, Charles
   Bondaruk, Jolanta
   Czerniak, Bogdan
   Akbani, Rehan
   Broom, Bradley M.
   Liu, Yuexin
   Zhang, Wei
   Weinstein, John N.
   Lerner, Seth
   Morgan, Margaret
   Kim, Jaegil
   Cherniack, Andrew D.
   Freeman, Samuel S.
   Pedamallu, Chandra Sekhar
   Noble, Michael S.
   Kwiatkowski, David J.
   Al-Ahmadie, Hikmat A.
   Bajorin, Dean F.
   Bochner, Bernard H.
   Solit, David B.
   Rosenberg, Jonathan E.
   Reuter, Victor E.
   Koppie, Theresa
   Robinson, Brian
   Skinner, Eila
   Ramirez, Ricardo
   Schultz, Nikolaus
   Hansel, Donna
   Kim, William Y.
   Guo, Charles
   Bondaruk, Jolanta
   Aldape, Kenneth
   Czerniak, Bogdan
   Jensen, Mark A.
   Kahn, Ari B.
   Pihl, Todd D.
   Pot, David A.
   Srinivasan, Deepak
   Wan, Yunhu
   Ferguson, Martin L.
   Zenklusen, Jean Claude
   Davidsen, Tanja
   Demchok, John A.
   Shaw, Kenna R. Mills
   Sheth, Margi
   Tarnuzzer, Roy
   Wang, Zhining
   Yang, Liming
   Hutter, Carolyn
   Ozenberger, Bradley A.
   Sofia, Heidi J.
   Eley, Greg
TI Comprehensive molecular characterization of urothelial bladder carcinoma
SO NATURE
LA English
DT Article
ID gene fusions; cancer; mutations; genm; kinase; fgfr
AB Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomasto provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
C1 [Weinstein, John N.; Akbani, Rehan; Broom, Bradley M.; Wang, Wenyi; Verhaak, Roeland G. W.; Liu, Wenbin; Ju, Zhenlin; Motter, Thomas; Peng, Bo; Ryan, Michael; Su, Xiaoping; Yang, Ji-Yeon; Lorenzi, Philip L.; Yao, Hui; Zhang, Nianxiang; Zhang, Jiexin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Liu, Wenbin; Ju, Zhenlin; Yang, Ji-Yeon; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   [McConkey, David; Shaw, Kenna R. Mills] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Lerner, Seth; Jian, Weiguo; Tello, Sebrina] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
   [Morgan, Margaret; Jian, Weiguo; Tello, Sebrina; Ittman, Michael; Castro, Patricia; McClenden, Whitney D.; Gibbs, Richard] Baylor Coll Med, TCRB, Houston, TX 77030 USA.
   [Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Creighton, Chad J.; Donehower, Lawrence] Baylor Coll Med, Human Genome Sequencing Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Smith, Carolyn] Baylor Coll Med, Houston, TX 77030 USA.
   [Kwiatkowski, David J.; Kwiatkowski, David J.; Cibulskis, Kristian; Lichtenstein, Lee; Sivachenko, Andrey; Stewart, Chip; Lawrence, Michael S.; Getz, Gad; Lander, Eric; Gabriel, Stacey B.; Carter, Scott L.; Saksena, Gordon; Schumacher, Steven E.; Freeman, Samuel S.; Jung, Joonil; Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Lin, Pei; Liu, Yingchun; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Kwiatkowski, David J.; Casasent, Tod D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Kwiatkowski, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Garcia-Grossman, Ilana R.; Regazzi, Ashley M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Koppie, Theresa] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA.
   Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
   [Gordenin, Dmitry A.; Fargo, David; Klimczak, Leszek J.; Roberts, Steven A.] NIEHS, Res Triangle Pk, NC 27709 USA.
   [Au, Jessie] OptimumTherapeutics LLC, San Diego, CA 92121 USA.
   [Shen, Hui; Bootwalla, Moiz S.; Triche, Timothy, Jr.; Lai, Phillip H.; Van den Berg, David J.; Weisenberger, Daniel J.] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90033 USA.
   [Schultz, Nikolaus; Ramirez, Ricardo; Gao, Jianjiong; Jacobsen, Anders; Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gross, Benjamin; Lee, William; Reva, Boris; Shen, Ronglai; Sinha, Rileen; Sumer, S. Onur; Weinhold, Nils; Ladanyi, Marc; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Hansel, Donna] UCSD Dept Pathol, La Jolla, CA 92093 USA.
   [Hoadley, Katherine A.; Balu, Saianand; Bodenheimer, Tom; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Simons, Janae V.; Soloway, Mathew G.; Wu, Junyuan; Parker, Joel S.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Parker, Joel S.; Perou, Charles M.; Wilkerson, Matthew D.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA.
   Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Donehower, Lawrence] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
   [Schumacher, Steven E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
   [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
   [Mungall, Andrew J.; Chu, Andy; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Dhalla, Noreen; Hirst, Carrie; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Wye, Natasja; Bowlby, Reanne; Chuah, Eric; Guin, Ranabir] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
   [Hayes, D. Neil] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
   [Roach, Jeffrey] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA.
   [Buda, Elizabeth; Jones, Corbin D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Jones, Corbin D.; Mieczkowski, Piotr A.; Tan, Donghui; Veluvolu, Umadevi; Waring, Scot] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Santoso, Netty; Parfenov, Michael; Ren, Xiaojia; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Hadjipanayis, Angela; Kucherlapati, Raju; Park, Peter J.; Xu, Andrew Wei] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Lee, Semin; Yang, Lixing; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Protopopov, Alexei; Zhang, Jianhua; Bristow, Christopher; Mahadeshwar, Harshad S.; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77030 USA.
   [Guo, Charles; Bondaruk, Jolanta; Czerniak, Bogdan; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Bernard, Brady; Kreisberg, Dick; Reynolds, Sheila; Rovira, Hector; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
   [Benz, Christopher] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Carlin, Daniel; Haussler, David; Ng, Sam; Paull, Evan O.; Stuart, Joshua; Zhu, Jing] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
   [Liu, Yuexin; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
   [Lichtenberg, Tara M.; Zmuda, Erik; Barr, Thomas; Black, Aaron D.; George, Myra; Hanf, Benjamin; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Weaver, Stephanie; Wise, Lisa; Bowen, Jay; Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
   [Ramirez, Nilsa C.; Gastier-Foster, Julie M.] Ohio State Univ, Columbus, OH 43210 USA.
   [Ittman, Michael; Castro, Patricia] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
   [Saller, Charles; Tarvin, Katherine] Analyt Biol Serv Inc, Wilmington, DE 19801 USA.
   [DiPiero, Jennifer M.; Owens, Jennifer] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   [Bollag, Roni; Li, Qiang; Weinberger, Paul] Georgia Regents Univ, Canc Ctr, Augusta, GA 30912 USA.
   [Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Swanson, Pat] Christiana Care, Helen F Graham Canc Ctr, Newark, DE 19713 USA.
   [Shelton, Troy; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Nguyen Van Bang; Phan Thi Hanh; Kohl, Bernard; Xuan Van Le; Bui Duc Phu; Thorp, Richard; Nguyen Viet Tien; Le Quang Vinh] ILSbio LLC, Chestertown, MD 21620 USA.
   Hue Cent Hosp, Hue City, Vietnam.
   [Sandusky, George] IU Sch Med, Indianapolis, IN 46202 USA.
   [Burks, Eric; Christ, Kimberly; Gee, Jason; Holway, Antonia; Moinzadeh, Alireza; Sorcini, Andrea; Sullivan, Travis] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA.
   [Boice, Lori; Rathmell, Wendy Kimryn; Thorne, Leigh] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
   [Bastacky, Sheldon; Davies, Benjamin; Dhir, Rajiv; Gingrich, Jeffrey; Hrebinko, Ronald; Maranchie, Jodi; Nelson, Joel; Parwani, Anil] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
   [Bshara, Wiam; Gaudioso, Carmelo; Morrison, Carl] Roswell Pk Canc Inst, Buffalo, NY 14063 USA.
   [Alexopoulou, Vina; Bartlett, John; Engel, Jay; Kodeeswaran, Sugy] St Josephs Healthcare Hamilton, Ontario Tumour Bank, Hamilton, ON L8N 3Z5, Canada.
   [Antic, Tatjana; O'Donnell, Peter H.; Smith, Norm D.; Steinberg, Gary D.] Univ Chicago, Chicago, IL 60637 USA.
   [Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Jorda, Merce; Soloway, Mark] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
   [Beaver, Allison; Carter, Suzie; Kapur, Payal; Lewis, Cheryl; Lotan, Yair] UT Southwestern Med Ctr, Dallas, TX 75390 USA.
   [Skinner, Eila] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
   [Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA.
   [Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
   [Zenklusen, Jean Claude; Davidsen, Tanja; Demchok, John A.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming] NCI, Bethesda, MD 20892 USA.
   [Hutter, Carolyn; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, Rockville, MD 20852 USA.
   [Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; 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; Memorial Sloan Kettering Cancer Center; Oregon Health & Science University; Cornell University; Weill Cornell Medicine; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); University of Southern California; Memorial Sloan Kettering Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Johns Hopkins University; Johns Hopkins Medicine; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Baylor College of Medicine; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; British Columbia Cancer Agency; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Institute for Systems Biology (ISB); Buck Institute for Research on Aging; University of California System; University of California Santa Cruz; University of Texas System; UTMD Anderson Cancer Center; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; University System of Ohio; Ohio State University; Baylor College of Medicine; Cleveland Clinic Foundation; University System of Georgia; Augusta University; Christiana Care Health System; Helen F. Graham Cancer Center & Research Institute; International Genomics Consortium; Indiana University System; Indiana University Bloomington; Lahey Hospital & Medical Center; University of North Carolina; University of North Carolina Chapel Hill; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Roswell Park Comprehensive Cancer Center; McMaster University; University of Chicago; University of Miami; University of Texas System; University of Texas Southwestern Medical Center; Stanford University; SRA International; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Weinstein, JN (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
EM jweinste@mdanderson.org; slerner@bcm.edu; dk@rics.bwh.harvard.edu
FU United States National Institutes of Health [U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, P01 CA120964]; National Cancer Institute [P30CA016086, P30CA008748, P30CA016672, P01CA120964] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL069768] Funding Source: NIH RePORTER
NR 39
TC 2418
Z9 2697
U1 3
U2 270
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2014
VL 507
IS 7492
BP 315
EP 322
DI 10.1038/nature12965
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000025
PM 24476821
DA 2026-03-09
ER

PT J
AU Moltke, I
   Grarup, N
   Jorgensen, ME
   Bjerregaard, P
   Treebak, JT
   Fumagalli, M
   Korneliussen, TS
   Andersen, MA
   Nielsen, TS
   Krarup, NT
   Gjesing, AP
   Zierath, JR
   Linneberg, A
   Wu, XL
   Sun, GQ
   Jin, X
   Al-Aama, J
   Wang, J
   Borch-Johnsen, K
   Pedersen, O
   Nielsen, R
   Albrechtsen, A
   Hansen, T
AF Moltke, Ida
   Grarup, Niels
   Jorgensen, Marit E.
   Bjerregaard, Peter
   Treebak, Jonas T.
   Fumagalli, Matteo
   Korneliussen, Thorfinn S.
   Andersen, Marianne A.
   Nielsen, Thomas S.
   Krarup, Nikolaj T.
   Gjesing, Anette P.
   Zierath, Juleen R.
   Linneberg, Allan
   Wu, Xueli
   Sun, Guangqing
   Jin, Xin
   Al-Aama, Jumana
   Wang, Jun
   Borch-Johnsen, Knut
   Pedersen, Oluf
   Nielsen, Rasmus
   Albrechtsen, Anders
   Hansen, Torben
TI A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes
SO NATURE
LA English
DT Article
ID glycemic traits; glucose; population; discovery; framework; mutation
AB The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years(1). Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose(beta=3.8 mmol l(-1), P = 2.5 X 10(-35)) and serum insulin (beta = 165 pmol l(-1), P = 1.5 X 10(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (beta = -0.18 mmol l(-1), P = 1.1 X 10(-6)) and fasting serum insulin (beta = -8.3 pmol l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 X 10(-24)). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (beta = 0.43 mmol l(-1), P = 5.3 X 10(-5)). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits(2-4) and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.
C1 [Moltke, Ida; Albrechtsen, Anders] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
   [Moltke, Ida] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Grarup, Niels; Krarup, Nikolaj T.; Gjesing, Anette P.; Wang, Jun; Pedersen, Oluf; Hansen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.
   [Jorgensen, Marit E.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
   [Bjerregaard, Peter] Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.
   [Treebak, Jonas T.; Andersen, Marianne A.; Nielsen, Thomas S.; Zierath, Juleen R.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Sect Integrat Physiol, DK-2200 Copenhagen, Denmark.
   [Fumagalli, Matteo; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Korneliussen, Thorfinn S.] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen, Denmark.
   [Zierath, Juleen R.] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
   [Linneberg, Allan] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.
   [Wu, Xueli; Sun, Guangqing; Jin, Xin; Al-Aama, Jumana; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Al-Aama, Jumana; Wang, Jun] King Abdulaziz Univ, Fac Med, Dept Med Genet, Jeddah 21589, Saudi Arabia.
   [Al-Aama, Jumana; Wang, Jun] King Abdulaziz Univ, Princess Al Jawhara Albrahim Ctr Excellence Res H, Jeddah 21589, Saudi Arabia.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] Macau Univ Sci & Technol, Macau 999078, Peoples R China.
   [Borch-Johnsen, Knut] Holbaek Cent Hosp, DK-4300 Holbaek, Denmark.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark.
C3 University of Copenhagen; University of Chicago; University of Copenhagen; Novo Nordisk Foundation; Steno Diabetes Center; University of Southern Denmark; University of Copenhagen; Novo Nordisk Foundation; University of California System; University of California Berkeley; University of Copenhagen; Karolinska Institutet; University of Copenhagen; Copenhagen University Hospital; Beijing Genomics Institute (BGI); King Abdulaziz University; King Abdulaziz University; University of Copenhagen; Macau University of Science & Technology; Holbaek Hospital; University of California System; University of California Berkeley; University of Southern Denmark
RP Hansen, T (corresponding author), Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.
EM albrecht@binf.ku.dk; torben.hansen@sund.ku.dk
FU Novo Nordisk Foundation; Danish Council for Independent Research (Medical Sciences); Steno Diabetes Center; Villum Foundation; Karen Elise Jensen's Foundation; NunaFonden; Medical Research Council of Denmark; Medical Research Council of Greenland; Commission for Scientific Research in Greenland; Villum Fonden [00007171] Funding Source: researchfish
NR 30
TC 324
Z9 363
U1 1
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 AUG 14
PY 2014
VL 512
IS 7513
BP 190
EP +
DI 10.1038/nature13425
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700031
PM 25043022
DA 2026-03-09
ER

PT J
AU Genovese, P
   Schiroli, G
   Escobar, G
   Di Tomaso, T
   Firrito, C
   Calabria, A
   Moi, D
   Mazzieri, R
   Bonini, C
   Holmes, MC
   Gregory, PD
   van der Burg, M
   Gentner, B
   Montini, E
   Lombardo, A
   Naldini, L
AF Genovese, Pietro
   Schiroli, Giulia
   Escobar, Giulia
   Di Tomaso, Tiziano
   Firrito, Claudia
   Calabria, Andrea
   Moi, Davide
   Mazzieri, Roberta
   Bonini, Chiara
   Holmes, Michael C.
   Gregory, Philip D.
   van der Burg, Mirjam
   Gentner, Bernhard
   Montini, Eugenio
   Lombardo, Angelo
   Naldini, Luigi
TI Targeted genome editing in human repopulating haematopoietic stem cells
SO NATURE
LA English
DT Article
ID zinc-finger nucleases; gene-therapy; lentiviral vector; t-cells; integration; safe; ccr5
AB Targeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene transfer and limited proficiency of the homology-directed DNA repair pathway constrain gene targeting in human HSCs. By tailoring delivery platforms and culture conditions we overcame these barriers and provide stringent evidence of targeted integration in human HSCs by long-term multilineage repopulation of transplanted mice. We demonstrate the therapeutic potential of our strategy by targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy donors and a subject with X-linked severe combined immunodeficiency (SCID-X1). Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional lymphoid cells that possess a selective growth advantage over those carrying disruptive IL2RG mutations. These results open up new avenues for treating SCID-X1 and other diseases.
C1 [Genovese, Pietro; Schiroli, Giulia; Escobar, Giulia; Di Tomaso, Tiziano; Firrito, Claudia; Calabria, Andrea; Moi, Davide; Mazzieri, Roberta; Gentner, Bernhard; Montini, Eugenio; Lombardo, Angelo; Naldini, Luigi] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, TIGET, I-20132 Milan, Italy.
   [Schiroli, Giulia; Escobar, Giulia; Gentner, Bernhard; Lombardo, Angelo; Naldini, Luigi] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
   [Bonini, Chiara] Ist Sci San Raffaele, Expt Hematol Unit, I-20132 Milan, Italy.
   [Holmes, Michael C.; Gregory, Philip D.] Sangamo BioSci Inc, Richmond, CA 94804 USA.
   [van der Burg, Mirjam] Univ Med Ctr, Erasmus MC, Dept Immunol, NL-3015 Rotterdam, Netherlands.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Fondazione Telethon; San Raffaele Telethon Institute For Gene Therapy (Sr-Tiget); Vita-Salute San Raffaele University; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Sangamo Therapeutics, Inc.; Erasmus University Rotterdam; Erasmus MC
RP Naldini, L (corresponding author), Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, TIGET, I-20132 Milan, Italy.
EM naldini.luigi@hsr.it
FU Telethon (TIGET grant) [D2]; EU [249845]; Italian Ministry of Health
NR 42
TC 478
Z9 565
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 JUN 12
PY 2014
VL 510
IS 7504
BP 235
EP +
DI 10.1038/nature13420
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400043
PM 24870228
DA 2026-03-09
ER

PT J
AU Bingol, B
   Tea, JS
   Phu, L
   Reichelt, M
   Bakalarski, CE
   Song, QH
   Foreman, O
   Kirkpatrick, DS
   Sheng, MG
AF Bingol, Baris
   Tea, Joy S.
   Phu, Lilian
   Reichelt, Mike
   Bakalarski, Corey E.
   Song, Qinghua
   Foreman, Oded
   Kirkpatrick, Donald S.
   Sheng, Morgan
TI The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy
SO NATURE
LA English
DT Article
ID dopaminergic neuron degeneration; drosophila model; disease; ubiquitination; mutations; pink1; phosphorylation; depolarization; dysfunction; p62/sqstm1
AB Cells maintain healthy mitochondria by degrading damaged mitochondria through mitophagy; defective mitophagy is linked to Parkinson's disease. Here we report that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase PINK1, which are encoded by two genes associated with Parkinson's disease. Parkin ubiquitinates and tags damaged mitochondria for clearance. Overexpression of USP 30 removes ubiquitin attached by parkin onto damaged mitochondria and blocks parkin's ability to drive mitophagy, whereas reducing USP30 activity enhances mitochondrial degradation in neurons. Global ubiquitination site profiling identified multiple mitochondrial substrates oppositely regulated by parkin and USP30. Knockdown of USP30 rescues the defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin-or PINK1-deficient flies. Knockdown of USP30 in dopaminergic neurons protects flies against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor function and organismal survival. Thus USP30 inhibition is potentially beneficial for Parkinson's disease by promoting mitochondrial clearance and quality control.
C1 [Bingol, Baris; Tea, Joy S.; Sheng, Morgan] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
   [Phu, Lilian; Kirkpatrick, Donald S.] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Reichelt, Mike; Foreman, Oded] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Bakalarski, Corey E.] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
   [Song, Qinghua] Genentech Inc, Dept Nonclin Biostat, 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; Genentech; Roche Holding USA
RP Bingol, B (corresponding author), Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
EM bingol.baris@gene.com
NR 41
TC 711
Z9 837
U1 1
U2 217
PU NATURE PUBLISHING 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 19
PY 2014
VL 510
IS 7505
BP 370
EP +
DI 10.1038/nature13418
PG 27
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0NG
UT WOS:000337350200029
PM 24896179
DA 2026-03-09
ER

PT J
AU Vinther, J
   Stein, M
   Longrich, NR
   Harper, DAT
AF Vinther, Jakob
   Stein, Martin
   Longrich, Nicholas R.
   Harper, David A. T.
TI A suspension-feeding anomalocarid from the Early Cambrian
SO NATURE
LA English
DT Article
ID sirius passet lagerstatte; north greenland; burgess shale; bony fishes; plankton; food; whales; origin; evolution; boundary
AB Large, actively swimming suspension feeders evolved several times in Earth's history, arising independently from groups as diverse as sharks, rays and stem teleost fishes(1), and in mysticete whales(2). However, animals occupying this niche have not been identified from the early Palaeozoic era. Anomalocarids, a group of stem arthropods that were the largest nektonic animals of the Cambrian and Ordovician periods, are generally thought to have been apex predators(3-5). Here we describe new material from Tamisiocaris borealis(6), an anomalocarid from the Early Cambrian (Series 2) Sirius Passet Fauna of North Greenland, and propose that its frontal appendage is specialized for suspension feeding. The appendage bears long, slender and equally spaced ventral spines furnished with dense rows of long and fine auxiliary spines. This suggests that T. borealis was a microphagous suspension feeder, using its appendages for sweep-net capture of food items down to 0.5 mm, within the size range of mesozooplankton such as copepods. Our observations demonstrate that large, nektonic suspension feeders first evolved during the Cambrian explosion, as part of an adaptive radiation of anomalocarids. The presence of nektonic suspension feeders in the Early Cambrian, together with evidence for a diverse pelagic community containing phytoplankton(7,8) and mesozooplankton(7,9,10), indicate the existence of a complex pelagic ecosystem(11) supported by high primary productivity and nutrient flux(12,13). Cambrian pelagic ecosystems seem to have been more modern than previously believed. [GRAPHICS] .
C1 [Vinther, Jakob] Univ Bristol, Sch Earth Sci, Bristol BS8, Avon, England.
   [Vinther, Jakob] Univ Bristol, Sch Biol Sci, Bristol BS8, Avon, England.
   [Stein, Martin] Univ Copenhagen, Nat Hist Museum Denmark, DK-2100 Copenhagen, Denmark.
   [Longrich, Nicholas R.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
   [Harper, David A. T.] Univ Durham, Dept Earth Sci, Palaeoecosyst Grp, Durham DH1 3LE, England.
C3 University of Bristol; University of Bristol; University of Copenhagen; University of Bath; Durham University
RP Vinther, J (corresponding author), Univ Bristol, Sch Earth Sci, Woodland Rd, Bristol BS8, Avon, England.
EM jakob.vinther@bristol.ac.uk
FU Geocenter Denmark; Agouron Institute; Carlsberg Foundation
NR 42
TC 132
Z9 143
U1 0
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 MAR 27
PY 2014
VL 507
IS 7493
BP 496
EP +
DI 10.1038/nature13010
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000040
PM 24670770
DA 2026-03-09
ER

PT J
AU Abril, G
   Martinez, JM
   Artigas, LF
   Moreira-Turcq, P
   Benedetti, MF
   Vidal, L
   Meziane, T
   Kim, JH
   Bernardes, MC
   Savoye, N
   Deborde, J
   Souza, EL
   Albéric, P
   de Souza, MFL
   Roland, F
AF Abril, Gwenael
   Martinez, Jean-Michel
   Artigas, L. Felipe
   Moreira-Turcq, Patricia
   Benedetti, Marc F.
   Vidal, Luciana
   Meziane, Tarik
   Kim, Jung-Hyun
   Bernardes, Marcelo C.
   Savoye, Nicolas
   Deborde, Jonathan
   Souza, Edivaldo Lima
   Alberic, Patrick
   Landim de Souza, Marcelo F.
   Roland, Fabio
TI Amazon River carbon dioxide outgassing fuelled by wetlands
SO NATURE
LA English
DT Article
ID net primary productivity; fresh-water wetlands; floodplain lake; gas-exchange; tropical reservoir; lago grande; co2; vegetation; respiration; inundation
AB River systems connect the terrestrial biosphere, the atmosphere and the ocean in the global carbon cycle(1). A recent estimate suggests that up to 3 petagrams of carbon per year could be emitted as carbon dioxide (CO2) from global inland waters, offsetting the carbon uptake by terrestrial ecosystems(2). It is generally assumed that inland waters emit carbon that has been previously fixed upstream by land plant photosynthesis, then transferred to soils, and subsequently transported downstream in run-off. But at the scale of entire drainage basins, the lateral carbon fluxes carried by small rivers upstream do not account for all of the CO2 emitted from inundated areas downstream(3,4). Three-quarters of the world's flooded land consists of temporary wetlands(5), but the contribution of these productive ecosystems(6) to the inland water carbon budget has been largely overlooked. Here we show that wetlands pump large amounts of atmospheric CO2 into river waters in the floodplains of the central Amazon. Flooded forests and floating vegetation export large amounts of carbon to river waters and the dissolved CO2 can be transported dozens to hundreds of kilometres downstream before being emitted. We estimate that Amazonian wetlands export half of their gross primary production to river waters as dissolved CO2 and organic carbon, compared with only a few per cent of gross primary production exported in upland (not flooded) ecosystems(1,7). Moreover, we suggest that wetland carbon export is potentially large enough to account for at least the 0.21 petagrams of carbon emitted per year as CO2 from the central Amazon River and its floodplains(8). Global carbon budgets should explicitly address temporary or vegetated flooded areas, because these ecosystems combine high aerial primary production with large, fast carbon export, potentially supporting a substantial fraction of CO2 evasion from inland waters.
C1 [Abril, Gwenael; Savoye, Nicolas; Deborde, Jonathan] Univ Bordeaux 1, CNRS, Lab Environm & Paleoenvironm Ocean & Continentaux, F-33405 Talence, France.
   [Abril, Gwenael; Martinez, Jean-Michel; Moreira-Turcq, Patricia] Univ Toulouse 3, Inst Rech Dev, Lab Geosci & Environm Toulouse, F-31400 Toulouse, France.
   [Artigas, L. Felipe] Univ Littoral Cote dOpale, CNRS, Lab Oceanol & Geosci, F-62930 Wimereux, France.
   [Benedetti, Marc F.] Univ Paris Diderot, Inst Phys Globe Paris, Sorbonne Paris Cite, Equipe Geochim Eaux, F-75205 Paris 13, France.
   [Vidal, Luciana; Roland, Fabio] Univ Fed Juiz de Fora, Dept Biol, Aquat Ecol Lab, BR-36036900 Juiz De Fora, MG, Brazil.
   [Meziane, Tarik] UPMC, Museum Natl Hist Nat, Lab Biol Organismes & Ecosyst Aquat BOREA, CNRS,IRD, F-75005 Paris, France.
   [Kim, Jung-Hyun] NIOZ Royal Netherlands Inst Sea Res, Dept Marine Organ Biogeochem, NL-1790 AB Den Burg, Netherlands.
   [Bernardes, Marcelo C.] Univ Fed Fluminense, Programa Geoquim, BR-24020015 Niteroi, RJ, Brazil.
   [Souza, Edivaldo Lima] Univ Brasilia, Inst Geociencias, BR-70910900 Brasilia, DF, Brazil.
   [Alberic, Patrick] Inst Sci Terre Orleans, F-45071 Orleans 2, France.
   [Landim de Souza, Marcelo F.] Univ Estadual Santa Cruz, Lab Oceanog Quim, BR-45662900 Ilheus, BA, Brazil.
C3 Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; Institut de Recherche pour le Developpement (IRD); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Universite du Littoral-Cote-d'Opale; Universite Paris Cite; Universidade Federal de Juiz de Fora; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Museum National d'Histoire Naturelle (MNHN); Sorbonne Universite; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Universidade Federal Fluminense; Universidade de Brasilia; Universidade Estadual de Santa Cruz
RP Abril, G (corresponding author), Univ Bordeaux 1, CNRS, Lab Environm & Paleoenvironm Ocean & Continentaux, Ave Fac, F-33405 Talence, France.
EM g.abril@epoc.u-bordeaux1.fr
FU French National Agency for Research [08-BLAN-0221]; French INSU national programme EC2CO; National Council of Research and Development (CNPq), Brazil [477655/2010-6]; Environmental Research Observatory Hydrology and Geochemistry of the Amazon Basin (HYBAM); INSU; IRD (Institute for Research and Development, France); CNPq; Brazilian 'Excellent Researcher' fellowship
NR 69
TC 309
Z9 360
U1 8
U2 567
PU NATURE PUBLISHING 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 16
PY 2014
VL 505
IS 7483
BP 395
EP +
DI 10.1038/nature12797
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800041
PM 24336199
DA 2026-03-09
ER

PT J
AU Whiteus, C
   Freitas, C
   Grutzendler, J
AF Whiteus, Christina
   Freitas, Catarina
   Grutzendler, Jaime
TI Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period
SO NATURE
LA English
DT Article
ID nitric-oxide synthase; endothelial-cells; barrel cortex; mechanism; ischemia; seizures; system
AB During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature(1,2). Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affects cortical microvascular development. Unexpectedly, chronic stimulation by repetitive sounds, whisker deflection or motor activity led to a near arrest of angiogenesis in barrel, auditory and motor cortices, respectively. Chemically induced seizures also caused robust reductions in microvascular density. However, altering neural activity in adult mice did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather to reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences for brain development, function and pathology.
C1 [Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06511 USA.
   [Whiteus, Christina; Grutzendler, Jaime] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
C3 Yale University; Yale University
RP Grutzendler, J (corresponding author), Yale Univ, Sch Med, Dept Neurol, 333 Cedar St, New Haven, CT 06511 USA.
EM jaime.grutzendler@yale.edu
FU AHA [10POST2570007];  [R01AG027855];  [R01HL106815];  [F31NS068041]; American Heart Association (AHA) [10POST2570007] Funding Source: American Heart Association (AHA)
NR 36
TC 98
Z9 113
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 JAN 16
PY 2014
VL 505
IS 7483
BP 407
EP +
DI 10.1038/nature12821
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800044
PM 24305053
DA 2026-03-09
ER

PT J
AU Vinothkumar, KR
   Zhu, JP
   Hirst, J
AF Vinothkumar, Kutti R.
   Zhu, Jiapeng
   Hirst, Judy
TI Architecture of mammalian respiratory complex I
SO NATURE
LA English
DT Article
ID nadh-ubiquinone oxidoreductase; acyl carrier protein; 3-dimensional structure; structural basis; subunit; mutations; environment; resolution; prediction; topology
AB Complex I (NADH: ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear-and mitochondrial-encoded subunits, with a combined mass of 1MDa. The 14 conserved 'core' subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 'supernumerary' subunits are unknown. Here we describe a 5 angstrom resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. Wepresent the structures of themammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we considerably advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases.
C1 [Vinothkumar, Kutti R.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Zhu, Jiapeng; Hirst, Judy] Wellcome Trust Res Labs, MRC Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
C3 MRC Laboratory Molecular Biology; Wellcome Trust Sanger Institute
RP 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]; MRC [MC_U105663141, MC_U105184322] Funding Source: UKRI; Medical Research Council [MC_U105184322, MC_U105663141] Funding Source: researchfish
NR 63
TC 349
Z9 400
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 NOV 6
PY 2014
VL 515
IS 7525
BP 80
EP +
DI 10.1038/nature13686
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500032
PM 25209663
DA 2026-03-09
ER

PT J
AU Laganowsky, A
   Reading, E
   Allison, TM
   Ulmschneider, MB
   Degiacomi, MT
   Baldwin, AJ
   Robinson, CV
AF Laganowsky, Arthur
   Reading, Eamonn
   Allison, Timothy M.
   Ulmschneider, Martin B.
   Degiacomi, Matteo T.
   Baldwin, Andrew J.
   Robinson, Carol V.
TI Membrane proteins bind lipids selectively to modulate their structure and function
SO NATURE
LA English
DT Article
ID mass-spectrometry; mycobacterium-tuberculosis; molecular-dynamics; complexes; mobility; channel; model; purification; polydispersity; tryptophan
AB Previous studies have established that the folding, structure and function of membrane proteins are influenced by their lipid environments(1-7) and that lipids can bind to specific sites, for example, in potassium channels(8). Fundamental questions remain however regarding the extent of membrane protein selectivity towards lipids. Here we report a mass spectrometry approach designed to determine the selectivity of lipid binding to membrane protein complexes. We investigate the mechanosensitive channel of large conductance (MscL) from Myco-bacterium tuberculosis and aquaporin Z (AqpZ) and the ammonia channel (AmtB) from Escherichia coli, using ion mobility mass spectrometry (IM-MS), which reports gas-phase collision cross-sections. We demonstrate that folded conformations of membrane protein complexes can exist in the gas phase. By resolving lipid-bound states, we then rank bound lipids on the basis of their ability to resist gas phase unfolding and thereby stabilize membrane protein structure. Lipids bind non-selectively and with high avidity to MscL, all imparting comparable stability; however, the highest-ranking lipid is phosphatidylinositol phosphate, in line with its proposed functional role in mechanosensation(9). AqpZ is also stabilized by many lipids, with cardiolipin imparting the most significant resistance to unfolding. Subsequently, through functional assays we show that cardiolipin modulates AqpZ function. Similar experiments identify AmtB as being highly selective for phosphatidylglycerol, prompting us to obtain an X-ray structure in this lipid membrane-like environment. The 2.3 angstrom resolution structure, when compared with others obtained without lipid bound, reveals distinct conformational changes that re-position AmtB residues to interact with the lipid bilayer. Our results demonstrate that resistance to unfolding correlates with specific lipid-binding events, enabling a distinction to be made between lipids that merely bind from those that modulate membrane protein structure and/or function. We anticipate that these findings will be important not only for defining the selectivity of membrane proteins towards lipids, but also for understanding the role of lipids in modulating protein function or drug binding.
C1 [Laganowsky, Arthur; Reading, Eamonn; Allison, Timothy M.; Degiacomi, Matteo T.; Baldwin, Andrew J.; Robinson, Carol V.] Univ Oxford, Dept Chem, Oxford OX1 5QY, England.
   [Ulmschneider, Martin B.] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21218 USA.
C3 University of Oxford; Johns Hopkins University
RP Laganowsky, A (corresponding author), Univ Oxford, Dept Chem, S Parks Rd, Oxford OX1 5QY, England.
EM art.laganowsky@chem.ox.ac.uk; carol.robinson@chem.ox.ac.uk
FU Medical Research Council (MRC); BBSRC; ERC; Biotechnology and Biological Sciences Research Council [BB/J014346/1] Funding Source: researchfish; Medical Research Council [G1000819, MC_PC_12020] Funding Source: researchfish; BBSRC [BB/J014346/1] Funding Source: UKRI; MRC [G1000819, MC_PC_12020] Funding Source: UKRI
NR 70
TC 650
Z9 770
U1 1
U2 564
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 5
PY 2014
VL 510
IS 7503
BP 172
EP +
DI 10.1038/nature13419
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI3NR
UT WOS:000336768900051
PM 24899312
DA 2026-03-09
ER

PT J
AU Benoit, RM
   Frey, D
   Hilbert, M
   Kevenaar, JT
   Wieser, MM
   Stirnimann, CU
   McMillan, D
   Ceska, T
   Lebon, F
   Jaussi, R
   Steinmetz, MO
   Schertler, GFX
   Hoogenraad, CC
   Capitani, G
   Kammerer, RA
AF Benoit, Roger M.
   Frey, Daniel
   Hilbert, Manuel
   Kevenaar, Josta T.
   Wieser, Mara M.
   Stirnimann, Christian U.
   McMillan, David
   Ceska, Tom
   Lebon, Florence
   Jaussi, Rolf
   Steinmetz, Michel O.
   Schertler, Gebhard F. X.
   Hoogenraad, Casper C.
   Capitani, Guido
   Kammerer, Richard A.
TI Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A
SO NATURE
LA English
DT Article
ID low ph; design; prion; dna; aggregation; prediction; dynamics; receptor; binding; motifs
AB Botulinum neurotoxin A (BoNT/A) belongs to the most dangerous class of bioweapons(1). Despite this, BoNT/A is used to treat a wide range of common medical conditions such as migraines and a variety of ocular motility and movement disorders(2). BoNT/A is probably best known for its use as an antiwrinkle agent in cosmetic applications (including Botox and Dysport)(3). BoNT/A application causes long-lasting flaccid paralysis of muscles through inhibiting the release of the neurotransmitter acetylcholine by cleaving synaptosomal-associated protein 25 (SNAP-25) within presynaptic nerve terminals(4). Two types of BoNT/A receptor have been identified, both of which are required for BoNT/A toxicity and are therefore likely to cooperate with each other(5): gangliosides and members of the synaptic vesicle glycoprotein 2 (SV2) family, which are putative transporter proteins that are predicted to have 12 transmembrane domains, associate with the receptor-binding domain of the toxin(5). Recently, fibroblast growth factor receptor 3 (FGFR3) has also been reported to be a potential BoNT/A receptor(6). In SV2 proteins, the BoNT/A-binding site has been mapped to the luminal domain(7), but the molecular details of the interaction between BoNT/A and SV2 are unknown. Here we determined the high-resolution crystal structure of the BoNT/A receptor-binding domain (BoNT/A-RBD) in complex with the SV2C luminal domain (SV2C-LD). SV2C-LD consists of a right-handed, quadrilateral beta-helix that associates with BoNT/A-RBD mainly through backbone-to-backbone interactions at open beta-strand edges, in a manner that resembles the inter-strand interactions in amyloid structures. Competition experiments identified a peptide that inhibits the formation of the complex. Our findings provide a strong platform for the development of novel antitoxin agents and for the rational design of BoNT/A variants with improved therapeutic properties.
C1 [Benoit, Roger M.; Frey, Daniel; Hilbert, Manuel; Wieser, Mara M.; Jaussi, Rolf; Steinmetz, Michel O.; Schertler, Gebhard F. X.; Capitani, Guido; Kammerer, Richard A.] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland.
   [Kevenaar, Josta T.; Hoogenraad, Casper C.] Univ Utrecht, Fac Sci, NL-3584 CH Utrecht, Netherlands.
   [Stirnimann, Christian U.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [McMillan, David; Ceska, Tom] UCB NewMed, UCB Pharma, UCB Celltech, Slough SL1 4EN, Berks, England.
   [Lebon, Florence] UCB NewMed, UCB Pharma, B-1420 Braine Lalleud, Belgium.
   [Schertler, Gebhard F. X.] ETH, Dept Biol, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Utrecht University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; UCB Pharma SA; Celltech Group Ltd; UCB Pharma SA; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Kammerer, RA (corresponding author), Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland.
EM richard.kammerer@psi.ch
FU UCB Pharma, UCB NewMedicines; Swiss National Science Foundation [310030B_138659]; Netherlands Organization for Scientific Research (NWO-ALW-VICI); Netherlands Organization for Health Research and Development (ZonMW-TOP); Swiss National Science Foundation (SNF) [310030B_138659] Funding Source: Swiss National Science Foundation (SNF)
NR 45
TC 105
Z9 116
U1 3
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 JAN 2
PY 2014
VL 505
IS 7481
BP 108
EP +
DI 10.1038/nature12732
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 282IB
UT WOS:000329163300033
PM 24240280
DA 2026-03-09
ER

PT J
AU Gatti, LV
   Gloor, M
   Miller, JB
   Doughty, CE
   Malhi, Y
   Domingues, LG
   Basso, LS
   Martinewski, A
   Correia, CSC
   Borges, VF
   Freitas, S
   Braz, R
   Anderson, LO
   Rocha, H
   Grace, J
   Phillips, OL
   Lloyd, J
AF Gatti, L. V.
   Gloor, M.
   Miller, J. B.
   Doughty, C. E.
   Malhi, Y.
   Domingues, L. G.
   Basso, L. S.
   Martinewski, A.
   Correia, C. S. C.
   Borges, V. F.
   Freitas, S.
   Braz, R.
   Anderson, L. O.
   Rocha, H.
   Grace, J.
   Phillips, O. L.
   Lloyd, J.
TI Drought sensitivity of Amazonian carbon balance revealed by atmospheric measurements
SO NATURE
LA English
DT Article
ID vertical profiles; co2; forests; fluxes; model; cycle; emissions; dioxide; trends
AB Feedbacks between land carbon pools and climate provide one of the largest sources of uncertainty in our predictions of global climate(1,2). Estimates of the sensitivity of the terrestrial carbon budget to climate anomalies in the tropics and the identification of the mechanisms responsible for feedback effects remain uncertain(3,4). The Amazon basin stores a vast amount of carbon(5), and has experienced increasingly higher temperatures and more frequent floods and droughts over the past two decades(6). Here we report seasonal and annual carbon balances across the Amazon basin, based on carbon dioxide and carbon monoxide measurements for the anomalously dry and wet years 2010 and 2011, respectively. We find that the Amazon basin lost 0.48 +/- 0.18 petagrams of carbon per year (Pg C yr(-1)) during the dry year but was carbon neutral (0.06 +/- 0.1 Pg C yr(-1)) during the wet year. Taking into account carbon losses from fire by using carbon monoxide measurements, we derived the basin net biome exchange (that is, the carbon flux between the non-burned forest and the atmosphere) revealing that during the dry year, vegetation was carbon neutral. During the wet year, vegetation was a net carbon sink of 0.25 +/- 0.14 Pg C yr(-1), which is roughly consistent with the mean long-term intact-forest biomass sink of 0.39 +/- 0.10 Pg C yr(-1) previously estimated from forest censuses(7). Observations from Amazonian forest plots suggest the suppression of photosynthesis during drought as the primary cause for the 2010 sink neutralization. Overall, our results suggest that moisture has an important role in determining the Amazonian carbon balance. If the recent trend of increasing precipitation extremes persists(6), the Amazon may become an increasing carbon source as a result of both emissions from fires and the suppression of net biome exchange by drought.
C1 [Gatti, L. V.; Domingues, L. G.; Basso, L. S.; Martinewski, A.; Correia, C. S. C.; Borges, V. F.] CNEN, IPEN, Atmospher Chem Lab, BR-05508000 Sao Paulo, Brazil.
   [Gloor, M.; Phillips, O. L.] Univ Leeds, Sch Geog, Leeds LS9 2JT, W Yorkshire, England.
   [Miller, J. B.] NOAA, Global Monitoring Div, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Miller, J. B.] Univ Colorado, CIRES, Boulder, CO 80309 USA.
   [Doughty, C. E.; Malhi, Y.; Anderson, L. O.] Univ Oxford, Sch Geog & Environm, Environm Change Inst, Oxford OX1 3QY, England.
   [Freitas, S.; Braz, R.] INPE, Ctr Weather Forecasts & Climate Studies, BR-12630000 Cachoeira Paulista, Brazil.
   [Anderson, L. O.] INPE, Remote Sensing Div, BR-12227010 Sao Jose Dos Campos, Brazil.
   [Rocha, H.] Univ Sao Paulo, IAG, Dept Ciencias Atmosfer, BR-05508090 Sao Paulo, Brazil.
   [Lloyd, J.] James Cook Univ, Sch Trop & Marine Biol, Cairns, Qld 4870, Australia.
   [Lloyd, J.] James Cook Univ, Ctr Terr Environm & Sustainabil Sci, Cairns, Qld 4870, Australia.
   [Lloyd, J.] Univ London Imperial Coll Sci Technol & Med, Ascot SL5 7PY, Berks, England.
C3 Comissao Nacional de Energia Nuclear (CNEN); Instituto de Pesquisas Energeticas e Nucleares (IPEN); University of Leeds; National Oceanic Atmospheric Admin (NOAA) - USA; University of Colorado System; University of Colorado Boulder; University of Oxford; Instituto Nacional de Pesquisas Espaciais (INPE); Instituto Nacional de Pesquisas Espaciais (INPE); Universidade de Sao Paulo; James Cook University; James Cook University; Imperial College London
RP Gatti, LV (corresponding author), CNEN, IPEN, Atmospher Chem Lab, 2242 Ave Prof Lineu Prestes,Cidade Univ, BR-05508000 Sao Paulo, Brazil.
EM lvgatti@gmail.com; eugloor@gmail.com; john.b.miller@noaa.gov
FU UK Environmental Research Council (NERC) via the consortium grant 'AMAZONICA' NERC [NE/F005806/1]; State of Sao Paulo Science Foundation (FAPESP) [08/58120-3]; EU [283080]; NERC; Moore Foundation; CNPq; CAPES; Fapesp; IPEN; ERC; NERC [NE/F005776/1, NE/I02982X/1, NE/F005040/1, NE/F005806/1, NE/D005590/1] Funding Source: UKRI; Natural Environment Research Council [NE/F005040/1, NE/F005806/1, NE/F005776/1, NER/A/S/2003/00609, NE/D005590/1, NE/I02982X/1] Funding Source: researchfish; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/58120-3] Funding Source: FAPESP
NR 47
TC 402
Z9 461
U1 3
U2 505
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 6
PY 2014
VL 506
IS 7486
BP 76
EP +
DI 10.1038/nature12957
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100034
PM 24499918
DA 2026-03-09
ER

PT J
AU Fuentes, I
   Stegemann, S
   Golczyk, H
   Karcher, D
   Bock, R
AF Fuentes, Ignacia
   Stegemann, Sandra
   Golczyk, Hieronim
   Karcher, Daniel
   Bock, Ralph
TI Horizontal genome transfer as an asexual path to the formation of new species
SO NATURE
LA English
DT Article
ID complete nucleotide-sequence; intercellular movement; tissue; plants; organization; polyploidy; protoplasm; diversity; nuclear; glauca
AB Allopolyploidization, the combination of the genomes from two different species, has been a major source of evolutionary innovation and a driver of speciation and environmental adaptation(1-4). Inplants, it has also contributed greatly to crop domestication, as the superior properties of many modern crop plants were conferred by ancient allopolyploidization events(5,6). It is generally thought that allopolyploidization occurred through hybridization events between species, accompanied or followed by genome duplication(6,7). Although many allopolyploids arose from closely related species (congeners), there are also allopolyploid species that were formed from more distantly related progenitor species belonging to different genera or even different tribes(8). Here we have examined the possibility that allopolyploidization can also occur by asexual mechanisms. We show that upon grafting-a mechanism of plant-plant interaction that is widespread in nature-entire nuclear genomes can be transferred between plant cells. We provide direct evidence for this process resulting in speciation by creating a new allopolyploid plant species from a herbaceous species and a woody species in the nightshade family. The new species is fertile and produces fertile progeny. Our data highlight natural grafting as a potential asexual mechanism of speciation and also provide a method for the generation of novel allopolyploid crop species.
C1 [Fuentes, Ignacia; Stegemann, Sandra; Karcher, Daniel; Bock, Ralph] Max Planck Inst Mol Pflanzenphysiol, D-14476 Potsdam, Germany.
   [Golczyk, Hieronim] John Paul II Catholic Univ Lublin, Inst Biotechnol, Dept Mol Biol, PL-20708 Lublin, Poland.
C3 Max Planck Society; Catholic University of Lublin
RP Bock, R (corresponding author), Max Planck Inst Mol Pflanzenphysiol, Muhlenberg 1, D-14476 Potsdam, Germany.
EM rbock@mpimp-golm.mpg.de
FU Max Planck Society
NR 37
TC 157
Z9 193
U1 3
U2 221
PU NATURE PUBLISHING 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 10
PY 2014
VL 511
IS 7508
BP 232
EP +
DI 10.1038/nature13291
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800046
PM 24909992
DA 2026-03-09
ER

PT J
AU Brooks-Pollock, E
   Roberts, GO
   Keeling, MJ
AF Brooks-Pollock, Ellen
   Roberts, Gareth O.
   Keeling, Matt J.
TI A dynamic model of bovine tuberculosis spread and control in Great Britain
SO NATURE
LA English
DT Article
ID mouth epidemic; cattle; transmission; england; foot
AB Bovine tuberculosis (TB) is one of the most complex, persistent and controversial problems facing the British cattle industry, costing the country an estimated 100 pound million per year(1). The low sensitivity of the standard diagnostic test leads to considerable ambiguity in determining the main transmission routes of infection, which exacerbates the continuing scientific debate(2-6). In turn this uncertainty fuels the fierce public and political disputes on the necessity of controlling badgers to limit the spread of infection. Here we present a dynamic stochastic spatial model for bovine TB in Great Britain that combines within-farm and between-farm transmission. At the farmscale the model incorporates stochastic transmission of infection, maintenance of infection in the environment and a testing protocol that mimics historical government policy. Between-farm transmission has a short-range environmental component and is explicitly driven by movements of individual cattle between farms, as recorded in the Cattle Tracing System(2). The resultant model replicates the observed annual increase of infection over time as well as the spread of infection into new areas. Given that our model is mechanistic, it can ascribe transmission pathways to each new case; the majority of newly detected cases involve several transmission routes with moving infected cattle, reinfection from an environmental reservoir and poor sensitivity of the diagnostic test all having substantive roles. This underpins our findings on the implications of control measures. Very few of the control options tested have the potential to reverse the observed annual increase, with only intensive strategies such as whole-herd culling or additional national testing proving highly effective, whereas controls focused on a single transmission route are unlikely to be highly effective.
C1 [Brooks-Pollock, Ellen] Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Cambridge CB3 0ES, England.
   [Brooks-Pollock, Ellen; Keeling, Matt J.] Univ Warwick, Math Inst, WIDER Ctr, Coventry CV4 7AL, W Midlands, England.
   [Brooks-Pollock, Ellen; Keeling, Matt J.] Univ Warwick, Sch Life Sci, Coventry CV4 7AL, W Midlands, England.
   [Roberts, Gareth O.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England.
C3 University of Cambridge; University of Warwick; University of Warwick; University of Warwick
RP Keeling, MJ (corresponding author), Univ Warwick, Math Inst, WIDER Ctr, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.
EM M.J.Keeling@warwick.ac.uk
FU BBSRC; Wellcome Trust; EPSRC; BBSRC [BB/H00811X/1, BB/I013482/1] Funding Source: UKRI; EPSRC [EP/H027270/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H00811X/1, BB/I013482/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/D002060/1, EP/H027270/1] Funding Source: researchfish
NR 26
TC 168
Z9 187
U1 1
U2 191
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2014
VL 511
IS 7508
BP 228
EP +
DI 10.1038/nature13529
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800045
PM 25008532
DA 2026-03-09
ER

PT J
AU Coen, P
   Clemens, J
   Weinstein, AJ
   Pacheco, DA
   Deng, Y
   Murthy, M
AF Coen, Philip
   Clemens, Jan
   Weinstein, Andrew J.
   Pacheco, Diego A.
   Deng, Yi
   Murthy, Mala
TI Dynamic sensory cues shape song structure in Drosophila
SO NATURE
LA English
DT Article
ID courtship song; auditory-feedback; motor control; behavior; neurobiology; mechanisms; decisions; genes
AB The generation of acoustic communication signals is widespread across the animal kingdom(1,2), and males of many species, including Drosophilidae, produce patterned courtship songs to increase their chance of success with a female. For some animals, song structure can vary considerably from one rendition to the next(3); neural noise within pattern generating circuits is widely assumed to be the primary source of such variability, and statistical models that incorporate neural noise are successful at reproducing the full variation present in natural songs(4). In direct contrast, here we demonstrate that much of the pattern variability in Drosophila courtship song can be explained by taking into account the dynamic sensory experience of the male. In particular, using a quantitative behavioural assay combined with computational modelling, we find that males use fast modulations in visual and self-motion signals to pattern their songs, a relationship that we show is evolutionarily conserved. Using neural circuit manipulations, we also identify the pathways involved in song patterning choices and show that females are sensitive to song features. Our data not only demonstrate that Drosophila song production is not a fixed action pattern(5,6), but establish Drosophila as a valuable new model for studies of rapid decision-making under both social and naturalistic conditions.
C1 [Coen, Philip; Clemens, Jan; Weinstein, Andrew J.; Pacheco, Diego A.; Murthy, Mala] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
   [Coen, Philip; Clemens, Jan; Weinstein, Andrew J.; Pacheco, Diego A.; Murthy, Mala] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Deng, Yi] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Murthy, M (corresponding author), Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
EM mmurthy@princeton.edu
FU HHMI International Predoctoral Fellowship; Alfred P. Sloan Foundation; Human Frontiers Science Program; NSF CAREER award; McKnight Endowment Fund; Klingenstein Foundation; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1054578] Funding Source: National Science Foundation
NR 34
TC 119
Z9 161
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 MAR 13
PY 2014
VL 507
IS 7491
BP 233
EP +
DI 10.1038/nature13131
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC6RJ
UT WOS:000332651800039
PM 24598544
DA 2026-03-09
ER

PT J
AU Li, YL
   Schwab, C
   Ryan, SL
   Papaemmanuil, E
   Robinson, HM
   Jacobs, P
   Moorman, AV
   Dyer, S
   Borrow, J
   Griffiths, M
   Heerema, NA
   Carroll, AJ
   Talley, P
   Bown, N
   Telford, N
   Ross, FM
   Gaunt, L
   McNally, RJQ
   Young, BD
   Sinclair, P
   Rand, V
   Teixeira, MR
   Joseph, O
   Robinson, B
   Maddison, M
   Dastugue, N
   Vandenberghe, P
   Haferlach, C
   Stephens, PJ
   Cheng, JQ
   Van Loo, P
   Stratton, MR
   Campbell, PJ
   Harrison, CJ
AF Li, Yilong
   Schwab, Claire
   Ryan, Sarra L.
   Papaemmanuil, Elli
   Robinson, Hazel M.
   Jacobs, Patricia
   Moorman, Anthony V.
   Dyer, Sara
   Borrow, Julian
   Griffiths, Mike
   Heerema, Nyla A.
   Carroll, Andrew J.
   Talley, Polly
   Bown, Nick
   Telford, Nick
   Ross, Fiona M.
   Gaunt, Lorraine
   McNally, Richard J. Q.
   Young, Bryan D.
   Sinclair, Paul
   Rand, Vikki
   Teixeira, Manuel R.
   Joseph, Olivia
   Robinson, Ben
   Maddison, Mark
   Dastugue, Nicole
   Vandenberghe, Peter
   Haferlach, Claudia
   Stephens, Philip J.
   Cheng, Jiqiu
   Van Loo, Peter
   Stratton, Michael R.
   Campbell, Peter J.
   Harrison, Christine J.
TI Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia
SO NATURE
LA English
DT Article
ID intrachromosomal amplification; cancer genm; children; iamp21; abnormality; event; risk
AB Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms(1). This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21)(2,3). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21) c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.
C1 [Li, Yilong; Papaemmanuil, Elli; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Stephens, Philip J.; Van Loo, Peter; Stratton, Michael R.; Campbell, Peter J.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Schwab, Claire; Ryan, Sarra L.; Moorman, Anthony V.; Young, Bryan D.; Sinclair, Paul; Rand, Vikki; Harrison, Christine J.] Newcastle Univ, Northern Inst Canc Res, Leukaemia Res Cytogenet Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Robinson, Hazel M.; Dyer, Sara; Borrow, Julian; Griffiths, Mike] Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Lab, Birmingham B15 2TG, W Midlands, England.
   [Jacobs, Patricia; Ross, Fiona M.] Salisbury NHS Fdn Trust, Wessex Reg Genet Lab, Salisbury SP2 8BJ, Wilts, England.
   [Dyer, Sara; Borrow, Julian; Griffiths, Mike] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England.
   [Heerema, Nyla A.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA.
   [Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35233 USA.
   [Talley, Polly] Sheffield Childrens NHS Fdn Trust, Sheffield Diagnost Genet Serv, Sheffield S10 2TH, S Yorkshire, England.
   [Bown, Nick] Northern Genet Serv, Cytogenet Lab, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
   [Telford, Nick] Christie NHS Fdn Trust, Manchester M20 4BX, Lancs, England.
   [Gaunt, Lorraine] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Reg Cytogenet Unit, Manchester M13 9WL, Lancs, England.
   [McNally, Richard J. Q.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
   [Teixeira, Manuel R.] Univ Porto, Portuguese Oncol Inst, Dept Genet, P-4200072 Oporto, Portugal.
   [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4200072 Oporto, Portugal.
   [Dastugue, Nicole] Hop Purpan, Lab Hematol, F-31059 Toulouse, France.
   [Vandenberghe, Peter; Cheng, Jiqiu; Van Loo, Peter] Katholieke Univ Leuven Hosp, Ctr Human Genet, B-3000 Louvain, Belgium.
   [Vandenberghe, Peter; Cheng, Jiqiu; Van Loo, Peter] Katholieke Univ Leuven, B-3000 Louvain, Belgium.
   [Haferlach, Claudia] MLL Munich Leukemia Lab, D-81377 Munich, Germany.
   [Cheng, Jiqiu] Katholieke Univ Leuven, Dept Elect Engn ESAT, B-3000 Louvain, Belgium.
   [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
C3 Wellcome Trust Sanger Institute; Newcastle University - UK; Salisbury District Hospital; University of Birmingham; University System of Ohio; Ohio State University; University of Alabama System; University of Alabama Birmingham; Sheffield Children's NHS Foundation Trust; Newcastle University - UK; Christie NHS Foundation Trust; University of Manchester; Newcastle University - UK; Portuguese Institute of Oncology; Universidade do Porto; Universidade do Porto; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; CHU de Toulouse; Flanders Institute for Biotechnology (VIB); KU Leuven; University Hospital Leuven; KU Leuven; MLL Munich Leukemia Laboratory; KU Leuven; University of Cambridge
RP Harrison, CJ (corresponding author), Newcastle Univ, Northern Inst Canc Res, Leukaemia Res Cytogenet Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM pc8@sanger.ac.uk; christine.harrison@newcastle.ac.uk
FU Wellcome Trust [077012/Z/05/Z, WT088340MA]; Leukaemia and Lymphoma Research Specialist Programme; European Research Council [249891]; Research Foundation - Flanders (F.W.O.); European Research Council (ERC) [249891] Funding Source: European Research Council (ERC); National Cancer Institute [U10CA180886] Funding Source: NIH RePORTER
NR 21
TC 219
Z9 241
U1 0
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 APR 3
PY 2014
VL 508
IS 7494
BP 98
EP +
DI 10.1038/nature13115
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900050
PM 24670643
DA 2026-03-09
ER

PT J
AU Zhang, LR
   Wang, SX
   Yin, S
   Hong, S
   Kim, KP
   Kleckner, N
AF Zhang, Liangran
   Wang, Shunxin
   Yin, Shen
   Hong, Soogil
   Kim, Keun P.
   Kleckner, Nancy
TI Topoisomerase II mediates meiotic crossover interference
SO NATURE
LA English
DT Article
ID synaptonemal complex-formation; double-strand breaks; saccharomyces-cerevisiae; crossing-over; chromosome synapsis; mitotic chromosm; chiasma formation; yeast meiosis; recombination; protein
AB Spatial patterning is a ubiquitous feature of biological systems. Meiotic crossovers provide an interesting example, defined by the classic phenomenon of crossover interference. Here we identify a molecular pathway for interference by analysing crossover patterns in budding yeast. Topoisomerase II plays a central role, thus identifying a new function for this critical molecule. SUMOylation (of topoisomerase II and axis component Red1) and ubiquitin-mediated removal of SUMOylated proteins are also required. The findings support the hypothesis that crossover interference involves accumulation, relief and redistribution of mechanical stress along the protein/ DNA meshwork of meiotic chromosome axes, with topoisomerase II required to adjust spatial relationships among DNA segments.
C1 [Zhang, Liangran; Wang, Shunxin; Yin, Shen; Kleckner, Nancy] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Hong, Soogil; Kim, Keun P.] Chung Ang Univ, Dept Life Sci, Seoul 156756, South Korea.
C3 Harvard University; Chung Ang University
RP Kleckner, N (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM kleckner@fas.harvard.edu
FU National Institutes of Health [RO1 GM044794]; National Research Foundation of Korea - Ministry of Science, ICT and Future Planning [2012-M3A9C6050367]; National Research Foundation of Korea [21A20131212408] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NR 67
TC 139
Z9 162
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 JUL 30
PY 2014
VL 511
IS 7511
BP 551
EP +
DI 10.1038/nature13442
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300026
PM 25043020
DA 2026-03-09
ER

PT J
AU Skowronska-Krawczyk, D
   Ma, Q
   Schwartz, M
   Scully, K
   Li, WB
   Liu, ZJ
   Taylor, H
   Tollkuhn, J
   Ohgi, KA
   Notani, D
   Kohwi, Y
   Kohwi-Shigematsu, T
   Rosenfeld, MG
AF Skowronska-Krawczyk, Dorota
   Ma, Qi
   Schwartz, Michal
   Scully, Kathleen
   Li, Wenbo
   Liu, Zhijie
   Taylor, Havilah
   Tollkuhn, Jessica
   Ohgi, Kenneth A.
   Notani, Dimple
   Kohwi, Yoshinori
   Kohwi-Shigematsu, Terumi
   Rosenfeld, Michael G.
TI Required enhancer-matrin-3 network interactions for a homeodomain transcription program
SO NATURE
LA English
DT Article
ID nuclear-matrix; attachment region; dna; protein; domain; pit-1; organization; scaffold; genome; satb1
AB Homeodomain proteins, described 30 years ago(1,2), exert essential roles in development as regulators of target gene expression(3,4); however, the molecular mechanisms underlying transcriptional activity of homeodomain factors remain poorly understood. Here investigation of a developmentally required POU-homeodomain transcription factor, Pit1 (also known as Pou1f1), has revealed that, unexpectedly, binding of Pit1-occupied enhancers(5) to a nuclear matrin-3-rich network/architecture(6,7) is a key event in effective activation of the Pit1-regulated enhancer/coding gene transcriptional program. Pit1 association with Satb1 (ref. 8) and beta-catenin is required for this tethering event. A naturally occurring, dominant negative, point mutation in human PIT1(R271W), causing combined pituitary hormone deficiency(9), results in loss of Pit1 association with beta-catenin and Satb1 and therefore the matrin-3-rich network, blocking Pit1-dependent enhancer/coding target gene activation. This defective activation can be rescued by artificial tethering of the mutant R271W Pit1 protein to the matrin-3 network, bypassing the pre-requisite association with beta-catenin and Satb1 otherwise required. The matrin-3 network-tethered R271W Pit1 mutant, but not the untethered protein, restores Pit1-dependent activation of the enhancers and recruitment of co-activators, exemplified by p300, causing both enhancer RNA transcription and target gene activation. These studies have thus revealed an unanticipated homeodomain factor/beta-catenin/Satb1-dependent localization of targetgene regulatory enhancer regions to a subnuclear architectural structure that serves as an underlying mechanism by which an enhancer-bound homeodomain factor effectively activates developmental gene transcriptional programs.
C1 [Skowronska-Krawczyk, Dorota; Ma, Qi; Schwartz, Michal; Scully, Kathleen; Li, Wenbo; Liu, Zhijie; Taylor, Havilah; Tollkuhn, Jessica; Ohgi, Kenneth A.; Notani, Dimple; Rosenfeld, Michael G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, Sch Med, La Jolla, CA 92093 USA.
   [Schwartz, Michal] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel.
   [Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; Bar Ilan University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, Sch Med, La Jolla, CA 92093 USA.
EM dkrawczyk@ucsd.edu; mrosenfeld@ucsd.edu
FU UCSD Neuroscience Microscopy Shared Facility [P30 NS047101]; NIH [NS034934, DK039949, DK018477, HL065445, CA173903]; EMBO Long Term Fellowship; Swiss National Science Foundation; San Diego Foundation; National Cancer Institute [P30CA023100] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK039949] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 33
TC 62
Z9 71
U1 2
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 OCT 9
PY 2014
VL 514
IS 7521
BP 257
EP +
DI 10.1038/nature13573
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100048
PM 25119036
DA 2026-03-09
ER

PT J
AU Fürst, MA
   McMahon, DP
   Osborne, JL
   Paxton, RJ
   Brown, MJF
AF Fuerst, M. A.
   McMahon, D. P.
   Osborne, J. L.
   Paxton, R. J.
   Brown, M. J. F.
TI Disease associations between honeybees and bumblebees as a threat to wild pollinators
SO NATURE
LA English
DT Article
ID deformed-wing-virus; emerging infectious-diseases; nosema-ceranae; bombus-terrestris; apis-mellifera; pathogen; bees; biodiversity; prevalence; parasite
AB Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly(1) and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops(2). Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens(3,4), and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline(5,6), one cause of which may be pathogen spillover from managed pollinators like honeybees(7,8) or commercial colonies of bumblebees(9). Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates(10,11) highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.
C1 [Fuerst, M. A.; Brown, M. J. F.] Royal Holloway Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
   [Fuerst, M. A.] IST Austria Inst Sci & Technol Austria, A-3400 Klosterneuburg, Austria.
   [McMahon, D. P.; Paxton, R. J.] Queens Univ Belfast, Sch Biol Sci, Belfast BT9 7BL, Antrim, North Ireland.
   [Osborne, J. L.] Rothamsted Res, Dept Agroecol, Harpenden AL5 2JQ, Herts, England.
   [Osborne, J. L.] Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
   [Paxton, R. J.] Univ Halle Wittenberg, Inst Biol Gen Zool, D-06120 Halle, Saale, Germany.
   [Paxton, R. J.] German Ctr Integrat Biodivers Res iDiv, D-04103 Leipzig, Germany.
C3 University of London; Royal Holloway University London; Institute of Science & Technology - Austria; Queens University Belfast; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; University of Exeter; Martin Luther University Halle Wittenberg; German Research Foundation (DFG); German Centre for Integrative Biodiversity Research (iDiv)
RP Fürst, MA (corresponding author), Royal Holloway Univ London, Sch Biol Sci, Bourne Bldg, Egham TW20 0EX, Surrey, England.
EM Apocrite@gmail.com
FU Insect Pollinators Initiative; Biotechnology and Biological Sciences Research Council; Department for Environment, Food and Rural Affairs; Natural Environment Research Council; Scottish Government; Wellcome Trust [BB/I000151/1, BB/I000100/1, BB/I000097/1]; Biotechnology and Biological Sciences Research Council [BB/I000097/2, BB/I000151/1, BB/I000097/1, BB/I000100/1] Funding Source: researchfish; BBSRC [BB/I000097/2, BB/I000100/1, BB/I000097/1, BB/I000151/1] Funding Source: UKRI
NR 56
TC 534
Z9 633
U1 6
U2 724
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 20
PY 2014
VL 506
IS 7488
BP 364
EP +
DI 10.1038/nature12977
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800040
PM 24553241
DA 2026-03-09
ER

PT J
AU de Kok, RJ
   Teanby, NA
   Maltagliati, L
   Irwin, PGJ
   Vinatier, S
AF de Kok, Remco J.
   Teanby, Nicholas A.
   Maltagliati, Luca
   Irwin, Patrick G. J.
   Vinatier, Sandrine
TI HCN ice in Titan's high-altitude southern polar cloud
SO NATURE
LA English
DT Article
ID optical-constants; stratospheric aerosols; atmosphere; condensation
AB Titan's middle atmosphere is currently experiencing a rapid change of season after northern spring arrived in 2009 (refs 1, 2). A large cloud was observed(3) for the first time above Titan's southern pole in May 2012, at an altitude of 300 kilometres. A temperature maximum was previously observed there, and condensation was not expected for any of Titan's atmospheric gases. Here we report that this cloud is composed of micrometre-sized particles of frozen hydrogen cyanide (HCN ice). The presence of HCN particles at this altitude, together with temperature determinations from mid-infrared observations, indicate a dramatic cooling of Titan's atmosphere inside the winter polar vortex in early 2012. Such cooling is in contrast to previously measured high-altitude warming in the polar vortex(1), and temperatures are a hundred degrees colder than predicted by circulation models(4). These results show that post-equinox cooling at the winter pole of Titan is much more efficient than previously thought.
C1 [de Kok, Remco J.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [de Kok, Remco J.] SRON Netherlands Inst Space Res, NL-3584 CA Utrecht, Netherlands.
   [Teanby, Nicholas A.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Maltagliati, Luca; Vinatier, Sandrine] Univ Paris Diderot, Univ Paris 06, CNRS, LESIA Observ Paris, F-92195 Meudon, France.
   [Irwin, Patrick G. J.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
C3 Leiden University - Excl LUMC; Leiden University; University of Bristol; Universite Paris Cite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; University of Oxford
RP de Kok, RJ (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM R.J.de.Kok@sron.nl
FU PEPSci programme of the Netherlands Organisation for Scientific Research (NWO); UK Science and Technology Facilities Council; Agence Nationale de la Recherche for support (ANR Project "APOSTIC", France) [11BS56002, 968]; STFC [ST/I001948/1, ST/F007957/2, ST/K00106X/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F007957/2, ST/K00106X/1, ST/I001948/1] Funding Source: researchfish
NR 28
TC 60
Z9 63
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 OCT 2
PY 2014
VL 514
IS 7520
BP 65
EP +
DI 10.1038/nature13789
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800035
PM 25279918
DA 2026-03-09
ER

PT J
AU Hönig, SF
   Watson, D
   Kishimoto, M
   Hjorth, J
AF Honig, Sebastian F.
   Watson, Darach
   Kishimoto, Makoto
   Hjorth, Jens
TI A dust-parallax distance of 19 megaparsecs to the supermassive black hole in NGC 4151
SO NATURE
LA English
DT Article
ID active galactic nuclei; broad-line region; inner radius; narrow-line; reverberation; kinematics; scale; mass; circumnuclear; emission
AB The active galaxy NGC 4151 has a crucial role as one of only two active galactic nuclei for which black hole mass measurements based on emission line reverberation mapping can be calibrated against other dynamical techniques(1-3). Unfortunately, effective calibration requires accurate knowledge of the distance to NGC 4151, which is not at present available(4). Recently reported distances range from 4 to 29 megaparsecs(5-7). Strong peculiar motions make a redshift-based distance very uncertain, and the geometry of the galaxy and its nucleus prohibit accurate measurements using other techniques. Here we report a dust-parallax distance to NGC 4151 of 19.0+(+2.4)(-2.6) megaparsecs. The measurement is based on an adaptation of a geometric method that uses the emission line regions of active galaxies(8). Because these regions are too small to be imaged with present technology, we use instead the ratio of the physical and angular sizes of the more extended hot-dust emission(9) as determined from time delays(10) and infrared interferometry(11-14). This distance leads to an approximately 1.4-fold increase in the dynamical black hole mass, implying a corresponding correction to emission line reverberation masses of black holes if they are calibrated against the two objects with additional dynamical masses.
C1 [Honig, Sebastian F.; Watson, Darach; Hjorth, Jens] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
   [Honig, Sebastian F.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Kishimoto, Makoto] Kyoto Sangyo Univ, Fac Sci, Dept Phys, Kita Ku, Kyoto 6038555, Japan.
C3 University of Copenhagen; Niels Bohr Institute; University of Southampton; Kyoto Sangyo University
RP Hönig, SF (corresponding author), Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, Juliane Maries Vej 30, DK-2100 Copenhagen O, Denmark.
EM s.hoenig@soton.ac.uk
FU Marie Curie International Incoming Fellowship within the Seventh European Community Framework Programme [PIIF-GA-2013-623804]; Danish National Research Foundation; NASA; Grants-in-Aid for Scientific Research [26887044] Funding Source: KAKEN
NR 30
TC 69
Z9 72
U1 0
U2 3
PU NATURE PUBLISHING 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 27
PY 2014
VL 515
IS 7528
BP 528
EP +
DI 10.1038/nature13914
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600047
PM 25428499
DA 2026-03-09
ER

PT J
AU Huang, RJ
   Zhang, YL
   Bozzetti, C
   Ho, KF
   Cao, JJ
   Han, YM
   Daellenbach, KR
   Slowik, JG
   Platt, SM
   Canonaco, F
   Zotter, P
   Wolf, R
   Pieber, SM
   Bruns, EA
   Crippa, M
   Ciarelli, G
   Piazzalunga, A
   Schwikowski, M
   Abbaszade, G
   Schnelle-Kreis, J
   Zimmermann, R
   An, ZS
   Szidat, S
   Baltensperger, U
   El Haddad, I
   Prévôt, ASH
AF Huang, Ru-Jin
   Zhang, Yanlin
   Bozzetti, Carlo
   Ho, Kin-Fai
   Cao, Jun-Ji
   Han, Yongming
   Daellenbach, Kaspar R.
   Slowik, Jay G.
   Platt, Stephen M.
   Canonaco, Francesco
   Zotter, Peter
   Wolf, Robert
   Pieber, Simone M.
   Bruns, Emily A.
   Crippa, Monica
   Ciarelli, Giancarlo
   Piazzalunga, Andrea
   Schwikowski, Margit
   Abbaszade, Guelcin
   Schnelle-Kreis, Juergen
   Zimmermann, Ralf
   An, Zhisheng
   Szidat, Soenke
   Baltensperger, Urs
   El Haddad, Imad
   Prevot, Andre S. H.
TI High secondary aerosol contribution to particulate pollution during haze events in China
SO NATURE
LA English
DT Article
ID organic aerosols; source apportionment; pm2.5; emissions; field
AB Rapid industrialization and urbanization in developing countries has led to an increase in air pollution, along a similar trajectory to that previously experienced by the developed nations(1). In China, particulate pollution is a serious environmental problem that is influencing air quality, regional and global climates, and human health(2,3). In response to the extremely severe and persistent haze pollution experienced by about 800 million people during the first quarter of 2013 (refs 4, 5), the Chinese State Council announced its aim to reduce concentrations of PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 micrometres) by up to 25 per cent relative to 2012 levels by 2017 (ref. 6). Such efforts however require elucidation of the factors governing the abundance and composition of PM2.5, which remain poorly constrained in China(3,7,8). Here we combine a comprehensive set of novel and state-of-the-art offline analytical approaches and statistical techniques to investigate the chemical nature and sources of particulate matter at urban locations in Beijing, Shanghai, Guangzhou and Xi'an during January 2013. We find that the severe haze pollution event was driven to a large extent by secondary aerosol formation, which contributed 30-77 per cent and 44-71 per cent (average for all four cities) of PM2.5 and of organic aerosol, respectively. On average, the contribution of secondary organic aerosol (SOA) and secondary inorganic aerosol (SIA) are found to be of similar importance (SOA/SIA ratios range from 0.6 to 1.4). Our results suggest that, in addition to mitigating primary particulate emissions, reducing the emissions of secondary aerosol precursors from, for example, fossil fuel combustion and biomass burning is likely to be important for controlling China's PM2.5 levels and for reducing the environmental, economic and health impacts resulting from particulate pollution.
C1 [Huang, Ru-Jin; Bozzetti, Carlo; Daellenbach, Kaspar R.; Slowik, Jay G.; Platt, Stephen M.; Canonaco, Francesco; Zotter, Peter; Wolf, Robert; Pieber, Simone M.; Bruns, Emily A.; Crippa, Monica; Ciarelli, Giancarlo; Baltensperger, Urs; El Haddad, Imad; Prevot, Andre S. H.] PSI, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
   [Huang, Ru-Jin; Cao, Jun-Ji; Han, Yongming; An, Zhisheng] Chinese Acad Sci, Inst Earth Environm, SKLLQG, Xian 710075, Peoples R China.
   [Huang, Ru-Jin; Cao, Jun-Ji; Han, Yongming; An, Zhisheng] Chinese Acad Sci, Inst Earth Environm, Key Lab Aerosol Chem & Phys, Xian 710075, Peoples R China.
   [Zhang, Yanlin; Schwikowski, Margit; Szidat, Soenke] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland.
   [Zhang, Yanlin; Schwikowski, Margit; Szidat, Soenke] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Zhang, Yanlin; Schwikowski, Margit] PSI, Lab Radiochem & Environm Chem, CH-5232 Villigen, Switzerland.
   [Ho, Kin-Fai] Chinese Univ Hong Kong, Jockey Club Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
   [Piazzalunga, Andrea] Univ Milano Bicocca, Dept Earth & Environm Sci, I-20126 Milan, Italy.
   [Abbaszade, Guelcin; Schnelle-Kreis, Juergen; Zimmermann, Ralf] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth GmbH, Joint Mass Spectrometry Ctr, Cooperat Grp Comprehens Mol Analyt, D-85764 Neuherberg, Germany.
   [Abbaszade, Guelcin; Schnelle-Kreis, Juergen; Zimmermann, Ralf] Helmholtz Virtual Inst Complex Mol Syst Environm, D-85764 Neuherberg, Germany.
   [Zimmermann, Ralf] Univ Rostock, Joint Mass Spectrometry Ctr, Inst Chem, D-18015 Rostock, Germany.
C3 Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Chinese Academy of Sciences; Institute of Earth Environment, CAS; Chinese Academy of Sciences; Institute of Earth Environment, CAS; University of Bern; University of Bern; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Chinese University of Hong Kong; University of Milano-Bicocca; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Rostock
RP Cao, JJ (corresponding author), Chinese Acad Sci, Inst Earth Environm, SKLLQG, Xian 710075, Peoples R China.
EM jjcao@ieecas.cn; andre.prevot@psi.ch
FU European Community [290605]; Swiss National Science Foundation (SAPMAV) [200021_13016]; Swiss National Science Foundation (WOOSHI) [200021L_140590]; Swiss National Science Foundation (Ambizione) [PZ00P2_131673]; Swiss Competence Center Environment and Sustainability; Swiss Competence Center Energy and Mobility under project OPTIWARES; National Science Foundation of China [40925009]; "Strategic Priority Research Program'' of the Chinese Academy of Sciences [XDA05100402]; Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health - Aerosol and Health (HICE); Swiss National Science Foundation (SNF) [200021L_140590, PZ00P2_131673] Funding Source: Swiss National Science Foundation (SNF)
NR 30
TC 3863
Z9 4454
U1 126
U2 6079
PU NATURE PUBLISHING 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 9
PY 2014
VL 514
IS 7521
BP 218
EP 222
DI 10.1038/nature13774
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100040
PM 25231863
DA 2026-03-09
ER

PT J
AU Woo, SH
   Ranade, S
   Weyer, AD
   Dubin, AE
   Baba, Y
   Qiu, ZZ
   Petrus, M
   Miyamoto, T
   Reddy, K
   Lumpkin, EA
   Stucky, CL
   Patapoutian, A
AF Woo, Seung-Hyun
   Ranade, Sanjeev
   Weyer, Andy D.
   Dubin, Adrienne E.
   Baba, Yoshichika
   Qiu, Zhaozhu
   Petrus, Matt
   Miyamoto, Takashi
   Reddy, Kritika
   Lumpkin, Ellen A.
   Stucky, Cheryl L.
   Patapoutian, Ardem
TI Piezo2 is required for Merkel-cell mechanotransduction
SO NATURE
LA English
DT Article
ID selective phototoxic destruction; hairy skin; cutaneous mechanoreceptors; sensory neurons; touch; responses; channels; receptor; currents; transmission
AB How we sense touch remains fundamentally unknown(1,2). The Merkel cell-neurite complex is a gentle touch receptor in the skin that mediates slowly adapting responses of A beta sensory fibres to encode fine details of objects(3-6). This mechanoreceptor complex was recognized to have an essential role in sensing gentle touch nearly 50 years ago(3,4). However, whether Merkel cells or afferent fibres themselves sense mechanical force is still debated, and the molecular mechanism of mechanotransduction is unknown(1,2,7-12). Synapse-like junctions are observed between Merkel cells and associated afferents(6,13-15), and yet it is unclear whether Merkel cells are inherently mechanosensitive or whether they can rapidly transmit such information to the neighbouring nerve(1,2,16,17). Here we show that Merkel cells produce touch-sensitive currents in vitro. Piezo2, a mechanically activated cation channel, is expressed in Merkel cells. We engineered mice deficient in Piezo2 in the skin, but not in sensory neurons, and show that Merkel-cell mechanosensitivity completely depends on Piezo2. In these mice, slowly adapting responses in vivo mediated by the Merkel cell-neurite complex show reduced static firing rates, and moreover, the mice display moderately decreased behavioural responses to gentle touch. Our results indicate that Piezo2 is the Merkel-cell mechanotransduction channel and provide the first line of evidence that Piezo channels have a physiological role in mechanosensation in mammals. Furthermore, our data present evidence for a two-receptor-site model, in which both Merkel cells and innervating afferents act together as mechanosensors. The two-receptor system could provide this mechanoreceptor complex with a tuning mechanism to achieve highly sophisticated responses to a given mechanical stimulus(15,18,19).
C1 [Woo, Seung-Hyun; Ranade, Sanjeev; Dubin, Adrienne E.; Qiu, Zhaozhu; Miyamoto, Takashi; Patapoutian, Ardem] Scripps Res Inst, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Weyer, Andy D.; Stucky, Cheryl L.] Med Coll Wisconsin, Dept Cell Biol, Milwaukee, WI 53226 USA.
   [Weyer, Andy D.; Stucky, Cheryl L.] Med Coll Wisconsin, Dept Neurobiol, Milwaukee, WI 53226 USA.
   [Weyer, Andy D.; Stucky, Cheryl L.] Med Coll Wisconsin, Dept Anat, Milwaukee, WI 53226 USA.
   [Baba, Yoshichika; Lumpkin, Ellen A.] Columbia Univ, Dept Dermatol, New York, NY 10032 USA.
   [Baba, Yoshichika; Lumpkin, Ellen A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Qiu, Zhaozhu; Petrus, Matt; Reddy, Kritika] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
C3 Scripps Research Institute; Howard Hughes Medical Institute; Medical College of Wisconsin; Medical College of Wisconsin; Medical College of Wisconsin; Columbia University; Columbia University; Novartis; Novartis USA
RP Patapoutian, A (corresponding author), Scripps Res Inst, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
EM ardem@scripps.edu
FU Howard Hughes Medical Institute; NIH [R01DE022358, R01AR051219]; National Institute of Neurological Disorders and Stroke [R01NS070711] Funding Source: NIH RePORTER
NR 35
TC 594
Z9 709
U1 5
U2 182
PU NATURE PUBLISHING 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 29
PY 2014
VL 509
IS 7502
BP 622
EP 626
DI 10.1038/nature13251
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100049
PM 24717433
DA 2026-03-09
ER

PT J
AU Pinan-Lucarré, B
   Tu, HJ
   Pierron, M
   Cruceyra, PI
   Zhan, H
   Stigloher, C
   Richmond, JE
   Bessereau, JL
AF Pinan-Lucarre, Berangere
   Tu, Haijun
   Pierron, Marie
   Cruceyra, Pablo Ibanez
   Zhan, Hong
   Stigloher, Christian
   Richmond, Janet E.
   Bessereau, Jean-Louis
TI C. elegans Punctin specifies cholinergic versus GABAergic identity of postsynaptic domains
SO NATURE
LA English
DT Article
ID receptor alpha-subunit; caenorhabditis-elegans; acetylcholine-receptor; neuromuscular-junction; extracellular-matrix; gaba receptor; gene encodes; protein; complex
AB Because most neurons receive thousands of synaptic inputs, the neuronal membrane is a mosaic of specialized microdomains where neurotransmitter receptors cluster in register with the corresponding presynaptic neurotransmitter release sites. In many cases the coordinated differentiation of presynaptic and postsynaptic domains implicates trans-synaptic interactions between membrane-associated proteins such as neurexins and neuroligins(1-3). The Caenorhabditis elegans neuromuscular junction (NMJ) provides a genetically tractable system in which to analyse the segregation of neurotransmitter receptors, because muscle cells receive excitatory innervation from cholinergic neurons and inhibitory innervation from GABAergic neurons(4). Here we show that Ce-Punctin/madd-4 (ref.5), the C. elegans orthologue of mammalian punctin-1 and punctin-2, encodes neurally secreted isoforms that specify the excitatory or inhibitory identity of postsynaptic NMJ domains. These proteins belong to the ADAMTS (a disintegrin and metalloprotease with thrombospondin repeats)like family, a class of extracellular matrix proteins related to the ADAM proteases but devoid of proteolytic activity(6). Ce-Punctin deletion causes the redistribution of synaptic acetylcholine and GABA(A) (gamma-aminobutyric acid type A) receptors into extrasynaptic clusters, whereas neuronal presynaptic boutons remain unaltered. Alternative promoters generate different Ce-Punctin isoforms with distinct functions. A short isoform is expressed by cholinergic and GABAergic motoneurons and localizes to excitatory and inhibitory NMJs, whereas long isoforms are expressed exclusively by cholinergic motoneurons and are confined to cholinergic NMJs. The differential expression of these isoforms controls the congruence between presynaptic and postsynaptic domains: specific disruption of the short isoform relocalizes GABAA receptors from GABAergic to cholinergic synapses, whereas expression of a long isoform in GABAergic neurons recruits acetylcholine receptors to GABAergic NMJs. These results identify Ce-Punctin as a previously unknown synaptic organizer and show that presynaptic and postsynaptic domain identities can be genetically uncoupled in vivo. Because human punctin-2 was identified as a candidate gene for schizophrenia(7), ADAMTS-like proteins may also control synapse organization in the mammalian central nervous system.
C1 [Pinan-Lucarre, Berangere; Tu, Haijun; Pierron, Marie; Cruceyra, Pablo Ibanez; Zhan, Hong; Stigloher, Christian; Bessereau, Jean-Louis] Ecole Normale Super, Inst Biol, F-75005 Paris, France.
   [Pinan-Lucarre, Berangere; Tu, Haijun; Pierron, Marie; Zhan, Hong; Bessereau, Jean-Louis] Univ Lyon 1, CGphiMC UMR CNRS 5534, F-69622 Villeurbanne, France.
   [Richmond, Janet E.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA.
C3 Universite PSL; Ecole Normale Superieure (ENS); Universite Lyon 1; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Bessereau, JL (corresponding author), Ecole Normale Super, Inst Biol, F-75005 Paris, France.
EM jean-louis.bessereau@univ-lyon1.fr
FU National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]; Association Francaise contre les Myopathies; Fondation pour la Recherche Medicale; Neuropole de Recherche Francilien; Fondation Pierre-Gilles de Gennes; Human Frontier Science Program Long-Term Fellowship; Agence Nationale de la Recherche [ANR-2010-BLAN-1618-01, ANR-11-BSV4-019]; Fondation pour la Recherche Medicale ('Equipe FRM' grant)
NR 41
TC 52
Z9 65
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 JUL 24
PY 2014
VL 511
IS 7510
BP 466
EP +
DI 10.1038/nature13313
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700046
PM 24896188
DA 2026-03-09
ER

PT J
AU Forrest, ARR
   Kawaji, H
   Rehli, M
   Baillie, JK
   de Hoon, MJL
   Haberle, V
   Lassmann, T
   Kulakovskiy, IV
   Lizio, M
   Itoh, M
   Andersson, R
   Mungall, CJ
   Meehan, TF
   Schmeier, S
   Bertin, N
   Jorgensen, M
   Dimont, E
   Arner, E
   Schmidl, C
   Schaefer, U
   Medvedeva, YA
   Plessy, C
   Vitezic, M
   Severin, J
   Semple, CA
   Ishizu, Y
   Young, RS
   Francescatto, M
   Alam, I
   Albanese, D
   Altschuler, GM
   Arakawa, T
   Archer, JAC
   Arner, P
   Babina, M
   Rennie, S
   Balwierz, PJ
   Beckhouse, AG
   Pradhan-Bhatt, S
   Blake, JA
   Blumenthal, A
   Bodega, B
   Bonetti, A
   Briggs, J
   Brombacher, F
   Burroughs, AM
   Califano, A
   Cannistraci, CV
   Carbajo, D
   Chen, Y
   Chierici, M
   Ciani, Y
   Clevers, HC
   Dalla, E
   Davis, CA
   Detmar, M
   Diehl, AD
   Dohi, T
   Drablos, F
   Edge, ASB
   Edinger, M
   Ekwall, K
   Endoh, M
   Enomoto, H
   Fagiolini, M
   Fairbairn, L
   Fang, H
   Farach-Carson, MC
   Faulkner, GJ
   Favorov, AV
   Fisher, ME
   Frith, MC
   Fujita, R
   Fukuda, S
   Furlanello, C
   Furuno, M
   Furusawa, J
   Geijtenbeek, TB
   Gibson, AP
   Gingeras, T
   Goldowitz, D
   Gough, J
   Guhl, S
   Guler, R
   Gustincich, S
   Ha, TJ
   Hamaguchi, M
   Hara, M
   Harbers, M
   Harshbarger, J
   Hasegawa, A
   Hasegawa, Y
   Hashimoto, T
   Herlyn, M
   Hitchens, KJ
   Sui, SJH
   Hofmann, OM
   Hoof, I
   Hori, F
   Huminiecki, L
   Iida, K
   Ikawa, T
   Jankovic, BR
   Jia, H
   Joshi, A
   Jurman, G
   Kaczkowski, B
   Kai, C
   Kaida, K
   Kaiho, A
   Kajiyama, K
   Kanamori-Katayama, M
   Kasianov, A
   Kasukawa, T
   Katayama, S
   Kato, S
   Kawaguchi, S
   Kawamoto, H
   Kawamura, YI
   Kawashima, T
   Kempfle, JS
   Kenna, TJ
   Kere, J
   Khachigian, LM
   Kitamura, T
   Klinken, SP
   Knox, AJ
   Kojima, M
   Kojima, S
   Kondo, N
   Koseki, H
   Koyasu, S
   Krampitz, S
   Kubosaki, A
   Kwon, AT
   Laros, JFJ
   Lee, W
   Lennartsson, A
   Li, K
   Lilje, B
   Lipovich, L
   Mackay-sim, A
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   Sajantila, A
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   Winteringham, LN
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   Freeman, TC
   Lenhard, B
   Bajic, VB
   Taylor, MS
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   Sandelin, A
   Hume, DA
   Carninci, P
   Hayashizaki, Y
AF Forrest, Alistair R. R.
   Kawaji, Hideya
   Rehli, Michael
   Baillie, J. Kenneth
   de Hoon, Michiel J. L.
   Haberle, Vanja
   Lassmann, Timo
   Kulakovskiy, Ivan V.
   Lizio, Marina
   Itoh, Masayoshi
   Andersson, Robin
   Mungall, Christopher J.
   Meehan, Terrence F.
   Schmeier, Sebastian
   Bertin, Nicolas
   Jorgensen, Mette
   Dimont, Emmanuel
   Arner, Erik
   Schmidl, Christian
   Schaefer, Ulf
   Medvedeva, Yulia A.
   Plessy, Charles
   Vitezic, Morana
   Severin, Jessica
   Semple, Colin A.
   Ishizu, Yuri
   Young, Robert S.
   Francescatto, Margherita
   Alam, Intikhab
   Albanese, Davide
   Altschuler, Gabriel M.
   Arakawa, Takahiro
   Archer, John A. C.
   Arner, Peter
   Babina, Magda
   Rennie, Sarah
   Balwierz, Piotr J.
   Beckhouse, Anthony G.
   Pradhan-Bhatt, Swati
   Blake, Judith A.
   Blumenthal, Antje
   Bodega, Beatrice
   Bonetti, Alessandro
   Briggs, James
   Brombacher, Frank
   Burroughs, A. Maxwell
   Califano, Andrea
   Cannistraci, Carlo V.
   Carbajo, Daniel
   Chen, Yun
   Chierici, Marco
   Ciani, Yari
   Clevers, Hans C.
   Dalla, Emiliano
   Davis, Carrie A.
   Detmar, Michael
   Diehl, Alexander D.
   Dohi, Taeko
   Drablos, Finn
   Edge, Albert S. B.
   Edinger, Matthias
   Ekwall, Karl
   Endoh, Mitsuhiro
   Enomoto, Hideki
   Fagiolini, Michela
   Fairbairn, Lynsey
   Fang, Hai
   Farach-Carson, Mary C.
   Faulkner, Geoffrey J.
   Favorov, Alexander V.
   Fisher, Malcolm E.
   Frith, Martin C.
   Fujita, Rie
   Fukuda, Shiro
   Furlanello, Cesare
   Furuno, Masaaki
   Furusawa, Jun-ichi
   Geijtenbeek, Teunis B.
   Gibson, Andrew P.
   Gingeras, Thomas
   Goldowitz, Daniel
   Gough, Julian
   Guhl, Sven
   Guler, Reto
   Gustincich, Stefano
   Ha, Thomas J.
   Hamaguchi, Masahide
   Hara, Mitsuko
   Harbers, Matthias
   Harshbarger, Jayson
   Hasegawa, Akira
   Hasegawa, Yuki
   Hashimoto, Takehiro
   Herlyn, Meenhard
   Hitchens, Kelly J.
   Sui, Shannan J. Ho
   Hofmann, Oliver M.
   Hoof, Ilka
   Hori, Fumi
   Huminiecki, Lukasz
   Iida, Kei
   Ikawa, Tomokatsu
   Jankovic, Boris R.
   Jia, Hui
   Joshi, Anagha
   Jurman, Giuseppe
   Kaczkowski, Bogumil
   Kai, Chieko
   Kaida, Kaoru
   Kaiho, Ai
   Kajiyama, Kazuhiro
   Kanamori-Katayama, Mutsumi
   Kasianov, ArtemS.
   Kasukawa, Takeya
   Katayama, Shintaro
   Kato, Sachi
   Kawaguchi, Shuji
   Kawamoto, Hiroshi
   Kawamura, Yuki I.
   Kawashima, Tsugumi
   Kempfle, Judith S.
   Kenna, Tony J.
   Kere, Juha
   Khachigian, Levon M.
   Kitamura, Toshio
   Klinken, S. Peter
   Knox, Alan J.
   Kojima, Miki
   Kojima, Soichi
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   Lipovich, Leonard
   Mackay-sim, Alan
   Manabe, Ri-ichiroh
   Mar, Jessica C.
   Marchand, Benoit
   Mathelier, Anthony
   Mejhert, Niklas
   Meynert, Alison
   Mizuno, Yosuke
   Morais, David A. de Lima
   Morikawa, Hiromasa
   Morimoto, Mitsuru
   Moro, Kazuyo
   Motakis, Efthymios
   Motohashi, Hozumi
   Mummery, Christine L.
   Murata, Mitsuyoshi
   Nagao-Sato, Sayaka
   Nakachi, Yutaka
   Nakahara, Fumio
   Nakamura, Toshiyuki
   Nakamura, Yukio
   Nakazato, Kenichi
   Van Nimwegen, Erik
   Ninomiya, Noriko
   Nishiyori, Hiromi
   Noma, Shohei
   Nozaki, Tadasuke
   Ogishima, Soichi
   Ohkura, Naganari
   Ohmiya, Hiroko
   Ohno, Hiroshi
   Ohshima, Mitsuhiro
   Okada-Hatakeyama, Mariko
   Okazaki, Yasushi
   Orlando, Valerio
   Ovchinnikov, Dmitry A.
   Pain, Arnab
   Passier, Robert
   Patrikakis, Margaret
   Persson, Helena
   Piazza, Silvano
   Prendergast, James G. D.
   Rackham, Owen J. L.
   Ramilowski, Jordan A.
   Rashid, Mamoon
   Ravasi, Timothy
   Rizzu, Patrizia
   Roncador, Marco
   Roy, Sugata
   Rye, Morten B.
   Saijyo, Eri
   Sajantila, Antti
   Saka, Akiko
   Sakaguchi, Shimon
   Sakai, Mizuho
   Sato, Hiroki
   Satoh, Hironori
   Savvi, Suzana
   Saxena, Alka
   Schneider, Claudio
   Schultes, Erik A.
   Schulze-Tanzil, Gundula G.
   Schwegmann, Anita
   Sengstag, Thierry
   Sheng, Guojun
   Shimoji, Hisashi
   Shimoni, Yishai
   Shin, Jay W.
   Simon, Christophe
   Sugiyama, Daisuke
   Sugiyama, Takaaki
   Suzuki, Masanori
   Suzuki, Naoko
   Swoboda, Rolf K.
   't Hoen, Peter A. C.
   Tagami, Michihira
   Takahashi, Naoko
   Takai, Jun
   Tanaka, Hiroshi
   Tatsukawa, Hideki
   Tatum, Zuotian
   Thompson, Mark
   Toyoda, Hiroo
   Toyoda, Tetsuro
   Valen, Eivind
   van de Wetering, Marc
   van den Berg, Linda M.
   Verardo, Roberto
   Vijayan, Dipti
   Vorontsov, Ilya E.
   Wasserman, Wyeth W.
   Watanabe, Shoko
   Wells, Christine A.
   Winteringham, Louise N.
   Wolvetang, Ernst
   Wood, Emily J.
   Yamaguchi, Yoko
   Yamamoto, Masayuki
   Yoneda, Misako
   Yonekura, Yohei
   Yoshida, Shigehiro
   Zabierowski, Susan E.
   Zhang, Peter G.
   Zhao, Xiaobei
   Zucchelli, Silvia
   Summers, Kim M.
   Suzuki, Harukazu
   Daub, Carsten O.
   Kawai, Jun
   Heutink, Peter
   Hide, Winston
   Freeman, Tom C.
   Lenhard, Boris
   Bajic, Vladimir B.
   Taylor, Martin S.
   Makeev, Vsevolod J.
   Sandelin, Albin
   Hume, David A.
   Carninci, Piero
   Hayashizaki, Yoshihide
TI A promoter-level mammalian expression atlas
SO NATURE
LA English
DT Article
ID transcription factor; gene-expression; homeobox gene; mice lacking; differentiation; mouse; classification; signatures; mutations; deafness
AB Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis revealskey transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
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   [Kitamura, Toshio; Nakahara, Fumio] Univ Tokyo, Div Stem Cell Signaling, Inst Med Sci, Tokyo 1088639, Japan.
   [Klinken, S. Peter; Winteringham, Louise N.] Univ Western Australia, Harry Perkins Inst Med Res, QEII Med Ctr, Perth, WA 6009, Australia.
   [Klinken, S. Peter; Winteringham, Louise N.] Univ Western Australia, Med Res Ctr, QEII Med Ctr, Perth, WA 6009, Australia.
   [Knox, Alan J.] Univ Nottingham, City Hosp, Nottingham NG5 1PB, England.
   [Lee, Weonju] Kyungpook Natl Univ, Sch Med, Dept Dermatol, Taegu 700721, South Korea.
   [Mackay-sim, Alan] Griffith Univ, Natl Ctr Adult Stem Cell Res, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia.
   [Mizuno, Yosuke; Nakachi, Yutaka; Okazaki, Yasushi] Saitama Med Univ, Div Funct Genom & Syst Med, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan.
   [Morais, David A. de Lima] Univ Bristol, Fac Engn, Clifton BS81UB, England.
   [Moro, Kazuyo] Japanese Sci & Technol Agcy JST, PRESTO, Tokyo 1020076, Japan.
   [Motohashi, Hozumi] Tohoku Univ, Ctr Radioisotope Sci, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan.
   [Mummery, Christine L.; Passier, Robert] Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands.
   [Nakachi, Yutaka; Okazaki, Yasushi] Saitama Med Univ, Div Translat Res, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan.
   [Nakamura, Yukio] RIKEN, BioResource Ctr BRC, Tsukuba, Ibaraki 3050074, Japan.
   [Nozaki, Tadasuke; Toyoda, Hiroo] Tokyo Univ Pharm & Life Sci, Dept Clin Mol Genet, Sch Pharm, Hachioji, Tokyo 1920392, Japan.
   [Ogishima, Soichi; Tanaka, Hiroshi] Tokyo Med & Dent Univ, Dept Bioinformat, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan.
   [Ohshima, Mitsuhiro] Ohu Univ, Dept Biochem, Sch Pharmaceut Sci, Koriyama, Fukushima 9638611, Japan.
   [Sajantila, Antti] Univ Helsinki, Dept Forens Med, Hjelt Inst, Helsinki 003000, Finland.
   [Schneider, Claudio] Univ Udine, DSMB, I-33100 Udine, Italy.
   [Schulze-Tanzil, Gundula G.] Charite, Dept Orthoped Trauma & Reconstruct Surg, D-14195 Berlin, Germany.
   [Sugiyama, Daisuke] Kyushu Univ Hosp, Ctr Clin & Translat Reseach, Higashi Ku, Fukuoka 8128582, Japan.
   [Tatsukawa, Hideki] Nagoya Univ, Grad Sch Pharmaceut Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Valen, Eivind] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Yamaguchi, Yoko] Nihon Univ, Dept Biochem, Sch Dent, Chiyoda Ku, Tokyo 1018310, Japan.
   [Lenhard, Boris] Univ Bergen, Dept Informat, NO-5008 Bergen, Norway.
   [Makeev, Vsevolod J.] MIPT, Dept Biol & Med Phys, Dolgoprudnyi 141700, Moscow Region, Russia.
C3 RIKEN; RIKEN; RIKEN; University of Regensburg; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of Edinburgh; University of Bergen; Imperial College London; Russian Academy of Sciences; Engelhardt Institute of Molecular Biology, RAS; Russian Academy of Sciences; Vavilov Institute of General Genetics; University of Copenhagen; University of Copenhagen; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; King Abdullah University of Science & Technology; Massey University; Harvard University; Harvard T.H. Chan School of Public Health; Karolinska Institutet; University of Edinburgh; Vrije Universiteit Amsterdam; Universidade do Porto; Fondazione Bruno Kessler; Karolinska Institutet; Karolinska University Hospital; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; University of Basel; University of Queensland; University of Queensland; University of Delaware; Jackson Laboratory; University of Queensland; IRCCS Santa Lucia; International Center for Genetic Engineering & Biotechnology (ICGEB); ICGEB Cape Town; University of Cape Town; Columbia University; Columbia University; Columbia University; Columbia University; King Abdullah University of Science & Technology; King Abdullah University of Science & Technology; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Cold Spring Harbor Laboratory; Swiss Federal Institutes of Technology Domain; ETH Zurich; State University of New York (SUNY) System; University at Buffalo, SUNY; Japan Institute for Health Security (JIHS); National Center for Global Health & Medicine - Japan; Norwegian University of Science & Technology (NTNU); Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts Eye & Ear Infirmary; Karolinska Institutet; RIKEN; RIKEN; RIKEN; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; University of Bristol; Rice University; University of Queensland; Mater Research; Johns Hopkins University; National Research Centre - Kurchatov Institute; Institute of Genetics & Selection of Industrial Microorganisms; National Institute of Advanced Industrial Science & Technology (AIST); Tohoku University; Keio University; University of Amsterdam; Academic Medical Center Amsterdam; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Child & Family Research Institute; University of British Columbia; International School for Advanced Studies (SISSA); University of Osaka; RIKEN; The Wistar Institute; RIKEN; Wayne State University; University of Tokyo; University of New South Wales Sydney; University of Tokyo; University of Tokyo; Harry Perkins Institute of Medical Research; University of Western Australia; University of Western Australia; Nottingham University Hospital NHS Trust; Nottingham City Hospital; University of Nottingham; Kyungpook National University (KNU); Griffith University; Saitama Medical University; University of Bristol; Japan Science & Technology Agency (JST); Tohoku University; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Saitama Medical University; RIKEN; Tokyo University of Pharmacy & Life Sciences; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); University of Helsinki; University of Udine; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Nagoya University; Harvard University; Nihon University; University of Bergen; Moscow Institute of Physics & Technology
RP Forrest, ARR (corresponding author), RIKEN, OSC, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.
EM alistair.forrest@gmail.com; carninci@riken.jp; yosihide@gsc.riken.jp
FU MEXT; MEXT, Japan; Research Grants for RIKEN Preventive Medicine and Diagnosis Innovation Program(RIKEN PMI); RIKEN Centre for Life Science Technologies, Division of Genomic Technologies (RIKEN CLST (DGT)) from the MEXT, Japan; Biotechnology and Biological Sciences Research Council [BBS/E/D/20231759, BBS/E/D/20211551, BB/G022771/1, BBS/E/D/20211552, BB/I001107/1, BB/I024801/1, BB/F003722/1, BB/I025018/1, BBS/E/D/20211550, BBS/E/D/20251969] Funding Source: researchfish; Lundbeck Foundation [R82-2010-6779] Funding Source: researchfish; Medical Research Council [MC_PC_U127597124, MC_UP_1102/1] Funding Source: researchfish; Novo Nordisk Fonden [NNF12OC1016371] Funding Source: researchfish; Wellcome Trust [103258/Z/13/Z] Funding Source: researchfish; Grants-in-Aid for Scientific Research [23689044, 22118002, 23790791, 26713029, 22228005, 22118001, 22122005] Funding Source: KAKEN; BBSRC [BB/I024801/1, BBS/E/D/20231759, BBS/E/D/20211552, BB/I025018/1, BBS/E/D/20251969, BBS/E/D/20211551, BB/F003722/1, BBS/E/D/20211550, BB/I001107/1, BB/G022771/1] Funding Source: UKRI; MRC [MC_PC_U127597124, MC_UP_1102/1] Funding Source: UKRI; Wellcome Trust [103258/Z/13/Z] Funding Source: Wellcome Trust
NR 54
TC 1514
Z9 1742
U1 2
U2 310
PU NATURE PUBLISHING 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 27
PY 2014
VL 507
IS 7493
BP 462
EP +
DI 10.1038/nature13182
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000033
PM 24670764
DA 2026-03-09
ER

PT J
AU Shi, Y
   Armus, L
   Helou, G
   Stierwalt, S
   Gao, Y
   Wang, JZ
   Zhang, ZY
   Gu, QS
AF Shi, Yong
   Armus, Lee
   Helou, George
   Stierwalt, Sabrina
   Gao, Yu
   Wang, Junzhi
   Zhang, Zhi-Yu
   Gu, Qiusheng
TI Inefficient star formation in extremely metal poor galaxies
SO NATURE
LA English
DT Article
ID co-to-h-2 conversion factor; low-metallicity; nearby galaxy; formation law; dust; gas; emission; abundances; disks
AB The first galaxies contain stars born out of gas with few or no 'metals' (that is, elements heavier than helium). The lack of metals is expected to inhibit efficient gas cooling and star formation(1,2), but this effect has yet to be observed in galaxies with an oxygen abundance (relative to hydrogen) below a tenth of that of the Sun(2-4). Extremely metal poor nearby galaxies may be our best local laboratories for studying in detail the conditions that prevailed in low metallicity galaxies at early epochs. Carbon monoxide emission is unreliable as a tracer of gas at low metallicities(5-7), and while dust has been used to trace gas in low-metallicity galaxies(5,8-10), low spatial resolution in the far-infrared has typically led to large uncertainties(9,10). Here we report spatially resolved infrared observations of two galaxies with oxygen abundances below ten per cent of the solar value, and show that stars formed very inefficiently in seven star-forming clumps in these galaxies. The efficiencies are less than a tenth of those found in normal, metal rich galaxies today, suggesting that star formation may have been very inefficient in the early Universe.
C1 [Shi, Yong; Gu, Qiusheng] Nanjing Univ, Sch Astron & Space Sci, Nanjing 210093, Jiangsu, Peoples R China.
   [Shi, Yong; Gu, Qiusheng] Nanjing Univ, Minist Educ, Key Lab Modern Astron & Astrophys, Nanjing 210093, Jiangsu, Peoples R China.
   [Armus, Lee; Helou, George] CALTECH, Infrared Proc & Anal Ctr, Pasadena, CA 91125 USA.
   [Stierwalt, Sabrina] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Gao, Yu] Chinese Acad Sci, Purple Mt Observ, Nanjing 210008, Peoples R China.
   [Gao, Yu] Chinese Acad Sci, Key Lab Radio Astron, Nanjing 210008, Peoples R China.
   [Wang, Junzhi] Chinese Acad Sci, Shanghai Astron Observ, Shanghai 200030, Peoples R China.
   [Zhang, Zhi-Yu] Univ Edinburgh, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
C3 Nanjing University; Nanjing University; California Institute of Technology; University of Virginia; Purple Mountain Observatory, CAS; Chinese Academy of Sciences; Nanjing Institute of Astronomical Optics & Technology, NAOC, CAS; Chinese Academy of Sciences; Chinese Academy of Sciences; Shanghai Astronomical Observatory, CAS; University of Edinburgh
RP Shi, Y (corresponding author), Nanjing Univ, Sch Astron & Space Sci, Nanjing 210093, Jiangsu, Peoples R China.
EM yshipku@gmail.com
FU Natural Science Foundation of China (NSFC) [11373021]; Chinese Academy of Sciences (CAS) [XDB09000000]; Nanjing University [985]; NSFC [11173059, 11390373, 11173013, 11273015, 11133001]; CAS [XDB09000000]; National 973 programme [2012CB821805, 2013CB834905]; European Research Council (ERC); Spitzer Space Telescope; NASA; NASA issued by JPL/Caltech [OT2_yshi_3]
NR 40
TC 57
Z9 61
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 OCT 16
PY 2014
VL 514
IS 7522
BP 335
EP +
DI 10.1038/nature13820
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600044
PM 25318522
DA 2026-03-09
ER

PT J
AU Yue, F
   Cheng, Y
   Breschi, A
   Vierstra, J
   Wu, WS
   Ryba, T
   Sandstrom, R
   Ma, ZH
   Davis, C
   Pope, BD
   Shen, Y
   Pervouchine, DD
   Djebali, S
   Thurman, RE
   Kaul, R
   Rynes, E
   Kirilusha, A
   Marinov, GK
   Williams, BA
   Trout, D
   Amrhein, H
   Fisher-Aylor, K
   Antoshechkin, I
   DeSalvo, G
   See, LH
   Fastuca, M
   Drenkow, J
   Zaleski, C
   Dobin, A
   Prieto, P
   Lagarde, J
   Bussotti, G
   Tanzer, A
   Denas, O
   Li, KW
   Bender, MA
   Zhang, MH
   Byron, R
   Groudine, MT
   McCleary, D
   Pham, L
   Ye, Z
   Kuan, S
   Edsall, L
   Wu, YC
   Rasmussen, MD
   Bansal, MS
   Kellis, M
   Keller, CA
   Morrissey, CS
   Mishra, T
   Jain, D
   Dogan, N
   Harris, RS
   Cayting, P
   Kawli, T
   Boyle, AP
   Euskirchen, G
   Kundaje, A
   Lin, S
   Lin, Y
   Jansen, C
   Malladi, VS
   Cline, MS
   Erickson, DT
   Kirkup, VM
   Learned, K
   Sloan, CA
   Rosenbloom, KR
   De Sousa, BL
   Beal, K
   Pignatelli, M
   Flicek, P
   Lian, J
   Kahveci, T
   Lee, D
   Kent, WJ
   Santos, MR
   Herrero, J
   Notredame, C
   Johnson, A
   Vong, S
   Lee, K
   Bates, D
   Neri, F
   Diegel, M
   Canfield, T
   Sabo, PJ
   Wilken, MS
   Reh, TA
   Giste, E
   Shafer, A
   Kutyavin, T
   Haugen, E
   Dunn, D
   Reynolds, AP
   Neph, S
   Humbert, R
   Hansen, RS
   De Bruijn, M
   Selleri, L
   Rudensky, A
   Josefowicz, S
   Samstein, R
   Eichler, EE
   Orkin, SH
   Levasseur, D
   Papayannopoulou, T
   Chang, KH
   Skoultchi, A
   Gosh, S
   Disteche, C
   Treuting, P
   Wang, Y
   Weiss, MJ
   Blobel, GA
   Cao, X
   Zhong, S
   Wang, T
   Good, PJ
   Lowdon, RF
   Adams, LB
   Zhou, XQ
   Pazin, MJ
   Feingold, EA
   Wold, B
   Taylor, J
   Mortazavi, A
   Weissman, SM
   Stamatoyannopoulos, JA
   Snyder, MP
   Guigo, R
   Gingeras, TR
   Gilbert, DM
   Hardison, RC
   Beer, MA
   Ren, B
AF Yue, Feng
   Cheng, Yong
   Breschi, Alessandra
   Vierstra, Jeff
   Wu, Weisheng
   Ryba, Tyrone
   Sandstrom, Richard
   Ma, Zhihai
   Davis, Carrie
   Pope, Benjamin D.
   Shen, Yin
   Pervouchine, Dmitri D.
   Djebali, Sarah
   Thurman, Robert E.
   Kaul, Rajinder
   Rynes, Eric
   Kirilusha, Anthony
   Marinov, Georgi K.
   Williams, Brian A.
   Trout, Diane
   Amrhein, Henry
   Fisher-Aylor, Katherine
   Antoshechkin, Igor
   DeSalvo, Gilberto
   See, Lei-Hoon
   Fastuca, Meagan
   Drenkow, Jorg
   Zaleski, Chris
   Dobin, Alex
   Prieto, Pablo
   Lagarde, Julien
   Bussotti, Giovanni
   Tanzer, Andrea
   Denas, Olgert
   Li, Kanwei
   Bender, M. A.
   Zhang, Miaohua
   Byron, Rachel
   Groudine, Mark T.
   McCleary, David
   Pham, Long
   Ye, Zhen
   Kuan, Samantha
   Edsall, Lee
   Wu, Yi-Chieh
   Rasmussen, Matthew D.
   Bansal, Mukul S.
   Kellis, Manolis
   Keller, Cheryl A.
   Morrissey, Christapher S.
   Mishra, Tejaswini
   Jain, Deepti
   Dogan, Nergiz
   Harris, Robert S.
   Cayting, Philip
   Kawli, Trupti
   Boyle, Alan P.
   Euskirchen, Ghia
   Kundaje, Anshul
   Lin, Shin
   Lin, Yiing
   Jansen, Camden
   Malladi, Venkat S.
   Cline, Melissa S.
   Erickson, Drew T.
   Kirkup, Vanessa M.
   Learned, Katrina
   Sloan, Cricket A.
   Rosenbloom, Kate R.
   De Sousa, Beatriz Lacerda
   Beal, Kathryn
   Pignatelli, Miguel
   Flicek, Paul
   Lian, Jin
   Kahveci, Tamer
   Lee, Dongwon
   Kent, W. James
   Santos, Miguel Ramalho
   Herrero, Javier
   Notredame, Cedric
   Johnson, Audra
   Vong, Shinny
   Lee, Kristen
   Bates, Daniel
   Neri, Fidencio
   Diegel, Morgan
   Canfield, Theresa
   Sabo, Peter J.
   Wilken, Matthew S.
   Reh, Thomas A.
   Giste, Erika
   Shafer, Anthony
   Kutyavin, Tanya
   Haugen, Eric
   Dunn, Douglas
   Reynolds, Alex P.
   Neph, Shane
   Humbert, Richard
   Hansen, R. Scott
   De Bruijn, Marella
   Selleri, Licia
   Rudensky, Alexander
   Josefowicz, Steven
   Samstein, Robert
   Eichler, Evan E.
   Orkin, Stuart H.
   Levasseur, Dana
   Papayannopoulou, Thalia
   Chang, Kai-Hsin
   Skoultchi, Arthur
   Gosh, Srikanta
   Disteche, Christine
   Treuting, Piper
   Wang, Yanli
   Weiss, Mitchell J.
   Blobel, Gerd A.
   Cao, Xiaoyi
   Zhong, Sheng
   Wang, Ting
   Good, Peter J.
   Lowdon, Rebecca F.
   Adams, Leslie B.
   Zhou, Xiao-Qiao
   Pazin, Michael J.
   Feingold, Elise A.
   Wold, Barbara
   Taylor, James
   Mortazavi, Ali
   Weissman, Sherman M.
   Stamatoyannopoulos, John A.
   Snyder, Michael P.
   Guigo, Roderic
   Gingeras, Thomas R.
   Gilbert, David M.
   Hardison, Ross C.
   Beer, Michael A.
   Ren, Bing
TI A comparative encyclopedia of DNA elements in the mouse genome
SO NATURE
LA English
DT Article
ID pervasive transcription; evolutionary dynamics; chromatin landscape; gene; reveals; differentiation; divergence; domains; models
AB The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.
C1 [Yue, Feng; Shen, Yin; McCleary, David; Pham, Long; Ye, Zhen; Kuan, Samantha; Edsall, Lee; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Yue, Feng; Shen, Yin; McCleary, David; Pham, Long; Ye, Zhen; Kuan, Samantha; Edsall, Lee; Ren, Bing] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
   [Yue, Feng] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
   [Cheng, Yong; Ma, Zhihai; Cayting, Philip; Kawli, Trupti; Boyle, Alan P.; Euskirchen, Ghia; Kundaje, Anshul; Lin, Shin; Lin, Yiing; Malladi, Venkat S.; Erickson, Drew T.; Sloan, Cricket A.; Snyder, Michael P.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Breschi, Alessandra; Pervouchine, Dmitri D.; Djebali, Sarah; Prieto, Pablo; Lagarde, Julien; Bussotti, Giovanni; Tanzer, Andrea; Notredame, Cedric; Guigo, Roderic] Ctr Genom Regulat, Barcelona 08003, Catalonia, Spain.
   [Breschi, Alessandra; Pervouchine, Dmitri D.; Djebali, Sarah; Prieto, Pablo; Lagarde, Julien; Bussotti, Giovanni; Tanzer, Andrea; Notredame, Cedric; Guigo, Roderic] UPF, Barcelona 08003, Catalonia, Spain.
   [Vierstra, Jeff; Sandstrom, Richard; Thurman, Robert E.; Kaul, Rajinder; Rynes, Eric; Johnson, Audra; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Canfield, Theresa; Sabo, Peter J.; Giste, Erika; Shafer, Anthony; Kutyavin, Tanya; Haugen, Eric; Dunn, Douglas; Reynolds, Alex P.; Neph, Shane; Humbert, Richard; Hansen, R. Scott; Eichler, Evan E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Wu, Weisheng; Keller, Cheryl A.; Morrissey, Christapher S.; Mishra, Tejaswini; Jain, Deepti; Dogan, Nergiz; Harris, Robert S.; Hardison, Ross C.] Penn State Univ, Huck Inst,Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Ryba, Tyrone; Pope, Benjamin D.; Gilbert, David M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
   [Davis, Carrie; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Zaleski, Chris; Dobin, Alex; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Kirilusha, Anthony; Marinov, Georgi K.; Williams, Brian A.; Trout, Diane; Amrhein, Henry; Fisher-Aylor, Katherine; Antoshechkin, Igor; DeSalvo, Gilberto; Wold, Barbara] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Tanzer, Andrea] Univ Vienna, Fac Chem, Dept Theoret Chem, A-1090 Vienna, Austria.
   [Denas, Olgert; Li, Kanwei; Taylor, James] Emory Univ, O Wayne Rollins Res Ctr, Dept Biol, Atlanta, GA 30322 USA.
   [Denas, Olgert; Li, Kanwei; Taylor, James] Emory Univ, O Wayne Rollins Res Ctr, Dept Math & Comp Sci, Atlanta, GA 30322 USA.
   [Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Bender, M. A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Zhang, Miaohua; Byron, Rachel; Groudine, Mark T.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Groudine, Mark T.] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA.
   [Wu, Yi-Chieh; Rasmussen, Matthew D.; Bansal, Mukul S.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Kellis, Manolis] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Jansen, Camden; Mortazavi, Ali] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
   [Cline, Melissa S.; Kirkup, Vanessa M.; Learned, Katrina; Rosenbloom, Kate R.; Kent, W. James] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [De Sousa, Beatriz Lacerda; Santos, Miguel Ramalho] Univ Calif San Francisco, Dept Obstet Gynecol, San Francisco, CA 94143 USA.
   [De Sousa, Beatriz Lacerda; Santos, Miguel Ramalho] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [De Sousa, Beatriz Lacerda; Santos, Miguel Ramalho] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA.
   [Beal, Kathryn; Pignatelli, Miguel; Flicek, Paul; Herrero, Javier; Levasseur, Dana] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Lian, Jin; Weissman, Sherman M.] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
   [Kahveci, Tamer] Univ Florida, Gainesville, FL 32611 USA.
   [Lee, Dongwon; Beer, Michael A.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Lee, Dongwon; Beer, Michael A.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA.
   [Herrero, Javier] UCL, UCL Canc Inst, Bill Lyons Informat Ctr, London WC1E 6DD, England.
   [Wilken, Matthew S.; Reh, Thomas A.; Wang, Yanli] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA.
   [De Bruijn, Marella] Univ Oxford, MRC Mol Haemotol Unit, Oxford OX3 9DS, England.
   [Selleri, Licia] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.
   [Rudensky, Alexander; Josefowicz, Steven; Samstein, Robert] Mem Sloan Kettering Canc Ctr, Program Immunol, HHMI & Ludwig Ctr, New York, NY 10065 USA.
   [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
   [Levasseur, Dana] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
   [Papayannopoulou, Thalia; Chang, Kai-Hsin] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA.
   [Skoultchi, Arthur; Gosh, Srikanta] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
   [Disteche, Christine] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Treuting, Piper] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
   [Wang, Yanli] Penn State Univ, Bioinformat & Genom Program, University Pk, PA 16802 USA.
   [Weiss, Mitchell J.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA.
   [Blobel, Gerd A.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
   [Blobel, Gerd A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Cao, Xiaoyi; Zhong, Sheng] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Wang, Ting] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, Dept Genet, St Louis, MO 63108 USA.
   [Good, Peter J.; Lowdon, Rebecca F.; Adams, Leslie B.; Zhou, Xiao-Qiao; Pazin, Michael J.; Feingold, Elise A.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Ludwig Institute for Cancer Research; University of California System; University of California San Diego; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; Stanford University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; University of Washington; University of Washington Seattle; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; State University System of Florida; Florida State University; Cold Spring Harbor Laboratory; California Institute of Technology; University of Vienna; Emory University; Emory University; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of California System; University of California Irvine; University of California System; University of California Santa Cruz; 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; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Yale University; State University System of Florida; University of Florida; Johns Hopkins University; Johns Hopkins University; University of London; University College London; University of Washington; University of Washington Seattle; University of Oxford; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Iowa; University of Washington; University of Washington Seattle; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; St Jude Children's Research Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of California System; University of California San Diego; Washington University (WUSTL); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Ren, B (corresponding author), Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM jstam@u.washington.edu; mpsnyder@stanford.edu; roderic.guigo@crg.cat; gingeras@cshl.edu; gilbert@bio.fsu.edu; ross@bx.psu.edu; mbeer@jhu.edu; biren@ucsd.edu
FU National Institutes of Health [R01HG003991, 1U54HG007004, 3RC2HG005602, GM083337, GM085354, F31CA165863, RC2HG005573, R01DK065806]; Spanish Plan Nacional [BIO2011-26205]; ERC [BIO2011-26205, 294653]; National Science Foundation Graduate Research Fellowship [DGE-071824]; Wellcome Trust [095908]; NHGRI [U01HG004695];  [R01HD043997-09];  [F32HL110473];  [K99HL119617]; Direct For Biological Sciences; Div Of Biological Infrastructure [0644282] Funding Source: National Science Foundation; European Research Council (ERC) [294653] Funding Source: European Research Council (ERC); Medical Research Council [MC_UU_12009/2] Funding Source: researchfish; National Cancer Institute [P30CA008748, P30CA045508] Funding Source: NIH RePORTER; National Eye Institute [R01EY021482] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG007175] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM083337] Funding Source: NIH RePORTER; MRC [MC_UU_12009/2] Funding Source: UKRI
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NR 71
TC 1298
Z9 1566
U1 1
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 NOV 20
PY 2014
VL 515
IS 7527
BP 355
EP +
DI 10.1038/nature13992
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600034
PM 25409824
DA 2026-03-09
ER

PT J
AU Zhang, J
   Zhang, KH
   Gao, ZG
   Paoletta, S
   Zhang, DD
   Han, GW
   Li, TT
   Ma, LM
   Zhang, WR
   Müller, CE
   Yang, HY
   Jiang, HL
   Cherezov, V
   Katritch, V
   Jacobson, KA
   Stevens, RC
   Wu, BL
   Zhao, Q
AF Zhang, Jin
   Zhang, Kaihua
   Gao, Zhan-Guo
   Paoletta, Silvia
   Zhang, Dandan
   Han, Gye Won
   Li, Tingting
   Ma, Limin
   Zhang, Wenru
   Mueller, Christa E.
   Yang, Huaiyu
   Jiang, Hualiang
   Cherezov, Vadim
   Katritch, Vsevolod
   Jacobson, Kenneth A.
   Stevens, Raymond C.
   Wu, Beili
   Zhao, Qiang
TI Agonist-bound structure of the human P2Y12 receptor
SO NATURE
LA English
DT Article
ID protein-coupled receptor; muscarinic acetylcholine-receptor; resolution crystal-structure; a(2a) adenosine receptor; membrane-proteins; identification; antagonists; activation; rhodopsin; complex
AB The P2Y(12) receptor (P2Y(12)R), one of eight members of the P2YR family expressed in humans, is one of the most prominent clinical drug targets for inhibition of platelet aggregation. Although mutagenesis and modelling studies of the P2Y(12)R provided useful insights into ligand binding(1-4), the agonist and antagonist recognition and function at the P2Y(12)R remain poorly understood at the molecular level. Here we report the structures of the human P2Y(12)R in complex with the full agonist 2-methylthio-adenosine-5'-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 angstrom resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5'-triphosphate (2MeSATP) at 3.1 angstrom resolution. These structures, together with the structure of the P2Y(12)R with antagonist ethyl 6-(4-((benzylsulfonyl) carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283)(5), reveal striking conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions. Further analysis of these changes provides insight into a distinct ligand binding landscape inthed-group of class AG-protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y(12)R, with only partially overlapped binding pockets. The agonist-bound P2Y(12)R structure answers long-standing questions surrounding P2Y(12)R-agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example, to our knowledge, of a GPCR in which agonist access to the binding pocket requires large-scale rearrangements in the highly malleable extracellular region, the structural and docking studies will therefore provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y(12)R and potentially for other closely related P2YRs.
C1 [Zhang, Jin; Zhang, Kaihua; Zhang, Dandan; Li, Tingting; Ma, Limin; Zhang, Wenru; Wu, Beili; Zhao, Qiang] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China.
   [Gao, Zhan-Guo; Paoletta, Silvia; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Han, Gye Won; Cherezov, Vadim; Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, D-53121 Bonn, Germany.
   [Yang, Huaiyu; Jiang, Hualiang] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China.
   [Stevens, Raymond C.] ShanghaiTech Univ, IHuman Inst, Shanghai 201203, Peoples R China.
C3 Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Scripps Research Institute; University of Bonn; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; ShanghaiTech University
RP Wu, BL (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China.
EM beiliwu@simm.ac.cn; zhaoq@simm.ac.cn
FU National Basic Research Program of China [2012CB910400, 2012CB518000, 2014CB910400]; National Institutes of Health [R01AI100604, U54 GM094618]; National Science Foundation of China [31370729]; National Science and Technology Major Project [2013ZX09507001, 2012ZX09301001]; National Institutes of Health NIDDK Intramural Research Program; National Natural Science Foundation of China [91313000]; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK031116, ZIADK031126] Funding Source: NIH RePORTER
NR 34
TC 280
Z9 319
U1 1
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 MAY 1
PY 2014
VL 509
IS 7498
BP 119
EP 122
DI 10.1038/nature13288
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100051
PM 24784220
DA 2026-03-09
ER

PT J
AU Wolff, SBE
   Gründemann, J
   Tovote, P
   Krabbe, S
   Jacobson, GA
   Müller, C
   Herry, C
   Ehrlich, I
   Friedrich, RW
   Letzkus, JJ
   Lüthi, A
AF Wolff, Steffen B. E.
   Gruendemann, Jan
   Tovote, Philip
   Krabbe, Sabine
   Jacobson, Gilad A.
   Mueller, Christian
   Herry, Cyril
   Ehrlich, Ingrid
   Friedrich, Rainer W.
   Letzkus, Johannes J.
   Luethi, Andreas
TI Amygdala interneuron subtypes control fear learning through disinhibition
SO NATURE
LA English
DT Article
ID rat basolateral amygdala; gabaergic neurons; lateral nucleus; circuit; somatostatin; inhibition; networks; identification; organization; acquisition
AB Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral amygdala, interneurons expressing parvalbumin (PV) and somatostatin (SOM) bidirectionally control the acquisition of fear conditioning-a simple form of associative learning-through two distinct disinhibitory mechanisms. During an auditory cue, PV+ interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM+ interneurons, thereby enhancing auditory responses and promoting cue-shock associations. During an aversive footshock, however, both PV+ and SOM+ interneurons are inhibited, which boosts postsynaptic footshock responses and gates learning. These results demonstrate that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local interneurons.
C1 [Wolff, Steffen B. E.; Gruendemann, Jan; Tovote, Philip; Krabbe, Sabine; Jacobson, Gilad A.; Mueller, Christian; Friedrich, Rainer W.; Letzkus, Johannes J.; Luethi, Andreas] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Wolff, Steffen B. E.] Univ Basel, CH-4000 Basel, Switzerland.
   [Herry, Cyril] INSERM, U862, Neuroctr Magendie, F-33077 Bordeaux, France.
   [Ehrlich, Ingrid] Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital
RP Lüthi, A (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM johannes.letzkus@brain.mpg.de; andreas.luthi@fmi.ch
FU Novartis Research Foundation; National Center of Competences in Research: 'SYNAPSY-The Synaptic Bases of Mental Diseases' - (Swiss National Science Foundation); SNSF core grant; Schering Foundation Fellowship; Swiss National Science Foundation Ambizione Fellowship; EMBO Long-Term Fellowships; Marie Curie Action Fellowships
NR 58
TC 381
Z9 474
U1 3
U2 145
PU NATURE PUBLISHING 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 22
PY 2014
VL 509
IS 7501
BP 453
EP +
DI 10.1038/nature13258
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000031
PM 24814341
DA 2026-03-09
ER

PT J
AU Ghidiu, M
   Lukatskaya, MR
   Zhao, MQ
   Gogotsi, Y
   Barsoum, MW
AF Ghidiu, Michael
   Lukatskaya, Maria R.
   Zhao, Meng-Qiang
   Gogotsi, Yury
   Barsoum, Michel W.
TI Conductive two-dimensional titanium carbide 'clay' with high volumetric capacitance
SO NATURE
LA English
DT Article
ID electrochemical energy-storage; intercalation; oxide; dense
AB Safe and powerful energy storage devices are becoming increasingly important. Charging times of seconds to minutes, with power densities exceeding those of batteries, can in principle be provided by electrochemical capacitors in particular, pseudocapacitors(1,2). Recent research has focused mainly on improving the gravimetric performance of the electrodes of such systems, but for portable electronics and vehicles volume is at a premium(3). The best volumetric capacitances of carbon-based electrodes are around 300 farads per cubic centimetre(4,5); hydrated ruthenium oxide can reach capacitances of 1,000 to 1,500 farads per cubic centimetre with great cydability, but only in thin films(6) Recently, electrodes made of two-dimensional titanium carbide (Ti3C2, a member of the 'MXene' family), produced by etching aluminium from titanium aluminium carbide (Ti3AlC2, a 'MAX' phase) in concentrated hydrofluoric acid, have been shown to have volumetric capacitances of over 300 farads per cubic centimetre(7,8). Here we report a method of producing this material using a solution of lithium fluoride and hydrochloric acid. The resulting hydrophilic material swells in volume when hydrated, and can be shaped like clay and dried into a highly conductive solid or rolled into films tens of micrometres thick. Additive-free films of this titanium carbide 'clay' have volumetric capacitances of up to 900 farads per cubic centimetre, with excellent cyclability and rate performances. This capacitance is almost twice that of our previous report(8), and our synthetic method also offers a much faster route to film production as well as the avoidance of handling hazardous concentrated hydrofluoric acid.
C1 [Ghidiu, Michael; Lukatskaya, Maria R.; Zhao, Meng-Qiang; Gogotsi, Yury; Barsoum, Michel W.] Drexel Univ, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
   [Ghidiu, Michael; Lukatskaya, Maria R.; Zhao, Meng-Qiang; Gogotsi, Yury; Barsoum, Michel W.] Drexel Univ, AJ Drexel Nanomat Inst, Philadelphia, PA 19104 USA.
C3 Drexel University; Drexel University
RP Gogotsi, Y (corresponding author), Drexel Univ, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
EM gogotsi@drexel.edu; barsoumw@drexel.edu
FU US National Science Foundation [DMR-1310245]; Fluid Interface Reactions, Structures and Transport (FIRST) Center, an Energy Frontier Research Center - US Department of Energy, Office of Science, and Office of Basic Energy Sciences; Direct For Mathematical & Physical Scien; Division Of Materials Research [1310245] Funding Source: National Science Foundation
NR 30
TC 5156
Z9 5635
U1 170
U2 6482
PU NATURE PUBLISHING 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 4
PY 2014
VL 516
IS 7529
BP 78
EP U171
DI 10.1038/nature13970
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800042
PM 25470044
DA 2026-03-09
ER

PT J
AU Zhou, YX
   Zhu, SY
   Cai, CZ
   Yuan, PF
   Li, CM
   Huang, YY
   Wei, WS
AF Zhou, Yuexin
   Zhu, Shiyou
   Cai, Changzu
   Yuan, Pengfei
   Li, Chunmei
   Huang, Yanyi
   Wei, Wensheng
TI High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells
SO NATURE
LA English
DT Article
ID capillary morphogenesis protein-2; receptor; nuclease; lethality
AB Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications(1-7). In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed(8,9). Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.
C1 [Zhou, Yuexin; Zhu, Shiyou; Cai, Changzu; Yuan, Pengfei; Wei, Wensheng] Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
   [Li, Chunmei; Huang, Yanyi] Peking Univ, Biodynam Opt Imaging Ctr BIOPIC, Coll Engn, Beijing 100871, Peoples R China.
C3 Peking University; Peking University
RP Wei, WS (corresponding author), Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
EM wswei@pku.edu.cn
FU National Basic Research Program of China [2010CB911800]; National Science Foundation of China [NSFC31170126, NSFC31070115]; Peking-Tsinghua Centre for Life Sciences
NR 26
TC 578
Z9 821
U1 5
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 MAY 22
PY 2014
VL 509
IS 7501
BP 487
EP +
DI 10.1038/nature13166
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4VE
UT WOS:000336126000038
PM 24717434
DA 2026-03-09
ER

PT J
AU Feng, Y
   Krumholz, MR
AF Feng, Yi
   Krumholz, Mark R.
TI Early turbulent mixing as the origin of chemical homogeneity in open star clusters
SO NATURE
LA English
DT Article
ID comprehensive abundance analysis; adaptive mesh refinement; h ii regions; elemental abundance; red giants; milky-way; evolution; fragmentation; signatures; collapse
AB The abundances of elements in stars are critical clues to stars' origins. Observed star-to-star variations in logarithmic abundance within an open star cluster-a gravitationally bound ensemble of stars in the Galactic plane-are typically only about 0.01 to 0.05 over many elements(1-9), which is noticeably smaller than the variation of about 0.06 to 0.3 seen in the interstellar medium from which the stars form(10-14). It is unknown why star clusters are so homogenous, and whether homogeneity should also prevail in regions of lower star formation efficiency that do not produce bound clusters. Here we report simulations that trace the mixing of chemical elements as star-forming clouds assemble and collapse. We show that turbulent mixing during cloud assembly naturally produces a stellar abundance scatter at least five times smaller than that in the gas, which is sufficient to explain the observed chemical homogeneity of stars. Moreover, mixing occurs very early, so that regions with star formation efficiencies of about 10 per cent are nearly as well mixed as those with formation efficiencies of about 50 per cent. This implies that even regions that do not form bound clusters are likely to be well mixed, and improves the prospects of using 'chemical tagging' to reconstruct (via their unique chemical signatures, or tags) star clusters whose constituent stars have become unbound from one another and spread across the Galactic disk.
C1 [Feng, Yi; Krumholz, Mark R.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz
RP Krumholz, MR (corresponding author), Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
EM mkrumhol@ucsc.edu
FU NSF [AST-0955300, AST-1405962, AST-1229745]; NASA ATP [NNX13AB84G]; NASA TCAN [NNX14AB52G]; NASA through Space Telescope Science Institute [13256]; NASA [NAS 5-26555]; NASA [686542, NNX14AB52G] Funding Source: Federal RePORTER; Direct For Mathematical & Physical Scien [0955300] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1229745] Funding Source: National Science Foundation; Division Of Astronomical Sciences [0955300] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1405962] Funding Source: National Science Foundation
NR 38
TC 79
Z9 87
U1 1
U2 10
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 25
PY 2014
VL 513
IS 7519
BP 523
EP +
DI 10.1038/nature13662
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800034
PM 25174709
DA 2026-03-09
ER

PT J
AU Cong, PY
   Ma, XY
   Hou, XG
   Edgecombe, GD
   Strausfeld, NJ
AF Cong, Peiyun
   Ma, Xiaoya
   Hou, Xianguang
   Edgecombe, Gregory D.
   Strausfeld, Nicholas J.
TI Brain structure resolves the segmental affinity of anomalocaridid appendages
SO NATURE
LA English
DT Article
ID burgess shale; arthropod; evolution; onychophora; origin; peripatopsidae; organization; morphology; suggests; labrum
AB Despite being among the most celebrated taxa from Cambrian biotas, anomalocaridids (order Radiodonta) have provoked intense debate about their affinities within the moulting-animal clade that includes Arthropoda. Current alternatives identify anomalocaridids as either stem-group euarthropods(1-3), crown-group euarthropods near the ancestry of chelicerates(4), or a segmented ecdysozoan lineage with convergent similarity to arthropods in appendage construction(5). Determining unambiguous affinities has been impeded by uncertainties about the segmental affiliation of anomalocaridid frontal appendages. These structures are variably homologized with jointed appendages of the second (deutocerebral) head segment, including antennae and 'great appendages' of Cambrian arthropods, or with the paired antenniform frontal appendages of living Onychophora and some Cambrian lobopodians. Here we describe Lyrarapax unguis-pinus, a new anomalocaridid from the early Cambrian Chengjiang biota, southwest China, nearly complete specimens of which preserve traces of muscles, digestive tract and brain. The traces of brain provide the first direct evidence for the segmental composition of the anomalocaridid head and its appendicular organization. Carbon-rich areas in the head resolve paired pre-protocerebral ganglia at the origin of paired frontal appendages. The ganglia connect to areas indicative of a bilateral pre-oral brain that receives projections from the eyestalk neuropils and compound retina. The dorsal, segmented brain of L. unguispinus reinforces an alliance between anomalocaridids and arthropods rather than cycloneuralians. Correspondences in brain organization between anomalocaridids and Onychophora resolve pre-protocerebral ganglia, associated with pre-ocular frontal appendages, as characters of the last common ancestor of euarthropods and onychophorans. A position of Radiodonta on the euarthropod stem-lineage implies the transformation of frontal appendages to another structure in crown-group euarthropods, with gene expression and neuroanatomy providing strong evidence that the paired, pre-oral labrum is the remnant of paired frontal appendages(1).
C1 [Cong, Peiyun; Ma, Xiaoya; Hou, Xianguang] Yunnan Univ, Yunnan Key Lab Palaeobiol, Kunming 650091, Peoples R China.
   [Ma, Xiaoya; Edgecombe, Gregory D.] Nat Hist Museum, Dept Earth Sci, London SW7 5BD, England.
   [Strausfeld, Nicholas J.] Univ Arizona, Dept Neurosci, Tucson, AZ 85721 USA.
   [Strausfeld, Nicholas J.] Univ Arizona, Ctr Insect Sci, Tucson, AZ 85721 USA.
C3 Yunnan University; Natural History Museum London; University of Arizona; University of Arizona
RP Hou, XG (corresponding author), Yunnan Univ, Yunnan Key Lab Palaeobiol, Kunming 650091, Peoples R China.
EM xghou@ynu.edu.cn; flybrain@neurobio.arizona.edu
FU National Natural Science Foundation of China [U1302232, 41372031, 40962001]; Leverhulme Trust [F/00 696/T]; Center for Insect Science, University of Arizona; Air Force Research Laboratory [FA86511010001]; NERC [NE/L011751/1] Funding Source: UKRI; Natural Environment Research Council [NE/L011751/1] Funding Source: researchfish
NR 28
TC 142
Z9 156
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 SEP 25
PY 2014
VL 513
IS 7519
BP 538
EP +
DI 10.1038/nature13486
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800038
PM 25043032
DA 2026-03-09
ER

PT J
AU Dickson, VK
   Pedi, L
   Long, SB
AF Dickson, Veronica Kane
   Pedi, Leanne
   Long, Stephen B.
TI Structure and insights into the function of a Ca2+-activated Cl- channel
SO NATURE
LA English
DT Article
ID vitelliform macular dystrophy; chloride channel; crystal-structure; mouse bestrophin-2; aromatic rings; family; protein; gene; mutations; release
AB Bestrophin calcium-activated chloride channels (CaCCs) regulate the flow of chloride and other monovalent anions across cellular membranes in response to intracellular calcium (Ca2+) levels. Mutations in bestrophin 1 (BEST1) cause certain eye diseases. Here we present X-ray structures of chicken BEST1-Fab complexes, at 2.85 angstrom resolution, with permeant anions and Ca2+. Representing, to our knowledge, the first structure of a CaCC, the eukaryotic BEST1 channel, which recapitulates CaCC function in liposomes, is formed from a pentameric assembly of subunits. Ca2+ binds to the channel's large cytosolic region. A single ion pore, approximately 95 angstrom in length, is located along the central axis and contains at least 15 binding sites for anions. A hydrophobic neck within the pore probably forms the gate. Phenylalanine residues within it may coordinate permeating anions via anion-pi interactions. Conformational changes observed near the 'Ca2+ clasp' hint at the mechanism of Ca2+-dependent gating. Disease-causing mutations are prevalent within the gating apparatus.
C1 [Dickson, Veronica Kane; Pedi, Leanne; Long, Stephen B.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center
RP Long, SB (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, 1275 York Ave, New York, NY 10065 USA.
EM Longs@mskcc.org
FU Burroughs Wellcome Career Award in the Biomedical Sciences; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 62
TC 178
Z9 194
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 DEC 11
PY 2014
VL 516
IS 7530
BP 213
EP +
DI 10.1038/nature13913
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500037
PM 25337878
DA 2026-03-09
ER

PT J
AU Ho, JWK
   June, YL
   Liu, T
   Alver, BH
   Lee, S
   Ikegami, K
   Sohn, KA
   Minoda, A
   Tolstorukov, MY
   Appert, A
   Parker, SCJ
   Gu, TT
   Kundaje, A
   Riddle, NC
   Bishop, E
   Egelhofer, TA
   Hu, SS
   Alekseyenko, AA
   Rechtsteiner, A
   Asker, D
   Belsky, JA
   Bowmanm, SK
   Chens, QB
   Chen, RAJ
   Day, DS
   Dong, Y
   Dose, AC
   Duan, XK
   Epstein, CB
   Ercan, S
   Feingold, EA
   Ferrari, F
   Garrigues, JM
   Gehlenborg, N
   Good, PJ
   Haseley, P
   He, D
   Herrmann, M
   Hoffman, MM
   Jeffers, TE
   Kharchenko, PV
   Kolasinska-Zwierz, P
   Kotwaliwale, CV
   Kumar, N
   Langley, SA
   Larschan, EN
   Latorre, I
   Libbrecht, MW
   Lin, XQ
   Park, R
   Pazin, MJ
   Pham, HN
   Plachetka, A
   Qin, B
   Schwartz, YB
   Shoresh, N
   Stempor, P
   Vielle, A
   Wang, CY
   Whittle, CM
   Xue, HL
   Kingstonm, RE
   Kim, JH
   Bernstein, BE
   Dernburg, AF
   Pirrotta, V
   Kuroda, MI
   Noble, WS
   Tullius, TD
   Kellis, M
   MacAlpine, DM
   Strome, S
   Elgin, SCR
   Liu, XS
   Lieb, JD
   Ahringer, J
   Karpen, GH
   Park, PJ
AF Ho, Joshua W. K.
   June, Youngsook L.
   Liu, Tao
   Alver, Burak H.
   Lee, Soohyun
   Ikegami, Kohta
   Sohn, Kyung-Ah
   Minoda, Aki
   Tolstorukov, Michael Y.
   Appert, Alex
   Parker, Stephen C. J.
   Gu, Tingting
   Kundaje, Anshul
   Riddle, Nicole C.
   Bishop, Eric
   Egelhofer, Thea A.
   Hu, Sheng'en Shawn
   Alekseyenko, Artyom A.
   Rechtsteiner, Andreas
   Asker, Dalal
   Belsky, Jason A.
   Bowmanm, Sarah K.
   Chens, Q. Brent
   Chen, Ron A. -J.
   Day, Daniel S.
   Dong, Yan
   Dose, Andrea C.
   Duan, Xikun
   Epstein, Charles B.
   Ercan, Sevinc
   Feingold, Elise A.
   Ferrari, Francesco
   Garrigues, Jacob M.
   Gehlenborg, Nils
   Good, Peter J.
   Haseley, Psalm
   He, Daniel
   Herrmann, Moritz
   Hoffman, Michael M.
   Jeffers, Tess E.
   Kharchenko, Peter V.
   Kolasinska-Zwierz, Paulina
   Kotwaliwale, Chitra V.
   Kumar, Nischay
   Langley, Sasha A.
   Larschan, Erica N.
   Latorre, Isabel
   Libbrecht, Maxwell W.
   Lin, Xueqiu
   Park, Richard
   Pazin, Michael J.
   Pham, Hoang N.
   Plachetka, Annette
   Qin, Bo
   Schwartz, Yuri B.
   Shoresh, Noam
   Stempor, Przemyslaw
   Vielle, Anne
   Wang, Chengyang
   Whittle, Christina M.
   Xue, Huiling
   Kingstonm, Robert E.
   Kim, Ju Han
   Bernstein, Bradley E.
   Dernburg, Abby F.
   Pirrotta, Vincenzo
   Kuroda, Mitzi I.
   Noble, William S.
   Tullius, Thomas D.
   Kellis, Manolis
   MacAlpine, David M.
   Strome, Susan
   Elgin, Sarah C. R.
   Liu, Xiaole Shirley
   Lieb, Jason D.
   Ahringer, Julie
   Karpen, Gary H.
   Park, Peter J.
TI Comparative analysis of metazoan chromatin organization
SO NATURE
LA English
DT Article
ID centromeric chromatin; genome; transcription; methylation
AB Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
C1 [Ho, Joshua W. K.; June, Youngsook L.; Alver, Burak H.; Lee, Soohyun; Tolstorukov, Michael Y.; Bishop, Eric; Day, Daniel S.; Ferrari, Francesco; Gehlenborg, Nils; Haseley, Psalm; Kharchenko, Peter V.; Park, Richard; Xue, Huiling; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Ho, Joshua W. K.; June, Youngsook L.; Tolstorukov, Michael Y.; Alekseyenko, Artyom A.; Haseley, Psalm; Plachetka, Annette; Xue, Huiling; Kuroda, Mitzi I.; Park, Peter J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA.
   [Liu, Tao; Liu, Xiaole Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
   [Liu, Tao; Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Liu, Tao; Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
   [Ikegami, Kohta; Chens, Q. Brent; Ercan, Sevinc; Jeffers, Tess E.; Lieb, Jason D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Ikegami, Kohta; Chens, Q. Brent; Ercan, Sevinc; Jeffers, Tess E.; Lieb, Jason D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Sohn, Kyung-Ah] Ajou Univ, Dept Informat & Comp Engn, Suwon 443749, South Korea.
   [Sohn, Kyung-Ah; Kim, Ju Han] Seoul Natl Univ, Coll Med, Syst Biomed Informat Res Ctr, Seoul 110799, South Korea.
   [Minoda, Aki; Langley, Sasha A.; Pham, Hoang N.; Vielle, Anne; Dernburg, Abby F.; Karpen, Gary H.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Dept Genome Dynam, Berkeley, CA 94720 USA.
   [Minoda, Aki; He, Daniel; Kotwaliwale, Chitra V.; Langley, Sasha A.; Pham, Hoang N.; Whittle, Christina M.; Dernburg, Abby F.; Karpen, Gary H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Tolstorukov, Michael Y.; Bowmanm, Sarah K.; Kingstonm, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Tolstorukov, Michael Y.; Bowmanm, Sarah K.; Kingstonm, Robert E.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Appert, Alex; Chen, Ron A. -J.; Dong, Yan; Herrmann, Moritz; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Stempor, Przemyslaw; Vielle, Anne; Ahringer, Julie] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
   [Appert, Alex; Chen, Ron A. -J.; Dong, Yan; Herrmann, Moritz; Kolasinska-Zwierz, Paulina; Latorre, Isabel; Stempor, Przemyslaw; Vielle, Anne; Ahringer, Julie] Univ Cambridge, Dept Genet, Cambridge CB2 1QN, England.
   [Parker, Stephen C. J.] NIGMS, NIH, Bethesda, MD 20892 USA.
   [Parker, Stephen C. J.; Feingold, Elise A.; Good, Peter J.; Pazin, Michael J.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Gu, Tingting; Riddle, Nicole C.; Elgin, Sarah C. R.] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
   [Kundaje, Anshul; Kumar, Nischay; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Alver, Burak H.; Kundaje, Anshul; Epstein, Charles B.; Gehlenborg, Nils; Kumar, Nischay; Shoresh, Noam; Vielle, Anne; Bernstein, Bradley E.; Kellis, Manolis; Liu, Xiaole Shirley] Broad Inst, Cambridge, MA 02141 USA.
   [Bishop, Eric; Park, Richard; Tullius, Thomas D.] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
   [Egelhofer, Thea A.; Rechtsteiner, Andreas; Garrigues, Jacob M.; Strome, Susan] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Hu, Sheng'en Shawn; Duan, Xikun; Lin, Xueqiu; Qin, Bo; Wang, Chengyang] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China.
   [Alekseyenko, Artyom A.; Plachetka, Annette; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Asker, Dalal; Schwartz, Yuri B.; Pirrotta, Vincenzo] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA.
   [Asker, Dalal] Univ Alexandria, Fac Agr, Food Sci & Technol Dept, Alexandria 21545, Egypt.
   [Belsky, Jason A.; MacAlpine, David M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Day, Daniel S.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Dose, Andrea C.] Univ Calif Davis, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA.
   [Ercan, Sevinc] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA.
   [Hoffman, Michael M.] Princess Margaret Canc Ctr, Toronto, ON M6G 1L7, Canada.
   [Kotwaliwale, Chitra V.; Pham, Hoang N.; Whittle, Christina M.; Bernstein, Bradley E.; Dernburg, Abby F.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Larschan, Erica N.] Brown Univ, Dept Mol Biol Cellular Biol & Biochem, Providence, RI 02912 USA.
   [Libbrecht, Maxwell W.; Noble, William S.] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA.
   [Schwartz, Yuri B.] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
   [Kim, Ju Han] Seoul Natl Univ, Coll Med, Div Biomed Informat, Seoul Natl Univ Biomed Informat, Seoul 110799, South Korea.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Noble, William S.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Tullius, Thomas D.] Boston Univ, Dept Chem, Boston, MA 02215 USA.
   [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's 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; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Ajou University; Seoul National University (SNU); 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; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Cambridge; University of Cambridge; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Washington University (WUSTL); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Boston University; University of California System; University of California Santa Cruz; Tongji University; Harvard University; Harvard Medical School; Rutgers University System; Rutgers University New Brunswick; Egyptian Knowledge Bank (EKB); Alexandria University; Duke University; Harvard University; University of California System; University of California Davis; New York University; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Howard Hughes Medical Institute; Brown University; University of Washington; University of Washington Seattle; Umea University; Seoul National University (SNU); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Washington; University of Washington Seattle; Boston University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP MacAlpine, DM (corresponding author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
EM david.macalpine@duke.edu; sstrome@ucsc.edu; selgin@biology2.wustl.edu; xsliu@jimmy.harvard.edu; jdlieb@uchicago.edu; ja219@cam.ac.uk; ghkarpen@lbl.gov; peter_park@hms.harvard.edu
FU NHGRI [U01HG004258, U01 HG004270, U01HG004279, U54HG004570, U01HG004695, K99HG006259]; NHBIB [5RL9EB008539]; NIGMS; NIH [U54CA121852]; NSF [1122374]; National Natural Science Foundation of China [31028011]; MEST Korea [MHW-2013-HI13C2164]; Wellcome Trust [54523];  [NRF-2012-0000994]; National Human Genome Research Institute [T32HG002295] Funding Source: NIH RePORTER; NIH Office of the Director [T32HG002295] Funding Source: NIH RePORTER; Div Of Biological Infrastructure; Direct For Biological Sciences [0644282] Funding Source: National Science Foundation
NR 24
TC 278
Z9 338
U1 0
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 AUG 28
PY 2014
VL 512
IS 7515
BP 449
EP U507
DI 10.1038/nature13415
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600038
PM 25164756
DA 2026-03-09
ER

PT J
AU Zhao, LD
   Lo, SH
   Zhang, YS
   Sun, H
   Tan, GJ
   Uher, C
   Wolverton, C
   Dravid, VP
   Kanatzidis, MG
AF Zhao, Li-Dong
   Lo, Shih-Han
   Zhang, Yongsheng
   Sun, Hui
   Tan, Gangjian
   Uher, Ctirad
   Wolverton, C.
   Dravid, Vinayak P.
   Kanatzidis, Mercouri G.
TI Ultralow thermal conductivity and high thermoelectric figure of merit in SnSe crystals
SO NATURE
LA English
DT Article
ID performance bulk thermoelectrics; nanostructures; efficiency; distortion
AB The thermoelectric effect enables direct and reversible conversion between thermal and electrical energy, and provides a viable route for power generation from waste heat. The efficiency of thermoelectric materials is dictated by the dimensionless figure of merit, ZT (where Z is the figure of merit and T is absolute temperature), which governs the Carnot efficiency for heat conversion. Enhancements above the generally high threshold value of 2.5 have important implications for commercial deployment(1,2), especially for compounds free of Pb and Te. Here we report an unprecedented ZT of 2.6 +/- 0.3 at 923 K, realized in SnSe single crystals measured along the b axis of the room-temperature orthorhombic unit cell. This material also shows a high ZT of 2.3 +/- 0.3 along thec axis but a significantly reduced ZT of 0.8 +/- 0.2 along the a axis. We attribute the remarkably high ZT along the b axis to the intrinsically ultralow lattice thermal conductivity in SnSe. The layered structure of SnSe derives from a distorted rock-salt structure, and features anomalously high Gruneisen parameters, which reflect the anharmonic and anisotropic bonding. We attribute the exceptionally low lattice thermal conductivity (0.2 +/- 0.03 Wm(-1) K-1 at 973 K) in SnSe to the anharmonicity. These findings highlight alternative strategies to nanostructuring for achieving high thermoelectric performance.
C1 [Zhao, Li-Dong; Tan, Gangjian; Kanatzidis, Mercouri G.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Lo, Shih-Han; Zhang, Yongsheng; Wolverton, C.; Dravid, Vinayak P.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Sun, Hui; Uher, Ctirad] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
C3 Northwestern University; Northwestern University; University of Michigan System; University of Michigan
RP Kanatzidis, MG (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM m-kanatzidis@northwestern.edu
FU Revolutionary Materials for Solid State Energy Conversion; Energy Frontier Research Center; US Department of Energy, Office of Science [DE-SC0001054]; US Department of Energy, Office of Basic Energy Sciences [DE-SC0001054]; NSF-NSEC; Keck Foundation; State of Illinois; Northwestern University; NSF-MRSEC; U.S. Department of Energy (DOE) [DE-SC0001054] Funding Source: U.S. Department of Energy (DOE)
NR 33
TC 4602
Z9 4995
U1 89
U2 3810
PU NATURE PUBLISHING 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 17
PY 2014
VL 508
IS 7496
BP 373
EP +
DI 10.1038/nature13184
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000047
PM 24740068
DA 2026-03-09
ER

PT J
AU Sandler, VM
   Lis, R
   Liu, Y
   Kedem, A
   James, D
   Elemento, O
   Butler, JM
   Scandura, JM
   Rafii, S
AF Sandler, Vladislav M.
   Lis, Raphael
   Liu, Ying
   Kedem, Alon
   James, Daylon
   Elemento, Olivier
   Butler, Jason M.
   Scandura, Joseph M.
   Rafii, Shahin
TI Reprogramming human endothelial cells to haematopoietic cells requires vascular induction
SO NATURE
LA English
DT Article
ID stem-cells; haemogenic endothelium; angiocrine signals; progenitor cells; self-renewal; cord blood; b-cells; differentiation; regeneration; niche
AB Generating engraftable human haematopoietic cells from autologous tissues is a potential route to new therapies for blood diseases. However, directed differentiation of pluripotent stem cells yields haematopoietic cells that engraft poorly. Here, we have devised a method to phenocopy the vascular-niche microenvironment of haemogenic cells, thereby enabling reprogramming of human endothelial cells into engraftable haematopoietic cells without transition through a pluripotent intermediate. Highly purifiednon-haemogenic human umbilical vein endothelial cells or adult dermalmicrovascular endothelial cells were transduced with the transcription factors FOSB, GFI1, RUNX1 and SPI1 (hereafter referred to as FGRS), and then propagated on serum-free instructive vascular niche monolayers to induce outgrowth of haematopoietic colonies containing cells with functional and immunophenotypic features of multipotent progenitor cells (MPPs). These endothelial cells that have been reprogrammed into human MPPs (rEC-hMPPs) acquire colony-forming-cell potential and durably engraft into immune-deficient mice after primary and secondary transplantation, producing long-term rEC-hMPP-derived myeloid (granulocytic/monocytic, erythroid, megakaryocytic) and lymphoid (natural killer and B cell) progenies. Conditional expression of FGRS transgenes, combined with vascular induction, activates endogenous FGRS genes, endowing rEC-hMPPs with a transcriptional and functional profile similar to that of self-renewing MPPs. Our approach underscores the role of inductive cues from the vascular niche in coordinating and sustaining haematopoietic specification and may prove useful for engineering autologous haematopoietic grafts to treat inherited and acquired blood disorders.
C1 [Sandler, Vladislav M.; Lis, Raphael; Liu, Ying; Kedem, Alon; James, Daylon; Butler, Jason M.; Rafii, Shahin] Weill Cornell Med Coll, Ansary Stem Cell Inst, Dept Med Genet, New York, NY 10065 USA.
   [Sandler, Vladislav M.; Lis, Raphael; Liu, Ying; Kedem, Alon; James, Daylon; Butler, Jason M.; Rafii, Shahin] Weill Cornell Med Coll, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Lis, Raphael; Kedem, Alon; James, Daylon] Weill Cornell Med Coll, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10065 USA.
   [Elemento, Olivier] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA.
   [Scandura, Joseph M.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
   [Scandura, Joseph M.] New York Presbyterian Hosp, New York, NY 10065 USA.
C3 Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital
RP Rafii, S (corresponding author), Weill Cornell Med Coll, Ansary Stem Cell Inst, Dept Med Genet, New York, NY 10065 USA.
EM srafii@med.cornell.edu
FU Empire State Stem Cell Board (ESSCB); New York State Department of Health [NYSDH C026878]; Ansary Stem Cell Institute (ASCI); HHMI; ESSCB/NYSDH [C024180, C026438, C026878, C028117]; NHLBI [R01HL097797, R01HL119872, U01 HL099997, HL119872, HL055748, U01-HL099997]; NIDDK [R01DK095039]; NCI [U54CA163167, CA159175, CA163167]; Qatar National Priorities Research Foundation [NPRP08-663-3-140]; Qatar Foundation BioMedical Research Program; Starr Foundation and a Leukemia & Lymphoma Society Scholar award; American Society of Hematology Scholar Award; Angiocrine Bioscience; ASCI
NR 43
TC 181
Z9 220
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 JUL 17
PY 2014
VL 511
IS 7509
BP 312
EP +
DI 10.1038/nature13547
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL2YR
UT WOS:000338992200028
PM 25030167
DA 2026-03-09
ER

PT J
AU Haig, J
   Nott, J
   Reichart, GJ
AF Haig, Jordahna
   Nott, Jonathan
   Reichart, Gert-Jan
TI Australian tropical cyclone activity lower than at any time over the past 550-1,500 years
SO NATURE
LA English
DT Article
ID stable-isotope ratios; intensity; variability; frequency; climate; hurricanes; trends; rain
AB The assessment of changes in tropical cyclone activity within the context of anthropogenically influenced climate change has been limited by the short temporal resolution of the instrumental tropical cyclone record(1,2) (less than 50 years). Furthermore, controversy exists regarding the robustness of the observational record, especially before 1990(3-5). Here we show, on the basis of a new tropical cyclone activity index (CAI), that the present low levels of storm activity on the mid west and northeast coasts of Australia are unprecedented over the past 550 to 1,500 years. The CAI allows for a direct comparison between the modern instrumental record and long-term palaeotempest (prehistoric tropical cyclone) records derived from the O-18/O-16 ratio of seasonally accreting carbonate layers of actively growing stalagmites. Our results reveal a repeated multicentennial cycle of tropical cyclone activity, the most recent of which commenced around AD 1700. The present cycle includes a sharp decrease in activity after 1960 in Western Australia. This is in contrast to the increasing frequency and destructiveness of Northern Hemisphere tropical cyclones since 1970 in the Atlantic Ocean(6-8) and the western North Pacific Ocean(6,7). Other studies project a decrease in the frequency of tropical cyclones towards the end of the twenty-first century in the southwest Pacific(7,9), southern Indian(9,10) and Australian(11) regions. Our results, although based on a limited record, suggest that this may be occurring much earlier than expected.
C1 [Haig, Jordahna; Nott, Jonathan] James Cook Univ, Cairns, Qld 4870, Australia.
   [Reichart, Gert-Jan] Univ Utrecht, Dept Geochem, NL-3508 TA Utrecht, Netherlands.
   [Reichart, Gert-Jan] Royal Netherlands Inst Sea Res, Dept Geol, NL-1797 SZ Den Hoorn, Texel, Netherlands.
C3 James Cook University; Utrecht University; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ)
RP Haig, J (corresponding author), James Cook Univ, Cairns, Qld 4870, Australia.
EM jordahna.haig@jcu.edu.au
FU Australian Research Council (ARC) [DP0772691]; Queensland Smart State Initiative; Australian Research Council [DP0772691] Funding Source: Australian Research Council
NR 37
TC 84
Z9 87
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 JAN 30
PY 2014
VL 505
IS 7485
BP 667
EP +
DI 10.1038/nature12882
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000038
PM 24476890
DA 2026-03-09
ER

PT J
AU Muppidi, JR
   Schmitz, R
   Green, JA
   Xiao, WM
   Larsens, AB
   Braun, SE
   An, JP
   Xu, Y
   Rosenwald, A
   Ott, G
   Gascoyne, RD
   Rimsza, LM
   Campo, E
   Jaffe, ES
   Delabie, J
   Smeland, EB
   Braziel, RM
   Tubbs, RR
   Cook, JR
   Weisenburger, DD
   Chan, WC
   Vaidehi, N
   Staudt, LM
   Cyster, JG
AF Muppidi, Jagan R.
   Schmitz, Roland
   Green, Jesse A.
   Xiao, Wenming
   Larsens, Adrien B.
   Braun, Sterling E.
   An, Jinping
   Xu, Ying
   Rosenwald, Andreas
   Ott, German
   Gascoyne, Randy D.
   Rimsza, Lisa M.
   Campo, Elias
   Jaffe, Elaine S.
   Delabie, Jan
   Smeland, Erlend B.
   Braziel, Rita M.
   Tubbs, Raymond R.
   Cook, J. R.
   Weisenburger, Dennis D.
   Chan, Wing C.
   Vaidehi, Nagarajan
   Staudt, Louis M.
   Cyster, Jason G.
TI Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma
SO NATURE
LA English
DT Article
ID somatic mutations; pathogenesis; ezh2; expression; physiology; defines; targets; genome; pten
AB Germinal centre B-cell-like diffuse large B-cell lymphoma(GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined(1,2). Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a G alpha 12 and G alpha 13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells(3,4). Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding G alpha 13) and S1PR2 (refs 5-7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. G alpha 13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and G alpha 13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in G alpha 13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the G alpha 13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of G alpha 13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via G alpha 13. These findings identify a G alpha 13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.
C1 [Muppidi, Jagan R.; Green, Jesse A.; Braun, Sterling E.; An, Jinping; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Muppidi, Jagan R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Muppidi, Jagan R.; Green, Jesse A.; Braun, Sterling E.; An, Jinping; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Schmitz, Roland; Xiao, Wenming; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Larsens, Adrien B.; Vaidehi, Nagarajan] City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA.
   [Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
   [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany.
   [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
   [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada.
   [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
   [Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
   [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Delabie, Jan] Univ Hosp, Rikshosp, Pathol Clin, N-0372 Oslo, Norway.
   [Smeland, Erlend B.] Univ Oslo, Univ Hosp, Rikshosp, Inst Canc Res, N-0310 Oslo, Norway.
   [Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, N-0310 Oslo, Norway.
   [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Tubbs, Raymond R.; Cook, J. R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
   [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
   [Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE 68198 USA.
   [Chan, Wing C.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE 68198 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; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); City of Hope; Beckman Research Institute of City of Hope; University of Wurzburg; Bosch; Robert Bosch Krankenhaus; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; British Columbia Cancer Agency; University of Arizona; University of Barcelona; Hospital Clinic de Barcelona; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Oslo; National Hospital Norway; University of Oslo; National Hospital Norway; University of Oslo; Oregon Health & Science University; Cleveland Clinic Foundation; City of Hope; University of Nebraska System; University of Nebraska Medical Center; University of Nebraska System; University of Nebraska Medical Center
RP Cyster, JG (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
EM lstaudt@mail.nih.gov; jason.cyster@ucsf.edu
FU Leukemia & Lymphoma Society; National Institutes of Health (NIH) [T32 DK007636, T32 CA1285835]; Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe); NIH [GM097261, AI45073]; Lymphoma/Leukemia Molecular Profiling Project; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute [T32CA128583, ZIABC011008] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI045073] Funding Source: NIH RePORTER
NR 37
TC 244
Z9 277
U1 0
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 DEC 11
PY 2014
VL 516
IS 7530
BP 254
EP +
DI 10.1038/nature13765
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500047
PM 25274307
DA 2026-03-09
ER

PT J
AU Paul, BD
   Sbodio, JI
   Xu, RS
   Vandiver, MS
   Cha, JY
   Snowman, AM
   Snyder, SH
AF Paul, Bindu D.
   Sbodio, Juan I.
   Xu, Risheng
   Vandiver, M. Scott
   Cha, Jiyoung Y.
   Snowman, Adele M.
   Snyder, Solomon H.
TI Cystathionine γ-lyase deficiency mediates neurodegeneration in Huntington's disease
SO NATURE
LA English
DT Article
ID neuronal intranuclear inclusions; hydrogen-sulfide; oxidative stress; h2s; sulfhydration; cysteine; mice; dysfunction; model
AB Huntington's disease is an autosomal dominant disease associated with a mutation in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and behavioural changes(1). Huntington's disease is characterized by highly selective and profound damage to the corpus striatum, which regulates motor function. Striatal selectivity of Huntington's disease may reflect the striatally selective small G protein Rhes binding to mHtt and enhancing its neurotoxicity(2). Specific molecular mechanisms by which mHtt elicits neurodegeneration have been hard to determine. Here we show a major depletion of cystathionine gamma-lyase (CSE), the biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may mediate Huntington's disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mHtt on specificity protein 1, a transcriptional activator for CSE. Consistent with the notion of loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses abnormalities in cultures of Huntington's disease tissues and in intact mouse models of Huntington's disease, suggesting therapeutic potential.
C1 [Paul, Bindu D.; Sbodio, Juan I.; Xu, Risheng; Vandiver, M. Scott; Cha, Jiyoung Y.; Snowman, Adele M.; Snyder, Solomon H.] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.
   [Xu, Risheng; Vandiver, M. Scott; Snyder, Solomon H.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
   [Snyder, Solomon H.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University
RP Snyder, SH (corresponding author), Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.
EM ssnyder@jhmi.edu
FU United States Public Health Service [MH18501]; CHDI; National Institutes of Health
NR 30
TC 348
Z9 378
U1 0
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 MAY 1
PY 2014
VL 509
IS 7498
BP 96
EP +
DI 10.1038/nature13136
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100046
PM 24670645
DA 2026-03-09
ER

PT J
AU Crossfield, IJM
   Biller, B
   Schlieder, JE
   Deacon, NR
   Bonnefoy, M
   Homeier, D
   Allard, F
   Buenzli, E
   Henning, T
   Brandner, W
   Goldman, B
   Kopytova, T
AF Crossfield, I. J. M.
   Biller, B.
   Schlieder, J. E.
   Deacon, N. R.
   Bonnefoy, M.
   Homeier, D.
   Allard, F.
   Buenzli, E.
   Henning, Th.
   Brandner, W.
   Goldman, B.
   Kopytova, T.
TI A global cloud map of the nearest known brown dwarf
SO NATURE
LA English
DT Article
ID atmospheric dynamics; infrared-spectra; stellar surfaces; carbon-monoxide; 2 pc; temperature; co; binary; band; transport
AB Brown dwarfs-substellar bodies more massive than planets but not massive enough to initiate the sustained hydrogen fusion that powers self-luminous stars(1,2)-are born hot and slowly cool as they age. As they cool below about 2,300 kelvin, liquid or crystalline particles composed of calcium aluminates, silicates and iron condense into atmospheric 'dust'(3,4), which disappears at still cooler temperatures (around 1,300 kelvin)(5,6). Models to explain this dust dispersal include both an abrupt sinking of the entire cloud deck into the deep, unobservable atmosphere(5,7) and breakup of the cloud into scattered patches(6,8) (as seen on Jupiter and Saturn(9)). However, hitherto observations of brown dwarfs have been limited to globally integrated measurements(10), which can reveal surface inhomogeneities but cannot unambiguously resolve surface features(11). Here we report a two-dimensional map of a brown dwarf's surface that allows identification of large-scale bright and dark features, indicative of patchy clouds. Monitoring suggests that the characteristic timescale for the evolution of global weather patterns is approximately one day.
C1 [Crossfield, I. J. M.; Biller, B.; Schlieder, J. E.; Deacon, N. R.; Bonnefoy, M.; Buenzli, E.; Henning, Th.; Brandner, W.; Goldman, B.; Kopytova, T.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Biller, B.] Univ Edinburgh, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Bonnefoy, M.] UJF Grenoble 1, CNRS INSU, UMR5274, IPAG, F-38041 Grenoble, France.
   [Homeier, D.; Allard, F.] CRAL ENS, F-69364 Lyon 07, France.
   [Kopytova, T.] Heidelberg Univ, Int Max Planck Res Sch Astron & Cosm Phys, D-69117 Heidelberg, Germany.
C3 Max Planck Society; University of Edinburgh; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut de Planetologie et d'Astrophysique de Grenoble (IPAG); Ecole Normale Superieure de Lyon (ENS de LYON); Ruprecht Karls University Heidelberg; Max Planck Society
RP Crossfield, IJM (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM ianc@mpia.de
FU European Research Council under the European Community [247060]; French National Research Agency (ANR) [ANR10-BLANC0504-01]; Swiss National Science Foundation (SNSF); European Southern Observatory Telescopes at the Paranal Observatory [ID 291.C-5006(A)]
NR 52
TC 139
Z9 162
U1 0
U2 68
PU NATURE PUBLISHING 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 30
PY 2014
VL 505
IS 7485
BP 654
EP +
DI 10.1038/nature12955
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000034
PM 24476888
DA 2026-03-09
ER

PT J
AU Fischer, ES
   Böhm, K
   Lydeard, JR
   Yang, HD
   Stadler, MB
   Cavadini, S
   Nagel, J
   Serluca, F
   Acker, V
   Lingaraju, GM
   Tichkule, RB
   Schebesta, M
   Forrester, WC
   Schirle, M
   Hassiepen, U
   Ottl, J
   Hild, M
   Beckwith, REJ
   Harper, JW
   Jenkins, JL
   Thomä, NH
AF Fischer, Eric S.
   Boehm, Kerstin
   Lydeard, John R.
   Yang, Haidi
   Stadler, Michael B.
   Cavadini, Simone
   Nagel, Jane
   Serluca, Fabrizio
   Acker, Vincent
   Lingaraju, Gondichatnahalli M.
   Tichkule, Ritesh B.
   Schebesta, Michael
   Forrester, William C.
   Schirle, Markus
   Hassiepen, Ulrich
   Ottl, Johannes
   Hild, Marc
   Beckwith, Rohan E. J.
   Harper, J. Wade
   Jenkins, Jeremy L.
   Thomae, Nicolas H.
TI Structure of the DDBI-CRBN E3 ubiquitin ligase in complex with thalidomide
SO NATURE
LA English
DT Article
ID multiple-myeloma; congenital abnormality; mental-retardation; lenalidomide; pomalidomide; cereblon; protein; cells; recognition; cancer
AB In the 1950s, the drug thalidomide, administered as a sedative to pregnant women, led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-associated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4(CRBN). Here we present crystal structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes that CRBN is a substrate receptor within CRL4(CRBN) and enantioselectively binds IMiDs. Using an unbiased screen, we identified the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4(CRBN). Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4(CRBN) while the ligase complex is recruiting IKZF1 or IKZF3 for degradation. This dual activity implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.
C1 [Fischer, Eric S.; Boehm, Kerstin; Stadler, Michael B.; Cavadini, Simone; Lingaraju, Gondichatnahalli M.; Thomae, Nicolas H.] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Fischer, Eric S.; Boehm, Kerstin; Stadler, Michael B.; Cavadini, Simone; Lingaraju, Gondichatnahalli M.; Thomae, Nicolas H.] Univ Basel, CH-4003 Basel, Switzerland.
   [Lydeard, John R.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Yang, Haidi; Nagel, Jane; Serluca, Fabrizio; Tichkule, Ritesh B.; Schebesta, Michael; Forrester, William C.; Schirle, Markus; Hild, Marc; Beckwith, Rohan E. J.; Jenkins, Jeremy L.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Stadler, Michael B.] Swiss Inst Bioinformat, CH-4058 Basel, Switzerland.
   [Acker, Vincent; Hassiepen, Ulrich; Ottl, Johannes] Novartis Pharma AG, Inst Biomed Res, CH-4056 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Harvard University; Harvard Medical School; Novartis; Novartis USA; Swiss Institute of Bioinformatics; Universita della Svizzera Italiana; Novartis
RP Thomä, NH (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM nicolas.thoma@fmi.ch
FU Novartis Research Foundation; European Research Council [260481-MoBa-CS]; National Institutes of Health [AG011085]; Damon Runyon Postdoctoral Fellowship [DRG 2061-10]; National Institute on Aging [R01AG011085] Funding Source: NIH RePORTER
NR 42
TC 880
Z9 1124
U1 10
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 AUG 7
PY 2014
VL 512
IS 7512
BP 49
EP +
DI 10.1038/nature13527
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM5NX
UT WOS:000339908000028
PM 25043012
DA 2026-03-09
ER

PT J
AU Gnad, T
   Scheibler, S
   von Kügelgen, I
   Scheele, C
   Kilic, A
   Glöde, A
   Hoffmann, LS
   Reverte-Salisa, L
   Horn, P
   Mutlu, S
   El-Tayeb, A
   Kranz, M
   Deuther-Conrad, W
   Brust, P
   Lidell, ME
   Betz, MJ
   Enerbäck, S
   Schrader, J
   Yegutkin, GG
   Müller, CE
   Pfeifer, A
AF Gnad, Thorsten
   Scheibler, Saskia
   von Kuegelgen, Ivar
   Scheele, Camilla
   Kilic, Ana
   Gloede, Anja
   Hoffmann, Linda S.
   Reverte-Salisa, Laia
   Horn, Philipp
   Mutlu, Samet
   El-Tayeb, Ali
   Kranz, Mathias
   Deuther-Conrad, Winnie
   Brust, Peter
   Lidell, Martin E.
   Betz, Matthias J.
   Enerbaeck, Sven
   Schrader, Juergen
   Yegutkin, Gennady G.
   Mueller, Christa E.
   Pfeifer, Alexander
TI Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors
SO NATURE
LA English
DT Article
ID fat; respiration; lipolysis; mouse; cells; atp
AB Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
C1 [Gnad, Thorsten; Scheibler, Saskia; von Kuegelgen, Ivar; Kilic, Ana; Gloede, Anja; Hoffmann, Linda S.; Reverte-Salisa, Laia; Horn, Philipp; Mutlu, Samet; Pfeifer, Alexander] Univ Bonn, Univ Hosp, Inst Pharmacol & Toxicol, D-53127 Bonn, Germany.
   [Scheibler, Saskia; Reverte-Salisa, Laia] Univ Bonn, Res Training Grp 1873, D-53127 Bonn, Germany.
   [Scheele, Camilla] Rigshosp, Ctr Inflammat & Metab, DK-2100 Copenhagen, Denmark.
   [Scheele, Camilla] Rigshosp, Ctr Phys Activ Res, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
   [El-Tayeb, Ali; Mueller, Christa E.] Univ Bonn, Inst Pharmaceut, D-53121 Bonn, Germany.
   [Kranz, Mathias; Deuther-Conrad, Winnie; Brust, Peter] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, D-04318 Leipzig, Germany.
   [Lidell, Martin E.; Betz, Matthias J.; Enerbaeck, Sven] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med & Clin Genet, S-41390 Gothenburg, Sweden.
   [Schrader, Juergen] Univ Dusseldorf, Dept Mol Cardiol, D-40225 Dusseldorf, Germany.
   [Yegutkin, Gennady G.] Univ Turku, Med Res Lab, FIN-20520 Turku, Finland.
   [Mueller, Christa E.; Pfeifer, Alexander] Univ Bonn, Pharma Ctr, D-53127 Bonn, Germany.
C3 University of Bonn; University of Bonn; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital; University of Bonn; Helmholtz Association; Helmholtz-Zentrum Dresden-Rossendorf (HZDR); University of Gothenburg; Heinrich Heine University Dusseldorf; University of Turku; University of Bonn
RP Pfeifer, A (corresponding author), Univ Bonn, Univ Hosp, Inst Pharmacol & Toxicol, D-53127 Bonn, Germany.
EM alexander.pfeifer@uni-bonn.de
FU Deutsche Forschungsgemeinschaft (DFG); Lundbeck Foundation; Novo Nordisk A/S; Danish National Research Foundation [DNRF55]; Trygfonden; BONFOR; Bonn International Graduate School DrugS; Swedish Research Council [2013-4466, 2010-3281, 2012-1652]; Knut and Alice Wallenberg Foundation; Sahlgrenska's University Hospital (LUA-ALF); European Union [HEALTH-F2-2011-278373]; Inga Britt and Arne Lundgren Foundation; Soderberg Foundation; King Gustaf V and Queen Victoria Freemason Foundation; Federal Ministry of Education and research
NR 27
TC 326
Z9 360
U1 3
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 18
PY 2014
VL 516
IS 7531
BP 395
EP +
DI 10.1038/nature13816
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800047
PM 25317558
DA 2026-03-09
ER

PT J
AU Watanabe, H
   Schmidt, HA
   Kuhn, A
   Höger, SK
   Kocagöz, Y
   Laumann-Lipp, N
   Özbek, S
   Holstein, TW
AF Watanabe, Hiroshi
   Schmidt, Heiko A.
   Kuhn, Anne
   Hoeger, Stefanie K.
   Kocagoez, Yigit
   Laumann-Lipp, Nico
   Oezbek, Suat
   Holstein, Thomas W.
TI Nodal signalling determines biradial asymmetry in Hydra
SO NATURE
LA English
DT Article
ID maximum-likelihood phylogeny; cartesian coordinate system; left-right axis; head organizer; gene family; body axes; evolution; wnt; expression; embryo
AB In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis(1). Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cni-darian polyp Hydra, and we report evidence of Nodal ina pre-bilaterian clade. We identified aNodal-related gene (Ndr) inHydra magnipa-pillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates(2,3), Nodal acts downstream of beta-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of b-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians.
C1 [Watanabe, Hiroshi; Kuhn, Anne; Hoeger, Stefanie K.; Kocagoez, Yigit; Laumann-Lipp, Nico; Oezbek, Suat; Holstein, Thomas W.] Heidelberg Univ, Dept Mol Evolut & Genom, Ctr Organismal Studies COS, D-69120 Heidelberg, Germany.
   [Schmidt, Heiko A.] Univ Vienna, Med Univ Vienna, Ctr Integrat Bioinformat Vienna CIBIV, Max F Perutz Labs MFPL, A-1030 Vienna, Austria.
C3 Ruprecht Karls University Heidelberg; Medical University of Vienna; University of Vienna
RP Holstein, TW (corresponding author), Heidelberg Univ, Dept Mol Evolut & Genom, Ctr Organismal Studies COS, D-69120 Heidelberg, Germany.
EM hiroshi.watanabe@cos.uni-heidelberg.de; thomas.holstein@cos.uni-heidelberg.de
FU TOYOBO Biotechnology Foundation; Alexander von Humboldt Foundation; Heidelberg Excellence Cluster Cellular Networks; German science foundation (DFG) [FOR 1036/TP1, SFB 873/A1, FOR 1036/TP2]
NR 35
TC 85
Z9 94
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 NOV 6
PY 2014
VL 515
IS 7525
BP 112
EP +
DI 10.1038/nature13666
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500040
PM 25156256
DA 2026-03-09
ER

PT J
AU Kode, A
   Manavalan, JS
   Mosialou, I
   Bhagat, G
   Rathinam, CV
   Luo, N
   Khiabanian, H
   Lee, A
   Murty, VV
   Friedman, R
   Brum, A
   Park, D
   Galili, N
   Mukherjee, S
   Teruya-Feldstein, J
   Raza, A
   Rabadan, R
   Berman, E
   Kousteni, S
AF Kode, Aruna
   Manavalan, John S.
   Mosialou, Ioanna
   Bhagat, Govind
   Rathinam, Chozha V.
   Luo, Na
   Khiabanian, Hossein
   Lee, Albert
   Murty, Vundavalli V.
   Friedman, Richard
   Brum, Andrea
   Park, David
   Galili, Naomi
   Mukherjee, Siddhartha
   Teruya-Feldstein, Julie
   Raza, Azra
   Rabadan, Raul
   Berman, Ellin
   Kousteni, Stavroula
TI Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts
SO NATURE
LA English
DT Article
ID bone-marrow niche; stem-cell niche; progenitor cells; notch activation; expression; pathway; identification; resistance; promoter; gene
AB Cells of the osteoblast lineage affect the homing(1,2) and the number of long-term repopulating haematopoietic stem cells(3,4), haematopoietic stem cell mobilization and lineage determination and B cell lymphopoiesis(5-7). Osteoblasts were recently implicated in pre-leukaemic conditions in mice(8,9). However, a single genetic change in osteoblasts that can induce leukaemogenesis has not been shown. Here we show that an activating mutation of beta-catenin in mouse osteoblasts alters the differentiation potential of myeloid and lymphoid progenitors leading to development of acute myeloid leukaemia with common chromosomal aberrations and cell autonomous progression. Activated beta-catenin stimulates expression of the Notch ligand jagged 1 in osteoblasts. Subsequent activation of Notch signalling in haematopoietic stem cell progenitors induces the malignant changes. Genetic or pharmacological inhibition of Notch signalling ameliorates acute myeloid leukaemia and demonstrates the pathogenic role of the Notch pathway. In 38% of patients with myelodysplastic syndromes or acute myeloid leukaemia, increased beta-catenin signalling and nuclear accumulation was identified in osteoblasts and these patients showed increased Notch signalling in haematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce acute myeloid leukaemia, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeutic approach to acute myeloid leukaemia.
C1 [Kode, Aruna; Manavalan, John S.; Mosialou, Ioanna; Luo, Na; Brum, Andrea; Kousteni, Stavroula] Columbia Univ, Coll Phys & Surg, Dept Med, Div Endocrinol, New York, NY 10032 USA.
   [Bhagat, Govind] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Rathinam, Chozha V.] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
   [Khiabanian, Hossein; Lee, Albert; Rabadan, Raul] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
   [Khiabanian, Hossein; Lee, Albert; Rabadan, Raul] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Murty, Vundavalli V.] Columbia Univ, Dept Pathol, New York, NY 10032 USA.
   [Murty, Vundavalli V.] Columbia Univ, Inst Canc Genet, Irving Canc Res Ctr, New York, NY 10032 USA.
   [Friedman, Richard] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Biomed Informat Shared Resource, New York, NY 10032 USA.
   [Friedman, Richard] Columbia Univ, Coll Phys & Surg, Dept Biomed Informat, New York, NY 10032 USA.
   [Brum, Andrea] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [Park, David; Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Galili, Naomi; Raza, Azra] Columbia Univ, Myelodysplast Syndromes Ctr, New York, NY 10032 USA.
   [Mukherjee, Siddhartha] Columbia Univ, Dept Med Hematol, New York, NY 10032 USA.
   [Mukherjee, Siddhartha] Columbia Univ, Dept Oncol, New York, NY 10032 USA.
   [Berman, Ellin] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
   [Kousteni, Stavroula] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Erasmus University Rotterdam; Erasmus MC; Memorial Sloan Kettering Cancer Center; Columbia University; Columbia University; Columbia University; Memorial Sloan Kettering Cancer Center; Columbia University
RP Kousteni, S (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Med, Div Endocrinol, New York, NY 10032 USA.
EM sk2836@columbia.edu
FU National Institutes of Health [R01 AR054447, P01 AG032959, R01 AR055931]; Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York; European Union [INTERBONE-FP7-PEOPLE-2011-IRSES-295181]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK063608] Funding Source: NIH RePORTER; National Institute on Aging [P01AG032959] Funding Source: NIH RePORTER
NR 51
TC 437
Z9 508
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 FEB 13
PY 2014
VL 506
IS 7487
BP 240
EP +
DI 10.1038/nature12883
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700042
PM 24429522
DA 2026-03-09
ER

PT J
AU Huskinson, B
   Marshak, MP
   Suh, C
   Er, S
   Gerhardt, MR
   Galvin, CJ
   Chen, XD
   Aspuru-Guzik, A
   Gordon, RG
   Aziz, MJ
AF Huskinson, Brian
   Marshak, Michael P.
   Suh, Changwon
   Er, Sueleyman
   Gerhardt, Michael R.
   Galvin, Cooper J.
   Chen, Xudong
   Aspuru-Guzik, Alan
   Gordon, Roy G.
   Aziz, Michael J.
TI A metal-free organic-inorganic aqueous flow battery
SO NATURE
LA English
DT Article
ID redox; anthraquinone; reduction; energy; progress; density; field
AB As the fraction of electricity generation from intermittent renewable sources-such as solar or wind-grows, the ability to store large amounts of electrical energy is of increasing importance. Solid-electrode batteries maintain discharge at peak power for far too short a time to fully regulate wind or solar power output(1,2). In contrast, flow batteries can independently scale the power (electrode area) and energy (arbitrarily large storage volume) components of the system by maintaining all of the electro-active species in fluid form(3-5). Wide-scale utilization of flow batteries is, however, limited by the abundance and cost of these materials, particularly those using redox-active metals and precious-metal electrocatalysts(6,7). Here we describe a class of energy storage materials that exploits the favourable chemical and electro-chemical properties of a family of molecules known as quinones. The example we demonstrate is ametal-free flow battery based on the redox chemistry of 9,10-anthraquinone-2,7-disulphonic acid (AQDS). AQDS undergoes extremely rapid and reversible two-electron two-proton reduction on a glassy carbon electrode in sulphuric acid. An aqueous flow battery with inexpensive carbon electrodes, combining the quinone/hydroquinone couple with the Br-2/Br- redox couple, yields a peak galvanic power density exceeding 0.6 W cm(-2) at 1.3 A cm(-2). Cycling of this quinone-bromide flow battery showed >99 per cent storage capacity retention per cycle. The organic anthraquinone species can be synthesized from inexpensive commodity chemicals(8). This organic approach permits tuning of important properties such as the reduction potential and solubility by adding functional groups: for example, we demonstrate that the addition of two hydroxy groups to AQDS increases the open circuit potential of the cell by 11% and we describe a pathway for further increases in cell voltage. The use of p-aromatic redox-active organic molecules instead of redox-active metals represents a new and promising direction for realizing massive electrical energy storage at greatly reduced cost.
C1 [Huskinson, Brian; Marshak, Michael P.; Gerhardt, Michael R.; Gordon, Roy G.; Aziz, Michael J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Marshak, Michael P.; Suh, Changwon; Er, Sueleyman; Galvin, Cooper J.; Chen, Xudong; Aspuru-Guzik, Alan; Gordon, Roy G.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Er, Sueleyman] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands.
C3 Harvard University; Harvard University; Eindhoven University of Technology
RP Aziz, MJ (corresponding author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St, Cambridge, MA 02138 USA.
EM maziz@harvard.edu
FU US Department of Energy ARPA-E Award [DE-AR0000348]; Harvard School of Engineering and Applied Sciences; Extreme Science and Engineering Discovery Environment (XSEDE); National Science Foundation [OCI-1053575]; NSF; Foundation for Fundamental Research on Matter (FOM); Netherlands Organization for Scientific Research (NWO)
NR 36
TC 1326
Z9 1577
U1 35
U2 1514
PU NATURE PUBLISHING 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 9
PY 2014
VL 505
IS 7482
BP 195
EP +
DI 10.1038/nature12909
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500034
PM 24402280
DA 2026-03-09
ER

PT J
AU Worobey, M
   Han, GZ
   Rambaut, A
AF Worobey, Michael
   Han, Guan-Zhu
   Rambaut, Andrew
TI A synchronized global sweep of the internal genes of modern avian influenza virus
SO NATURE
LA English
DT Article
ID equine influenza; maximum-likelihood; a virus; evolution; dates; dna; transmission; emergence
AB Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health(1). However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood(2,3). Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts(3-8). Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including 'relaxed' molecular clock models(9), can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds-as well as those from humans, swine and the equine H3N8 lineage-sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.
C1 [Worobey, Michael; Han, Guan-Zhu] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
C3 University of Arizona; University of Edinburgh; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC)
RP Worobey, M (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
EM worobey@email.arizona.edu; a.rambaut@ed.ac.uk
FU David and Lucile Packard Foundation; Wellcome Trust [092807]; European Union [278433-PREDEMICS]; European Research Council [260864]; National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01AI084691]
NR 44
TC 187
Z9 206
U1 1
U2 101
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 10
PY 2014
VL 508
IS 7495
BP 254
EP +
DI 10.1038/nature13016
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900046
PM 24531761
DA 2026-03-09
ER

PT J
AU Rahimi, A
   Ulbrich, A
   Coon, JJ
   Stahl, SS
AF Rahimi, Alireza
   Ulbrich, Arne
   Coon, Joshua J.
   Stahl, Shannon S.
TI Formic-acid-induced depolymerization of oxidized lignin to aromatics
SO NATURE
LA English
DT Article
ID pine wood; oxidation; valorization; biomass; photodegradation; degradation; strategy
AB Lignin is a heterogeneous aromatic biopolymer that accounts for nearly 30% of the organic carbon on Earth(1) and is one of the few renewable sources of aromatic chemicals(2). As the most recalcitrant of the three components of lignocellulosic biomass (cellulose, hemicellulose and lignin)(3), lignin has been treated as a waste product in the pulp and paper industry, where it is burned to supply energy and recover pulping chemicals in the operation of paper mills(4). Extraction of higher value from lignin is increasingly recognized as being crucial to the economic viability of integrated biorefineries(5,6). Depolymerization is an important starting point for many lignin valorization strategies, because it could generate valuable aromatic chemicals and/or provide a source of low-molecular-mass feedstocks suitable for downstream processing(7). Commercial precedents show that certain types of lignin(lignosulphonates) may be converted into vanillin and other marketable products(8,9), but new technologies are needed to enhance the lignin value chain. The complex, irregular structure of lignin complicates chemical conversion efforts, and known depolymerization methods typically afford ill-defined products in low yields (that is, less than 10-20wt%)(2,10,11). Here we describe a method for the depolymerization of oxidized lignin under mild conditions in aqueous formic acid that results in more than 60wt% yield of low-molecular-mass aromatics. We present the discovery of this facile C-O cleavage method, its application to aspen lignin depolymerization, and mechanistic insights into the reaction. The broader implications of these results for lignin conversion and biomass refining are also considered.
C1 [Rahimi, Alireza; Ulbrich, Arne; Coon, Joshua J.; Stahl, Shannon S.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
   [Coon, Joshua J.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; 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 1001
Z9 1147
U1 30
U2 1370
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2014
VL 515
IS 7526
BP 249
EP 252
DI 10.1038/nature13867
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400046
PM 25363781
DA 2026-03-09
ER

PT J
AU Tiecke, TG
   Thompson, JD
   de Leon, NP
   Liu, LR
   Vuletic, V
   Lukin, MD
AF Tiecke, T. G.
   Thompson, J. D.
   de Leon, N. P.
   Liu, L. R.
   Vuletic, V.
   Lukin, M. D.
TI Nanophotonic quantum phase switch with a single atom
SO NATURE
LA English
DT Article
ID photon; cavity; state; network; shifts; logic; light
AB By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks(1-3). Operated at the fundamental limit where a single quantum of light or matter controls another field or material system(4), such a switch may enable applications such as long-distance quantum communication(5), distributed quantum information processing(2) and metrology(6), and the exploration of novel quantum states of matter(7). Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a photon and a single photon modifies the atom's phase. We experimentally demonstrate an atom-induced optical phase shift(8) that is nonlinear at the two-photon level(9), a photon number router that separates individual photons and photon pairs into different output modes(10), and a single-photon switch in which a single 'gate' photon controls the propagation of a subsequent probe field(11,12). These techniques pave the way to integrated quantum nanophotonic networks involving multiple atomic nodes connected by guided light.
C1 [Tiecke, T. G.; Thompson, J. D.; de Leon, N. P.; Liu, L. R.; Lukin, M. D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Tiecke, T. G.; Vuletic, V.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Tiecke, T. G.; Vuletic, V.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [de Leon, N. P.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM vuletic@mit.edu; lukin@fas.harvard.edu
FU US NSF; Center for Ultracold Atoms; Natural Sciences and Engineering Research Council of Canada; Air Force Office of Scientific Research Multidisciplinary University Research Initiative; Packard Foundation; Fannie and John Hertz Foundation; NSF Graduate Research Fellowship Program; NSF [ECS-0335765]; Direct For Mathematical & Physical Scien; Division Of Physics [0969816] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1205554, 1125846] Funding Source: National Science Foundation
NR 30
TC 488
Z9 575
U1 3
U2 306
PU NATURE PUBLISHING 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 10
PY 2014
VL 508
IS 7495
BP 241
EP 244
DI 10.1038/nature13188
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900043
PM 24717513
DA 2026-03-09
ER

PT J
AU Santos, MA
   Faryabi, RB
   Ergen, AV
   Day, AM
   Malhowski, A
   Canela, A
   Onozawa, M
   Lee, JE
   Callen, E
   Gutierrez-Martinez, P
   Chen, HT
   Wong, N
   Finkel, N
   Deshpande, A
   Sharrow, S
   Rossi, DJ
   Ito, K
   Ge, K
   Aplan, PD
   Armstrong, SA
   Nussenzweig, A
AF Santos, Margarida A.
   Faryabi, Robert B.
   Ergen, Aysegul V.
   Day, Amanda M.
   Malhowski, Amy
   Canela, Andres
   Onozawa, Masahiro
   Lee, Ji-Eun
   Callen, Elsa
   Gutierrez-Martinez, Paula
   Chen, Hua-Tang
   Wong, Nancy
   Finkel, Nadia
   Deshpande, Aniruddha
   Sharrow, Susan
   Rossi, Derrick J.
   Ito, Keisuke
   Ge, Kai
   Aplan, Peter D.
   Armstrong, Scott A.
   Nussenzweig, Andre
TI DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; oxidative stress; rna-seq; mll; progenitors; breaks; resistance; discovery; lymphoma; renewal
AB Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells(1). Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks(2-4), we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma(5,6), is required for stem-cell activity and an aggressive form of acutemyeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL-/- MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.
C1 [Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Callen, Elsa; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
   [Onozawa, Masahiro; Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Lee, Ji-Eun; Ge, Kai] NIDDKD, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
   [Gutierrez-Martinez, Paula; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Gutierrez-Martinez, Paula; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Deshpande, Aniruddha; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Deshpande, Aniruddha; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA.
   [Sharrow, Susan] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Ito, Keisuke] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Dept Cell Biol, Bronx, NY 10461 USA.
   [Ito, Keisuke] Albert Einstein Coll Med, Dept Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University
RP Nussenzweig, A (corresponding author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
FU Leukemia and Lymphoma Society; National Cancer Institute [CA66996, CA140575]; National Institutes of Health; National Cancer Institute; Center for Cancer Research; Ellison Medical Foundation; National Cancer Institute [P30CA008748, P01CA066996, ZIABC010983, ZICBC009255] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK075003, R01DK098263] Funding Source: NIH RePORTER
NR 40
TC 173
Z9 194
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 OCT 2
PY 2014
VL 514
IS 7520
BP 107
EP +
DI 10.1038/nature13483
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP9SS
UT WOS:000342420800045
PM 25079327
DA 2026-03-09
ER

PT J
AU Constantinides, MG
   McDonald, BD
   Verhoef, PA
   Bendelac, A
AF Constantinides, Michael G.
   McDonald, Benjamin D.
   Verhoef, Philip A.
   Bendelac, Albert
TI A committed precursor to innate lymphoid cells
SO NATURE
LA English
DT Article
ID ror-gamma-t; transcription factor gata3; leukemia zinc-finger; type-2 immunity; nkp46(+) cells; inflammation; lineage; fetal; nk; differentiation
AB Innate lymphoid cells (ILCs) specialize in the rapid secretion of polarized sets of cytokines and chemokines to combat infection and promote tissue repair at mucosal barriers(1-9). Their diversity and similarities with previously characterized natural killer (NK) cells and lymphoid tissue inducers (LTi) have prompted a provisional classification of all innate lymphocytes into groups 1, 2 and 3 solely on the basis of cytokine properties(10), but their developmental pathways and lineage relationships remain elusive. Here we identify and characterize a novel subset of lymphoid precursors in mouse fetal liver and adult bone marrow that transiently express high amounts of PLZF, a transcription factor previously associated with NK T cell development(11,12), by using lineage tracing and transfer studies. PLZF(high) cells were committed ILC progenitors with multiple ILC1, ILC2 and ILC3 potential at the clonal level. They excluded classical LTi and NK cells, but included a peculiar subset of NK1.1(+)DX5(-) 'NK-like' cells residing in the liver. Deletion of PLZF markedly altered the development of several ILC subsets, but not LTi or NK cells. PLZF(high) precursors also expressed high amounts of ID2 and GATA3, as well as TOX, a known regulator of PLZF-independent NK and LTi lineages(13). These findings establish novel lineage relationships between ILC, NK and LTi cells, and identify the common precursor to ILCs, termed ILCP. They also reveal the broad, defining role of PLZF in the differentiation of innate lymphocytes.
C1 [Constantinides, Michael G.; McDonald, Benjamin D.; Verhoef, Philip A.; Bendelac, Albert] Univ Chicago, Howard Hughes Med Inst, Dept Pathol, Comm Immunol, Chicago, IL 60637 USA.
C3 University of Chicago; Howard Hughes Medical Institute
RP Bendelac, A (corresponding author), Univ Chicago, Howard Hughes Med Inst, Dept Pathol, Comm Immunol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM abendela@bsd.uchicago.edu
FU NIH [R01HL118092, R01AI038339, P30DK42086]; Howard Hughes Medical Institute; National Heart Lung and Blood Institute [T32HL007605] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007090] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK042086] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007281] Funding Source: NIH RePORTER
NR 29
TC 677
Z9 798
U1 0
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 APR 17
PY 2014
VL 508
IS 7496
BP 397
EP +
DI 10.1038/nature13047
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF0KP
UT WOS:000334403000052
PM 24509713
DA 2026-03-09
ER

PT J
AU King, AM
   Reid-Yu, SA
   Wang, WL
   King, DT
   De Pascale, G
   Strynadka, NC
   Walsh, TR
   Coombes, BK
   Wright, GD
AF King, Andrew M.
   Reid-Yu, Sarah A.
   Wang, Wenliang
   King, Dustin T.
   De Pascale, Gianfranco
   Strynadka, Natalie C.
   Walsh, Timothy R.
   Coombes, Brian K.
   Wright, Gerard D.
TI Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance
SO NATURE
LA English
DT Article
ID angiotensin-converting enzyme; klebsiella-pneumoniae; microbial inhibitors
AB The emergence and spread of carbapenem-resistant Gram-negative pathogens is a global public health problem. The acquisition of metallo-beta-lactamases (MBLs) such as NDM-1 is a principle contributor to the emergence of carbapenem-resistant Gram-negative pathogens that threatens the use of penicillin, cephalosporin and carbapenem antibiotics to treat infections. To date, a clinical inhibitor of MBLs that could reverse resistance and re-sensitize resistant Gram-negative pathogens to carbapenems has not been found. Here we have identified a fungal natural product, aspergillomarasmine A (AMA), that is a rapid and potent inhibitor of the NDM-1 enzyme and another clinically relevant MBL, VIM-2. AMA also fully restored the activity of meropenem against Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. possessing either VIM or NDM-type alleles. In mice infected with NDM-1-expressing Klebsiella pneumoniae, AMA efficiently restored meropenem activity, demonstrating that a combination of AMA and a carbapenem antibiotic has therapeutic potential to address the clinical challenge of MBL-positive carbapenem-resistant Gram-negative pathogens.
C1 [King, Andrew M.; Wang, Wenliang; De Pascale, Gianfranco; Wright, Gerard D.] McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada.
   [King, Andrew M.; Wright, Gerard D.] McMaster Univ, Dept Chem & Chem Biol, Hamilton, ON L8S 4K1, Canada.
   [Reid-Yu, Sarah A.; Coombes, Brian K.; Wright, Gerard D.] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4K1, Canada.
   [King, Dustin T.; Strynadka, Natalie C.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
   [Walsh, Timothy R.] Cardiff Univ, Cardiff Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
C3 McMaster University; McMaster University; McMaster University; University of British Columbia; Cardiff University
RP Wright, GD (corresponding author), McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada.
EM wrightge@mcmaster.ca
FU UK Medical Research Council [G1100135]; Canadian Institutes of Health Research [MT-13536]; Natural Sciences and Engineering Research Council [237480]; Canada Research Chair in Infectious Disease Pathogenesis; Antibiotic Biochemistry; Medical Research Council [G1100135] Funding Source: researchfish; MRC [G1100135] Funding Source: UKRI
NR 30
TC 467
Z9 527
U1 7
U2 250
PU NATURE PUBLISHING 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 26
PY 2014
VL 510
IS 7506
BP 503
EP +
DI 10.1038/nature13445
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ6LK
UT WOS:000337806300039
PM 24965651
DA 2026-03-09
ER

PT J
AU Weber, SJ
   Chantasri, A
   Dressel, J
   Jordan, AN
   Murch, KW
   Siddiqi, I
AF Weber, S. J.
   Chantasri, A.
   Dressel, J.
   Jordan, A. N.
   Murch, K. W.
   Siddiqi, I.
TI Mapping the optimal route between two quantum states
SO NATURE
LA English
DT Article
ID symmetry; qubit
AB A central feature of quantum mechanics is that a measurement result is intrinsically probabilistic. Consequently, continuously monitoring a quantum system will randomly perturb its natural unitary evolution. The ability to control a quantum system in the presence of these fluctuations is of increasing importance in quantum information processing and finds application in fields ranging from nuclear magnetic resonance(1) to chemical synthesis(2). A detailed understanding of this stochastic evolution is essential for the development of optimized control methods. Here we reconstruct the individual quantum trajectories(3-5) of a superconducting circuit that evolves under the competing influences of continuous weak measurement and Rabi drive. By tracking individual trajectories that evolve between any chosen initial and final states, we can deduce the most probable path through quantum state space. These pre- and post-selected quantum trajectories also reveal the optimal detector signal in the form of a smooth, time-continuous function that connects the desired boundary conditions. Our investigation reveals the rich interplay between measurement dynamics, typically associated with wave function collapse, and unitary evolution of the quantum state as described by the Schrodinger equation. These results and the underlying theory(6), based on a principle of least action, reveal the optimal route from initial to final states, and may inform new quantum control methods for state steering and information processing.
C1 [Weber, S. J.; Siddiqi, I.] Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
   [Chantasri, A.; Jordan, A. N.] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA.
   [Chantasri, A.; Jordan, A. N.] Univ Rochester, Ctr Coherence & Quantum Opt, Rochester, NY 14627 USA.
   [Dressel, J.] Univ Calif Riverside, Dept Elect Engn, Riverside, CA 92521 USA.
   [Jordan, A. N.] Chapman Univ, Inst Quantum Studies, Orange, CA 92866 USA.
   [Murch, K. W.] Washington Univ, Dept Phys, St Louis, MO 63130 USA.
C3 University of California System; University of California Berkeley; University of Rochester; University of Rochester; University of California System; University of California Riverside; Chapman University System; Chapman University; Washington University (WUSTL)
RP Murch, KW (corresponding author), Washington Univ, Dept Phys, St Louis, MO 63130 USA.
EM murch@physics.wustl.edu
FU Army Research Office; Office of Naval Research; Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through the Army Research Office; NSF [DMR-0844899]
NR 30
TC 178
Z9 210
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 JUL 30
PY 2014
VL 511
IS 7511
BP 570
EP +
DI 10.1038/nature13559
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300030
PM 25079554
DA 2026-03-09
ER

PT J
AU Garrick-Bethell, I
   Perera, V
   Nimmo, F
   Zuber, MT
AF Garrick-Bethell, Ian
   Perera, Viranga
   Nimmo, Francis
   Zuber, Maria T.
TI The tidal-rotational shape of the Moon and evidence for polar wander
SO NATURE
LA English
DT Article
ID internal structure; gravity-field; lunar; asymmetry
AB The origin of the Moon's large-scale topography is important for understanding lunar geology(1), lunar orbital evolution(2) and the Moon's orientation in the sky(3). Previous hypotheses for its origin have included late accretion events(4), large impacts(5), tidal effects(6) and convection processes(7). However, testing these hypotheses and quantifying the Moon's topography is complicated by the large basins that have formed since the crust crystallized. Here we estimate the large-scale lunar topography and gravity spherical harmonics outside these basins and show that the bulk of the spherical harmonic degree-2 topography is consistent with a crust-building process controlled by early tidal heating throughout the Moon. The remainder of the degree-2 topography is consistent with a frozen tidal-rotational bulge that formed later, at a semi-major axis of about 32 Earth radii. The probability of the degree-2 shape having both tidal-heating and frozen shape characteristics by chance is less than 1%. We also infer that internal density contrasts eventually reoriented the Moon's polar axis by 36 +/- 4 degrees, to the configuration we observe today. Together, these results link the geology of the near and far sides, and resolve long-standing questions about the Moon's large-scale shape, gravity and history of polar wander.
C1 [Garrick-Bethell, Ian; Perera, Viranga; Nimmo, Francis] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Garrick-Bethell, Ian] Kyung Hee Univ, Sch Space Res, Yongin 446701, Gyeonggi Do, South Korea.
   [Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
C3 University of California System; University of California Santa Cruz; Kyung Hee University; Massachusetts Institute of Technology (MIT)
RP Garrick-Bethell, I (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, 1156 High St, Santa Cruz, CA 95064 USA.
EM igarrick@ucsc.edu
FU National Research Foundation (NRF) - Ministry of Education of Korea
NR 30
TC 36
Z9 41
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 AUG 14
PY 2014
VL 512
IS 7513
BP 181
EP 184
DI 10.1038/nature13639
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700029
PM 25079322
DA 2026-03-09
ER

PT J
AU Kim, TH
   Li, FG
   Ferreiro-Neira, I
   Ho, LL
   Luyten, A
   Nalapareddy, K
   Long, H
   Verzi, M
   Shivdasani, RA
AF Kim, Tae-Hee
   Li, Fugen
   Ferreiro-Neira, Isabel
   Ho, Li-Lun
   Luyten, Annouck
   Nalapareddy, Kodandaramireddy
   Long, Henry
   Verzi, Michael
   Shivdasani, Ramesh A.
TI Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity
SO NATURE
LA English
DT Article
ID atonal homolog 1; secretase inhibitors; stem-cells; differentiation; enhancers; reveals; identification; recombination; requirement; genes
AB Cells differentiate when transcription factors bind accessible cis-regulatory elements to establish specific gene expression programs. In differentiating embryonic stem cells, chromatin at lineage-restricted genes becomes sequentially accessible(1-4), probably by means of 'pioneer' transcription factor activity(5), but tissues may use other strategies in vivo. Lateral inhibition is a pervasive process in which one cell forces a different identity on its neighbours(6), and it is unclear how chromatin in equipotent progenitors undergoing lateral inhibition quickly enables distinct, transiently reversible cell fates. Here we report the chromatin and transcriptional underpinnings of differentiation in mouse small intestine crypts, where notch signalling mediates lateral inhibition to assign progenitor cells into absorptive or secretory lineages(7-9). Transcript profiles in isolated LGR5(+) intestinal stem cells(10) and secretory and absorptive progenitors indicated that each cell population was distinct and the progenitors specified. Nevertheless, secretory and absorptive progenitors showed comparable levels of H3K4me2 and H3K27ac histone marks and DNase I hypersensitivity-signifying accessible, permissive chromatin-at most of the same cis-elements. Enhancers acting uniquely in progenitors were well demarcated in LGR5(+) intestinal stem cells, revealing early priming of chromatin for divergent transcriptional programs, and retained active marks well after lineages were specified. On this chromatin background, ATOH1, a secretory-specific transcription factor, controls lateral inhibition through delta-like notch ligand genes and also drives the expression of numerous secretory lineage genes. Depletion of ATOH1 from specified secretory cells converted them into functional enterocytes, indicating prolonged responsiveness of marked enhancers to the presence or absence of a key transcription factor. Thus, lateral inhibition and intestinal crypt lineage plasticity involve interaction of a lineage-restricted transcription factor with broadly permissive chromatin established in multipotent stem cells.
C1 [Kim, Tae-Hee; Li, Fugen; Ferreiro-Neira, Isabel; Ho, Li-Lun; Luyten, Annouck; Nalapareddy, Kodandaramireddy; Long, Henry; Verzi, Michael; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Kim, Tae-Hee; Li, Fugen; Ferreiro-Neira, Isabel; Ho, Li-Lun; Luyten, Annouck; Nalapareddy, Kodandaramireddy; Long, Henry; Verzi, Michael; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
   [Kim, Tae-Hee; Ferreiro-Neira, Isabel; Ho, Li-Lun; Luyten, Annouck; Nalapareddy, Kodandaramireddy; Verzi, Michael; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
   [Kim, Tae-Hee; Ferreiro-Neira, Isabel; Ho, Li-Lun; Luyten, Annouck; Nalapareddy, Kodandaramireddy; Verzi, Michael; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Shivdasani, RA (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM ramesh_shivdasani@dfci.harvard.edu
FU NIH [R01DK082889, R01DK081113, K99DK095983, K01DK088868, P50CA127003]; North American Neuroendocrine Tumor Society; Caring For Carcinoid Foundation; National Cancer Institute [P50CA127003] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK081113, R01DK082889] Funding Source: NIH RePORTER
NR 41
TC 205
Z9 248
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 FEB 27
PY 2014
VL 506
IS 7489
BP 511
EP +
DI 10.1038/nature12903
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100043
PM 24413398
DA 2026-03-09
ER

PT J
AU Rey, PF
   Coltice, N
   Flament, N
AF Rey, Patrice F.
   Coltice, Nicolas
   Flament, Nicolas
TI Spreading continents kick-started plate tectonics
SO NATURE
LA English
DT Article
ID mantle convection; lithospheric mantle; greenstone-belt; evolution; deformation; subduction; strength; crust; earth; constraints
AB Stresses acting on cold, thick and negatively buoyant oceanic lithosphere are thought to be crucial to the initiation of subduction and the operation of plate tectonics(1,2), which characterizes the present-day geodynamics of the Earth. Because the Earth's interior was hotter in the Archaean eon, the oceanic crust may have been thicker, thereby making the oceanic lithosphere more buoyant than at present(3), and whether subduction and plate tectonics occurred during this time is ambiguous, both in the geological record and in geodynamic models(4). Here we show that because the oceanic crust was thick and buoyant(5), early continents may have produced intra-lithospheric gravitational stresses large enough to drive their gravitational spreading, to initiate subduction at their margins and to trigger episodes of subduction. Our model predicts the co-occurrence of deep to progressively shallower mafic volcanics and arc magmatism within continents in a self-consistent geodynamic framework, explaining the enigmatic multimodal volcanism and tectonic record of Archaean cratons(6). Moreover, our model predicts a petrological stratification and tectonic structure of the sub-continental lithospheric mantle, two predictions that are consistent with xenolith(5) and seismic studies, respectively, and consistent with the existence of amid-lithospheric seismic discontinuity(7). The slow gravitational collapse of early continents could have kick-started transient episodes of plate tectonics until, as the Earth's interior cooled and oceanic lithosphere became heavier, plate tectonics became self-sustaining.
C1 [Rey, Patrice F.; Flament, Nicolas] Univ Sydney, Earthbyte Res Grp, Sch Geosci, Sydney, NSW 2006, Australia.
   [Coltice, Nicolas] Univ Lyon 1, Ecole Normale Super Lyon, UMR CNRS 5276, Lab Geol Lyon, F-69622 Villeurbanne, France.
   [Coltice, Nicolas] Inst Univ France, F-75005 Paris, France.
C3 University of Sydney; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Institut Universitaire de France
RP Rey, PF (corresponding author), Univ Sydney, Earthbyte Res Grp, Sch Geosci, Sydney, NSW 2006, Australia.
EM patrice.rey@sydney.edu.au
FU Australian Government; Institut Universitaire de France; European Research Council (ERC) [617588]; Statoil ASA
NR 44
TC 99
Z9 116
U1 0
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 SEP 18
PY 2014
VL 513
IS 7518
BP 405
EP +
DI 10.1038/nature13728
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900057
PM 25230662
DA 2026-03-09
ER

PT J
AU Lollar, BS
   Onstott, TC
   Lacrampe-Couloume, G
   Ballentine, CJ
AF Lollar, Barbara Sherwood
   Onstott, T. C.
   Lacrampe-Couloume, G.
   Ballentine, C. J.
TI The contribution of the Precambrian continental lithosphere to global H2 production
SO NATURE
LA English
DT Article
ID witwatersrand basin; hydrogen generation; radiolytic h-2; noble-gases; serpentinization; crust; rocks; water; fluids; geochemistry
AB Microbial ecosystems can be sustained by hydrogen gas (H-2)-producing water-rock interactions in the Earth's subsurface and at deep ocean vents(1-4). Current estimates of global H-2 production from the marine lithosphere by water-rock reactions (hydration) are in the range of 10(11) moles per year(5-9). Recent explorations of saline fracture waters in the Precambrian continental subsurface have identified environments as rich in H-2 as hydrothermal vents and seafloor-spreading centres(1,2) and have suggested a link between dissolved H-2 and the radiolytic dissociation of water(10,11). However, extrapolation of a regional H-2 flux based on the deep gold mines of the Witwatersrand basin in South Africa(11) yields a contribution of the Precambrian lithosphere to global H-2 production that was thought to be negligible (0.009 x 10(11) moles per year)(6). Here we present a global compilation of published and new H-2 concentration data obtained from Precambrian rocks and find that the H-2 production potential of the Precambrian continental lithosphere has been underestimated. We suggest that this can be explained by a lack of consideration of additional H-2-producing reactions, such as serpentinization, and the absence of appropriate scaling of H-2 measurements from these environments to account for the fact that Precambrian crust represents over 70 per cent of global continental crust surface area(12). If H-2 production via both radiolysis and hydration reactions is taken into account, our estimate of H-2 production rates from the Precambrian continental lithosphere of 0.36-2.27 x 10(11) moles per year is comparable to estimates from marine systems.
C1 [Lollar, Barbara Sherwood; Lacrampe-Couloume, G.] Univ Toronto, Dept Earth Sci, Toronto, ON M5S 3B1, Canada.
   [Onstott, T. C.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Ballentine, C. J.] Univ Oxford, Dept Earth Sci, Oxford OX1 3AN, England.
C3 University of Toronto; Princeton University; University of Oxford
RP Lollar, BS (corresponding author), Univ Toronto, Dept Earth Sci, 22 Russell St, Toronto, ON M5S 3B1, Canada.
EM bslollar@chem.utoronto.ca
FU Canada Research Chairs programme; NSERC; Sloan Foundation Deep Carbon Observatory; Canadian Space Agency; National Science Foundation [EAR-0948659.f]; NERC [NE/F002823/1, NE/F002823/2] Funding Source: UKRI; Natural Environment Research Council [NE/F002823/2, NE/F002823/1] Funding Source: researchfish
NR 62
TC 233
Z9 279
U1 10
U2 137
PU NATURE PUBLISHING 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 18
PY 2014
VL 516
IS 7531
BP 379
EP +
DI 10.1038/nature14017
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800043
PM 25519136
DA 2026-03-09
ER

PT J
AU Schleich, S
   Strassburger, K
   Janiesch, PC
   Koledachkina, T
   Miller, KK
   Haneke, K
   Cheng, YS
   Küchler, K
   Stoecklin, G
   Duncan, KE
   Teleman, AA
AF Schleich, Sibylle
   Strassburger, Katrin
   Janiesch, Philipp Christoph
   Koledachkina, Tatyana
   Miller, Katharine K.
   Haneke, Katharina
   Cheng, Yong-Sheng
   Kuechler, Katrin
   Stoecklin, Georg
   Duncan, Kent E.
   Teleman, Aurelio A.
TI DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth
SO NATURE
LA English
DT Article
ID msl-2 messenger-rna; open reading frames; candidate oncogene; insulin-receptor; gene-expression; sex-lethal; drosophila; mechanism; protein; mct-1
AB During cap-dependent eukaryotic translation initiation, ribosomes scan messenger RNA from the 5' end to the first AUG start codon with favourable sequence context(1,2). For many mRNAs this AUG belongs to a short upstream open reading frame (uORF)(3), and translation of the main downstream ORF requires re-initiation, an incompletely understood process(1,4-6). Re-initiation is thought to involve the same factors as standard initiation(1,5,7). It is unknown whether any factors specifically affect translation re-initiation without affecting standard cap-dependent translation. Here we uncover the non-canonical initiation factors density regulated protein (DENR) and multiple copies in T-cell lymphoma-1(MCT-1; also called MCTS1 inhumans) as the first selective regulators of eukaryotic re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR-MCT-1 for their proper translation, yielding a novel class of mRNAs that can be co-regulated and that is enriched for regulatory proteins such as oncogenic kinases. Collectively, our data reveal that cells have a previously unappreciated translational control system with a key role in supporting proliferation and tissue growth.
C1 [Schleich, Sibylle; Strassburger, Katrin; Haneke, Katharina; Cheng, Yong-Sheng; Stoecklin, Georg; Teleman, Aurelio A.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Schleich, Sibylle; Janiesch, Philipp Christoph; Koledachkina, Tatyana; Miller, Katharine K.; Kuechler, Katrin; Duncan, Kent E.] Univ Med Ctr Hamburg Eppendorf UKE, Ctr Mol Neurobiol ZMNH, D-20251 Hamburg, Germany.
   [Haneke, Katharina; Stoecklin, Georg] Univ Heidelberg ZMBH, Zentrum Mol Biol, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); University of Hamburg; University Medical Center Hamburg-Eppendorf; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg
RP Duncan, KE (corresponding author), Univ Med Ctr Hamburg Eppendorf UKE, Ctr Mol Neurobiol ZMNH, Falkenried 94, D-20251 Hamburg, Germany.
EM kent.duncan@zmnh.uni-hamburg.de; a.teleman@dkfz.de
FU Hans und Ilse Breuer Foundation; Fritz Thyssen Foundation; Deutsche Forschungsgemeinschaft (DFG); ERC
NR 41
TC 142
Z9 152
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 AUG 14
PY 2014
VL 512
IS 7513
BP 208
EP +
DI 10.1038/nature13401
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM9KO
UT WOS:000340200700035
PM 25043021
DA 2026-03-09
ER

PT J
AU Elsworth, B
   Matthews, K
   Nie, CQ
   Kalanon, M
   Charnaud, SC
   Sanders, PR
   Chisholm, SA
   Counihan, NA
   Shaw, PJ
   Pino, P
   Chan, JA
   Azevedo, MF
   Rogerson, SJ
   Beeson, JG
   Crabb, BS
   Gilson, PR
   de Koning-Ward, TF
AF Elsworth, Brendan
   Matthews, Kathryn
   Nie, Catherine Q.
   Kalanon, Ming
   Charnaud, Sarah C.
   Sanders, Paul R.
   Chisholm, Scott A.
   Counihan, Natalie A.
   Shaw, Philip J.
   Pino, Paco
   Chan, Jo-Anne
   Azevedo, Mauro F.
   Rogerson, Stephen J.
   Beeson, James G.
   Crabb, Brendan S.
   Gilson, Paul R.
   de Koning-Ward, Tania F.
TI PTEX is an essential nexus for protein export in malaria parasites
SO NATURE
LA English
DT Article
ID falciparum-infected erythrocytes; plasmodium-falciparum; parasitophorous vacuole; chondroitin sulfate; placental malaria; surface; virulence; invasion; antibody; antigen
AB During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol(1-6). These proteins have a variety of roles that are essential to virulence or parasite growth(7). There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins(8,9). One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX)(10). Although PTEX has been linked to the export of one class of exported proteins(10,11), there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D)(1,2) and PEXEL-negative exported proteins (PNEPs)(6). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite's capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target.
C1 [Elsworth, Brendan; Nie, Catherine Q.; Charnaud, Sarah C.; Sanders, Paul R.; Chan, Jo-Anne; Azevedo, Mauro F.; Beeson, James G.; Crabb, Brendan S.; Gilson, Paul R.] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia.
   [Elsworth, Brendan; Charnaud, Sarah C.; Beeson, James G.; Crabb, Brendan S.; Gilson, Paul R.] Monash Univ, Clayton, Vic 3800, Australia.
   [Matthews, Kathryn; Kalanon, Ming; Chisholm, Scott A.; Counihan, Natalie A.; de Koning-Ward, Tania F.] Deakin Univ, Waurn Ponds, Vic 3216, Australia.
   [Shaw, Philip J.] Natl Ctr Genet Engn & Biotechnol BIOTEC, Pathum Thani 12120, Thailand.
   [Pino, Paco] Univ Geneva, CH-1211 Geneva 4, Switzerland.
   [Rogerson, Stephen J.; Beeson, James G.; Crabb, Brendan S.] Univ Melbourne, Parkville, Vic 3010, Australia.
C3 Burnet Institute; Monash University; Deakin University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); University of Geneva; University of Melbourne
RP de Koning-Ward, TF (corresponding author), Deakin Univ, Waurn Ponds, Vic 3216, Australia.
EM crabb@burnet.edu.au; gilson@burnet.edu.au; taniad@deakin.edu.au
FU National Health and Medical Research Council (NHMRC) of Australia [1021560, 1025665, 637406]; Victorian State Government; Australian Postgraduate Awards; National Health and Medical Research Council (NHMRC) [1021560] Funding Source: National Health and Medical Research Council (NHMRC)
NR 42
TC 201
Z9 236
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 JUL 30
PY 2014
VL 511
IS 7511
BP 587
EP +
DI 10.1038/nature13555
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300034
PM 25043043
DA 2026-03-09
ER

PT J
AU Eckel, S
   Lee, JG
   Jendrzejewski, F
   Murray, N
   Clark, CW
   Lobb, CJ
   Phillips, WD
   Edwards, M
   Campbell, GK
AF Eckel, Stephen
   Lee, Jeffrey G.
   Jendrzejewski, Fred
   Murray, Noel
   Clark, Charles W.
   Lobb, Christopher J.
   Phillips, William D.
   Edwards, Mark
   Campbell, Gretchen K.
TI Hysteresis in a quantized superfluid 'atomtronic' circuit
SO NATURE
LA English
DT Article
ID bose-einstein condensate; states; gas; rotation
AB Atomtronics(1,2) is an emerging interdisciplinary field that seeks to develop new functional methods by creating devices and circuits where ultracold atoms, often superfluids, have a role analogous to that of electrons in electronics. Hysteresis is widely used in electronic circuits-it is routinely observed in superconducting circuits(3) and is essential in radio-frequency superconducting quantum interference devices(4). Furthermore, it is as fundamental to superfluidity(5) (and superconductivity) as quantized persistent currents(6-8), critical velocity(9-14) and Josephson effects(15,16). Nevertheless, despite multiple theoretical predictions(5,17-19), hysteresis has not been previously observed in any superfluid, atomic-gas Bose-Einstein condensate. Here we directly detect hysteresis between quantized circulation states in an atomtronic circuit formed from a ring of superfluid Bose-Einstein condensate obstructed by a rotating weak link (a region of low atomic density). This contrasts with previous experiments on superfluid liquid helium where hysteresis was observed directly in systems in which the quantization of flow could not be observed(20), and indirectly in systems that showed quantized flow(21,22). Our techniques allow us to tune the size of the hysteresis loop and to consider the fundamental excitations that accompany hysteresis. The results suggest that the relevant excitations involved in hysteresis are vortices, and indicate that dissipation has an important role in the dynamics. Controlled hysteresis in atomtronic circuits may prove to be a crucial feature for the development of practical devices, just as it has in electronic circuits such as memories, digital noise filters (for example Schmitt triggers) and magnetometers (for example superconducting quantum interference devices).
C1 [Eckel, Stephen; Lee, Jeffrey G.; Jendrzejewski, Fred; Clark, Charles W.; Lobb, Christopher J.; Phillips, William D.; Campbell, Gretchen K.] NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
   [Eckel, Stephen; Lee, Jeffrey G.; Jendrzejewski, Fred; Clark, Charles W.; Lobb, Christopher J.; Phillips, William D.; Campbell, Gretchen K.] Univ Maryland, Gaithersburg, MD 20899 USA.
   [Murray, Noel; Edwards, Mark] Georgia So Univ, Dept Phys, Statesboro, GA 30460 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; University System of Georgia; Georgia Southern University
RP Campbell, GK (corresponding author), NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
EM gretchen.campbell@nist.gov
FU ONR; ARO atomtronics MURI; NSF through the PFC at the JQI; National Research Council;  [PHY-1068761]; Direct For Mathematical & Physical Scien; Division Of Physics [1068761] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0822671] Funding Source: National Science Foundation
NR 33
TC 311
Z9 341
U1 1
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 FEB 13
PY 2014
VL 506
IS 7487
BP 200
EP +
DI 10.1038/nature12958
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700033
PM 24522597
DA 2026-03-09
ER

PT J
AU Schurr, B
   Asch, G
   Hainzl, S
   Bedford, J
   Hoechner, A
   Palo, M
   Wang, RJ
   Moreno, M
   Bartsch, M
   Zhang, Y
   Oncken, O
   Tilmann, F
   Dahm, T
   Victor, P
   Barrientos, S
   Vilotte, JP
AF Schurr, Bernd
   Asch, Guenter
   Hainzl, Sebastian
   Bedford, Jonathan
   Hoechner, Andreas
   Palo, Mauro
   Wang, Rongjiang
   Moreno, Marcos
   Bartsch, Mitja
   Zhang, Yong
   Oncken, Onno
   Tilmann, Frederik
   Dahm, Torsten
   Victor, Pia
   Barrientos, Sergio
   Vilotte, Jean-Pierre
TI Gradual unlocking of plate boundary controlled initiation of the 2014 Iquique earthquake
SO NATURE
LA English
DT Article
ID short-term; chile; rupture; models; fault; deformation; phase; zone; hypocenter; magnitude
AB On 1 April 2014, Northern Chile was struck by a magnitude 8.1 earthquake following a protracted series of foreshocks. The Integrated Plate Boundary Observatory Chile monitored the entire sequence of events, providing unprecedented resolution of the build-up to the main event and its rupture evolution. Here we show that the Iquique earthquake broke a central fraction of the so-called northern Chile seismic gap, the last major segment of the South American plate boundary that had not ruptured in the past century(1,2). Since July 2013 three seismic clusters, each lasting a few weeks, hit this part of the plate boundary with earthquakes of increasing peak magnitudes. Starting with the second cluster, geodetic observations show surface displacements that can be associated with slip on the plate interface. These seismic clusters and their slip transients occupied a part of the plate interface that was transitional between a fully locked and a creeping portion. Leading up to this earthquake, the b value of the foreshocks gradually decreased during the years before the earthquake, reversing its trend a few days before the Iquique earthquake. The mainshock finally nucleated at the northern end of the foreshock area, which skirted a locked patch, and ruptured mainly downdip towards higher locking. Peak slip was attained immediately downdip of the foreshock region and at the margin of the locked patch. We conclude that gradual weakening of the central part of the seismic gap accentuated by the foreshock activity in a zone of intermediate seismic coupling was instrumental in causing final failure, distinguishing the Iquique earthquake from most great earthquakes. Finally, only one-third of the gap was broken and the remaining locked segments nowpose a significant, increased seismic hazard with the potential to host an earthquake with a magnitude of > 8.5.
C1 [Schurr, Bernd; Asch, Guenter; Hainzl, Sebastian; Bedford, Jonathan; Hoechner, Andreas; Palo, Mauro; Wang, Rongjiang; Moreno, Marcos; Bartsch, Mitja; Oncken, Onno; Tilmann, Frederik; Dahm, Torsten; Victor, Pia] German Res Ctr Geosci, GFZ Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
   [Zhang, Yong] Peking Univ, Sch Earth & Space Sci, Beijing 100871, Peoples R China.
   [Barrientos, Sergio] Univ Chile, Ctr Sismol Natl, Fac Ciencias Fis & Matemat, Santiago 2002, Chile.
   [Vilotte, Jean-Pierre] Inst Phys Globe Paris, F-75238 Paris 05, France.
C3 Helmholtz Association; GFZ Helmholtz Centre for Geosciences; Peking University; Universidad de Chile; Universite Paris Cite
RP Schurr, B (corresponding author), German Res Ctr Geosci, GFZ Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
EM schurr@gfz-potsdam.de
FU GFZ; Hannover Re
NR 55
TC 289
Z9 320
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 AUG 21
PY 2014
VL 512
IS 7514
BP 299
EP +
DI 10.1038/nature13681
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200032
PM 25119049
DA 2026-03-09
ER

PT J
AU Gerstein, MB
   Rozowsky, J
   Yan, KK
   Wang, DF
   Cheng, C
   Brown, JB
   Davis, CA
   Hillier, L
   Sisu, C
   Li, JJ
   Pei, BK
   Harmanci, AO
   Duff, MO
   Djebali, S
   Alexander, RP
   Alver, BH
   Auerbach, R
   Bell, K
   Bickel, PJ
   Boeck, ME
   Boley, NP
   Booth, BW
   Cherbas, L
   Cherbas, P
   Di, C
   Dobins, A
   Drenkows, J
   Ewing, B
   Fang, G
   Fastucas, M
   Feingold, EA
   Frankish, A
   Gao, GJ
   Good, PJ
   Guigó, R
   Hammonds, A
   Harrow, J
   Hoskins, RA
   Howald, C
   Hu, L
   Huang, HY
   Hubbard, TJP
   Huynh, C
   Jhas, S
   Kasper, D
   Kato, M
   Kaufman, TC
   Kitchen, RR
   Ladewig, E
   Lagarde, J
   Lai, E
   Leng, L
   Lu, Z
   MacCoss, M
   May, G
   McWhirter, R
   Merrihew, G
   Miller, DM
   Mortazavi, A
   Murad, R
   Oliver, B
   Olson, S
   Park, PJ
   Pazin, MJ
   Perrimon, N
   Pervouchine, D
   Reinke, V
   Reymond, A
   Robinson, G
   Samsonova, A
   Saunders, GI
   Schlesingers, F
   Sethi, A
   Slack, FJ
   Spencer, WC
   Stoiber, MH
   Strasbourger, P
   Tanzer, A
   Thompson, OA
   Wan, KH
   Wang, GL
   Wang, H
   Watkins, KL
   Wen, JY
   Wen, KJ
   Xue, CH
   Yang, L
   Yip, K
   Zaleskis, C
   Zhang, Y
   Zheng, H
   Brenner, SE
   Graveley, BR
   Ceniker, SE
   Gingeras, TR
   Waterston, R
AF Gerstein, Mark B.
   Rozowsky, Joel
   Yan, Koon-Kiu
   Wang, Daifeng
   Cheng, Chao
   Brown, James B.
   Davis, Carrie A.
   Hillier, LaDeana
   Sisu, Cristina
   Li, Jingyi Jessica
   Pei, Baikang
   Harmanci, Arif O.
   Duff, Michael O.
   Djebali, Sarah
   Alexander, Roger P.
   Alver, Burak H.
   Auerbach, Raymond
   Bell, Kimberly
   Bickel, Peter J.
   Boeck, Max E.
   Boley, Nathan P.
   Booth, Benjamin W.
   Cherbas, Lucy
   Cherbas, Peter
   Di, Chao
   Dobins, Alex
   Drenkows, Jorg
   Ewing, Brent
   Fang, Gang
   Fastucas, Megan
   Feingold, Elise A.
   Frankish, Adam
   Gao, Guanjun
   Good, Peter J.
   Guigo, Roderic
   Hammonds, Ann
   Harrow, Jen
   Hoskins, Roger A.
   Howald, Cedric
   Hu, Long
   Huang, Haiyan
   Hubbard, Tim J. P.
   Huynh, Chau
   Jhas, Sonali
   Kasper, Dionna
   Kato, Masaomi
   Kaufman, Thomas C.
   Kitchen, Robert R.
   Ladewig, Erik
   Lagarde, Julien
   Lai, Eric
   Leng, Ling
   Lu, Zhi
   MacCoss, Michael
   May, Gemma
   McWhirter, Rebecca
   Merrihew, Gennifer
   Miller, David M.
   Mortazavi, Ali
   Murad, Rabi
   Oliver, Brian
   Olson, Sara
   Park, Peter J.
   Pazin, Michael J.
   Perrimon, Norbert
   Pervouchine, Dmitri
   Reinke, Valerie
   Reymond, Alexandre
   Robinson, Garrett
   Samsonova, Anastasia
   Saunders, Gary I.
   Schlesingers, Felix
   Sethi, Anurag
   Slack, Frank J.
   Spencer, William C.
   Stoiber, Marcus H.
   Strasbourger, Pnina
   Tanzer, Andrea
   Thompson, Owen A.
   Wan, Kenneth H.
   Wang, Guilin
   Wang, Huaien
   Watkins, Kathie L.
   Wen, Jiayu
   Wen, Kejia
   Xue, Chenghai
   Yang, Li
   Yip, Kevin
   Zaleskis, Chris
   Zhang, Yan
   Zheng, Henry
   Brenner, Steven E.
   Graveley, Brenton R.
   Ceniker, Susan E.
   Gingeras, Thomas R.
   Waterston, Robert
TI Comparative analysis of the transcriptome across distant species
SO NATURE
LA English
DT Article
ID gene-expression; landscape; evolution; tissue; genome; cells
AB The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features(1-6). Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.
C1 [Gerstein, Mark B.; Rozowsky, Joel; Yan, Koon-Kiu; Wang, Daifeng; Sisu, Cristina; Pei, Baikang; Harmanci, Arif O.; Alexander, Roger P.; Auerbach, Raymond; Fang, Gang; Kitchen, Robert R.; Leng, Ling; Mortazavi, Ali; Sethi, Anurag; Zhang, Yan; Zheng, Henry] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Gerstein, Mark B.; Rozowsky, Joel; Yan, Koon-Kiu; Wang, Daifeng; Sisu, Cristina; Pei, Baikang; Harmanci, Arif O.; Alexander, Roger P.; Auerbach, Raymond; Fang, Gang; Kitchen, Robert R.; Leng, Ling; Mortazavi, Ali; Sethi, Anurag; Zhang, Yan; Zheng, Henry] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA.
   [Cheng, Chao] Geisel Sch Med Dartmouth, Dept Genet, Hanover, NH 03755 USA.
   [Cheng, Chao] Geisel Sch Med Dartmouth, Inst Quantitat Biomed Sci, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA.
   [Brown, James B.; Boley, Nathan P.; Booth, Benjamin W.; Hammonds, Ann; Hoskins, Roger A.; Stoiber, Marcus H.; Wan, Kenneth H.; Ceniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA.
   [Brown, James B.; Li, Jingyi Jessica; Bickel, Peter J.; Huang, Haiyan; Robinson, Garrett] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Davis, Carrie A.; Bell, Kimberly; Dobins, Alex; Drenkows, Jorg; Fastucas, Megan; Jhas, Sonali; Schlesingers, Felix; Wang, Huaien; Xue, Chenghai; Zaleskis, Chris; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Hillier, LaDeana; Boeck, Max E.; Ewing, Brent; Huynh, Chau; MacCoss, Michael; Merrihew, Gennifer; Strasbourger, Pnina; Thompson, Owen A.; Waterston, Robert] Dept Genome Sci, Seattle, WA 98195 USA.
   [Hillier, LaDeana; Boeck, Max E.; Ewing, Brent; Huynh, Chau; MacCoss, Michael; Merrihew, Gennifer; Strasbourger, Pnina; Thompson, Owen A.; Waterston, Robert] Univ Washington, Sch Med, Seattle, WA 98195 USA.
   [Li, Jingyi Jessica] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA.
   [Li, Jingyi Jessica] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Duff, Michael O.; May, Gemma; Olson, Sara; Yang, Li; Graveley, Brenton R.] Univ Connecticut, Ctr Hlth, Inst Syst Genom, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
   [Djebali, Sarah; Guigo, Roderic; Lagarde, Julien; Pervouchine, Dmitri] Ctr Genom Regulat, Barcelona 08003, Catalonia, Spain.
   [Djebali, Sarah; Guigo, Roderic; Lagarde, Julien; Pervouchine, Dmitri] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona 08003, Catalonia, Spain.
   [Alver, Burak H.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Boley, Nathan P.; Stoiber, Marcus H.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Cherbas, Lucy; Cherbas, Peter; Kaufman, Thomas C.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Cherbas, Lucy; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA.
   [Di, Chao; Gao, Guanjun; Hu, Long; Lu, Zhi; Wen, Kejia] Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China.
   [Feingold, Elise A.; Good, Peter J.; Pazin, Michael J.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Frankish, Adam; Harrow, Jen; Hubbard, Tim J. P.; Saunders, Gary I.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Howald, Cedric; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Howald, Cedric] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Hubbard, Tim J. P.] Kings Coll London, London WC2R 2LS, England.
   [Kasper, Dionna; Reinke, Valerie; Wang, Guilin] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Kato, Masaomi; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Ladewig, Erik; Lai, Eric; Wen, Jiayu] Sloan Kettering Inst, New York, NY 10065 USA.
   [May, Gemma] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
   [McWhirter, Rebecca; Miller, David M.; Spencer, William C.; Watkins, Kathie L.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA.
   [Mortazavi, Ali; Murad, Rabi] Univ Calif Irvine, Irvine, CA 92697 USA.
   [Mortazavi, Ali; Murad, Rabi] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA.
   [Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Perrimon, Norbert; Samsonova, Anastasia] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Perrimon, Norbert; Samsonova, Anastasia] Harvard Univ, Sch Med, Drosophila RNAi Screening Ctr, Boston, MA 02115 USA.
   [Perrimon, Norbert; Samsonova, Anastasia] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Saunders, Gary I.] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Tanzer, Andrea] Univ Pompeu Fabra, Ctr Genom Regulat, Bioinformat & Genom Programme, Barcelona 08003, Catalonia, Spain.
   [Tanzer, Andrea] Univ Vienna, Theoret Biochem Grp TBI, Inst Theoret Chem, A-1090 Vienna, Austria.
   [Yang, Li] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China.
   [Yip, Kevin] Chinese Univ Hong Kong, Hong Kong Bioinformat Ctr, Shatin, Hong Kong, Peoples R China.
   [Yip, Kevin] Chinese Univ Hong Kong, CUHK BGI Innovat Inst Trans Omics 5, Shatin, Hong Kong, Peoples R China.
   [Brenner, Steven E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
C3 Yale University; Yale University; Yale University; Dartmouth College; Dartmouth College; Dartmouth Cancer Center; 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; Cold Spring Harbor Laboratory; University of Washington; University of Washington Seattle; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of Connecticut; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Harvard University; Harvard Medical School; University of California System; University of California Berkeley; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; Tsinghua University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Wellcome Trust Sanger Institute; University of Lausanne; Swiss Institute of Bioinformatics; University of London; King's College London; Yale University; Yale University; Memorial Sloan Kettering Cancer Center; Carnegie Mellon University; Vanderbilt University; University of California System; University of California Irvine; University of California System; University of California Irvine; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); University of Vienna; Max Planck Society; Chinese Academy of Sciences; Chinese University of Hong Kong; Chinese University of Hong Kong; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Gerstein, MB (corresponding author), Yale Univ, Program Computat Biol & Bioinformat, Bass 432,266 Whitney Ave, New Haven, CT 06520 USA.
EM cmptxn@gersteinlab.org
FU NHGRI; ENCODE; modENCODE project; National Human Genome Research Institute modENCODE Project under Department of Energy [U01 HG004271, U54 HG006944]; Department of Energy [R01 GM076655, DE-AC02-05CH11231, U54 HG007005]; NHGRI [K99 HG006698]; DOE [DE-AC02-05CH11231]; modENCODE DAC sub award [5710003102, 1 U01HG007031-01]; ENCODE DAC [5U01HG004695-04]; NIH [HG007000, HG007355]; Indiana METACyt Initiative of Indiana University - Lilly Endowment, Inc.; National Institutes of Health [U01HG004258, 5U54HG004555]; Wellcome Trust [WT098051]; Spanish Ministry of Education [BIO2011-26205];  [U01-HG004261];  [RC2-HG005639]; [U01 HG 004263]; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER; National Human Genome Research Institute [U41HG007355] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK015600] Funding Source: NIH RePORTER; National Library of Medicine [T15LM007056] Funding Source: NIH RePORTER
NR 19
TC 209
Z9 259
U1 1
U2 156
PU NATURE PUBLISHING 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 28
PY 2014
VL 512
IS 7515
BP 445
EP +
DI 10.1038/nature13424
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600037
PM 25164755
DA 2026-03-09
ER

PT J
AU Kraus, D
   Yang, Q
   Kong, D
   Banks, AS
   Zhang, L
   Rodgers, JT
   Pirinen, E
   Pulinilkunnil, TC
   Gong, FY
   Wang, YC
   Cen, YN
   Sauve, AA
   Asara, JM
   Peroni, OD
   Monia, BP
   Bhanot, S
   Alhonen, L
   Puigserver, P
   Kahn, BB
AF Kraus, Daniel
   Yang, Qin
   Kong, Dong
   Banks, Alexander S.
   Zhang, Lin
   Rodgers, Joseph T.
   Pirinen, Eija
   Pulinilkunnil, Thomas C.
   Gong, Fengying
   Wang, Ya-chin
   Cen, Yana
   Sauve, Anthony A.
   Asara, John M.
   Peroni, Odile D.
   Monia, Brett P.
   Bhanot, Sanjay
   Alhonen, Leena
   Puigserver, Pere
   Kahn, Barbara B.
TI Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity
SO NATURE
LA English
DT Article
ID adipose-tissue; cdna cloning; expression; mouse; liver; sirt1; mice; metabolism; resistance; cancer
AB In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes(1). Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity(2). Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue(WAT) from adipose-specific Glut4k-nockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor(3,4). Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism(5). SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation(6). Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine-spermine N-1-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism(7,8). We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD(+)-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes.
C1 [Kraus, Daniel; Yang, Qin; Kong, Dong; Zhang, Lin; Pulinilkunnil, Thomas C.; Gong, Fengying; Wang, Ya-chin; Peroni, Odile D.; Kahn, Barbara B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
   [Kraus, Daniel; Yang, Qin; Kong, Dong; Zhang, Lin; Pulinilkunnil, Thomas C.; Gong, Fengying; Wang, Ya-chin; Asara, John M.; Peroni, Odile D.; Kahn, Barbara B.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Banks, Alexander S.; Rodgers, Joseph T.; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Pirinen, Eija; Alhonen, Leena] Univ Eastern Finland, Bioctr Kuopio, AI Virtanen Inst Mol Sci, FI-70211 Kuopio, Finland.
   [Cen, Yana; Sauve, Anthony A.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10065 USA.
   [Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA.
   [Monia, Brett P.; Bhanot, Sanjay] ISIS Pharmaceut, Carlsbad, CA 92008 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; University of Eastern Finland; Cornell University; Weill Cornell Medicine; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Ionis Pharmaceuticals, Inc.
RP Kahn, BB (corresponding author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02215 USA.
EM qin.yang@uci.edu; bkahn@bidmc.harvard.edu
FU Deutsche Forschungsgemeinschaft [KR 3475/1-1]; American Heart Association (AHA) [09POST2250499]; NIH [R37 DK43051, P30 DK57521, KO8 DK090149, R01 DK100385, BNORC P30 DK046200, NORCH P30 DK040561]; JPB foundation; AHA [13SDG14620005, PF P30 DK0460200]; Ellison Medical Foundation New Scholar in Aging Award; academy of Finland [118590];  [RO1 DK69966];  [P01CA120964];  [P30CA006516-46]; Academy of Finland (AKA) [118590] Funding Source: Academy of Finland (AKA); American Heart Association (AHA) [09POST2250499, 13SDG14620005] Funding Source: American Heart Association (AHA); National Cancer Institute [P30CA006516, P01CA120964] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK046200, P30DK040561, T32DK007516] Funding Source: NIH RePORTER
NR 43
TC 402
Z9 448
U1 6
U2 224
PU NATURE PUBLISHING 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 10
PY 2014
VL 508
IS 7495
BP 258
EP +
DI 10.1038/nature13198
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900047
PM 24717514
DA 2026-03-09
ER

PT J
AU Di Stefano, B
   Sardina, JL
   van Oevelen, C
   Collombet, S
   Kallin, EM
   Vicent, GP
   Lu, J
   Thieffry, D
   Beato, M
   Graf, T
AF Di Stefano, Bruno
   Sardina, Jose Luis
   van Oevelen, Chris
   Collombet, Samuel
   Kallin, Eric M.
   Vicent, Guillermo P.
   Lu, Jun
   Thieffry, Denis
   Beato, Miguel
   Graf, Thomas
TI C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID network; transdifferentiation; macrophages; tet2; requirement; reveals
AB CCAAT/enhancer binding protein-alpha (C/EBP alpha) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and Myc (hereafter called OSKM)(1,2). However, how C/EBP alpha accomplishes these effects is unclear. Here we find that in mouse primary B cells transient C/EBP alpha expression followed by OSKM activation induces a 100-fold increase in iPS cell reprogramming efficiency, involving 95% of the population. During this conversion, pluripotency and epithelial-mesenchymal transition genes become markedly upregulated, and 60% of the cells express Oct4 within 2 days. C/EBP alpha acts as a 'path-breaker' as it transiently makes the chromatin of pluripotency genes more accessible to DNase I. C/EBP alpha also induces the expression of the dioxygenase Tet2 and promotes its translocation to the nucleus where it binds to regulatory regions of pluripotency genes that become demethylated after OSKM induction. In line with these findings, overexpression of Tet2 enhances OSKM-induced B-cell reprogramming. Because the enzyme is also required for efficient C/EBP alpha-induced immune cell conversion(3), our data indicate that Tet2 provides a mechanistic link between iPS cell reprogramming and B-cell transdifferentiation. The rapid iPS reprogramming approach described here should help to fully elucidate the process and has potential clinical applications.
C1 [Di Stefano, Bruno; Sardina, Jose Luis; van Oevelen, Chris; Kallin, Eric M.; Vicent, Guillermo P.; Beato, Miguel; Graf, Thomas] CRG, Gene Regulat Stem Cells & Canc Programme, Barcelona 08003, Spain.
   [Di Stefano, Bruno; Sardina, Jose Luis; van Oevelen, Chris; Kallin, Eric M.; Vicent, Guillermo P.; Beato, Miguel; Graf, Thomas] UPF, Barcelona 08003, Spain.
   [Collombet, Samuel; Thieffry, Denis] ENS, Inst Biol, F-75005 Paris, France.
   [Collombet, Samuel; Thieffry, Denis] INSERM, U1024, F-75005 Paris, France.
   [Collombet, Samuel; Thieffry, Denis] CNRS, UMR 8197, F-75005 Paris, France.
   [Lu, Jun] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06510 USA.
   [Graf, Thomas] Pg Lluis Co 23, ICREA, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Yale University; Yale New Haven Hospital; ICREA
RP Graf, T (corresponding author), UPF, Dr Aiguader 88, Barcelona 08003, Spain.
EM Thomas.Graf@crg.eu
FU Ministerio de Educacion y Ciencia [SAF.2007-63058, AGAUR 2009 SGR768]; La Caixa International PhD Fellowship; ICREA Funding Source: Custom
NR 30
TC 162
Z9 205
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 FEB 13
PY 2014
VL 506
IS 7487
BP 235
EP +
DI 10.1038/nature12885
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700041
PM 24336202
DA 2026-03-09
ER

PT J
AU Marcott, SA
   Bauska, TK
   Buizert, C
   Steig, EJ
   Rosen, JL
   Cuffey, KM
   Fudge, TJ
   Severinghaus, JP
   Ahn, J
   Kalk, ML
   McConnell, JR
   Sowers, T
   Taylor, KC
   White, JWC
   Brook, EJ
AF Marcott, Shaun A.
   Bauska, Thomas K.
   Buizert, Christo
   Steig, Eric J.
   Rosen, Julia L.
   Cuffey, Kurt M.
   Fudge, T. J.
   Severinghaus, Jeffery P.
   Ahn, Jinho
   Kalk, Michael L.
   McConnell, Joseph R.
   Sowers, Todd
   Taylor, Kendrick C.
   White, James W. C.
   Brook, Edward J.
TI Centennial-scale changes in the global carbon cycle during the last deglaciation
SO NATURE
LA English
DT Article
ID vostok ice core; atmospheric co2; antarctic ice; polar ice; chronology aicc2012; greenland; climate; air; ocean; age
AB Global climate and the concentration of atmospheric carbon dioxide (CO2) are correlated over recent glacial cycles(1,2). The combination of processes responsible for a rise in atmospheric CO2 at the last glacial termination(1,3) (23,000 to 9,000 years ago), however, remains uncertain(1-3). Establishing the timing and rate of CO2 changes in the past provides critical insight into the mechanisms that influence the carbon cycle and helps put present and future anthropogenic emissions in context. Here we present CO2 and methane (CH4) records of the last deglaciation from a new high-accumulation West Antarctic ice core with unprecedented temporal resolution and precise chronology. We show that although low-frequency CO2 variations parallel changes in Antarctic temperature, abrupt CO2 changes occur that have a clear relationship with abrupt climate changes in the Northern Hemisphere. A significant proportion of the direct radiative forcing associated with the rise in atmospheric CO2 occurred in three sudden steps, each of 10 to 15 parts per million. Every step took place in less than two centuries and was followed by no notable change in atmospheric CO2 for about 1,000 to 1,500 years. Slow, millennial-scale ventilation of Southern Ocean CO2-rich, deep-ocean water masses is thought to have been fundamental to the rise in atmospheric CO2 associated with the glacial termination(4), given the strong covariance of CO2 levels and Antarctic temperatures(5). Our data establish a contribution from an abrupt, centennial-scale mode of CO2 variability that is not directly related to Antarctic temperature. We suggest that processes operating on centennial timescales, probably involving the Atlantic meridional overturning circulation, seem to be influencing global carbon-cycle dynamics and are at present not widely considered in Earth system models.
C1 [Marcott, Shaun A.; Bauska, Thomas K.; Buizert, Christo; Rosen, Julia L.; Kalk, Michael L.; Brook, Edward J.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Marcott, Shaun A.] Univ Wisconsin Madison, Dept Geosci, Madison, WI 53706 USA.
   [Steig, Eric J.; Fudge, T. J.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Cuffey, Kurt M.] Univ Calif Berkeley, Dept Geog, Berkeley, CA 94720 USA.
   [Severinghaus, Jeffery P.] Univ Calif San Diego, Scripps Inst Oceanog, San Diego, CA 92037 USA.
   [Ahn, Jinho] Seoul Natl Univ, Sch Earth & Environm Sci, Seoul 151742, South Korea.
   [McConnell, Joseph R.; Taylor, Kendrick C.] Nevada Syst Higher Educ, Desert Res Inst, Reno, NV 89512 USA.
   [Sowers, Todd] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [White, James W. C.] Univ Colorado, INSTAAR, Boulder, CO 80309 USA.
C3 Oregon State University; University of Wisconsin System; University of Wisconsin Madison; University of Washington; University of Washington Seattle; University of California System; University of California Berkeley; University of California System; University of California San Diego; Scripps Institution of Oceanography; Seoul National University (SNU); Nevada System of Higher Education (NSHE); Desert Research Institute NSHE; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Colorado System; University of Colorado Boulder
RP Marcott, SA (corresponding author), Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
EM smarcott@wisc.edu
FU US National Science Foundation (NSF) [0739766-ANT, 1043518-ANT, 1043092-ANT, 0839093-ANT, 1142166-ANT]; NSF [0230396, 0440817, 0944348, 0944266]; NSF Office of Polar Programs through Ice Drilling Program Office; NSF Office of Polar Programs through Ice Drilling Design and Operations group; Korea Meteorological Administration Research and Development Program [CATER 2012-7030]; Directorate For Geosciences; Division Of Polar Programs [0944191] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [1142166, 1246465, 0944348] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0944197, 1043167, 1043092, 1043522, 1043518] Funding Source: National Science Foundation; Office Of The Director; Office Of Internatl Science &Engineering [0968391] Funding Source: National Science Foundation
NR 59
TC 399
Z9 450
U1 2
U2 348
PU NATURE PUBLISHING 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 30
PY 2014
VL 514
IS 7524
BP 616
EP +
DI 10.1038/nature13799
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500046
PM 25355363
DA 2026-03-09
ER

PT J
AU Kernbauer, E
   Ding, Y
   Cadwell, K
AF Kernbauer, Elisabeth
   Ding, Yi
   Cadwell, Ken
TI An enteric virus can replace the beneficial function of commensal bacteria
SO NATURE
LA English
DT Article
ID autophagy gene atg16l1; day-care-center; gut microbiota; infection; disease; virome; pathogenesis; inflammation; replication; resistance
AB Intestinal microbial communities have profound effects on host physiology(1). Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined(2,3). Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Mmine norovirus (MNV) infection of germ-free or antibiotictreated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-a receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.
C1 [Kernbauer, Elisabeth; Cadwell, Ken] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Kernbauer, Elisabeth; Cadwell, Ken] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
   [Ding, Yi] New York Presbyterian Hosp, New York, NY 10065 USA.
   [Ding, Yi] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
C3 New York University; New York University; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital; New York University
RP Cadwell, K (corresponding author), NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
EM ken.cadwell@med.nyu.edu
FU Cancer Center Support Grant [P30CA016087]; National Institutes of Health [R01 DK093668]; New York University Whitehead Fellowship; Vilcek Fellowship; Erwin Schrodinger Fellowship from the Austrian Science Foundation; Austrian Science Fund (FWF) [J 3435] Funding Source: researchfish; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK093668] Funding Source: NIH RePORTER
NR 38
TC 390
Z9 463
U1 4
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 DEC 4
PY 2014
VL 516
IS 7529
BP 94
EP U223
DI 10.1038/nature13960
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800046
PM 25409145
DA 2026-03-09
ER

PT J
AU Williams, AL
   Jacobs, SBR
   Moreno-Macías, H
   Huerta-Chagoya, A
   Churchhouse, C
   Márquez-Luna, C
   García-Ortiz, H
   Gómez-Vázquez, MJ
   Burtt, NP
   Aguilar-Salinas, CA
   González-Villalpando, C
   Florez, JC
   Orozco, L
   Haiman, CA
   Tusié-Luna, T
   Altshuler, D
   Williams, AL
   Márquez-Luna, C
   Huerta-Chagoya, A
   Ripke, S
   Gómez-Vázquez, MJ
   Manning, AK
   Moreno-Macías, H
   García-Ortíz, H
   Neale, B
   Burtt, NP
   Aguilar-Salinas, CA
   Reich, D
   Stram, DO
   Fernández-López, JC
   Romero-Hidalgo, S
   Altshuler, D
   Florez, JC
   Tusié-Luna, T
   Patterson, N
   Haiman, CA
   Aguilar-Delfín, I
   Martínez-Hernández, A
   Centeno-Cruz, F
   Mendoza-Caamal, E
   Revilla-Monsalve, C
   Islas-Andrade, S
   Córdova, E
   Rodríguez-Arellano, E
   Soberón, X
   Orozco, L
   Florez, JC
   González-Villalpando, C
   González-Villalpando, ME
   Haiman, CA
   Henderson, BE
   Monroe, K
   Wilkens, L
   Kolonel, LN
   Le Marchand, L
   Riba, L
   Ordóñez-Sánchez, ML
   Rodríguez-Guillén, R
   Cruz-Bautista, I
   Rodríguez-Torres, M
   Muñoz-Hernández, LL
   Sáenz, T
   Gómez, D
   Alvirde, U
   Burtt, NP
   Onofrio, RC
   Brodeur, WM
   Gage, D
   Murphy, J
   Franklin, J
   Mahan, S
   Ardlie, K
   Crenshaw, AT
   Winckler, W
   Prüfer, K
   Shunkov, MV
   Sawyer, S
   Stenzel, U
   Kelso, J
   Lek, M
   Sankararaman, S
   Williams, AL
   Patterson, N
   MacArthur, DG
   Reich, D
   Derevianko, AP
   Pääbo, S
   Jacobs, SBR
   Churchhouse, C
   Gopal, S
   Grammatikos, JA
   Smith, IC
   Bullock, KH
   Deik, AA
   Souza, AL
   Pierce, KA
   Clish, CB
   Altshuler, D
   Fennell, T
   Farjoun, Y
   Gabriel, S
   Stram, DO
   Gross, MD
   Pereira, MA
   Seielstad, M
   Koh, WP
   Tai, ES
   Flannick, J
   Fontanillas, P
   Morris, A
   Teslovich, TM
   Burtt, NP
   Atzmon, G
   Blangero, J
   Bowden, DW
   Chambers, J
   Cho, YS
   Duggirala, R
   Glaser, B
   Hanis, C
   Kooner, J
   Laakso, M
   Lee, JY
   Tai, ES
   Teo, YY
   Wilson, JG
   Haiman, CA
   Henderson, BE
   Monroe, K
   Wilkens, L
   Kolonel, LN
   Le Marchand, L
   Puppala, S
   Farook, VS
   Thameem, F
   Abboud, HE
   DeFronzo, RA
   Jenkinson, CP
   Lehman, DM
   Curran, JE
   Blangero, J
   Duggirala, R
   Burtt, NP
   Cortes, ML
   Altshuler, D
   Florez, JC
   Haiman, CA
   Henderson, BE
   Aguilar-Salinas, CA
   González-Villalpando, C
   Orozco, L
   Tusié-Luna, T
AF Williams, Amy L.
   Jacobs, Suzanne B. R.
   Moreno-Macias, Hortensia
   Huerta-Chagoya, Alicia
   Churchhouse, Claire
   Marquez-Luna, Carla
   Garcia-Ortiz, Humberto
   Jose Gomez-Vazquez, Maria
   Burtt, Noel P.
   Aguilar-Salinas, Carlos A.
   Gonzalez-Villalpando, Clicerio
   Florez, Jose C.
   Orozco, Lorena
   Haiman, Christopher A.
   Tusie-Luna, Teresa
   Altshuler, David
   Williams, Amy L.
   Marquez-Luna, Carla
   Huerta-Chagoya, Alicia
   Ripke, Stephan
   Jose Gomez-Vazquez, Maria
   Manning, Alisa K.
   Moreno-Macias, Hortensia
   Garcia-Ortiz, Humberto
   Neale, Benjamin
   Burtt, Noel P.
   Aguilar-Salinas, Carlos A.
   Reich, David
   Stram, Daniel O.
   Carlos Fernandez-Lopez, Juan
   Romero-Hidalgo, Sandra
   Altshuler, David
   Florez, Jose C.
   Tusie-Luna, Teresa
   Patterson, Nick
   Haiman, Christopher A.
   Aguilar-Delfin, Irma
   Martinez-Hernandez, Angelica
   Centeno-Cruz, Federico
   Mendoza-Caamal, Elvia
   Revilla-Monsalve, Cristina
   Islas-Andrade, Sergio
   Cordova, Emilio
   Rodriguez-Arellano, Eunice
   Soberon, Xavier
   Orozco, Lorena
   Florez, Jose C.
   Gonzalez-Villalpando, Clicerio
   Elena Gonzalez-Villalpando, Maria
   Haiman, Christopher A.
   Henderson, Brian E.
   Monroe, Kristine
   Wilkens, Lynne
   Kolonel, Laurence N.
   Le Marchand, Loic
   Riba, Laura
   Luisa Ordonez-Sanchez, Maria
   Rodriguez-Guillen, Rosario
   Cruz-Bautista, Ivette
   Rodriguez-Torres, Maribel
   Liliana Munoz-Hernandez, Linda
   Saenz, Tamara
   Gomez, Donaji
   Alvirde, Ulices
   Burtt, Noel P.
   Onofrio, Robert C.
   Brodeur, Wendy M.
   Gage, Diane
   Murphy, Jacquelyn
   Franklin, Jennifer
   Mahan, Scott
   Ardlie, Kristin
   Crenshaw, Andrew T.
   Winckler, Wendy
   Prufer, Kay
   Shunkov, Michael V.
   Sawyer, Susanna
   Stenzel, Udo
   Kelso, Janet
   Lek, Monkol
   Sankararaman, Sriram
   Williams, Amy L.
   Patterson, Nick
   MacArthur, Daniel G.
   Reich, David
   Derevianko, Anatoli P.
   Paabo, Svante
   Jacobs, Suzanne B. R.
   Churchhouse, Claire
   Gopal, Shuba
   Grammatikos, James A.
   Smith, Ian C.
   Bullock, Kevin H.
   Deik, Amy A.
   Souza, Amanda L.
   Pierce, Kerry A.
   Clish, Clary B.
   Altshuler, David
   Fennell, Timothy
   Farjoun, Yossi
   Gabriel, Stacey
   Stram, Daniel O.
   Gross, Myron D.
   Pereira, Mark A.
   Seielstad, Mark
   Koh, Woon-Puay
   Tai, E-Shyong
   Flannick, Jason
   Fontanillas, Pierre
   Morris, Andrew
   Teslovich, Tanya M.
   Burtt, Noel P.
   Atzmon, Gil
   Blangero, John
   Bowden, Donald W.
   Chambers, John
   Cho, Yoon Shin
   Duggirala, Ravindranath
   Glaser, Benjamin
   Hanis, Craig
   Kooner, Jaspal
   Laakso, Markku
   Lee, Jong-Young
   Tai, E-Shyong
   Teo, Yik Ying
   Wilson, James G.
   Haiman, Christopher A.
   Henderson, Brian E.
   Monroe, Kristine
   Wilkens, Lynne
   Kolonel, Laurence N.
   Le Marchand, Loic
   Puppala, Sobha
   Farook, Vidya S.
   Thameem, Farook
   Abboud, Hanna E.
   DeFronzo, Ralph A.
   Jenkinson, Christopher P.
   Lehman, Donna M.
   Curran, Joanne E.
   Blangero, John
   Duggirala, Ravindranath
   Burtt, Noel P.
   Cortes, Maria L.
   Altshuler, David
   Florez, Jose C.
   Haiman, Christopher A.
   Henderson, Brian E.
   Aguilar-Salinas, Carlos A.
   Gonzalez-Villalpando, Clicerio
   Orozco, Lorena
   Tusie-Luna, Teresa
TI Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico
SO NATURE
LA English
DT Article
ID association; susceptibility; transporter; ancestry; kcnq1
AB Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others(1), with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings(2-4), we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P=3.9x10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P=1.1x10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at similar to 50% frequency in Native American samples and similar to 10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.
C1 [Williams, Amy L.; Jacobs, Suzanne B. R.; Churchhouse, Claire; Florez, Jose C.; Altshuler, David; Ripke, Stephan; Manning, Alisa K.; Neale, Benjamin; Burtt, Noel P.; Murphy, Jacquelyn; Sankararaman, Sriram; Patterson, Nick; MacArthur, Daniel G.; Reich, David; Flannick, Jason; Fontanillas, Pierre] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Reich, David; Altshuler, David; Sankararaman, Sriram] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Moreno-Macias, Hortensia; Moreno-Macias, Hortensia] Univ Autonoma Metropolitana, Mexico City 14387, DF, Mexico.
   [Jose Gomez-Vazquez, Maria; Tusie-Luna, Teresa; Jose Gomez-Vazquez, Maria; Luisa Ordonez-Sanchez, Maria; Rodriguez-Guillen, Rosario; Cruz-Bautista, Ivette; Rodriguez-Torres, Maribel; Liliana Munoz-Hernandez, Linda; Saenz, Tamara; Gomez, Donaji; Alvirde, Ulices] Inst Nacl Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico.
   [Riba, Laura; Reich, David] Univ Nacl Autonoma Mexico, Unidad Biol Mol & Med Genom, UNAM INCMNSZ, Inst Invest Biomed, Mexico City 04510, DF, Mexico.
   [Marquez-Luna, Carla; Orozco, Lorena; Marquez-Luna, Carla; Carlos Fernandez-Lopez, Juan; Romero-Hidalgo, Sandra; Aguilar-Delfin, Irma; Martinez-Hernandez, Angelica; Centeno-Cruz, Federico; Mendoza-Caamal, Elvia; Cordova, Emilio; Soberon, Xavier] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
   [Jose Gomez-Vazquez, Maria; Jose Gomez-Vazquez, Maria] Univ Autonoma Nuevo Leon, San Nicolas De Los Garza 66451, Nuevo Leon, Mexico.
   [Gonzalez-Villalpando, Clicerio; Elena Gonzalez-Villalpando, Maria] Inst Nacl Salud Publ, Ctr Invest Salud Poblac, Unidad Invest Diabet & Riesgo Cardiovasc, Ctr Estudios Diabet, Mexico City 01120, DF, Mexico.
   [Flannick, Jason] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Flannick, Jason] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Haiman, Christopher A.; Stram, Daniel O.; Henderson, Brian E.; Monroe, Kristine] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
   Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02114 USA.
   MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Ripke, Stephan; Neale, Benjamin; Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Revilla-Monsalve, Cristina; Islas-Andrade, Sergio] Inst Seguro Social SXXI, Unidad Invest Med Enfermedades Metab, Mexico City 06720, DF, Mexico.
   [Rodriguez-Arellano, Eunice] Inst Seguridad & Serv Sociales Trabajadores Estad, Mexico City 01030, DF, Mexico.
   [Wilkens, Lynne; Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
   [Onofrio, Robert C.; Brodeur, Wendy M.; Gage, Diane; Franklin, Jennifer; Mahan, Scott; Ardlie, Kristin; Crenshaw, Andrew T.; Winckler, Wendy; Fennell, Timothy; Farjoun, Yossi; Gabriel, Stacey] Broad Inst Harvard & MIT, Genom Platform, Cambridge, MA 02142 USA.
   [Prufer, Kay; Sawyer, Susanna; Stenzel, Udo; Kelso, Janet; Paabo, Svante] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Shunkov, Michael V.; Derevianko, Anatoli P.] Russian Acad Sci, Siberian Branch, Inst Archaeol & Ethnog, Palaeolith Dept, Novosibirsk 630090, Russia.
   [Gopal, Shuba; Grammatikos, James A.; Bullock, Kevin H.; Deik, Amy A.; Souza, Amanda L.; Pierce, Kerry A.; Clish, Clary B.] Broad Inst Harvard & MIT, Metabolite Profiling Platform, Cambridge, MA 02142 USA.
   [Smith, Ian C.] Broad Inst Harvard & MIT, Canc Biol Program, Cambridge, MA 02142 USA.
   [Gross, Myron D.; Pereira, Mark A.] Univ Minnesota, Minneapolis, MN 55455 USA.
   [Seielstad, Mark] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Koh, Woon-Puay; Tai, E-Shyong] Duke Natl Univ Singapore, Grad Med Sch, Singapore SINGAPORE16, Singapore.
   [Koh, Woon-Puay] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
   Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117597, Singapore.
   [Morris, Andrew] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Teslovich, Tanya M.] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Atzmon, Gil] Albert Einstein Coll Med, Dept Genet, Dept Med, Bronx, NY 10461 USA.
   [Blangero, John; Duggirala, Ravindranath; Le Marchand, Loic; Puppala, Sobha; Farook, Vidya S.; Curran, Joanne E.] Texas Biomed Res Inst, Dept Med, San Antonio, TX 78227 USA.
   [Bowden, Donald W.] Wake Forest Sch Med, Dept Internal Med, Dept Biochem, Ctr Genom & Personalized Med Res,Ctr Diabet Res, Winston Salem, NC 27157 USA.
   [Chambers, John] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London SW7 2AZ, England.
   [Kooner, Jaspal] Imperial Coll Healthcare NHS Trust, London W2 1NY, England.
   [Kooner, Jaspal] Ealing Hosp Natl Hlth Serv NHS Trust, Southall UB1 3HW, Middx, England.
   [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon 200702, Gangwon Do, South Korea.
   [Glaser, Benjamin] Hadassah Hebrew Univ, Sch Med, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel.
   [Glaser, Benjamin] E Wolfson Med Ctr, IDRG, Diabet Unit, IL-58100 Holon, Israel.
   [Hanis, Craig] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
   [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, NHLI, London W12 0HS, England.
   [Laakso, Markku] Univ Eastern Finland, Dept Med, FI-70211 Kuopio, Finland.
   [Laakso, Markku] Kuopio Univ Hosp, FI-70211 Kuopio, Finland.
   [Lee, Jong-Young] Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do 363951, South Korea.
   [Teo, Yik Ying] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117597, Singapore.
   Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117456, Singapore.
   Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore.
   Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117456, Singapore.
   Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore.
   [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
   [Thameem, Farook; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA.
   [DeFronzo, Ralph A.; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA.
   [Lehman, Donna M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA.
   [Cortes, Maria L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Universidad Autonoma Metropolitana - Mexico; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran - Mexico; Universidad Nacional Autonoma de Mexico; Instituto Nacional de Medicina Genomica; Universidad Autonoma de Nuevo Leon; Instituto Nacional de Salud Publica; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Southern California; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Cancer Research Center of Hawaii; University of Hawaii System; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Max Planck Society; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Archaeology & Ethnography, Siberian Branch of Russian Academy of Sciences; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California San Francisco; National University of Singapore; National University of Singapore; University of Oxford; Wellcome Centre for Human Genetics; University of Michigan System; University of Michigan; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Texas Biomedical Research Institute; Wake Forest University; Imperial College London; Imperial College London; Hallym University; Hebrew University of Jerusalem; Hadassah University Medical Center; Tel Aviv University; University of Texas System; University of Texas Health Science Center Houston; Imperial College London; University of Eastern Finland; University of Eastern Finland; University of Eastern Finland Hospital; Kuopio University Hospital; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Genome Science; National University of Singapore; National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); National University of Singapore; National University of Singapore; University of Mississippi; University of Mississippi Medical Center; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Altshuler, D (corresponding author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
EM mttusie@gmail.com; altshuler@molbio.mgh.harvard.edu
FU Carlos Slim Health Institute; Consejo Nacional de Ciencia y Tecnologia [138826, 128877, 86867, 2092, M9303, F677-M9407, 251M, 2005-C01-14502, SALUD 2010-2-151165]; CONACyT-SALUD [2009-01-115250]; Direccion General de Asuntos del Personal Academico, UNAM [IT 214711]; Instituto Carlos Slim de la Salud; National Institutes of Health (NIH) [R01HL24799, CA164973, CA054281, CA063464, R01 CA55069, R35 CA53890, R01 CA80205, R01 CA144034, U01DK085526]; National Medical Research Council of Singapore; Veterans Administration Epidemiologic grant; National Institutes of Health Ruth L. Kirschstein National Research Service [F32 HG005944];  [R01 DK042273];  [R01 DK047482];  [R01 DK053889];  [R01 DK057295];  [P01 HL045522]; Academy of Finland (AKA) [138826, 128877] Funding Source: Academy of Finland (AKA); National Cancer Institute [U01CA164973] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER
NR 29
TC 115
Z9 174
U1 0
U2 6
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 6
PY 2014
VL 506
IS 7486
BP 97
EP +
DI 10.1038/nature12828
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100039
PM 24390345
DA 2026-03-09
ER

PT J
AU Sun, L
   Petrenko, A
   Leghtas, Z
   Vlastakis, B
   Kirchmair, G
   Sliwa, KM
   Narla, A
   Hatridge, M
   Shankar, S
   Blumoff, J
   Frunzio, L
   Mirrahimi, M
   Devoret, MH
   Schoelkopf, RJ
AF Sun, L.
   Petrenko, A.
   Leghtas, Z.
   Vlastakis, B.
   Kirchmair, G.
   Sliwa, K. M.
   Narla, A.
   Hatridge, M.
   Shankar, S.
   Blumoff, J.
   Frunzio, L.
   Mirrahimi, M.
   Devoret, M. H.
   Schoelkopf, R. J.
TI Tracking photon jumps with repeated quantum non-demolition parity measurements
SO NATURE
LA English
DT Article
ID schrodinger cat states; number states; cavity; spin; amplification; decoherence; information; feedback; collapse; limit
AB Quantum error correction is required for a practical quantum computer because of the fragile nature of quantum information. In quantum error correction, information is redundantly stored in a large quantum state space and one or more observables must be monitored to reveal the occurrence of an error, without disturbing the information encoded in an unknown quantum state. Such observables, typically multi-quantum-bit parities, must correspond to a special symmetry property inherent in the encoding scheme. Measurements of these observables, or error syndromes, must also be performed in a quantum non-demolition way (projecting without further perturbing the state) and more quickly than errors occur. Previously, quantum non-demolition measurements of quantum jumps between states of well-defined energy have been performed in systems such as trapped ions(1-3), electrons(4), cavity quantum electrodynamics(5,6), nitrogen-vacancy centres(7-9) and superconducting quantum bits(10,11). So far, however, no fast and repeated monitoring of an error syndrome has been achieved. Here we track the quantum jumps of a possible error syndrome, namely the photon number parity of a microwave cavity, by mapping this property onto an ancilla quantum bit, whose only role is to facilitate quantum state manipulation and measurement. This quantity is just the error syndrome required in a recently proposed scheme for a hardware efficient protected quantum memory using Schrodinger cat states (quantum superpositions of different coherent states of light) in a harmonic oscillator(12). We demonstrate the projective nature of this measurement onto a region of state space with well-defined parity by observing the collapse of a coherent state onto even or odd cat states. The measurement is fast compared with the cavity lifetime, has a high single-shot fidelity and has a 99.8 per cent probability per single measurement of leaving the parity unchanged. In combination with the deterministic encoding of quantum information in cat states realized earlier(13,14), the quantum non-demolition parity tracking that we demonstrate represents an important step towards implementing an active system that extends the lifetime of a quantum bit.
C1 [Sun, L.; Petrenko, A.; Leghtas, Z.; Vlastakis, B.; Kirchmair, G.; Sliwa, K. M.; Narla, A.; Hatridge, M.; Shankar, S.; Blumoff, J.; Frunzio, L.; Mirrahimi, M.; Devoret, M. H.; Schoelkopf, R. J.] Yale Univ, Dept Appl Phys, New Haven, CT 06511 USA.
   [Sun, L.; Petrenko, A.; Leghtas, Z.; Vlastakis, B.; Kirchmair, G.; Sliwa, K. M.; Narla, A.; Hatridge, M.; Shankar, S.; Blumoff, J.; Frunzio, L.; Mirrahimi, M.; Devoret, M. H.; Schoelkopf, R. J.] Yale Univ, Dept Phys, New Haven, CT 06511 USA.
   [Mirrahimi, M.] INRIA Paris Rocquencourt, F-78153 Le Chesnay, France.
C3 Yale University; Yale University
RP Sun, L (corresponding author), Tsinghua Univ, Inst Interdisciplinary Informat Sci, Ctr Quantum Informat, Beijing 100084, Peoples R China.
EM luyansun@mail.tsinghua.edu.cn; robert.schoelkopf@yale.edu
FU Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through the Army Research Office [W911NF-09-1-0369]; US Army Research Office [W911NF-09-1-0514]; Agence National de Recherche [EPOQ2, ANR-09-JCJC-0070]; NSF [PHY-1309996]; Agence Nationale de la Recherche (ANR) [ANR-09-JCJC-0070] Funding Source: Agence Nationale de la Recherche (ANR); Direct For Mathematical & Physical Scien; Division Of Physics [1309996] Funding Source: National Science Foundation
NR 35
TC 219
Z9 289
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 JUL 24
PY 2014
VL 511
IS 7510
BP 444
EP +
DI 10.1038/nature13436
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700041
PM 25043007
DA 2026-03-09
ER

PT J
AU Sherwood, RK
   Scaduto, CM
   Torres, SE
   Bennett, RJ
AF Sherwood, Racquel Kim
   Scaduto, Christine M.
   Torres, Sandra E.
   Bennett, Richard J.
TI Convergent evolution of a fused sexual cycle promotes the haploid lifestyle
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; candida-lusitaniae; transcription factor; signal-transduction; pichia-pastoris; yeast; meiosis; ste12; sporulation; expression
AB Sexual reproduction is restricted to eukaryotic species and involves the fusion of haploid gametes to forma diploid cell that subsequently undergoes meiosis to generate recombinant haploid forms. This process has been extensively studied in the unicellular yeast Saccharomyces cerevisiae, which exhibits separate regulatory control over mating and meiosis. Here we address the mechanism of sexual reproduction in the related hemiascomycete species Candida lusitaniae. We demonstrate that, in contrast to S. cerevisiae, C. lusitaniae exhibits a highly integrated sexual program in which the programs regulating mating and meiosis have fused. Profiling of the C. lusitaniae sexual cycle revealed that gene expression patterns during mating and meiosis were overlapping, indicative of co-regulation. This was particularly evident for genes involved in pheromone MAPK signalling, which were highly induced throughout the sexual cycle of C. lusitaniae. Furthermore, genetic analysis showed that the orthologue of IME2, a 'diploid-specific' factor in S. cerevisiae(1,2), and STE12, the master regulator of S. cerevisiae mating(3,4), were each required for progression through both mating and meiosis in C. lusitaniae. Together, our results establish that sexual reproduction has undergone significant rewiring between S. cerevisiae and C. lusitaniae, and that a concerted sexual cycle operates in C. lusitaniae that is more reminiscent of the distantly related ascomycete, Schizosaccharomyces pombe. We discuss these results in light of the evolution of sexual reproduction in yeast, and propose that regulatory coupling of mating and meiosis has evolved multiple times as an adaptation to promote the haploid lifestyle.
C1 [Sherwood, Racquel Kim; Scaduto, Christine M.; Torres, Sandra E.; Bennett, Richard J.] Brown Univ, Dept Microbiol & Immunol, Providence, RI 02912 USA.
C3 Brown University
RP Bennett, RJ (corresponding author), Brown Univ, Dept Microbiol & Immunol, 171 Meeting St, Providence, RI 02912 USA.
EM Richard_Bennett@brown.edu
FU National Science Foundation [MCB1021120]; National Institutes of Health [AI081704]; Burroughs Wellcome Fund;  [T32GM007601];  [F31AI075607]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1021120] Funding Source: National Science Foundation
NR 45
TC 30
Z9 30
U1 2
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 FEB 20
PY 2014
VL 506
IS 7488
BP 387
EP +
DI 10.1038/nature12891
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800045
DA 2026-03-09
ER

PT J
AU Redondo, RL
   Kim, J
   Arons, AL
   Ramirez, S
   Liu, X
   Tonegawa, S
AF Redondo, Roger L.
   Kim, Joshua
   Arons, Autumn L.
   Ramirez, Steve
   Liu, Xu
   Tonegawa, Susumu
TI Bidirectional switch of the valence associated with a hippocampal contextual memory engram
SO NATURE
LA English
DT Article
ID basolateral amygdala; neuronal-activity; reward-seeking; basal amygdala; fear; discrimination; stimulation; responses; rats
AB The valence of memories is malleable because of their intrinsic reconstructive property(1). This property of memory has been used clinically to treat maladaptive behaviours(2). However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell-manipulation technique(3),(4). We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.
C1 [Redondo, Roger L.; Kim, Joshua; Arons, Autumn L.; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu] MIT, Dept Biol, RIKEN Ctr Neural Circuit Genet, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Redondo, Roger L.; Kim, Joshua; Arons, Autumn L.; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Redondo, Roger L.; Arons, Autumn L.; Liu, Xu; Tonegawa, Susumu] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); RIKEN; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Tonegawa, S (corresponding author), MIT, Dept Biol, RIKEN Ctr Neural Circuit Genet, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tonegawa@mit.edu
FU RIKEN Brain Science Institute; Howard Hughes Medical Institute; The JPB Foundation; National Institutes of Health [T32GM007287]
NR 28
TC 340
Z9 436
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 SEP 18
PY 2014
VL 513
IS 7518
BP 426
EP +
DI 10.1038/nature13725
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP1GD
UT WOS:000341814900062
PM 25162525
DA 2026-03-09
ER

PT J
AU Wilhelm, M
   Schlegl, J
   Hahne, H
   Gholami, AM
   Lieberenz, M
   Savitski, MM
   Ziegler, E
   Butzmann, L
   Gessulat, S
   Marx, H
   Mathieson, T
   Lemeer, S
   Schnatbaum, K
   Reimer, U
   Wenschuh, H
   Mollenhauer, M
   Slotta-Huspenina, J
   Boese, JH
   Bantscheff, M
   Gerstmair, A
   Faerber, F
   Kuster, B
AF Wilhelm, Mathias
   Schlegl, Judith
   Hahne, Hannes
   Gholami, Amin Moghaddas
   Lieberenz, Marcus
   Savitski, Mikhail M.
   Ziegler, Emanuel
   Butzmann, Lars
   Gessulat, Siegfried
   Marx, Harald
   Mathieson, Toby
   Lemeer, Simone
   Schnatbaum, Karsten
   Reimer, Ulf
   Wenschuh, Holger
   Mollenhauer, Martin
   Slotta-Huspenina, Julia
   Boese, Joos-Hendrik
   Bantscheff, Marcus
   Gerstmair, Anja
   Faerber, Franz
   Kuster, Bernhard
TI Mass-spectrometry-based draft of the human proteome
SO NATURE
LA English
DT Article
ID growth-factor receptor; noncoding rnas; identification; expression; quantification; proteins; database; reveals; peptide; project
AB Proteomes are characterized by large protein-abundance differences, cell-type- and time-dependent expression patterns and post-translational modifications, all of which carry biological information that is not accessible by genomics or transcriptomics. Here we present a mass-spectrometry-based draft of the human proteome and a public, high-performance, in-memory database for real-time analysis of terabytes of big data, called ProteomicsDB. The information assembled from human tissues, cell lines and body fluids enabled estimation of the size of the protein-coding genome, and identified organ-specific proteins and a large number of translated lincRNAs (long intergenic non-coding RNAs). Analysis of messenger RNA and protein-expression profiles of human tissues revealed conserved control of protein abundance, and integration of drug-sensitivity data enabled the identification of proteins predicting resistance or sensitivity. The proteome profiles also hold considerable promise for analysing the composition and stoichiometry of protein complexes. ProteomicsDB thus enables navigation of proteomes, provides biological insight and fosters the development of proteomic technology.
C1 [Wilhelm, Mathias; Hahne, Hannes; Gholami, Amin Moghaddas; Marx, Harald; Lemeer, Simone; Kuster, Bernhard] Tech Univ Munich, Chair Prote & Bioanalyt, D-85354 Freising Weihenstephan, Germany.
   [Wilhelm, Mathias; Schlegl, Judith; Lieberenz, Marcus; Ziegler, Emanuel; Butzmann, Lars; Gessulat, Siegfried; Boese, Joos-Hendrik; Gerstmair, Anja; Faerber, Franz] SAP AG, D-69190 Walldorf, Germany.
   [Savitski, Mikhail M.; Mathieson, Toby; Bantscheff, Marcus] Cellzome GmbH, D-69117 Heidelberg, Germany.
   [Schnatbaum, Karsten; Reimer, Ulf; Wenschuh, Holger] JPT Peptide Technol GmbH, D-12489 Berlin, Germany.
   [Mollenhauer, Martin; Slotta-Huspenina, Julia] Tech Univ Munich, Inst Pathol, D-81675 Munich, Germany.
   [Kuster, Bernhard] Ctr Integrated Prot Sci Munich, Munich, Germany.
C3 Technical University of Munich; SAP; GlaxoSmithKline; Cellzome GmbH; Technical University of Munich; University of Munich
RP Kuster, B (corresponding author), Tech Univ Munich, Chair Prote & Bioanalyt, Emil Erlenmeyer Forum 5, D-85354 Freising Weihenstephan, Germany.
EM kuster@tum.de
NR 46
TC 1475
Z9 1725
U1 3
U2 655
PU NATURE PUBLISHING 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 29
PY 2014
VL 509
IS 7502
BP 582
EP +
DI 10.1038/nature13319
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100041
PM 24870543
DA 2026-03-09
ER

PT J
AU Fisher, DB
   Bolatto, AD
   Herrera-Camus, R
   Draine, BT
   Donaldson, J
   Walter, F
   Sandstrom, KM
   Leroy, AK
   Cannon, J
   Gordon, K
AF Fisher, David B.
   Bolatto, Alberto D.
   Herrera-Camus, Rodrigo
   Draine, Bruce T.
   Donaldson, Jessica
   Walter, Fabian
   Sandstrom, Karin M.
   Leroy, Adam K.
   Cannon, John
   Gordon, Karl
TI The rarity of dust in metal-poor galaxies
SO NATURE
LA English
DT Article
ID infrared-emission; molecular gas; metallicity; redshift; i-zw-18
AB Galaxies observed at redshift z>6, when the Universe was less than a billion years old, thus far very rarely show evidence(1-3) of the cold dust that accompanies star formation in the local Universe, where the dust-to-gas mass ratio is around one per cent. A prototypical example is the galaxy Himiko (z = 6.6), which-a mere 840 million years after the Big Bang-is forming stars at a rate of 30-100 solar masses per year, yielding a mass assembly time of about 150 x 10(6) years. Himiko is thought to have a low fraction (2-3 per cent of the Sun's) of elements heavier than helium (low metallicity), and although its gas mass cannot yet be determined its dust-to-stellar mass ratio is constrained(3) to be less than 0.05 per cent. The local dwarf galaxy I Zwicky 18, which has a metallicity about 4 per cent that of the Sun's(4) and is forming stars less rapidly (assembly time about 1.6 x 10(9) years) than Himiko but still vigorously for its mass(5), is also very dust deficient and is perhaps one of the best analogues of primitive galaxies accessible to detailed study. Here we report observations of dust emission from I Zw 18, from which we determine its dust mass to be 450-1,800 solar masses, yielding a dust-to-stellar mass ratio of about 10(-6) to 10(-5) and a dust-to-gas mass ratio of 3.2-13 x 10(-6). If I Zw 18 is a reasonable analogue of Himiko, then Himiko's dust mass must be around 50,000 solar masses, a factor of 100 below the current upper limit. These numbers are quite uncertain, but if most high-z galaxies are more like Himiko than like the very-high-dust-mass galaxy SDSS J114816.64 + 525150.3 at z approximate to 6, which hosts a quasar(6), then our prospects for detecting the gas and dust inside such galaxies are much poorer than hitherto anticipated.
C1 [Fisher, David B.; Bolatto, Alberto D.; Herrera-Camus, Rodrigo; Donaldson, Jessica] Univ Maryland, Dept Astron, Lab Millimeter Wave Astron, College Pk, MD 20742 USA.
   [Fisher, David B.; Bolatto, Alberto D.; Herrera-Camus, Rodrigo; Donaldson, Jessica] Univ Maryland, Joint Space Inst, College Pk, MD 20742 USA.
   [Fisher, David B.] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [Draine, Bruce T.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Walter, Fabian; Sandstrom, Karin M.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Leroy, Adam K.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Cannon, John] Macalester Coll, Dept Phys & Astron, St Paul, MN 55105 USA.
   [Gordon, Karl] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
C3 University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; Swinburne University of Technology; Princeton University; Max Planck Society; National Radio Astronomy Observatory (NRAO); Macalester College; Space Telescope Science Institute
RP Fisher, DB (corresponding author), Univ Maryland, Dept Astron, Lab Millimeter Wave Astron, College Pk, MD 20742 USA.
EM dfisher@swin.edu.au; bolatto@astro.umd.edu
FU University of Maryland; Laboratory for Millimeter Astronomy; NSF [AST0838178, AST1008570, AST1211683]; CAREER NSF [AST0955836, AST1139998]; Research Corporation for Science Advancement Cottrell Scholar award; Marie Curie International Incoming fellowship; BMVIT (Austria); ESA-PRODEX (Belgium); CEA/CNES (France); DLR (Germany); ASI/INAF (Italy); CICYT/MCYT (Spain); Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1008570, 1211683] Funding Source: National Science Foundation
NR 26
TC 80
Z9 84
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 9
PY 2014
VL 505
IS 7482
BP 186
EP 189
DI 10.1038/nature12765
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500032
PM 24317694
DA 2026-03-09
ER

PT J
AU Lee, HM
   Brott, BK
   Kirkby, LA
   Adelson, JD
   Cheng, S
   Feller, MB
   Datwani, A
   Shatz, CJ
AF Lee, Hanmi
   Brott, Barbara K.
   Kirkby, Lowry A.
   Adelson, Jaimie D.
   Cheng, Sarah
   Feller, Marla B.
   Datwani, Akash
   Shatz, Carla J.
TI Synapse elimination and learning rules co-regulated by MHC class I H2-Db
SO NATURE
LA English
DT Article
ID long-term depression; ampa receptors; retinal waves; retinogeniculate; plasticity; ltp; cns; transmission; segregation; requirement
AB The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D-b is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K-b and H2-D-b ((KDb-/-)-D-b), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-Db in (KDb-/-)-D-b mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in (KDb-/-)-D-b mice. This change is due to an increase in Ca2+-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D-b to (KDb-/-)-D-b neurons renders AMPA receptors Ca2+ impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D-b in functional and structural synapse pruning in CNS neurons.
C1 [Lee, Hanmi; Brott, Barbara K.; Adelson, Jaimie D.; Cheng, Sarah; Datwani, Akash; Shatz, Carla J.] James H Clark Ctr, Dept Biol & Neurobiol, Stanford, CA 94305 USA.
   [Lee, Hanmi; Brott, Barbara K.; Adelson, Jaimie D.; Cheng, Sarah; Datwani, Akash; Shatz, Carla J.] James H Clark Ctr, Dept BioX, Stanford, CA 94305 USA.
   [Kirkby, Lowry A.; Feller, Marla B.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Kirkby, Lowry A.; Feller, Marla B.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Shatz, CJ (corresponding author), James H Clark Ctr, Dept Biol & Neurobiol, 318 Campus Dr, Stanford, CA 94305 USA.
EM cshatz@stanford.edu
FU NIH [R01 MH071666, EY02858, RO1 EY13528]; G. Harold and Leila Y. Mathers Charitable Foundation; NDSEG; NSF; National Eye Institute [R01EY013528] Funding Source: NIH RePORTER; National Institute of Mental Health; National Institute of General Medical Sciences; National Institute on Aging [T32MH020016] Funding Source: NIH RePORTER
NR 49
TC 175
Z9 221
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 8
PY 2014
VL 509
IS 7499
BP 195
EP +
DI 10.1038/nature13154
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300032
PM 24695230
DA 2026-03-09
ER

PT J
AU Wasio, NA
   Quardokus, RC
   Forrest, RP
   Lent, CS
   Corcelli, SA
   Christie, JA
   Henderson, KW
   Kandel, SA
AF Wasio, Natalie A.
   Quardokus, Rebecca C.
   Forrest, Ryan P.
   Lent, Craig S.
   Corcelli, Steven A.
   Christie, John A.
   Henderson, Kenneth W.
   Kandel, S. Alex
TI Self-assembly of hydrogen-bonded two-dimensional quasicrystals
SO NATURE
LA English
DT Article
ID van-der-waals; acid; molecules; energy; surface; order; model
AB The process of molecular self-assembly on solid surfaces is essentially one of crystallization in two dimensions, and the structures that result depend on the interplay between intermolecular forces and the interaction between adsorbates and the underlying substrate(1). Because a single hydrogen bond typically has an energy between 15 and 35 kilojoules per mole, hydrogen bonding can be a strong driver of molecular assembly; this is apparent from the dominant role of hydrogen bonding in nucleic-acid base pairing, as well as in the secondary structure of proteins. Carboxylic acid functional groups, which provide two hydrogen bonds, are particularly promising and reliable in creating and maintaining surface order, and self-assembled monolayers of benzoic acids produce structure that depends on the number and relative placement of carboxylic acid groups(2-6). Here we use scanning tunnelling microscopy to study self-assembled monolayers of ferrocenecarboxylic acid (FcCOOH), and find that, rather than producing dimeric or linear structures typical of carboxylic acids, FcCOOH forms highly unusual cyclic hydrogen-bonded pentamers, which combine with simultaneously formed FcCOOH dimers to form two-dimensional quasicrystallites that exhibit local five-fold symmetry and maintain translational and rotational order (without periodicity) for distances of more than 400 angstroms.
C1 [Wasio, Natalie A.; Quardokus, Rebecca C.; Forrest, Ryan P.; Corcelli, Steven A.; Christie, John A.; Henderson, Kenneth W.; Kandel, S. Alex] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
   [Lent, Craig S.] Univ Notre Dame, Dept Elect Engn, Notre Dame, IN 46556 USA.
C3 University of Notre Dame; University of Notre Dame
RP Kandel, SA (corresponding author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
EM skandel@nd.edu
FU US National Science Foundation [NSF CHE-1124762]; Center for Research Computing at the University of Notre Dame; Division Of Chemistry; Direct For Mathematical & Physical Scien [1124762] Funding Source: National Science Foundation
NR 37
TC 205
Z9 233
U1 5
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 MAR 6
PY 2014
VL 507
IS 7490
BP 86
EP +
DI 10.1038/nature12993
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400047
PM 24598637
DA 2026-03-09
ER

PT J
AU Meyer, M
   Fu, QM
   Aximu-Petri, A
   Glocke, I
   Nickel, B
   Arsuaga, JL
   Martínez, I
   Gracia, A
   de Castro, JMB
   Carbonell, E
   Pääbo, S
AF Meyer, Matthias
   Fu, Qiaomei
   Aximu-Petri, Ayinuer
   Glocke, Isabelle
   Nickel, Birgit
   Arsuaga, Juan-Luis
   Martinez, Ignacio
   Gracia, Ana
   Maria Bermudez de Castro, Jose
   Carbonell, Eudald
   Paeaebo, Svante
TI A mitochondrial genome sequence of a hominin from Sima de los Huesos
SO NATURE
LA English
DT Article
ID middle-pleistocene site; dna; atapuerca; ancient; sierra; evolution; (sierra; spain).; cave; alignment
AB Excavations of a complex of caves in the Sierra de Atapuerca in northern Spain have unearthed hominin fossils that range in age from the early Pleistocene to the Holocene(1). One of these sites, the 'Sima de los Huesos' ('pit of bones'), has yielded the world's largest assemblage of Middle Pleistocene hominin fossils(2,3), consisting of at least 28 individuals(4) dated to over 300,000 years ago(5). The skeletal remains share a number of morphological features with fossils classified as Homo heidelbergensis and also display distinct Neanderthal-derived traits(6-8). Here we determine an almost complete mitochondrial genome sequence of a hominin from Sima de los Huesos and show that it is closely related to the lineage leading to mitochondrial genomes of Denisovans(9,10), an eastern Eurasian sister group to Neanderthals. Our results pave the way for DNA research on hominins from the Middle Pleistocene.
C1 [Meyer, Matthias; Fu, Qiaomei; Aximu-Petri, Ayinuer; Glocke, Isabelle; Nickel, Birgit; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Fu, Qiaomei] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Arsuaga, Juan-Luis; Martinez, Ignacio; Gracia, Ana] Univ Complutense Madrid, Inst Salud Carlos III, Ctr Invest Evoluc & Comportamiento Humanos, Madrid 28029, Spain.
   [Arsuaga, Juan-Luis] Univ Complutense Madrid, Fac Ciencias Geol, Dept Paleontol, E-28040 Madrid, Spain.
   [Martinez, Ignacio; Gracia, Ana] Univ Alcala, Dept Geog & Geol, Area Paleontol, Madrid 28871, Spain.
   [Maria Bermudez de Castro, Jose] Ctr Nacl Invest Evoluc Humana, Burgos 09002, Spain.
   [Carbonell, Eudald] Inst Catala Paleoecol Humana & Evolucio Social, Tarragona 43007, Spain.
   [Carbonell, Eudald] Univ Rovira & Virgili, Dept Hist & Hist Art, Area Prehist, Tarragona 43002, Spain.
C3 Max Planck Society; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Instituto de Salud Carlos III; Complutense University of Madrid; Complutense University of Madrid; Universidad de Alcala; Centro Nacional de Investigacion de La Evolucion Humana (CENIEH); Universitat Rovira i Virgili; Catalan Institute of Human Paleo-Ecology & Social Evolution (IPHES); ICREA; Universitat Rovira i Virgili
RP Meyer, M (corresponding author), Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Deutsch Pl 6, D-04103 Leipzig, Germany.
EM mmeyer@eva.mpg.de
FU Max Planck ?Society; Presidential Innovation Fund; Junta de Castilla y Leon; Fundacion Atapuerca; Spanish Ministerio de Ciencia e Innovacion [CGL2009-12703-C03]; Spanish Ministerio de Economia y Competitividad [CGL2012-38434-C03]
NR 51
TC 369
Z9 407
U1 2
U2 292
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 16
PY 2014
VL 505
IS 7483
BP 403
EP +
DI 10.1038/nature12788
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800043
PM 24305051
DA 2026-03-09
ER

PT J
AU McCalley, CK
   Woodcroft, BJ
   Hodgkins, SB
   Wehr, RA
   Kim, EH
   Mondav, R
   Crill, PM
   Chanton, JP
   Rich, VI
   Tyson, GW
   Saleska, SR
AF McCalley, Carmody K.
   Woodcroft, Ben J.
   Hodgkins, Suzanne B.
   Wehr, Richard A.
   Kim, Eun-Hae
   Mondav, Rhiannon
   Crill, Patrick M.
   Chanton, Jeffrey P.
   Rich, Virginia I.
   Tyson, Gene W.
   Saleska, Scott R.
TI Methane dynamics regulated by microbial community response to permafrost thaw
SO NATURE
LA English
DT Article
ID global wetland extent; stable carbon; present state; peatland; climate; pathways; environments; oxidation; fluxes
AB Permafrost contains about 50% of the global soil carbon(1). It is thought that the thawing of permafrost can lead to a loss of soil carbon in the form of methane and carbon dioxide emissions(2,3). The magnitude of the resulting positive climate feedback of such greenhouse gas emissions is still unknown(3) and may to a large extent depend on the poorly understood role of microbial community composition in regulating the metabolic processes that drive such ecosystem-scale greenhouse gas fluxes. Here we show that changes in vegetation and increasing methane emissions with permafrost thaw are associated with a switch from hydrogenotrophic to partly acetoclastic methanogenesis, resulting in a large shift in the delta C-13 signature (1015 parts per thousand) of emitted methane. We used a natural landscape gradient of permafrost thaw in northern Sweden(4,5) as a model to investigate the role of microbial communities in regulating methane cycling, and to test whether a knowledge of community dynamics could improve predictions of carbon emissions under loss of permafrost. Abundance of the methanogen Candidatus Methanoflorens stordalenmirensis(6) is a key predictor of the shifts in methane isotopes, which in turn predicts the proportions of carbon emitted as methane and as carbon dioxide, an important factor for simulating the climate feedback associated with permafrost thaw in global models(3,7). By showing that the abundance of key microbial lineages can be used to predict atmospherically relevant patterns in methane isotopes and the proportion of carbon metabolized to methane during permafrost thaw, we establish a basis for scaling changing microbial communities to ecosystem isotope dynamics. Our findings indicate that microbial ecology may be important in ecosystem-scale responses to global change.
C1 [McCalley, Carmody K.; Wehr, Richard A.; Saleska, Scott R.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
   [Woodcroft, Ben J.; Mondav, Rhiannon; Tyson, Gene W.] Univ Queensland, Australian Ctr Ecogen, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia.
   [Hodgkins, Suzanne B.; Chanton, Jeffrey P.] Florida State Univ, Dept Earth Ocean & Atmospher Sci, Tallahassee, FL 32306 USA.
   [Kim, Eun-Hae; Rich, Virginia I.] Univ Arizona, Dept Soil Water & Environm Sci, Tucson, AZ 85721 USA.
   [Crill, Patrick M.] Stockholm Univ, Dept Geol Sci, S-10691 Stockholm, Sweden.
C3 University of Arizona; University of Queensland; State University System of Florida; Florida State University; University of Arizona; Stockholm University
RP McCalley, CK (corresponding author), Univ New Hampshire, Earth Syst Res Ctr, Durham, NH 03824 USA.
EM carmody.mccalley@unh.edu; saleska@email.arizona.edu
FU US Department of Energy Office of Biological and Environmental Research [DE-SC0004632]; University of Arizona Technology and Research Initiative Fund, through the Water, Environmental and Energy Solutions Initiative; Australian Postgraduate Award Scholarship; U.S. Department of Energy (DOE) [DE-SC0004632] Funding Source: U.S. Department of Energy (DOE)
NR 57
TC 327
Z9 405
U1 20
U2 732
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2014
VL 514
IS 7523
BP 478
EP +
DI 10.1038/nature13798
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900037
PM 25341787
DA 2026-03-09
ER

PT J
AU Durdu, S
   Iskar, M
   Revenu, C
   Schieber, N
   Kunze, A
   Bork, P
   Schwab, Y
   Gilmour, D
AF Durdu, Sevi
   Iskar, Murat
   Revenu, Celine
   Schieber, Nicole
   Kunze, Andreas
   Bork, Peer
   Schwab, Yannick
   Gilmour, Darren
TI Luminal signalling links cell communication to tissue architecture during organogenesis
SO NATURE
LA English
DT Article
ID lumen formation; fgf; migration; morphogenesis; mechanism; dynamics
AB Morphogenesis is the process whereby cell collectives are shaped into differentiated tissues and organs(1). The self-organizing nature of morphogenesis has been recently demonstrated by studies showing that stem cells in three-dimensional culture can generate complex organoids, such as mini-guts(2), optic-cups(3) and even mini-brains(4). To achieve this, cell collectives must regulate the activity of secreted signalling molecules that control cell differentiation, presumably through the self-assembly of microenvironments or niches. However, mechanisms that allow changes in tissue architecture to feedback directly on the activity of extracellular signals have not been described. Here we investigate how the process of tissue assembly controls signalling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium(5). We show that fibroblast growth factor (FGF) activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs. Live imaging reveals that FGF becomes specifically concentrated in microluminal structures that assemble at the centre of these organs and spatially constrain its signalling activity. Genetic inhibition of microlumen assembly and laser micropuncture experiments demonstrate that microlumina increase signalling responses in participating cells, thus allowing FGF to coordinate the migratory behaviour of cell groups at the tissue rear. As the formation of a central lumen is a self-organizing property of many cell types, such as epithelia(6) and embryonic stem cells(7), luminal signalling provides a potentially general mechanism to locally restrict, coordinate and enhance cell communication within tissues.
C1 [Durdu, Sevi; Iskar, Murat; Revenu, Celine; Schieber, Nicole; Kunze, Andreas; Bork, Peer; Schwab, Yannick; Gilmour, Darren] European Mol Biol Lab Heidelberg, D-69117 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL)
RP Gilmour, D (corresponding author), European Mol Biol Lab Heidelberg, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM gilmour@embl.de
FU European Molecular Biology Organization; EMBL Interdisciplinary Postdocs (EIPOD); Deutsche Forschungsgemeinschaft [SFB 488]
NR 42
TC 122
Z9 138
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 6
PY 2014
VL 515
IS 7525
BP 120
EP +
DI 10.1038/nature13852
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500042
PM 25337877
DA 2026-03-09
ER

PT J
AU Signer, RAJ
   Magee, JA
   Salic, A
   Morrison, SJ
AF Signer, Robert A. J.
   Magee, Jeffrey A.
   Salic, Adrian
   Morrison, Sean J.
TI Haematopoietic stem cells require a highly regulated protein synthesis rate
SO NATURE
LA English
DT Article
ID diamond-blackfan anemia; translational control; proteasome activity; progenitor cells; s19 deficiency; mtor pathway; self-renewal; bone-marrow; in-vivo; pten
AB Many aspects of cellular physiology remain unstudied in somatic stem cells, for example, there are almost no data on protein synthesis in any somatic stem cell. Here we set out to compare protein synthesis in haematopoietic stem cells (HSCs) and restricted haematopoietic progenitors. We found that the amount of protein synthesized per hour in HSCs in vivo was lower than in most other haematopoietic cells, even if we controlled for differences in cell cycle status or forced HSCs to undergo self-renewing divisions. Reduced ribosome function in Rpl24(Bst/+) mice further reduced protein synthesis in HSCs and impaired HSC function. Pten deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24(Bst/+) cell-autonomously rescued the effects of Pten deletion in HSCs; blocking the increase in protein synthesis, restoring HSC function, and delaying leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly by increasing protein synthesis. Either increased or decreased protein synthesis impairs HSC function.
C1 [Signer, Robert A. J.; Magee, Jeffrey A.; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA.
   [Salic, Adrian] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Morrison, SJ (corresponding author), Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA.
EM sean.morrison@utsouthwestern.edu
FU Cancer Prevention and Research Institute of Texas; National Institute on Aging [R37 AG024945]; Leukemia & Lymphoma Society [5541-11]; Canadian Institutes of Health Research [MFE-106993]; UT Southwestern K12 Pediatrics Training Grant [K12-HD068369]
NR 47
TC 530
Z9 600
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 MAY 1
PY 2014
VL 509
IS 7498
BP 49
EP +
DI 10.1038/nature13035
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100037
PM 24670665
DA 2026-03-09
ER

PT J
AU Ubil, E
   Duan, J
   Pillai, ICL
   Rosa-Garrido, M
   Wu, Y
   Bargiacchi, F
   Lu, Y
   Stanbouly, S
   Huang, J
   Rojas, M
   Vondriska, TM
   Stefani, E
   Deb, A
AF Ubil, Eric
   Duan, Jinzhu
   Pillai, Indulekha C. L.
   Rosa-Garrido, Manuel
   Wu, Yong
   Bargiacchi, Francesca
   Lu, Yan
   Stanbouly, Seta
   Huang, Jie
   Rojas, Mauricio
   Vondriska, Thomas M.
   Stefani, Enrico
   Deb, Arjun
TI Mesenchymal-endothelial transition contributes to cardiac neovascularization
SO NATURE
LA English
DT Article
ID ischemic-myocardium; bone-marrow; cells; fibroblasts; p53; repair; microscopy; fibrosis; hypoxia; tissue
AB Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.
C1 [Ubil, Eric] Univ N Carolina, Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Rosa-Garrido, Manuel; Lu, Yan; Stanbouly, Seta; Huang, Jie; Vondriska, Thomas M.; Deb, Arjun] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Rosa-Garrido, Manuel; Lu, Yan; Stanbouly, Seta; Huang, Jie; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab, Los Angeles, CA 90095 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Lu, Yan; Stanbouly, Seta; Huang, Jie; Deb, Arjun] Univ Calif Los Angeles, Eli & Edythe Broad Inst Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Lu, Yan; Stanbouly, Seta; Huang, Jie; Deb, Arjun] Univ Calif Los Angeles, Coll Letters & Sci, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Lu, Yan; Stanbouly, Seta; Huang, Jie; Deb, Arjun] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Duan, Jinzhu; Pillai, Indulekha C. L.; Lu, Yan; Stanbouly, Seta; Huang, Jie; Vondriska, Thomas M.; Deb, Arjun] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Rosa-Garrido, Manuel; Wu, Yong; Vondriska, Thomas M.; Stefani, Enrico] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Div Mol Med, Los Angeles, CA 90095 USA.
   [Rosa-Garrido, Manuel; Vondriska, Thomas M.; Stefani, Enrico] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
   [Bargiacchi, Francesca] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Rojas, Mauricio] Univ N Carolina, McAllister Heart Inst, Dept Med, 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 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; UCLA Jonsson Comprehensive Cancer Center; 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 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 School of Medicine; University of North Carolina; University of North Carolina Chapel Hill
RP Deb, A (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA.
EM adeb@mednet.ucla.edu
FU National Institutes of Health [NIH R01HL102190]; NIH [HL088640, HL105699]; American Heart Association; National Heart Lung and Blood Institute [R01HL105699] Funding Source: NIH RePORTER
NR 40
TC 303
Z9 337
U1 3
U2 68
PU NATURE PUBLISHING 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 30
PY 2014
VL 514
IS 7524
BP 585
EP +
DI 10.1038/nature13839
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500039
PM 25317562
DA 2026-03-09
ER

PT J
AU Maddalo, D
   Manchado, E
   Concepcion, CP
   Bonetti, C
   Vidigal, JA
   Han, YC
   Ogrodowski, P
   Crippa, A
   Rekhtman, N
   de Stanchina, E
   Lowe, SW
   Ventura, A
AF Maddalo, Danilo
   Manchado, Eusebio
   Concepcion, Carla P.
   Bonetti, Ciro
   Vidigal, Joana A.
   Han, Yoon-Chi
   Ogrodowski, Paul
   Crippa, Alessandra
   Rekhtman, Natasha
   de Stanchina, Elisa
   Lowe, Scott W.
   Ventura, Andrea
TI In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system
SO NATURE
LA English
DT Article
ID anaplastic lymphoma kinase; acute-leukemia; mouse models; fusion gene; cre-loxp; cancer; translocations; alk; resistance; npm
AB Chromosomal rearrangements have a central role in the pathogenesis of human cancers and often result in the expression of therapeutically actionable gene fusions(1). A recently discovered example is a fusion between the genes echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK), generated by an inversion on the short arm of chromosome 2: inv(2) (p21p23). The EML4-ALK oncogene is detected in a subset of human non-small cell lung cancers (NSCLC)(2) and is clinically relevant because it confers sensitivity to ALK inhibitors(3). Despite their importance, modelling such genetic events in mice has proven challenging and requires complex manipulation of the germ line. Here we describe an efficient method to induce specific chromosomal rearrangements in vivo using viral-mediated delivery of the CRISPR/Cas9 system to somatic cells of adult animals. We apply it to generate a mouse model of Eml4-Alk-driven lung cancer. The resulting tumours invariably harbour the Eml4-Alk inversion, express the Eml4-Alk fusion gene, display histopathological and molecular features typical of ALK(+) human NSCLCs, and respond to treatment with ALK inhibitors. The general strategy described here substantially expands our ability to model human cancers in mice and potentially in other organisms.
C1 [Maddalo, Danilo; Manchado, Eusebio; Concepcion, Carla P.; Bonetti, Ciro; Vidigal, Joana A.; Han, Yoon-Chi; Ogrodowski, Paul; Lowe, Scott W.; Ventura, Andrea] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
   [Concepcion, Carla P.] Cornell Univ, Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA.
   [Crippa, Alessandra] Milano Bicocca Univ, Dept Med Oncol, San Gerardo Hosp, I-20052 Monza, Italy.
   [Rekhtman, Natasha] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [de Stanchina, Elisa] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA.
   [Lowe, Scott W.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; University of Milano-Bicocca; San Gerardo Hospital; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute
RP Ventura, A (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10065 USA.
EM venturaa@mskcc.org
FU Geoffrey Beene Cancer Research Foundation; NCI (Cancer Center Support Grant) [P30 CA008748]; HHMI; NCI; American Italian Cancer Foundation; Foundation Blanceflor Boncompagni Ludovisi, nee Bildt; Jane Coffin Childs Foundation; National Cancer Institute [P01CA013106, P01CA129243, P30CA008748] Funding Source: NIH RePORTER
NR 30
TC 510
Z9 619
U1 1
U2 241
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 423
EP +
DI 10.1038/nature13902
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800053
PM 25337876
DA 2026-03-09
ER

PT J
AU Molofsky, AV
   Kelley, KW
   Tsai, HH
   Redmond, SA
   Chang, SM
   Madireddy, L
   Chan, JR
   Baranzini, SE
   Ullian, EM
   Rowitch, DH
AF Molofsky, Anna V.
   Kelley, Kevin W.
   Tsai, Hui-Hsin
   Redmond, Stephanie A.
   Chang, Sandra M.
   Madireddy, Lohith
   Chan, Jonah R.
   Baranzini, Sergio E.
   Ullian, Erik M.
   Rowitch, David H.
TI Astrocyte-encoded positional cues maintain sensorimotor circuit integrity
SO NATURE
LA English
DT Article
ID developing spinal-cord; motor-neurons; semaphorin-iii; brain-development; sensory axons; adult-mouse; specification; generation; expression; identification
AB Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded semaphorin 3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a leads to dysregulated alpha-motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of alpha- but not of adjacent gamma-motor neurons. In addition, a subset of TrkA(+) sensory afferents projects to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
C1 [Molofsky, Anna V.; Kelley, Kevin W.; Tsai, Hui-Hsin; Chang, Sandra M.; Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Molofsky, Anna V.; Kelley, Kevin W.; Tsai, Hui-Hsin; Chang, Sandra M.; Rowitch, David H.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Molofsky, Anna V.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
   [Kelley, Kevin W.; Tsai, Hui-Hsin; Rowitch, David H.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Kelley, Kevin W.] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA.
   [Kelley, Kevin W.; Redmond, Stephanie A.] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94143 USA.
   [Redmond, Stephanie A.; Madireddy, Lohith; Chan, Jonah R.; Baranzini, Sergio E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Ullian, Erik M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
   [Rowitch, David H.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
C3 Howard Hughes Medical 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 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 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 Rowitch, DH (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM rowitchd@peds.ucsf.edu
FU NIMH [5T32MH089920-04, R01MH099595-01]; APA/Pfizer MD/PhD Psychiatric Research Fellowship; California Institute for Regenerative Medicine [TG2-01153]; Ruth L. Kirschstein NRSA [FNS081905A]; NINDS [R01 NS059893]; NIH [1DP2OD006507-01]
NR 44
TC 244
Z9 293
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 MAY 8
PY 2014
VL 509
IS 7499
BP 189
EP +
DI 10.1038/nature13161
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300031
PM 24776795
DA 2026-03-09
ER

PT J
AU Johnson, LM
   Du, JM
   Hale, CJ
   Bischof, S
   Feng, SH
   Chodavarapu, RK
   Zhong, XH
   Marson, G
   Pellegrini, M
   Segal, DJ
   Patel, DJ
   Jacobsen, SE
AF Johnson, Lianna M.
   Du, Jiamu
   Hale, Christopher J.
   Bischof, Sylvain
   Feng, Suhua
   Chodavarapu, Ramakrishna K.
   Zhong, Xuehua
   Marson, Giuseppe
   Pellegrini, Matteo
   Segal, David J.
   Patel, Dinshaw J.
   Jacobsen, Steven E.
TI SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation
SO NATURE
LA English
DT Article
ID structural basis; recognition; iv; transcription; association; patterns; requires; mutants; uhrf1
AB RNA-directed DNA methylation in Arabidopsis thaliana depends on the upstream synthesis of 24-nucleotide small interfering RNAs (siRNAs) by RNA POLYMERASE IV (Pol IV) 1,2 and downstream synthesis of non-coding transcripts by Pol V. Pol V transcripts are thought to interact with siRNAs which then recruit DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) to methylate DNA(3-7). The SU(VAR) 3-9 homologues SUVH2 and SUVH9 act in this downstream step but the mechanism of their action is unknown(8,9). Here we show that genome-wide Pol V association with chromatin redundantly requires SUVH2 and SUVH9. Although SUVH2 and SUVH9 resemble histone methyltransferases, a crystal structure reveals that SUVH9 lacks a peptide-substrate binding cleft and lacks a properly formed S-adenosyl methionine (SAM)-binding pocket necessary for normal catalysis, consistent with a lack of methyltransferase activity for these proteins(8). SUVH2 and SUVH9 both contain SRA (SET- and RING-ASSOCIATED) domains capable of binding methylated DNA(8), suggesting that they function to recruit Pol V through DNA methylation. Consistent with this model, mutation of DNA METHYLTRANSFERASE 1 (MET1) causes loss of DNA methylation, a nearly complete loss of Pol V at its normal locations, and redistribution of Pol V to sites that become hypermethylated. Furthermore, tethering SUVH2 with a zinc finger to an unmethylated site is sufficient to recruit Pol V and establish DNA methylation and gene silencing. These results indicate that Pol V is recruited to DNA methylation through the methyl-DNA binding SUVH2 and SUVH9 proteins, and our mechanistic findings suggest a means for selectively targeting regions of plant genomes for epigenetic silencing.
C1 [Johnson, Lianna M.; Hale, Christopher J.; Bischof, Sylvain; Feng, Suhua; Chodavarapu, Ramakrishna K.; Zhong, Xuehua; Pellegrini, Matteo; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Du, Jiamu; Marson, Giuseppe; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Segal, David J.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA.
   [Segal, David J.] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA.
C3 University of California System; University of California Los Angeles; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; University of California System; University of California Los Angeles; University of California System; University of California Davis; University of California System; University of California Davis
RP Jacobsen, SE (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM pateld@mskcc.org; jacobsen@ucla.edu
FU Abby Rockefeller Mauze Trust; Maloris foundation; STARR foundation; NIH [GM60398]; Damon Runyon post-doctoral fellowship; Swiss National Science Foundation; Ruth L. Kirschstein National Research Service [F32GM096483-01]; National Cancer Institute [P30CA016042, P30CA008748] Funding Source: NIH RePORTER
NR 41
TC 272
Z9 312
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 MAR 6
PY 2014
VL 507
IS 7490
BP 124
EP +
DI 10.1038/nature12931
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400055
PM 24463519
DA 2026-03-09
ER

PT J
AU Hayes, GP
   Herman, MW
   Barnhart, WD
   Furlong, KP
   Riquelme, S
   Benz, HM
   Bergman, E
   Barrientos, S
   Earle, PS
   Samsonov, S
AF Hayes, Gavin P.
   Herman, Matthew W.
   Barnhart, William D.
   Furlong, Kevin P.
   Riquelme, Sebastian
   Benz, Harley M.
   Bergman, Eric
   Barrientos, Sergio
   Earle, Paul S.
   Samsonov, Sergey
TI Continuing megathrust earthquake potential in Chile after the 2014 Iquique earthquake
SO NATURE
LA English
DT Article
ID inversion; deformation; resolution; iran; gps
AB The seismic gap theory(1) identifies regions of elevated hazard based on a lack of recent seismicity in comparison with other portions of a fault. It has successfully explained past earthquakes (see, for example, ref. 2) and is useful for qualitatively describing where large earthquakes might occur. A large earthquake had been expected in the subduction zone adjacent to northern Chile(3-6), which had not ruptured in a megathrust earthquake since a M similar to 8.8 event in 1877. On 1 April 2014 a M8.2 earthquake occurred within this seismic gap. Here we present an assessment of the seismotectonics of the March-April 2014 Iquique sequence, including analyses of earthquake relocations, moment tensors, finite fault models, moment deficit calculations and cumulative Coulomb stress transfer. This ensemble of information allows us to place the sequence within the context of regional seismicity and to identify areas of remaining and/or elevated hazard. Our results constrain the size and spatial extent of rupture, and indicate that this was not the earthquake that had been anticipated. Significant sections of the northern Chile subduction zone have not ruptured in almost 150 years, so it is likely that future megathrust earthquakes will occur to the south and potentially to the north of the 2014 Iquique sequence.
C1 [Hayes, Gavin P.; Barnhart, William D.; Benz, Harley M.; Earle, Paul S.] US Geol Survey, Natl Earthquake Informat Ctr, Golden, CO 80401 USA.
   [Herman, Matthew W.; Furlong, Kevin P.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Riquelme, Sebastian; Barrientos, Sergio] Univ Chile, Ctr Sismol Nacl, Santiago 8370449, Chile.
   [Bergman, Eric] Global Seismol Serv, Golden, CO 80401 USA.
   [Samsonov, Sergey] Nat Resources Canada, Canada Ctr Mapping & Earth Observat, Ottawa, ON K1A 0E4, Canada.
C3 United States Department of the Interior; United States Geological Survey; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Universidad de Chile; Natural Resources Canada; Strategic Policy & Results Sector - Natural Resources Canada; Canada Centre for Mapping & Earth Observation (CCMEO)
RP Hayes, GP (corresponding author), US Geol Survey, Natl Earthquake Informat Ctr, Golden, CO 80401 USA.
EM ghayes@usgs.gov
FU National Science Foundation [EAR-1153317]; Directorate For Geosciences; Division Of Earth Sciences [1153317] Funding Source: National Science Foundation
CR Unknown -, 1986, BOLETIN LA ACAD. CHIL. CIENCIAS, V0, P0
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   Barnhart WD, 2014, GEOPHYS RES LETT, V41, P32, DOI 10.1002/2013GL058096
   Bedford J, 2013, EARTH PLANET SC LETT, V383, P26, DOI 10.1016/j.epsl.2013.09.020
   Béjar-Pizarro M, 2010, GEOPHYS J INT, V183, P390, DOI 10.1111/j.1365-246X.2010.04748.x
   Béjar-Pizarro M, 2013, NAT GEOSCI, V6, P462, DOI 10.1038/NGEO1802
   Blaser L, 2010, B SEISMOL SOC AM, V100, P2914, DOI 10.1785/0120100111
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   Ekström G, 2005, PHYS EARTH PLANET IN, V148, P327, DOI 10.1016/j.pepi.2004.09.006
   Hayes GP, 2014, EARTH PLANET SC LETT, V388, P265, DOI 10.1016/j.epsl.2013.11.010
   Hayes GP, 2013, GEOPHYS J INT, V195, P1034, DOI 10.1093/gji/ggt238
   Hayes GP, 2012, J GEOPHYS RES-SOL EA, V117, P0, DOI 10.1029/2011JB008524
   Hayes GP, 2011, SEISMOL RES LETT, V82, P481, DOI 10.1785/gssrl.82.4.481
   Herrmann RB, 2011, B SEISMOL SOC AM, V101, P2609, DOI 10.1785/0120110095
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   JORDAN TH, 1981, B SEISMOL SOC AM, V71, P1105
   Jordan TH, 2010, SEISMOL RES LETT, V81, P571, DOI 10.1785/gssrl.81.4.571
   Lay T, 2014, GEOPHYS RES LETT, V41, P3818, DOI 10.1002/2014GL060238
   Lay T, 2009, J GEOPHYS RES-SOL EA, V114, P0, DOI 10.1029/2008JB006280
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   MCCANN WR, 1979, PURE APPL GEOPHYS, V117, P1082, DOI 10.1007/BF00876211
   Métois M, 2013, GEOPHYS J INT, V194, P1283, DOI 10.1093/gji/ggt183
   OKADA Y, 1992, B SEISMOL SOC AM, V82, P1018
   Podlaha A, 2014, IMPACT FORECASTING A, V0, P0
   Sambridge M, 1999, GEOPHYS J INT, V138, P479, DOI 10.1046/j.1365-246X.1999.00876.x
   Stein RS, 1997, GEOPHYS J INT, V128, P594, DOI 10.1111/j.1365-246X.1997.tb05321.x
   Walker RT, 2005, GEOPHYS J INT, V160, P707, DOI 10.1111/j.1365-246X.2005.02516.x
   Wessel P, 1991, EOS T AM GEOPHYS UN, V72, P441, DOI 10.1029/90E000319
   Witze A, 2014, NATURE, V508, P440, DOI 10.1038/508440a
NR 36
TC 159
Z9 181
U1 1
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 AUG 21
PY 2014
VL 512
IS 7514
BP 295
EP +
DI 10.1038/nature13677
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN3SF
UT WOS:000340508200031
PM 25119028
DA 2026-03-09
ER

PT J
AU Dail, M
   Wong, J
   Lawrence, J
   O'Connor, D
   Nakitandwe, J
   Chen, SC
   Xu, J
   Lee, LB
   Akagi, K
   Li, Q
   Aster, JC
   Pear, WS
   Downing, JR
   Sampath, D
   Shannon, K
AF Dail, Monique
   Wong, Jason
   Lawrence, Jessica
   O'Connor, Daniel
   Nakitandwe, Joy
   Chen, Shann-Ching
   Xu, Jin
   Lee, Leslie B.
   Akagi, Keiko
   Li, Qing
   Aster, Jon C.
   Pear, Warren S.
   Downing, James R.
   Sampath, Deepak
   Shannon, Kevin
TI Loss of oncogenic Notch1 with resistance to a PI3K inhibitor in T-cell leukaemia
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; pten; mutations; frequency
AB Mutations that deregulate Notch1 and Ras/phosphoinositide 3 kinase (PI3K)/Akt signalling are prevalent in T-cell acute lymphoblastic leukaemia (T-ALL), and often coexist. Here we show that the PI3K inhibitor GDC-0941 is active against primary T-ALLs from wild-type and Kras(G12D) mice, and addition of the MEK inhibitor PD0325901 increases its efficacy. Mice invariably relapsed after treatment with drug-resistant clones, most of which unexpectedly had reduced levels of activated Notch1 protein, downregulated many Notch1 target genes, and exhibited cross-resistance to gamma-secretase inhibitors. Multiple resistant primary T-ALLs that emerged in vivo did not contain somatic Notch1 mutations present in the parental leukaemia. Importantly, resistant clones upregulated PI3K signalling. Consistent with these data, inhibiting Notch1 activated the PI3K pathway, providing a likely mechanism for selection against oncogenic Notch1 signalling. These studies validate PI3K as a therapeutic target in T-ALL and raise the unexpected possibility that dual inhibition of PI3K and Notch1 signalling could promote drug resistance in T-ALL.
C1 [Dail, Monique; Wong, Jason; Lawrence, Jessica; O'Connor, Daniel; Xu, Jin; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Dail, Monique; Wong, Jason; Lawrence, Jessica; O'Connor, Daniel; Xu, Jin; Shannon, Kevin] Univ Calif San Francisco, Benniof Childrens Hosp, San Francisco, CA 94143 USA.
   [Nakitandwe, Joy; Chen, Shann-Ching; Downing, James R.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Lee, Leslie B.; Sampath, Deepak] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA.
   [Akagi, Keiko] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [Li, Qing] Univ Michigan, Dept Med, Div Haematol Oncol, Ann Arbor, MI 48109 USA.
   [Aster, Jon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Pear, Warren S.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; St Jude Children's Research Hospital; Roche Holding; Roche Holding USA; Genentech; University System of Ohio; Ohio State University; University of Michigan System; University of Michigan; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Pennsylvania; University of Pennsylvania
RP Shannon, K (corresponding author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
EM shannonk@peds.ucsf.edu
FU William Lawrence and Blanche Hughes Foundation; Specialized Center of Research (SCOR) from the Leukaemia and Lymphoma Society of America [7019, 7703]; National Institutes of Health [R37 CA72614, R01 CA180037, K99 CA157950, K08 CA134649, P01 CA119070]; ALSAC of St. Jude Children's Research Hospital; Ohio Supercomputer Center [PAS0425]; Ohio Cancer Research Associate [GRT00024299]; American Cancer Society (ACS); National Health and Medical Research Council (NHMRC) [7703] Funding Source: National Health and Medical Research Council (NHMRC); National Cancer Institute [P30CA021765, T32CA128583] Funding Source: NIH RePORTER
NR 33
TC 54
Z9 56
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 SEP 25
PY 2014
VL 513
IS 7519
BP 512
EP +
DI 10.1038/nature13495
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800032
PM 25043004
DA 2026-03-09
ER

PT J
AU Wang, XT
   Ota, N
   Manzanillo, P
   Kates, L
   Zavala-Solorio, J
   Eidenschenk, C
   Zhang, J
   Lesch, J
   Lee, WP
   Ross, J
   Diehl, L
   van Bruggen, N
   Kolumam, G
   Ouyang, WJ
AF Wang, Xiaoting
   Ota, Naruhisa
   Manzanillo, Paolo
   Kates, Lance
   Zavala-Solorio, Jose
   Eidenschenk, Celine
   Zhang, Juan
   Lesch, Justin
   Lee, Wyne P.
   Ross, Jed
   Diehl, Lauri
   van Bruggen, Nicholas
   Kolumam, Ganesh
   Ouyang, Wenjun
TI Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes
SO NATURE
LA English
DT Article
ID induced insulin-resistance; food-intake; citrobacter-rodentium; gut microbiome; ppar-gamma; obesity; leptin; cells; inflammation; mice
AB The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established(1,2). Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development ofmetabolic syndrome(3-5). Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine(6,7). Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.
C1 [Wang, Xiaoting; Ota, Naruhisa; Manzanillo, Paolo; Eidenschenk, Celine; Zhang, Juan; Lesch, Justin; Lee, Wyne P.; Ouyang, Wenjun] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
   [Kates, Lance; Zavala-Solorio, Jose; Ross, Jed; van Bruggen, Nicholas; Kolumam, Ganesh] Genentech Inc, Dept Biomed Imaging, San Francisco, CA 94080 USA.
   [Diehl, Lauri] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
RP Ouyang, WJ (corresponding author), Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
EM kolumam@gene.com; ouyang@gene.com
NR 37
TC 399
Z9 465
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 OCT 9
PY 2014
VL 514
IS 7521
BP 237
EP +
DI 10.1038/nature13564
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100044
PM 25119041
DA 2026-03-09
ER

PT J
AU Behnia, R
   Clark, DA
   Carter, AG
   Clandinin, TR
   Desplan, C
AF Behnia, Rudy
   Clark, Damon A.
   Carter, Adam G.
   Clandinin, Thomas R.
   Desplan, Claude
TI Processing properties of ON and OFF pathways for Drosophila motion detection
SO NATURE
LA English
DT Article
ID visual interneurons; optic lobe; wild-type; melanogaster; patterns; medulla; circuit; lamina
AB The algorithms and neural circuits that process spatio-temporal changes in luminance to extract visual motion cues have been the focus of intense research. An influential model, the Hassenstein-Reichardt correlator(1), relies on differential temporal filtering of two spatially separated input channels, delaying one input signal with respect to the other. Motion in a particular direction causes these delayed and non-delayed luminance signals to arrive simultaneously at a subsequent processing step in the brain; these signals are then nonlinearly amplified to produce a direction-selective response. Recent work in Drosophila has identified two parallel pathways that selectively respond to either moving light or dark edges(2,3). Each of these pathways requires two critical processing steps to be applied to incoming signals: differential delay between the spatial input channels, and distinct processing of brightness increment and decrement signals. Here we demonstrate, using in vivo patch-clamp recordings, that four medulla neurons implement these two processing steps. The neurons Mi1 and Tm3 respond selectively to brightness increments, with the response of Mi1 delayed relative to Tm3. Conversely, Tm1 and Tm2 respond selectively to brightness decrements, with the response of Tm1 delayed compared with Tm2. Remarkably, constraining Hassenstein-Reichardt correlator models using these measurements produces outputs consistent with previously measured properties of motion detectors, including temporal frequency tuning and specificity for light versus dark edges. We propose that Mi1 and Tm3 perform critical processing of the delayed and non-delayed input channels of the correlator responsible for the detection of light edges, while Tm1 and Tm2 play analogous roles in the detection of moving dark edges. Our data show that specific medulla neurons possess response properties that allow them to implement the algorithmic steps that precede the correlative operation in the Hassenstein-Reichardt correlator, revealing elements of the long-sought neural substrates of motion detection in the fly.
C1 [Behnia, Rudy; Desplan, Claude] NYU, Dept Biol, Ctr Dev Genet, New York, NY 10003 USA.
   [Clark, Damon A.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA.
   [Clark, Damon A.; Clandinin, Thomas R.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   [Carter, Adam G.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Desplan, Claude] New York Univ Abu Dhabi Inst, Ctr Genom & Syst Biol, Abu Dhabi, U Arab Emirates.
C3 New York University; Yale University; Stanford University; New York University
RP Behnia, R (corresponding author), NYU, Dept Biol, Ctr Dev Genet, New York, NY 10003 USA.
EM rb141@nyu.edu; damon.clark@yale.edu
FU National Institutes of Health (NIH) [R01EY017916]; New York University Abu Dhabi Institute [G1205C]; EMBO; Human Frontier Science Program; NIH [R01EY022638, DP1 OD003530]; NIH; Jane Coffin Childs postdoctoral fellowship; McKnight Foundation; National Eye Institute [R01EY017916, R01EY022638] Funding Source: NIH RePORTER
NR 38
TC 177
Z9 232
U1 1
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 AUG 28
PY 2014
VL 512
IS 7515
BP 427
EP U443
DI 10.1038/nature13427
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600033
PM 25043016
DA 2026-03-09
ER

PT J
AU Sankararaman, S
   Mallick, S
   Dannemann, M
   Prüfer, K
   Kelso, J
   Pääbo, S
   Patterson, N
   Reich, D
AF Sankararaman, Sriram
   Mallick, Swapan
   Dannemann, Michael
   Pruefer, Kay
   Kelso, Janet
   Paeaebo, Svante
   Patterson, Nick
   Reich, David
TI The genomic landscape of Neanderthal ancestry in present-day humans
SO NATURE
LA English
DT Article
ID sex-chromosm; east asians; sequence; evolution; history
AB Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture(1,2). The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci(1,3-8). We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans(9). Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes(10-12). These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.
C1 [Sankararaman, Sriram; Mallick, Swapan; Patterson, Nick; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Sankararaman, Sriram; Mallick, Swapan; Patterson, Nick; Reich, David] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Dannemann, Michael; Pruefer, Kay; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
   [Reich, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Max Planck Society; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Sankararaman, S (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM sankararaman@genetics.med.harvard.edu; reich@genetics.med.harvard.edu
FU Presidential Innovation Fund of the Max Planck Society; NSF HOMINID [1032255]; NIH [GM100233]; Initiative for the Science of the Human Past at Harvard University; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1032255] Funding Source: National Science Foundation; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER
NR 39
TC 677
Z9 838
U1 8
U2 602
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2014
VL 507
IS 7492
BP 354
EP +
DI 10.1038/nature12961
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000033
PM 24476815
DA 2026-03-09
ER

PT J
AU Mankowsky, R
   Subedi, A
   Först, M
   Mariager, SO
   Chollet, M
   Lemke, HT
   Robinson, JS
   Glownia, JM
   Minitti, MP
   Frano, A
   Fechner, M
   Spaldin, NA
   Loew, T
   Keimer, B
   Georges, A
   Cavalleri, A
AF Mankowsky, R.
   Subedi, A.
   Foerst, M.
   Mariager, S. O.
   Chollet, M.
   Lemke, H. T.
   Robinson, J. S.
   Glownia, J. M.
   Minitti, M. P.
   Frano, A.
   Fechner, M.
   Spaldin, N. A.
   Loew, T.
   Keimer, B.
   Georges, A.
   Cavalleri, A.
TI Nonlinear lattice dynamics as a basis for enhanced superconductivity in YBa2Cu3O6.5
SO NATURE
LA English
DT Article
ID wave; phononics; order; mode
AB Terahertz-frequency optical pulses can resonantly drive selected vibrational modes in solids and deform their crystal structures(1-3). In complex oxides, this method has been used to melt electronic order(4-6), drive insulator-to-metal transitions(7) and induce superconductivity(8). Strikingly, coherent interlayer transport strongly reminiscent of superconductivity can be transiently induced up to room temperature (300 kelvin) in IrBa2Cu3O6+x (refs 9, 10). Here we report the crystal structure of this exotic non-equilibrium state, determined by femtosecond X-ray diffraction and ab initio density functional theory calculations. We find that nonlinear lattice excitation in normal-state IrBa2Cu3O6-x at above the transition temperature of 52 kelvin causes a simultaneous increase and decrease in the Cu-O-2 intra-bilayer and, respectively, inter-bilayer distances, accompanied by anisotropic changes in the in-plane O-Cu-O bond buckling. Density functional theory calculations indicate that these motions cause drastic changes in the electronic structure. Among these, the enhancement in the d(x2-y2) character of the in-plane electronic structure is likely to favour superconductivity.
C1 [Mankowsky, R.; Foerst, M.; Cavalleri, A.] Max Planck Inst Struct & Dynam Matter, D-22761 Hamburg, Germany.
   [Mankowsky, R.; Cavalleri, A.] Univ Hamburg, D-22761 Hamburg, Germany.
   [Mankowsky, R.; Foerst, M.; Cavalleri, A.] Ctr Free Elect Laser Sci CFEL, D-22761 Hamburg, Germany.
   [Subedi, A.; Georges, A.] Ecole Polytech, CNRS, Ctr Phys Theor, F-91128 Palaiseau, France.
   [Mariager, S. O.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Chollet, M.; Lemke, H. T.; Robinson, J. S.; Glownia, J. M.] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
   [Frano, A.; Loew, T.; Keimer, B.] Max Planck Inst Solid State Res, D-70599 Stuttgart, Germany.
   [Fechner, M.; Spaldin, N. A.] ETH, CH-8093 Zurich, Switzerland.
   [Georges, A.] Coll France, F-75005 Paris, France.
   [Georges, A.] Univ Geneva, Dept Phys Mat Condensee MaNEP, CH-1211 Geneva, Switzerland.
   [Cavalleri, A.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
C3 Max Planck Society; University of Hamburg; Centre National de la Recherche Scientifique (CNRS); Institut Polytechnique de Paris; Ecole Polytechnique; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Max Planck Society; Swiss Federal Institutes of Technology Domain; ETH Zurich; Universite PSL; College de France; University of Geneva; University of Oxford
RP Mankowsky, R (corresponding author), Max Planck Inst Struct & Dynam Matter, D-22761 Hamburg, Germany.
EM roman.mankowsky@mpsd.mpg.de; andrea.cavalleri@mpsd.mpg.de
FU European Research Council under the European Union [319286]; German Science Foundation [SFB925]; Swiss National Supercomputing Centre [s404]; Swiss National Science Foundation through its National Centre of Competences in Research MUST
NR 25
TC 434
Z9 480
U1 5
U2 368
PU NATURE PUBLISHING 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 4
PY 2014
VL 516
IS 7529
BP 71
EP 73
DI 10.1038/nature13875
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800040
PM 25471882
DA 2026-03-09
ER

PT J
AU Bi, SD
   Wang, YQ
   Guan, J
   Sheng, X
   Meng, J
AF Bi, Shundong
   Wang, Yuanqing
   Guan, Jian
   Sheng, Xia
   Meng, Jin
TI Three new Jurassic euharamiyidan species reinforce early divergence of mammals
SO NATURE
LA English
DT Article
ID functional-adaptive anatomy; marsupials mayulestes-ferox; evolution; diversification; mammaliaform; paleobiology; skeleton; bearing; teeth
AB The phylogeny of Allotheria, including Multituberculata and Haramiyida, remains unsolved and has generated contentious views on the origin and earliest evolution of mammals. Here we report three new species of a new clade, Euharamiyida, based on six well-preserved fossils from the Jurassic period of China. These fossils reveal many craniodental and post-cranial features of euharamiyidans and clarify several ambiguous structures that are currently the topic of debate. Our phylogenetic analyses recognize Euharamiyida as the sister group of Multituberculata, and place Allotheria within the Mammalia. The phylogeny suggests that allotherian mammals evolved from a Late Triassic (approximately 208 million years ago) Haramiyavia-like ancestor and diversified into euharamiyidans and multituberculates with a cosmopolitan distribution, implying homologous acquisition of many craniodental and postcranial features in the two groups. Our findings also favour a Late Triassic origin of mammals in Laurasia and two independent detachment events of the middle ear bones during mammalian evolution.
C1 [Bi, Shundong; Wang, Yuanqing] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Bi, Shundong] Indiana Univ Penn, Dept Biol, Indiana, PA 15705 USA.
   [Guan, Jian] Beijing Nat Hist Museum, Beijing 100050, Peoples R China.
   [Sheng, Xia] Shenyang Normal Univ, Paleontol Museum Liaoning, Shenyang 110034, Liaoning, Peoples R China.
   [Meng, Jin] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Pennsylvania State System of Higher Education (PASSHE); Indiana University of Pennsylvania; Shenyang Normal University; American Museum of Natural History (AMNH)
RP Meng, J (corresponding author), Amer Museum Nat Hist, Div Paleontol, Cent Pk West & 79th St, New York, NY 10024 USA.
EM wangyuanqing@ivpp.ac.cn; jmeng@amnh.org
FU National Basic Research Program of China (973 program) [2012CB821906]; Strategic Priority Research Program of Chinese Academy of Sciences [XDB03020501]; National Science Foundation of China [41128002]; Hundred Talents Programs of the Chinese Academy of Sciences
NR 50
TC 111
Z9 133
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 OCT 30
PY 2014
VL 514
IS 7524
BP 579
EP +
DI 10.1038/nature13718
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR8BW
UT WOS:000343801500038
PM 25209669
DA 2026-03-09
ER

PT J
AU De Rubeis, S
   He, X
   Goldberg, AP
   Poultney, CS
   Samocha, K
   Cicek, AE
   Kou, Y
   Liu, L
   Fromer, M
   Walker, S
   Singh, T
   Klei, L
   Kosmicki, J
   Fu, SC
   Aleksic, B
   Biscaldi, M
   Bolton, PF
   Brownfeld, JM
   Cai, JL
   Campbell, NG
   Carracedo, A
   Chahrour, MH
   Chiocchetti, AG
   Coon, H
   Crawford, EL
   Crooks, L
   Curran, SR
   Dawson, G
   Duketis, E
   Fernandez, BA
   Gallagher, L
   Geller, E
   Guter, SJ
   Hill, RS
   Ionita-Laza, I
   Gonzalez, PJ
   Kilpinen, H
   Klauck, SM
   Kolevzon, A
   Lee, I
   Lei, J
   Lehtimäki, T
   Lin, CF
   Ma'ayan, A
   Marshall, CR
   McInnes, AL
   Neale, B
   Owen, MJ
   Ozaki, N
   Parellada, M
   Parr, JR
   Purcell, S
   Puura, K
   Rajagopalan, D
   Rehnström, K
   Reichenberg, A
   Sabo, A
   Sachse, M
   Sanders, SJ
   Schafer, C
   Schulte-Rüther, M
   Skuse, D
   Stevens, C
   Szatmari, P
   Tammimies, K
   Valladares, O
   Voran, A
   Wang, LS
   Weiss, LA
   Willsey, AJ
   Yu, TW
   Yuen, RKC
   Cook, EH
   Freitag, CM
   Gill, M
   Hultman, CM
   Lehner, T
   Palotie, A
   Schellenberg, GD
   Skiar, P
   State, MW
   Sutcliffe, JS
   Walsh, CA
   Scherer, SW
   Zwick, ME
   Barrett, JC
   Cutler, DJ
   Roeder, K
   Devlin, B
   Daly, MJ
   Buxbaum, JD
AF De Rubeis, Silvia
   He, Xin
   Goldberg, Arthur P.
   Poultney, Christopher S.
   Samocha, Kaitlin
   Cicek, A. Ercument
   Kou, Yan
   Liu, Li
   Fromer, Menachem
   Walker, Susan
   Singh, Tarjinder
   Klei, Lambertus
   Kosmicki, Jack
   Fu, Shih-Chen
   Aleksic, Branko
   Biscaldi, Monica
   Bolton, Patrick F.
   Brownfeld, Jessica M.
   Cai, Jinlu
   Campbell, Nicholas G.
   Carracedo, Angel
   Chahrour, Maria H.
   Chiocchetti, Andreas G.
   Coon, Hilary
   Crawford, Emily L.
   Crooks, Lucy
   Curran, Sarah R.
   Dawson, Geraldine
   Duketis, Eftichia
   Fernandez, Bridget A.
   Gallagher, Louise
   Geller, Evan
   Guter, Stephen J.
   Hill, R. Sean
   Ionita-Laza, Iuliana
   Gonzalez, Patricia Jimenez
   Kilpinen, Helena
   Klauck, Sabine M.
   Kolevzon, Alexander
   Lee, Irene
   Lei, Jing
   Lehtimaeki, Terho
   Lin, Chiao-Feng
   Ma'ayan, Avi
   Marshall, Christian R.
   McInnes, Alison L.
   Neale, Benjamin
   Owen, Michael J.
   Ozaki, Norio
   Parellada, Mara
   Parr, Jeremy R.
   Purcell, Shaun
   Puura, Kaija
   Rajagopalan, Deepthi
   Rehnstrom, Karola
   Reichenberg, Abraham
   Sabo, Aniko
   Sachse, Michael
   Sanders, Stephan J.
   Schafer, Chad
   Schulte-Ruether, Martin
   Skuse, David
   Stevens, Christine
   Szatmari, Peter
   Tammimies, Kristiina
   Valladares, Otto
   Voran, Annette
   Wang, Li-San
   Weiss, Lauren A.
   Willsey, A. Jeremy
   Yu, Timothy W.
   Yuen, Ryan K. C.
   Cook, Edwin H.
   Freitag, Christine M.
   Gill, Michael
   Hultman, Christina M.
   Lehner, Thomas
   Palotie, Aarno
   Schellenberg, Gerard D.
   Skiar, Pamela
   State, Matthew W.
   Sutcliffe, James S.
   Walsh, Christopher A.
   Scherer, Stephen W.
   Zwick, Michael E.
   Barrett, Jeffrey C.
   Cutler, David J.
   Roeder, Kathryn
   Devlin, Bernie
   Daly, Mark J.
   Buxbaum, Joseph D.
TI Synaptic, transcriptional and chromatin genes disrupted in autism
SO NATURE
LA English
DT Article
ID de-novo mutations; copy-number variation; framework; network; risk; discovery; ubiquitin
AB The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
C1 [De Rubeis, Silvia; Goldberg, Arthur P.; Poultney, Christopher S.; Kou, Yan; Fu, Shih-Chen; Brownfeld, Jessica M.; Cai, Jinlu; Kolevzon, Alexander; Reichenberg, Abraham; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
   [De Rubeis, Silvia; Goldberg, Arthur P.; Poultney, Christopher S.; Kou, Yan; Fromer, Menachem; Fu, Shih-Chen; Brownfeld, Jessica M.; Cai, Jinlu; Kolevzon, Alexander; Purcell, Shaun; Reichenberg, Abraham; Skiar, Pamela; Buxbaum, Joseph D.] Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA.
   [He, Xin; Cicek, A. Ercument; Roeder, Kathryn] Carnegie Mellon Univ, Ray & Stephanie Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA.
   [Goldberg, Arthur P.; Fromer, Menachem; Skiar, Pamela; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Samocha, Kaitlin; Fromer, Menachem; Kosmicki, Jack; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Liu, Li; Lei, Jing; Schafer, Chad; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
   [Walker, Susan; Marshall, Christian R.; Rajagopalan, Deepthi; Tammimies, Kristiina; Yuen, Ryan K. C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Program Genet & Genome Biol, Toronto, ON M5G 0A4, Canada.
   [Singh, Tarjinder; Crooks, Lucy; Rehnstrom, Karola; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
   [Aleksic, Branko; Ozaki, Norio; UK10K Consortium] Nagoya Univ, Sch Med, Dept Psychiat, Nagoya, Aichi 4668550, Japan.
   [Biscaldi, Monica] Univ Med Ctr Freiburg, Dept Child & Adolescent Psychiat Psychotherapy &, D-79106 Freiburg, Germany.
   [Biscaldi, Monica] Ctr Mental Disorders, D-79106 Freiburg, Germany.
   [Bolton, Patrick F.; Curran, Sarah R.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child Psychiat, London SE5 8AF, England.
   [Bolton, Patrick F.; Curran, Sarah R.] Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London SE5 8AF, England.
   [Campbell, Nicholas G.; Crawford, Emily L.; Sutcliffe, James S.] Vanderbilt Univ, Sch Med, Vanderbilt Brain Inst, Nashville, TN 37212 USA.
   [Campbell, Nicholas G.; Crawford, Emily L.; Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA.
   [Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Santiago De Compostela 15706, Spain.
   [Carracedo, Angel] Galician Fdn Genom Med SERGAS, Santiago De Compostela 15706, Spain.
   [Carracedo, Angel] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21589, Saudi Arabia.
   [Chahrour, Maria H.; Hill, R. Sean; Yu, Timothy W.; Walsh, Christopher A.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Chahrour, Maria H.; Hill, R. Sean; Yu, Timothy W.; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA.
   [Chiocchetti, Andreas G.; Duketis, Eftichia; Sachse, Michael; Freitag, Christine M.] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany.
   [Coon, Hilary] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA.
   [Coon, Hilary] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA.
   [Dawson, Geraldine] Duke Univ, Duke Inst Brain Sci, Durham, NC 27708 USA.
   [Fernandez, Bridget A.] Mem Univ Newfoundland, Disciplines Genet & Med, St John, NF A1B 3V6, Canada.
   [Gallagher, Louise; Gill, Michael] Trinity Coll Dublin, Sch Med, Dept Psychiat, Dublin 8, Ireland.
   [Geller, Evan; Lin, Chiao-Feng; Valladares, Otto; Wang, Li-San; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Guter, Stephen J.; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA.
   [Ionita-Laza, Iuliana] Columbia Univ, Dept Biostat, New York, NY 10032 USA.
   [Gonzalez, Patricia Jimenez] Hosp Nacl de Ninos Dr Saenz Herrera, CCSS, Child Dev & Behav Unit, San Jose, Costa Rica.
   [Kilpinen, Helena] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Klauck, Sabine M.] German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany.
   [Kolevzon, Alexander] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
   [Lee, Irene; Skuse, David] UCL, Inst Child Hlth, London WC1N 1EH, England.
   [Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, SF-33100 Tampere, Finland.
   [Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [McInnes, Alison L.] Kaiser Permanente, Dept Psychiat, San Francisco, CA 94118 USA.
   [Neale, Benjamin; Stevens, Christine; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Owen, Michael J.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales.
   [Owen, Michael J.] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF24 4HQ, S Glam, Wales.
   [Parellada, Mara] Univ Complutense, Hosp Gen Univ Gregorio Maranon, Child & Adolescent Psychiat Dept, IiSGM,CIBERSAM, E-28040 Madrid, Spain.
   [Parr, Jeremy R.] Newcastle Univ, Sch Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Puura, Kaija] Tampere Univ, Dept Child Psychiat, Tampere 33521, Finland.
   [Puura, Kaija] Tampere Univ Hosp, Tampere 33521, Finland.
   [Reichenberg, Abraham] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
   [Sabo, Aniko] Baylor Coll Med, Dept Human Mol Genet, Houston, TX 77030 USA.
   [Sanders, Stephan J.; Weiss, Lauren A.; Willsey, A. Jeremy; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
   [Schulte-Ruether, Martin] Univ Hosp RWTH Aachen, JARA Brain Translat Med, Translat Brain Med Psychiat & Neurol, Dept Child & Adolescent Psychiat Psychosomat Psyc, D-52056 Aachen, Germany.
   [Skuse, David] Great Ormond St Hosp Sick Children, Natl Hlth Serv Fdn Trust, Dept Child & Adolescent Mental Hlth, London WC1N 3JH, England.
   [Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Offord Ctr Child Studies, Hamilton, ON L8S 4K1, Canada.
   [Voran, Annette] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, D-66424 Homburg, Germany.
   [Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Lehner, Thomas] NIMH, NIH, Bethesda, MD 20892 USA.
   [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FI-00014 Helsinki, Finland.
   [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
   [Skiar, Pamela; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
   [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada.
   [Zwick, Michael E.; Cutler, David J.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
   [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
   [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Carnegie Mellon University; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Carnegie Mellon University; University of Toronto; Hospital for Sick Children (SickKids); Wellcome Trust Sanger Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Nagoya University; University of Freiburg; University of London; King's College London; University of London; King's College London; Vanderbilt University; Vanderbilt University; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Universidade de Santiago de Compostela; King Abdulaziz University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Goethe University Frankfurt; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Duke University; Memorial University Newfoundland; Trinity College Dublin; University of Pennsylvania; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Columbia University; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Helmholtz Association; German Cancer Research Center (DKFZ); Icahn School of Medicine at Mount Sinai; University of London; University College London; Icahn School of Medicine at Mount Sinai; Kaiser Permanente; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cardiff University; Cardiff University; General University Gregorio Maranon Hospital; CIBER - Centro de Investigacion Biomedica en Red; CIBERSAM; Complutense University of Madrid; Newcastle University - UK; Tampere University; Tampere University; Tampere University Hospital; Icahn School of Medicine at Mount Sinai; Baylor College of Medicine; University of California System; University of California San Francisco; RWTH Aachen University; RWTH Aachen University Hospital; University of London; University College London; Great Ormond Street Hospital for Children NHS Foundation Trust; McMaster University; Universitatsklinikum des Saarlandes; Karolinska Institutet; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Helsinki; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; University of Toronto; Emory University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Buxbaum, JD (corresponding author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
EM mjdaly@broadinstitute.org; joseph.buxbaum@mssm.edu
FU National Institutes of Health (NIH) [U01MH100233, U01MH100209, U01MH100229, U01MH100239]; NIH grants [R01MH089208, U54 HG003067]; NIH [R01 MH089482, R37 MH057881, R01 MH061009, UL1TR000445, P50 HD055751, MH089482, NIH RO1 MH083565, RC2MH089952, NIMH MH095034, MH077139, 5UL1 RR024975, P30 HD15052]; Charles and Ann Schlaifer Memorial Fund; UK National Institute for Health Research (NIHR) Senior Investigator award; NIHR Biomedical Research Centre in Mental Health at the South LondonAMP;Maudsley Hospital; Maria Jose Jove Foundation; Strategic Action from Health Carlos III Institute (FEDER) [FIS PI13/01136];  [HICF-1009-003];  [WT098051];  [WT091310]; National Institute of Mental Health [R37MH057881, R01MH097849, R01MH095797] Funding Source: NIH RePORTER; NIH Office of the Director; National Human Genome Research Institute [T32HG002295] Funding Source: NIH RePORTER; Medical Research Council [G9817803B, MR/L010305/1, G0500870] Funding Source: researchfish; National Institute for Health Research [NF-SI-0510-10268] Funding Source: researchfish; MRC [G0500870] Funding Source: UKRI
NR 47
TC 2031
Z9 2393
U1 10
U2 328
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 13
PY 2014
VL 515
IS 7526
BP 209
EP +
DI 10.1038/nature13772
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AT0MZ
UT WOS:000344631400038
PM 25363760
DA 2026-03-09
ER

PT J
AU Shen, P
   Roch, T
   Lampropoulou, V
   O'Connor, RA
   Stervbo, U
   Hilgenberg, E
   Ries, S
   Dang, VD
   Jaimes, Y
   Daridon, C
   Li, R
   Jouneau, L
   Boudinot, P
   Wilantri, S
   Sakwa, I
   Miyazaki, Y
   Leech, MD
   McPherson, RC
   Wirtz, S
   Neurath, M
   Hoehlig, K
   Meinl, E
   Grützkau, A
   Grün, JR
   Horn, K
   Kühl, AA
   Dörner, T
   Bar-Or, A
   Kaufmann, SHE
   Anderton, SM
   Fillatreau, S
AF Shen, Ping
   Roch, Toralf
   Lampropoulou, Vicky
   O'Connor, Richard A.
   Stervbo, Ulrik
   Hilgenberg, Ellen
   Ries, Stefanie
   Van Duc Dang
   Jaimes, Yarua
   Daridon, Capucine
   Li, Rui
   Jouneau, Luc
   Boudinot, Pierre
   Wilantri, Siska
   Sakwa, Imme
   Miyazaki, Yusei
   Leech, Melanie D.
   McPherson, Rhoanne C.
   Wirtz, Stefan
   Neurath, Markus
   Hoehlig, Kai
   Meinl, Edgar
   Gruetzkau, Andreas
   Gruen, Joachim R.
   Horn, Katharina
   Kuehl, Anja A.
   Doerner, Thomas
   Bar-Or, Amit
   Kaufmann, Stefan H. E.
   Anderton, Stephen M.
   Fillatreau, Simon
TI IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases
SO NATURE
LA English
DT Article
ID t-cells; salmonella-typhimurium; ulcerative-colitis; depletion; rituximab; cytokine; activation; expression; prevention; arthritis
AB B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens(1,2). Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM1 CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35 producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.
C1 [Shen, Ping; Roch, Toralf; Lampropoulou, Vicky; Stervbo, Ulrik; Hilgenberg, Ellen; Ries, Stefanie; Van Duc Dang; Jaimes, Yarua; Daridon, Capucine; Wilantri, Siska; Sakwa, Imme; Hoehlig, Kai; Gruetzkau, Andreas; Gruen, Joachim R.; Horn, Katharina; Doerner, Thomas; Fillatreau, Simon] Deutsch Rheuma Forschungszentrum, Charite Pl 1, D-10117 Berlin, Germany.
   [O'Connor, Richard A.; Leech, Melanie D.; McPherson, Rhoanne C.; Anderton, Stephen M.] Univ Edinburgh, Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland.
   [O'Connor, Richard A.; Leech, Melanie D.; McPherson, Rhoanne C.; Anderton, Stephen M.] Univ Edinburgh, Ctr Multiple Sclerosis Res, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland.
   [Daridon, Capucine; Doerner, Thomas] Charite, Dept Med Rheumatol & Clin Immunol, CC12, D-10117 Berlin, Germany.
   [Li, Rui; Miyazaki, Yusei; Bar-Or, Amit] McGill Univ, Montreal Neurol Inst & Hosp, Neuroimmunol Unit, Montreal, PQ H3A 2B4, Canada.
   [Jouneau, Luc; Boudinot, Pierre] INRA, Virol & Immunol Mol, F-78352 Jouy En Josas, France.
   [Wirtz, Stefan; Neurath, Markus] Univ Erlangen Nurnberg, Med Clin 1, D-91054 Erlangen, Germany.
   [Meinl, Edgar] Univ Munich, Inst Klin Neuroimmunol Klinikum, D-81377 Munich, Germany.
   [Kuehl, Anja A.] Res Ctr ImmunoSci, D-12203 Berlin, Germany.
   [Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany.
C3 Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ); University of Edinburgh; University of Edinburgh; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; McGill University; Universite Paris Saclay; INRAE; University of Erlangen Nuremberg; University of Munich; Max Planck Society
RP Fillatreau, S (corresponding author), Deutsch Rheuma Forschungszentrum, Charite Pl 1, D-10117 Berlin, Germany.
EM fillatreau@drfz.de
FU Deutsche Forschungsgemeinschaft [SFB-650, TRR-36, TRR-130, FI-1238/02, Do491/7-2, Do491/8-2]; Hertie Stiftung; Merieux Institute; INRA; CIHR/MSSC New Emerging Team grant in Clinical Autoimmunity; UK Medical Research Council; Wellcome Trust; Clinical Competence Network for Multiple Sclerosis;  [SFB-TR128]; Medical Research Council [G0901697, G1100084, G0801924] Funding Source: researchfish; MRC [G1100084, G0801924, G0901697] Funding Source: UKRI
NR 31
TC 866
Z9 998
U1 2
U2 140
PU NATURE PUBLISHING 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 20
PY 2014
VL 507
IS 7492
BP 366
EP +
DI 10.1038/nature12979
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000036
PM 24572363
DA 2026-03-09
ER

PT J
AU Ding, YL
   Tang, Y
   Kwok, CK
   Zhang, Y
   Bevilacqua, PC
   Assmann, SM
AF Ding, Yiliang
   Tang, Yin
   Kwok, Chun Kit
   Zhang, Yu
   Bevilacqua, Philip C.
   Assmann, Sarah M.
TI In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features
SO NATURE
LA English
DT Article
ID ribosomal-rna; environmental responses; oxygen deprivation; primer extension; translation; polyadenylation; transcriptome; prediction; intron
AB RNA structure has critical roles in processes ranging from ligand sensing to the regulation of translation, polyadenylation and splicing(1-4). However, a lack of genome-wide in vivo RNA structural data has limited our understanding of how RNA structure regulates gene expression in living cells. Here we present a high-throughput, genome-wide in vivo RNA structure probing method, structure-seq, in which dimethyl sulphate methylation of unprotected adenines and cytosines is identified by next-generation sequencing. Application of this method to Arabidopsis thaliana seedlings yielded the first in vivo genome-wide RNA structure map at nucleotide resolution for any organism, with quantitative structural information across more than 10,000 transcripts. Our analysis reveals a three-nucleotide periodic repeat pattern in the structure of coding regions, as well as a less-structured region immediately upstream of the start codon, and shows that these features are strongly correlated with translation efficiency. We also find patterns of strong and weak secondary structure at sites of alternative polyadenylation, as well as strong secondary structure at 59 splice sites that correlates with unspliced events. Notably, in vivo structures of messenger RNAs annotated for stress responses are poorly predicted in silico, whereas mRNA structures of genes related to cell function maintenance are well predicted. Global comparison of several structural features between these two categories shows that the mRNAs associated with stress responses tend to have more single-strandedness, longer maximal loop length and higher free energy per nucleotide, features that may allow these RNAs to undergo conformational changes in response to environmental conditions. Structure-seq allows the RNA structurome and its biological roles to be interrogated on a genome-wide scale and should be applicable to any organism.
C1 [Ding, Yiliang; Tang, Yin; Assmann, Sarah M.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [Ding, Yiliang; Kwok, Chun Kit; Bevilacqua, Philip C.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA.
   [Ding, Yiliang; Tang, Yin; Kwok, Chun Kit; Bevilacqua, Philip C.; Assmann, Sarah M.] Penn State Univ, Ctr RNA Mol Biol, University Pk, PA 16802 USA.
   [Tang, Yin; Zhang, Yu; Assmann, Sarah M.] Penn State Univ, Bioinformat & Genom Grad Program, University Pk, PA 16802 USA.
   [Zhang, Yu] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
   [Bevilacqua, Philip C.; Assmann, Sarah M.] Penn State Univ, Plant Biol Grad Program, University Pk, PA 16802 USA.
C3 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; 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
RP Assmann, SM (corresponding author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM pcb5@psu.edu; sma3@psu.edu
FU Human Frontier Science Program (HFSP) [RGP0002/2009-C]; Penn State Eberly College of Science; Penn State Huck Institutes HITS; National Science Foundation [OCI-0821527]
NR 37
TC 615
Z9 765
U1 7
U2 219
PU NATURE PUBLISHING 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 30
PY 2014
VL 505
IS 7485
BP 696
EP +
DI 10.1038/nature12756
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 298JV
UT WOS:000330321000044
PM 24270811
DA 2026-03-09
ER

PT J
AU Moresi, L
   Betts, PG
   Miller, MS
   Cayley, RA
AF Moresi, L.
   Betts, P. G.
   Miller, M. S.
   Cayley, R. A.
TI Dynamics of continental accretion
SO NATURE
LA English
DT Article
ID lachlan fold belt; southeastern australia; cenozoic tectonics; eastern australia; numerical-models; subduction zones; evolution; mantle; asia; convergence
AB Subduction zones become congested when they try to consume buoyant, exotic crust. The accretionary mountain belts (orogens) that format these convergent plate margins have been the principal sites of lateral continental growth through Earth's history. Modern examples of accretionary margins are the North American Cordilleras and southwest Pacific subduction zones. The geologic record contains abundant accretionary orogens, such as the Tasmanides(1), along the eastern margin of the supercontinent Gondwana, and the Altaides, which formed on the southern margin of Laurasia(2). In modern and ancient examples of long-lived accretionary orogens, the overriding plate is subjected to episodes of crustal extension and back-arc basin development, often related to subduction rollback(3) and transient episodes of orogenesis and crustal shortening(4-7), coincident with accretion of exotic crust. Here we present three-dimensional dynamic models that show how accretionary margins evolve from the initial collision, through a period of plate margin instability, to re-establishment of a stable convergent margin. The models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region. The complexity of the morphology and the evolution of the system are caused by lateral rollback of a tightly arcuate trench migrating parallel to the plate boundary and orthogonally to the convergence direction. We find geological and geophysical evidence for this process in the Tasmanides of eastern Australia, and infer that this is a recurrent and global phenomenon.
C1 [Moresi, L.; Betts, P. G.] Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
   [Moresi, L.] Monash Univ, Sch Math Sci, Clayton, Vic 3800, Australia.
   [Moresi, L.] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
   [Miller, M. S.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
   [Cayley, R. A.] Geol Survey Victoria, Melbourne, Vic 3001, Australia.
C3 Monash University; Monash University; University of Melbourne; University of Southern California
RP Moresi, L (corresponding author), Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
EM louis.moresi@unimelb.edu.au
FU Australian Research Council [DP130101946, DP110101697]; Australian Commonwealth Government; Monash Research Accelerator Program; National Science Foundation [EAR-1054638]
NR 35
TC 239
Z9 258
U1 5
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 APR 10
PY 2014
VL 508
IS 7495
BP 245
EP +
DI 10.1038/nature13033
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE4UK
UT WOS:000333979900044
PM 24670638
DA 2026-03-09
ER

PT J
AU Cambier, CJ
   Takaki, KK
   Larson, RP
   Hernandez, RE
   Tobin, DM
   Urdahl, KB
   Cosma, CL
   Ramakrishnan, L
AF Cambier, C. J.
   Takaki, Kevin K.
   Larson, Ryan P.
   Hernandez, Rafael E.
   Tobin, David M.
   Urdahl, Kevin B.
   Cosma, Christine L.
   Ramakrishnan, Lalita
TI Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids
SO NATURE
LA English
DT Article
ID marinum infection; immune-response; nitric-oxide; tuberculosis; zebrafish; susceptibility; granuloma; virulence; humans; mice
AB The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis infects macrophages, which transport it to deeper tissues(1). How mycobacteria survive in these broadly microbicidal cells is an important question. Here we show in mice and zebrafish that M. tuberculosis, and its close pathogenic relative Mycobacterium marinum, preferentially recruit and infect permissive macrophages while evading microbicidal ones. This immune evasion is accomplished by using cell-surface-associated phthiocerol dimycoceroserate (PDIM) lipids(2) to mask underlying pathogen-associated molecular patterns (PAMPs). In the absence of PDIM, these PAMPs signal a Toll-like receptor (TLR)-dependent recruitment of macrophages that produce microbicidal reactive nitrogen species. Concordantly, the related phenolic glycolipids (PGLs)(2) promote the recruitment of permissive macrophages through a host chemokine receptor 2 (CCR2)-mediated pathway. Thus, we have identified coordinated roles for PDIM, known to be essential for mycobacterial virulence(3), and PGL, which (along with CCR2) is known to be associated with human tuberculosis(4,5). Our findings also suggest an explanation for the longstanding observation that M. tuberculosis initiates infection in the relatively sterile environment of the lower respiratory tract, rather than in the upper respiratory tract, where resident microflora and inhaled environmental microbes may continually recruit microbicidal macrophages through TLR-dependent signalling.
C1 [Cambier, C. J.; Larson, Ryan P.; Urdahl, Kevin B.; Ramakrishnan, Lalita] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
   [Takaki, Kevin K.; Tobin, David M.; Cosma, Christine L.; Ramakrishnan, Lalita] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [Larson, Ryan P.; Urdahl, Kevin B.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Hernandez, Rafael E.; Urdahl, Kevin B.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Ramakrishnan, Lalita] Univ Washington, Dept Med, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Center for Infectious Disease Research; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Ramakrishnan, L (corresponding author), Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
EM lalitar@uw.edu
FU National Science Foundation; American Lung Association; National Institutes of Health (NIH); NIH; American Cancer Society Postdoctoral Fellowship; NIH Bacterial Pathogenesis Training Grant; National Institute of Allergy and Infectious Diseases [R37AI054503, R01AI054503] Funding Source: NIH RePORTER
NR 39
TC 376
Z9 470
U1 0
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 JAN 9
PY 2014
VL 505
IS 7482
BP 218
EP +
DI 10.1038/nature12799
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500039
PM 24336213
DA 2026-03-09
ER

PT J
AU Handa, IT
   Aerts, R
   Berendse, F
   Berg, MP
   Bruder, A
   Butenschoen, O
   Chauvet, E
   Gessner, MO
   Jabiol, J
   Makkonen, M
   McKie, BG
   Malmqvist, B
   Peeters, ETHM
   Scheu, S
   Schmid, B
   van Ruijven, J
   Vos, VCA
   Hättenschwiler, S
AF Handa, I. Tanya
   Aerts, Rien
   Berendse, Frank
   Berg, Matty P.
   Bruder, Andreas
   Butenschoen, Olaf
   Chauvet, Eric
   Gessner, Mark O.
   Jabiol, Jeremy
   Makkonen, Marika
   McKie, Brendan G.
   Malmqvist, Bjoern
   Peeters, Edwin T. H. M.
   Scheu, Stefan
   Schmid, Bernhard
   van Ruijven, Jasper
   Vos, Veronique C. A.
   Haettenschwiler, Stephan
TI Consequences of biodiversity loss for litter decomposition across biomes
SO NATURE
LA English
DT Article
ID species functional diversity; leaf-litter; ecosystems; patterns; services; climate; traits
AB The decomposition of dead organic matter is a major determinant of carbon and nutrient cycling in ecosystems, and of carbon fluxes between the biosphere and the atmosphere(1-3). Decomposition is driven by a vast diversity of organisms that are structured in complex food webs(2,4). Identifying the mechanisms underlying the effects of biodiversity on decomposition is critical(4-6) given the rapid loss of species worldwide and the effects of this loss on human well-being(7-9). Yet despite comprehensive syntheses of studies on how biodiversity affects litter decomposition(4-6,10), key questions remain, including when, where and how biodiversity has a role and whether general patterns and mechanisms occur across ecosystems and different functional types of organism(4,9-12). Here, in field experiments across five terrestrial and aquatic locations, ranging from the subarctic to the tropics, we show that reducing the functional diversity of decomposer organisms and plant litter types slowed the cycling of litter carbon and nitrogen. Moreover, we found evidence of nitrogen transfer from the litter of nitrogen-fixing plants to that of rapidly decomposing plants, but not between other plant functional types, highlighting that specific interactions in litter mixtures control carbon and nitrogen cycling during decomposition. The emergence of this general mechanism and the coherence of patterns across contrasting terrestrial and aquatic ecosystems suggest that biodiversity loss has consistent consequences for litter decomposition and the cycling of major elements on broad spatial scales.
C1 [Handa, I. Tanya; Haettenschwiler, Stephan] CNRS, CEFE, F-34293 Montpellier, France.
   [Handa, I. Tanya] Univ Quebec, Dept Sci Biol, Montreal, PQ H3C 3P8, Canada.
   [Aerts, Rien; Berg, Matty P.; Makkonen, Marika] Vrije Univ Amsterdam, Dept Ecol Sci, NL-1081 HV Amsterdam, Netherlands.
   [Berendse, Frank; van Ruijven, Jasper; Vos, Veronique C. A.] Wageningen Univ, Nat Conservat & Plant Ecol Grp, NL-6708 PB Wageningen, Netherlands.
   [Bruder, Andreas; Gessner, Mark O.] Eawag Swiss Fed Inst Aquat Sci & Technol, Dept Aquat Ecol, CH-8600 Dubendorf, Switzerland.
   [Bruder, Andreas; Gessner, Mark O.] ETH, Inst Integrat Biol IBZ, CH-8092 Zurich, Switzerland.
   [Butenschoen, Olaf; Scheu, Stefan] Univ Gottingen, JF Blumenbach Inst Zool & Anthropol, D-37073 Gottingen, Germany.
   [Chauvet, Eric; Jabiol, Jeremy] Univ Toulouse, INP, UPS, EcoLab Lab Ecol Fonctionnelle & Environm, F-31062 Toulouse, France.
   [Chauvet, Eric; Jabiol, Jeremy] CNRS, EcoLab, F-31062 Toulouse, France.
   [Gessner, Mark O.] Leibniz Inst Freshwater Ecol & Inland Fisheries I, D-16775 Stechlin, Germany.
   [Gessner, Mark O.] TU Berlin, Berlin Inst Technol, Dept Ecol, D-10587 Berlin, Germany.
   [Makkonen, Marika] Finnish Environm Inst, Climate Change Programme, Helsinki 00251, Finland.
   [McKie, Brendan G.] Umea Univ, Dept Ecol & Environm Sci, S-90187 Umea, Sweden.
   [McKie, Brendan G.] Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, S-75007 Uppsala, Sweden.
   [Peeters, Edwin T. H. M.] Wageningen Univ, Aquat Ecol & Water Qual Management Grp, NL-6700 AA Wageningen, Netherlands.
   [Schmid, Bernhard] Univ Zurich, Inst Evolutionary Biol & Environm Studies, CH-8057 Zurich, Switzerland.
   [Schmid, Bernhard] Univ Zurich, Zurich Basel Plant Sci Ctr, CH-8057 Zurich, Switzerland.
C3 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 Quebec; University of Quebec Montreal; Vrije Universiteit Amsterdam; Wageningen University & Research; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Gottingen; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Institut National Polytechnique de Toulouse; Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Institut National Polytechnique de Toulouse; Centre National de la Recherche Scientifique (CNRS); Leibniz Association; Leibniz Institut fur Gewasserokologie und Binnenfischerei (IGB); Technical University of Berlin; Finnish Environment Institute; Umea University; Swedish University of Agricultural Sciences; Wageningen University & Research; University of Zurich; University of Zurich
RP Hättenschwiler, S (corresponding author), CNRS, CEFE, 1919 Route Mende, F-34293 Montpellier, France.
EM stephan.hattenschwiler@cefe.cnrs.fr
FU European Science Foundation (ESF) as part of its EUROCORES programme EuroDIVERSITY
NR 35
TC 643
Z9 743
U1 25
U2 1332
PU NATURE PUBLISHING 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 8
PY 2014
VL 509
IS 7499
BP 218
EP +
DI 10.1038/nature13247
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG5JC
UT WOS:000335454300037
PM 24805346
DA 2026-03-09
ER

PT J
AU Forsberg, KJ
   Patel, S
   Gibson, MK
   Lauber, CL
   Knight, R
   Fierer, N
   Dantas, G
AF Forsberg, Kevin J.
   Patel, Sanket
   Gibson, Molly K.
   Lauber, Christian L.
   Knight, Rob
   Fierer, Noah
   Dantas, Gautam
TI Bacterial phylogeny structures soil resistomes across habitats
SO NATURE
LA English
DT Article
ID antibiotic-resistance genes; microbial community; protein; diversity; identification; mechanisms; ecology; unifrac; drives; tool
AB Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil(1-3), including genes identical to those in human pathogens(4). Despite the apparent overlap between soil and clinical resistomes(4-6), factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown(3). General metagenome functions often correlate with the underlying structure of bacterial communities(7-12). However, ARGs are proposed to be highly mobile(4,5,13), prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions(13,14). To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2,895 ARGs we discovered were mostly new, and represent all major resistance mechanisms(15). We demonstrate that distinct soil types harbour distinct resistomes, and that the addition of nitrogen fertilizer strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements (genes responsible for horizontal gene transfer between bacteria such as transposases and integrases) syntenic with ARGs were rare in soil by comparison with sequenced pathogens, suggesting that ARGs may not transfer between soil bacteria as readily as is observed between human pathogens. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny(13,14).
C1 [Forsberg, Kevin J.; Patel, Sanket; Gibson, Molly K.; Dantas, Gautam] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Patel, Sanket; Dantas, Gautam] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
   [Lauber, Christian L.; Fierer, Noah] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Knight, Rob] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
   [Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA.
   [Fierer, Noah] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
   [Dantas, Gautam] Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Howard Hughes Medical Institute; University of Colorado System; University of Colorado Boulder; Washington University (WUSTL)
RP Dantas, G (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
EM dantas@wustl.edu
FU Children's Discovery Institute [MD-II-2011-117]; International Center for Advanced Renewable Energy and Sustainability at Washington University; National Academies Keck Futures Initiatives [SB2]; NIH Director's New Innovator Award [DP2-DK-098089]; Mr and Mrs Spencer T. Olin Fellowship for Women in Graduate Study at Washington University; NIGMS [GM 007067]; NHGRI Genome Analysis Training Program [T32 HG000045];  [DGE-1143954]; Direct For Biological Sciences; Division Of Environmental Biology [0953331] Funding Source: National Science Foundation; National Human Genome Research Institute [T32HG000045] Funding Source: NIH RePORTER
NR 42
TC 1013
Z9 1161
U1 27
U2 1180
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2014
VL 509
IS 7502
BP 612
EP +
DI 10.1038/nature13377
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100047
PM 24847883
DA 2026-03-09
ER

PT J
AU Zovkic, IB
   Paulukaitis, BS
   Day, JJ
   Etikala, DM
   Sweatt, JD
AF Zovkic, Iva B.
   Paulukaitis, Brynna S.
   Day, Jeremy J.
   Etikala, Deepa M.
   Sweatt, J. David
TI Histone H2A.Z subunit exchange controls consolidation of recent and remote memory
SO NATURE
LA English
DT Article
ID dna methylation; regulates memory; gene-expression; transcription; acetylation; nucleosm; plasticity; pathway; brain
AB Memory formation is a multi-stage process that initially requires cellular consolidation in the hippocampus, after which memories are downloaded to the cortex for maintenance, in a process termed systems consolidation(1). Epigenetic mechanisms regulate both types of consolidation(2-7), but histone variant exchange, in which canonical histones are replaced with their variant counterparts, is an entire branch of epigenetics that has received limited attention in the brain(8-12) and has never, to our knowledge, been studied in relation to cognitive function. Here we show that histone H2A.Z, a variant of histone H2A, is actively exchanged in response to fear conditioning in the hippocampus and the cortex, where it mediates gene expression and restrains the formation of recent and remote memory. Our data provide evidence for H2A.Z involvement in cognitive function and specifically implicate H2A.Z as a negative regulator of hippocampal consolidation and systems consolidation, probably through downstream effects on gene expression. Moreover, alterations in H2A.Z binding at later stages of systems consolidation suggest that this histone has the capacity to mediate stable molecular modifications required for memory retention. Overall, our data introduce histone variant exchange as a novel mechanism contributing to the molecular basis of cognitive function and implicate H2A.Z as a potential therapeutic target for memory disorders.
C1 [Zovkic, Iva B.; Paulukaitis, Brynna S.; Day, Jeremy J.; Etikala, Deepa M.; Sweatt, J. David] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA.
   [Zovkic, Iva B.; Paulukaitis, Brynna S.; Day, Jeremy J.; Etikala, Deepa M.; Sweatt, J. David] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Birmingham, AL 35294 USA.
C3 University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham
RP Sweatt, JD (corresponding author), Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA.
EM dsweatt@uab.edu
FU DARPA [HR0011-12-1-0015]; NIH [MH091122, MH57014]; NSERC-PDF [PDF 387473-10]
NR 28
TC 142
Z9 180
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 NOV 27
PY 2014
VL 515
IS 7528
BP 582
EP +
DI 10.1038/nature13707
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW4JP
UT WOS:000346247600002
PM 25219850
DA 2026-03-09
ER

PT J
AU Forcada, J
   Hoffman, JI
AF Forcada, Jaume
   Hoffman, Joseph Ivan
TI Climate change selects for heterozygosity in a declining fur seal population
SO NATURE
LA English
DT Article
ID inbreeding depression; genetics; success; stress; size; long
AB Global environmental change is expected to alter selection pressures in many biological systems(1-3), but the long-term molecular and life history data required to quantify changes in selection are rare(4). An unusual opportunity is afforded by three decades of individual-based data collected from a declining population of Antarctic fur seals in the South Atlantic. Here, climate change has reduced prey availability and caused a significant decline in seal birth weight. However, the mean age and size of females recruiting into the breeding population are increasing. We show that such females have significantly higher heterozygosity (a measure of within-individual genetic variation) than their non-recruiting siblings and their own mothers. Thus, breeding female heterozygosity has increased by 8.5% per generation over the last two decades. Nonetheless, as heterozygosity is not inherited from mothers to daughters, substantial heterozygote advantage is not transmitted from one generation to the next and the decreasing viability of homozygous individuals causes the population to decline. Our results provide compelling evidence that selection due to climate change is intensifying, with far-reaching consequences for demography as well as phenotypic and genetic variation.
C1 [Forcada, Jaume] British Antarctic Survey, Nat Environm Res Council, Cambridge CB3 0ET, England.
   [Hoffman, Joseph Ivan] Univ Bielefeld, Dept Anim Behav, D-33501 Bielefeld, Germany.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of Bielefeld
RP Forcada, J (corresponding author), British Antarctic Survey, Nat Environm Res Council, Madingley Rd, Cambridge CB3 0ET, England.
EM jfor@bas.ac.uk
FU Marie Curie FP7-Reintegration-Grant within the 7th European Community Framework Programme [PCIG-GA-2011-303618]; Deutsche Forschungsgemeinschaft standard grant [HO 5122/3-1]
NR 26
TC 120
Z9 140
U1 0
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 24
PY 2014
VL 511
IS 7510
BP 462
EP +
DI 10.1038/nature13542
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL7SO
UT WOS:000339335700045
PM 25056064
DA 2026-03-09
ER

PT J
AU Wang, LH
   Yamaguchi, S
   Burstein, MD
   Terashima, K
   Chang, K
   Ng, HK
   Nakamura, H
   He, ZX
   Doddapaneni, H
   Lewis, L
   Wang, M
   Suzuki, T
   Nishikawa, R
   Natsume, A
   Terasaka, S
   Dauser, R
   Whitehead, W
   Adekunle, A
   Sun, JY
   Qiao, Y
   Marth, G
   Muzny, DM
   Gibbs, RA
   Leal, SM
   Wheeler, DA
   Lau, CC
AF Wang, Linghua
   Yamaguchi, Shigeru
   Burstein, Matthew D.
   Terashima, Keita
   Chang, Kyle
   Ng, Ho-Keung
   Nakamura, Hideo
   He, Zongxiao
   Doddapaneni, Harshavardhan
   Lewis, Lora
   Wang, Mark
   Suzuki, Tomonari
   Nishikawa, Ryo
   Natsume, Atsushi
   Terasaka, Shunsuke
   Dauser, Robert
   Whitehead, William
   Adekunle, Adesina
   Sun, Jiayi
   Qiao, Yi
   Marth, Gabor
   Muzny, Donna M.
   Gibbs, Richard A.
   Leal, Suzanne M.
   Wheeler, David A.
   Lau, Ching C.
TI Novel somatic and germline mutations in intracranial germ cell tumours
SO NATURE
LA English
DT Article
ID cancer-cells; lung-cancer; gene; resistance; common; jmjd1c; heterozygosity; corepressor; discovery; variants
AB Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries(1), with peak incidence near the time of puberty(2). About half of the tumours are located in the pineal region. The male to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region(3). Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.
C1 [Wang, Linghua; Chang, Kyle; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Muzny, Donna M.; Gibbs, Richard A.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Yamaguchi, Shigeru; Terashima, Keita; Lau, Ching C.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
   [Yamaguchi, Shigeru; Terashima, Keita; Lau, Ching C.] Baylor Coll Med, Texas Childrens Hematol Ctr, Houston, TX 77030 USA.
   [Burstein, Matthew D.] Baylor Coll Med, Struct & Computat Biol & Mol Biophys Program, Houston, TX 77030 USA.
   [Burstein, Matthew D.; Sun, Jiayi; Lau, Ching C.] Baylor Coll Med, Med Scientist Training Program, Houston, TX 77030 USA.
   [Terashima, Keita] Natl Ctr Child Hlth & Dev, Tokyo 1578535, Japan.
   [Ng, Ho-Keung] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China.
   [Nakamura, Hideo] Kumamoto Univ, Dept Neurosurg, Kumamoto 8600862, Japan.
   [He, Zongxiao; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA.
   [Suzuki, Tomonari; Nishikawa, Ryo] Saitama Med Univ, Dept Neurosurg, Saitama 3500495, Japan.
   [Natsume, Atsushi] Nagoya Univ, Dept Neurosurg, Nagoya, Aichi 4668550, Japan.
   [Terasaka, Shunsuke] Hokkaido Univ, Dept Neurosurg, Sapporo, Hokkaido 0600808, Japan.
   [Dauser, Robert; Whitehead, William] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA.
   [Adekunle, Adesina] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
   [Qiao, Yi; Marth, Gabor] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA.
   [Lau, Ching C.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Texas Children's Cancer Center; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; National Center for Child Health & Development - Japan; Prince of Wales Hospital Hong Kong; Chinese University of Hong Kong; Kumamoto University; Baylor College of Medicine; Saitama Medical University; Nagoya University; Hokkaido University; Baylor College of Medicine; Baylor College of Medicine; Boston College; Baylor College of Medicine
RP Wheeler, DA (corresponding author), Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
EM wheeler@bcm.edu; cclau@txch.org
FU National Human Genome Research Institute (NHGRI) [5U54HG003273]; Children Brain Tumor Foundation; Gillson Longenbaugh Foundation; Anderson Charitable Foundation; CCBTP Fellowship from the Cancer Prevention & Research Institute of Texas (CPRIT) [RP101489]; St Baldrick's Foundation; NLM predoctoral fellowships [5T15 LM07093-18, 5T15 LM07093-19]
NR 41
TC 159
Z9 178
U1 0
U2 39
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 10
PY 2014
VL 511
IS 7508
BP 241
EP +
DI 10.1038/nature13296
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800048
PM 24896186
DA 2026-03-09
ER

PT J
AU Kim, D
   Shi, Z
   Simmons, CB
   Ward, DR
   Prance, JR
   Koh, TS
   Gamble, JK
   Savage, DE
   Lagally, MG
   Friesen, M
   Coppersmith, SN
   Eriksson, MA
AF Kim, Dohun
   Shi, Zhan
   Simmons, C. B.
   Ward, D. R.
   Prance, J. R.
   Koh, Teck Seng
   Gamble, John King
   Savage, D. E.
   Lagally, M. G.
   Friesen, Mark
   Coppersmith, S. N.
   Eriksson, Mark A.
TI Quantum control and process tomography of a semiconductor quantum dot hybrid qubit
SO NATURE
LA English
DT Article
ID single-electron spin; oscillations; computation
AB The similarities between gated quantum dots and the transistors in modern microelectronics(1,2)-in fabrication methods, physical structure and voltage scales for manipulation-have led to great interest in the development of quantum bits (qubits) in semiconductor quantum dots(3-18). Although quantum dot spin qubits have demonstrated long coherence times, their manipulation is often slower than desired for important future applications, such as factoring(19). Furthermore, scalability and manufacturability are enhanced when qubits are as simple as possible. Previous work has increased the speed of spin qubit rotations by making use of integrated micromagnets(11), dynamic pumping of nuclear spins(12) or the addition of a third quantum dot(17). Here we demonstrate a qubit that is a hybrid of spin and charge. It is simple, requiring neither nuclear-state preparation nor micromagnets. Unlike previous double-dot qubits, the hybrid qubit enables fast rotations about two axes of the Bloch sphere. We demonstrate full control on the Bloch sphere with pi-rotation times of less than 100 picoseconds in two orthogonal directions, which is more than an order of magnitude faster than any other double-dot qubit. The speed arises from the qubit's charge-like characteristics, and its spin-like features result in resistance to decoherence over a wide range of gate voltages. We achieve full process tomography in our electrically controlled semiconductor quantum dot qubit, extracting high fidelities of 85 per cent for X rotations (transitions between qubit states) and 94 per cent for Z rotations (phase accumulation between qubit states).
C1 [Kim, Dohun; Shi, Zhan; Simmons, C. B.; Ward, D. R.; Prance, J. R.; Koh, Teck Seng; Friesen, Mark; Coppersmith, S. N.; Eriksson, Mark A.] Univ Wisconsin, Dept Phys, Madison, WI 53706 USA.
   [Gamble, John King] Sandia Natl Labs, Albuquerque, NM 87185 USA.
   [Savage, D. E.; Lagally, M. G.] Univ Wisconsin, Dept Mat Sci & Engn, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; United States Department of Energy (DOE); Sandia National Laboratories; University of Wisconsin System; University of Wisconsin Madison
RP Eriksson, MA (corresponding author), Univ Wisconsin, Dept Phys, 1150 Univ Ave, Madison, WI 53706 USA.
EM maeriksson@wisc.edu
FU ARO [W911NF-12-0607]; NSF [PHY-1104660]; Laboratory Directed Research and Development programme at Sandia National Laboratories; US Department of Energy's National Nuclear Security Administration [DE-AC04-94AL85000]; Division Of Physics; Direct For Mathematical & Physical Scien [1104660] Funding Source: National Science Foundation
NR 30
TC 250
Z9 293
U1 0
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 JUL 3
PY 2014
VL 511
IS 7507
BP 70
EP 74
DI 10.1038/nature13407
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK1TN
UT WOS:000338199400037
PM 24990747
DA 2026-03-09
ER

PT J
AU Dupret, V
   Sanchez, S
   Goujet, D
   Tafforeau, P
   Ahlberg, PE
AF Dupret, Vincent
   Sanchez, Sophie
   Goujet, Daniel
   Tafforeau, Paul
   Ahlberg, Per E.
TI A primitive placoderm sheds light on the origin of the jawed vertebrate face
SO NATURE
LA English
DT Article
ID developmental morphology; evolution; embryology; braincase; mesoderm; lamprey; shark; china; fish
AB Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures(1,2). These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and hypophysis originate from a single placode in cyclostomes but from separate placodes in gnathostomes, and infraoptic ectomesenchyme migrates forward either side of the single placode in cyclostomes but between the placodes in gnathostomes(3-8). Fossil stem gnathostomes preserve cranial anatomies rich in landmarks that provide proxies for developmental processes and allow the transition from jawless to jawed vertebrates to be broken down into evolutionary steps(7,9-12). Here we use propagation phase contrast synchrotron microtomography to image the cranial anatomy of the primitive placoderm (jawed stem gnathostome) Romundina(13), and show that itcombines jawed vertebrate architecture with cranial and cerebral proportions resembling those of cyclostomes and the galeaspid (jawless stem gnathostome) Shuyu(11). This combination seems to be primitive for jawed vertebrates, and suggests a decoupling between ectomesenchymal growth trajectory, ectomesenchymal proliferation, and cerebral shape change during the origin of gnathostomes.
C1 [Dupret, Vincent; Sanchez, Sophie; Ahlberg, Per E.] Uppsala Univ, Dept Organismal Biol, Subdept Evolut & Dev, SE-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Tafforeau, Paul] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
   [Goujet, Daniel] UPMC, MNHN, CNRS, UMR 7207,CR2P, F-75231 Paris 05, France.
C3 Uppsala University; European Synchrotron Radiation Facility (ESRF); Museum National d'Histoire Naturelle (MNHN); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Dupret, V (corresponding author), Uppsala Univ, Dept Organismal Biol, Subdept Evolut & Dev, Norbyvagen 18A, SE-75236 Uppsala, Sweden.
EM vincent.dupret@ebc.uu.se; per.ahlberg@ebc.uu.se
FU European Research Council [233111]; Wallenberg Scholarship from the Knut and Alice Wallenberg Foundation
NR 30
TC 110
Z9 127
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 MAR 27
PY 2014
VL 507
IS 7493
BP 500
EP +
DI 10.1038/nature12980
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000041
PM 24522530
DA 2026-03-09
ER

PT J
AU Karayannis, T
   Au, E
   Patel, JC
   Kruglikov, I
   Markx, S
   Delorme, R
   Héron, D
   Salomon, D
   Glessner, J
   Restituito, S
   Gordon, A
   Rodriguez-Murillo, L
   Roy, NC
   Gogos, JA
   Rudy, B
   Rice, ME
   Karayiorgou, M
   Hakonarson, H
   Keren, B
   Huguet, G
   Bourgeron, T
   Hoeffer, C
   Tsien, RW
   Peles, E
   Fishell, G
AF Karayannis, T.
   Au, E.
   Patel, J. C.
   Kruglikov, I.
   Markx, S.
   Delorme, R.
   Heron, D.
   Salomon, D.
   Glessner, J.
   Restituito, S.
   Gordon, A.
   Rodriguez-Murillo, L.
   Roy, N. C.
   Gogos, J. A.
   Rudy, B.
   Rice, M. E.
   Karayiorgou, M.
   Hakonarson, H.
   Keren, B.
   Huguet, G.
   Bourgeron, T.
   Hoeffer, C.
   Tsien, R. W.
   Peles, E.
   Fishell, G.
TI Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission
SO NATURE
LA English
DT Article
ID cortical interneurons; gaba(a) receptors; prepulse inhibition; tourettes-syndrome; schizophrenia; synapses; number; association; linkage; release
AB Although considerable evidence suggests that the chemical synapse is a lynchpin underlying affective disorders, how molecular insults differentially affect specific synaptic connections remains poorly understood. For instance, Neurexin 1a and 2 (NRXN1 and NRXN2) and CNTNAP2 (also known as CASPR2), all members of the neurexin superfamily of transmembrane molecules, have been implicated in neuropsychiatric disorders. However, their loss leads to deficits that have been best characterized with regard to their effect on excitatory cells(1,2). Notably, other disease-associated genes such as BDNF and ERBB4 implicate specific interneuron synapses in psychiatric disorders(3,4). Consistent with this, cortical interneuron dysfunction has been linked to epilepsy, schizophrenia and autism(5,6). Using a microarray screen that focused upon synapse-associated molecules, we identified Cntnap4 (contactin associated protein-like 4, also known as Caspr4) as highly enriched in developing murine interneurons. In this study we show that Cntnap4 is localized presynaptically and its loss leads to a reduction in the output of cortical parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid producing) basket cells. Paradoxically, the loss of Cntnap4 augments midbrain dopaminergic release in the nucleus accumbens. In Cntnap4 mutant mice, synaptic defects in these disease-relevant neuronal populations are mirrored by sensory-motor gating and grooming endophenotypes; these symptoms could be pharmacologically reversed, providing promise for therapeutic intervention in psychiatric disorders.
C1 [Karayannis, T.; Au, E.; Kruglikov, I.; Restituito, S.; Roy, N. C.; Rudy, B.; Hoeffer, C.; Tsien, R. W.; Fishell, G.] NYU, Dept Neurosci & Physiol, Neurosci Inst, New York, NY 10016 USA.
   [Patel, J. C.; Rice, M. E.] NYU, Dept Neurosurg Neurosci & Physiol, Langone Med Ctr, New York, NY 10016 USA.
   [Markx, S.; Rodriguez-Murillo, L.; Karayiorgou, M.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Delorme, R.; Hakonarson, H.; Huguet, G.; Bourgeron, T.] Inst Pasteur, Human Genet & Cognit Funct Unit, F-75724 Paris, France.
   [Delorme, R.; Huguet, G.; Bourgeron, T.] Inst Pasteur, URA Genes Synapses & Cognit 2182, CNRS, F-75724 Paris, France.
   [Delorme, R.] Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France.
   [Heron, D.] Grp Hosp Pitie Salpetriere, AP HP, Unite Fonct Genet Med, Dept Genet & Cytogenet,Ctr Reference,CRicm,UMR S9, F-75013 Paris, France.
   [Salomon, D.; Gordon, A.] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Glessner, J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Roy, N. C.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIH, Bethesda, MD 20892 USA.
   [Gogos, J. A.] Columbia Univ, Med Ctr, Dept Physiol, New York, NY 10032 USA.
   [Gogos, J. A.] Columbia Univ, Med Ctr, Dept Cellular Biophys & Neurosci, New York, NY 10032 USA.
   [Keren, B.] Grp Hosp Pitie Salpetriere, AP HP, Unite Fonct Genet Chromosom, Dept Genet & Cytogenet,CRicm,UMR S975, F-75013 Paris, France.
   [Huguet, G.; Bourgeron, T.] Univ Paris Diderot, Sorbonne Paris Cite, F-75005 Paris, France.
   [Bourgeron, T.] FondaMental Fdn, F-94000 Creteil, France.
C3 New York University; New York University; NYU Langone Medical Center; Columbia University; Universite Paris Cite; Pasteur Network; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Robert-Debre - APHP; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite; Weizmann Institute of Science; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD); Columbia University; Columbia University; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite; Universite Paris Cite
RP Fishell, G (corresponding author), NYU, Dept Neurosci & Physiol, Neurosci Inst, New York, NY 10016 USA.
EM gordon.fishell@med.nyu.edu
FU NIH [R01 NS081297, R01 MH071679, R01 NS074972, P01 NS074972, R01 NS036362, R01 DA033811, NS30989, NS50220]; Simons Foundation [94534]; Attilio and Olympia Ricciardi Research Fund; Israel Science Foundation; Patterson Trust; Roche; New York State through its NYSTEM initiative [C024326]; Canadian Institutes of Health Research; NYU COE Addiction Seed Grant; Institut Pasteur; INSERM; AP-HP; University Paris Diderot; Bettencourt-Schueller foundation; Orange foundation; FondaMental foundation; Conny-Maeva foundation; Cognacq-Jay foundation
NR 66
TC 142
Z9 169
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 JUL 10
PY 2014
VL 511
IS 7508
BP 236
EP +
DI 10.1038/nature13248
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AK8AP
UT WOS:000338649800047
PM 24870235
DA 2026-03-09
ER

PT J
AU Wang, F
   Chan, C
   Weir, NR
   Denic, V
AF Wang, Fei
   Chan, Charlene
   Weir, Nicholas R.
   Denic, Vladimir
TI The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase
SO NATURE
LA English
DT Article
ID er membrane; tail; mechanism; biogenesis
AB Hundreds of tail-anchored proteins, including soluble N-ethylmaleimide-sensitive factor attachment receptors (SNAREs) involved in vesicle fusion, are inserted post-translationally into the endoplasmic reticulum membrane by a dedicated protein-targeting pathway(1-4). Before insertion, the carboxy-terminal transmembrane domains of tail-anchored proteins are shielded in the cytosol by the conserved targeting factor Get3 (in yeast; TRC40 inmammals)(5-7). The Get3 endoplasmic-reticulum receptor comprises the cytosolic domains of the Get1/2 (WRB/CAML) transmembrane complex, which interact individually with the targeting factor to drive a conformational change that enables substrate release and, as a consequence, insertion(8-11). Because tail-anchored protein insertion is not associated with significant translocation of hydrophilic protein sequences across the membrane, it remains possible that Get1/2 cytosolic domains are sufficient to place Get3 in proximity with the endoplasmic-reticulum lipid bilayer and permit spontaneous insertion to occur(12,13). Here we use cell reporters and biochemical reconstitution to define mutations in the Get1/2 transmembrane domain that disrupt tail-anchored protein insertion without interfering with Get1/2 cytosolic domain function. These mutations reveal a novel Get1/2 insertase function, in the absence of which substrates stay bound to Get3 despite their proximity to the lipid bilayer; as a consequence, the notion of spontaneous transmembrane domain insertion is a non sequitur. Instead, the Get1/2 transmembrane domain helps to release substrates from Get3 by capturing their transmembrane domains, and these transmembrane interactions define a bona fide pre-integrated intermediate along a facilitated route for tail-anchor entry into the lipid bilayer. Our work sheds light on the fundamental point of convergence between co-translational and post-translational endoplasmic-reticulum membrane protein targeting and insertion: a mechanism for reducing the ability of a targeting factor to shield its substrates enables substrate handover to a transmembrane-domain-docking site embedded in the endoplasmic-reticulum membrane.
C1 [Wang, Fei; Chan, Charlene; Weir, Nicholas R.; Denic, Vladimir] Harvard Univ, Dept Mol & Cellular Biol, Northwest Labs, Cambridge, MA 02138 USA.
C3 Harvard University
RP Denic, V (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Northwest Labs, Cambridge, MA 02138 USA.
EM vdenic@mcb.harvard.edu
FU National Institutes of Health [RO1GM0999943-01]; Sara Elizabeth O'Brien Trust Postdoctoral Fellowship Program, Bank of America
NR 24
TC 104
Z9 129
U1 2
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 28
PY 2014
VL 512
IS 7515
BP 441
EP U486
DI 10.1038/nature13471
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AN8GC
UT WOS:000340840600036
PM 25043001
DA 2026-03-09
ER

PT J
AU Ekert, A
   Renner, R
AF Ekert, Artur
   Renner, Renato
TI The ultimate physical limits of privacy
SO NATURE
LA English
DT Article
ID quantum key distribution; bell inequality; side information; cryptography; violation; security; amplification; systems; theorem; randomness
AB Among those who make a living from the science of secrecy, worry and paranoia are just signs of professionalism. Can we protect our secrets against those who wield superior technological powers? Can we trust those who provide us with tools for protection? Can we even trust ourselves, our own freedom of choice? Recent developments in quantum cryptography show that some of these questions can be addressed and discussed in precise and operational terms, suggesting that privacy is indeed possible under surprisingly weak assumptions.
C1 [Ekert, Artur] Univ Oxford, Math Inst, Oxford OX2 9GG, England.
   [Ekert, Artur] Natl Univ Singapore, Ctr Quantum Technol, Singapore 117543, Singapore.
   [Renner, Renato] Swiss Fed Inst Technol, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
C3 University of Oxford; National University of Singapore; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Ekert, A (corresponding author), Univ Oxford, Math Inst, Oxford OX2 9GG, England.
EM artur.ekert@quibit.org; renner@phys.ethz.ch
NR 68
TC 94
Z9 104
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 MAR 27
PY 2014
VL 507
IS 7493
BP 443
EP 447
DI 10.1038/nature13132
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000030
PM 24670761
DA 2026-03-09
ER

PT J
AU Stephenson, NL
   Das, AJ
   Condit, R
   Russo, SE
   Baker, PJ
   Beckman, NG
   Coomes, DA
   Lines, ER
   Morris, WK
   Rüger, N
   Alvarez, E
   Blundo, C
   Bunyavejchewin, S
   Chuyong, G
   Davies, SJ
   Duque, A
   Ewango, CN
   Flores, O
   Franklin, JF
   Grau, HR
   Hao, Z
   Harmon, ME
   Hubbell, SP
   Kenfack, D
   Lin, Y
   Makana, JR
   Malizia, A
   Malizia, LR
   Pabst, RJ
   Pongpattananurak, N
   Su, SH
   Sun, IF
   Tan, S
   Thomas, D
   van Mantgem, PJ
   Wang, X
   Wiser, SK
   Zavala, MA
AF Stephenson, N. L.
   Das, A. J.
   Condit, R.
   Russo, S. E.
   Baker, P. J.
   Beckman, N. G.
   Coomes, D. A.
   Lines, E. R.
   Morris, W. K.
   Rueger, N.
   Alvarez, E.
   Blundo, C.
   Bunyavejchewin, S.
   Chuyong, G.
   Davies, S. J.
   Duque, A.
   Ewango, C. N.
   Flores, O.
   Franklin, J. F.
   Grau, H. R.
   Hao, Z.
   Harmon, M. E.
   Hubbell, S. P.
   Kenfack, D.
   Lin, Y.
   Makana, J. -R.
   Malizia, A.
   Malizia, L. R.
   Pabst, R. J.
   Pongpattananurak, N.
   Su, S. -H.
   Sun, I-F.
   Tan, S.
   Thomas, D.
   van Mantgem, P. J.
   Wang, X.
   Wiser, S. K.
   Zavala, M. A.
TI Rate of tree carbon accumulation increases continuously with tree size
SO NATURE
LA English
DT Article
ID age-related decline; growth efficiency; biomass; stand; competition; limitation; allometry; capacity; gradient; rules
AB Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations(1). Our ability to understand and predict changes in the forest carbon cycle-particularly net primary productivity and carbon storage-increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands(2,3). Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree(4-7), in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level(8-10) and stand-level(10) productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to under-tand and model forest carbon dynamics, and have additional implications for theories of resource allocation(11) and plant senescence(12).
C1 [Stephenson, N. L.; Das, A. J.] US Geol Survey, Western Ecol Res Ctr, Three Rivers, CA 93271 USA.
   [Condit, R.; Rueger, N.; Hubbell, S. P.] Smithsonian Trop Res Inst, Balboa, Panama.
   [Russo, S. E.; Beckman, N. G.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
   [Baker, P. J.] Univ Melbourne, Dept Forest & Ecosyst Sci, Melbourne, Vic 3121, Australia.
   [Coomes, D. A.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
   [Lines, E. R.] UCL, Dept Geog, London WC1E 6BT, England.
   [Morris, W. K.] Univ Melbourne, Sch Bot, Melbourne, Vic 3010, Australia.
   [Rueger, N.] Univ Leipzig, spebot, D-04103 Leipzig, Germany.
   [Alvarez, E.] Jardin Bot Medellin, Medellin, Colombia.
   [Blundo, C.; Grau, H. R.; Malizia, A.] Univ Nacl Tucuman, Inst Ecol Reg, RA-4107 Yerba Buena, Tucuman, Argentina.
   [Bunyavejchewin, S.] Dept Natl Pk Wildlife & Plant Conservat, Res Off, Bangkok 10900, Thailand.
   [Chuyong, G.] Dept Bot & Plant Physiol, Buea, Southwest Provi, Cameroon.
   [Davies, S. J.; Kenfack, D.] Smithsonian Inst, Ctr Trop Forest Sci, Global Earth Observ, Washington, DC 20013 USA.
   [Duque, A.] Univ Nacl Colombia, Dept Ciencias Forestales, Medellin, Colombia.
   [Ewango, C. N.; Makana, J. -R.] Wildlife Conservat Soc, Kinshasa, DEM REP CONGO.
   [Flores, O.] Univ Reunion, CIRAD, Unite Mixte Rech Peuplements Vegetaux & Bioagrees, F-97410 St Pierre, France.
   [Franklin, J. F.] Univ Washington, Sch Environm & Forest Sci, Seattle, WA 98195 USA.
   [Hao, Z.; Wang, X.] Chinese Acad Sci, Inst Appl Ecol, State Key Lab Forest & Soil Ecol, Shenyang 110164, Peoples R China.
   [Harmon, M. E.; Pabst, R. J.] Oregon State Univ, Dept Forest Ecosyst & Soc, Corvallis, OR 97331 USA.
   [Hubbell, S. P.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Lin, Y.] Tunghai Univ, Dept Life Sci, Taichung 40704, Taiwan.
   [Malizia, A.] Univ Nacl Jujuy, Fac Ciencias Agr, RA-4600 San Salvador De Jujuy, Argentina.
   [Pongpattananurak, N.] Kasetsart Univ, Fac Forestry, Chatuchak Bangkok 10900, Thailand.
   [Su, S. -H.] Taiwan Forestry Res Inst, Taipei 10066, Taiwan.
   [Sun, I-F.] Natl Dong Hwa Univ, Dept Nat Resources & Environm Studies, Hualien 97401, Taiwan.
   [Tan, S.] Sarawak Forestry Dept, Kuching 93660, Sarawak, Malaysia.
   [Thomas, D.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
   [van Mantgem, P. J.] US Geol Survey, Western Ecol Res Ctr, Arcata, CA 95521 USA.
   [Wiser, S. K.] Landcare Res, Lincoln 7640, New Zealand.
   [Zavala, M. A.] Univ Alcala de Henares, Dept Life Sci, Forest Ecol & Restorat Grp, Madrid 28805, Spain.
C3 United States Department of the Interior; United States Geological Survey; Smithsonian Institution; Smithsonian Tropical Research Institute; University of Nebraska System; University of Nebraska Lincoln; University of Melbourne; University of Cambridge; University of London; University College London; University of Melbourne; Leipzig University; Universidad Nacional de Tucuman; Smithsonian Institution; Universidad Nacional de Colombia; CIRAD; University of La Reunion; University of Washington; University of Washington Seattle; Chinese Academy of Sciences; Shenyang Institute of Applied Ecology, CAS; Oregon State University; University of California System; University of California Los Angeles; Tunghai University; Kasetsart University; National Dong Hwa University; Jabatan Hutan Sarawak; Oregon State University; United States Department of the Interior; United States Geological Survey; Landcare Research - New Zealand; Universidad de Alcala
RP Stephenson, NL (corresponding author), US Geol Survey, Western Ecol Res Ctr, Three Rivers, CA 93271 USA.
EM nstephenson@usgs.gov
FU United States Geological Survey (USGS) John Wesley Powell Center for Analysis and Synthesis; USGS Ecosystems and Climate and Land Use Change mission areas; Smithsonian Institution Global Earth Observatory-Center for Tropical Forest Science (CTFS); University of Nebraska-Lincoln Program of Excellence in Population Biology Postdoctoral Fellowship; National Natural Science Foundation of China [31370444]; State Key Laboratory of Forest and Soil Ecology [LFSE2013-11]; USGS; CTFS; US National Science Foundation; Andrews LTER [NSF-LTER DEB-0823380]; US National Park Service; US Forest Service (USFS); USFS Forest Inventory and Analysis Program; John D. and Catherine T. MacArthur Foundation; Andrew W. Mellon Foundation; MAGRAMA; Council of Agriculture of Taiwan; National Science Council of Taiwan; National Natural Science Foundation of China; Knowledge Innovation Program of the Chinese Academy of Sciences; Landcare Research; National Vegetation Survey Database (NVS) of New Zealand; French Fund for the Global Environment; Fundacion ProYungas; Direct For Biological Sciences; Division Of Environmental Biology [0823380, 1354741] Funding Source: National Science Foundation
NR 50
TC 758
Z9 896
U1 24
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 MAR 6
PY 2014
VL 507
IS 7490
BP 90
EP +
DI 10.1038/nature12914
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400048
PM 24429523
DA 2026-03-09
ER

PT J
AU van Galen, P
   Kreso, A
   Mbong, N
   Kent, DG
   Fitzmaurice, T
   Chambers, JE
   Xie, S
   Laurenti, E
   Hermans, K
   Eppert, K
   Marciniak, SJ
   Goodall, JC
   Green, AR
   Wouters, BG
   Wienholds, E
   Dick, JE
AF van Galen, Peter
   Kreso, Antonija
   Mbong, Nathan
   Kent, David G.
   Fitzmaurice, Timothy
   Chambers, Joseph E.
   Xie, Stephanie
   Laurenti, Elisa
   Hermans, Karin
   Eppert, Kolja
   Marciniak, Stefan J.
   Goodall, Jane C.
   Green, Anthony R.
   Wouters, Bradly G.
   Wienholds, Erno
   Dick, John E.
TI The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress
SO NATURE
LA English
DT Article
ID er-stress; messenger-rna; identification; translation; dephosphorylation; reinitiation; inhibitor; hierarchy; death; ire1
AB The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage(1,2). Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis(3,4). Despite the importance of maintaining cell integrity throughout life, how the HSC pool achieves this and how individual HSCs respond to stress remain poorly understood. Many sources of stress cause misfolded protein accumulation in the endoplasmic reticulum (ER), and subsequent activation of the unfolded protein response (UPR) enables the cell to either resolve stress or initiate apoptosis(5,6). Here we show that human HSCs are predisposed to apoptosis through strong activation of the PERK branch of the UPR after ER stress, whereas closely related progenitors exhibit an adaptive response leading to their survival. Enhanced ER protein folding by overexpression of the cochaperone ERDJ4 (also called DNAJB9) increases HSC repopulation capacity in xenograft assays, linking the UPR to HSC function. Because the UPR is a focal point where different sources of stress converge, our study provides a framework for understanding how stress signalling is coordinated within tissue hierarchies and integrated with stemness. Broadly, these findings reveal that the HSC pool maintains clonal integrity by clearance of individual HSCs after stress to prevent propagation of damaged stem cells.
C1 [van Galen, Peter; Kreso, Antonija; Mbong, Nathan; Xie, Stephanie; Laurenti, Elisa; Hermans, Karin; Wienholds, Erno; Dick, John E.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
   [van Galen, Peter; Kreso, Antonija; Mbong, Nathan; Xie, Stephanie; Laurenti, Elisa; Hermans, Karin; Wienholds, Erno; Dick, John E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Kent, David G.; Chambers, Joseph E.; Marciniak, Stefan J.; Green, Anthony R.] Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust, MRC Stem Cell Inst, Cambridge CB2 0XY, England.
   [Kent, David G.; Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England.
   [Fitzmaurice, Timothy; Goodall, Jane C.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Sch Clin Med, Cambridge CB2 0QQ, England.
   [Eppert, Kolja] McGill Univ, Dept Pediat, Westmount, PQ H3Z 2Z3, Canada.
   [Eppert, Kolja] McGill Univ, Ctr Hlth, Res Inst, Westmount, PQ H3Z 2Z3, Canada.
   [Wouters, Bradly G.] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada.
   [Wouters, Bradly G.] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
C3 University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University of Cambridge; Wellcome Trust; Wellcome Trust Sanger Institute; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; McGill University; McGill University; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre
RP Dick, JE (corresponding author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
EM jdick@uhnresearch.ca
FU Canadian Institutes for Health Research; Canadian Cancer Society; Terry Fox Foundation; Genome Canada through the Ontario Genomics Institute; Ontario Institute for Cancer Research; province of Ontario; Canada Research Chair; Ontario Ministry of Health and Long Term Care (OMOHLTC); Leukemia and Lymphoma Research; Cancer Research UK; Kay Kendall Leukaemia Fund; NIHR Cambridge Biomedical Research Centre; Cambridge Experimental Cancer Medicine Centre; Leukemia & Lymphoma Society of America; Arthritis Research UK; Medical Research Council (UK); Terry Fox New Frontiers Research Program [PPG09-020005]; Canadian Institute for Health Research (CIHR) [201592]; MRC [G0601840, G1001765, G1002610] Funding Source: UKRI; Medical Research Council [G0601840, G1001765, G1002610] Funding Source: researchfish; Versus Arthritis [19639] Funding Source: researchfish
NR 39
TC 288
Z9 328
U1 0
U2 68
PU NATURE PUBLISHING 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 12
PY 2014
VL 510
IS 7504
BP 268
EP +
DI 10.1038/nature13228
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400050
PM 24776803
DA 2026-03-09
ER

PT J
AU Fan, J
   Ye, JB
   Kamphorst, JJ
   Shlomi, T
   Thompson, CB
   Rabinowitz, JD
AF Fan, Jing
   Ye, Jiangbin
   Kamphorst, Jurre J.
   Shlomi, Tomer
   Thompson, Craig B.
   Rabinowitz, Joshua D.
TI Quantitative flux analysis reveals folate-dependent NADPH production
SO NATURE
LA English
DT Article
ID pyruvate-kinase m2; methenyltetrahydrofolate cyclohydrolase; metabolomic analysis; serine synthesis; cancer; dehydrogenase; glycine; contributes; inhibition; mechanism
AB ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis(1). The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important(2,3). Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP(+) to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP(+) and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.
C1 [Fan, Jing; Kamphorst, Jurre J.; Shlomi, Tomer; Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08540 USA.
   [Ye, Jiangbin; Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Shlomi, Tomer] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
C3 Princeton University; Memorial Sloan Kettering Cancer Center; Technion Israel Institute of Technology
RP Rabinowitz, JD (corresponding author), Princeton Univ, Dept Chem, Princeton, NJ 08540 USA.
EM joshr@genomics.princeton.edu
FU Stand Up To Cancer; NIH [CA163591, AI097382, CA105463, CA104838, GM071508]; Hope [HFCR-11-03-01]; National Cancer Institute [P30CA072720, R01CA163591] Funding Source: NIH RePORTER
NR 40
TC 916
Z9 1068
U1 6
U2 375
PU NATURE PUBLISHING 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 12
PY 2014
VL 510
IS 7504
BP 298
EP +
DI 10.1038/nature13236
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AI7AT
UT WOS:000337032400056
PM 24805240
DA 2026-03-09
ER

PT J
AU Mlynarski, SN
   Schuster, CH
   Morken, JP
AF Mlynarski, Scott N.
   Schuster, Christopher H.
   Morken, James P.
TI Asymmetric synthesis from terminal alkenes by cascades of diboration and cross-coupling
SO NATURE
LA English
DT Article
ID palladium; alkyl; esters; alkylboranes; catalysts; amination; halides
AB Terminal, monosubstituted alkenes are ideal prospective starting materials for organic synthesis because they are manufactured on very large scales and can be functionalized via a broad range of chemical transformations. Alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic alpha-olefins into chiral products with an enantiomeric excess greater then 90 per cent. With the exception of site-controlled isotactic polymerization of alpha-olefins(1), none of these catalytic enantioselective processes results in chain-extending carbon-carbon bond formation to the terminal carbon(2-6). Here we describe a strategy that directly addresses this gap in synthetic methodology, and present a single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products. These reactions are facilitated by a neighbouring functional group that accelerates palladium-catalysed cross-coupling of 1,2-bis(boronates) relative to non-functionalized alkyl boronate analogues. In tandem with enantioselective diboration, this reactivity feature transforms alkene starting materials into a diverse array of chiral products. We note that the tandem diboration/cross-coupling reaction generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), uses low loadings (1-2 mol per cent) of commercially available catalysts and reagents, offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology.
C1 [Mlynarski, Scott N.; Schuster, Christopher H.; Morken, James P.] Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
C3 Boston College
RP Morken, JP (corresponding author), Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
EM morken@bc.edu
FU US National Institutes of Health, Institute of General Medical Sciences [GM-59417]; John LaMattina graduate fellowships
NR 30
TC 226
Z9 262
U1 1
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 JAN 16
PY 2014
VL 505
IS 7483
BP 386
EP 390
DI 10.1038/nature12781
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800039
PM 24352229
DA 2026-03-09
ER

PT J
AU Beck, JR
   Muralidharan, V
   Oksman, A
   Goldberg, DE
AF Beck, Josh R.
   Muralidharan, Vasant
   Oksman, Anna
   Goldberg, Daniel E.
TI PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes
SO NATURE
LA English
DT Article
ID plasmodium-falciparum protein; plasmepsin v; food vacuole; virulence; biosynthesis; localization; translocon; parasites; membrane; cells
AB To mediate its survival and virulence, the malaria parasite Plasmodium falciparum exports hundreds of proteins into the host erythrocyte(1). To enter the host cell, exported proteins must cross the parasitophorous vacuolar membrane (PVM) within which the parasite resides, but the mechanism remains unclear. A putative Plasmodium translocon of exported proteins (PTEX) has been suggested to be involved for at least one class of exported proteins; however, direct functional evidence for this has been elusive(2-4). Here we show that export across the PVM requires heat shock protein 101 (HSP101), a ClpB-likeAAA+ ATPase component of PTEX. Using a chaperone auto-inhibition strategy, we achieved rapid, reversible ablation of HSP101 function, resulting in a nearly complete block in export with substrates accumulating in the vacuole in both asexual and sexual parasites. Surprisingly, this block extended to all classes of exported proteins, revealing HSP101-dependent translocation across the PVM as a convergent step in the multi-pathway export process. Under export-blocked conditions, association between HSP101 and other components of the PTEX complex was lost, indicating that the integrity of the complex is required for efficient protein export. Our results demonstrate an essential and universal role for HSP101 in protein export and provide strong evidence for PTEX function in protein translocation into the host cell.
C1 [Beck, Josh R.; Oksman, Anna; Goldberg, Daniel E.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Muralidharan, Vasant; Oksman, Anna; Goldberg, Daniel E.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Muralidharan, Vasant; Oksman, Anna; Goldberg, Daniel E.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Howard Hughes Medical Institute
RP Goldberg, DE (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
EM dgoldberg@wustl.edu
FU National Institutes of Health [AI047798, T32-AI007172, AI099156]; National Institute of Allergy and Infectious Diseases [T32AI007172] Funding Source: NIH RePORTER
NR 40
TC 196
Z9 234
U1 0
U2 32
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 30
PY 2014
VL 511
IS 7511
BP 592
EP +
DI 10.1038/nature13574
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AM0VT
UT WOS:000339566300035
PM 25043010
DA 2026-03-09
ER

PT J
AU Scafidi, J
   Hammond, TR
   Scafidi, S
   Ritter, J
   Jablonska, B
   Roncal, M
   Szigeti-Buck, K
   Coman, D
   Huang, YG
   McCarter, RJ
   Hyder, F
   Horvath, TL
   Gallo, V
AF Scafidi, Joseph
   Hammond, Timothy R.
   Scafidi, Susanna
   Ritter, Jonathan
   Jablonska, Beata
   Roncal, Maria
   Szigeti-Buck, Klara
   Coman, Daniel
   Huang, Yuegao
   McCarter, Robert J., Jr.
   Hyder, Fahmeed
   Horvath, Tamas L.
   Gallo, Vittorio
TI Intranasal epidermal growth factor treatment rescues neonatal brain injury
SO NATURE
LA English
DT Article
ID white-matter abnormality; central-nervous-system; oligodendrocyte progenitors; mouse model; factor-i; cells; egfr; myelination; delivery; preterm
AB There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments(1,2). As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI3. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development(4). Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.
C1 [Scafidi, Joseph; Hammond, Timothy R.; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Gallo, Vittorio] Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA.
   [Scafidi, Joseph] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
   [Hammond, Timothy R.] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA.
   [Scafidi, Susanna] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA.
   [Szigeti-Buck, Klara] Yale Univ, Dept Neurobiol, New Haven, CT 06520 USA.
   [Coman, Daniel; Huang, Yuegao; Hyder, Fahmeed] Yale Univ, Dept Diagnost Radiol, MRRC, New Haven, CT 06520 USA.
   [McCarter, Robert J., Jr.] Childrens Natl Med Ctr, Ctr Translat Sci, Washington, DC 20010 USA.
C3 Children's National Health System; Children's National Health System; George Washington University; Johns Hopkins University; Yale University; Yale University; Children's National Health System
RP Gallo, V (corresponding author), Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA.
EM vgallo@childrensnational.org
FU National Institutes of Health [K08NS073793, NSADA K12NS052159, K08NS069815, P01 NS062686, R01NS045702, R01NS056427, P30HD040677, R01MH067528, P30 NS05219, DP1 OD006850]; Childhood Brain Tumor Foundation; National Brain Tumor Society; National Institute of Mental Health [R01MH067528] Funding Source: NIH RePORTER
NR 48
TC 199
Z9 230
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 13
PY 2014
VL 506
IS 7487
BP 230
EP +
DI 10.1038/nature12880
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA5AK
UT WOS:000331107700040
PM 24390343
DA 2026-03-09
ER

PT J
AU de Loubresse, NG
   Prokhorova, I
   Holtkamp, W
   Rodnina, MV
   Yusupova, G
   Yusupov, M
AF de Loubresse, Nicolas Garreau
   Prokhorova, Irina
   Holtkamp, Wolf
   Rodnina, Marina V.
   Yusupova, Gulnara
   Yusupov, Marat
TI Structural basis for the inhibition of the eukaryotic ribosome
SO NATURE
LA English
DT Article
ID protein-synthesis; aminoglycoside antibiotics; saccharomyces-cerevisiae; transfer-rna; cryptopleurine resistance; translation initiation; crystal-structure; blasticidin s; yeast; cells
AB The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development.
C1 [de Loubresse, Nicolas Garreau; Prokhorova, Irina; Yusupova, Gulnara; Yusupov, Marat] Univ Strasbourg, CNRS, IGBMC, INSERM,U964,UMR7104, F-67404 Illkirch Graffenstaden, France.
   [Holtkamp, Wolf; Rodnina, Marina V.] Max Planck Inst Biophys Chem, Dept Phys Biochem, D-37077 Gottingen, Germany.
C3 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); Max Planck Society
RP Yusupov, M (corresponding author), Univ Strasbourg, CNRS, IGBMC, INSERM,U964,UMR7104, F-67404 Illkirch Graffenstaden, France.
EM marat@igbmc.fr
FU AFM-Telethon; SATT Conectus Technology Maturation [I12-042]; ERC [294312]; Human Frontier Science Program [RGP0062/2012]; Russian Government Program of Competitive Growth of Kazan Federal University; French National Research Agency [ANR-11-BSV8-006 01]; Deutsche Forschungsgemeinschaft; European Research Council (ERC) [294312] Funding Source: European Research Council (ERC)
NR 76
TC 427
Z9 510
U1 4
U2 142
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 517
EP +
DI 10.1038/nature13737
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800033
PM 25209664
DA 2026-03-09
ER

PT J
AU Guo, YY
   Dong, LY
   Qiu, XL
   Wang, YS
   Zhang, BL
   Liu, HN
   Yu, Y
   Zang, Y
   Yang, MJ
   Huang, ZW
AF Guo, Yingying
   Dong, Liyong
   Qiu, Xiaolin
   Wang, Yishu
   Zhang, Bailing
   Liu, Hongnan
   Yu, You
   Zang, Yi
   Yang, Maojun
   Huang, Zhiwei
TI Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif
SO NATURE
LA English
DT Article
ID ubiquitin ligase; socs box; enzyme apobec3g; protein; dna; degradation; hypermutation; infection; software; motif
AB The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors(1-6); however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif-CBF-beta-CUL5-ELOB-ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-beta, CUL5 and ELOC. The larger domain (alpha/beta domain) of Vif binds to the same side of CBF-beta as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-beta binding. Interactions of the smaller domain (alpha-domain) of Vif with ELOCand CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the alpha-domain, which may be important for Vif-CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-beta and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.
C1 [Guo, Yingying; Dong, Liyong; Qiu, Xiaolin; Wang, Yishu; Zhang, Bailing; Liu, Hongnan; Zang, Yi; Huang, Zhiwei] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150080, Peoples R China.
   [Yu, You; Yang, Maojun] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, MOE 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 [31300605, 31030020, 31170679]; Program for New Century Excellent Talents in University [AUGA5710060713]; Ministry of Science and Technology of China [2012CB911101, 2011CB910502]
NR 36
TC 177
Z9 221
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 JAN 9
PY 2014
VL 505
IS 7482
BP 229
EP +
DI 10.1038/nature12884
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 286CG
UT WOS:000329441500041
PM 24402281
DA 2026-03-09
ER

PT J
AU Kiefer, F
   des Etangs, AL
   Boissier, J
   Vidal-Madjar, A
   Beust, H
   Lagrange, AM
   Hébrard, G
   Ferlet, R
AF Kiefer, F.
   des Etangs, A. Lecavelier
   Boissier, J.
   Vidal-Madjar, A.
   Beust, H.
   Lagrange, A-M.
   Hebrard, G.
   Ferlet, R.
TI Two families of exocomets in the β Pictoris system
SO NATURE
LA English
DT Article
ID infalling evaporating body; young planetary system; circumstellar disk; ca-ii; hst-ghrs; comets; model
AB The young planetary system surrounding the star beta Pictoris harbours active minor bodies(1-6). These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System(7). Spectroscopic observations of beta Pictoris reveal a high rate of transits of small evaporating bodies(8-11), that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the beta Pictoris system are analogous to the comets in our own Solar System.
C1 [Kiefer, F.; des Etangs, A. Lecavelier; Vidal-Madjar, A.; Hebrard, G.; Ferlet, R.] CNRS, Inst Astrophys Paris, UMR 7095, F-75014 Paris, France.
   [Kiefer, F.; des Etangs, A. Lecavelier; Vidal-Madjar, A.; Hebrard, G.; Ferlet, R.] Univ Paris 06, Inst Astrophys Paris, UMR 7095, F-75014 Paris, France.
   [Kiefer, F.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Boissier, J.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Beust, H.; Lagrange, A-M.] Univ Grenoble 1, CNRS, Inst Natl Sci Univers, Inst Planetol & Astrophys Grenoble,UMR 5274, F-38400 St Martin Dheres, France.
C3 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; Tel Aviv University; 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)
RP Kiefer, F (corresponding author), CNRS, Inst Astrophys Paris, UMR 7095, 98 Bis Blvd Arago, F-75014 Paris, France.
EM kiefer@iap.fr; lecaveli@iap.fr
FU Fondation Simone et Cino Del Duca; French Agence Nationale de la Recherche (ANR) [ANR-12-13505-0012 Exo-Atmos, ANR-2010 BLAN-0505-01]
NR 25
TC 114
Z9 119
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 OCT 23
PY 2014
VL 514
IS 7523
BP 462
EP +
DI 10.1038/nature13849
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AR7RC
UT WOS:000343775900033
PM 25341784
DA 2026-03-09
ER

PT J
AU Smith, BT
   McCormack, JE
   Cuervo, AM
   Hickerson, MJ
   Aleixo, A
   Cadena, CD
   Pérez-Emán, J
   Burney, CW
   Xie, XO
   Harvey, MG
   Faircloth, BC
   Glenn, TC
   Derryberry, EP
   Prejean, J
   Fields, S
   Brumfield, RT
AF Smith, Brian Tilston
   McCormack, John E.
   Cuervo, Andres M.
   Hickerson, Michael. J.
   Aleixo, Alexandre
   Cadena, Carlos Daniel
   Perez-Eman, Jorge
   Burney, Curtis W.
   Xie, Xiaoou
   Harvey, Michael G.
   Faircloth, Brant C.
   Glenn, Travis C.
   Derryberry, Elizabeth P.
   Prejean, Jesse
   Fields, Samantha
   Brumfield, Robb T.
TI The drivers of tropical speciation
SO NATURE
LA English
DT Article
ID extinction rates; climate-change; amazonia; patterns; birds; diversification; seasonality; abundance; evolution; island
AB Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance(1). In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation(2-5). An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape(6,7). Landscape change is not a necessity for speciation in this model(8). Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests.
C1 [Smith, Brian Tilston; McCormack, John E.; Cuervo, Andres M.; Burney, Curtis W.; Harvey, Michael G.; Derryberry, Elizabeth P.; Prejean, Jesse; Fields, Samantha; Brumfield, Robb T.] Louisiana State Univ, Museum Nat Sci, Baton Rouge, LA 70803 USA.
   [Smith, Brian Tilston] Amer Museum Nat Hist, Dept Ornithol, New York, NY 10024 USA.
   [Cuervo, Andres M.; Burney, Curtis W.; Harvey, Michael G.; Prejean, Jesse; Fields, Samantha; Brumfield, Robb T.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Hickerson, Michael. J.; Xie, Xiaoou] CUNY City Coll, Dept Biol, New York, NY 10031 USA.
   [Hickerson, Michael. J.] Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA.
   [Aleixo, Alexandre] Museu Paraense Emilio Goeldi, BR-66040170 Belem, Para, Brazil.
   [Cadena, Carlos Daniel] Univ Los Andes, Dept Ciencias Biol, Lab Biol Evolut Vertebrados, Bogota, Colombia.
   [Perez-Eman, Jorge] Cent Univ Venezuela, Inst Zool & Ecol Trop, Caracas 1041A, Venezuela.
   [Perez-Eman, Jorge] Colecc Ornitol Phelps, Caracas 1010A, Venezuela.
   [Faircloth, Brant C.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Glenn, Travis C.] Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA.
C3 Louisiana State University System; Louisiana State University; American Museum of Natural History (AMNH); Louisiana State University System; Louisiana State University; City University of New York (CUNY) System; City College of New York (CUNY); American Museum of Natural History (AMNH); Museu Paraense Emilio Goeldi; Universidad de los Andes (Colombia); University of Central Venezuela; University of California System; University of California Los Angeles; University System of Georgia; University of Georgia
RP Brumfield, RT (corresponding author), Louisiana State Univ, Museum Nat Sci, Baton Rouge, LA 70803 USA.
EM robb@lsu.edu
FU NSF [DEB-0841729, DEB 1253710, DEB 1343578]; CUNY HPCC [CNS-0855217]; Coypu Foundation; Brazilian Research Council (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [574008-2008-0, 490131/2009-3, 310593/2009-3, 574008/2008-0, 563236/2010-8, 471342/ 2011-4]; FAPESPA [ICAAF 023/2011]; CDCH; INPMA; Direct For Biological Sciences; Division Of Environmental Biology [0841729] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1343578] Funding Source: National Science Foundation
NR 30
TC 478
Z9 553
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 NOV 20
PY 2014
VL 515
IS 7527
BP 406
EP +
DI 10.1038/nature13687
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600044
PM 25209666
DA 2026-03-09
ER

PT J
AU Engels, S
   Schneider, NL
   Lefeldt, N
   Hein, CM
   Zapka, M
   Michalik, A
   Elbers, D
   Kittel, A
   Hore, PJ
   Mouritsen, H
AF Engels, Svenja
   Schneider, Nils-Lasse
   Lefeldt, Nele
   Hein, Christine Maira
   Zapka, Manuela
   Michalik, Andreas
   Elbers, Dana
   Kittel, Achim
   Hore, P. J.
   Mouritsen, Henrik
TI Anthropogenic electromagnetic noise disrupts magnetic compass orientation in a migratory bird
SO NATURE
LA English
DT Article
ID magnetoreception; mechanism; model; cues
AB Electromagnetic noise is emitted everywhere humans use electronic devices. For decades, it has been hotly debated whether man-made electric and magnetic fields affect biological processes, including human health(1-5). So far, no putative effect of anthropogenic electromagnetic noise at intensities below the guidelines adopted by the World Health Organization(1,2) has withstood the test of independent replication under truly blinded experimental conditions. No effect has therefore been widely accepted as scientifically proven(1-6). Here we show that migratory birds are unable to use their magnetic compass in the presence of urban electromagnetic noise. When European robins, Erithacus rubecula, were exposed to the background electromagnetic noise present in unscreened wooden huts at the University of Oldenburg campus, they could not orient using their magnetic compass. Their magnetic orientation capabilities reappeared inelectrically grounded, aluminium-screened huts, which attenuated electromagnetic noise in the frequency range from 50 kHz to 5 MHz by approximately two orders of magnitude. When the grounding was removed or when broadband electromagnetic noise was deliberately generated inside the screened and grounded huts, the birds again lost their magnetic orientation capabilities. The disruptive effect of radiofrequency electromagnetic fields is not confined to a narrow frequency band and birds tested far from sources of electromagnetic noise required no screening to orient with their magnetic compass. These fully double-blinded tests document a reproducible effect of anthropogenic electromagnetic noise on the behaviour of an intact vertebrate.
C1 [Engels, Svenja; Schneider, Nils-Lasse; Lefeldt, Nele; Hein, Christine Maira; Zapka, Manuela; Michalik, Andreas; Elbers, Dana; Mouritsen, Henrik] Carl von Ossietzky Univ Oldenburg, Inst Biol & Umweltwissensch, D-26111 Oldenburg, Germany.
   [Engels, Svenja; Schneider, Nils-Lasse; Lefeldt, Nele; Hein, Christine Maira; Zapka, Manuela; Michalik, Andreas; Elbers, Dana; Mouritsen, Henrik] Carl von Ossietzky Univ Oldenburg, Res Ctr Neurosensory Sci, D-26111 Oldenburg, Germany.
   [Kittel, Achim] Carl von Ossietzky Univ Oldenburg, Inst Phys, D-26111 Oldenburg, Germany.
   [Hore, P. J.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
C3 Carl von Ossietzky Universitat Oldenburg; Carl von Ossietzky Universitat Oldenburg; Carl von Ossietzky Universitat Oldenburg; University of Oxford
RP Mouritsen, H (corresponding author), Carl von Ossietzky Univ Oldenburg, Inst Biol & Umweltwissensch, D-26111 Oldenburg, Germany.
EM henrik.mouritsen@uni-oldenburg.de
FU Defense Advanced Research Projects Agency [QuBE: N66001-10-1-4061]; VW-Stiftung; DFG [FOR 701, MO 1408/2-2]; Heinz Neumuller Stiftung; BMBF; European Research Council; EMF Biological Research Trust
NR 36
TC 305
Z9 338
U1 6
U2 332
PU NATURE PUBLISHING 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 15
PY 2014
VL 509
IS 7500
BP 353
EP +
DI 10.1038/nature13290
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH4TM
UT WOS:000336121200037
PM 24805233
DA 2026-03-09
ER

PT J
AU Aubert, M
   Brumm, A
   Ramli, M
   Sutikna, T
   Saptomo, EW
   Hakim, B
   Morwood, MJ
   van den Bergh, GD
   Kinsley, L
   Dosseto, A
AF Aubert, M.
   Brumm, A.
   Ramli, M.
   Sutikna, T.
   Saptomo, E. W.
   Hakim, B.
   Morwood, M. J.
   van den Bergh, G. D.
   Kinsley, L.
   Dosseto, A.
TI Pleistocene cave art from Sulawesi, Indonesia
SO NATURE
LA English
DT Article
ID rock art; human colonization; australia; series; corals; record
AB Archaeologists have long been puzzled by the appearance in Europe similar to 40-35 thousand years (kyr) ago of a rich corpus of sophisticated art-works, including parietal art (that is, paintings, drawings and engravings on immobile rock surfaces)(1,2) and portable art (for example, carved figurines)(3,4), and the absence or scarcity of equivalent, well-dated evidence elsewhere, especially along early human migration routes in South Asia and the Far East, including Wallacea and Australia(5-8), where modern humans (Homo sapiens) were established by 50 kyr ago(9,10). Here, using uranium-series dating of coralloid speleothems directly associated with 12 human hand stencils and two figurative animal depictions from seven cave sites in the Maros karsts of Sulawesi, we show that rock art traditions on this Indonesian island are at least compatible in age with the oldest European art(11). The earliest dated image from Maros, with a minimum age of 39.9 kyr, is now the oldest known hand stencil in the world. In addition, a painting of a babirusa ('pig-deer') made at least 35.4 kyr ago is among the earliest dated figurative depictions worldwide, if not the earliest one. Among the implications, it can now be demonstrated that humans were producing rock art by similar to 40 kyr ago at opposite ends of the Pleistocene Eurasian world.
C1 [Aubert, M.; Brumm, A.; Sutikna, T.; van den Bergh, G. D.] Univ Wollongong, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [Aubert, M.] Griffith Univ, PERAHU, Gold Coast, Qld 4222, Australia.
   [Ramli, M.] Balai Pelestarian Peninggalan Purbakala, Makassar 90111, Indonesia.
   [Sutikna, T.; Saptomo, E. W.] Natl Ctr Archaeol ARKENAS, Jakarta 12001, Indonesia.
   [Hakim, B.] Balai Arkeol Makassar, Makassar 90242, Indonesia.
   [Kinsley, L.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Dosseto, A.] Univ Wollongong, Wollongong Isotope Geochronol Lab, Wollongong, NSW 2522, Australia.
   [Dosseto, A.] Univ Wollongong, GeoQuEST Res Ctr, Wollongong, NSW 2522, Australia.
C3 University of Wollongong; Griffith University; Australian National University; University of Wollongong; University of Wollongong
RP Aubert, M (corresponding author), Univ Wollongong, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
EM m.aubert@griffith.edu.au
FU University of Wollongong; Australian Research Council [DP110102898/DE140100254, DP0879624/DE130101560]; Centre for Archaeological Science (CAS), University of Wollongong
NR 35
TC 367
Z9 428
U1 1
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 OCT 9
PY 2014
VL 514
IS 7521
BP 223
EP +
DI 10.1038/nature13422
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ3BG
UT WOS:000342663100041
PM 25297435
DA 2026-03-09
ER

PT J
AU Roy, MG
   Livraghi-Butrico, A
   Fletcher, AA
   McElwee, MM
   Evans, SE
   Boerner, RM
   Alexander, SN
   Bellinghausen, LK
   Song, AS
   Petrova, YM
   Tuvim, MJ
   Adachi, R
   Romo, I
   Bordt, AS
   Bowden, MG
   Sisson, JH
   Woodruff, PG
   Thornton, DJ
   Rousseau, K
   De la Garza, MM
   Moghaddam, SJ
   Karmouty-Quintana, H
   Blackburn, MR
   Drouin, SM
   Davis, CW
   Terrell, KA
   Grubb, BR
   O'Neal, WK
   Flores, SC
   Cota-Gomez, A
   Lozupone, CA
   Donnelly, JM
   Watson, AM
   Hennessy, CE
   Keith, RC
   Yang, IV
   Barthel, L
   Henson, PM
   Janssen, WJ
   Schwartz, DA
   Boucher, RC
   Dickey, BF
   Evans, CM
AF Roy, Michelle G.
   Livraghi-Butrico, Alessandra
   Fletcher, Ashley A.
   McElwee, Melissa M.
   Evans, Scott E.
   Boerner, Ryan M.
   Alexander, Samantha N.
   Bellinghausen, Lindsey K.
   Song, Alfred S.
   Petrova, Youlia M.
   Tuvim, Michael J.
   Adachi, Roberto
   Romo, Irlanda
   Bordt, Andrea S.
   Bowden, M. Gabriela
   Sisson, Joseph H.
   Woodruff, Prescott G.
   Thornton, David J.
   Rousseau, Karine
   De la Garza, Maria M.
   Moghaddam, Seyed J.
   Karmouty-Quintana, Harry
   Blackburn, Michael R.
   Drouin, Scott M.
   Davis, C. William
   Terrell, Kristy A.
   Grubb, Barbara R.
   O'Neal, Wanda K.
   Flores, Sonia C.
   Cota-Gomez, Adela
   Lozupone, Catherine A.
   Donnelly, Jody M.
   Watson, Alan M.
   Hennessy, Corinne E.
   Keith, Rebecca C.
   Yang, Ivana V.
   Barthel, Lea
   Henson, Peter M.
   Janssen, William J.
   Schwartz, David A.
   Boucher, Richard C.
   Dickey, Burton F.
   Evans, Christopher M.
TI Muc5b is required for airway defence
SO NATURE
LA English
DT Article
ID mucociliary clearance; clara cells; mucin; lung; expression; iron; gene; phagocytosis; contributes; infection
AB Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC)(1,2). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases(1). MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus(1,3). Genetic variants are linked to diverse lung diseases(4-6), but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally(7). Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b(-/-) mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum(1,8). However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%(9-11). By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.
C1 [Roy, Michelle G.; McElwee, Melissa M.; Evans, Scott E.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; De la Garza, Maria M.; Moghaddam, Seyed J.; Dickey, Burton F.; Evans, Christopher M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Livraghi-Butrico, Alessandra; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Boucher, Richard C.] Univ N Carolina, Chapel Hill, NC 27599 USA.
   [Fletcher, Ashley A.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Evans, Christopher M.] Univ Colorado, Sch Med, Aurora, CO 80045 USA.
   [Boerner, Ryan M.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.] Univ Texas Hlth Sci Ctr Houston, Sch Med, Houston, TX 77030 USA.
   [Romo, Irlanda] Inst Tecnol & Estudios Super Monterrey, Monterrey 64849, Nuevo Leon, Mexico.
   [Bordt, Andrea S.; Bowden, M. Gabriela] Texas A&M Hlth Sci Ctr, Houston, TX 77030 USA.
   [Bowden, M. Gabriela] Univ Houston Downtown, Houston, TX 77002 USA.
   [Sisson, Joseph H.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
   [Woodruff, Prescott G.] Univ Calif San Francisco, San Francisco, CA 27599 USA.
   [Thornton, David J.; Rousseau, Karine] Univ Manchester, Manchester M13 9PT, Lancs, England.
   [Barthel, Lea; Henson, Peter M.; Janssen, William J.] Natl Jewish Hlth, Denver, CO 80206 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Texas System; University of Texas Health Science Center Houston; Tecnologico de Monterrey; Texas A&M University System; Texas A&M University College Station; Texas A&M Health Science Center; University of Houston System; University of Houston; University of Houston Downtown; University of Nebraska System; University of Nebraska Medical Center; University of California System; University of California San Francisco; University of Manchester; National Jewish Health
RP Evans, CM (corresponding author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM Christopher.Evans@ucdenver.edu
FU National Institutes of Health [R01 HL080396, R01 AA008769, R01 HL109517, R01 HL114381, R01 HL097000, P01 HL108808, P01 HL110873, P50 HL107168, P30DK065988]; Medical Research Council [G1000450]; Cystic Fibrosis Foundation [06IO, RDP R026-CR11]; National Institutes of Health Cancer Center [CA016672, CA046934];  [CA016086]; MRC [G1000450] Funding Source: UKRI; National Cancer Institute [P30CA016672, P30CA046934, P30CA016086] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [P01HL107202, R01HL080396, P01HL108808] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [U19AI077439] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK065988] Funding Source: NIH RePORTER; Medical Research Council [G1000450] Funding Source: researchfish
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   Preciado D, 2010, PEDIATR RES, V68, P231, DOI 10.1203/00006450-201011001-00451
   Rowe SM, 2005, NEW ENGL J MED, V352, P1992, DOI 10.1056/NEJMra043184
   Roy MG, 2011, AM J RESP CELL MOL, V44, P755, DOI 10.1165/rcmb.2010-0020OC
   Seibold MA, 2011, NEW ENGL J MED, V364, P1503, DOI 10.1056/NEJMoa1013660
   Sisson JH, 2003, J MICROSC-OXFORD, V211, P103, DOI 10.1046/j.1365-2818.2003.01209.x
   Stark MA, 2005, IMMUNITY, V22, P285, DOI 10.1016/j.immuni.2005.01.011
   STEINKAMP JA, 1982, SCIENCE, V215, P64, DOI 10.1126/science.7053559
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   Thornton DJ, 2008, ANNU REV PHYSIOL, V70, P459, DOI 10.1146/annurev.physiol.70.113006.100702
   Van der Sluis M, 2006, GASTROENTEROLOGY, V131, P117, DOI 10.1053/j.gastro.2006.04.020
   Velcich A, 2002, SCIENCE, V295, P1726, DOI 10.1126/science.1069094
   Voronina VA, 2009, J CELL BIOL, V185, P225, DOI 10.1083/jcb.200809144
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   Woodruff PG, 2009, AM J RESP CRIT CARE, V180, P388, DOI 10.1164/rccm.200903-0392OC
   You YJ, 2002, AM J PHYSIOL-LUNG C, V283, PL1315, DOI 10.1152/ajplung.00169.2002
   Young HWJ, 2007, AM J RESP CELL MOL, V37, P273, DOI 10.1165/rcmb.2005-0460OC
   Yu DG, 2000, P NATL ACAD SCI USA, V97, P5978, DOI 10.1073/pnas.100127597
   Zhu Y, 2008, J PHYSIOL-LONDON, V586, P1977, DOI 10.1113/jphysiol.2007.149310
NR 51
TC 601
Z9 704
U1 2
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 JAN 16
PY 2014
VL 505
IS 7483
BP 412
EP +
DI 10.1038/nature12807
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 288OR
UT WOS:000329621800045
PM 24317696
DA 2026-03-09
ER

PT J
AU Colegio, OR
   Chu, NQ
   Szabo, AL
   Chu, T
   Rhebergen, AM
   Jairam, V
   Cyrus, N
   Brokowski, CE
   Eisenbarth, SC
   Phillips, GM
   Cline, GW
   Phillips, AJ
   Medzhitov, R
AF Colegio, Oscar R.
   Ngoc-Quynh Chu
   Szabo, Alison L.
   Chu, Thach
   Rhebergen, Anne Marie
   Jairam, Vikram
   Cyrus, Nika
   Brokowski, Carolyn E.
   Eisenbarth, Stephanie C.
   Phillips, Gillian M.
   Cline, Gary W.
   Phillips, Andrew J.
   Medzhitov, Ruslan
TI Functional polarization of tumour-associated macrophages by tumour-derived lactic acid
SO NATURE
LA English
DT Article
ID angiogenesis; activation; cells; inflammation; hypoxia; growth
AB Macrophages have an important role in the maintenance of tissue homeostasis(1). To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition(2). Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth(3-5). However, the signals involved in communication between tumours and macrophages are poorly defined. Here we show that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages. Furthermore, we demonstrate that this effect of lactic acid is mediated by hypoxia-inducible factor 1 alpha (HIF1 alpha). Finally, we show that the lactate-induced expression of arginase 1 by macrophages has an important role in tumour growth. Collectively, these findings identify a mechanism of communication between macrophages and their client cells, including tumour cells. This communication most probably evolved to promote homeostasis in normal tissues but can also be engaged in tumours to promote their growth.
C1 [Colegio, Oscar R.; Ngoc-Quynh Chu; Szabo, Alison L.; Chu, Thach; Rhebergen, Anne Marie; Jairam, Vikram; Cyrus, Nika; Brokowski, Carolyn E.; Eisenbarth, Stephanie C.; Medzhitov, Ruslan] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06519 USA.
   [Colegio, Oscar R.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA.
   [Colegio, Oscar R.] Yale Univ, Sch Med, Yale New Haven Transplantat Ctr, New Haven, CT 06519 USA.
   [Colegio, Oscar R.; Medzhitov, Ruslan] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06520 USA.
   [Eisenbarth, Stephanie C.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Phillips, Gillian M.; Phillips, Andrew J.] Yale Univ, Sch Med, Dept Chem, New Haven, CT 06520 USA.
   [Cline, Gary W.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
   [Medzhitov, Ruslan] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Yale University; Yale University; Yale University; Yale University; Yale New Haven Hospital; Yale University; Yale University; Yale University; Howard Hughes Medical Institute
RP Medzhitov, R (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06519 USA.
EM ruslan.medzhitov@yale.edu
FU National Cancer Institute [1K08CA172580-01]; Yale Center for Clinical Investigation [5KL2RR024138]; Yale SPORE in Skin Cancer [1 P50 CA121974]; Damon Runyon Cancer Research Foundation [DRG 108-09]; Dermatology Foundation; Blavatnik Family Foundation; National Institutes of Health [AI046688, AI089771, CA157461]; Howard Hughes Medical Institute; National Cancer Institute [P50CA121974, P30CA016359] Funding Source: NIH RePORTER
NR 23
TC 2389
Z9 2679
U1 18
U2 626
PU NATURE PUBLISHING 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 25
PY 2014
VL 513
IS 7519
BP 559
EP +
DI 10.1038/nature13490
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AP4VB
UT WOS:000342075800043
PM 25043024
DA 2026-03-09
ER

PT J
AU Jin, FF
   Boucharel, J
   Lin, II
AF Jin, F. -F.
   Boucharel, J.
   Lin, I. -I.
TI Eastern Pacific tropical cyclones intensified by El Nino delivery of subsurface ocean heat
SO NATURE
LA English
DT Article
ID part i; climate; model; variability; genesis; enso
AB The El Nino Southern Oscillation (ENSO) creates strong variations in sea surface temperature in the eastern equatorial Pacific, leading to major climatic and societal impacts(1,2). In particular, ENSO influences the yearly variations of tropical cyclone (TC) activities in both the Pacific and Atlantic basins through atmospheric dynamical factors such as vertical wind shear and stability(3-6). Until recently, however, the direct ocean thermal control of ENSO on TCs has not been taken into consideration because of an apparent mismatch in both timing and location: ENSO peaks in winter and its surface warming occurs mostly along the Equator, a region without TC activity. Here we show that El Nino the warm phase of an ENSO cycle effectively discharges heat into the eastern North Pacific basin two to three seasons after its wintertime peak, leading to intensified TCs. This basin is characterized by abundant TC activity and is the second most active TC region in the world(5-7). As a result of the time involved in ocean transport, El Ninio's equatorial subsurface 'heat reservoir', built up in boreal winter, appears in the eastern North Pacific several months later during peak TC season (boreal summer and autumn). By means of this delayed ocean transport mechanism, ENSO provides an additional heat supply favourable for the formation of strong hurricanes. This thermal control on intense TC variability has significant implications for seasonal predictions and long-term projections of TC activity over the eastern North Pacific.
C1 [Jin, F. -F.; Boucharel, J.] Univ Hawaii Manoa, SOEST, Dept Atmospher Sci, Honolulu, HI 96822 USA.
   [Lin, I. -I.] Natl Taiwan Univ, Dept Atmospher Sci, Taipei 10617, Taiwan.
   [Jin, F. -F.] Chinese Meteorol Agcy, Beijing Climate Ctr, Lab Climate Studies, Beijing 100081, Peoples R China.
C3 University of Hawaii System; University of Hawaii Manoa; National Taiwan University
RP Jin, FF (corresponding author), Univ Hawaii Manoa, SOEST, Dept Atmospher Sci, Honolulu, HI 96822 USA.
EM jff@hawaii.edu; bouch@hawaii.edu
FU US National Science Foundation [ATM 1034798, ATM 1406601]; US Department of Energy [DESC005110]; US NOM [NA100AR4310200]; China Meteorological Special Project [GYHY201206033]; 973 Program of China [2010CB950404, 2013CB430203]; Taiwan's Ministry of Science and Technology [NSC 101-2111-M-002-002-MY2, NSC 101-2628-M-002-001-MY4, 102R7803]; Directorate For Geosciences [1406601] Funding Source: National Science Foundation; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1034798] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1406601] Funding Source: National Science Foundation
NR 43
TC 132
Z9 153
U1 3
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 DEC 4
PY 2014
VL 516
IS 7529
BP 82
EP U178
DI 10.1038/nature13958
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW5JD
UT WOS:000346310800043
PM 25471884
DA 2026-03-09
ER

PT J
AU Cleary, AS
   Leonard, TL
   Gestl, SA
   Gunther, EJ
AF Cleary, Allison S.
   Leonard, Travis L.
   Gestl, Shelley A.
   Gunther, Edward J.
TI Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers
SO NATURE
LA English
DT Article
ID clonal evolution; progenitor cells; transgenic mice; breast-tumors; progression; activation; tumorigenesis; recurrence; expression; induce
AB Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones(1-4). As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors(5,6). Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models(7,8), definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy(9). Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.
C1 [Cleary, Allison S.; Leonard, Travis L.; Gestl, Shelley A.; Gunther, Edward J.] Penn State Univ, Coll Med, Jake Gittlen Labs Canc Res, Hershey, PA 17033 USA.
   [Cleary, Allison S.; Leonard, Travis L.; Gestl, Shelley A.; Gunther, Edward J.] Penn State Univ, Coll Med, Penn State Hershey Canc Inst, Hershey, PA 17033 USA.
   [Gunther, Edward J.] Penn State Univ, Coll Med, Dept Med Hematol Oncol, Hershey, PA 17033 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health
RP Gunther, EJ (corresponding author), Penn State Univ, Coll Med, Jake Gittlen Labs Canc Res, Hershey, PA 17033 USA.
EM ejg12@psu.edu
FU National Institutes of Health/National Cancer Institute; Mary Kay Foundation; Donald B. and Dorothy L. Stabler Foundation; Pennsylvania Department of Health; Department of Defense Predoctoral Traineeship Award [W81XWH-11-1-0038]
NR 30
TC 378
Z9 449
U1 2
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 3
PY 2014
VL 508
IS 7494
BP 113
EP +
DI 10.1038/nature13187
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900053
PM 24695311
DA 2026-03-09
ER

PT J
AU Deng, L
   Ignacio-Espinoza, JC
   Gregory, AC
   Poulos, BT
   Weitz, JS
   Hugenholtz, P
   Sullivan, MB
AF Deng, Li
   Ignacio-Espinoza, J. Cesar
   Gregory, Ann C.
   Poulos, Bonnie T.
   Weitz, Joshua S.
   Hugenholtz, Philip
   Sullivan, Matthew B.
TI Viral tagging reveals discrete populations in Synechococcus viral genome sequence space
SO NATURE
LA English
DT Article
ID marine virus; gene-transfer; cyanophages; evolution; diversity; bacteriophage; community; prophages; abundance; bacterial
AB Microbes and their viruses drive myriad processes across ecosystems ranging from oceans and soils to bioreactors and humans(1-4). Despite this importance, microbial diversity is only now being mapped at scales relevant to nature(5), while the viral diversity associated with any particular host remains little researched. Here we quantify host-associated viral diversity using viral-tagged metagenomics, which links viruses to specific host cells for high-throughput screening and sequencing. In a single experiment, we screened 10(7) Pacific Ocean viruses against a single strain of Synechococcus and found that naturally occurring cyanophage genome sequence space is statistically clustered into discrete populations. These population-based, host-linked viral ecological data suggest that, for this single host and seawater sample alone, there are at least 26 double-stranded DNA viral populations with estimated relative abundances ranging from 0.06 to 18.2%. These populations include previously cultivated cyanophage and new viral types missed by decades of isolate-based studies. Nucleotide identities of homologous genes mostly varied by less than 1% within populations, even in hypervariable genome regions, and by 42-71% between populations, which provides benchmarks for viral metagenomics and genome-based viral species definitions. Together these findings showcase a new approach to viral ecology that quantitatively links objectively defined environmental viral populations, and their genomes, to their hosts.
C1 [Deng, Li; Gregory, Ann C.; Poulos, Bonnie T.; Sullivan, Matthew B.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85719 USA.
   [Ignacio-Espinoza, J. Cesar; Sullivan, Matthew B.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85719 USA.
   [Weitz, Joshua S.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Weitz, Joshua S.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Hugenholtz, Philip] Univ Queensland, Australian Ctr Ecogen, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia.
   [Hugenholtz, Philip] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
C3 University of Arizona; University of Arizona; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; University of Queensland; University of Queensland
RP Sullivan, MB (corresponding author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85719 USA.
EM mbsulli@email.arizona.edu
FU US Department of Energy (DOE) Joint Genome Institute (JGI) Community Sequencing Program; Biosphere 2; BIO5; US National Science Foundation (NSF) [OCE0940390]; Gordon and Betty Moore Foundation grants; NSF [OCE1233760]; Burroughs Wellcome Fund grants; University Information Technology Services Research Computing Group; ARL Biotechnology Computing for high-performance computing clusters (HPCC); DOE JGI Community Sequencing Program under the Office of Science of the US DOE [DE-AC02-05CH11231]; Direct For Mathematical & Physical Scien; Division Of Physics [1205878] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1233760] Funding Source: National Science Foundation
NR 58
TC 147
Z9 169
U1 4
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 SEP 11
PY 2014
VL 513
IS 7517
BP 242
EP +
DI 10.1038/nature13459
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AO5DP
UT WOS:000341362800052
PM 25043051
DA 2026-03-09
ER

PT J
AU Kazimierczuk, T
   Fröhlich, D
   Scheel, S
   Stolz, H
   Bayer, M
AF Kazimierczuk, T.
   Froehlich, D.
   Scheel, S.
   Stolz, H.
   Bayer, M.
TI Giant Rydberg excitons in the copper oxide Cu2O
SO NATURE
LA English
DT Article
ID absorption; positronium; spectra; atoms
AB A highly excited atom having an electron that has moved into a level with large principal quantum number is a hydrogen-like object, termed a Rydberg atom. The giant size of Rydberg atoms(1) leads to huge interaction effects. Monitoring these interactions has provided in-sights into atomic and molecular physics on the single-quantum level. Excitons-the fundamental optical excitations in semiconductors(2), consisting of an electron and a positively charged hole-are the condensed-matter analogues of hydrogen. Highly excited excitons with extensions similar to those of Rydberg atoms are of interest because they can be placed and moved in a crystal with high precision using microscopic energy potential landscapes. The interaction of such Rydberg excitons may allow the formation of ordered exciton phases or the sensing of elementary excitations in their surroundings on a quantum level. Here we demonstrate the existence of Rydberg excitons in the copper oxide Cu2O, with principal quantum numbers as large as n = 25. These states have giant wavefunction extensions (that is, the average distance between the electron and the hole) of more than two micrometres, compared to about a nanometre for the ground state. The strong dipole-dipole interaction between such excitons is indicated by a blockade effect in which the presence of one exciton prevents the excitation of another in its vicinity.
C1 [Kazimierczuk, T.; Froehlich, D.; Bayer, M.] Tech Univ Dortmund, D-44221 Dortmund, Germany.
   [Scheel, S.; Stolz, H.] Univ Rostock, Inst Phys, D-18051 Rostock, Germany.
   [Bayer, M.] Russian Acad Sci, AF Ioffe Phys Tech Inst, St Petersburg 194021, Russia.
C3 Dortmund University of Technology; University of Rostock; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; Ioffe Physical Technical Institute
RP Fröhlich, D (corresponding author), Tech Univ Dortmund, D-44221 Dortmund, Germany.
EM dietmar.froehlich@tu-dortmund.de
FU Deutsche Forschungsgemeinschaft [BA 1549/18-1, SFB 652]; Russian Ministry of Science and Education [14.Z50.31.0021]
NR 22
TC 321
Z9 352
U1 2
U2 232
PU NATURE PUBLISHING 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 16
PY 2014
VL 514
IS 7522
BP 343
EP 347
DI 10.1038/nature13832
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AQ7JH
UT WOS:000342988600046
PM 25318523
DA 2026-03-09
ER

PT J
AU Park, IU
   Peacey, MW
   Munafò, MR
AF Park, In-Uck
   Peacey, Mike W.
   Munafo, Marcus R.
TI Modelling the effects of subjective and objective decision making in scientific peer review
SO NATURE
LA English
DT Article
ID published research; reliability; science; trials; false
AB The objective of science is to advance knowledge, primarily in two interlinked ways: circulating ideas, and defending or criticizing the ideas of others. Peer review acts as the gatekeeper to these mechanisms. Given the increasing concern surrounding the reproducibility of much published research(1), it is critical to understand whether peer review is intrinsically susceptible to failure, or whether other extrinsic factors are responsible that distort scientists' decisions. Here we show that even when scientists are motivated to promote the truth, their behaviour may be influenced, and even dominated, by information gleaned from their peers' behaviour, rather than by their personal dispositions. This phenomenon, known as herding, subjects the scientific community to an inherent risk of converging on an incorrect answer and raises the possibility that, under certain conditions, science may not be self-correcting. We further demonstrate that exercising some subjectivity in reviewer decisions, which serves to curb the herding process, can be beneficial for the scientific community in processing available information to estimate truth more accurately. By examining the impact of different models of reviewer decisions on the dynamic process of publication, and thereby on eventual aggregation of knowledge, we provide a new perspective on the ongoing discussion of how the peer-review process may be improved.
C1 [Park, In-Uck; Peacey, Mike W.] Univ Bristol, Dept Econ, Bristol BS8 1TN, Avon, England.
   [Park, In-Uck] Sungkyunkwan Univ, Dept Econ, Seoul 110745, South Korea.
   [Peacey, Mike W.] Univ Bath, Dept Econ, Bath BA2 7AY, Avon, England.
   [Munafo, Marcus R.] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol BS8 1BN, Avon, England.
   [Munafo, Marcus R.] Univ Bristol, UK Ctr Tobacco & Alcohol Studies, Bristol BS8 1TU, Avon, England.
   [Munafo, Marcus R.] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TU, Avon, England.
C3 University of Bristol; Sungkyunkwan University (SKKU); University of Bath; University of Bristol; University of Bristol; University of Bristol
RP Munafò, MR (corresponding author), Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol BS8 1BN, Avon, England.
EM marcus.munafo@bristol.ac.uk
FU Economics and Social Research Council UK; British Heart Foundation; Cancer Research UK; Economic and Social Research Council; Medical Research Council; National Institute for Health Research under the UK Clinical Research Collaboration; Economic and Social Research Council [ES/H005331/1] Funding Source: researchfish; Medical Research Council [MC_UU_12013/6] Funding Source: researchfish; ESRC [ES/H005331/1] Funding Source: UKRI; MRC [MC_UU_12013/6] Funding Source: UKRI
NR 29
TC 71
Z9 80
U1 5
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 6
PY 2014
VL 506
IS 7486
BP 93
EP +
DI 10.1038/nature12786
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 303BA
UT WOS:000330648100038
PM 24305052
DA 2026-03-09
ER

PT J
AU Vagizov, F
   Antonov, V
   Radeonychev, YV
   Shakhmuratov, RN
   Kocharovskaya, O
AF Vagizov, Farit
   Antonov, Vladimir
   Radeonychev, Y. V.
   Shakhmuratov, R. N.
   Kocharovskaya, Olga
TI Coherent control of the waveforms of recoilless γ-ray photons
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency
AB The concepts and ideas of coherent, nonlinear and quantum optics have been extended to photon energies in the range of 10-100 kilo-electronvolts, corresponding to soft gamma-ray radiation (the term used when the radiation is produced in nuclear transitions) or, equivalently, hard X-ray radiation (the term used when the radiation is produced by electron motion). The recent experimental achievements in this energy range include the demonstration of parametric down-conversion in the Langevin regime(1), electromagnetically induced transparency in a cavity(2), the collective Lamb shift(3), vacuum-assisted generation of atomic coherences(4) and single-photon revival in nuclear absorbing multilayer structures(5). Also, realization of single-photon coherent storage(6) and stimulated Raman adiabatic passage(7) were recently proposed in this regime. More related work is discussed in a recent review(8). However, the number of tools for the coherent manipulation of interactions between gamma-ray photons and nuclear ensembles remains limited. Here we suggest and implement an efficient method to control the waveforms of gamma-ray photons coherently. In particular, we demonstrate the conversion of individual recoilless gamma-ray photons into a coherent, ultrashort pulse train and into a double pulse. Our method is based on the resonant interaction of gamma-ray photons with an ensemble of nuclei with a resonant transition frequency that is periodically modulated in time. The frequency modulation, which is achieved by a uniform vibration of the resonant absorber, owing to the Doppler effect, renders resonant absorption and dispersion both time dependent, allowing us to shape the waveforms of the incident gamma-ray photons. We expect that this technique will lead to advances in the emerging fields of coherent and quantum gamma-ray photon optics, providing a basis for the realization of gamma-ray-photon/nuclear-ensemble interfaces and quantum interference effects at nuclear gamma-ray transitions.
C1 [Vagizov, Farit; Antonov, Vladimir; Radeonychev, Y. V.; Kocharovskaya, Olga] Texas A&M Univ, Dept Phys & Astron, College Stn, TX 77843 USA.
   [Vagizov, Farit; Antonov, Vladimir; Radeonychev, Y. V.; Kocharovskaya, Olga] Texas A&M Univ, Inst Quantum Sci & Engn, College Stn, TX 77843 USA.
   [Vagizov, Farit; Shakhmuratov, R. N.] Kazan Fed Univ, Kazan 420008, Russia.
   [Vagizov, Farit; Shakhmuratov, R. N.] Russian Acad Sci, Kazan Phys Tech Inst, Kazan 420029, Russia.
   [Antonov, Vladimir; Radeonychev, Y. V.] Russian Acad Sci, Inst Appl Phys, Nizhnii Novgorod 603950, Russia.
   [Antonov, Vladimir; Radeonychev, Y. V.] NI Lobachevsky State Univ, Nizhnii Novgorod 603950, Russia.
C3 Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; Kazan Federal University; Russian Academy of Sciences; Kazan Scientific Centre of the Russian Academy of Sciences; Zavoisky Physical-Technical Institute; Russian Academy of Sciences; Institute of Applied Physics of the Russian Academy of Sciences; Lobachevsky State University of Nizhni Novgorod
RP Kocharovskaya, O (corresponding author), Texas A&M Univ, Dept Phys & Astron, College Stn, TX 77843 USA.
EM kochar@physics.tamu.edu
FU US NSF [PHY-1307346]; RFBR [13-02-00831, 12-02-00263]; Ministry of Education and Science of the Russian Federation [11.G34.31.0011]; Dynasty Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1307346] Funding Source: National Science Foundation
NR 30
TC 111
Z9 123
U1 2
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 APR 3
PY 2014
VL 508
IS 7494
BP 80
EP +
DI 10.1038/nature13018
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900046
PM 24670656
DA 2026-03-09
ER

PT J
AU Rios, AC
   Fu, NY
   Lindeman, GJ
   Visvader, JE
AF Rios, Anne C.
   Fu, Nai Yang
   Lindeman, Geoffrey J.
   Visvader, Jane E.
TI In situ identification of bipotent stem cells in the mammary gland
SO NATURE
LA English
DT Article
ID life-span; mouse; basal; expression; hierarchy; adult; gene; candidate
AB The mammary epithelium undergoes profound morphogenetic changes during development. Architecturally, it comprises two primary lineages, the inner luminal and outer myoepithelial cell layers. Two opposing concepts on the nature of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model, based on classical transplantation assays, postulates that bipotent MaSCs have a key role in coordinating ductal epithelial expansion and maintenance in the adult gland, whereas the second model proposes that only unipotent MaSCs identified by lineage tracing contribute to these processes. Through clonal cell-fate mapping studies using a stochastic multicolour cre reporter combined with a new three-dimensional imaging strategy, we provide evidence for the existence of bipotent MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at different developmental stages support a model in which both stem and progenitor cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate ductal homeostasis and remodelling of the mouse adult gland.
C1 [Rios, Anne C.; Fu, Nai Yang; Lindeman, Geoffrey J.; Visvader, Jane E.] Walter & Eliza Hall Inst Med Res, Stem Cells & Canc Div, Parkville, Vic 3052, Australia.
   [Rios, Anne C.; Fu, Nai Yang; Visvader, Jane E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Lindeman, Geoffrey J.] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia.
   [Lindeman, Geoffrey J.] Royal Melbourne Hosp, Dept Med Oncol, Parkville, Vic 3050, Australia.
   [Lindeman, Geoffrey J.] Royal Melbourne Hosp, Familial Canc Ctr, Parkville, Vic 3050, Australia.
C3 Walter & Eliza Hall Institute; University of Melbourne; University of Melbourne; Melbourne Health; Royal Melbourne Hospital; Melbourne Health; Royal Melbourne Hospital
RP Visvader, JE (corresponding author), Walter & Eliza Hall Inst Med Res, Stem Cells & Canc Div, Parkville, Vic 3052, Australia.
EM visvader@wehi.edu.au
FU Australian National Health and Medical Research Council (NHMRC); Victorian State Government through VCA funding of the Victorian Breast Cancer Research Consortium; Victorian State Government through Operational Infrastructure Support; Australian Cancer Research Foundation; Qualtrough Family Bequest; National Breast Cancer Foundation/Cure Cancer Australia Fellowship; NHMRC Research Fellowship; Australia Fellowship
NR 37
TC 409
Z9 512
U1 0
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 FEB 20
PY 2014
VL 506
IS 7488
BP 322
EP +
DI 10.1038/nature12948
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AB0JL
UT WOS:000331477800032
PM 24463516
DA 2026-03-09
ER

PT J
AU Pflug, A
   Guilligay, D
   Reich, S
   Cusack, S
AF Pflug, Alexander
   Guilligay, Delphine
   Reich, Stefan
   Cusack, Stephen
TI Structure of influenza A polymerase bound to the viral RNA promoter
SO NATURE
LA English
DT Article
ID virus pb1 protein; crystal-structure; virion rna; mutational analysis; terminal domain; cap-binding; fork model; 5' end; subunit; endonuclease
AB The influenza virus polymerase transcribes or replicates the segmented RNA genome (viral RNA) into viral messenger RNA or full-length copies. To initiate RNA synthesis, the polymerase binds to the conserved 39 and 59 extremities of the viral RNA. Here we present the crystal structure of the heterotrimeric bat influenza A polymerase, comprising subunits PA, PB1 and PB2, bound to its viral RNA promoter. PB1 contains a canonical RNA polymerase fold that is stabilized by large interfaces with PA and PB2. The PA endonuclease and the PB2 cap-binding domain, involved in transcription by cap-snatching, form protrusions facing each other across a solvent channel. The 59 extremity of the promoter folds into a compact hook that is bound in a pocket formed by PB1 and PA close to the polymerase active site. This structure lays the basis for an atomic-level mechanistic understanding of the many functions of influenza polymerase, and opens new opportunities for anti-influenza drug design.
C1 [Pflug, Alexander; Guilligay, Delphine; Reich, Stefan; Cusack, Stephen] European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France.
   [Pflug, Alexander; Guilligay, Delphine; Reich, Stefan; Cusack, Stephen] Univ Grenoble Alpes, Ctr Natl Rech Sci, EMBL Unit Virus Host Cell Interact, F-38042 Grenoble 9, France.
C3 European Molecular Biology Laboratory (EMBL); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Cusack, S (corresponding author), European Mol Biol Lab, Grenoble Outstn, 71 Ave Martyrs,CS 90181, F-38042 Grenoble 9, France.
EM cusack@embl.fr
FU ERC [322586]; European Research Council (ERC) [322586] Funding Source: European Research Council (ERC)
NR 57
TC 405
Z9 462
U1 0
U2 140
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 18
PY 2014
VL 516
IS 7531
BP 355
EP +
DI 10.1038/nature14008
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW8BE
UT WOS:000346484800038
PM 25409142
DA 2026-03-09
ER

PT J
AU Hitti, FL
   Siegelbaum, SA
AF Hitti, Frederick L.
   Siegelbaum, Steven A.
TI The hippocampal CA2 region is essential for social memory
SO NATURE
LA English
DT Article
ID vasopressin 1b receptor; synaptic plasticity; gene-expression; area ca2; neurons; cells; brain; dorsal; mice; projection
AB The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where and when(1). Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus to CA3 and then to CA1, the main hippocampal output(2). Genetic lesions of EC(ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and CA1 (ref. 6) regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output(7). Here we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioural role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory-the ability of an animal to remember a conspecific-with no change in sociability or several other hippocampus-dependent behaviours, including spatial and contextual memory. These behavioural and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.
C1 [Hitti, Frederick L.; Siegelbaum, Steven A.] Columbia Univ, Coll Phys & Surg, Kavli Inst, Dept Neurosci, New York, NY 10032 USA.
   [Siegelbaum, Steven A.] Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, Dept Pharmacol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute
RP Siegelbaum, SA (corresponding author), Columbia Univ, Coll Phys & Surg, Kavli Inst, Dept Neurosci, 1051 Riverside Dr, New York, NY 10032 USA.
EM sas8@columbia.edu
FU Ruth L. Kirschstein F30 National Research Service Award from the National Institute of Mental Health; Howard Hughes Medical Institute
NR 45
TC 728
Z9 890
U1 1
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 3
PY 2014
VL 508
IS 7494
BP 88
EP +
DI 10.1038/nature13028
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD9UL
UT WOS:000333609900048
PM 24572357
DA 2026-03-09
ER

PT J
AU Zuppinger-Dingley, D
   Schmid, B
   Petermann, JS
   Yadav, V
   De Deyn, GB
   Flynn, DFB
AF Zuppinger-Dingley, Debra
   Schmid, Bernhard
   Petermann, Jana S.
   Yadav, Varuna
   De Deyn, Gerlinde B.
   Flynn, Dan F. B.
TI Selection for niche differentiation in plant communities increases biodiversity effects
SO NATURE
LA English
DT Article
ID diversity-productivity relationships; grassland experiment; species-diversity; evolution; genotypes; richness
AB In experimental plant communities, relationships between biodiversity and ecosystem functioning have been found to strengthen over time(1,2), a fact often attributed to increased resource complementarity between species in mixtures(3) and negative plant-soil feedbacks in monocultures(4). Here we show that selection for niche differentiation between species can drive this increasing biodiversity effect. Growing 12 grassland species in test monocultures and mixtures, we found character displacement between species and increased biodiversity effects when plants had been selected over 8 years in species mixtures rather than in monocultures. When grown in mixtures, relative differences in height and specific leaf area between plant species selected in mixtures (mixture types) were greater than between species selected inmonocultures (monoculture types). Furthermore, net biodiversity and complementarity effects(1,2) were greater in mixtures of mixture types than inmixtures of monoculture types. Our study demonstrates a novel mechanism for the increase in biodiversity effects: selection for increased niche differentiation through character displacement. Selection in diverse mixtures may therefore increase species coexistence and ecosystem functioning in natural communities and may also allow increased mixture yields in agriculture or forestry. However, loss of biodiversity and prolonged selection of crops in monoculture may compromise this potential for selection in the longer term.
C1 [Zuppinger-Dingley, Debra; Schmid, Bernhard; Yadav, Varuna; Flynn, Dan F. B.] Univ Zurich, Inst Evolutionary Biol & Environm Studies, CH-8057 Zurich, Switzerland.
   [Zuppinger-Dingley, Debra; Schmid, Bernhard; Yadav, Varuna; Flynn, Dan F. B.] Univ Zurich, Zurich Basel Plant Sci Ctr, CH-8057 Zurich, Switzerland.
   [Petermann, Jana S.] Free Univ Berlin, Inst Biol, D-14195 Berlin, Germany.
   [Petermann, Jana S.] Berlin Brandenburg Inst Adv Biodivers Res BBIB, D-14195 Berlin, Germany.
   [De Deyn, Gerlinde B.] Wageningen Univ, NL-6708 PB Wageningen, Netherlands.
   [Flynn, Dan F. B.] Harvard Univ, Arnold Arboretum, Boston, MA 02131 USA.
C3 University of Zurich; University of Zurich; Free University of Berlin; Wageningen University & Research; Harvard University
RP Schmid, B (corresponding author), Univ Zurich, Inst Evolutionary Biol & Environm Studies, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM bernhard.schmid@ieu.uzh.ch; dan.flynn@ieu.uzh.ch
FU Swiss National Science Foundation [130720]; University Research Priority Program Global Change and Biodiversity of the University of Zurich; NWO-ALW VIDI grant
NR 30
TC 339
Z9 392
U1 20
U2 561
PU NATURE PUBLISHING 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 6
PY 2014
VL 515
IS 7525
BP 108
EP +
DI 10.1038/nature13869
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AS3OE
UT WOS:000344187500039
PM 25317555
DA 2026-03-09
ER

PT J
AU Wahlquist, C
   Jeong, D
   Rojas-Muñoz, A
   Kho, C
   Lee, A
   Mitsuyama, S
   van Mil, A
   Park, WJ
   Sluijter, JPG
   Doevendans, PAF
   Hajjar, RJ
   Mercola, M
AF Wahlquist, Christine
   Jeong, Dongtak
   Rojas-Munoz, Agustin
   Kho, Changwon
   Lee, Ahyoung
   Mitsuyama, Shinichi
   van Mil, Alain
   Park, Woo Jin
   Sluijter, Joost P. G.
   Doevendans, Pieter A. F.
   Hajjar, Roger J.
   Mercola, Mark
TI Inhibition of miR-25 improves cardiac contractility in the failing heart
SO NATURE
LA English
DT Article
ID microrna expression; failure; dysfunction; signature; reversal; myocytes; reveals; targets; serca2a; nox4
AB Heart failure is characterized by a debilitating decline in cardiac function(1), and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy(2,3). MicroRNAs (miRNAs) are dysregulated in heart failure(4,5) but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.
C1 [Wahlquist, Christine; Rojas-Munoz, Agustin; van Mil, Alain; Mercola, Mark] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92037 USA.
   [Wahlquist, Christine; Rojas-Munoz, Agustin; van Mil, Alain; Mercola, Mark] Sanford Burnham Med Res Inst, Muscle Dev & Regenerat Program, La Jolla, CA 92037 USA.
   [Jeong, Dongtak; Kho, Changwon; Lee, Ahyoung; Mitsuyama, Shinichi; Hajjar, Roger J.] Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, New York, NY 10029 USA.
   [van Mil, Alain; Sluijter, Joost P. G.; Doevendans, Pieter A. F.] Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands.
   [van Mil, Alain; Sluijter, Joost P. G.; Doevendans, Pieter A. F.] ICIN Netherlands Heart Inst, NL-3584 CX Utrecht, Netherlands.
   [Park, Woo Jin] Gwangju Inst Sci & Technol, Global Res Lab, Kwangju 500712, South Korea.
C3 University of California System; University of California San Diego; Sanford Burnham Prebys Medical Discovery Institute; Icahn School of Medicine at Mount Sinai; Utrecht University; Utrecht University Medical Center; Gwangju Institute of Science & Technology (GIST)
RP Mercola, M (corresponding author), Univ Calif San Diego, Dept Bioengn, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM mmercola@sanfordburnham.org
FU California Institute for Regenerative Medicine [RC1-000132]; National Institutes of Health (NIH) [R01HL113601, P01HL098053, R01HL108176]; Fondation Leducq; NIH [NIH R01HL093183, R01HL088434, P20HL100396, HHSN26820100045C, P50HL112324]; Global Research Laboratory Program of the South Korean Government [M6-0605-00-0001]; Netherlands Heart foundation; BioMedical Materials institute [P1.05 LUST]; Dutch Ministry of Economic Affairs, Agriculture and Innovation; Spanish National Research Council;  [P30CA030199];  [P30AR061303]; National Cancer Institute [P30CA030199] Funding Source: NIH RePORTER
NR 44
TC 350
Z9 404
U1 1
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 APR 24
PY 2014
VL 508
IS 7497
BP 531
EP +
DI 10.1038/nature13073
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AF5GI
UT WOS:000334741600038
PM 24670661
DA 2026-03-09
ER

PT J
AU Goyal, P
   Krasteva, PV
   Van Genven, N
   Gubellini, F
   Van den Broeck, I
   Troupiotis-Tsaïlaki, A
   Jonckheere, W
   Péhau-Arnaudet, G
   Pinkner, JS
   Chapman, MR
   Hultgren, SJ
   Howorka, S
   Fronzes, R
   Remaut, H
AF Goyal, Parveen
   Krasteva, Petya V.
   Van Genven, Nani
   Gubellini, Francesca
   Van den Broeck, Imke
   Troupiotis-Tsailaki, Anastassia
   Jonckheere, Wim
   Pehau-Arnaudet, Gerard
   Pinkner, Jerome S.
   Chapman, Matthew R.
   Hultgren, Scott J.
   Howorka, Stefan
   Fronzes, Remi
   Remaut, Han
TI Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG
SO NATURE
LA English
DT Article
ID escherichia-coli; protein translocation; phenylalanine clamp; surface organelles; binding curli; system; refinement; biogenesis; simulation; membrane
AB Curli are functional amyloid fibres that constitute the major protein component of the extracellular matrix in pellicle biofilms formed by Bacteroidetes and Proteobacteria (predominantly of the alpha and gamma classes)(1-3). They provide a fitness advantage in pathogenic strains and induce a strong pro-inflammatory response during bacteraemia(1,4,5). Curli formation requires a dedicated protein secretion machinery comprising the outer membrane lipoprotein CsgG and two soluble accessory proteins, CsgE and CsgF(6,7). Here we report the X-ray structure of Escherichia coli CsgGin a non-lipidated, soluble form as well as in its native membrane-extracted conformation. CsgG forms an oligomeric transport complex composed of nine anticodon-binding-domain-like units that give rise to a 36-stranded beta-barrel that traverses the bilayer and is connected to a cage-like vestibule in the periplasm. The transmembrane and periplasmic domains are separated by a 0.9-nm channel constriction composed of three stacked concentric phenylalanine, asparagine and tyrosine rings that may guide the extended polypeptide substrate through the secretion pore. The specificity factor CsgE forms a nonameric adaptor that binds and closes off the periplasmic face of the secretion channel, creating a 24,000 angstrom(3) pre-constriction chamber. Our structural, functional and electrophysiological analyses imply that CsgG is an ungated, non-selective protein secretion channel that is expected to employ a diffusion-based, entropy-driven transport mechanism.
C1 [Goyal, Parveen; Van Genven, Nani; Van den Broeck, Imke; Jonckheere, Wim; Remaut, Han] VIB, Struct Biol Res Ctr, B-1050 Brussels, Belgium.
   [Goyal, Parveen; Van Genven, Nani; Van den Broeck, Imke; Jonckheere, Wim; Remaut, Han] Vrije Univ Brussel, Struct Biol Brussels, B-1050 Brussels, Belgium.
   [Krasteva, Petya V.; Gubellini, Francesca; Fronzes, Remi] Inst Pasteur, Unite Biol Struct Secret Bacterienne G5, F-75015 Paris, France.
   [Krasteva, Petya V.; Gubellini, Francesca; Pehau-Arnaudet, Gerard; Fronzes, Remi] Inst Pasteur, CNRS, UMR 3528, F-75015 Paris, France.
   [Troupiotis-Tsailaki, Anastassia] Univ Libre Bruxelles, B-1050 Brussels, Belgium.
   [Pinkner, Jerome S.; Hultgren, Scott J.] Washington Univ, Dept Mol Microbiol & Microbial Pathogenesis, Sch Med, St Louis, MO 63110 USA.
   [Chapman, Matthew R.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
   [Howorka, Stefan] UCL, Inst Struct & Mol Biol, Dept Chem, London WC1H 0AJ, England.
C3 Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; 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); Universite Libre de Bruxelles; Washington University (WUSTL); University of Michigan System; University of Michigan; University of London; Birkbeck University London; University College London
RP Remaut, H (corresponding author), VIB, Struct Biol Res Ctr, Pl Laan 2, B-1050 Brussels, Belgium.
EM remi.fronzes@pasteur.fr; han.remaut@vib-vub.be
FU VIB [PRJ9]; Hercules Foundation [UABR/09/005]; National Institutes of Health [AI099099, AI048689, A1073847]; Institut Pasteur; Centre national de la recherche scientifique; Engineering and Physical Sciences Research Council; National Physical Laboratory; University College London Chemistry; 'Bourse Roux' from Institut Pasteur; European Research Council (ERC)
NR 56
TC 244
Z9 329
U1 0
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 DEC 11
PY 2014
VL 516
IS 7530
BP 250
EP +
DI 10.1038/nature13768
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AW6ML
UT WOS:000346383500046
PM 25219853
DA 2026-03-09
ER

PT J
AU Almand-Hunter, AE
   Li, H
   Cundiff, ST
   Mootz, M
   Kira, M
   Koch, SW
AF Almand-Hunter, A. E.
   Li, H.
   Cundiff, S. T.
   Mootz, M.
   Kira, M.
   Koch, S. W.
TI Quantum droplets of electrons and holes
SO NATURE
LA English
DT Article
ID pseudogap; liquid; spectroscopy; excitation; phase; order
AB Interacting many-body systems are characterized by stable configurations of objects-ranging from elementary particles to cosmological formations(1-3)-that also act as building blocks for more complicated structures. It is often possible to incorporate interactions in theoretical treatments of crystalline solids by introducing suitable quasiparticles that have an effective mass, spin or charge(4,5) which in turn affects the material's conductivity, optical response or phase transitions(2,6,7). Additional quasiparticle interactions may also create strongly correlated configurations yielding new macroscopic phenomena, such as the emergence of a Mott insulator(8), superconductivity or the pseudogap phase of high-temperature superconductors(9-11). In semiconductors, a conduction-band electron attracts a valence-band hole (electronic vacancy) to create a bound pair, known as an exciton(12,13), which is yet another quasiparticle. Two excitons may also bind together to give molecules, often referred to as biexcitons(14), and even polyexcitons may exist(15,16). In indirect-gap semiconductors such as germanium or silicon, a thermodynamic phase transition may produce electron-hole droplets whose diameter can approach the micrometre range(17,18). In direct-gap semiconductors such as gallium arsenide, the exciton lifetime is too short for such a thermodynamic process. Instead, different quasiparticle configurations are stabilized dominantly by many-body interactions, not by thermalization. The resulting non-equilibrium quantum kinetics is so complicated that stable aggregates containing three or more Coulomb-correlated electron-hole pairs remain mostly unexplored. Here we study such complex aggregates and identify a new stable configuration of charged particles that we call a quantum droplet. This configuration exists in a plasma and exhibits quantization owing to its small size. It is charge neutral and contains a small number of particles with a pair-correlation function that is characteristic of a liquid. We present experimental and theoretical evidence for the existence of quantum droplets in an electron-hole plasma created in a gallium arsenide quantum well by ultrashort optical pulses.
C1 [Almand-Hunter, A. E.; Li, H.; Cundiff, S. T.] Univ Colorado, JILA, Boulder, CO 80309 USA.
   [Almand-Hunter, A. E.; Li, H.; Cundiff, S. T.] NIST, Boulder, CO 80309 USA.
   [Almand-Hunter, A. E.; Cundiff, S. T.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Mootz, M.; Kira, M.; Koch, S. W.] Univ Marburg, Dept Phys, D-35032 Marburg, Germany.
C3 University of Colorado System; University of Colorado Boulder; National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; Philipps University Marburg
RP Kira, M (corresponding author), Univ Marburg, Dept Phys, Renthof 5, D-35032 Marburg, Germany.
EM mackillo.kira@physik.uni-marburg.de
FU Deutsche Forschungsgemeinschaft [KI 917/2-1]; NSF [1125844]; NIST; Alexander von Humboldt Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1125844] Funding Source: National Science Foundation
NR 29
TC 105
Z9 121
U1 0
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 FEB 27
PY 2014
VL 506
IS 7489
BP 471
EP 475
DI 10.1038/nature12994
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0DN
UT WOS:000332165100034
PM 24572422
DA 2026-03-09
ER

PT J
AU Wright, KE
   Hjerrild, KA
   Bartlett, J
   Douglas, AD
   Jin, J
   Brown, RE
   Illingworth, JJ
   Ashfield, R
   Clemmensen, SB
   de Jongh, WA
   Draper, SJ
   Higgins, MK
AF Wright, Katherine E.
   Hjerrild, Kathryn A.
   Bartlett, Jonathan
   Douglas, Alexander D.
   Jin, Jing
   Brown, Rebecca E.
   Illingworth, Joseph J.
   Ashfield, Rebecca
   Clemmensen, Stine B.
   de Jongh, Willem A.
   Draper, Simon J.
   Higgins, Matthew K.
TI Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies
SO NATURE
LA English
DT Article
ID multiple sequence alignments; size-distribution analysis; plasmodium-falciparum; pfrh5 polymorphisms; homolog; ultracentrifugation; constraints; prediction; receptor; system
AB Invasion of host erythrocytes is essential to the life cycle of Plasmodium parasites and development of the pathology of malaria. The stages of erythrocyte invasion, including initial contact, apical reorientation, junction formation, and active invagination, are directed by coordinated release of specialized apical organelles and their parasite protein contents'. Among these proteins, and central to invasion by all species, are two parasite protein families, the reticulocyte-binding protein homologue (RH) and erythrocyte-binding like proteins, which mediate host-parasite interactions(2). RH5 from Plasmodium falciparum (PfRH5) is the only member of either family demonstrated to be necessary for erythrocyte invasion in all tested strains, through its interaction with the erythrocyte surface protein basigin (also known as CD 147 and EMMPRIN)(3,4). Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in vitro(4-9), making PfRH5 an excellent vaccine candidate. Here we present crystal structures of PfRH5 in complex with basigin and two distinct inhibitory antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come together in a kite-like architecture, presenting binding sites for basigin and inhibitory antibodies at one tip. This provides the first structural insight into erythrocyte binding by the Plasmodium RH protein family and identifies novel inhibitory epitopes to guide design of a new generation of vaccines against the blood-stage parasite.
C1 [Wright, Katherine E.; Bartlett, Jonathan; Higgins, Matthew K.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [Hjerrild, Kathryn A.; Douglas, Alexander D.; Jin, Jing; Brown, Rebecca E.; Illingworth, Joseph J.; Ashfield, Rebecca; Draper, Simon J.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
   [Clemmensen, Stine B.; de Jongh, Willem A.] ExpreS2 Biotechnol, DK-2970 Horsholm, Denmark.
C3 University of Oxford; University of Oxford; Jenner Institute
RP Higgins, MK (corresponding author), Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England.
EM simon.draper@ndm.ox.ac.uk; matthew.higgins@bioch.ox.ac.uk
FU UK Medical Research Council (MRC) [G1000527]; European Vaccine Initiative(EVI)(InnoMalVac); UK MRC [MR/K025554/1]; European Community [242095 EVIMalaR]; Wellcome Trust [089455/2/09/z]; Medical Research Council [G1000527, MR/K025554/1] Funding Source: researchfish; Wellcome Trust [101020/Z/13/Z] Funding Source: researchfish; MRC [MR/K025554/1, G1000527] Funding Source: UKRI; Wellcome Trust [101020/Z/13/Z] Funding Source: Wellcome Trust
NR 47
TC 171
Z9 194
U1 0
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 NOV 20
PY 2014
VL 515
IS 7527
BP 427
EP +
DI 10.1038/nature13715
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AU7HE
UT WOS:000345770600049
PM 25132548
DA 2026-03-09
ER

PT J
AU Siyushev, P
   Stein, G
   Wrachtrup, JR
   Gerhardt, I
AF Siyushev, Petr
   Stein, Guilherme
   Wrachtrup, Joeg
   Gerhardt, Ilja
TI Molecular photons interfaced with alkali atoms
SO NATURE
LA English
DT Article
ID single-molecule; crystalline system; p-terphenyl; spectroscopy; excitation; emission; dibenzoterrylene; terrylene; vapor
AB Future quantum communication will rely on the integration of single-photon sources, quantum memories and systems with strong single-photon nonlinearities(1). Two key parameters are crucial for the single-photon source: a high photon flux with a very small bandwidth, and a spectral match to other components of the system. Atoms or ions may act as single-photon sources-owing to their narrow-band emission and their intrinsic spectral match to other atomic systems-and can serve as quantum nonlinear elements. Unfortunately, their emission rates are still limited, even for highly efficient cavity designs(2). Single solid-state emitters such as single organic dye molecules are significantly brighter(3) and allow for narrowband photons(4); they have shown potential in a variety of quantum optical experiments(5,6) but have yet to be interfaced with other components such as stationary memory qubits. Here we describe the optical interaction between Fourier-limited photons from a single organic molecule and atomic alkali vapours, which can constitute an efficient quantum memory. Single-photon emission rates reach up to several hundred thousand counts per second and show a high spectral brightness of 30,000 detectable photons per second per megahertz of bandwidth. The molecular emission is robust and we demonstrate perfect tuning to the spectral transitions of the sodium D line and efficient filtering, even for emitters at ambient conditions. In addition, we achieve storage of molecular photons originating from a single dibenzanthanthrene molecule in atomic sodium vapour. Given the large set of molecular emission lines matching to atomic transitions, our results enable the combination of almost ideal single-photon sources with various atomic vapours, such that experiments with giant single photon nonlinearities, mediated, for example, by Rydberg atoms(7,8), become feasible.
C1 [Siyushev, Petr; Stein, Guilherme; Wrachtrup, Joeg; Gerhardt, Ilja] Univ Stuttgart, Inst Phys 3, Stuttgart Res Ctr Photon Engn SCoPE, D-70569 Stuttgart, Germany.
   [Siyushev, Petr; Stein, Guilherme; Wrachtrup, Joeg; Gerhardt, Ilja] Ctr Integrated Quantum Sci & Technol IQST, D-70569 Stuttgart, Germany.
   [Wrachtrup, Joeg; Gerhardt, Ilja] Max Planck Inst Solid State Res, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; Max Planck Society
RP Gerhardt, I (corresponding author), Univ Stuttgart, Inst Phys 3, Stuttgart Res Ctr Photon Engn SCoPE, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM i.gerhardt@fkf.mpg.de
FU Max Planck Society; BMBF; EU
NR 33
TC 76
Z9 83
U1 1
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 MAY 1
PY 2014
VL 509
IS 7498
BP 66
EP +
DI 10.1038/nature13191
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG1TM
UT WOS:000335199100040
PM 24784217
DA 2026-03-09
ER

PT J
AU Poulter, B
   Frank, D
   Ciais, P
   Myneni, RB
   Andela, N
   Bi, J
   Broquet, G
   Canadell, JG
   Chevallier, F
   Liu, YY
   Running, SW
   Sitch, S
   van der Werf, GR
AF Poulter, Benjamin
   Frank, David
   Ciais, Philippe
   Myneni, Ranga B.
   Andela, Niels
   Bi, Jian
   Broquet, Gregoire
   Canadell, Josep G.
   Chevallier, Frederic
   Liu, Yi Y.
   Running, Steven W.
   Sitch, Stephen
   van der Werf, Guido R.
TI Contribution of semi-arid ecosystems to interannual variability of the global carbon cycle
SO NATURE
LA English
DT Article
ID biomass burning emissions; atmospheric co2 growth; terrestrial carbon; vegetation index; dynamics; cover; australia; responses; land
AB The land and ocean act as a sink for fossil-fuel emissions, thereby slowing the rise of atmospheric carbon dioxide concentrations(1). Although the uptake of carbon by oceanic and terrestrial processes has kept pace with accelerating carbon dioxide emissions until now, atmospheric carbon dioxide concentrations exhibit a large variability on interannual timescales(2), considered to be driven primarily by terrestrial ecosystem processes dominated by tropical rainforests(3). We use a terrestrial biogeochemical model, atmospheric carbon dioxide inversion and global carbon budget accounting methods to investigate the evolution of the terrestrial carbon sink over the past 30 years, with a focus on the underlying mechanisms responsible for the exceptionally large land carbon sink reported in 2011 (ref. 2). Here we show that our three terrestrial carbon sink estimates are in good agreement and support the finding of a 2011 record land carbon sink. Surprisingly, we find that the global carbon sink anomaly was driven by growth of semi-arid vegetation in the Southern Hemisphere, with almost 60 per cent of carbon uptake attributed to Australian ecosystems, where prevalent La Nina conditions caused up to six consecutive seasons of increased precipitation. In addition, since 1981, a six per cent expansion of vegetation cover over Australia was associated with a fourfold increase in the sensitivity of continental net carbon uptake to precipitation. Our findings suggest that the higher turnover rates of carbon pools in semi-arid biomes are an increasingly important driver of global carbon cycle inter-annual variability and that tropical rainforests may become less relevant drivers in the future. More research is needed to identify to what extent the carbon stocks accumulated during wet years are vulnerable to rapid decomposition or loss through fire in subsequent years.
C1 [Poulter, Benjamin] Montana State Univ, Inst Ecosyst, Bozeman, MT 59717 USA.
   [Poulter, Benjamin] Dept Ecol, Bozeman, MT 59717 USA.
   [Poulter, Benjamin; Ciais, Philippe; Broquet, Gregoire; Chevallier, Frederic] CEA CNRS UVSQ, LSCE, F-91191 Gif Sur Yvette, France.
   [Frank, David] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Frank, David] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Myneni, Ranga B.; Bi, Jian] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Andela, Niels; van der Werf, Guido R.] Vrije Univ Amsterdam, Fac Earth & Life Sci, NL-1081 HV Amsterdam, Netherlands.
   [Canadell, Josep G.] CSIRO, Global Carbon Project, Marine & Atmospher Res, Canberra, ACT 2601, Australia.
   [Liu, Yi Y.] Univ New S Wales, ARC Ctr Excellence Climate Syst Sci, Sydney, NSW 2052, Australia.
   [Liu, Yi Y.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Running, Steven W.] Univ Montana, Dept Ecosyst & Conservat Sci, Missoula, MT 59812 USA.
   [Sitch, Stephen] Univ Exeter, Coll Engn Comp & Math, Exeter EX4 4QF, Devon, England.
C3 Montana State University System; Montana State University Bozeman; CEA; Universite Paris Saclay; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Bern; Boston University; Vrije Universiteit Amsterdam; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; University of New South Wales Sydney; University of Montana System; University of Montana; University of Exeter
RP Poulter, B (corresponding author), Montana State Univ, Inst Ecosyst, Bozeman, MT 59717 USA.
EM benjamin.poulter@montana.edu
FU EU FP7 GEOCARBON programme [283080]; Australian Climate Change Science Program; NASA Earth Science Division; Office of Integrative Activities; Office Of The Director [1443108] Funding Source: National Science Foundation
NR 40
TC 1177
Z9 1341
U1 25
U2 998
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 29
PY 2014
VL 509
IS 7502
BP 600
EP +
DI 10.1038/nature13376
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AH9JC
UT WOS:000336457100045
PM 24847888
DA 2026-03-09
ER

